Objective To investigate the chemical compositions of Maxing Shigan Decoction(麻杏石甘汤,MXSGD)and elucidate its anti-influenza A virus(IAV)mechanism from prediction to validation.Methods Ultra high-performance liquid...Objective To investigate the chemical compositions of Maxing Shigan Decoction(麻杏石甘汤,MXSGD)and elucidate its anti-influenza A virus(IAV)mechanism from prediction to validation.Methods Ultra high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was employed to analyze the chemical compositions of MXSGD.Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV.A protein-protein interaction(PPI)network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations.A total of 24 BALB/c mice were infected with IAV to build IAV mouse models.After successful modelling,the mouse models were randomly divided into model,MXSGD high-dose(2.8 g/kg),MXSGD low-dose(1.4 g/kg),and oseltamivir(20.14 mg/kg)groups,with an additional normal mice as control group(n=6 per group).The treatments were administered by gavage daily between 8:00 a.m.and 10:00 a.m.for five consecutive days.Upon completion of the administration,the body weight ratio,lung index,protein content in the bronchoalveolar lavage fluid(BALF),and the levels of inflammatory factors including interleukin(IL)-6 and tumor necrosis factor(TNF)-αin mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection.Furthermore,the expression levels of mechanistic target of rapamycin(mTOR),hypoxia inducible factor(HIF)-1α,and vascular endothelial growth factor(VEGF)proteins in the HIF-1 signaling pathway,which was enriched by network pharmacology,were detected by Western blot.Results A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method.These chemical components can be classified into 9 primary categories and 31 secondary categories.After intersecting the chemical component targets with IAV-related targets,a total of 567 potential MXSGD components targeting IAV were identified.The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways,including apoptosis,TNF,HIF-1,and IL-17 signaling pathways.The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α,mTOR,and VEGF were all lower than–5.0 kcal/mol.Furthermore,molecular dynamics simulations confirmed the structural stability of the resulting complexes.Animal experiments showed that compared with the normal controls,IAV-infected mice showed significantly reduced body weight ratio,markedly increased lung index,protein content in BALF,and the levels of inflammatory factors such as IL-6 and TNF-α(P<0.01),thereby causing damage to the lung tissue;consequently,the expression levels of mTOR,HIF-1α,and VEGF proteins in the lung tissues of these mice were significantly elevated(P<0.01).However,after MXSGD treatment,the mouse models presented a significant increase in body weight ratio,as well as marked decreases in lung index,protein content in BALF,and the levels of inflammatory factors including IL-6 and TNF-α(P<0.01).Furthermore,the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR,HIF-1α,and VEGF proteins in lung tissues(P<0.01 or P<0.05).Conclusion MXSGD exerts anti-IAV effects through multi-component,multi-target,and multi-pathway synergism.Among them,1-methoxyphaseollin is identified as a potential key component,which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway,providing experimental evidence for the clinical application of MXSGD.展开更多
BACKGROUND Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor prognosis.MicroRNA(miR)-1304 is a newly discovered non-coding RNA,which shows differential expression in other cancers,and its cli...BACKGROUND Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor prognosis.MicroRNA(miR)-1304 is a newly discovered non-coding RNA,which shows differential expression in other cancers,and its clinical value in esophageal carcinoma remains unclear.AIM To explore the expression of miR-1304 in patients with esophageal carcinoma and its clinical value.METHODS The expression of miR-1304 in patients with esophageal carcinoma was analyzed based on the data on miR in esophageal carcinoma downloaded from The Cancer Genome Atlas database.Quantitative real-time polymerase chain reaction was adopted to determine the expression of miR-1304 in the tissues and serum of patients.The clinical diagnostic value of miR-1304 and independent factors for recurrence and prognosis of esophageal carcinoma were then analyzed.The potential target genes of miR-1304 were predicted,and then analyzed based on gene ontology,Kyoto Encyclopedia of Genes,and Genomes,and protein-protein interaction.RESULTS The expression of miR-1304 in the tissues and serum of patients with esophageal carcinoma increased,and was also increased according to the database.Patients with high expression of miR-1304 suffered increased rates of tumor≥3 