Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine

The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.

Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment

Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.

P2X7 receptor activation aggravates NADPH oxidase 2-induced oxidative stress after intracerebral hemorrhage

Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor(P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079(100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079(100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2(ERK1/2) and nuclear factor kappa-B(NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126(2 μg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23(3.5 μg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039(100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China(approval No. TJ-A20160805) on August 26, 2016.

BTB-BACK-TAZ domain protein MdBT2-mediated MdMYB73 ubiquitination negatively regulates malate accumulation and vacuolar acidification in apple

As an important primary metabolite,malate plays a key role in regulating osmotic pressure,pH homeostasis,stress tolerance,and fruit quality of apple.The R2R3-MYB transcription factor(TF)MdMYB73 was identified as a protein that plays a critical role in determining malate accumulation and vacuolar acidification by directly regulating the transcription of aluminum-activated malate transporter 9(MdALMT9),vacuolar ATPase subunit A(MdVHA-A),and vacuolar pyrophosphatase 1(MdVHP1)in apple.In addition,the bHLH TF MdCIbHLH1 interacts with MdMYB73 and enhances the transcriptional activity of MdMYB73.Our previous studies demonstrated that the BTB-BACK-TAZ domain protein MdBT2 can degrade MdCIbHLH1 to influence malate accumulation and vacuolar acidification.However,the potential upstream regulators of MdMYB73 are currently unknown.In this study,we found that MdBT2 directly interacts with and degrades MdMYB73 through the ubiquitin/26S proteasome pathway to regulate malate accumulation and vacuolar acidification.A series of functional assays with apple calli and fruit showed that MdBT2 controls malate accumulation and vacuolar acidification in an MdMYB73-dependent manner.Overall,our findings shed light on the mechanism by which the BTB-BACK-TAZ domain protein MdBT2 regulates malate accumulation and vacuolar acidification by targeting MdMYB73 and MdCIbHLH1 for ubiquitination in apple.This information may help guide traditional breeding programs and fruit tree molecular breeding,and lead to improvements in fruit quality and stress tolerance.

肝苏颗粒治疗慢性乙型肝炎疗效的Meta分析

目的系统评价肝苏颗粒对慢性乙型肝炎疗效,为临床用药提供可靠的依据。方法搜索自成立到2017年10月的Pubmed、Cochrane图书馆、Embase、Web of Science、中国知网、CBM、VIP、万方数据库中该研究的临床随机对照实验,制定放入与清除的标准,并对放入文献质量进行评价,提取数据进行Meta分析。结果共纳入7个研究,受试对象为893例,治疗组较对照组疗效好,差异有统计学意义(P <0.05)。结论肝苏颗粒治疗慢性乙型肝炎有确定的效果,但目前证据缺乏质量,需要高质量的证据进一步验证。

The MADS transcription factor CmANR1 positively modulates root system development by directly regulating CmPIN2 in chrysanthemum

Plant root systems are essential for many physiological processes,including water and nutrient absorption.MADS-box transcription factor(TF)genes have been characterized as the important regulators of root development in plants;however,the underlying mechanism is largely unknown,including chrysanthemum.Here,it was found that the overexpression of CmANR1,a chrysanthemum MADS-box TF gene,promoted both adventitious root(AR)and lateral root(LR)development in chrysanthemum.Whole transcriptome sequencing analysis revealed a series of differentially expressed unigenes(DEGs)in the roots of CmANR1-transgenic chrysanthemum plants compared to wild-type plants.Functional annotation of these DEGs by alignment with Gene Ontology(GO)terms and biochemical pathway Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indicated that CmANR1 TF exhibited“DNA binding”and“catalytic”activity,as well as participated in“phytohormone signal transduction”.Both chromatin immunoprecipitation–polymerase chain reaction(ChIP-PCR)and gel electrophoresis mobility shift assays(EMSA)indicated the direct binding of CmPIN2 to the recognition site CArG-box motif by CmANR1.Finally,a firefly luciferase imaging assay demonstrated the transcriptional activation of CmPIN2 by CmANR1 in vivo.Overall,our results provide novel insights into the mechanisms of MADS-box TF CmANR1 modulation of both AR and LR development,which occurs by directly regulating auxin transport gene CmPIN2 in chrysanthemum.

