Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect ...Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.展开更多
Lateral intakes are common in rivers.The pump effciency and sediment deposition are determined by the local hydrodynamic characteristics and mainstream division width.The hydraulic characteristics of lateral withdrawa...Lateral intakes are common in rivers.The pump effciency and sediment deposition are determined by the local hydrodynamic characteristics and mainstream division width.The hydraulic characteristics of lateral withdrawal from inclined river slopes at different intake elevations should be investigated.Meanwhile,the division width exhibits significant vertical non-uniformity at an inclined river slope,which should be clarified.Hence,a three-dimensional(3-D)hydrodynamic and particle-tracking model was developed with the Open Source Field Operation and Manipulation(Open FOAM),and the model was validated with physical model tests for 90°lateral withdrawal from an inclined side bank.The flow fields,withdrawal sources,and division widths were investigated with different intake bottom elevations,withdrawal discharges,and main channel velocities.This study showed that under inclined side bank conditions,water entered the intake at an oblique angle,causing significant 3-D spiral flows in the intake rather than two-dimensional closed recirculation.A lower withdrawal discharge,a lower bottom elevation of the intake,or a higher main channel velocity could further strengthen this phenomenon.The average division width and turbulent kinetic energy were smaller under inclined side bank conditions than under vertical bank conditions.With a low intake bottom elevation,a low withdrawal discharge,or a high main channel velocity,the sources of lateral withdrawal were in similar ranges near the local inclined bank in the vertical direction.Under inclined slope conditions,sediment deposition near the intake entrance could be reduced,compared to that under vertical slope conditions.The results provide hydrodynamic and sediment references for engineering designs for natural rivers with inclined terrains.展开更多
Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In th...Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In this work,an ion‐polymer‐modified gas‐diffusion electrode is used to tackle this proton limit.It is found that gas diffusion electrode‐Nafion shows an impressive performance of 75.2%Faradaic efficiency in multicarbon products at an industrial current density of 1.16 A/cm^(2).Significantly,in‐depth electrochemical characterizations combined with in situ Raman have been used to determine the full workflow of protons,and it is found that HCO_(3)^(−)acts as a proton pool near the reaction environment,and HCO_(3)^(−)and H_(3)O^(+)are local proton donors that interact with the proton shuttle−SO_(3)^(−)from Nafion.With rich proton hopping sites that decrease the activation energy,a“Grotthuss”mechanism for proton transport in the above system has been identified rather than the“Vehicle”mechanism with a higher energy barrier.Therefore,this work could be very useful in terms of the achievement of industrial CO_(2)reduction fundamentally and practically.展开更多
●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,...●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.展开更多
How to achieve synergistic improvement of permittivity(ε_(r))and breakdown strength(E_(b))is a huge challenge for polymer dielectrics.Here,for the first time,theπ-conjugated comonomer(MHT)can simultaneously promote ...How to achieve synergistic improvement of permittivity(ε_(r))and breakdown strength(E_(b))is a huge challenge for polymer dielectrics.Here,for the first time,theπ-conjugated comonomer(MHT)can simultaneously promote theε_(r)and E_(b)of linear poly(methyl methacrylate)(PMMA)copolymers.The PMMA-based random copolymer films(P(MMA-co-MHT)),block copolymer films(PMMA-b-PMHT),and PMMA-based blend films were prepared to investigate the effects of sequential structure,phase separation structure,and modification method on dielectric and energy storage properties of PMMA-based dielectric films.As a result,the random copolymer P(MMA-coMHT)can achieve a maximumε_(r)of 5.8 at 1 kHz owing to the enhanced orientation polarization and electron polarization.Because electron injection and charge transfer are limited by the strong electrostatic attraction ofπ-conjugated benzophenanthrene group analyzed by the density functional theory(DFT),the discharge energy density value of P(MMA-co-PMHT)containing 1 mol%MHT units with the efficiency of 80%reaches15.00 J cm^(-3)at 872 MV m^(-1),which is 165%higher than that of pure PMMA.This study provides a simple and effective way to fabricate the high performance of polymer dielectrics via copolymerization with the monomer of P-type semi-conductive polymer.展开更多