cm,low differentiation and stage II+III.miR-1304 had a diagnostic value in identifying esophageal carcinoma,tumor size,differentiation and TNM stage.Tumor size,differentiation,TNM stage,and miR-1304 were independent risk factors for recurrence of esophageal carcinoma,and they had certain predictive and diagnostic value for the recurrence of esophageal carcinoma.Seventy-eight patients showed a 3-year survival rate of 38.46%,and patients with high expression of miR-1304 had a relatively lower survival rate.Multivariate analysis revealed that tumor size,differentiation,recurrence and miR-1304 were independent factors for the prognosis of patients.MiRTarBase,miRDB,and Targetscan predicted 20 target genes in total.Gene ontology enrichment analysis found 18 functions with aP<0.05,and Kyoto Encyclopedia of Genes,and Genomes analysis found 11 signal pathways with aP<0.05.String analysis of protein co-expression found 269 relationship pairs,of which co-expression with epidermal growth factor was the most common.CONCLUSION miR-1304 can be used as a potential indicator for the diagnosis and recurrence of esophageal carcinoma and for survival of patients with this disease.展开更多
BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains el...BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.展开更多
Flood disasters pose serious threats to human life and property worldwide.Exploring the spatial drivers of flood disasters on a macroscopic scale is of great significance for mitigating their impacts.This study propos...Flood disasters pose serious threats to human life and property worldwide.Exploring the spatial drivers of flood disasters on a macroscopic scale is of great significance for mitigating their impacts.This study proposes a comprehensive framework for integrating driving-factor optimization and interpretability,while considering spatial heterogeneity.In this framework,the Optimal Parameter-based Geographic Detector(OPGD),Recursive Feature Estimation(RFE),and Light Gradient Boosting Machine(LGBM)models were utilized to construct the OPGD–RFE–LGBM coupled model to identify the essential driving factors and simulate the spatial distribution of flood disasters.The SHapley Additive ExPlanation(SHAP)interpreter was employed to quantitatively explain the driving mechanisms behind the spatial distribution of flood disasters.Yunnan Province,a typical mountainous and plateau area in Southwest China,was selected to implement the proposed framework and conduct a case study.For this purpose,a flood disaster inventory of 7332 historical events was prepared,and 22 potential driving factors related to precipitation,surface environment,and human activity were initially selected.Results revealed that flood disasters in Yunnan Province exhibit high spatial heterogeneity,with geomorphic zoning accounting for 66.1%of the spatial variation in historical flood disasters.The OPGD–RFE–LGBM coupled model offers clear advantages over a single LGBM in identifying essential driving factors and quantitatively analyzing their impacts.Moreover,the simulation performance shows a slight improvement(a 6%average decrease in RMSE and an average increase of 1%in R2)even with reduced factor data.Factor explanatory analysis indicated that the combination of the essential driving factor sets varied across different subregions;nevertheless,precipitation-related factors,such as precipitation intensity index(SDII),wet days(R10MM),and 5-day maximum precipitation(RX5day),were the main driving factors controlling flood disasters.This study provides a quantitative analytical framework for the spatial drivers of flood disasters at large scales with significant heterogeneity,offering a reference for disaster management authorities in developing macro-strategies for disaster prevention.展开更多
目的:总结成人急性胰腺炎住院病人疼痛管理的最佳证据。方法:计算机检索BMJ best practice、Up To Date、CINAHL等关于成人急性胰腺炎病人疼痛管理的所有证据,经过方法学质量评价后,根据主题对证据进行提取与汇总。结果:纳入文献14篇,...目的:总结成人急性胰腺炎住院病人疼痛管理的最佳证据。方法:计算机检索BMJ best practice、Up To Date、CINAHL等关于成人急性胰腺炎病人疼痛管理的所有证据,经过方法学质量评价后,根据主题对证据进行提取与汇总。结果:纳入文献14篇,其中指南2篇、专家共识3篇、文献综述4篇等,从疼痛评估、干预策略、教育与培训3个方面总结了16条最佳证据。结论:将16条最佳证据结合临床情景,为成人急性胰腺炎住院病人疼痛的综合管理提供循证依据。展开更多
Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has bee...Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has been proved to be efficient tunneling mediator. While how it exactly modulates charge transport in a long peptide sequence remains poorly explored. In this work, we studied charge transport of a model peptide junction, where oligo-alanine peptide was doped by histidine at different position,and the series of peptides were self-assembled into a monolayer on gold electrode with soft EGa In as top electrode to form molecular junction. It was found that histidine increased the overall conductance of the peptide, meanwhile, its position modulated the conductance as well. Quantitative analysis by transport model and ultraviolet photoelectron spectroscopy(UPS) indicated a sequence dependent energy landscape of the tunneling barrier of the junction. Density-functional theory(DFT) calculation on the electronic structure of histidine doped oligo-alanine peptides revealed localized highest occupied molecular orbital(HOMO) on imidazole group of the histidine, which decreased charge transport barrier.展开更多
