Since triple-negative breast cancer(TNBC)was first defined over a decade ago,increasing studies have focused on its genetic and molecular characteristics.Patients diagnosed with TNBC,compared to those diagnosed with o...Since triple-negative breast cancer(TNBC)was first defined over a decade ago,increasing studies have focused on its genetic and molecular characteristics.Patients diagnosed with TNBC,compared to those diagnosed with other breast cancer subtypes,have relatively poor outcomes due to high tumor aggressiveness and lack of targeted treatment.Metabolic reprogramming,an emerging hallmark of cancer,is hijacked by TNBC to fulfill bioenergetic and biosynthetic demands;maintain the redox balance;and further promote oncogenic signaling,cell proliferation,and metastasis.Understanding the mechanisms of metabolic remodeling may guide the design of metabolic strategies for the effective intervention of TNBC.Here,we review the metabolic reprogramming of glycolysis,oxidative phosphorylation,amino acid metabolism,lipid metabolism,and other branched pathways in TNBC and explore opportunities for new biomarkers,imaging modalities,and metabolically targeted therapies.展开更多
Importance:Post-intubation subglottic stenosis(SGS)in children can be life threatening.Definitive treatment varies and lacks a universally accepted approach.Objective:We performed a prospective study to assess the saf...Importance:Post-intubation subglottic stenosis(SGS)in children can be life threatening.Definitive treatment varies and lacks a universally accepted approach.Objective:We performed a prospective study to assess the safety and feasibility of holmium laser combined with cryotherapy delivered via flexible bronchoscopy for the treatment of post-intubation SGS in children.Methods:This study involved all patients with post-intubation SGS seen at the Interventional Pulmonology Department of Beijing Children's Hospital between July 2014 and December 2016.Holmium laser treatment and cryotherapy was then performed under flexible bronchoscopy,whose parents refused to accept the alternative standard treatment of tracheotomy and balloon dilation under direct laryngoscopy.results:Sixteen patients with post-intubation SGS were included in this study.Ages ranged from 2 months to 12.25 years old.According to the Cotton-Myer grading system,three cases were Grade II,12 cases were Grade III,and one case was Grade IV.According to the McCaffrey system,eight cases were Stage 1,two cases were Stage 2,and six cases were Stage 3.The average number of procedures was 4.88.Fifteen of the 16 patients achieved clinical cure.One patient achieved clinical improvement.The average treatment course duration was 55.31 days.No severe complications were seen.Post-treatment clinical symptoms,endoscopic findings and quality of life showed marked improvement.Interpretation:Our study supports the conclusion that holmium laser treatment combined with cryotherapy via flexible bronchoscopy appears to be a safe and feasible treatment for post-intubation SGS in children.展开更多
The pitch-angle distribution of energetic particles is important for space physics studies on magnetic storm and particle acceleration.A‘pin-hole’imaging structure is built with the‘pin-hole’technique and a positi...The pitch-angle distribution of energetic particles is important for space physics studies on magnetic storm and particle acceleration.A‘pin-hole’imaging structure is built with the‘pin-hole’technique and a position sensitive detector,which can be used to measure the pitch angle distribution of energetic particles.To calibrate the angular response of the‘pin-hole’imaging structure,special experiment facilities are needed,such as the particle accelerator with special design.The features of this kind of particle accelerator are:1)The energy range of the outgoing particles should be mid-energy particles(tens keV to several hundred keV);2)the particle flux should be consistent in time-scale;3)the directions of the outgoing particles should be the same and 4)the particle number within the spot should be low enough.In this paper,a method to calibrate the angular response of the‘pin-hole’imaging structure by the90Sr/90Y β source with a collimator is introduced and simulated by Geant4 software.The result of the calibration with the collimated β source is in accord with the Geant4 simulations,which verifies the validity of this method.展开更多
A large class of non-coding RNAs found in small molecule RNAs are closely associated with the regula-tion of gene expression, which are called microRNA (miRNA). MiRNAs are coded in intergenic or intronic regions and c...A large class of non-coding RNAs found in small molecule RNAs are closely associated with the regula-tion of gene expression, which are called microRNA (miRNA). MiRNAs are coded in intergenic or intronic regions and can be formed into foldback hairpin RNAs. These transcripts are cleaved by Dicer, generating mature miRNAs that can silence their target genes in different modes of action. Now, research on small molecule RNAs has gotten breakthrough advance in biology. To discover miRNA genes and their target genes has become hot topics in RNA research. This review attempts to look back the history of miRNA discovery, to introduce the methods of screening miRNAs, to localize miRNA loci in genome, to seek miRNA target genes and the biological func-tion, and to discuss the working mechanisms of miRNAs. Finally, we will discuss the potential important roles of miRNAs in modulating the genesis, development, growth, and differentiation of organisms. Thus, it can be predicted that a complete understanding of miRNA functions will bring us some new concepts, approaches and strategies for the study of living beings.展开更多