Background:Exploring the protective mechanism of the Liangxue Huayu(LXHY)decoction on human retinal pigment epithelial(RPE)cells induced by hypoxia through the autophagy pathway.Methods:The appropriate LXHY decoction ...Background:Exploring the protective mechanism of the Liangxue Huayu(LXHY)decoction on human retinal pigment epithelial(RPE)cells induced by hypoxia through the autophagy pathway.Methods:The appropriate LXHY decoction concentration was determined by CCK-8.ARPE-19 cells were divided into the normal control group(A group),CoCl_(2)group(B group),3-Methyladenine(3-MA)group(treated with 3-MA(the inhibition of autophagy pathway))(C group),blank serum(BS)group(D group),LXHY drug-contained serum(DCS)group(E group),and Rapamycin(RAP)group[treated with LXHY drug-contained serum combined with rapamycin group(the activation of autophagy pathway)](F group).Counting the number of autophagosomes and autolysosomes in each group of cells under transmission electron microscopy.After infection of cells in each group by mRFP-GFP-LC3 fusion protein adenovirus,the strength of autophagic flux was detected.The mRNA expression levels of LC3 and Beclin-1 were detected by Q-PCR.Results:CCK-8 assay results showed that LXHY DCS could inhibit the cell proliferation of ARPE-19 under hypoxia(all P<0.05).As the transmission electron microscopy assay result showed,compared with the normal control group,the number of autolysosomes was significantly increased in the CoCl_(2)group(P<0.05).Compared with CoCl_(2)group,the number of autolysosomes was significantly reduced the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).As autophagic flux assay result showed,compared with the normal control group,the level of autophagosomes and autolysosomes were significantly risen in CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the level of autophagosomes and autolysosomes were significantly fell down in 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.05).The level of autolysosomes in the LXHY drug-contained serum group was lower than in the blank serum group(P<0.05).Compared with the LXHY drug-contained serum group,the levels of autophagosomes and autolysosomes were significantly risen in the LXHY drug-contained serum combined with the rapamycin group(all P<0.05).As the Q-PCR result showed,compared with the normal control group,the expression of LC3 and Beclin-1 mRNA were significantly reduced in the CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the expression of LC3 mRNA were significantly increased in the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).Beclin-1 mRNA expression was increased significantly(all P<0.001)in the blank serum group and the LXHY drug-contained serum group.And Beclin-1 mRNA expression in the LXHY drug-contained serum group was statistically significant increased than blank serum group(P<0.001).In the LXHY drug-contained serum combined with the rapamycin group,the LC3 and Beclin-1 mRNA expression was reduced significantly compared with the LXHY drug-contained serum group(all P<0.001).Conclusion:The LXHY DCS has the ability to protect the human retinal pigment epithelial cell(ARPE-19)damage under hypoxia through the autophagy pathway.展开更多
背景与目的肺大细胞神经内分泌癌(lung large cell neuroendocrine carcinoma,LCNEC)是一种罕见且预后极差的肺恶性肿瘤。目前对LCNEC的研究大多基于回顾性研究,缺乏现实世界的验证。本研究旨在识别独立的危险因素,建立并验证LCNEC预后...背景与目的肺大细胞神经内分泌癌(lung large cell neuroendocrine carcinoma,LCNEC)是一种罕见且预后极差的肺恶性肿瘤。目前对LCNEC的研究大多基于回顾性研究,缺乏现实世界的验证。本研究旨在识别独立的危险因素,建立并验证LCNEC预后的预测模型。方法从2010至2015年监测、流行病学和结果数据库(Surveillance,Epidemiology,and End Results,SEER)和我科2016至2020年住院患者中提取患者资料。采用Kaplan-Meier法评估总生存期(overall survival,OS)。OS被定义为患者从确诊到死亡或最后一次随访时间。单因素Cov回归分析和多因素Cox回归分析确定显著的预后因素。从而构建预测LCNEC预后的Nomogram。结果共纳入1892例LCNEC患者,分为训练队列(n=1288)和两个验证队列(n=552,n=52)。单因素Cox回归分析显示年龄、性别、肿瘤原发部位、偏侧、肿瘤原发灶-淋巴结-转移(tumor-node-metastasis,TNM)各分期、手术、放疗可影响LCNEC的预后(P<0.05),多因素Cox分析显示年龄、性别、肿瘤原发部位、T分期、N分期、M分期、手术、放疗是LCNEC患者预后的独立危险因素(P<0.05)。校准曲线和一致性指数(内部:0.744±0.015;外部:0.763±0.020、0.832±0.055)显示模型预测性能良好。结论年龄≥65岁、男性、TNM分期晚、未经过手术或放疗的患者预后不佳。列线图可以对患者的个性化临床决策提供一定的参考。展开更多