While the expression of programmed death ligand-1(PD-L1)is associated with response to immune therapy,PD-L1-negative patients may still benefit from immune treatment.Programmed death ligand-2(PD-L2),another crucial im...While the expression of programmed death ligand-1(PD-L1)is associated with response to immune therapy,PD-L1-negative patients may still benefit from immune treatment.Programmed death ligand-2(PD-L2),another crucial immune checkpoint molecule interacting with PD-1,correlates with the efficacy of various tumor immune therapies.This study investigates the expression of PD-L2 in non-small cell lung cancer(NSCLC)patients following anti-PD-1 therapy and its predictive value for clinical survival outcomes.Additionally,we explore the noninvasive,real-time,and dynamic quantitative analysis potential of PD-L2 positron emission tomography(PET)imaging in transplanted tumors.We utilized[^(68)Ga]Ga-labeled peptide HN11-1 for PD-L2 PET imaging.The results indicate a higher response rate to anti-PD-1 therapy in patients positive for both PD-L1 and PD-L2,with PD-L2 status independently predicting progression-free survival(PFS)with pembrolizumab treatment.Furthermore,[^(68)Ga]Ga-HN11-1 PET imaging demonstrates specificity in assessing PD-L2 status.Overall,we confirm the correlation between high PD-L2 expression and favorable PFS in NSCLC patients post anti-PD-1 therapy and highlight the promising potential of[^(68)Ga]Ga-HN11-1 as a specific tracer for PD-L2 in preclinical and initial human trials.展开更多
Organic memristors,integrating chemically designed resistive switching and mechanical flexibility,present promising hardware opportunities for neuromorphic computing,particularly in the development of next-generation ...Organic memristors,integrating chemically designed resistive switching and mechanical flexibility,present promising hardware opportunities for neuromorphic computing,particularly in the development of next-generation wearable artificial intelligence devices.However,challenges persist in achieving high yield,controllable switching,and multi-modal information processing.In this study,we introduce an efficient distribution of conversion bridges(EDCB)strategy by dispersing organic semiconductor(poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene],PBTTT)in elastomer(polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene,SEBS).This innovative approach results in memristors with exceptional yield,high stretchability,and reliable switching performance.By fine-tuning the semiconductor content,we shift the primary charge carriers from ions to electrons,realizing modulable non-volatile,and volatile duo-mode memristors.This advancement enables multi-modal signal processing at distinct operational mechanisms—non-volatile mode for image recognition in convolutional neural networks(CNNs)and volatile mode for dynamic classification and prediction in reservoir computing(RC).A fully analog RC hardware system is further demonstrated by integrating the distinct volatile and non-volatile modes of the EDCB-based memristor into the dynamic neuron network and the linear regression layer of the RC respectively,achieving high accuracy in online arrhythmia detection tasks.Our work paves the way for high-yield organic memristors with mechanical flexibility,advancing efficient multi-mode neuromorphic computing within a unified memristor system integrating volatile and non-volatile functionalities.展开更多
基金Natural Science Foundation of Hunan Province(2025JJ80078)Open Fund of Hunan University of Chinese Medicine(21PTKF1005)。
文摘Objective To investigate the chemical compositions of Maxing Shigan Decoction(麻杏石甘汤,MXSGD)and elucidate its anti-influenza A virus(IAV)mechanism from prediction to validation.Methods Ultra high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was employed to analyze the chemical compositions of MXSGD.Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV.A protein-protein interaction(PPI)network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations.A total of 24 BALB/c mice were infected with IAV to build IAV mouse models.After successful modelling,the mouse models were randomly divided into model,MXSGD high-dose(2.8 g/kg),MXSGD low-dose(1.4 g/kg),and oseltamivir(20.14 mg/kg)groups,with an additional normal mice as control group(n=6 per group).The treatments were administered by gavage daily between 8:00 a.m.and 10:00 a.m.for five consecutive days.Upon completion of the administration,the body weight ratio,lung index,protein content in the bronchoalveolar lavage fluid(BALF),and the levels of inflammatory factors including interleukin(IL)-6 and tumor necrosis factor(TNF)-αin mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection.Furthermore,the expression levels of mechanistic target of rapamycin(mTOR),hypoxia inducible factor(HIF)-1α,and vascular endothelial growth factor(VEGF)proteins in the HIF-1 signaling pathway,which was enriched by network pharmacology,were detected by Western blot.Results A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method.These chemical components can be classified into 9 primary categories and 31 secondary categories.After intersecting the chemical component targets with IAV-related targets,a total of 567 potential MXSGD components targeting IAV were identified.The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways,including apoptosis,TNF,HIF-1,and IL-17 signaling pathways.The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α,mTOR,and VEGF were all lower than–5.0 kcal/mol.Furthermore,molecular dynamics simulations confirmed the structural stability of the resulting complexes.Animal experiments showed that compared with the normal controls,IAV-infected mice showed significantly reduced body weight ratio,markedly increased lung index,protein content in BALF,and the levels of inflammatory factors such as IL-6 and TNF-α(P<0.01),thereby causing damage to the lung tissue;consequently,the expression levels of mTOR,HIF-1α,and VEGF proteins in the lung tissues of these mice were significantly elevated(P<0.01).However,after MXSGD treatment,the mouse models presented a significant increase in body weight ratio,as well as marked decreases in lung index,protein content in BALF,and the levels of inflammatory factors including IL-6 and TNF-α(P<0.01).Furthermore,the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR,HIF-1α,and VEGF proteins in lung tissues(P<0.01 or P<0.05).Conclusion MXSGD exerts anti-IAV effects through multi-component,multi-target,and multi-pathway synergism.Among them,1-methoxyphaseollin is identified as a potential key component,which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway,providing experimental evidence for the clinical application of MXSGD.
文摘BACKGROUND Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor prognosis.MicroRNA(miR)-1304 is a newly discovered non-coding RNA,which shows differential expression in other cancers,and its clinical value in esophageal carcinoma remains unclear.AIM To explore the expression of miR-1304 in patients with esophageal carcinoma and its clinical value.METHODS The expression of miR-1304 in patients with esophageal carcinoma was analyzed based on the data on miR in esophageal carcinoma downloaded from The Cancer Genome Atlas database.Quantitative real-time polymerase chain reaction was adopted to determine the expression of miR-1304 in the tissues and serum of patients.The clinical diagnostic value of miR-1304 and independent factors for recurrence and prognosis of esophageal carcinoma were then analyzed.The potential target genes of miR-1304 were predicted,and then analyzed based on gene ontology,Kyoto Encyclopedia of Genes,and Genomes,and protein-protein interaction.RESULTS The expression of miR-1304 in the tissues and serum of patients with esophageal carcinoma increased,and was also increased according to the database.Patients with high expression of miR-1304 suffered increased rates of tumor≥3 cm,low differentiation and stage II+III.miR-1304 had a diagnostic value in identifying esophageal carcinoma,tumor size,differentiation and TNM stage.Tumor size,differentiation,TNM stage,and miR-1304 were independent risk factors for recurrence of esophageal carcinoma,and they had certain predictive and diagnostic value for the recurrence of esophageal carcinoma.Seventy-eight patients showed a 3-year survival rate of 38.46%,and patients with high expression of miR-1304 had a relatively lower survival rate.Multivariate analysis revealed that tumor size,differentiation,recurrence and miR-1304 were independent factors for the prognosis of patients.MiRTarBase,miRDB,and Targetscan predicted 20 target genes in total.Gene ontology enrichment analysis found 18 functions with aP<0.05,and Kyoto Encyclopedia of Genes,and Genomes analysis found 11 signal pathways with aP<0.05.String analysis of protein co-expression found 269 relationship pairs,of which co-expression with epidermal growth factor was the most common.CONCLUSION miR-1304 can be used as a potential indicator for the diagnosis and recurrence of esophageal carcinoma and for survival of patients with this disease.