Effect of external electric field on the terahertz transmission characteristics of electrolyte solutions

We fabricated a microfluidic chip with simple structure and good sealing performance,and studied the influence of the electric field on THz absorption intensity of liquid samples treated at different times by using THz time domain spectroscopy system.The tested liquids were deionised water and CuSO_(4),CuC_(l2),NaHCO_(3),Na_(2)CO_(3) and NaCl solutions.The transmission intensity of the THz wave increases as the standing time of the electrolyte solution in the electric field increases.The applied electric field alters the dipole moment of water molecules in the electrolyte solution,which affects the vibration and rotation of the whole water molecules,breaks the hydrogen bonds in the water,increases the number of single water molecules and leads to the enhancement of the THz transmission spectrum.

Terahertz generation and detection of LT-GaAs thin film photoconductive antennas excited by lasers of different wavelengths

A new method of generating and detecting terahertz waves is proposed.Low-temperature-grown gallium arsenide(LT-Ga As)thin films are prepared by etching a sacrificial layer(Al As)in a four-layer epitaxial structure constituted with LT-Ga As,Al As,Ga As,and semi-insulating gallium arsenide(SI-Ga As).The thin films are then transferred to clean silicon for fabricating the LT-Ga As thin film antennas.The quality and transmission characteristics of the films are analyzed by an800-nm asynchronous ultrafast time domain spectroscopy system,and the degree of bonding between the film and silicon wafer is determined.Two LT-Ga As thin film antennas for generating and detecting the terahertz waves are tested with a1550-nm femtosecond laser.The terahertz signal is successfully detected,proving the feasibility of this home-made LTGa As photoconductive antennas.This work lays a foundation for studying the mechanism of terahertz wave generation in Ga As photoconductive antennas below the semiconductor band gap.

Effects of Cu and Co additions on the crystallization and magnetic properties of FeNbB alloy

The nanocrystalline-forming element Cu and magnetic element Co are commonly used as additive elements to tune the structure and improve the properties of alloys.In this study,four kinds of amorphous alloys,Fe_(72)Nb_(12)B_(16),Fe_(72)Nb_(12)B_(15)Cu_(1),Fe_(36)Co_(36)Nb_(12)B_(16),and Fe_(36)Co_(36)Nb_(12)B_(15)Cu_(1),were prepared by melt-spinning and annealed at various temperatures to investigate the effects of Cu and Co additions,individually and in combination,on the crystallization and magnetic properties of Fe_(72)Nb_(12)B_(16)alloy.The four kinds of alloys exhibited different crystallization behaviors with different primary crystallization phases observed.For the Fe_(72)Nb_(12)B_(16)alloy,only theα-Mn-type metastable phase formed after annealing.The addition of 1 at.%Cu and 36 at.%Co led to the observation of theα-Mn-type andβ-Mn-type metastable phases,respectively,and a reduction in the crystallization volume fraction in the metastable phase.The Fe_(36)Co_(36)Nb_(12)B_(15)Cu_(1)alloy only exhibitedα-Fe(Co)phase as a primary phase,and the addition of both Cu and Co completely inhibited the precipitation of the metastable phase.Cu clusters were found in energy dispersive spectroscopy elemental maps.Compared with other alloys,Fe_(36)Co_(36)Nb_(12)B_(15)Cu_(1)alloy with both Cu and Co exhibited a lower coercivity(Hc)below 973 K.

