Background Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflamm...Background Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflammation. The present study was to ascertain the possible correlations between chronic hepatitis B virus (HBV) infection and the RANTES gene polymorphisms and their expression. Methods The study included 130 HBV negative healthy donors and 152 patients with chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet depleted plasma were detected by enzyme linked immunosorbent assay (ELISA). Results RANTES alleles -403G, -28C and In1.1T were the predominant alleles in the subjects studied. No significant correlation was found between CHB infection and the RANTES alleles, while a significant correlation was found between CHB infection and increased RANTES expression in platelet depleted plasma (P<0.05). Conclusions SNPs in RANTES gene do not affect chronic HBV infection or the outcome of interferon-α treatment in patients positive for HBV “e” antigen (HBeAg+). However, patients with CHB infection express the higher levels of plasma RANTES, which is thus associated with CHB infection.展开更多
Concrete-filled steel tube(CFST)has been widely applied in bridges due to its excellent structural and constructional performance.In CFST bridges,temperature action is not only an important but also a special load tha...Concrete-filled steel tube(CFST)has been widely applied in bridges due to its excellent structural and constructional performance.In CFST bridges,temperature action is not only an important but also a special load that must be considered in bridge design,construction and structural evaluation.This paper presents an overview on current researches of the temperature action and effect of CFST bridges.The historical and spatial characteristics as well as corresponding influencing factors of temperature distributions are summarized,and classifications of temperature actions are also reviewed.Results show that in-depth investigations of the contributions of temperature influencing factors can help to effectively reduce the adverse temperature effects on CFST bridges in the design stage.Due to the lack of long-term measurements and insufficient use of historical meteorological data,research on the representative value along with correlation analysis of CFST temperature actions and meteorological parameters have to be further carried out.In the meanwhile,a decomposition method of temperature distribution is proposed based on structural effects of CFST bridges in this paper.The decomposed temperature actions can be used for more accurate effect calculation than traditional temperature action classification method,especially for CFST truss bridges.At last,specific temperature action patterns still need to be investigated in some of the special problems,such as longitudinal temperature differences along the CFST arch rib and thermal debonding in the CFST interface.Further investigations are required on the accurate simulation of temperature distribution of CFST bridges considering the shading effects of components and terrain.展开更多
Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs,targeted therapeutic drugs have become mainstream cancer treatments.Since the first tyrosine kinase inhibitor imatinib was appr...Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs,targeted therapeutic drugs have become mainstream cancer treatments.Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration(FDA)in 2001,an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies.By December 2020,89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration(NMPA)of China.Despite great progress,small-molecule targeted anti-cancer drugs still face many challenges,such as a low response rate and drug resistance.To better promote the development of targeted anti-cancer drugs,we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification.We present all the approved drugs as well as important drug candidates in clinical trials for each target,discuss the current challenges,and provide insights and perspectives for the research and development of anti-cancer drugs.展开更多
Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect...Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region.Three-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair.Here,we used modified bioinks comprising gelatin,gelatin methacryloyl(GelMA),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds.Moreover,MSNs sustainably released BMP-4 for long-term effectiveness.In 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors.BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds.Furthermore,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment.And 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone repair.In conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.展开更多
