Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response.Multiple organs can develop fibrosis,including the liver,kidney,heart,and lung...Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response.Multiple organs can develop fibrosis,including the liver,kidney,heart,and lung.Fibrosis such as liver cirrhosis,idiopathic pulmonary fibrosis,and cystic fibrosis caused substantial disease burden.Persistent abnormal activation of myofibroblasts mediated by various signals,such as transforming growth factor,platelet-derived growth factor,and fibroblast growh factor,has been recongized as a major event in the occurrence and progression of fibrosis.Although the mechanisms driving organ-specific fibrosis have not been fully elucidated,drugs targeting these identified aberrant signals have achieved potent anti-fibrotic efficacy in clinical trials.In this review,we briefly introduce the aetiology and epidemiology of several fibrosis diseases,including liver fibrosis,kidney fibrosis,cardiac fibrosis,and pulmonary fibrosis.Then,we summarise the abnormal cells(epithelial cells,endothelial cells,immune cells,and fibroblasts)and their interactions in fibrosis.In addition,we also focus on the aberrant signaling pathways and therapeutic targets that regulate myofibroblast activation,extracellular matrix cross-linking,metabolism,and inflammation in fibrosis.Finally,we discuss the anti-fibrotic drugs based on their targets and clinical trials.This review provides reference for further research on fibrosis mechanism,drug development,and clinical trials.展开更多
Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region ...Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.展开更多
We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an ext...We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral genome replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.展开更多
Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in...Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in regulating IAV infection.Here,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation sites.Additionally,for the first time,we provide evidence that PB2 can also be acetylated at site K187.Notably,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based MS.Both S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life cycle.Bioinformatic analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein structure.While continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in mice.Mechanistically,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory responses.Therefore,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic studies.Meanwhile,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.展开更多
As an important hub on the East Asian-Australian Flyway(EAAF),Hongze Lake is an important migratory stopover and wintering site for hundreds of thousands of birds.However,research on bird community diversity in this a...As an important hub on the East Asian-Australian Flyway(EAAF),Hongze Lake is an important migratory stopover and wintering site for hundreds of thousands of birds.However,research on bird community diversity in this area is still lacking.We conducted a bird survey from July 2020 to June 2021 using the line transect method on the terrestrial habitat,as well as the fixed-point method in the lake wetland at the Sihong Hongze Lake Wetland National Nature Reserve located in northwestern Hongze Lake,and analyzed the temporal-spatial variation in the bird community.The results showed that a total of 170432 detections of 215 bird species belonging to 18 orders and 55 families were recorded.In terms of species composition,the proportion of terrestrial birds was relatively high,followed by waterfowl richness,with high numbers of Anatidae species and shorebirds.For bird species abundance,waterfowl had the highest abundance of common coot(Fulica atra),belonging to the Rallidae family,followed by Anatidae and Ardeidae species.The abundance of shorebirds was extremely low,and that of non-waterfowl was also low.In terms of temporal patterns,the number of bird species and richness index were higher in spring and autumn but lower in winter and summer.The bird abundance was the highest in winter,and the remaining three seasons were similar in terms of bird abundance.The diversity index and evenness index were higher in spring,summer and autumn,and lowest in winter.For the spatial pattern,the open water in the western part of the reserve included the most densely distributed areas for birds,and the number of bird species and their abundance were both the highest in that part.There were significant differences in the bird community structures among the four habitats.The species number and richness index of birds in the reed habitat were the highest,and the bird abundance was also high,but the diversity index and evenness index were low.Although the bird abundance in the lake habitat was much higher than in the other habitats,the div展开更多
Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)reg...Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.展开更多
Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences ...Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plastici展开更多
In this study, ion mobility separation coupled with tandem mass spectrometry （IM-tandem MS） was utilized to investigate the ionization behaviors of two amino acids including leucine and isoleucine. Under the electro...In this study, ion mobility separation coupled with tandem mass spectrometry （IM-tandem MS） was utilized to investigate the ionization behaviors of two amino acids including leucine and isoleucine. Under the electrospray ionization （ESI） mode, two protonation sites in each molecular sturcture caused two forms of protomer. One arose from the amino being protonated （amino-protomer） and the other from the carboxyl being protonated （car- boxyl-protomer）. In the two-dimensional （drift time, m/z） spectrum, the protomers had the same mass, but the dis- tinguishable drift times and fragmentation patterns. For the characterization purpose, the theoretical collision cross section （CCS） values of the protomers were calculated and proven to be consistent with the experimental. Moreover, the quantified relationship between the amino acids and their protomers was evaluated. It showed that the abun- dance of the carboxyl-protomer was proportional to the concentration of the amino acid, whereas that of the amino- protomer did not have the same trend. Under the atmospheric pressure chemical ionization （APCI） mode, only the carboxyl-protomer was observed. In addition, the amino-protomer and the cluster ions observed under ESI were absent completely. The results demonstrate that the ionization mode impacts heavily on the ionization behaviors of leucine and isoleucine not only on the form of therir protomers but also On the quantified relationship.展开更多
