Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechani...Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPI and PII exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepatotoxicity of PPI and PII was associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the cholesterol synthesis,selected as the potential targets,were confirmed by the molecular docking,the overexpression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPI could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPI-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.展开更多
To enhance system stability,solar collectors have been integrated with air-source heat pumps.This integration facilitates the concurrent utilization of solar and air as energy sources for the system,leading to an impr...To enhance system stability,solar collectors have been integrated with air-source heat pumps.This integration facilitates the concurrent utilization of solar and air as energy sources for the system,leading to an improvement in the system’s heat generation coefficient,overall efficiency,and stability.In this study,we focus on a residential building located in Lhasa as the target for heating purposes.Initially,we simulate and analyze a solar-air source heat pump combined heating system.Subsequently,while ensuring the system meets user requirements,we examine the influence of solar collector installation angles and collector area on the performance of the solar-air source heat pump dual heating system.Through this analysis,we determine the optimal installation angle and collector area to optimize system performance.展开更多
The protein encoded by bcl-2 proto-oncogene plays an important role in the mitochondria-mediated apoptotic pathway. Although the general role of Bcl-2 is anti-apoptotic, previous work showed that Bcl-2 fragments cleav...The protein encoded by bcl-2 proto-oncogene plays an important role in the mitochondria-mediated apoptotic pathway. Although the general role of Bcl-2 is anti-apoptotic, previous work showed that Bcl-2 fragments cleaved by caspases could promote apoptotic process. We report herein that Bcl-2 protein was cleaved to produce two fragments of around 23 kDa in human hepatocarcinoma BEL-7404 cells or in Bcl-2 overexpressing CHO cells induced by cisplatin. Treating cells with the general caspase inhibitor z-VAD-fmk blocked the induced cleavage of Bcl-2. Mutagenesis analyses showed that Bcl-2 was cleaved by caspases at two adjacent recognition sites in the loop domain (YEWD31↓AGD34↓V), which could be inhibited by caspase-8 and -3 inhibitors, respectively. Overexpression of the carboxyl terminal 23 kDa fragments increased the sensitivity of CHO cells to cisplatin-induced apoptosis. These results indicate that Bcl-2 can be cleaved into two close fragments by different caspases during cisplatin-induced apoptosis, both of which contribute to the acceleration ofapoptotic process.展开更多
The effects of aerosol-radiation interactions(ARI)are not only important for regional and global climate,but they can also drive particulate matter(PM)pollution.In this study,the ARI contribution to the near-surface f...The effects of aerosol-radiation interactions(ARI)are not only important for regional and global climate,but they can also drive particulate matter(PM)pollution.In this study,the ARI contribution to the near-surface fine PM(PM_(2.5))concentrations in the Guanzhong Basin(GZB)is evaluated under four unfavorable synoptic patterns,including“northlow”,“transition”,“southeast-trough”,and“inland-high”,based on WRF-Chem model simulations of a persistent heavy PM pollution episode in January 2019.Simulations show that ARI consistently decreases both solar radiation reaching down to the surface(SWDOWN)and surface temperature(TSFC),which then reduces wind speed,induces sinking motion,and influences cloud formation in the GZB.However,large differences under the four synoptic patterns still exist.The average reductions of SWDOWN and daytime TSFC in the GZB range from 15.2%and 1.04°C in the case of the“transition”pattern to 26.7%and 1.69°C in the case of the“north-low”pattern,respectively.Furthermore,ARI suppresses the development of the planetary boundary layer(PBL),with the decrease of PBL height(PBLH)varying from 18.7%in the case of the“transition”pattern to 32.0%in the case of the“north-low”pattern.The increase of daytime near-surface PM_(2.5)in the GZB due to ARI is 12.0%,8.1%,9.5%,and 9.7%under the four synoptic patterns,respectively.Ensemble analyses also reveal that when near-surface PM_(2.5)concentrations are low,ARI tends to lower PM_(2.5)concentrations with decreased PBLH,which is caused by enhanced divergence or a transition from divergence to convergence in an area.ARI contributes 15%-25%toward the near-surface PM_(2.5)concentrations during the severe PM pollution period under the four synoptic patterns.展开更多
Objective:To systematically evaluate the clinical efficacy and safety of Qingkailing (QKL) injection for pediatric acute upper respiratory infection (AURI).Methods:We searched for randomized controlled trials (RCTs) o...Objective:To systematically evaluate the clinical efficacy and safety of Qingkailing (QKL) injection for pediatric acute upper respiratory infection (AURI).Methods:We searched for randomized controlled trials (RCTs) of pediatric AURI treated by QKL and western medicine (WM) in the China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang,Chinese Biomedical Literature Database,PubMed and Cochrane Library from inception to August,2016.Two reviewers independently retrieved the RCTs and extracted information.The Cochrane Collaboration Risk of Bias Assessment Tool was used to evaluate the methodological quality of RCTs.The data were meta-analyzed by RevMan 5.3 software.Results:Ultimately,21 RCTs that involved 2364 participants were included,and the quality of RCTs was generally poor.According to the meta-analysis,the combined use of QKL and WM for treating AURI can be effective,with a higher total effective rate,less defervescence time and less recovery time of tonsil and throat inflammation.Twenty-five adverse drug reactions (ADRs) were reported in three RCTs,but there were no serious ADRs.Conclusion:The combination of QKL and WM for treating pediatric AURI can result in better effects,but no definitive conclusions can be made regarding its safety.More rigorous RCTs are needed to support the clinical application of QKL.展开更多