For a water supply system with long-distance diversion pipelines, in addition to the water hammer problems that occur beyond pumps, the safety of the water diversion pipeline in front of pumps also deserves attention....For a water supply system with long-distance diversion pipelines, in addition to the water hammer problems that occur beyond pumps, the safety of the water diversion pipeline in front of pumps also deserves attention. In this study, a water hammer protection scheme combined with an overflow surge tank and a regulating valve was developed. A mathematical model of the overflow surge tank was developed, and an analytical formula for the height of the overflow surge tank was derived. Furthermore, a practical water supply project was used to evaluate the feasibility of the combined protection scheme and analyze the sensitivity of valve regulation rules. The results showed that the combined protection scheme effectively reduced the height of the surge tank, lessened the difficulties related to construction, and reduced the necessary financial investment for the project. The two-stage closing rule articulated as fast first and then slow could minimize the overflow volume of the surge tank when the power failure occurred, while the two-stage opening rule articulated as slow first and then fast could be more conducive to the safety of the water supply system when the pump started up.展开更多
Three materials(agar,konjac glucomannan(KGM)andκ-carrageenan)were used to prepare ternary systems,i.e.,sol-gels and their dried composites conditioned at varied relative humidity(RH)(33%,54%and 75%).Combined methods,...Three materials(agar,konjac glucomannan(KGM)andκ-carrageenan)were used to prepare ternary systems,i.e.,sol-gels and their dried composites conditioned at varied relative humidity(RH)(33%,54%and 75%).Combined methods,e.g.,scanning electron microscopy,small-angle X-ray scattering,infrared spectroscopy(IR)and X-ray diffraction(XRD),were used to disclose howκ-carrageenan addition tailors the features of agar/KGM/κ-carrageenan ternary system.As affirmed by IR and XRD,the ternary systems withκ-carrageenan below 25%(agar/KGM/carrageenan,50:25:25,m/m)displayed proper component interactions,which increased the sol-gel transition temperature and the hardness of obtained gels.For instance,the ternary composites could show hardness about 3 to 4 times higher than that for binary counterpart.These gels were dehydrated to acquire ternary composites.Compared to agar/KGM composite,the ternary composites showed fewer crystallites and nanoscale orders,and newly-formed nanoscale structures from chain assembly.Such multi-scale structures,for composites withκ-carrageenan below 25%,showed weaker changes with RH,as revealed by especially morphologic and crystalline features.Consequently,the ternary composites with lessκ-carrageenan(below 25%)exhibited stabilized elongation at break and hydrophilicity at different RHs.This hints to us that agar/KGM/κ-carrageenan composite systems can display series applications with improved features,e.g.,increased sol-gel transition point.展开更多
Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as diffi...Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the antiIgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in antiIgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.展开更多
The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial...The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.展开更多
High-entropy materials are composed of five or more metal elements with equimolar or near-equimolar concentrations within one crystal structure,which offer remarkable structural properties for many applications.Despit...High-entropy materials are composed of five or more metal elements with equimolar or near-equimolar concentrations within one crystal structure,which offer remarkable structural properties for many applications.Despite previously reported entropy-driven stabilization mechanisms,many high-entropy materials still tend to decompose to produce a variety of derivatives under operating conditions.In this study,we use transition-metal(Ni,Co,Ni,Zn,V)-based high-entropy metal-organic frameworks(HE-MOFs)as the precursors to produce different derivatives under acidic/alkaline treatment.We have shown that HE-MOFs and derivatives have shown favorable kinetics for N_(2)electrofixation in different pH electrolytes,specifically cathodic nitrogen reduction reaction in acidic media and anodic oxygen evolution reaction in alkaline media.To buffer the pH mismatch,we have further constructed an asymmetric acidic/alkaline device prototype by using bipolar membranes.As expected,the prototype showed remarkable activities,with an NH_(3)yield rate of 42.76μg h^(−1)mg^(−1),and Faradaic efficiency of 14.75%and energy efficiency of 2.59%,which are 14.4 and 4.4 times larger than those of its symmetric acidic and alkaline counterparts,respectively.展开更多
基金supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC)Shanghai Outstanding Young Scholars Project+2 种基金Shanghai Talent Development Project,No.2019044(to SC)Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ)the National Natural Science Foundation of China,No.82201558(to QZ)。
文摘Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.