The year 2022 featured an unprecedented hot summer that has attracted worldwide attention.Abnormal warming spread over most of the Eurasian continent and North America(Fig.1),with Europe and China especially suffering...The year 2022 featured an unprecedented hot summer that has attracted worldwide attention.Abnormal warming spread over most of the Eurasian continent and North America(Fig.1),with Europe and China especially suffering from extraordinarily long-lasting extreme heat events.In addition,severe droughts,which are a common accompaniment to heat waves,attacked Europe and the Yangtze River basin in China.Droughts in Sichuan Province,which is in the upstream region of the Yangtze River basin and is proud of its water resources and hydro power,led to power shortages and adverse effects on the lives and productivity of local people.Extremely high temperatures and severe drought induced massive wildfires in Europe,North America,and Asia,including Chongqing(Fig.2),a neighboring municipality of Sichuan Province.展开更多
The development of wearable multifunctional electromagnetic protective fabrics with multifunctional,low cost,and high efficiency remains a challenge.Here,inspired by the unique flower branch shape of“Thunberg’s mead...The development of wearable multifunctional electromagnetic protective fabrics with multifunctional,low cost,and high efficiency remains a challenge.Here,inspired by the unique flower branch shape of“Thunberg’s meadowsweet”in nature,a nanofibrous composite membrane with hierarchical structure was constructed.Integrating sophisticated 0D@2D@1D hierarchical structures with multiple heterointerfaces can fully unleash the multifunctional application potential of composite membrane.The targeted induction method was used to precisely regulate the formation site and morphology of the metal–organic framework precursor,and intelligently integrate multiple heterostructures to enhance dielectric polarization,which improves the impedance matching and loss mechanisms of the electromagnetic wave absorbing materials.Due to the synergistic enhancement of electrospinning-derived carbon nanofiber“stems”,MOF-derived carbon nanosheet“petals”and transition metal selenide nano-particle“stamens”,the CoxSey/NiSe@CNSs@CNFs(CNCC)composite membrane obtains a minimum reflection loss value(RL_(min))of-68.40 dB at 2.6 mm and a maximum effective absorption bandwidth(EAB)of 8.88 GHz at a thin thickness of 2.0 mm with a filling amount of only 5 wt%.In addition,the multi-component and hierarchical heterostructure endow the fibrous membrane with excellent flexibility,water resistance,thermal management,and other multifunctional properties.This work provides unique perspectives for the precise design and rational application of multifunctional fabrics.展开更多
Dear Editors, Terahertz technology has been applied in many fields [1-3]. The protection and restoration of historical relics and cul- tural heritage, which is a new application area of terahertz technology, have been...Dear Editors, Terahertz technology has been applied in many fields [1-3]. The protection and restoration of historical relics and cul- tural heritage, which is a new application area of terahertz technology, have been attracting much attention recently [4,5] because of its social significance and market prospects The most important premise is to obtain information of the cultural relics without damaging them again. Therefore the appropriate non-destructively testing methods are urgently needed in this area. Terahertz （THz） wave bridges the gap between microwave and infrared waves.展开更多
A tiny ultrasonic motor was constructed by using a piezoelectric ceramic cylindrical rod as a vibration generator of the stator. The fabricated tiny motor has a di- ameter of 1 mm, a length of 5 mm and a weight of 36 ...A tiny ultrasonic motor was constructed by using a piezoelectric ceramic cylindrical rod as a vibration generator of the stator. The fabricated tiny motor has a di- ameter of 1 mm, a length of 5 mm and a weight of 36 mg. The resonant frequency is 32 kHz with one fixed boundary or 83 kHz with two free boundaries. Four silver electrodes were deposited on the cylindrical surface. The spacing be- tween two adjacent electrodes was carefully designed. A method was developed for the polarization of the stator. By using the bending vibration mode of the stator, the motor shows a performance with a speed of 1800 rpm and a stalled torque of 4 μ Nm, and can bear a high driving voltage up to 350 Vpp. The motor was used to drive an optical prism for circular scanning in an endoscopic OCT system. The tomo- graphic images of the inner cavities of a plastic tube and a scallion were obtained, and the resolution was of the order of micrometer-scale.展开更多
Background: Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mo...Background: Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.Methods: FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.Results: FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.Conclusions: Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, di展开更多