Objective:Amphibian skin secretions are an abundant source of bioactive peptides,some of which could be developed as candidate drugs.Among these natural peptides,cytolytic peptides have attracted the most attention gi...Objective:Amphibian skin secretions are an abundant source of bioactive peptides,some of which could be developed as candidate drugs.Among these natural peptides,cytolytic peptides have attracted the most attention given that they might replace conventional antibiotics and help deal with the problem of microbial resistance.This study discovered two bioactive peptides,Brevinin-1-PLr and Nigrocin-2-OV,from two species frogs,the Chinese bamboo leaf odorous frog (Odorrana versabilis) and the North American pickerel frog (Rana palustris),respectively.Their antimicrobial,anticancer and hemolytic activities were also investigated.Methods:cDNA sequences encoding peptides were cloned from cDNA libraries constructed from the lyophilized secretions of the Chinese bamboo leaf odorous frog and the North American pickerel frog.By reversed-phase HPLC and MS/MS fragmentation sequencing,the encoded novel peptides,named Nigrocin-2-OV and Brevinin-1-PLr,were identified in skin secretions and their structures were confirmed.Replicates of both peptides were produced through solid phase peptide synthesis.Their antimicrobial and anticancer activity was studied against three types of microorganisms (Staphylococcus aureus,Candida albicans,and Escherichia coli) and five cancer cell lines (NCI-H157,PC-3,MDA-MB-435s,MCF-7,and U251MG).Their hemolytic activity was investigated using whole horse blood.Results:In this research,cDNA sequences encoding two novel 24-mer peptides were cloned from cDNA libraries constructed from the lyophilized skin secretions of the Chinese bamboo leaf odorous frog and the North American pickerel frog.Both of the peptides had the strongest inhibitory effect against C.albicans,and IC50 values against five cancer cell lines were all under 6 μM.Conclusions:Nigrocin-2-OV and Brevinin-1-PLr had the strong ability to inhibit the proliferation of studied microorganisms and tumor cell lines,with slight hemolytic activity.Compared with Brevinin-1-PLr,Nigrocin-2-OV exhibited higher antimicrobial and anticancer activity but slightly higher hemolytic activity.展开更多
The study aimed to analyze the reporting and methodological quality of systematic reviews(SRs)/meta-analyses(MAs)of animal models to provide references for later studies and avoid the waste of medical resources.EMBASE...The study aimed to analyze the reporting and methodological quality of systematic reviews(SRs)/meta-analyses(MAs)of animal models to provide references for later studies and avoid the waste of medical resources.EMBASE and MEDLINE databases were searched from inception to November 2017,with no language restriction.Two reviewers selected inclusion dependently and extracted the basic characteristics.Review Manager 5.3,stata 12.0,and SPSS 21 software were used to conduct analyses.A total of 46 SRs/MAs were included.The results showed that the English databases with high retrieval frequency are PubMed/MEDLINE,EMBASE,and Web of Science.67.31%(31/46)of the articles reported the search strategy in the full text or the appendix.65.22%(30/46)reported the literature screening flow diagram,and only 19.57%(9/46)reported the number of works of literature retrieved in each database.60.87%(28/46)illustrated supplement retrieval.Through 2 subgroup analyses,it was found that there were no significant differences in the quality of reports of PRISMA items.But referring to the methodological quality or reporting of PRESS items,SCI was better than that of non-SCI,while there seemed a source of funding to have no significant impact on the methodological quality or the items of PRESS.The results of PRESS,AMSTAR 2,and PRISMA were correlated,and the correlation between PRISMA and AMSTAR 2 was strong.These results demonstrated that search strategies of animal model SRs/MAs are still not enough comprehensive,report specification and methodological quality still need to be ameliorated.To show users the scientificity and rigor of the study,future research should focus on these various guidelines like PRESS,PRISMA,and AMSTAR 2 checklists that have been issued,it can help to increase the value of research and improve the utilization of medical resources.展开更多
Objective:To explore Yan Zhenghua’s drug selection rule for treating digestive system diseases using data mining.Methods:The 609 medical records of digestive system diseases treated by Yan Zhenghua were collected and...Objective:To explore Yan Zhenghua’s drug selection rule for treating digestive system diseases using data mining.Methods:The 609 medical records of digestive system diseases treated by Yan Zhenghua were collected and the herbs in these recipes were examined using a data mining technique.The correlativity between herb pairs and association rules was studied using an Apriori algorithm and the correlativity among multi-herbs was studied using a complex system entropy cluster technique.Results:Yan Zhenghua’s treatment of digestive system diseases featured 15 herbs prescribed at least 159 times each,22 herb pairs prescribed at least 155 times each,and eight frequently used herb core combinations.A confidence greater than 0.91 and a support level greater than 20%were achieved using the modified mutual information method.Conclusion:The data mining results conformed to findings from clinical practice.The data mining method is a valuable technique with which to study the experience of famous,elderly traditional Chinese medicine physicians.展开更多
Background:Tibetan medicinal substances(TMS)has a complete theory that is based on five source doctrines.The theories of“Liuwei”,“Baxing”,“Shiqi Gongxiao”,and“Sanhuawei”constitute the prominent core components...Background:Tibetan medicinal substances(TMS)has a complete theory that is based on five source doctrines.The theories of“Liuwei”,“Baxing”,“Shiqi Gongxiao”,and“Sanhuawei”constitute the prominent core components of the five source doctrines with significant Tibetan characteristics.Objective:This review summarizes the existing literature on the metabolomics and its use in TMS and offers recommendations for future research.Methods:Studies on TMS and the application of metabolomics on TMS are reviewed and summarized.The shortcomings of existing studies and recommendations for future studies are discussed.Conclusions:The recent researches have studied on the theory of TMS.Metabolomics will be increasingly applied to the identification of compounds in TMS,and the resultant detection of biomarkers will help elucidate the metabolic pathways of these substances.展开更多
Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Meth...Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.展开更多
Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction....Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction.Therefore,the prevention of OA progression in the early and middle stages is an urgent clinical problem.In a previous study,we demonstrated that NDRG3-mediated hypoxic response might be closely related to the development and progression of OA.In this study,an injectable thermosensitive hydrogel was established by cross-linking Pluronic F-127 and hyaluronic acid(HA)for the sustained release of hypoxia-induced exosomes(HExos)derived from adipose-derived mesenchymal stem cells.We demonstrated that for OA at the early and middle stages,the HExos-loaded HP hydrogel could maintain the chondrocyte phenotype by enhancing chondrocyte autophagy,reducing chondrocyte apoptosis,and promoting chondrocyte activity and proliferation through the NDRG3-mediated hypoxic response.This novel composite hydrogel,which could activate the NDRG3-mediated hypoxic response,may provide new ideas and a theoretical basis for the treatment of early-and mid-stage OA.展开更多
Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose ...Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose tissue and the development of NAFLD.Using community-based cohort data,we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),and incident NAFLD in 2830 participants(1205 males and 1625 females)aged 55–70 years.During a 4.6-year median follow-up,the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in females.Further analyses showed that the abovementioned positive associations were stronger in males than in females,especially in participants under 60 years old.In contrast,these sex differences disappeared in those over 60 years old.Furthermore,the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific pattern.Additionally,sex-specific potential mediators,such as insulin resistance,lipid metabolism,inflammation,and adipokines,may exist in the associations between adipose tissue and NAFLD.This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age,highlighting the potential need for sex-and age-specific management of NAFLD.展开更多
Little is known about how chronic inflammation contributes to the progression of hepatoceUular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HC...Little is known about how chronic inflammation contributes to the progression of hepatoceUular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c.myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker (DNB) model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms. Meanwhile, the DNB-associated network showed a drastic inversion of protein expression and coexpression levels before and after the critical transition. Two members of DNB, PLA2G6 and CYP2C44, along with their associated differentially expressed proteins, were found to induce dysfunction of arachidonic acid metabolism, further activate inflammatory responses through inflammatory mediator regulation of transient receptor potential channels, and finally lead to impairments of liver detoxification and malignant transition to cancer. As a c-Myc target, PLA2G6 positively correlated with c-Myc in expression, showing a trend from decreasing to increasing during carcinogenesis, with the minimal point at the critical transition or tipping point. Such trend of homologous PLA2G6 and c-Myc was also observed during human hepatocarcinogenesis, with the minimal point at high-grade dysplastic nodules (a stage just before the carcinogenesis). Our study implies that PLA2G6 might function as an oncogene like famous c-Myc during hepatocar- cinogenesis, while downregulation of PLA2G6 and c-Myc could be a warning signal indicating imminent carcinogenesis.展开更多
Dear Editor, Type 2 diabetes mellitus (T2DM) develops only in insulin-resistant subjects when pancreatic β-cell compensation fails (Matveyenko and Butler, 2006). Decreased insulin secretory function and reduced ...Dear Editor, Type 2 diabetes mellitus (T2DM) develops only in insulin-resistant subjects when pancreatic β-cell compensation fails (Matveyenko and Butler, 2006). Decreased insulin secretory function and reduced cell mass are traditionally viewed as major contributing factors in β-cell insufficiency. A recent study using a diabetic rodent model suggests that progressive β-cell de- differentiation is an important underlying mechanism in β-cell failure (Talchai et al., 2012). β-cell dedifferentiation in diabetes refers to the loss by healthy β-cells of key components characteristic of the differen- tiated state (Dor and Glaser, 2013), including insulin (for its secretory product), Glut2 (for glucose intake), and PDX-1 (for critical insulin transcription factor), β-cell dedifferentiation may be largely respon- sible for not only β-cell secretory dysfunction but also impaired β-cell identity. In view of findings that bariatric surgery in a rodent T2DM model led to increased β-cell mass and improved islet morphology (Strader et al., 2009), we investigated the effects of gastric bypass surgery on dedifferentiated β-cells.展开更多
This multicenter phase-II trial aimed to investigate the efficacy,safety,and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC.Patients who fai...This multicenter phase-II trial aimed to investigate the efficacy,safety,and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC.Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled.Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles,followed by the maintenance of toripalimab and pemetrexed.The primary endpoint was objective-response rate(ORR).Integrated biomarker analysis of PD-L1 expression,tumor mutational burden(TMB),CD8+tumor-infiltrating lymphocyte(TIL)density,whole-exome,and transcriptome sequencing on tumor biopsies were also conducted.Forty patients were enrolled with an overall ORR of 50.0%and disease-control rate(DCR)of 87.5%.The median progression free survival(PFS)and overall survival were 7.0 and 23.5 months,respectively.The most common treatment-related adverse effects were leukopenia,neutropenia,anemia,ALT/AST elevation,and nausea.Biomarker analysis showed that none of PD-L1 expression,TMB level,and CD8+TIL density could serve as a predictive biomarker.Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type.Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC.DSPP mutation might serve as a potential biomarker for this combination.A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing(NCT03924050).展开更多