基金supported by the National Natural Science Foundation of China(Grant No.52379061)the Natural Science Foundation of Jiangsu Province(Grant No.BK20230099)the Key Laboratory of Water Grid Project and Regulation of Ministry of Water Resources(Grant No.QTKS0034W23292).
文摘Lateral intakes are common in rivers.The pump effciency and sediment deposition are determined by the local hydrodynamic characteristics and mainstream division width.The hydraulic characteristics of lateral withdrawal from inclined river slopes at different intake elevations should be investigated.Meanwhile,the division width exhibits significant vertical non-uniformity at an inclined river slope,which should be clarified.Hence,a three-dimensional(3-D)hydrodynamic and particle-tracking model was developed with the Open Source Field Operation and Manipulation(Open FOAM),and the model was validated with physical model tests for 90°lateral withdrawal from an inclined side bank.The flow fields,withdrawal sources,and division widths were investigated with different intake bottom elevations,withdrawal discharges,and main channel velocities.This study showed that under inclined side bank conditions,water entered the intake at an oblique angle,causing significant 3-D spiral flows in the intake rather than two-dimensional closed recirculation.A lower withdrawal discharge,a lower bottom elevation of the intake,or a higher main channel velocity could further strengthen this phenomenon.The average division width and turbulent kinetic energy were smaller under inclined side bank conditions than under vertical bank conditions.With a low intake bottom elevation,a low withdrawal discharge,or a high main channel velocity,the sources of lateral withdrawal were in similar ranges near the local inclined bank in the vertical direction.Under inclined slope conditions,sediment deposition near the intake entrance could be reduced,compared to that under vertical slope conditions.The results provide hydrodynamic and sediment references for engineering designs for natural rivers with inclined terrains.
基金National Key R&D Program of China,Grant/Award Number:2021YFF0500700Fundamental Research Funds for the Central Universities,Grant/Award Numbers:30921013103,30920041113+1 种基金Jiangsu Natural Science Foundation,Grant/Award Number:BK20190460National Natural Science Foundation of China,Grant/Award Numbers:51888103,52006105,92163124。
文摘Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In this work,an ion‐polymer‐modified gas‐diffusion electrode is used to tackle this proton limit.It is found that gas diffusion electrode‐Nafion shows an impressive performance of 75.2%Faradaic efficiency in multicarbon products at an industrial current density of 1.16 A/cm^(2).Significantly,in‐depth electrochemical characterizations combined with in situ Raman have been used to determine the full workflow of protons,and it is found that HCO_(3)^(−)acts as a proton pool near the reaction environment,and HCO_(3)^(−)and H_(3)O^(+)are local proton donors that interact with the proton shuttle−SO_(3)^(−)from Nafion.With rich proton hopping sites that decrease the activation energy,a“Grotthuss”mechanism for proton transport in the above system has been identified rather than the“Vehicle”mechanism with a higher energy barrier.Therefore,this work could be very useful in terms of the achievement of industrial CO_(2)reduction fundamentally and practically.