The early determination of disease-related biomarkers can significantly improve the survival rate of patients.Thus,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,ha...The early determination of disease-related biomarkers can significantly improve the survival rate of patients.Thus,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,have been devoted to life and health monitoring.Organic thin-film transistor(OTFT),as a state-of-the-art nano-sensing technology,has attracted significant attention from construction to application owing to the merits of being label-free,low-cost,facial,and rapid detection with multi-parameter responses.Nevertheless,interference from non-specific adsorption is inevitable in complex biological samples such as body liquid and exhaled gas,so the reliability and accuracy of the biosensor need to be further improved while ensuring sensitivity,selectivity,and stability.Herein,we overviewed the composition,mechanism,and construction strategies of OTFTs for the practical determination of disease-related biomarkers in both body fluids and exhaled gas.The results show that the realization of bio-inspired applications will come true with the rapid development of high-effective OTFTs and related devices.展开更多
The high and steep slopes along a high-speed railway in the mountainous area of Southwest China are mostly composed of loose accumulations of debris with large internal pores and poor stability,which can easily induce...The high and steep slopes along a high-speed railway in the mountainous area of Southwest China are mostly composed of loose accumulations of debris with large internal pores and poor stability,which can easily induce adverse geological disasters under rainfall conditions.To ensure the smooth construction of the high-speed railway and the subsequent safe operation,it is necessary to master the stability evolution process of the loose accumulation slope under rainfall.This article simulates rainfall using the finite element analysis software’s hydromechanical coupling module.The slope stability under various rainfall situations is calculated and analysed based on the strength reduction method.To validate the simulation results,a field monitoring system is established to study the deformation characteristics of the slope under rainfall.The results show that rainfall duration is the key factor affecting slope stability.Given a constant amount of rainfall,the stability of the slope decreases with increasing duration of rainfall.Moreover,when the amount and duration of rainfall are constant,continuous rainfall has a greater impact on slope stability than intermittent rainfall.The setting of the field retaining structures has a significant role in improving slope stability.The field monitoring data show that the slope is in the initial deformation stage and has good stability,which verifies the rationality of the numerical simulation method.The research results can provide some references for understanding the influence of rainfall on the stability of loose accumulation slopes along high-speed railways and establishing a monitoring system.展开更多
Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antip...Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative activity.Methods:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and HPLC.The structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS data.The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)procedure.The antiproliferative activity was evaluated using MTT assay.Results:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative activity.Conclusion:Compound 1 was a new glycoside.Compounds 2 and 3 were obtained for the first time from natural source.The 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from M.hemsleyana for the first time.This is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus Macaranga.The isolated compounds,11,14–16,and 20–22 established taxonomic classification of M.hemsleyana in Euphorbiaceae family.Flavonoids were outstanding as chemosystematic markers展开更多