In this paper,the structure evolution of cerium cobaltohexanoate(Ce[Co(CN)6],Ce-Co Prussian blue analog(PBA))has been realized by solvent catalysis at room temperature.The hexagonal bipyramidal microcrystals of Ce-Co ...In this paper,the structure evolution of cerium cobaltohexanoate(Ce[Co(CN)6],Ce-Co Prussian blue analog(PBA))has been realized by solvent catalysis at room temperature.The hexagonal bipyramidal microcrystals of Ce-Co PBA can be gradually transformed into dendrites by different proportions of ethanol(EtOH)and water.At the same time,the porous dendrites CeO_(2)/Co@carbon nanotub(CNT)with oxygen-rich vacancies(OVs)can be obtained by annealing Ce-Co PBA at 700℃.The microstructure study shows that carbon nanotubes will be catalyzed after annealing at high temperature,and the cobalt metal particles encapsulated in carbon nanotubes will be anchored in the matrix,regulating the impedance matching and multi-polarization suppression of the material,and its unique structure,vacancies,and strong interface effect make the material exhibit excellent electromagnetic wave(EMW)absorption performance.When the matching thickness is 2.5 mm,the minimum reflection loss(RLmin)of the composite is-51.68 dB,and the effective absorption bandwidth(RL<-10 dB)is 7.76 GHz.These results show that the prepared CeO_(2)/Co@CNT composite has excellent EMW absorption properties.It is expected to be a candidate material for EMW absorption.展开更多
The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the de...The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.展开更多
To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of A...To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal(PT)conversion efficiency,remarkable photoacoustic(PA)imaging and high computed tomography(CT)performance;these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging.Subsequently,poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs(Au@Bi2S3-PVP NBs)were successfully loaded with the anticancer drug doxorubicin(DOX),and a satisfactory pH sensitive release profile was achieved,thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells.Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy,including extremely low toxicity,good biocompatibility,high drug loading ability,precise tumor targeting and effective accumulation.Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy(PTT).As both a contrast enhancement probe and therapeutic agent,Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.展开更多
Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too ...Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too late for effective therapy.The tRNA-derived small RNAs(tsRNAs)play vital roles in tumorigenesis and are stable in circulation.However,the diagnostic values and biological functions of circulating tsRNAs,especially for HCC,are still unknown.In this study,we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum.We identified tRF-Gln-TTG-006,which was remarkably upregulated in HCC serum(training cohort:24 HCC patients vs.24 healthy controls).In the validation stage,we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity(80.4%)and specificity(79.4%)even in the early stage(Stage I:sensitivity,79.0%;specificity,74.8%;155 healthy controls vs.153 HCC patients from two cohorts).Moreover,in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells,and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays.In summary,our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.展开更多
We use the share pledge context in China to examine how affiliated analysts whose securities companies are pledgees of share pledge firms issue stock recommendations on these listed firms.We find that their recommenda...We use the share pledge context in China to examine how affiliated analysts whose securities companies are pledgees of share pledge firms issue stock recommendations on these listed firms.We find that their recommendations are more optimistic than those of non-affiliated analysts,and they are more likely to issue Buy and Add recommendations,suggesting that they issue optimistic rating reports for share pledge firms due to their conflicts of interest.We also find a dynamic adjustment in the stock recommendation behavior of these analysts,and their probability after issuing optimistic stock recommendations is significantly reduced before and after the years that the affiliation relationship between them and share pledge firms both began and ended.These affiliated analysts continue to issue optimistic stock recommendations after visiting the share pledge firms if they work in the same location as the firms,or if they are star analysts among New Fortune’s‘‘top five analysts,"and when the information transparency of the share pledge firms is higher.In addition,the optimistic stock recommendation behavior of affiliated analysts is more significant in our sample of firms with high share pledge ratios and downward stock price pressure.The earnings forecast quality of affiliated analysts is also found to be lower,and they are less inclined to downgrade stock recommendations for these share pledge firms.Buy recommendations issued by both nonaffiliated and affiliated analysts can bring cumulative excess returns in the short event window,but those issued by affiliated analysts are significantly negative in the long-term event window,and significantly lower than those issued by non-affiliated analysts.Overall,our study shows that affiliated analysts issue optimistic rating reports on share pledge firms due to conflicts of interest,which leads to decision-making bias in investors and thus decreases the stock price crash risk of the firms.Our findings further reveal the economic consequences of share pledging and extend o展开更多