文摘●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.
基金the funding of National Key R&D Program of China(No.2020YFA0711700)Hunan National Natural Science Foundation(2021JJ30652)+3 种基金National Natural Science Foundation of China(52002404)Natural Science Foundation of Guangdong Province(2020A1515011198)Characteristic Innovation Projects of Colleges and Universities in Guangdong Province(2020KT SCX081)State Key Laboratory of Powder Metallurgy,Central South University,Changsha,China
文摘How to achieve synergistic improvement of permittivity(ε_(r))and breakdown strength(E_(b))is a huge challenge for polymer dielectrics.Here,for the first time,theπ-conjugated comonomer(MHT)can simultaneously promote theε_(r)and E_(b)of linear poly(methyl methacrylate)(PMMA)copolymers.The PMMA-based random copolymer films(P(MMA-co-MHT)),block copolymer films(PMMA-b-PMHT),and PMMA-based blend films were prepared to investigate the effects of sequential structure,phase separation structure,and modification method on dielectric and energy storage properties of PMMA-based dielectric films.As a result,the random copolymer P(MMA-coMHT)can achieve a maximumε_(r)of 5.8 at 1 kHz owing to the enhanced orientation polarization and electron polarization.Because electron injection and charge transfer are limited by the strong electrostatic attraction ofπ-conjugated benzophenanthrene group analyzed by the density functional theory(DFT),the discharge energy density value of P(MMA-co-PMHT)containing 1 mol%MHT units with the efficiency of 80%reaches15.00 J cm^(-3)at 872 MV m^(-1),which is 165%higher than that of pure PMMA.This study provides a simple and effective way to fabricate the high performance of polymer dielectrics via copolymerization with the monomer of P-type semi-conductive polymer.
基金support of the foundation projects:Fujian Province Traditional Chinese Medicine Research Project Plan(No.2021ZYJC08).
文摘Background:Exploring the protective mechanism of the Liangxue Huayu(LXHY)decoction on human retinal pigment epithelial(RPE)cells induced by hypoxia through the autophagy pathway.Methods:The appropriate LXHY decoction concentration was determined by CCK-8.ARPE-19 cells were divided into the normal control group(A group),CoCl_(2)group(B group),3-Methyladenine(3-MA)group(treated with 3-MA(the inhibition of autophagy pathway))(C group),blank serum(BS)group(D group),LXHY drug-contained serum(DCS)group(E group),and Rapamycin(RAP)group[treated with LXHY drug-contained serum combined with rapamycin group(the activation of autophagy pathway)](F group).Counting the number of autophagosomes and autolysosomes in each group of cells under transmission electron microscopy.After infection of cells in each group by mRFP-GFP-LC3 fusion protein adenovirus,the strength of autophagic flux was detected.The mRNA expression levels of LC3 and Beclin-1 were detected by Q-PCR.Results:CCK-8 assay results showed that LXHY DCS could inhibit the cell proliferation of ARPE-19 under hypoxia(all P<0.05).As the transmission electron microscopy assay result showed,compared with the normal control group,the number of autolysosomes was significantly increased in the CoCl_(2)group(P<0.05).Compared with CoCl_(2)group,the number of autolysosomes was significantly reduced the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).As autophagic flux assay result showed,compared with the normal control group,the level of autophagosomes and autolysosomes were significantly risen in CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the level of autophagosomes and autolysosomes were significantly fell down in 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.05).The level of autolysosomes in the LXHY drug-contained serum group was lower than in the blank serum group(P<0.05).Compared with the LXHY drug-contained serum group,the levels of autophagosomes and autolysosomes were significantly risen in the LXHY drug-contained serum combined with the rapamycin group(all P<0.05).As the Q-PCR result showed,compared with the normal control group,the expression of LC3 and Beclin-1 mRNA were significantly reduced in the CoCl_(2)group(all P<0.001).Compared with the CoCl_(2)group,the expression of LC3 mRNA were significantly increased in the 3-Methyladenine group,blank serum group and LXHY drug-contained serum group(all P<0.001).Beclin-1 mRNA expression was increased significantly(all P<0.001)in the blank serum group and the LXHY drug-contained serum group.And Beclin-1 mRNA expression in the LXHY drug-contained serum group was statistically significant increased than blank serum group(P<0.001).In the LXHY drug-contained serum combined with the rapamycin group,the LC3 and Beclin-1 mRNA expression was reduced significantly compared with the LXHY drug-contained serum group(all P<0.001).Conclusion:The LXHY DCS has the ability to protect the human retinal pigment epithelial cell(ARPE-19)damage under hypoxia through the autophagy pathway.