One of the physiological functions of cellular prion protein(PrP C )is believed to work as a cellular resistance to oxidative stress,in which the octarepeats region within PrP plays an important role.However,the detai...One of the physiological functions of cellular prion protein(PrP C )is believed to work as a cellular resistance to oxidative stress,in which the octarepeats region within PrP plays an important role.However,the detailed mechanism is less clear.In this study,the expressing plasmids of wild-type PrP (PrP-PG5)and various PrP mutants containing 0(PrP-PG0),9(PrP-PG9)and 12(PrP-PG12)octarepeats were generated and PrP proteins were expressed both in E.coli and in mammalian cells.Protein aggregation and formation of carbonyl groups were clearly seen in the recombinant PrPs expressed from E.coli after treatment of H2O2.MTT and trypan blue staining assays revealed that the cells expressing the mutated PrPs within octarepeats are less viable than the cells expressing wild-type PrP.Statistically significant high levels of intracellular free radicals and low levels of glutathione peroxidase were observed in the cells transfected with plasmids containing deleted or inserted octarepeats.Remarkably more productions of carbonyl groups were detected in the cells expressing PrPs with deleted and inserted octarepeats after exposing to H2O2.Furthermore,cells expressing wild-type PrP showed stronger resistant activity to the challenge of H2O2 at certain extent than the mutated PrPs and mock. These data provided the evidences that the octarepeats number within PrP is critical for maintaining its activity of antioxidation.Loss of its protective function against oxidative stress may be one of the possible pathways for the mutated PrPs to involve in the pathogenesis of familial Creutzfeldt-Jacob diseases.展开更多
Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment o...Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.展开更多
Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin(AVP) in the brain of patients with Alzheimer’s disease(AD). AVP(4-8), different from its pre...Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin(AVP) in the brain of patients with Alzheimer’s disease(AD). AVP(4-8), different from its precursor AVP, plays memory enhancement roles in the CNS without peripheral side-effects. However, it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD. Here, we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation(LTP) in APP/PS1-AD mice.The results showed that:(1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type(WT) mice, and this was significantly reversed by AVP(4-8);(2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8), and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment;(3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice, and this was partly rescued by AVP(4-8);(4) AVP(4-8)significantly up-regulated the expression levels of postsynaptic density 95(PSD95) and nerve growth factor(NGF)in the hippocampus of AD mice. These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice,showing that the intranasal administration of AVP(4-8)effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice, which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.展开更多
Epithelial-mesenchymal Transition(EMT)is a de-differentiation program that imparts tumor cells with the phenotypic and cellular plasticity required for drug resistance,metastasis,and recurrence.This dynamic and revers...Epithelial-mesenchymal Transition(EMT)is a de-differentiation program that imparts tumor cells with the phenotypic and cellular plasticity required for drug resistance,metastasis,and recurrence.This dynamic and reversible events is governed by a network of EMT-transcription factors(EMT-TFs)through epigenetic regulation.Many chromatin modifying-enzymes utilize metabolic intermediates as cofactors or substrates;this suggests that EMT is subjected to the metabolic regulation.Conversely,EMT rewires metabolic program to accommodate cellular changes during EMT.Here we summarize the latest findings regarding the epigenetic regulation of EMT,and discuss the mutual interactions among metabolism,epigenetic regulation,and EMT.Finally,we provide perspectives of how this interplay contributes to cellular plasticity,which may result in the clinical manifestation of tumor heterogeneity.展开更多
Evergreen broad-leaved forestis one of the most important vegetation types in China.Because of the human activities,evergreen broad-leaved forest has been destroyed extensively,leading to degraded ecosystem.It is urge...Evergreen broad-leaved forestis one of the most important vegetation types in China.Because of the human activities,evergreen broad-leaved forest has been destroyed extensively,leading to degraded ecosystem.It is urgent to conserve and restore these natural forests in China. In this paper,the tendency and rate of species diversity restoration of the evergreen broad-leaved forest in Daming Mountain has been studied.The main resultsare as follows:(a)In subtropical mid-mountain area,species diversity in degraded evergreen broad-leaved forestcan be restored. Through analyzing b diversity index of communities in different time and space,it was found that the species composition of communities tend to be the same as that in the zonal evergreen broad-leaved forest.(b)The restoration rate of evergreen broad-leaved forest was very fast.Planting Chinese fir after clear-cutting and controlled burning of the forest,178 species appeared in a 600m^2 sample area after 20 years’natural recovering.Among the sespecies,58 were tree layer and the height of community reached 18m.The survey suggested that it would take only 20 years for the degraded forest to develop into community composed of lightdemanding broad-leaved pioneer trees and min-tolerance broad-leaved trees,and it need another 40~80 years to reach the stage consisting of min-tolerance evergreen broad-leaved trees.(c)Species number increased quickly at the early stage(2-20years)during vegetation recovering process toward the climax,and decreased at the min-stage (50-60 years),then maintained a relatively stable level at the late-stage (over 150 years).展开更多