Tailoring water supply to achieve confined heating has proven to be an effective strategy for boosting solar interfacial evaporation rates.However,because of salt clogging during desalination,a critical point of const...Tailoring water supply to achieve confined heating has proven to be an effective strategy for boosting solar interfacial evaporation rates.However,because of salt clogging during desalination,a critical point of constriction occurs when controlling the water rate for confined heating.In this study,we demonstrate a facile and scalable weaving technique for fabricating core-sheath photothermal yarns that facilitate controlled water supply for stable and efficient interracial solar desalination.The core-sheath yarn comprises modal fibers as the core and carbon fibers as the sheaths.Because of the core-sheath design,remarkable liquid pumping can be enabled in the carbon fiber bundle of the dispersed superhydrophilic modal fibers.Our woven fabrics absorb a high proportion(92%)of the electromagnetic radiation in the solar spectrum because of the weaving structure and the carbon fiber sheath.Under one-sun(1 kW·m^(-2))illumination,our woven fabric device can achieve the highest evaporation rate(of 2.12kg·m^(-2)·h^(-1) with energy conversion efficiency:93.7%)by regulating the number of core-sheath yarns.Practical application tests demonstrate that our device can maintain high and stable desalination performance in a 5 wt%NaCl solution.展开更多
As an essential infrastructure,the rural power grid is vital in promoting agricultural and rural carbon sequestration and improving rural energy electrification.It is necessary to carry out in-depth research on its co...As an essential infrastructure,the rural power grid is vital in promoting agricultural and rural carbon sequestration and improving rural energy electrification.It is necessary to carry out in-depth research on its comprehensive efficiency.Based on the requirements of“double carbon”and rural revitalization strategy for the rural Power Grid,this paper focuses on the modernization and low-carbon transformation of the rural Power Grid.It constructs an input-output index system for the investment efficiency of the rural Power Grid in China under the new situation.It uses the primary data of the rural Power Grid of 30 prefecture-level cities in China from 2019 to 2021 to evaluate the investment efficiency of the rural Power Grid in China through a three-stage DEA model.The empirical results show that:considering the regional differences,the comprehensive efficiency of the rural Power Grid in backward areas is significantly improved;that is,the three-stage DEA method can more objectively evaluate the comprehensive efficiency of the rural Power Grid.In the context of the continued promotion of the rural revitalization strategy,to improve the comprehensive efficiency of the rural Power Grid,it is necessary to improve the technical level of the rural Power Grid further and appropriately expand the scale of investment in the rural Power Grid.展开更多
Swine farm wastewater is extremely harmful to the environment if not treated before it is discharged.In this study,a system was developed and optimized for testing the high levels of organic matter in swine farm waste...Swine farm wastewater is extremely harmful to the environment if not treated before it is discharged.In this study,a system was developed and optimized for testing the high levels of organic matter in swine farm wastewater utilizing a microalgae/bacteria co-culture combined with a novel closed-loop extraction and dilution process.Importantly,the system produces biomass that also could be harvested and used in value-added applications.The efficacy of biomass as a biofertilizer was demonstrated by using a model plant of Arabidopsis.In addition,the analysis of biomass indicates that it also has potential as a source for biofuel.After a 20-d cultivation period,a yield of biomass was achieved to 2.063 g/L of wastewater.The highest removal rates recorded in steady state conditions were:13.8 mg/L·d of Total Nitrogen(TN);11.5 mg/L·d of Ammonia Nitrogen(NH_(4)^(+)-N);24.8 mg/L·d of Chemical Oxygen Demand(COD);and 16.9 mg/L·d of Total Phosphorus(TP).After cultivation,the composition of the biomass was analyzed on a dry basis;the major components were protein(44.9%),lipids(24.6%),carbohydrates(19.9%),Chlorophyll-A(2.75%),Chlorophyll-B(1.66%),and carotenoids(0.57%).This biomass was diluted with water(5%by weight)and used as a biofertilizer to grow Arabidopsis.The results showed that the average root and stem lengths of Arabidopsis were 43.0%and 55.0%longer compared to those of the control group.Additionally,the number of leaves and the maximum leaf length increased by 30.2%and 39.7%;and the fresh and dry leaf weights increased by 44.0%and 33.7%,respectively.These results demonstrate the efficacy of this system for treating swine farm wastewater whilst simultaneously producing a value-added microalgae/bacteria biomass.This paper also demonstrated the use of biomass as a fertilizer for cultivating a value-added crop and,based on the compositional analyses,propose that the biomass could be used as a raw material for biofuel production due to its high lipid content of 24.6%.By constructing a microalgae/bacteria symbiosis sys展开更多