Analysis on formula principles for“head wind”disease based on apriori and clustering algorithm

Objective:To explore the formula principles for“head wind”disease by data-mining and provide reference for the treatment of“head wind”disease.Methods:Prescriptions for headache from“Dictionary of Traditional Chinese Medicine Prescriptions”were collected,sorted and entered into the“Traditional Chinese Medicine Inheritance System”(V2.5)to analyze the composition principles by the methods of revised mutual information,complex system entropy cluster and unsupervised hierarchical cluster.Results:The herbs with high usage frequency in these prescriptions for“head wind”disease included Chuan-xiong,Bai-zhi,Xi-xin,Fang-feng,Gan-cao,Shi-Gao and Qiang-Huo.Three new prescriptions were obtained based on the composition principles and rules.The first new prescription is composed of Quan-xie,Xiong-huang,Jiang-can,Zhi-chuan-wu and Di-long.The second new prescription is composed of Du-huo,Rou-gui,Ku-shen;Fang-feng,Gao-ben,Qiang-huo.The third new prescription is composed of Fu-zi,Sheng-chuan-wu,Tian-nan-xing,Chuan-xiong,Bai-zhi,Shi-gao.Conclusion:We found that the most of herbs used to treat the“head wind”disease are warm and spicy,mainly belong to diaphoretic herbs,wind-expelling herbs,and dampness-dispelling herbs.In addition,the new prescriptions for infertility mainly focus on eliminating evil,with the characteristics of“eliminating phlegm and turbid”,“dredging the channels and collaterals”,“expelling wind-evil”and“promoting blood circulation”.

Bioinformatics analysis of hepatic fibrosis based on hepatic stellate cells

Objective:To analyze differentially expressed genes in human hepatic stellate cells(HSCs)based on data from the GEO database and to identify important target genes for hepatic fibrosis(HF).Methods:In GEO database,microarray GSE11954 of the GEO database was used to obtain data on differential gene expression in human HSCs and was analyzed using GEO2R,using a P value of<0.01 and log2FC value of≥2 for the screening.The genes were input into the DAVID database for enrichment analysis of genes and pathways,followed by protein interaction analysis and module analysis.The results were compared with the results found through text mining.Results:Two hundred sixty two differentially expressed genes(DEGs)were identified.The results of gene bulk enrichment showed that the functional molecules encoded by the DEGS were mainly located in the cytoplasm,extracellular matrix and nucleosome,while the molecular functions were mainly related to"regulating actin binding","protein kinase binding"and"kinase activity".The biological processes they were found to be involved in"regulating cell division","immune response"and"collagen decomposition reaction".KEGG signaling pathway analysis found that they were mainly involved in"cell cycle signaling pathway","ECM receptor interaction signaling pathway","p53 signaling pathway"and"FOXO signaling pathway".Text mining results suggested that MMP1 and ETV6 are potential molecular targets for HF therapy.Conclusion:The results of bioinformatics analysis identified targets and signaling pathways involved in the pathogenesis of HF,but these require further experimental verification.

Network meta-analysis of the compensatory effect of different Chinese herbal compounds combined with Entecavir in the treatment of hepatitis B cirrhosis