The variation of the flux of energetic electrons in the magnetosphere has been proven to be strongly related to the solar wind speed. Observations of GEO orbit show that the flux of low-energy electrons is not only mo...The variation of the flux of energetic electrons in the magnetosphere has been proven to be strongly related to the solar wind speed. Observations of GEO orbit show that the flux of low-energy electrons is not only modulated by the solar wind speed, but, if a time delay is added, is also positively correlated to the flux of high-energy electrons. This feature provides a possible method to forecast the flux of high-energy electrons in GEO orbit. In this study, the correlations of the fluxes between the high-energy electrons and low-middle-energy electrons obtained at different L values and in different orbits are investigated to develop the application of this feature. Based on the analysis of long–term data observed by NOAA POES and GOES, the correlations between the fluxes of high-energy electrons and low–middle–energy electrons are good enough at different L values and in different orbits in quiet time, but this correlation is strongly affected by CME–driven geomagnetic storms.展开更多
Multi-sensor measurement iswidely employed in rotatingmachinery to ensure the safety ofmachines.The information provided by the single sensor is not comprehensive.Multi-sensor signals can provide complementary informa...Multi-sensor measurement iswidely employed in rotatingmachinery to ensure the safety ofmachines.The information provided by the single sensor is not comprehensive.Multi-sensor signals can provide complementary information in characterizing the health condition of machines.This paper proposed a multi-sensor fusion convolution neural network(MF-CNN)model.The proposed model adds a 2-D convolution layer before the classical 1-D CNN to automatically extract complementary features of multi-sensor signals and minimize the loss of information.A series of experiments are carried out on a rolling bearing test rig to verify the model.Vibration and sound signals are fused to achieve higher classification accuracy than typical machine learning model.In addition,the model is further applied to gas turbine abnormal detection,and shows great robustness and generalization.展开更多
Significant changes in the Raman spectrum of single-layer graphene grown on a copper film were observed after the spontaneous oxidation of the underlying substrate that occurred under ambient conditions. The frequenci...Significant changes in the Raman spectrum of single-layer graphene grown on a copper film were observed after the spontaneous oxidation of the underlying substrate that occurred under ambient conditions. The frequencies of the graphene G and 2D Raman modes were found to undergo red shifts, while the intensities of the two bands change by more than an order of magnitude. To understand the origin of these effects, we further characterized the samples by scanning tunneling microscopy （STM）, scanning tunneling spectroscopy （STS）, and atomic force microscopy （AFM）. The oxidation of the substrate produced an appreciable corrugation in the substrate without disrupting the crystalline order of the graphene overlayer and/or changing the carrier doping level. We explain the red shifts of the Raman frequencies in terms of tensile strain induced by corrugation of the graphene layer. The changes in Raman intensity with oxidation arise from the influence of the thin cuprous oxide film on the efficiency of light coupling with the graphene layer in the Raman scattering process.展开更多
基金supported by grants from the Key Program of Zhejiang Provincial Natural Science Foundation(Grant No.LZ17H160002)National Natural Science Foundation of China(Grant No.81972456 and 81772801)+2 种基金the National Key R&D Program of China(Grant No.2016YFC1303200)the Fundamental Research Funds for Central Universities of China(to C.D.)the Thousand Young Talents Plan of China(to C.D.)。
文摘Since triple-negative breast cancer(TNBC)was first defined over a decade ago,increasing studies have focused on its genetic and molecular characteristics.Patients diagnosed with TNBC,compared to those diagnosed with other breast cancer subtypes,have relatively poor outcomes due to high tumor aggressiveness and lack of targeted treatment.Metabolic reprogramming,an emerging hallmark of cancer,is hijacked by TNBC to fulfill bioenergetic and biosynthetic demands;maintain the redox balance;and further promote oncogenic signaling,cell proliferation,and metastasis.Understanding the mechanisms of metabolic remodeling may guide the design of metabolic strategies for the effective intervention of TNBC.Here,we review the metabolic reprogramming of glycolysis,oxidative phosphorylation,amino acid metabolism,lipid metabolism,and other branched pathways in TNBC and explore opportunities for new biomarkers,imaging modalities,and metabolically targeted therapies.