Native animals are facing long-term coexistence with invasive plants worldwide,the impacts of which on animal behavior remain poorly known.Potential ecological traps could threaten native birds breeding in invasive pl...Native animals are facing long-term coexistence with invasive plants worldwide,the impacts of which on animal behavior remain poorly known.Potential ecological traps could threaten native birds breeding in invasive plant habitats,but behavioral strategies for birds to avoid such risks are few concerned.The invasion of Smooth Cordgrass(Spartina alterniflra) has seriously varied the vegetation landscape in the coastal wetlands of eastern China,and affected the habitat selection of native birds.Here,we investigated the nesting and breeding characteristics of a common native passerine,the Vinous-throated Parrotbill(Sinosuthora webbiana),in habitats dominated by native Common Reed(Phragmites australis) and exotic cordgrass.We found that parrotbills could complete their breeding cycle in cordgrass habitat.Most nest failure was attributed to predation in native habitat but tide inundation in cordgrass habitat.However,the nest success rate and daily survival rate(DSR) in cordgrass habitat were higher.Moreover,nest height was markedly higher in cordgrass habitat and was the most important influencing variable(positively correlated with the DSR).These results suggest that cordgrass habitat is a potential ecological trap due to the tide inundation,but some parrotbills seem to effectively avoid this risk by increasing nest height.Our study reveals that a native passerine changes its nesting behavior to accommodate invasive plant habitat and highlights that habitat changes caused by invasive plants may drive the adaptive evolution of native animal behavior.The limitation of these results must be acknowledged for the small sample size,and there is a need for a larger sample and long-term data for further verification.展开更多
Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 mac...Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 sign展开更多
Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinas...Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics(PD)and pharmacokinetics(PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structureeactivity relationship study,inhibited the proliferation of vascular endothelial cells(ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patientderived tumor xenograft(PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles.In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.展开更多
The a3＊ nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous syste...The a3＊ nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The α-conotoxin （α-CTx） LvlA has been identified as the most selective inhibitor of α3β2 nAChRs known to date, and it can distinguish the α3132 nAChR subtype from the α6/α3β2β3 and α3β4 nAChR subtypes. However, the mechanism of its selectivity towards α3132, α6/α3β2β3, and α3β4 nAChRs remains elusive. Here we report the co-crystal structure of LvlA in complex with Aplysia californica acetylcholine binding protein （Ac-AChBP） at a resolution of 3.4 A. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvlA plays an important role in the selectivity of LvlA towards α3132 and α31o6132133 nAChRs by making a salt bridge with Lys-155 of the rat α3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat β2 subunit in the α3β2 nAChR model, revealing the reason for its more potent selectivity towards the a3β2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target α3β2 nAChRs, with significant implications for the design of new therapeutic a-CTxs.展开更多
Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes a...Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes as well as the inconvenient form of usage.To overcome these shortcomings,freeze-dried PRP(LyPRP)was encapsulated into bioactive Col I hydrogel to induce osteogenic dif-ferentiation of rabbit bone marrow mesenchymal stem cells(rBMSCs).And PRP/Col I composite hydrogel was prepared as a control.Compared with Col I hydrogel,the introduction of platelets significantly improved the mechanical properties of hydrogels.Meanwhile,platelets were evenly distributed in the composite hydrogels network.The sustainable release of related factors in the composite hydrogels could last for more than 14days to maintain its long-term biological activity.Further cell experiments confirmed that PRP and LyPRP could effectively alleviate the contraction of collagen hydrogel in vitro,and promote the adhesion,proliferation and osteogenesis differentia-tion of rBMSCs.The results of osteogenic gene expression indicated that the 10%LyPRP/Col I composite hydrogel could facilitate the early expression of BMP-2 and late osteogenic associated protein formation with higher expression of alkaline phosphatase and Osteocalcin(OCN).These results might provide new insights for the clinical application of 10%LyPRP/Col I composite hydro-gel as practical bone repair injection.展开更多
The electrical and thermal characteristics of metal oxide varistor(MOV)are essential for the study of MOV performance and degradation.This paper provides a modelling method of MOV to simulate its microstructure geomet...The electrical and thermal characteristics of metal oxide varistor(MOV)are essential for the study of MOV performance and degradation.This paper provides a modelling method of MOV to simulate its microstructure geometry with the Voronoi network and derive the electrical functions on the grain boundaries.A series of discrete data to describe the resistance-voltage(R-V)characteristics of MOV from experiments is applied to the pro-posed model.Through 8/20μs surge current experiments,the electrical conductivity of MOV is determined to achieve the simulation of the clamping voltage.With this model,the current distribution and temperature distribution over a MOV sample are simulated and analysed by the finite element method(FEM).The simulation results show good agreement with the experimental measurement and inherent feature of MOV.展开更多