Achieving strong coupling between plasmonic oscillators can significantly modulate their intrinsic optical properties.Here,we report the direct observation of ultrafast plasmonic hot electron transfer from an Au grati...Achieving strong coupling between plasmonic oscillators can significantly modulate their intrinsic optical properties.Here,we report the direct observation of ultrafast plasmonic hot electron transfer from an Au grating array to an MoS_(2) monolayer in the strong coupling regime between localized surface plasmons(LSPs)and surface plasmon polaritons(SPPs).By means of femtosecond pump-probe spectroscopy,the measured hot electron transfer time is approximately 40 fs with a maximum external quantum yield of 1.65%.Our results suggest that strong coupling between LSPs and SPPs has synergetic effects on the generation of plasmonic hot carriers,where SPPs with a unique nonradiative feature can act as an‘energy recycle bin’to reuse the radiative energy of LSPs and contribute to hot carrier generation.Coherent energy exchange between plasmonic modes in the strong coupling regime can further enhance the vertical electric field and promote the transfer of hot electrons between the Au grating and the MoS_(2) monolayer.Our proposed plasmonic strong coupling configuration overcomes the challenge associated with utilizing hot carriers and is instructive in terms of improving the performance of plasmonic opto-electronic devices.展开更多
Transgenic technology allows a gene of interest to be introduced into the genome of a laboratory animal,and provides an extremely powerful tool to dissect the molecular mechanisms of disease.Transgenic mouse models ma...Transgenic technology allows a gene of interest to be introduced into the genome of a laboratory animal,and provides an extremely powerful tool to dissect the molecular mechanisms of disease.Transgenic mouse models made by microinjection of DNA into zygotic pronuclei in particular have been widely used by the genetics community for 30 years.However,it remains a rather crude approach:injected sequences randomly insert in multiple copies as concatamers,they can be mutagenic,and they have variable or silenced expression depending on the site of integration,a phenomenon called position effects.As a result,multiple lines are required in order to confirm appropriate transgene expression.This can be partially overcome by flanking transgenes with insulator sequences to protect the transgene from the influence of the surrounding regulatory elements.Large(\300 kb)BACbased transgenic vectors have also been shown to be more resistant to position effects.However,animals carrying extra copies of fairly large regions of the genome could have unpredictable phenotypes.The most effective method used to control for position effects is to target transgene insertion to specific genomic loci,the so-called targeted transgenesis;for instance,the fast,site-specific transgenic technology Targatt TM.The purpose of this review is to provide an overview on the current existing methods for making targeted transgenic mouse models.展开更多
OBJECTIVE: To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of diabeticperi pheral neuropathy(DPN).METHODS: Randomized controlled trials investigating the efficacy of ...OBJECTIVE: To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of diabeticperi pheral neuropathy(DPN).METHODS: Randomized controlled trials investigating the efficacy of puerarin injection on DPN were searched for in China National Knowledge Infrastructure Database, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from establishment to April 30.Two reviewers independently retrieved and extracted the information.The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.2 software.RESULTS: Twenty-two studies involving 1664 participants were included. The quality of the studies was found to be relatively low. Meta-analysis showed that puerarin injection combined with western medication was more effective than conventional therapy for rate, nerve conduction velocity(NCV), and hemorheology index. Six adverse drug reactions(ADRs) from puerarin injection were reported in two studies. Reactions included facial flushing, palpitations, and pain at infusion locations. However,noserious ADRs were reported.CONCLUSION: Puerarin injection was effective for the treatment of DPN. Puerarin can improve the total effective rate, correct NCV that was decreased by diabetes, and improve the hemorheology index.Puerarin was also relatively safe clinically. However,since the articles included in the study were not high-quality, more studies should be conducted to strengthen their findings.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82204753),the Scientific Research Staring Foundation for the New Teachers of Beijing University of Chinese Medicine(Grant No.:2020-JYB-XJSJJ-009),and Special Scientific Research for Traditional Chinese Medicine of State Administration of Traditional Chinese Medicine of China(Grant No.:201507004).The funders had no role in the study design,data collection,data analysis,interpretation,or writing of the report.
文摘Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPI and PII exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepatotoxicity of PPI and PII was associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the cholesterol synthesis,selected as the potential targets,were confirmed by the molecular docking,the overexpression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPI could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPI-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
文摘To enhance system stability,solar collectors have been integrated with air-source heat pumps.This integration facilitates the concurrent utilization of solar and air as energy sources for the system,leading to an improvement in the system’s heat generation coefficient,overall efficiency,and stability.In this study,we focus on a residential building located in Lhasa as the target for heating purposes.Initially,we simulate and analyze a solar-air source heat pump combined heating system.Subsequently,while ensuring the system meets user requirements,we examine the influence of solar collector installation angles and collector area on the performance of the solar-air source heat pump dual heating system.Through this analysis,we determine the optimal installation angle and collector area to optimize system performance.