文摘背景与目的肺大细胞神经内分泌癌(lung large cell neuroendocrine carcinoma,LCNEC)是一种罕见且预后极差的肺恶性肿瘤。目前对LCNEC的研究大多基于回顾性研究,缺乏现实世界的验证。本研究旨在识别独立的危险因素,建立并验证LCNEC预后的预测模型。方法从2010至2015年监测、流行病学和结果数据库(Surveillance,Epidemiology,and End Results,SEER)和我科2016至2020年住院患者中提取患者资料。采用Kaplan-Meier法评估总生存期(overall survival,OS)。OS被定义为患者从确诊到死亡或最后一次随访时间。单因素Cov回归分析和多因素Cox回归分析确定显著的预后因素。从而构建预测LCNEC预后的Nomogram。结果共纳入1892例LCNEC患者,分为训练队列(n=1288)和两个验证队列(n=552,n=52)。单因素Cox回归分析显示年龄、性别、肿瘤原发部位、偏侧、肿瘤原发灶-淋巴结-转移(tumor-node-metastasis,TNM)各分期、手术、放疗可影响LCNEC的预后(P<0.05),多因素Cox分析显示年龄、性别、肿瘤原发部位、T分期、N分期、M分期、手术、放疗是LCNEC患者预后的独立危险因素(P<0.05)。校准曲线和一致性指数(内部:0.744±0.015;外部:0.763±0.020、0.832±0.055)显示模型预测性能良好。结论年龄≥65岁、男性、TNM分期晚、未经过手术或放疗的患者预后不佳。列线图可以对患者的个性化临床决策提供一定的参考。
基金supported by the National Natural Science Foundation of China(Grants No.52179062 and 51879087).
文摘For a water supply system with long-distance diversion pipelines, in addition to the water hammer problems that occur beyond pumps, the safety of the water diversion pipeline in front of pumps also deserves attention. In this study, a water hammer protection scheme combined with an overflow surge tank and a regulating valve was developed. A mathematical model of the overflow surge tank was developed, and an analytical formula for the height of the overflow surge tank was derived. Furthermore, a practical water supply project was used to evaluate the feasibility of the combined protection scheme and analyze the sensitivity of valve regulation rules. The results showed that the combined protection scheme effectively reduced the height of the surge tank, lessened the difficulties related to construction, and reduced the necessary financial investment for the project. The two-stage closing rule articulated as fast first and then slow could minimize the overflow volume of the surge tank when the power failure occurred, while the two-stage opening rule articulated as slow first and then fast could be more conducive to the safety of the water supply system when the pump started up.