Estuarial saline wetlands have been recognized as a vital role in CO_2 cycling.However,insufficient attention has been paid to estimating CO_2 fluxes from estuarial saline wetlands.In this study,the static chamber-gas...Estuarial saline wetlands have been recognized as a vital role in CO_2 cycling.However,insufficient attention has been paid to estimating CO_2 fluxes from estuarial saline wetlands.In this study,the static chamber-gas chromatography(GC) method was used to quantify CO_2 budget of an estuarial saline reed(Phragmites australis) wetland in Jiaozhou Bay in Qingdao City of Shandong Province,China during the reed growing season(May to October) in 2014.The CO_2 budget study involved net ecosystem CO_2 exchange(NEE),ecosystem respiration(Reco) and gross primary production(GPP).Temporal variation in CO_2 budget and the impact of air/soil temperature,illumination intensity and aboveground biomass exerted on CO_2 budget were analyzed.Results indicated that the wetland was acting as a net sink of 1129.16 g/m^2 during the entire growing season.Moreover,the values of Reco and GPP were 1744.89 g/m^2 and 2874.05 g/m^2,respectively;the ratio of Reco and GPP was 0.61.Diurnal and monthly patterns of CO_2 budget varied significantly during the study period.Reco showed exponential relationships with air temperature and soil temperature at 5 cm,10 cm,20 cm depths,and soil temperature at 5 cm depth was the most crucial influence factor among them.Meanwhile,temperature sensitivity(Q10) of Reco was negatively correlated with soil temperature.Light and temperature exerted strong controls over NEE and GPP.Aboveground biomass over the whole growing season showed non-linear relationships with CO_2 budget,while those during the early and peak growing season showed significant linear relationships with CO_2 budget.This research provides valuable reference for CO_2 exchange in estuarial saline wetland ecosystem.展开更多
Since the dynamics of thin‐walled structures instantaneously varies during the milling process,accurate and efficient prediction of the in‐process workpiece(IPW)dynamics is critical for the prediction of chatter sta...Since the dynamics of thin‐walled structures instantaneously varies during the milling process,accurate and efficient prediction of the in‐process workpiece(IPW)dynamics is critical for the prediction of chatter stability of milling of thin‐walled structures.This article presents a surrogate model of the IPW dynamics of thin‐walled structures by combining Gaussian process regression(GPR)with proper orthogonal decomposition(POD)when IPW dynamics at a large number of cutting positions has to be predicted.The GPR method is used to learn the mapping between a set of the known IPW dynamics and the corresponding cutting positions.POD is used to reduce the order of the matrix assembled by the mode shape vectors at different cutting positions,before the GPR model of the IPW mode shape is established.The computation time of the proposed model is mainly composed of the time taken for predicting a known set of IPW dynamics and the time taken for training GPR models.Simulation shows that the proposed model requires less computation time.Moreover,the accuracy of the proposed model is comparable to that of the existing methods.Comparison between the predicted stability lobe diagram and the experimental results shows that IPW dynamics predicted by the proposed model is accurate enough for predicting the stability of milling of thin‐walled structures.展开更多
The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great ...The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great prospects for replacing fossil energy and attracted attention from the society. The use of catalytic approach to transform biomass into high-value chemicals is an effective way to use biomass efficiently. In this work, Nisupported catalysts has been developed for the selective cleavage of C–O bonds in lignin model compounds with 2-propanol as the hydrogen source solvent. Among these catalysts, it was indicated that zirconium phosphate(Zr P)-supported Ni catalysts were highly efficient and recyclable for alkyl-aryl ether(α-O-4 and β-O-4) cleavage in lignin model compounds. The further investigation demonstrated that the transfer hydrogenolysis of the C–O bond is highly selective, which afforded phenols and aromatics as dominant products without the products arising from hydrogenation of aromatic rings. Through a series of characterization of the catalyst, it was demonstrated that the medium strong acid sites of the Zr P support promoted the cleavage of alkyl-aryl ethers(α-O-4 and β-O-4),and Br?nsted acid sites favored for achieving high selectivity toward C–O bond cleavage. Additionally, Ni(0) sites on the Zr P catalysts were responsible for the catalytic transfer hydrogenolysis.展开更多
基金supported by the National Science Foundation of China(No.81773375)the National Major Scientific and Technological Special Project(No.2019ZX09201001)。
文摘Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response.Multiple organs can develop fibrosis,including the liver,kidney,heart,and lung.Fibrosis such as liver cirrhosis,idiopathic pulmonary fibrosis,and cystic fibrosis caused substantial disease burden.Persistent abnormal activation of myofibroblasts mediated by various signals,such as transforming growth factor,platelet-derived growth factor,and fibroblast growh factor,has been recongized as a major event in the occurrence and progression of fibrosis.Although the mechanisms driving organ-specific fibrosis have not been fully elucidated,drugs targeting these identified aberrant signals have achieved potent anti-fibrotic efficacy in clinical trials.In this review,we briefly introduce the aetiology and epidemiology of several fibrosis diseases,including liver fibrosis,kidney fibrosis,cardiac fibrosis,and pulmonary fibrosis.Then,we summarise the abnormal cells(epithelial cells,endothelial cells,immune cells,and fibroblasts)and their interactions in fibrosis.In addition,we also focus on the aberrant signaling pathways and therapeutic targets that regulate myofibroblast activation,extracellular matrix cross-linking,metabolism,and inflammation in fibrosis.Finally,we discuss the anti-fibrotic drugs based on their targets and clinical trials.This review provides reference for further research on fibrosis mechanism,drug development,and clinical trials.