基金Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Municipal Administration,No.XTZD20180105.
文摘Importance:Post-intubation subglottic stenosis(SGS)in children can be life threatening.Definitive treatment varies and lacks a universally accepted approach.Objective:We performed a prospective study to assess the safety and feasibility of holmium laser combined with cryotherapy delivered via flexible bronchoscopy for the treatment of post-intubation SGS in children.Methods:This study involved all patients with post-intubation SGS seen at the Interventional Pulmonology Department of Beijing Children's Hospital between July 2014 and December 2016.Holmium laser treatment and cryotherapy was then performed under flexible bronchoscopy,whose parents refused to accept the alternative standard treatment of tracheotomy and balloon dilation under direct laryngoscopy.results:Sixteen patients with post-intubation SGS were included in this study.Ages ranged from 2 months to 12.25 years old.According to the Cotton-Myer grading system,three cases were Grade II,12 cases were Grade III,and one case was Grade IV.According to the McCaffrey system,eight cases were Stage 1,two cases were Stage 2,and six cases were Stage 3.The average number of procedures was 4.88.Fifteen of the 16 patients achieved clinical cure.One patient achieved clinical improvement.The average treatment course duration was 55.31 days.No severe complications were seen.Post-treatment clinical symptoms,endoscopic findings and quality of life showed marked improvement.Interpretation:Our study supports the conclusion that holmium laser treatment combined with cryotherapy via flexible bronchoscopy appears to be a safe and feasible treatment for post-intubation SGS in children.
基金supported by the National Natural Science Foundation of China(Grant Nos.40704026 and 41374167)
文摘The pitch-angle distribution of energetic particles is important for space physics studies on magnetic storm and particle acceleration.A‘pin-hole’imaging structure is built with the‘pin-hole’technique and a position sensitive detector,which can be used to measure the pitch angle distribution of energetic particles.To calibrate the angular response of the‘pin-hole’imaging structure,special experiment facilities are needed,such as the particle accelerator with special design.The features of this kind of particle accelerator are:1)The energy range of the outgoing particles should be mid-energy particles(tens keV to several hundred keV);2)the particle flux should be consistent in time-scale;3)the directions of the outgoing particles should be the same and 4)the particle number within the spot should be low enough.In this paper,a method to calibrate the angular response of the‘pin-hole’imaging structure by the90Sr/90Y β source with a collimator is introduced and simulated by Geant4 software.The result of the calibration with the collimated β source is in accord with the Geant4 simulations,which verifies the validity of this method.