基金Supported by Construction of Engineering Laboratory of Jilin Development and Reform Commission(grant no.3J115AK93429)Jilin Provincial Science and Technology Department Medical Health Project(grant no.3D5195001429)
文摘BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.
基金the National Key Research and Development Program of China(Grant No.2022YFF1302405)the Yunnan Province Key Research and Development Program(Grant No.202203AC100005)+1 种基金the National Natural Science Foundation of China(Grant No.42061005,42067033)Applied Basic Research Programs of Yunnan Province(Grant No.202101AT070110,202001BB050073).
文摘Flood disasters pose serious threats to human life and property worldwide.Exploring the spatial drivers of flood disasters on a macroscopic scale is of great significance for mitigating their impacts.This study proposes a comprehensive framework for integrating driving-factor optimization and interpretability,while considering spatial heterogeneity.In this framework,the Optimal Parameter-based Geographic Detector(OPGD),Recursive Feature Estimation(RFE),and Light Gradient Boosting Machine(LGBM)models were utilized to construct the OPGD–RFE–LGBM coupled model to identify the essential driving factors and simulate the spatial distribution of flood disasters.The SHapley Additive ExPlanation(SHAP)interpreter was employed to quantitatively explain the driving mechanisms behind the spatial distribution of flood disasters.Yunnan Province,a typical mountainous and plateau area in Southwest China,was selected to implement the proposed framework and conduct a case study.For this purpose,a flood disaster inventory of 7332 historical events was prepared,and 22 potential driving factors related to precipitation,surface environment,and human activity were initially selected.Results revealed that flood disasters in Yunnan Province exhibit high spatial heterogeneity,with geomorphic zoning accounting for 66.1%of the spatial variation in historical flood disasters.The OPGD–RFE–LGBM coupled model offers clear advantages over a single LGBM in identifying essential driving factors and quantitatively analyzing their impacts.Moreover,the simulation performance shows a slight improvement(a 6%average decrease in RMSE and an average increase of 1%in R2)even with reduced factor data.Factor explanatory analysis indicated that the combination of the essential driving factor sets varied across different subregions;nevertheless,precipitation-related factors,such as precipitation intensity index(SDII),wet days(R10MM),and 5-day maximum precipitation(RX5day),were the main driving factors controlling flood disasters.This study provides a quantitative analytical framework for the spatial drivers of flood disasters at large scales with significant heterogeneity,offering a reference for disaster management authorities in developing macro-strategies for disaster prevention.
文摘目的:总结成人急性胰腺炎住院病人疼痛管理的最佳证据。方法:计算机检索BMJ best practice、Up To Date、CINAHL等关于成人急性胰腺炎病人疼痛管理的所有证据,经过方法学质量评价后,根据主题对证据进行提取与汇总。结果:纳入文献14篇,其中指南2篇、专家共识3篇、文献综述4篇等,从疼痛评估、干预策略、教育与培训3个方面总结了16条最佳证据。结论:将16条最佳证据结合临床情景,为成人急性胰腺炎住院病人疼痛的综合管理提供循证依据。
基金supported by the National Natural Science Foundation of China (Nos. 21773169, 21973069, 21805144)Natural Science Foundation of Zhejiang Province (No. LY18B020016)the PEIYANG Young Scholars Program of Tianjin University (No. 2018XRX-0007)。
文摘Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has been proved to be efficient tunneling mediator. While how it exactly modulates charge transport in a long peptide sequence remains poorly explored. In this work, we studied charge transport of a model peptide junction, where oligo-alanine peptide was doped by histidine at different position,and the series of peptides were self-assembled into a monolayer on gold electrode with soft EGa In as top electrode to form molecular junction. It was found that histidine increased the overall conductance of the peptide, meanwhile, its position modulated the conductance as well. Quantitative analysis by transport model and ultraviolet photoelectron spectroscopy(UPS) indicated a sequence dependent energy landscape of the tunneling barrier of the junction. Density-functional theory(DFT) calculation on the electronic structure of histidine doped oligo-alanine peptides revealed localized highest occupied molecular orbital(HOMO) on imidazole group of the histidine, which decreased charge transport barrier.