文摘Background: Hand, foot and mouth disease (HFMD) remains an important public health problem in China. Many studies on the epidemiological characteristics of HFMD have been reported, but studies in North Sichuan region have been neglected. Methods: HFMD-related enterovirus infected cases were clinically confirmed and underwent real-time RT-PCR (rRT-PCR) from May 2018 to October 2023 in Guangyuan Central Hospital. Results: During 2018-2023, other EV (437 cases, 81.08%) was the most predominant serotype followed by CV-A16 (94 cases, 17.44%), EV-A71 (8 cases, 1.48%) was the least predominant serotype. Peak infections occurred in July and October. There were no significant differences in gender, age and serotypes. HFMD was concentrated in children under 47 months of age, with the highest incidence in children aged 12 - 23 months and the highest proportion of other EV infections in the whole age group. COVID-19 did not cause significant changes in gender, age and serotype. Overall, there was a significant increase in the proportion of children aged 12 - 23 months infected with CV-A16, and an increase in the proportion of children aged over 36 months infected with other EVs. Conclusions: The incidence of HFMD caused by EV-A71 has decreased significantly, and other EVs have become the main pathogens of HFMD in North Sichuan region in recent years. In the prevention and control of CV-A16, more attention should be paid to children aged 12 - 23 months and the dominant serotype should be closely monitored. Our study highlights the importance of developing of new diagnostic reagents and vaccines for the prevention and control of enterovirus infection. This study for the first time provides insights into district interventions to local conditions.
文摘We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral genome replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.
基金supported by the National Natural Science Foundation of China(32072832,32372976)by the National Key Research and Development Project of China(2021YFD1800202)+3 种基金by Jiangsu Province Agricultural Science&Technology Independent Innovation Funds[CX(21)3141]by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3553 and KYCX21_3277)by the Earmarked Fund for China Agriculture Research System(CARS-40)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in regulating IAV infection.Here,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation sites.Additionally,for the first time,we provide evidence that PB2 can also be acetylated at site K187.Notably,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based MS.Both S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life cycle.Bioinformatic analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein structure.While continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in mice.Mechanistically,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory responses.Therefore,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic studies.Meanwhile,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.
基金The Forestry Bureau of Jiangsu Province(202004120).
文摘As an important hub on the East Asian-Australian Flyway(EAAF),Hongze Lake is an important migratory stopover and wintering site for hundreds of thousands of birds.However,research on bird community diversity in this area is still lacking.We conducted a bird survey from July 2020 to June 2021 using the line transect method on the terrestrial habitat,as well as the fixed-point method in the lake wetland at the Sihong Hongze Lake Wetland National Nature Reserve located in northwestern Hongze Lake,and analyzed the temporal-spatial variation in the bird community.The results showed that a total of 170432 detections of 215 bird species belonging to 18 orders and 55 families were recorded.In terms of species composition,the proportion of terrestrial birds was relatively high,followed by waterfowl richness,with high numbers of Anatidae species and shorebirds.For bird species abundance,waterfowl had the highest abundance of common coot(Fulica atra),belonging to the Rallidae family,followed by Anatidae and Ardeidae species.The abundance of shorebirds was extremely low,and that of non-waterfowl was also low.In terms of temporal patterns,the number of bird species and richness index were higher in spring and autumn but lower in winter and summer.The bird abundance was the highest in winter,and the remaining three seasons were similar in terms of bird abundance.The diversity index and evenness index were higher in spring,summer and autumn,and lowest in winter.For the spatial pattern,the open water in the western part of the reserve included the most densely distributed areas for birds,and the number of bird species and their abundance were both the highest in that part.There were significant differences in the bird community structures among the four habitats.The species number and richness index of birds in the reed habitat were the highest,and the bird abundance was also high,but the diversity index and evenness index were low.Although the bird abundance in the lake habitat was much higher than in the other habitats,the div
基金This work was supported in part by the National Natural Science Foundation of China(82370417,81970320,82270273)the Certificate of China Postdoctoral Science Foundation Grant(2021M693826)+1 种基金the postdoctoral funding from Heilongjiang Province(21042230046)the Hai Yan Youth Fund from Harbin Medical University Cancer Hospital(JJQN2021-09).
文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
基金the National Key Research and Development Program of China(2022YFC2009700)the National Science Foundation of China(82372582)+1 种基金the Medical Applications Basic Research Project of Suzhou Science and Technology Bureau(SKY2023033)the Wujiang District Science,Education,Health and Promotion Project(WWK202021).
文摘Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plastici
文摘In this study, ion mobility separation coupled with tandem mass spectrometry （IM-tandem MS） was utilized to investigate the ionization behaviors of two amino acids including leucine and isoleucine. Under the electrospray ionization （ESI） mode, two protonation sites in each molecular sturcture caused two forms of protomer. One arose from the amino being protonated （amino-protomer） and the other from the carboxyl being protonated （car- boxyl-protomer）. In the two-dimensional （drift time, m/z） spectrum, the protomers had the same mass, but the dis- tinguishable drift times and fragmentation patterns. For the characterization purpose, the theoretical collision cross section （CCS） values of the protomers were calculated and proven to be consistent with the experimental. Moreover, the quantified relationship between the amino acids and their protomers was evaluated. It showed that the abun- dance of the carboxyl-protomer was proportional to the concentration of the amino acid, whereas that of the amino- protomer did not have the same trend. Under the atmospheric pressure chemical ionization （APCI） mode, only the carboxyl-protomer was observed. In addition, the amino-protomer and the cluster ions observed under ESI were absent completely. The results demonstrate that the ionization mode impacts heavily on the ionization behaviors of leucine and isoleucine not only on the form of therir protomers but also On the quantified relationship.
