A novel pulmonary fibrosis murine model with immune-related liver injury

Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.

细辛的毒性研究进展

细辛作为一种传统中药,具有祛风散寒、止痛、化痰等功效,然而,其显著的毒性一定程度限制了临床应用。本文整合了近年来对细辛毒性成分的研究进展,全面概述了细辛的毒性成分及其机制,探讨了其潜在的肝毒性、基因毒性、神经毒性和肺毒性及其相关的分子机制。本文总结了细辛的化学成分,主要包括挥发油、木脂素、脂肪酸、黄酮和含氮化合物等。重点探讨了细辛的肝毒性、遗传毒性、神经毒性和肺毒性,分析了相关的毒性成分和分子机制。综述强调了在临床应用中平衡细辛的治疗效益与毒性风险的重要性,建议未来研究应关注安全剂量的确定以及个体对细辛成分反应的差异。通过深入研究这些机制,可以更安全有效地利用细辛这一传统中药。

大黄肝毒性的精确亚细胞器靶向分析

[目的]药物性肝损伤(DILI)是急性肝功能衰竭的主要原因,对人类健康构成重大挑战。大黄(Rheumofficinale Baill,Da Huang)因其具有清热利尿的作用已应用于临床。然而,它对肝脏不同细胞器的毒性作用需要进一步验证。[方法]分析大黄肝毒性的潜在靶点及其与微粒体、线粒体、内质网(ER)、高尔基体(GA)和溶酶体等五种主要细胞器的潜在损伤关系。通过整合传统中药(ITCM)数据库、HERB数据库和网络药理学,我们分离和纯化了不同的细胞器,将它们与大黄的不同组分和单体在三磷酸腺苷(ATP)培养系统中孵育,并使用粒度分析和分子生物学实验检查了细胞器的结构和功能变化,以评估大黄是否会对肝脏主要细胞器造成损伤。[结果]通过虚拟预测和实验验证相结合,我们的研究证实,从大黄蒽醌中分离的大黄素、大黄鞣质中的儿茶素和大黄有机酸中的棕榈酸对代表性细胞器造成了最显著的功能和结构损伤。在所有单体化合物中,大黄素对微粒体、线粒体、内质网和溶酶体的损伤最大;儿茶素诱导微粒体和GA损伤;棕榈酸对肝脏微粒体和GA的损伤最大。表明大黄成分可能通过多细胞器损伤发挥肝毒性。[结论]我们的研究结果表明,大黄对不同的细胞器具有不同程度的损伤作用,进而通过损害细胞器的形态和功能来影响细胞的生命活动。本研究为大黄毒性成分和靶点的精细分析提供了理论依据和技术支持。

Efficacy of Chinese herbal medicine in functional dyspepsia: A meta-analysis of randomized, double-blind, placebo-controlled trials

Objective:To evaluate the efficacy and safety of Chinese herbal medicine(CHM)for the treatment of functional dyspepsia(FD).Methods:Web of Science,PubMed,EMBASE,Cochrane Library,and four other Chinese electronic databases,including China National Knowledge Infrastructure(CNKI),Chinese Biological Medical Database(CBM),Chinese Scientific Journals Database(VIP),and WanFang Database were used to search(up to Feb,2016)for randomized,double-blind,placebocontrolled trials recruiting adults with FD treated with CHM.Study selection,data extraction,quality assessment,and data analyses were conducted based on Cochrane standards using Review Manager software.Results:Fourteen publications(1424 patients)were included.Evidence revealed that CHM was more efficacious than the placebo in improving global dyspepsia symptoms(RR,1.45;95%CI,1.31e1.60),Chinese medicine syndrome(CMS)(RR,1.36;95%CI,1.23e1.50),and quality of life(SMD,0.30;95%CI,0.15e0.45)in FD patients.Furthermore,the difference in the incidence of adverse events between CHM and placebo groups had no statistical significance(RR,1.06;95%CI,0.66e1.70).Conclusion:This meta-analysis demonstrates that CHM has a therapeutic potential in treating FD with a certain safety.However,due to the restricted number of trials included,wellplanned,long-term studies are necessary to provide credible evidence.