We conducted rapid inversions of rupture process for the 2023 earthquake doublet occurred in SE Türkiye,the first with a magnitude of M_(W)7.8 and the second with a magnitude of M_(W)7.6,using teleseismic and str...We conducted rapid inversions of rupture process for the 2023 earthquake doublet occurred in SE Türkiye,the first with a magnitude of M_(W)7.8 and the second with a magnitude of M_(W)7.6,using teleseismic and strong-motion data.The teleseismic rupture models of the both events were obtained approximately 88 and 55 minutes after their occurrences,respectively.The rupture models indicated that the first event was an asymmetric bilateral event with ruptures mainly propagating to the northeast,while the second one was a unilateral event with ruptures propagating to the west.This information could be useful in locating the meizoseismal areas.Compared with teleseismic models,the strong-motion models showed relatively higher resolution.A noticeable difference was found for the M_(W)7.6 earthquake,for which the strong-motion models shows a bilateral event,rather than a unilateral event,but the dominant rupture direction is still westward.Nevertheless,all strong-motion models are consistent with the teleseismic models in terms of magnitudes,durations,and dominant rupture directions.This suggests that both teleseismic and strong-motion data can be used for fast determination of major source characteristics.In contrast,the strong-motion data would be preferable in future emergency responses since they are recorded earlier and have a better resolution ability on the source ruptures.展开更多
High-temperature stress threatens the growth and yield of crops. Basic helix-loop-helix(bHLH) transcription factors(TFs) have been shown to play important roles in regulating high-temperature resistance in plants. How...High-temperature stress threatens the growth and yield of crops. Basic helix-loop-helix(bHLH) transcription factors(TFs) have been shown to play important roles in regulating high-temperature resistance in plants. However, the bHLH TFs responsible for high-temperature tolerance in cucumbers have not been identified. We used transcriptome profiling to screen the high temperature-responsive candidate bHLH TFs in cucumber. Here, we found that the expression of 75 CsbHLH genes was altered under high-temperature stress. The expression of the CsSPT gene was induced by high temperatures in TT(Thermotolerant) cucumber plants. However, the Csspt mutant plants obtained by the CRISPR-Cas9 system showed severe thermosensitive symptoms, including wilted leaves with brown margins and reduced root density and cell activity.The Csspt mutant plants also exhibited elevated H_(2)O_(2) levels and down-regulated photosystem-related genes under normal conditions.Furthermore, there were high relative electrolytic leakage(REC), malondialdehyde(MDA), glutathione(GSH), and superoxide radical(O_(2)^(·-)) levels in the Csspt mutant plants, with decreased Proline content after the high-temperature treatment. Transcriptome analysis showed that the photosystem and chloroplast activities in Csspt mutant plants were extremely disrupted by the high-temperature stress compared with wildtype(WT) plants. Moreover, the plant hormone signal transduction, as well as MAPK and calcium signaling pathways were activated in Csspt mutant plants under high-temperature stress. The HSF and HSP family genes shared the same upregulated expression patterns in Csspt and WT plants under high-temperature conditions. However, most bHLH, NAC, and bZIP family genes were significantly down-regulated by heat in Csspt mutant plants. Thus, these results demonstrated that CsSPT regulated the high-temperature response by recruiting photosynthesis components, signaling pathway molecules, and transcription factors. Our results provide important insights into the heat response 展开更多
Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-deri...Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.展开更多
文摘Background Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflammation. The present study was to ascertain the possible correlations between chronic hepatitis B virus (HBV) infection and the RANTES gene polymorphisms and their expression. Methods The study included 130 HBV negative healthy donors and 152 patients with chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet depleted plasma were detected by enzyme linked immunosorbent assay (ELISA). Results RANTES alleles -403G, -28C and In1.1T were the predominant alleles in the subjects studied. No significant correlation was found between CHB infection and the RANTES alleles, while a significant correlation was found between CHB infection and increased RANTES expression in platelet depleted plasma (P<0.05). Conclusions SNPs in RANTES gene do not affect chronic HBV infection or the outcome of interferon-α treatment in patients positive for HBV “e” antigen (HBeAg+). However, patients with CHB infection express the higher levels of plasma RANTES, which is thus associated with CHB infection.
基金funded by the National Natural Science Foundation of China (51978061)the Special Fund for Basic Scientific Research of Central College of Chang’an University (300 102 219 310).