基金financial support from the National Natural Science Foundation of China(52103064 and U21A2095)the Key Research and Development Program of Hubei Province(2021BAA068)National Local Joint Laboratory for Advanced Textile Processing and Clean Production(FX2022001)。
文摘Tailoring water supply to achieve confined heating has proven to be an effective strategy for boosting solar interfacial evaporation rates.However,because of salt clogging during desalination,a critical point of constriction occurs when controlling the water rate for confined heating.In this study,we demonstrate a facile and scalable weaving technique for fabricating core-sheath photothermal yarns that facilitate controlled water supply for stable and efficient interracial solar desalination.The core-sheath yarn comprises modal fibers as the core and carbon fibers as the sheaths.Because of the core-sheath design,remarkable liquid pumping can be enabled in the carbon fiber bundle of the dispersed superhydrophilic modal fibers.Our woven fabrics absorb a high proportion(92%)of the electromagnetic radiation in the solar spectrum because of the weaving structure and the carbon fiber sheath.Under one-sun(1 kW·m^(-2))illumination,our woven fabric device can achieve the highest evaporation rate(of 2.12kg·m^(-2)·h^(-1) with energy conversion efficiency:93.7%)by regulating the number of core-sheath yarns.Practical application tests demonstrate that our device can maintain high and stable desalination performance in a 5 wt%NaCl solution.
基金supported by the State Grid Science and Technology Project (1300-202157362A-0-0-00).
文摘As an essential infrastructure,the rural power grid is vital in promoting agricultural and rural carbon sequestration and improving rural energy electrification.It is necessary to carry out in-depth research on its comprehensive efficiency.Based on the requirements of“double carbon”and rural revitalization strategy for the rural Power Grid,this paper focuses on the modernization and low-carbon transformation of the rural Power Grid.It constructs an input-output index system for the investment efficiency of the rural Power Grid in China under the new situation.It uses the primary data of the rural Power Grid of 30 prefecture-level cities in China from 2019 to 2021 to evaluate the investment efficiency of the rural Power Grid in China through a three-stage DEA model.The empirical results show that:considering the regional differences,the comprehensive efficiency of the rural Power Grid in backward areas is significantly improved;that is,the three-stage DEA method can more objectively evaluate the comprehensive efficiency of the rural Power Grid.In the context of the continued promotion of the rural revitalization strategy,to improve the comprehensive efficiency of the rural Power Grid,it is necessary to improve the technical level of the rural Power Grid further and appropriately expand the scale of investment in the rural Power Grid.
基金supported by National Key R&D Program of China(Grant No.2022YFC3902403)Beijing excellent talent training project(Grant No.2018000020144G074)+3 种基金Special project on green campus of Beijing Union University(Grant No.zk50202101)Research innovation grant for graduate students of Beijing Union University(Grant No.yz2020k001)Scientific research project grants from Beijing Union University(Grant No.ZK130202103,JB202101,XP202004)University of Minnesota Mn Drive Environment(MNE12)and Center for Biorefining.
文摘Swine farm wastewater is extremely harmful to the environment if not treated before it is discharged.In this study,a system was developed and optimized for testing the high levels of organic matter in swine farm wastewater utilizing a microalgae/bacteria co-culture combined with a novel closed-loop extraction and dilution process.Importantly,the system produces biomass that also could be harvested and used in value-added applications.The efficacy of biomass as a biofertilizer was demonstrated by using a model plant of Arabidopsis.In addition,the analysis of biomass indicates that it also has potential as a source for biofuel.After a 20-d cultivation period,a yield of biomass was achieved to 2.063 g/L of wastewater.The highest removal rates recorded in steady state conditions were:13.8 mg/L·d of Total Nitrogen(TN);11.5 mg/L·d of Ammonia Nitrogen(NH_(4)^(+)-N);24.8 mg/L·d of Chemical Oxygen Demand(COD);and 16.9 mg/L·d of Total Phosphorus(TP).After cultivation,the composition of the biomass was analyzed on a dry basis;the major components were protein(44.9%),lipids(24.6%),carbohydrates(19.9%),Chlorophyll-A(2.75%),Chlorophyll-B(1.66%),and carotenoids(0.57%).This biomass was diluted with water(5%by weight)and used as a biofertilizer to grow Arabidopsis.The results showed that the average root and stem lengths of Arabidopsis were 43.0%and 55.0%longer compared to those of the control group.Additionally,the number of leaves and the maximum leaf length increased by 30.2%and 39.7%;and the fresh and dry leaf weights increased by 44.0%and 33.7%,respectively.These results demonstrate the efficacy of this system for treating swine farm wastewater whilst simultaneously producing a value-added microalgae/bacteria biomass.This paper also demonstrated the use of biomass as a fertilizer for cultivating a value-added crop and,based on the compositional analyses,propose that the biomass could be used as a raw material for biofuel production due to its high lipid content of 24.6%.By constructing a microalgae/bacteria symbiosis sys
基金the National Natural Science Foundation of China(32171526,32201267)Natural Science Foundation of Anhui Province(2208085QC71)the Key University Science Research Project of Anhui Province(KJ2020A0085,KJ2021A0128).