文摘A large class of non-coding RNAs found in small molecule RNAs are closely associated with the regula-tion of gene expression, which are called microRNA (miRNA). MiRNAs are coded in intergenic or intronic regions and can be formed into foldback hairpin RNAs. These transcripts are cleaved by Dicer, generating mature miRNAs that can silence their target genes in different modes of action. Now, research on small molecule RNAs has gotten breakthrough advance in biology. To discover miRNA genes and their target genes has become hot topics in RNA research. This review attempts to look back the history of miRNA discovery, to introduce the methods of screening miRNAs, to localize miRNA loci in genome, to seek miRNA target genes and the biological func-tion, and to discuss the working mechanisms of miRNAs. Finally, we will discuss the potential important roles of miRNAs in modulating the genesis, development, growth, and differentiation of organisms. Thus, it can be predicted that a complete understanding of miRNA functions will bring us some new concepts, approaches and strategies for the study of living beings.
基金supported by the National Natural Science Foundation of China(Nos.21925405,22104141,22104142,22004122,and 201874005)the National Key Research and Development Program of China Grant(Nos.2018YFA0208800 and 2021YFD1700300)+1 种基金the Chinese Academy of Sciences(Nos.XDA23030106 and YJKYYQ20180044)the China Postdoctoral Science Foundation(Nos.2020M680676 and 2021T140680).
文摘The early determination of disease-related biomarkers can significantly improve the survival rate of patients.Thus,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,have been devoted to life and health monitoring.Organic thin-film transistor(OTFT),as a state-of-the-art nano-sensing technology,has attracted significant attention from construction to application owing to the merits of being label-free,low-cost,facial,and rapid detection with multi-parameter responses.Nevertheless,interference from non-specific adsorption is inevitable in complex biological samples such as body liquid and exhaled gas,so the reliability and accuracy of the biosensor need to be further improved while ensuring sensitivity,selectivity,and stability.Herein,we overviewed the composition,mechanism,and construction strategies of OTFTs for the practical determination of disease-related biomarkers in both body fluids and exhaled gas.The results show that the realization of bio-inspired applications will come true with the rapid development of high-effective OTFTs and related devices.
基金supported by the National Natural Science Foundation of China (No.51978588).
文摘The high and steep slopes along a high-speed railway in the mountainous area of Southwest China are mostly composed of loose accumulations of debris with large internal pores and poor stability,which can easily induce adverse geological disasters under rainfall conditions.To ensure the smooth construction of the high-speed railway and the subsequent safe operation,it is necessary to master the stability evolution process of the loose accumulation slope under rainfall.This article simulates rainfall using the finite element analysis software’s hydromechanical coupling module.The slope stability under various rainfall situations is calculated and analysed based on the strength reduction method.To validate the simulation results,a field monitoring system is established to study the deformation characteristics of the slope under rainfall.The results show that rainfall duration is the key factor affecting slope stability.Given a constant amount of rainfall,the stability of the slope decreases with increasing duration of rainfall.Moreover,when the amount and duration of rainfall are constant,continuous rainfall has a greater impact on slope stability than intermittent rainfall.The setting of the field retaining structures has a significant role in improving slope stability.The field monitoring data show that the slope is in the initial deformation stage and has good stability,which verifies the rationality of the numerical simulation method.The research results can provide some references for understanding the influence of rainfall on the stability of loose accumulation slopes along high-speed railways and establishing a monitoring system.
基金supported by the National Natural Science Foundation of China(No.81860615,82260682)Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001).