Objective:To evaluate the efficacy and safety of different Chinese herbal compounds combined with Entecavir in the treatment of hepatitis B cirrhosis during the compensatory period by using mesh meta-analysis.Methods:PubMed,CNKI,Wanfang and VIP databases were searched by computer,and the retrieval time was from the establishment of each database to October 5,2022.According to inclusion and exclusion criteria,literature search was conducted independently by two researchers.RevMan5.4.1 software provided by Cochrane was used for evaluation,and Stata16.0 software was used for statistical analysis.Results:A total of 34 RCTs were included,involving 16 TCM compounds and 1543 patients.The results of network meta-analysis showed that ALT indexes of liver function were listed as Yiqi Jiedu Tongluo Method>Luoshugan Tablet>Anluo Huaxian Wan>Qishenrugan Capsule>Qingganhuaji Decoction>Ganshuang Granules>Compound Biejia Rugan Tablet>Rougan Sanjie Decoction>Shugan Jianpi Decoction>Shenqi Fuzheng Huayu Decoction>Peituhua Decoction>Shugan Jianpi Huoxu prescription>Rhubarb Zhezhan Capsule combined with Entecavir treatment respectively;The order of HA index of liver fibrosis was Heluo Shugan Tablet>Shugan Jianpi Huoxui prescription>Anluo Huaxian Wan>Compound Biejia Ruangan Tablet>Rougan Sanjie Decoction>Ganshuang Granules>Danji Huoxui Decoction>Yiqi Jiedu Tongluo Method>Rhubarb Zhezhe Capsule>Fuzheng Huayu Table>Shugan Jianpi Decoction>Rougan Huayu Decoction>Peitu Huayu Decoction>Qingganhuaji Prescription>Shenqi Fuzheng Huayu prescription combined with Entecavir respectively;In order of adverse reactions from best to worst,Shuganjianpi Decoction,Qishenrugangan Capsule,Ganshuang Granules,Peituhuazhi Decoction,compound Biejiruganpian,and He Shugan Pian combined with entecavir,respectively;The effective rate of treatment was listed as Ganshuang Granules>Compound Biejia Ruangan Tablets>uoshugan Tablets>Rougansanjie Decoction>Rhubarb Zhezhe Capsules>Yiqi Jiedu Tongluo Method>Qingganhuaji prescription>Anluo Huaxia Wan>Shugan Jianpi Decoction>Fuzheng Huayu tablets>Peituhuazhi Decoction>Shenqi Fuzheng Huayu prescription combined with Entecavir respectively.Conclusion:Entecavir combined with supplementing qi and detoxifying and dredging collages is the best method to recover ALT index of liver function during the compensation period for hepatitis B cirrhosis;Entecavir combination and Luoshugan tablet were the best treatment for HA index of hepatic fibrosis;Entecavir combined with Shuganjianpi Decoction was the best treatment for adverse reactions;The best treatment efficiency was Entecavir combined with Ganshuang granules.

Exploration of the mechanism of action of Xiayuxue Tang against hepatic fibrosis based on GEO data mining,network pharmacology and molecular docking technology

Objective:To study the mechanism of action of Xiayuxue Tang in treating hepatic fibrosis by combining GEO data mining,network pharmacology,and molecular docking technology,and provide new research directions for the treatment of hepatic fibrosis.Method:Utilizing multiple databases,we aim to identify the relevant targets of various components in Xiayuxue Tang and their associations with hepatic fibrosis.After pinpointing the key targets through interaction analysis,we will construct both the compound-target network and the protein interaction network for Xiayuxue Tang.Conclusively,we will conduct GO and KEGG enrichment analyses on these key targets,followed by molecular docking verification.Result:Through mining the GEO database,171 related targets were identified.When combined with other databases,a total of 2,343 hepatic fibrosis-related targets were obtained.Xiayuxue Tang comprises 82 related components,which include 26 active components from rhubarb,1 from ground beetle worm,46 from peach kernels,with a total of 314 predicted targets.The GO enrichment analysis revealed 748 biological processes,32 cellular components,and 73 molecular functions,while the KEGG enrichment analysis identified 222 pathways.Molecular docking verification confirmed that effective compounds can bind stably to key proteins,exhibiting strong binding activity.This underscores the potential efficacy of Xiayuxue Tang in addressing hepatic fibrosis.Conclusion:Xiayuxue Tang exerts regulatory effects on hepatic fibrosis through different targets and pathways,suggesting that the herbal compound has the characteristics of multiple pathways and targets.

Formation of free-surface vortex and vortex suppression by rotating stopper-rod at end of tundish casting

A rotating stopper-rod technique was proposed to suppress the formation of free-surface vortex in the tundish.The large eddy simulation model coupled with volume of fluid model was developed to study the steel–slag–gas three-phase flow behavior.The critical slag entrapment height of the free-surface vortex and mass of residual steel were predicted at different rotating speeds(30,60,90 and 120 r/min)of the rotating stopper-rod.The numerical model was verified by water model experiment.The results showed that by rotating the stopper-rod in the opposite direction of the vortex above the submerged entry nozzle,the formation of vortex can be effectively disturbed and the critical height of the free-surface vortex can be reduced.Particularly for the 2nd strand,when the rotating speeds are 30,60,90 and 120 r/min,the critical height of the free-surface vortex above the 2nd strand is 7.3,4.7,6.3 and 7.4 cm,respectively.A reasonable rotating speed should be 60 r/min,which can reduce about 2 tons of residual steel.Other rotating speeds just can reduce about 1.6 tons of residual steel.