文摘Native animals are facing long-term coexistence with invasive plants worldwide,the impacts of which on animal behavior remain poorly known.Potential ecological traps could threaten native birds breeding in invasive plant habitats,but behavioral strategies for birds to avoid such risks are few concerned.The invasion of Smooth Cordgrass(Spartina alterniflra) has seriously varied the vegetation landscape in the coastal wetlands of eastern China,and affected the habitat selection of native birds.Here,we investigated the nesting and breeding characteristics of a common native passerine,the Vinous-throated Parrotbill(Sinosuthora webbiana),in habitats dominated by native Common Reed(Phragmites australis) and exotic cordgrass.We found that parrotbills could complete their breeding cycle in cordgrass habitat.Most nest failure was attributed to predation in native habitat but tide inundation in cordgrass habitat.However,the nest success rate and daily survival rate(DSR) in cordgrass habitat were higher.Moreover,nest height was markedly higher in cordgrass habitat and was the most important influencing variable(positively correlated with the DSR).These results suggest that cordgrass habitat is a potential ecological trap due to the tide inundation,but some parrotbills seem to effectively avoid this risk by increasing nest height.Our study reveals that a native passerine changes its nesting behavior to accommodate invasive plant habitat and highlights that habitat changes caused by invasive plants may drive the adaptive evolution of native animal behavior.The limitation of these results must be acknowledged for the small sample size,and there is a need for a larger sample and long-term data for further verification.
基金This work was supported by the National Natural Science Foundation of China(81970320 and 82003749).
文摘Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 sign
基金supported by the National Major Scientific and Technological Special Project(Nos.2018ZX09201002,2018ZX09711001-011 and 2019ZX09201001)the National Natural Science Foundation of China(No.81773375)
文摘Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics(PD)and pharmacokinetics(PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structureeactivity relationship study,inhibited the proliferation of vascular endothelial cells(ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patientderived tumor xenograft(PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles.In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.
基金ACKNOWLEDGEMENTS We thank scientists at SSRF BL17U beam line for assistance in diffraction data collection. This work was supported by the National Natural Science Foundation of China （Grant Nos. 31470751 and U1405228 to Xinquan Wang） and the Beijing Advanced Innovation Center for Structural Biology. This work was also supported, in part, by the Major Intemational Joint Research Project of National Natural Science Foundation of China （81420108028）, and Changjiang Scholars and Innovative Research Teams in Universities Grant （IRT_I 5R15）.
文摘The a3＊ nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The α-conotoxin （α-CTx） LvlA has been identified as the most selective inhibitor of α3β2 nAChRs known to date, and it can distinguish the α3132 nAChR subtype from the α6/α3β2β3 and α3β4 nAChR subtypes. However, the mechanism of its selectivity towards α3132, α6/α3β2β3, and α3β4 nAChRs remains elusive. Here we report the co-crystal structure of LvlA in complex with Aplysia californica acetylcholine binding protein （Ac-AChBP） at a resolution of 3.4 A. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvlA plays an important role in the selectivity of LvlA towards α3132 and α31o6132133 nAChRs by making a salt bridge with Lys-155 of the rat α3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat β2 subunit in the α3β2 nAChR model, revealing the reason for its more potent selectivity towards the a3β2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target α3β2 nAChRs, with significant implications for the design of new therapeutic a-CTxs.
基金This work was sponsored by National Key Research and Development Project of China(Grant No.2018YFC1106800)National Nature Science Foundation of China(Grant Nos 32071352 and 81860392)+2 种基金Sichuan Province Scientific and Technological Achievements Transformation and Guidance Project(Grant No.2016CZYD0004)Sichuan Province Key R&D Program(Grant No.2019YFS0007)Sichuan University Innovation Spark Project(Grant No.2018SCUH0089).
文摘Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes as well as the inconvenient form of usage.To overcome these shortcomings,freeze-dried PRP(LyPRP)was encapsulated into bioactive Col I hydrogel to induce osteogenic dif-ferentiation of rabbit bone marrow mesenchymal stem cells(rBMSCs).And PRP/Col I composite hydrogel was prepared as a control.Compared with Col I hydrogel,the introduction of platelets significantly improved the mechanical properties of hydrogels.Meanwhile,platelets were evenly distributed in the composite hydrogels network.The sustainable release of related factors in the composite hydrogels could last for more than 14days to maintain its long-term biological activity.Further cell experiments confirmed that PRP and LyPRP could effectively alleviate the contraction of collagen hydrogel in vitro,and promote the adhesion,proliferation and osteogenesis differentia-tion of rBMSCs.The results of osteogenic gene expression indicated that the 10%LyPRP/Col I composite hydrogel could facilitate the early expression of BMP-2 and late osteogenic associated protein formation with higher expression of alkaline phosphatase and Osteocalcin(OCN).These results might provide new insights for the clinical application of 10%LyPRP/Col I composite hydro-gel as practical bone repair injection.
基金the High Performance Computing Centre of Shanghai University and Shanghai Engineering Research Centre of Intelligent Computing System(No.19DZ2252600)for providing the computing resources and technical support.the TBT Program(19TBT018)the TBT Program(20TBT010)of Shanghai Industry and Commerce Administration Bureau.