文摘Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative activity.Methods:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and HPLC.The structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS data.The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)procedure.The antiproliferative activity was evaluated using MTT assay.Results:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative activity.Conclusion:Compound 1 was a new glycoside.Compounds 2 and 3 were obtained for the first time from natural source.The 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from M.hemsleyana for the first time.This is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus Macaranga.The isolated compounds,11,14–16,and 20–22 established taxonomic classification of M.hemsleyana in Euphorbiaceae family.Flavonoids were outstanding as chemosystematic markers
基金the National Science and Technology Task Force Project(Grant No.2006BAD06A13-2)National Basic Research Program(973 Program)of China(Grant No.2007CB310505)National Natural Science Foundation of China(Grant Nos.30571672,30500018 and 30771914)
文摘One of the physiological functions of cellular prion protein(PrP C )is believed to work as a cellular resistance to oxidative stress,in which the octarepeats region within PrP plays an important role.However,the detailed mechanism is less clear.In this study,the expressing plasmids of wild-type PrP (PrP-PG5)and various PrP mutants containing 0(PrP-PG0),9(PrP-PG9)and 12(PrP-PG12)octarepeats were generated and PrP proteins were expressed both in E.coli and in mammalian cells.Protein aggregation and formation of carbonyl groups were clearly seen in the recombinant PrPs expressed from E.coli after treatment of H2O2.MTT and trypan blue staining assays revealed that the cells expressing the mutated PrPs within octarepeats are less viable than the cells expressing wild-type PrP.Statistically significant high levels of intracellular free radicals and low levels of glutathione peroxidase were observed in the cells transfected with plasmids containing deleted or inserted octarepeats.Remarkably more productions of carbonyl groups were detected in the cells expressing PrPs with deleted and inserted octarepeats after exposing to H2O2.Furthermore,cells expressing wild-type PrP showed stronger resistant activity to the challenge of H2O2 at certain extent than the mutated PrPs and mock. These data provided the evidences that the octarepeats number within PrP is critical for maintaining its activity of antioxidation.Loss of its protective function against oxidative stress may be one of the possible pathways for the mutated PrPs to involve in the pathogenesis of familial Creutzfeldt-Jacob diseases.
基金supported in part by the grants from the National Natural Science Foundation of China (Grant No. 81472462)Medical Guidance Foundation of Shanghai Municipal Science and Technology Commission (Grant No. 15411966400)Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission (Grant No. 14411950200, 14411950201) and Sanofi
文摘Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.
基金the National Natural Science Foundation of China(31471080)the Scientific Program for“Sanjin Scholars”of Shanxi Province,Shanxi“1331 Project”Key Subjects Construction(1331KSC)Science Foundation for Excellent Young Scholars of Shanxi Province,China(201801D211005)。
文摘Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin(AVP) in the brain of patients with Alzheimer’s disease(AD). AVP(4-8), different from its precursor AVP, plays memory enhancement roles in the CNS without peripheral side-effects. However, it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD. Here, we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation(LTP) in APP/PS1-AD mice.The results showed that:(1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type(WT) mice, and this was significantly reversed by AVP(4-8);(2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8), and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment;(3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice, and this was partly rescued by AVP(4-8);(4) AVP(4-8)significantly up-regulated the expression levels of postsynaptic density 95(PSD95) and nerve growth factor(NGF)in the hippocampus of AD mice. These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice,showing that the intranasal administration of AVP(4-8)effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice, which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.
基金We apologize to the many contributors to this field whose work are important while we were unable to cite due to space limitation.Our study is supported by the grants from National Institutes of Health(NIH)(RO1s CA125454 and CA188118)Department of Defense(DOD)Breakthrough Award(BC140733P1)Mary Kay Ash Foundation(to B.P.Zhou),and the Basic Public Welfare Research Program of Zhejiang Province(LGF18H290003 to Y.Wang).
文摘Epithelial-mesenchymal Transition(EMT)is a de-differentiation program that imparts tumor cells with the phenotypic and cellular plasticity required for drug resistance,metastasis,and recurrence.This dynamic and reversible events is governed by a network of EMT-transcription factors(EMT-TFs)through epigenetic regulation.Many chromatin modifying-enzymes utilize metabolic intermediates as cofactors or substrates;this suggests that EMT is subjected to the metabolic regulation.Conversely,EMT rewires metabolic program to accommodate cellular changes during EMT.Here we summarize the latest findings regarding the epigenetic regulation of EMT,and discuss the mutual interactions among metabolism,epigenetic regulation,and EMT.Finally,we provide perspectives of how this interplay contributes to cellular plasticity,which may result in the clinical manifestation of tumor heterogeneity.