Relationship between FGF12 expression in high-grade gliomas and clinical features

Objective:gliomas are the most common intracranial tumors.Fibroblast growth factor-12(FGF12),which belongs to the fibroblast growth factor(FGFs)family,plays an important role in cell mitosis,as well as in other life functions,such as embryo development,tissue repair,cell proliferation,and tumor growth and invasion.The purpose of this study was to explore the potential value of FGF12 in high-grade gliomas and to predict its drug sensitivity.To provide a possible therapeutic target for glioma.Methods:high-grade glioma gene expression data and clinical information were downloaded from the gene expression omnibus(GEO)database,using the R language“impute”and“survival”survival analysis package.The FGF12 genes closely related to survival were screened,a survival curve was drawn,and clinical correlation analysis was conducted.The differentially expressed genes(DEGs)were defined as |logFC|>1,adj.PVal<0.05 as the standard.We used the David for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,and constructed the protein-protein interactions(PPI)network.Then we used the Connectivity Map(CMAP)database for drug location,and the validation group was verified by the Chinese Glioma Genome Atlas(CGGA)database in the same way.Results:we found that high FGF12 expression was associated with a higher survival rate.The same validation was performed in the validation group through the CGGA database,and the survival curve showed the same trend.The expression level of FGF12 is an independent factor that affects the life time and status of the samples,and it is a low risk factor.GO enrichment analysis showed that differential genes were enriched in matrix transmembrane transporter activity,ion channels and calcium ion active channels.KEGG showed that DEGs were enriched in the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,dopaminergic synapse and cyclic adenosine monophosphate(cAMP)signaling pathway.Four seed genes,GRIA2,COLLA2,GRIA4 and HES6,were obtained by PPI network analysis.The cAMP was used to analyze and obtained 7 small molecule drugs,such as merbromin,naloxone,AH-2384&ticarcillin,vincamine,amoxicillin,azacyclonol,which may be helpful in the prognosis of high-grade gliomas.Conclusion:FGF12 and its pathway may serve as a biomarker or therapeutic target for high-grade gliomas.

Visible-infrared-terahertz optical modulation of few-layer graphene through lithium intercalation

Optical modulation is significant and ubiquitous to telecommunication technologies,smart windows,and military devices.However,due to the limited tunability of traditional doping,achieving broadband optical property change is a tough problem.Here,we demonstrate a remarkable transformation of optical transmittance in few-layer graphene(FLG)covering the electromagnetic spectra from the visible to the terahertz wave after lithium(Li)intercalation.It results in the transmittance being higher than 90%from the wavelengths of 480 to 1040 nm,and it increases most from 86.4%to 94.1%at 600 nm,reduces from∼80%to∼68%in the wavelength range from 2.5 to 11μm,has∼20%reduction over a wavelength range from 0.4 to 1.2 THz,and reduces from 97.2%to 68.2%at the wavelength of 1.2 THz.The optical modification of lithiated FLG is attributed to the increase of Fermi energy(Ef)due to the charge transfer from Li to graphene layers.Our results may provide a new strategy for the design of broadband optical modulation devices.

Cassiae Semen improves non-alcoholic fatty liver disease through autophagy-related pathway

Objective:Cassiae Semen(CS,Juemingzi in Chinese)has been used for thousands of years in ancient Chinese history for relieving constipation,improving liver function as well as preventing myopia.Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease(NAFLD).Methods:High-performance liquid chromatography(HPLC)was used to identify the major components of CS water extract.Mice were fed with a high-fat and sugar-water(HFSW)diet to induce hepatic steatosis and then treated with CS.The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining.Additionally,the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid(OAPA)-treated HepG2 cells were measured.The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism.Results:Five compounds,including aurantio-obtusin,rubrofusarin gentiobioside,cassiaside C,emodin and rhein were simultaneously identified in CS extract.CS not only improved the diet-induced hepatic steatosis in vivo,as indicated by decreased number and size of lipid droplets,hepatic and serum triglycerides(TG)levels,but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes.These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase(FASN)and the activation of autophagy-related signaling,including AMP-activated protein kinase(AMPK),light chain 3-II(LC3-II)/LC3-1 and autophagy-related gene5(ATG5).Conclusion:Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy,which might become a promising therapeutic strategy for relieving NAFLD.

Proteomics analysis of IBS-D with spleen and kidney yang deficiency

Objective:To investigate the molecular mechanism underlying the development of diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen and kidney yang deficiency (SKYD) using a proteomics approach.Methods:Male Sprague-Dawley rats (n =22) were divided into IBS-D (n =12) and normal control (n =10) groups.SKYD was then modeled in IBS-D rats by a combination of acetic acid enema,bondage,rectal dilation,tail stimulation,and Senna gavage.Colon tissue samples were subsequently collected and examined by Q Exactive mass spectrometry to identify differentially expressed proteins between the two groups.Results:The occurrence of SKYD/IBS-D was associated with ribosomal protein S23 (Rps23),protein phosphatase 2 catalytic subunit alpha (Pp2a),and growth factor receptor-bound protein 2 (Grb2),which are involved in the ribosome,neurotrophin signaling,and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways.Conclusion:These data suggest that SKYD/IBS-D pathophysiology likely involves inflammation,cell growth,apoptosis,stress granule formation,immune activation,loss of epithelial cell integrity,and visceral hypersensitivity.