文摘The electrical and thermal characteristics of metal oxide varistor(MOV)are essential for the study of MOV performance and degradation.This paper provides a modelling method of MOV to simulate its microstructure geometry with the Voronoi network and derive the electrical functions on the grain boundaries.A series of discrete data to describe the resistance-voltage(R-V)characteristics of MOV from experiments is applied to the pro-posed model.Through 8/20μs surge current experiments,the electrical conductivity of MOV is determined to achieve the simulation of the clamping voltage.With this model,the current distribution and temperature distribution over a MOV sample are simulated and analysed by the finite element method(FEM).The simulation results show good agreement with the experimental measurement and inherent feature of MOV.
基金Under the auspices of National Natural Science Foundation of China(No.41101080)Shandong Natural Science Foundation of China(No.ZR2014DQ028,ZR2015DM004)
文摘Estuarial saline wetlands have been recognized as a vital role in CO_2 cycling.However,insufficient attention has been paid to estimating CO_2 fluxes from estuarial saline wetlands.In this study,the static chamber-gas chromatography(GC) method was used to quantify CO_2 budget of an estuarial saline reed(Phragmites australis) wetland in Jiaozhou Bay in Qingdao City of Shandong Province,China during the reed growing season(May to October) in 2014.The CO_2 budget study involved net ecosystem CO_2 exchange(NEE),ecosystem respiration(Reco) and gross primary production(GPP).Temporal variation in CO_2 budget and the impact of air/soil temperature,illumination intensity and aboveground biomass exerted on CO_2 budget were analyzed.Results indicated that the wetland was acting as a net sink of 1129.16 g/m^2 during the entire growing season.Moreover,the values of Reco and GPP were 1744.89 g/m^2 and 2874.05 g/m^2,respectively;the ratio of Reco and GPP was 0.61.Diurnal and monthly patterns of CO_2 budget varied significantly during the study period.Reco showed exponential relationships with air temperature and soil temperature at 5 cm,10 cm,20 cm depths,and soil temperature at 5 cm depth was the most crucial influence factor among them.Meanwhile,temperature sensitivity(Q10) of Reco was negatively correlated with soil temperature.Light and temperature exerted strong controls over NEE and GPP.Aboveground biomass over the whole growing season showed non-linear relationships with CO_2 budget,while those during the early and peak growing season showed significant linear relationships with CO_2 budget.This research provides valuable reference for CO_2 exchange in estuarial saline wetland ecosystem.
基金The National Natural Science Foundation of China,Grant/Award Numbers:52175437,12032018Young Talents Support Project of Shaanxi Province,Grant/Award Number:20190404+5 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:31020210506003Natural Science Foundation of Shannxi Province,Grant/Award Number:2021JM‐043supported by the National Natural Science Foundation of China(Nos.52175437 and 12032018)the Young Talents Support Project of Shaanxi Province(No.20190404)the Fundamental Research Funds for the Central Universities(No.31020210506003)the Project supported by the Natural Science Foundation of Shannxi Province(No.2021JM‐043).
文摘Since the dynamics of thin‐walled structures instantaneously varies during the milling process,accurate and efficient prediction of the in‐process workpiece(IPW)dynamics is critical for the prediction of chatter stability of milling of thin‐walled structures.This article presents a surrogate model of the IPW dynamics of thin‐walled structures by combining Gaussian process regression(GPR)with proper orthogonal decomposition(POD)when IPW dynamics at a large number of cutting positions has to be predicted.The GPR method is used to learn the mapping between a set of the known IPW dynamics and the corresponding cutting positions.POD is used to reduce the order of the matrix assembled by the mode shape vectors at different cutting positions,before the GPR model of the IPW mode shape is established.The computation time of the proposed model is mainly composed of the time taken for predicting a known set of IPW dynamics and the time taken for training GPR models.Simulation shows that the proposed model requires less computation time.Moreover,the accuracy of the proposed model is comparable to that of the existing methods.Comparison between the predicted stability lobe diagram and the experimental results shows that IPW dynamics predicted by the proposed model is accurate enough for predicting the stability of milling of thin‐walled structures.
基金support from the National Natural Science Foundation of China(21773061,21978095)the Open Research Fund of Shanghai Key Laboratory of Green Chemistry and Chemical Processes。
文摘The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great prospects for replacing fossil energy and attracted attention from the society. The use of catalytic approach to transform biomass into high-value chemicals is an effective way to use biomass efficiently. In this work, Nisupported catalysts has been developed for the selective cleavage of C–O bonds in lignin model compounds with 2-propanol as the hydrogen source solvent. Among these catalysts, it was indicated that zirconium phosphate(Zr P)-supported Ni catalysts were highly efficient and recyclable for alkyl-aryl ether(α-O-4 and β-O-4) cleavage in lignin model compounds. The further investigation demonstrated that the transfer hydrogenolysis of the C–O bond is highly selective, which afforded phenols and aromatics as dominant products without the products arising from hydrogenation of aromatic rings. Through a series of characterization of the catalyst, it was demonstrated that the medium strong acid sites of the Zr P support promoted the cleavage of alkyl-aryl ethers(α-O-4 and β-O-4),and Br?nsted acid sites favored for achieving high selectivity toward C–O bond cleavage. Additionally, Ni(0) sites on the Zr P catalysts were responsible for the catalytic transfer hydrogenolysis.