基金This item was supportedby the National ScienceFoundationof P.R.China (No.39330040,39460022)
文摘Evergreen broad-leaved forestis one of the most important vegetation types in China.Because of the human activities,evergreen broad-leaved forest has been destroyed extensively,leading to degraded ecosystem.It is urgent to conserve and restore these natural forests in China. In this paper,the tendency and rate of species diversity restoration of the evergreen broad-leaved forest in Daming Mountain has been studied.The main resultsare as follows:(a)In subtropical mid-mountain area,species diversity in degraded evergreen broad-leaved forestcan be restored. Through analyzing b diversity index of communities in different time and space,it was found that the species composition of communities tend to be the same as that in the zonal evergreen broad-leaved forest.(b)The restoration rate of evergreen broad-leaved forest was very fast.Planting Chinese fir after clear-cutting and controlled burning of the forest,178 species appeared in a 600m^2 sample area after 20 years’natural recovering.Among the sespecies,58 were tree layer and the height of community reached 18m.The survey suggested that it would take only 20 years for the degraded forest to develop into community composed of lightdemanding broad-leaved pioneer trees and min-tolerance broad-leaved trees,and it need another 40~80 years to reach the stage consisting of min-tolerance evergreen broad-leaved trees.(c)Species number increased quickly at the early stage(2-20years)during vegetation recovering process toward the climax,and decreased at the min-stage (50-60 years),then maintained a relatively stable level at the late-stage (over 150 years).
基金supported by the National Natural Science Foundation of China(Grant Nos.41374167,41074117&41374166)
文摘The variation of the flux of energetic electrons in the magnetosphere has been proven to be strongly related to the solar wind speed. Observations of GEO orbit show that the flux of low-energy electrons is not only modulated by the solar wind speed, but, if a time delay is added, is also positively correlated to the flux of high-energy electrons. This feature provides a possible method to forecast the flux of high-energy electrons in GEO orbit. In this study, the correlations of the fluxes between the high-energy electrons and low-middle-energy electrons obtained at different L values and in different orbits are investigated to develop the application of this feature. Based on the analysis of long–term data observed by NOAA POES and GOES, the correlations between the fluxes of high-energy electrons and low–middle–energy electrons are good enough at different L values and in different orbits in quiet time, but this correlation is strongly affected by CME–driven geomagnetic storms.
基金support from the National Natural Science Foundation of China (Grant No.U1809219)the Key Research and Development Project of Zhejiang Province (Grant No.2020C01088).
文摘Multi-sensor measurement iswidely employed in rotatingmachinery to ensure the safety ofmachines.The information provided by the single sensor is not comprehensive.Multi-sensor signals can provide complementary information in characterizing the health condition of machines.This paper proposed a multi-sensor fusion convolution neural network(MF-CNN)model.The proposed model adds a 2-D convolution layer before the classical 1-D CNN to automatically extract complementary features of multi-sensor signals and minimize the loss of information.A series of experiments are carried out on a rolling bearing test rig to verify the model.Vibration and sound signals are fused to achieve higher classification accuracy than typical machine learning model.In addition,the model is further applied to gas turbine abnormal detection,and shows great robustness and generalization.
文摘Significant changes in the Raman spectrum of single-layer graphene grown on a copper film were observed after the spontaneous oxidation of the underlying substrate that occurred under ambient conditions. The frequencies of the graphene G and 2D Raman modes were found to undergo red shifts, while the intensities of the two bands change by more than an order of magnitude. To understand the origin of these effects, we further characterized the samples by scanning tunneling microscopy （STM）, scanning tunneling spectroscopy （STS）, and atomic force microscopy （AFM）. The oxidation of the substrate produced an appreciable corrugation in the substrate without disrupting the crystalline order of the graphene overlayer and/or changing the carrier doping level. We explain the red shifts of the Raman frequencies in terms of tensile strain induced by corrugation of the graphene layer. The changes in Raman intensity with oxidation arise from the influence of the thin cuprous oxide film on the efficiency of light coupling with the graphene layer in the Raman scattering process.