基金the National Natural Science Foundation of China(32172240)BL19U2 beamline of National Facility for Protein Science in Shanghai(NFPS)at Shanghai Synchrotron Radiation Facility,for their assistance during data collection。
文摘Three materials(agar,konjac glucomannan(KGM)andκ-carrageenan)were used to prepare ternary systems,i.e.,sol-gels and their dried composites conditioned at varied relative humidity(RH)(33%,54%and 75%).Combined methods,e.g.,scanning electron microscopy,small-angle X-ray scattering,infrared spectroscopy(IR)and X-ray diffraction(XRD),were used to disclose howκ-carrageenan addition tailors the features of agar/KGM/κ-carrageenan ternary system.As affirmed by IR and XRD,the ternary systems withκ-carrageenan below 25%(agar/KGM/carrageenan,50:25:25,m/m)displayed proper component interactions,which increased the sol-gel transition temperature and the hardness of obtained gels.For instance,the ternary composites could show hardness about 3 to 4 times higher than that for binary counterpart.These gels were dehydrated to acquire ternary composites.Compared to agar/KGM composite,the ternary composites showed fewer crystallites and nanoscale orders,and newly-formed nanoscale structures from chain assembly.Such multi-scale structures,for composites withκ-carrageenan below 25%,showed weaker changes with RH,as revealed by especially morphologic and crystalline features.Consequently,the ternary composites with lessκ-carrageenan(below 25%)exhibited stabilized elongation at break and hydrophilicity at different RHs.This hints to us that agar/KGM/κ-carrageenan composite systems can display series applications with improved features,e.g.,increased sol-gel transition point.
基金supported by Shanghai Shuguang Plan Project,No. 18SG15Shanghai Outstanding Young Scholars Project+1 种基金Shanghai Talent Development Project,No. 2019044Clinical Research Plan of SHDC,No. SHDC 2020CR2027B (all to SC)。
文摘Anti-IgLON5 disease is a recently defined autoimmune disorder of the nervous system associated with autoantibodies against IgLON5. Given its broad clinical spectrum and extremely complex pathogenesis, as well as difficulties in its early diagnosis and treatment, anti-IgLON5 disease has become the subject of considerable research attention in the field of neuroimmunology. Anti-IgLON5 disease has characteristics of both autoimmunity and neurodegeneration due to the unique activity of the antiIgLON5 antibody. Neuropathologic examination revealed the presence of a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum, potentially broadening our understanding of tauopathies. In contrast to that seen with other autoimmune encephalitis-related antibodies, basic studies have demonstrated that IgLON5 antibody-induced neuronal damage and degeneration are irreversible, indicative of a potential link between autoimmunity and neurodegeneration in antiIgLON5 disease. Herein, we comprehensively review and discuss basic and clinical studies relating to anti-IgLON5 disease to better understand this complicated disorder.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82071287,81870916)the National Natural Science Foundation of China(Grant No.:81971097)+3 种基金the Basic Public Interests Research Plan of Zhejiang Province,China(Grant No.:GF18H090006)the National Natural Science Foundation of China(Grant No.:81701214)the National Natural Science Foundation of China(Grant No.:82001299)the Natural Science Foundation of Zhejiang Province,China(Grant No.:TGD23C040017).
文摘The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.
基金Fundamental Research Funds for the Central Universities,Grant/Award Numbers:30920041113,30921013103Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20190460+2 种基金Jiangsu innovative/entre‐preneurial talent program,Grant/Award Number:2019Basic Science Center Program for Ordered Energy Conversion of the National Natural Science Foundation of China,Grant/Award Number:51888103National Natural Science Foundation of China,Grant/Award Numbers:52006105,92163124。
文摘High-entropy materials are composed of five or more metal elements with equimolar or near-equimolar concentrations within one crystal structure,which offer remarkable structural properties for many applications.Despite previously reported entropy-driven stabilization mechanisms,many high-entropy materials still tend to decompose to produce a variety of derivatives under operating conditions.In this study,we use transition-metal(Ni,Co,Ni,Zn,V)-based high-entropy metal-organic frameworks(HE-MOFs)as the precursors to produce different derivatives under acidic/alkaline treatment.We have shown that HE-MOFs and derivatives have shown favorable kinetics for N_(2)electrofixation in different pH electrolytes,specifically cathodic nitrogen reduction reaction in acidic media and anodic oxygen evolution reaction in alkaline media.To buffer the pH mismatch,we have further constructed an asymmetric acidic/alkaline device prototype by using bipolar membranes.As expected,the prototype showed remarkable activities,with an NH_(3)yield rate of 42.76μg h^(−1)mg^(−1),and Faradaic efficiency of 14.75%and energy efficiency of 2.59%,which are 14.4 and 4.4 times larger than those of its symmetric acidic and alkaline counterparts,respectively.