基金grants of National Natural Science Foundation of China (#30230110, #0637S 12442, #30670433)
文摘The protein encoded by bcl-2 proto-oncogene plays an important role in the mitochondria-mediated apoptotic pathway. Although the general role of Bcl-2 is anti-apoptotic, previous work showed that Bcl-2 fragments cleaved by caspases could promote apoptotic process. We report herein that Bcl-2 protein was cleaved to produce two fragments of around 23 kDa in human hepatocarcinoma BEL-7404 cells or in Bcl-2 overexpressing CHO cells induced by cisplatin. Treating cells with the general caspase inhibitor z-VAD-fmk blocked the induced cleavage of Bcl-2. Mutagenesis analyses showed that Bcl-2 was cleaved by caspases at two adjacent recognition sites in the loop domain (YEWD31↓AGD34↓V), which could be inhibited by caspase-8 and -3 inhibitors, respectively. Overexpression of the carboxyl terminal 23 kDa fragments increased the sensitivity of CHO cells to cisplatin-induced apoptosis. These results indicate that Bcl-2 can be cleaved into two close fragments by different caspases during cisplatin-induced apoptosis, both of which contribute to the acceleration ofapoptotic process.
基金This work is financially supported by the National Key R&D Plan(Grant No.2017YFC0210000)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB40030200)+1 种基金the National Natural Science Foundation of China(Grant No.41975175)the Fundamental Research Funds for the Central Universities of China。
文摘The effects of aerosol-radiation interactions(ARI)are not only important for regional and global climate,but they can also drive particulate matter(PM)pollution.In this study,the ARI contribution to the near-surface fine PM(PM_(2.5))concentrations in the Guanzhong Basin(GZB)is evaluated under four unfavorable synoptic patterns,including“northlow”,“transition”,“southeast-trough”,and“inland-high”,based on WRF-Chem model simulations of a persistent heavy PM pollution episode in January 2019.Simulations show that ARI consistently decreases both solar radiation reaching down to the surface(SWDOWN)and surface temperature(TSFC),which then reduces wind speed,induces sinking motion,and influences cloud formation in the GZB.However,large differences under the four synoptic patterns still exist.The average reductions of SWDOWN and daytime TSFC in the GZB range from 15.2%and 1.04°C in the case of the“transition”pattern to 26.7%and 1.69°C in the case of the“north-low”pattern,respectively.Furthermore,ARI suppresses the development of the planetary boundary layer(PBL),with the decrease of PBL height(PBLH)varying from 18.7%in the case of the“transition”pattern to 32.0%in the case of the“north-low”pattern.The increase of daytime near-surface PM_(2.5)in the GZB due to ARI is 12.0%,8.1%,9.5%,and 9.7%under the four synoptic patterns,respectively.Ensemble analyses also reveal that when near-surface PM_(2.5)concentrations are low,ARI tends to lower PM_(2.5)concentrations with decreased PBLH,which is caused by enhanced divergence or a transition from divergence to convergence in an area.ARI contributes 15%-25%toward the near-surface PM_(2.5)concentrations during the severe PM pollution period under the four synoptic patterns.
基金the National Natural Science Foundation of China(81473547,81673829).
文摘Objective:To systematically evaluate the clinical efficacy and safety of Qingkailing (QKL) injection for pediatric acute upper respiratory infection (AURI).Methods:We searched for randomized controlled trials (RCTs) of pediatric AURI treated by QKL and western medicine (WM) in the China National Knowledge Infrastructure Database,China Science and Technology Journal Database,Wanfang,Chinese Biomedical Literature Database,PubMed and Cochrane Library from inception to August,2016.Two reviewers independently retrieved the RCTs and extracted information.The Cochrane Collaboration Risk of Bias Assessment Tool was used to evaluate the methodological quality of RCTs.The data were meta-analyzed by RevMan 5.3 software.Results:Ultimately,21 RCTs that involved 2364 participants were included,and the quality of RCTs was generally poor.According to the meta-analysis,the combined use of QKL and WM for treating AURI can be effective,with a higher total effective rate,less defervescence time and less recovery time of tonsil and throat inflammation.Twenty-five adverse drug reactions (ADRs) were reported in three RCTs,but there were no serious ADRs.Conclusion:The combination of QKL and WM for treating pediatric AURI can result in better effects,but no definitive conclusions can be made regarding its safety.More rigorous RCTs are needed to support the clinical application of QKL.