基金the National Natural Science Foundation of China(Grant numbers 91859207 and 81771873)the Science and Technology Innovation Team Talent Project of Hunan Province(Grant number 2021RC4056)+2 种基金the Natural Science Foundation of Hunan Province(Grant number 2023JJ30976)the National Natural Science Foundation of China(Grant number 82372003)the Postdoctoral Fellowship Program of CPSF(Grant number GZC20233586).
文摘While the expression of programmed death ligand-1(PD-L1)is associated with response to immune therapy,PD-L1-negative patients may still benefit from immune treatment.Programmed death ligand-2(PD-L2),another crucial immune checkpoint molecule interacting with PD-1,correlates with the efficacy of various tumor immune therapies.This study investigates the expression of PD-L2 in non-small cell lung cancer(NSCLC)patients following anti-PD-1 therapy and its predictive value for clinical survival outcomes.Additionally,we explore the noninvasive,real-time,and dynamic quantitative analysis potential of PD-L2 positron emission tomography(PET)imaging in transplanted tumors.We utilized[^(68)Ga]Ga-labeled peptide HN11-1 for PD-L2 PET imaging.The results indicate a higher response rate to anti-PD-1 therapy in patients positive for both PD-L1 and PD-L2,with PD-L2 status independently predicting progression-free survival(PFS)with pembrolizumab treatment.Furthermore,[^(68)Ga]Ga-HN11-1 PET imaging demonstrates specificity in assessing PD-L2 status.Overall,we confirm the correlation between high PD-L2 expression and favorable PFS in NSCLC patients post anti-PD-1 therapy and highlight the promising potential of[^(68)Ga]Ga-HN11-1 as a specific tracer for PD-L2 in preclinical and initial human trials.
基金National Natural Science Foundation of China,Grant/Award Numbers:52121002,52173179,92370103ISF-NSFC Joint Scientific Research Program,Grant/Award Number:22361142833+1 种基金Fundamental Research Funds for the Central UniversitiesOpen Project of the State Key Laboratory of Supramolecular Structure and Materials,Grant/Award Number:SKLSSM2024035。
文摘Organic memristors,integrating chemically designed resistive switching and mechanical flexibility,present promising hardware opportunities for neuromorphic computing,particularly in the development of next-generation wearable artificial intelligence devices.However,challenges persist in achieving high yield,controllable switching,and multi-modal information processing.In this study,we introduce an efficient distribution of conversion bridges(EDCB)strategy by dispersing organic semiconductor(poly[2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene],PBTTT)in elastomer(polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene,SEBS).This innovative approach results in memristors with exceptional yield,high stretchability,and reliable switching performance.By fine-tuning the semiconductor content,we shift the primary charge carriers from ions to electrons,realizing modulable non-volatile,and volatile duo-mode memristors.This advancement enables multi-modal signal processing at distinct operational mechanisms—non-volatile mode for image recognition in convolutional neural networks(CNNs)and volatile mode for dynamic classification and prediction in reservoir computing(RC).A fully analog RC hardware system is further demonstrated by integrating the distinct volatile and non-volatile modes of the EDCB-based memristor into the dynamic neuron network and the linear regression layer of the RC respectively,achieving high accuracy in online arrhythmia detection tasks.Our work paves the way for high-yield organic memristors with mechanical flexibility,advancing efficient multi-mode neuromorphic computing within a unified memristor system integrating volatile and non-volatile functionalities.