Chemical Constituents from Mycelia and Spores of Fungus Cordyceps cicadae

Objective To isolate and identify the chemical constituents from mycelia and spores of the fungus Cordyceps cicadae,respectively.Methods The chemical constituents were isolated and purified by repeated silica gel,Sephadex LH-20,and reversed phase HPLC.The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis,including 1 D and 2D NMR.Results Nine known sterols such as ergosterol（1）,ergosterol peroxide（2）,9,11-dehydroergosterol peroxide（3）,3β,5α,9α-trihydroxy-（22E,24R）-ergosta-7,22-dien-6-one（4）,3β,5α,9α,14α-tetrahydroxy-（22E,24R）-ergosta-7,22-dien-6-one（5）,5 α,6α-e poxy-（22 E,,24 R）-e rgosta-8（14）,22-diene-3α,7α-diol （6）, 3β,5α,6β-（22E,24R）-ergosta-7,22-dien-3,5,6-triol （7）, 3β,5α,6α-6- methoxyergosta-（22E,24R）-7,22-diene-3,5-diol （8）, 4-hydroxy-17R-methylincisterol （9）, together with a resorcinol derivative, 5-n-nonadecylresorcinol （10）, a cydo- desipeptide, beauvericin （11）, and a nucleoside, N^6-（2-hydroxyethyl）adenosine （12） were successively isolated from the cultivated C. cicadaemycelia and spores. Conclusion Compounds 3-10 are reported for the first time from the title sample, beauvericin exhibits significant cytotoxicity against human leukemia cell line and human lung cancer cell line.

MdbHLH3 modulates apple soluble sugar content by activating phosphofructokinase gene expression

Sugars are involved in plant growth,fruit quality,and signaling perception.Therefore,understanding the mechanisms involved in soluble sugar accumulation is essential to understand fruit development.Here,we report that Md PFPβ,a pyrophosphatedependent phosphofructokinase gene,regulates soluble sugar accumulation by enhancing the photosynthetic performance and sugar-metabolizing enzyme activities in apple(Malus domestica Borkh.).Biochemical analysis revealed that a basic helix-loop-helix(b HLH)transcription factor,Mdb HLH3,binds to the Md PFPβpromoter and activates its expression,thus promoting soluble sugar accumulation in apple fruit.In addition,Md PFPβoverexpression in tomato influenced photosynthesis and carbon metabolism in the plant.Furthermore,we determined that Mdb HLH3 increases photosynthetic rates and soluble sugar accumulation in apple by activating Md PFPβexpression.Our results thus shed light on the mechanism of soluble sugar accumulation in apple leaves and fruit:Mdb HLH3 regulates soluble sugar accumulation by activating Md PFPβgene expression and coordinating carbohydrate allocation.

Regulation of a vacuolar proton-pumping P-ATPase MdPH5 by MdMYB73 and its role in malate accumulation and vacuolar acidification

As the main organic acid in fruits,malate is produced in the cytoplasm and is then transported into the vacuole.It accumulates by vacuolar proton pumps,transporters,and channels,affecting the taste and flavor of fruits.Among the three types of proton pumps(V-ATPases,V-PPases,and P-ATPases),the P-ATPases play an important role in the transport of malate into vacuoles.In this study,the transcriptome data,collected at different stages after blooming and during storage,were analyzed and the results demonstrated that the expression of MdPH5,a vacuolar proton-pumping P-ATPase,was associated with both pre-and post-harvest malate contents.Moreover,MdPH5 is localized at the tonoplast and regulates malate accumulation and vacuolar pH.In addition,MdMYB73,an upstream MYB transcription factor of MdPH5,directly binds to its promoter,thereby transcriptionally activating its expression and enhancing its activity.In this way,MdMYB73 can also affect malate accumulation and vacuolar pH.Overall,this study clarifies how MdMYB73 and MdPH5 act to regulate vacuolar malate transport systems,thereby affecting malate accumulation and vacuolar pH.