文摘Objective:Amphibian skin secretions are an abundant source of bioactive peptides,some of which could be developed as candidate drugs.Among these natural peptides,cytolytic peptides have attracted the most attention given that they might replace conventional antibiotics and help deal with the problem of microbial resistance.This study discovered two bioactive peptides,Brevinin-1-PLr and Nigrocin-2-OV,from two species frogs,the Chinese bamboo leaf odorous frog (Odorrana versabilis) and the North American pickerel frog (Rana palustris),respectively.Their antimicrobial,anticancer and hemolytic activities were also investigated.Methods:cDNA sequences encoding peptides were cloned from cDNA libraries constructed from the lyophilized secretions of the Chinese bamboo leaf odorous frog and the North American pickerel frog.By reversed-phase HPLC and MS/MS fragmentation sequencing,the encoded novel peptides,named Nigrocin-2-OV and Brevinin-1-PLr,were identified in skin secretions and their structures were confirmed.Replicates of both peptides were produced through solid phase peptide synthesis.Their antimicrobial and anticancer activity was studied against three types of microorganisms (Staphylococcus aureus,Candida albicans,and Escherichia coli) and five cancer cell lines (NCI-H157,PC-3,MDA-MB-435s,MCF-7,and U251MG).Their hemolytic activity was investigated using whole horse blood.Results:In this research,cDNA sequences encoding two novel 24-mer peptides were cloned from cDNA libraries constructed from the lyophilized skin secretions of the Chinese bamboo leaf odorous frog and the North American pickerel frog.Both of the peptides had the strongest inhibitory effect against C.albicans,and IC50 values against five cancer cell lines were all under 6 μM.Conclusions:Nigrocin-2-OV and Brevinin-1-PLr had the strong ability to inhibit the proliferation of studied microorganisms and tumor cell lines,with slight hemolytic activity.Compared with Brevinin-1-PLr,Nigrocin-2-OV exhibited higher antimicrobial and anticancer activity but slightly higher hemolytic activity.
文摘The study aimed to analyze the reporting and methodological quality of systematic reviews(SRs)/meta-analyses(MAs)of animal models to provide references for later studies and avoid the waste of medical resources.EMBASE and MEDLINE databases were searched from inception to November 2017,with no language restriction.Two reviewers selected inclusion dependently and extracted the basic characteristics.Review Manager 5.3,stata 12.0,and SPSS 21 software were used to conduct analyses.A total of 46 SRs/MAs were included.The results showed that the English databases with high retrieval frequency are PubMed/MEDLINE,EMBASE,and Web of Science.67.31%(31/46)of the articles reported the search strategy in the full text or the appendix.65.22%(30/46)reported the literature screening flow diagram,and only 19.57%(9/46)reported the number of works of literature retrieved in each database.60.87%(28/46)illustrated supplement retrieval.Through 2 subgroup analyses,it was found that there were no significant differences in the quality of reports of PRISMA items.But referring to the methodological quality or reporting of PRESS items,SCI was better than that of non-SCI,while there seemed a source of funding to have no significant impact on the methodological quality or the items of PRESS.The results of PRESS,AMSTAR 2,and PRISMA were correlated,and the correlation between PRISMA and AMSTAR 2 was strong.These results demonstrated that search strategies of animal model SRs/MAs are still not enough comprehensive,report specification and methodological quality still need to be ameliorated.To show users the scientificity and rigor of the study,future research should focus on these various guidelines like PRESS,PRISMA,and AMSTAR 2 checklists that have been issued,it can help to increase the value of research and improve the utilization of medical resources.
基金the National Science and Technology Support Program of China(No.2007BAI10B01)the Science and Technology Development Project of TCM of Beijing(No.JJ-2010-70)+1 种基金the Scientific Research Innovation Team Project of Beijing University of Chinese Medicine(No.2011-CXTD-14)the open project of key disciplines of Beijing University of Chinese Medicine(No.2013-ZDXKKF-19).
文摘Objective:To explore Yan Zhenghua’s drug selection rule for treating digestive system diseases using data mining.Methods:The 609 medical records of digestive system diseases treated by Yan Zhenghua were collected and the herbs in these recipes were examined using a data mining technique.The correlativity between herb pairs and association rules was studied using an Apriori algorithm and the correlativity among multi-herbs was studied using a complex system entropy cluster technique.Results:Yan Zhenghua’s treatment of digestive system diseases featured 15 herbs prescribed at least 159 times each,22 herb pairs prescribed at least 155 times each,and eight frequently used herb core combinations.A confidence greater than 0.91 and a support level greater than 20%were achieved using the modified mutual information method.Conclusion:The data mining results conformed to findings from clinical practice.The data mining method is a valuable technique with which to study the experience of famous,elderly traditional Chinese medicine physicians.
基金the Beijing Municipal Natural Science Foundation(No.7152094).
文摘Background:Tibetan medicinal substances(TMS)has a complete theory that is based on five source doctrines.The theories of“Liuwei”,“Baxing”,“Shiqi Gongxiao”,and“Sanhuawei”constitute the prominent core components of the five source doctrines with significant Tibetan characteristics.Objective:This review summarizes the existing literature on the metabolomics and its use in TMS and offers recommendations for future research.Methods:Studies on TMS and the application of metabolomics on TMS are reviewed and summarized.The shortcomings of existing studies and recommendations for future studies are discussed.Conclusions:The recent researches have studied on the theory of TMS.Metabolomics will be increasingly applied to the identification of compounds in TMS,and the resultant detection of biomarkers will help elucidate the metabolic pathways of these substances.
基金supported by the National Natural Science Foundation of China(82074584)the National Key Innovative Talents Training Project Of Traditional Chinese Medicine(2019-128).
文摘Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.