SDH网规划仿真系统业务部署模块的设计与实现

本文研究的重点是电力通信网业务部署模块的设计与实现。业务部署是SDH网络规划的一个重要环节,SDH网络的设备以及链路搭建的主要目的正是为了承载业务。本文首先介绍了电力通信网规划这一概念提出的背景、电力通信网规划仿真系统的技术基础、电力通信网规划仿真系统的功能分析。其次,对仿真系统的业务部署模块进行了需求分析和概要设计。再次,本文针对电力通信网规划仿真系统业务部署模块进行了详细设计,提出了配置管理仿真系统的实现架构,并阐述了各子模块之间的关系。最后基于Eclipse和FLEX开发工具实现了该仿真模块。

Marine red yeast supplementation improves laying performance by regulating small intestinal homeostasis in aging chickens

Recent studies have shown that age-related aging evolution is accompanied by imbalances in intestinal homeostasis.Marine red yeast(MRY)is a functional probiotic that has been shown to have antioxidant,immune and other properties.Therefore,we chose 900 healthy Hy-Line Brown hens at 433 d old as the research subjects and evaluated the correlation between intestinal health,laying performance,and egg quality in aged hens through the supplementation of MRY.These laying hens were assigned into 5 groups and received diet supplementation with 0%,0.5%,1.0%,1.5%,and 2%MRY for 12 weeks.The results showed that MRY supplementation increased egg production rate,average egg weight,and egg quality,and decreased feed conversion ratio and daily feed intake(P<0.05).The MRY supplement improved antioxidant indicators such as superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),stimulated villus height,and increased the villus height to crypt depth ratio(V/C ratio)in the intestine(P<0.05).It also regulated the expression of intestinal inflammatory factors(transforming growth factor-β[TGF-β],interleukin[IL]-1β,IL-8,tumor necrosis factor-α[TNF-α])while increasing serum immunoglobulin G(IgG)levels(P<0.05).Furthermore,MRY supplementation upregulated the mRNA expression of tight junction proteins(occludin and zonula occludens-1[ZO-1]),anti-apoptotic gene(Bcl-2),and autophagy-related proteins(beclin-1 and light chain 3I[LC3I])in the intestine(P<0.05).The MRY supplement also led to an increase in the concentration of short-chain fatty acids in the cecum,and the relative abundance of the phylum Bacteroidetes,and genera Bacteroides and Rikenellaceae_RC9_gut_group.The LEfSe analysis revealed an enrichment of Sutterella and Akkermansia muciniphila.In conclusion,the results of this experiment indicated that the additional supplementation of MRY can improve the production performance of laying hens and may contribute to the restoration and balance of intestinal homeostasis,which supports the application potential of MRY as a green and efficient feed additive for improving the laying performance in chickens.

New insights for infection mechanism and potential targets of COVID-19:Three Chinese patent medicines and three Chinese medicine formulas as promising therapeutic approaches

The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide.Currently,there is no accepted specific drug for COVID-19 treatment.Therefore,it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19.According to several reliable reports from China,traditional Chinese medicine(TCM),especially for three Chinese patent medicines and three Chinese medicine formulas,has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines.In this review,we systematically summarized and analyzed the pathogenesis of COVID-19,the detailed clinical practice,active ingredients investigation,network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat.Additionally,we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism,which provides guidance for the development of new drugs against COVID-19.Collectively,by addressing critical challenges,for example,unclear targets and complicated active ingredients of these medicines and formulas,we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.

Distribution and spectral characteristics of chromophoric dissolved organic matter in a coastal bay in northern China

The absorption spectra of chromophoric dissolved organic matter（CDOM）,along with general physical,chemical and biological variables,were determined in the Bohai Bay,China,in the springs of 2011 and 2012. The absorption coefficient of CDOM at 350 nm（a350） in surface water ranged from 1.00 to 1.83 m-1（mean： 1.35 m-1） in May 2011 and from 0.78 to 1.92 m-1（mean：1.19 m-1） in April 2012. Little surface-bottom difference was observed due to strong vertical mixing. The a350 was weakly anti-correlated to salinity but positively correlated to chlorophyll a（Chl-a） concentration. A shoulder over 260–290 nm,suggestive of biogenic molecules,superimposed the overall pattern of exponentially decreasing CDOM absorption with wavelength. The wavelength distribution of the absorption spectral slope manifested a pronounced peak at ca. 300 nm characteristic of algal-derived CDOM. All a250/a365 ratios exceeded 6,corresponding to CDOM molecular weights（Mw） of less than 1 kDa. Spectroscopically,CDOM in the Bohai Bay differed substantively from that in the Haihe River,the bay＇s dominant source of land runoff; photobleaching of the riverine CDOM enlarged the difference.Results point to marine biological production being the principal source of CDOM in the Bohai Bay during the sampling seasons. Relatively low runoff,fast dilution,and selective photodegradation are postulated to be among the overarching elements responsible for the lack of terrigenous CDOM signature in the bay water.