文摘Concrete-filled steel tube(CFST)has been widely applied in bridges due to its excellent structural and constructional performance.In CFST bridges,temperature action is not only an important but also a special load that must be considered in bridge design,construction and structural evaluation.This paper presents an overview on current researches of the temperature action and effect of CFST bridges.The historical and spatial characteristics as well as corresponding influencing factors of temperature distributions are summarized,and classifications of temperature actions are also reviewed.Results show that in-depth investigations of the contributions of temperature influencing factors can help to effectively reduce the adverse temperature effects on CFST bridges in the design stage.Due to the lack of long-term measurements and insufficient use of historical meteorological data,research on the representative value along with correlation analysis of CFST temperature actions and meteorological parameters have to be further carried out.In the meanwhile,a decomposition method of temperature distribution is proposed based on structural effects of CFST bridges in this paper.The decomposed temperature actions can be used for more accurate effect calculation than traditional temperature action classification method,especially for CFST truss bridges.At last,specific temperature action patterns still need to be investigated in some of the special problems,such as longitudinal temperature differences along the CFST arch rib and thermal debonding in the CFST interface.Further investigations are required on the accurate simulation of temperature distribution of CFST bridges considering the shading effects of components and terrain.
基金supported by the National Natural Science Foundation of China(81930125,81702286,81773633,and 21772130)the Research Project of Science and Technology Department of Sichuan Province(2021YJ0134,2019YFS0514,and 2020YFS0006)+2 种基金the 1.3.5 project for disciplines of excellence.West China Hospital,Sichuan University(ZYGD18001)partially by the fast-track grants from West China Hospital,Sichuan University(HX-2019-nCoV-053)the Open Project of Radiation Oncology Key Laboratory of Sichuan Province(2020FSZLX04).
文摘Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs,targeted therapeutic drugs have become mainstream cancer treatments.Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration(FDA)in 2001,an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies.By December 2020,89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration(NMPA)of China.Despite great progress,small-molecule targeted anti-cancer drugs still face many challenges,such as a low response rate and drug resistance.To better promote the development of targeted anti-cancer drugs,we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification.We present all the approved drugs as well as important drug candidates in clinical trials for each target,discuss the current challenges,and provide insights and perspectives for the research and development of anti-cancer drugs.
基金supported by National Key R&D Program of China(2018YFB1105600/2018YFC2002300/2018YFA0703000)National Natural Science Foundation of China(81772326/81702124/81902195)+3 种基金Fundamental research program funding of Ninth People's Hospital affiliated to Shanghai JiaoTong University School of Medicine(JYZZ070)Project of Shanghai Science and Technology Commission(18441903700/19XD1434200/18431903700/19441908700/19441917500)Translational Medicine Innovation Project of Shanghai Jiao Tong University School of Medicine(TM201613/TM201915)Project of Shanghai Jiading National Health and Family Planning Commission(KYXM 2018-KY-03).
文摘Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region.Three-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair.Here,we used modified bioinks comprising gelatin,gelatin methacryloyl(GelMA),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds.Moreover,MSNs sustainably released BMP-4 for long-term effectiveness.In 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors.BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds.Furthermore,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment.And 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone repair.In conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(STEP)program[grant number 2019QZKK0102].
文摘The year 2022 featured an unprecedented hot summer that has attracted worldwide attention.Abnormal warming spread over most of the Eurasian continent and North America(Fig.1),with Europe and China especially suffering from extraordinarily long-lasting extreme heat events.In addition,severe droughts,which are a common accompaniment to heat waves,attacked Europe and the Yangtze River basin in China.Droughts in Sichuan Province,which is in the upstream region of the Yangtze River basin and is proud of its water resources and hydro power,led to power shortages and adverse effects on the lives and productivity of local people.Extremely high temperatures and severe drought induced massive wildfires in Europe,North America,and Asia,including Chongqing(Fig.2),a neighboring municipality of Sichuan Province.
基金supported by the National Natural Science Foundation of China(No.51407134,No.52002196)Natural Science Foundation of Shandong Province(No.ZR2019YQ24,No.ZR2020QF084)+2 种基金Taishan Scholars and Young Experts Program of Shandong Province(No.tsqn202103057)the Qingchuang Talents Induction Program of Shandong Higher Education Institution(Research and Innovation Team of Structural-Functional Polymer Composites)Special Financial of Shandong Province(Structural Design of Highefficiency Electromagnetic Wave-absorbing Composite Materials and Construction of Shandong Provincial Talent Teams(No.37000022P990304116449)).