基金supported by the National Natural Science Foundation of China(Nos.81960404,81960401 and 82060308)Guizhou Province Science and Technology Project(Nos.[2019]1429 and[2019]2798)+2 种基金Guizhou Provincial People’s Hospital Doctoral Fund(No.GZSYBS[2019]01)Guizhou Provincial People’s Hospital Youth Fund(No.GZSYQN[2019]04)Guizhou Provincial Health Commission Science and Technology Fund(No.gzwkj2021-251).
文摘Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction.Therefore,the prevention of OA progression in the early and middle stages is an urgent clinical problem.In a previous study,we demonstrated that NDRG3-mediated hypoxic response might be closely related to the development and progression of OA.In this study,an injectable thermosensitive hydrogel was established by cross-linking Pluronic F-127 and hyaluronic acid(HA)for the sustained release of hypoxia-induced exosomes(HExos)derived from adipose-derived mesenchymal stem cells.We demonstrated that for OA at the early and middle stages,the HExos-loaded HP hydrogel could maintain the chondrocyte phenotype by enhancing chondrocyte autophagy,reducing chondrocyte apoptosis,and promoting chondrocyte activity and proliferation through the NDRG3-mediated hypoxic response.This novel composite hydrogel,which could activate the NDRG3-mediated hypoxic response,may provide new ideas and a theoretical basis for the treatment of early-and mid-stage OA.
基金supported by Shanghai Key Clinical Center for Metabolic Disease(2017ZZ01013)Shanghai Municipal Key Clinical Specialty,the National Natural Science Foundation of China-National Health and Medical Research Council joint research grant(81561128016)+4 种基金the Natural Science Foundation of Shanghai(18ZR1429000)Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)Shanghai Key Discipline of Public Health(GWVI-11.1-20)Shanghai Health Commission(JKKPYC-2022-12)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38020000 and XDB38000000).
文摘Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose tissue and the development of NAFLD.Using community-based cohort data,we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),and incident NAFLD in 2830 participants(1205 males and 1625 females)aged 55–70 years.During a 4.6-year median follow-up,the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in females.Further analyses showed that the abovementioned positive associations were stronger in males than in females,especially in participants under 60 years old.In contrast,these sex differences disappeared in those over 60 years old.Furthermore,the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific pattern.Additionally,sex-specific potential mediators,such as insulin resistance,lipid metabolism,inflammation,and adipokines,may exist in the associations between adipose tissue and NAFLD.This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age,highlighting the potential need for sex-and age-specific management of NAFLD.
文摘Little is known about how chronic inflammation contributes to the progression of hepatoceUular carcinoma (HCC), especially the initiation of cancer. To uncover the critical transition from chronic inflammation to HCC and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c.myc mice and age-matched wt-C57BL/6 mice using our dynamical network biomarker (DNB) model. DNB analysis indicated that the 5th month after birth of transgenic mice was the critical period of cancer initiation, just before the critical transition, which is consistent with clinical symptoms. Meanwhile, the DNB-associated network showed a drastic inversion of protein expression and coexpression levels before and after the critical transition. Two members of DNB, PLA2G6 and CYP2C44, along with their associated differentially expressed proteins, were found to induce dysfunction of arachidonic acid metabolism, further activate inflammatory responses through inflammatory mediator regulation of transient receptor potential channels, and finally lead to impairments of liver detoxification and malignant transition to cancer. As a c-Myc target, PLA2G6 positively correlated with c-Myc in expression, showing a trend from decreasing to increasing during carcinogenesis, with the minimal point at the critical transition or tipping point. Such trend of homologous PLA2G6 and c-Myc was also observed during human hepatocarcinogenesis, with the minimal point at high-grade dysplastic nodules (a stage just before the carcinogenesis). Our study implies that PLA2G6 might function as an oncogene like famous c-Myc during hepatocar- cinogenesis, while downregulation of PLA2G6 and c-Myc could be a warning signal indicating imminent carcinogenesis.
文摘Dear Editor, Type 2 diabetes mellitus (T2DM) develops only in insulin-resistant subjects when pancreatic β-cell compensation fails (Matveyenko and Butler, 2006). Decreased insulin secretory function and reduced cell mass are traditionally viewed as major contributing factors in β-cell insufficiency. A recent study using a diabetic rodent model suggests that progressive β-cell de- differentiation is an important underlying mechanism in β-cell failure (Talchai et al., 2012). β-cell dedifferentiation in diabetes refers to the loss by healthy β-cells of key components characteristic of the differen- tiated state (Dor and Glaser, 2013), including insulin (for its secretory product), Glut2 (for glucose intake), and PDX-1 (for critical insulin transcription factor), β-cell dedifferentiation may be largely respon- sible for not only β-cell secretory dysfunction but also impaired β-cell identity. In view of findings that bariatric surgery in a rodent T2DM model led to increased β-cell mass and improved islet morphology (Strader et al., 2009), we investigated the effects of gastric bypass surgery on dedifferentiated β-cells.
基金This study was also supported in part by grants from the National Natural Science Foundation of China(No.81871865,81874036,81972167,82102859,31930022,31771476,and 12026608)National Science and Technology Major Project(No.2017YFA0505500)+5 种基金the Strategic Priority Project of Chinese Academy of Sciences(No.XDB38040400,XDB38020000)the Backbone Program of Shanghai Pulmonary Hospital(No.FKGG1802)Shanghai Pujiang Talent Plan(No.2019PJD048)Shanghai Science and Technology Committee Foundation(NO.19411950300)Shanghai Key disciplines of Respiratory(No.2017ZZ02012)the Shanghai Sailing Program(No.20YF1407500).