文摘The development of wearable multifunctional electromagnetic protective fabrics with multifunctional,low cost,and high efficiency remains a challenge.Here,inspired by the unique flower branch shape of“Thunberg’s meadowsweet”in nature,a nanofibrous composite membrane with hierarchical structure was constructed.Integrating sophisticated 0D@2D@1D hierarchical structures with multiple heterointerfaces can fully unleash the multifunctional application potential of composite membrane.The targeted induction method was used to precisely regulate the formation site and morphology of the metal–organic framework precursor,and intelligently integrate multiple heterostructures to enhance dielectric polarization,which improves the impedance matching and loss mechanisms of the electromagnetic wave absorbing materials.Due to the synergistic enhancement of electrospinning-derived carbon nanofiber“stems”,MOF-derived carbon nanosheet“petals”and transition metal selenide nano-particle“stamens”,the CoxSey/NiSe@CNSs@CNFs(CNCC)composite membrane obtains a minimum reflection loss value(RL_(min))of-68.40 dB at 2.6 mm and a maximum effective absorption bandwidth(EAB)of 8.88 GHz at a thin thickness of 2.0 mm with a filling amount of only 5 wt%.In addition,the multi-component and hierarchical heterostructure endow the fibrous membrane with excellent flexibility,water resistance,thermal management,and other multifunctional properties.This work provides unique perspectives for the precise design and rational application of multifunctional fabrics.
基金supported by the National Natural Science Foundation of China(Grant Nos.11204191 and 11574408)the National Instrumentation Program(Grant No.2012YQ140005)Beijing Science and Technology Project(Grant No.D151100006015002)
文摘Dear Editors, Terahertz technology has been applied in many fields [1-3]. The protection and restoration of historical relics and cul- tural heritage, which is a new application area of terahertz technology, have been attracting much attention recently [4,5] because of its social significance and market prospects The most important premise is to obtain information of the cultural relics without damaging them again. Therefore the appropriate non-destructively testing methods are urgently needed in this area. Terahertz （THz） wave bridges the gap between microwave and infrared waves.
基金supported by the National Natural Science Foundation of China(Grant No.50235010)973 Project(No.001CB510307)the National Science Foundation of Beijing(3012007)the Technology Foundation of Shenzhen.
文摘A tiny ultrasonic motor was constructed by using a piezoelectric ceramic cylindrical rod as a vibration generator of the stator. The fabricated tiny motor has a di- ameter of 1 mm, a length of 5 mm and a weight of 36 mg. The resonant frequency is 32 kHz with one fixed boundary or 83 kHz with two free boundaries. Four silver electrodes were deposited on the cylindrical surface. The spacing be- tween two adjacent electrodes was carefully designed. A method was developed for the polarization of the stator. By using the bending vibration mode of the stator, the motor shows a performance with a speed of 1800 rpm and a stalled torque of 4 μ Nm, and can bear a high driving voltage up to 350 Vpp. The motor was used to drive an optical prism for circular scanning in an endoscopic OCT system. The tomo- graphic images of the inner cavities of a plastic tube and a scallion were obtained, and the resolution was of the order of micrometer-scale.
基金This work was supported by grants from the Natural Science Foundation of Beijing Municipality(No.7202169)the Beijing Nova Program of Science and Technology(No.Z191100001119065)the CAMS Innovation Fund for Medical Sciences(No.2017-I2M-1-006)。
文摘Background: Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.Methods: FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.Results: FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.Conclusions: Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, di
基金supported by the National Natural Science Foundation of China(Nos.52377026 and 52301192)the Natural Science Foundation of Shandong Province(Nos.ZR2019YQ24 and ZR2020QF084)+2 种基金the Taishan Scholars and Young Experts Program of Shandong Province(No.tsqn202103057)the Qingchuang Talents Induction Program of Shandong Higher Education Institution(Research and Innovation Team of Structural-Functional Polymer Composites)the Special Financial of Shandong Province(Structural Design of High-efficiency Electromagnetic Wave-absorbing Composite Materials and Construction of Shandong Provincial Talent Teams).
文摘In this paper,the structure evolution of cerium cobaltohexanoate(Ce[Co(CN)6],Ce-Co Prussian blue analog(PBA))has been realized by solvent catalysis at room temperature.The hexagonal bipyramidal microcrystals of Ce-Co PBA can be gradually transformed into dendrites by different proportions of ethanol(EtOH)and water.At the same time,the porous dendrites CeO_(2)/Co@carbon nanotub(CNT)with oxygen-rich vacancies(OVs)can be obtained by annealing Ce-Co PBA at 700℃.The microstructure study shows that carbon nanotubes will be catalyzed after annealing at high temperature,and the cobalt metal particles encapsulated in carbon nanotubes will be anchored in the matrix,regulating the impedance matching and multi-polarization suppression of the material,and its unique structure,vacancies,and strong interface effect make the material exhibit excellent electromagnetic wave(EMW)absorption performance.When the matching thickness is 2.5 mm,the minimum reflection loss(RLmin)of the composite is-51.68 dB,and the effective absorption bandwidth(RL<-10 dB)is 7.76 GHz.These results show that the prepared CeO_(2)/Co@CNT composite has excellent EMW absorption properties.It is expected to be a candidate material for EMW absorption.
文摘The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.
基金This work was financially supported by the Natural Science Foundation of Shanghai(19ZR1434800,19ZR1461900)the National Natural Science Foundation of China(21305090)+1 种基金the Fundamental Research Funds for the Central Universities(to Shuang Zhou)The authors greatly appreciated these supports.
文摘To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal(PT)conversion efficiency,remarkable photoacoustic(PA)imaging and high computed tomography(CT)performance;these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging.Subsequently,poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs(Au@Bi2S3-PVP NBs)were successfully loaded with the anticancer drug doxorubicin(DOX),and a satisfactory pH sensitive release profile was achieved,thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells.Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy,including extremely low toxicity,good biocompatibility,high drug loading ability,precise tumor targeting and effective accumulation.Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy(PTT).As both a contrast enhancement probe and therapeutic agent,Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.
基金This study was supported by the Training Program of the Major Research Plan of the National Natural Science Foundation of China(No.92049109)the National Natural Science Foundation of China(Nos.32000549 and 82003024)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK2020041989)the Natural Science Foundation of Nanjing University of Chinese Medicine(No.NZY82003024).
文摘Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too late for effective therapy.The tRNA-derived small RNAs(tsRNAs)play vital roles in tumorigenesis and are stable in circulation.However,the diagnostic values and biological functions of circulating tsRNAs,especially for HCC,are still unknown.In this study,we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum.We identified tRF-Gln-TTG-006,which was remarkably upregulated in HCC serum(training cohort:24 HCC patients vs.24 healthy controls).In the validation stage,we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity(80.4%)and specificity(79.4%)even in the early stage(Stage I:sensitivity,79.0%;specificity,74.8%;155 healthy controls vs.153 HCC patients from two cohorts).Moreover,in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells,and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays.In summary,our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.
基金financial support from the National Natural Science Foundation of China(No.71902006,71790604)Scientific Research Program of Beijing Municipal Education Commission(No.SM202010011007).
文摘We use the share pledge context in China to examine how affiliated analysts whose securities companies are pledgees of share pledge firms issue stock recommendations on these listed firms.We find that their recommendations are more optimistic than those of non-affiliated analysts,and they are more likely to issue Buy and Add recommendations,suggesting that they issue optimistic rating reports for share pledge firms due to their conflicts of interest.We also find a dynamic adjustment in the stock recommendation behavior of these analysts,and their probability after issuing optimistic stock recommendations is significantly reduced before and after the years that the affiliation relationship between them and share pledge firms both began and ended.These affiliated analysts continue to issue optimistic stock recommendations after visiting the share pledge firms if they work in the same location as the firms,or if they are star analysts among New Fortune’s‘‘top five analysts,"and when the information transparency of the share pledge firms is higher.In addition,the optimistic stock recommendation behavior of affiliated analysts is more significant in our sample of firms with high share pledge ratios and downward stock price pressure.The earnings forecast quality of affiliated analysts is also found to be lower,and they are less inclined to downgrade stock recommendations for these share pledge firms.Buy recommendations issued by both nonaffiliated and affiliated analysts can bring cumulative excess returns in the short event window,but those issued by affiliated analysts are significantly negative in the long-term event window,and significantly lower than those issued by non-affiliated analysts.Overall,our study shows that affiliated analysts issue optimistic rating reports on share pledge firms due to conflicts of interest,which leads to decision-making bias in investors and thus decreases the stock price crash risk of the firms.Our findings further reveal the economic consequences of share pledging and extend o
基金supported by the National Key Research and Development Program of China(2022YFF0800603).