文摘This multicenter phase-II trial aimed to investigate the efficacy,safety,and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC.Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled.Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles,followed by the maintenance of toripalimab and pemetrexed.The primary endpoint was objective-response rate(ORR).Integrated biomarker analysis of PD-L1 expression,tumor mutational burden(TMB),CD8+tumor-infiltrating lymphocyte(TIL)density,whole-exome,and transcriptome sequencing on tumor biopsies were also conducted.Forty patients were enrolled with an overall ORR of 50.0%and disease-control rate(DCR)of 87.5%.The median progression free survival(PFS)and overall survival were 7.0 and 23.5 months,respectively.The most common treatment-related adverse effects were leukopenia,neutropenia,anemia,ALT/AST elevation,and nausea.Biomarker analysis showed that none of PD-L1 expression,TMB level,and CD8+TIL density could serve as a predictive biomarker.Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type.Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC.DSPP mutation might serve as a potential biomarker for this combination.A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing(NCT03924050).
基金supported by the National Key Research and Development Program of China(Grant No.2017YFA0205700)National Basic Research Program of China(Grant Nos.2015CB932403,2017YFA0206000)+4 种基金National Science Foundation of China(Grant Nos.11674012,61422501,11374023,61521004 and 21790364)Beijing Natural Science Foundation(Grant No.L140007)Foundation for the Author of National Excellent Doctoral Dissertation of PR China(Grant No.201420)National Program for Support of Top-notch Young Professionals(Grant No.W02070003)Ministry of Education Singapore under Grant No.MOE2015-T2-2-043.
文摘Achieving strong coupling between plasmonic oscillators can significantly modulate their intrinsic optical properties.Here,we report the direct observation of ultrafast plasmonic hot electron transfer from an Au grating array to an MoS_(2) monolayer in the strong coupling regime between localized surface plasmons(LSPs)and surface plasmon polaritons(SPPs).By means of femtosecond pump-probe spectroscopy,the measured hot electron transfer time is approximately 40 fs with a maximum external quantum yield of 1.65%.Our results suggest that strong coupling between LSPs and SPPs has synergetic effects on the generation of plasmonic hot carriers,where SPPs with a unique nonradiative feature can act as an‘energy recycle bin’to reuse the radiative energy of LSPs and contribute to hot carrier generation.Coherent energy exchange between plasmonic modes in the strong coupling regime can further enhance the vertical electric field and promote the transfer of hot electrons between the Au grating and the MoS_(2) monolayer.Our proposed plasmonic strong coupling configuration overcomes the challenge associated with utilizing hot carriers and is instructive in terms of improving the performance of plasmonic opto-electronic devices.
文摘Transgenic technology allows a gene of interest to be introduced into the genome of a laboratory animal,and provides an extremely powerful tool to dissect the molecular mechanisms of disease.Transgenic mouse models made by microinjection of DNA into zygotic pronuclei in particular have been widely used by the genetics community for 30 years.However,it remains a rather crude approach:injected sequences randomly insert in multiple copies as concatamers,they can be mutagenic,and they have variable or silenced expression depending on the site of integration,a phenomenon called position effects.As a result,multiple lines are required in order to confirm appropriate transgene expression.This can be partially overcome by flanking transgenes with insulator sequences to protect the transgene from the influence of the surrounding regulatory elements.Large(\300 kb)BACbased transgenic vectors have also been shown to be more resistant to position effects.However,animals carrying extra copies of fairly large regions of the genome could have unpredictable phenotypes.The most effective method used to control for position effects is to target transgene insertion to specific genomic loci,the so-called targeted transgenesis;for instance,the fast,site-specific transgenic technology Targatt TM.The purpose of this review is to provide an overview on the current existing methods for making targeted transgenic mouse models.
基金Supported by Detection Technology Procedures and Normative Research of Priority Species of TCM of National Science and Technology Support Program(No.2006BAI21B11)Scientific Research Innovation Team Project of Beijing University of Chinese Medicine(No.2011-CXTD-14)Postgraduate Independent Topics(No.2014-JYBZZ-XS-078)
文摘OBJECTIVE: To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of diabeticperi pheral neuropathy(DPN).METHODS: Randomized controlled trials investigating the efficacy of puerarin injection on DPN were searched for in China National Knowledge Infrastructure Database, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from establishment to April 30.Two reviewers independently retrieved and extracted the information.The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.2 software.RESULTS: Twenty-two studies involving 1664 participants were included. The quality of the studies was found to be relatively low. Meta-analysis showed that puerarin injection combined with western medication was more effective than conventional therapy for rate, nerve conduction velocity(NCV), and hemorheology index. Six adverse drug reactions(ADRs) from puerarin injection were reported in two studies. Reactions included facial flushing, palpitations, and pain at infusion locations. However,noserious ADRs were reported.CONCLUSION: Puerarin injection was effective for the treatment of DPN. Puerarin can improve the total effective rate, correct NCV that was decreased by diabetes, and improve the hemorheology index.Puerarin was also relatively safe clinically. However,since the articles included in the study were not high-quality, more studies should be conducted to strengthen their findings.