文摘We conducted rapid inversions of rupture process for the 2023 earthquake doublet occurred in SE Türkiye,the first with a magnitude of M_(W)7.8 and the second with a magnitude of M_(W)7.6,using teleseismic and strong-motion data.The teleseismic rupture models of the both events were obtained approximately 88 and 55 minutes after their occurrences,respectively.The rupture models indicated that the first event was an asymmetric bilateral event with ruptures mainly propagating to the northeast,while the second one was a unilateral event with ruptures propagating to the west.This information could be useful in locating the meizoseismal areas.Compared with teleseismic models,the strong-motion models showed relatively higher resolution.A noticeable difference was found for the M_(W)7.6 earthquake,for which the strong-motion models shows a bilateral event,rather than a unilateral event,but the dominant rupture direction is still westward.Nevertheless,all strong-motion models are consistent with the teleseismic models in terms of magnitudes,durations,and dominant rupture directions.This suggests that both teleseismic and strong-motion data can be used for fast determination of major source characteristics.In contrast,the strong-motion data would be preferable in future emergency responses since they are recorded earlier and have a better resolution ability on the source ruptures.
基金supported by grants from the Key Project of Guangzhou (Grant No.202103000085)National Natural Science Foundation of China (Grant No.31902014)+1 种基金Guangzhou Science and Technology Project (Grant No.202102020502)Fruit and Vegetable Industry System Innovation Team Project of Guangdong (Grant No.2021KJ110)。
文摘High-temperature stress threatens the growth and yield of crops. Basic helix-loop-helix(bHLH) transcription factors(TFs) have been shown to play important roles in regulating high-temperature resistance in plants. However, the bHLH TFs responsible for high-temperature tolerance in cucumbers have not been identified. We used transcriptome profiling to screen the high temperature-responsive candidate bHLH TFs in cucumber. Here, we found that the expression of 75 CsbHLH genes was altered under high-temperature stress. The expression of the CsSPT gene was induced by high temperatures in TT(Thermotolerant) cucumber plants. However, the Csspt mutant plants obtained by the CRISPR-Cas9 system showed severe thermosensitive symptoms, including wilted leaves with brown margins and reduced root density and cell activity.The Csspt mutant plants also exhibited elevated H_(2)O_(2) levels and down-regulated photosystem-related genes under normal conditions.Furthermore, there were high relative electrolytic leakage(REC), malondialdehyde(MDA), glutathione(GSH), and superoxide radical(O_(2)^(·-)) levels in the Csspt mutant plants, with decreased Proline content after the high-temperature treatment. Transcriptome analysis showed that the photosystem and chloroplast activities in Csspt mutant plants were extremely disrupted by the high-temperature stress compared with wildtype(WT) plants. Moreover, the plant hormone signal transduction, as well as MAPK and calcium signaling pathways were activated in Csspt mutant plants under high-temperature stress. The HSF and HSP family genes shared the same upregulated expression patterns in Csspt and WT plants under high-temperature conditions. However, most bHLH, NAC, and bZIP family genes were significantly down-regulated by heat in Csspt mutant plants. Thus, these results demonstrated that CsSPT regulated the high-temperature response by recruiting photosynthesis components, signaling pathway molecules, and transcription factors. Our results provide important insights into the heat response
基金This work was supported by the National Nature Science Foundation of China grant 82170978(to K.J.)the Distinguished Young Scientists Funds of Shannxi Province 2021JC-34(to K.J.).
文摘Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.
