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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau xiang Zhang Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Metaanalysis

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1128-1137页

作者： Xiao-Yan Wang hong-Wei Deng Jian Yang Xue-Mei Zhu Feng-Ling xiang Jing Tu Ming-Xue Huang Yun Wang Jin-Hua Gan Wei-Hua Yang School of Nursing Southwest Medical UniversityLuzhou 646600Sichuan ProvinceChina Shenzhen Eye Institute Shenzhen Eye HospitalJinan UniversityShenzhen 518040Guangdong ProvinceChina Luzhou Traditional Chinese Medicine Hospital Luzhou 646000Sichuan ProvinceChina The Affiliated Hospital of Southwest Medical University Luzhou 646099Sichuan ProvinceChina

AIM:To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of ***:A systematic search was conducted across the Cochrane Library,PubMed,Web of Science,EMBASE,CNKI,CBM,VIP,and Wanfang database,encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17,*** extraction and quality assessment were performed,and a network Meta-analysis was executed using Stata version 14.0 *** were visually represented through ***:Fourteen papers comprising 2475 cases were included;five different concentrations of atropine solution were *** network Meta-analysis,along with the surface under the cumulative ranking curve(SUCRA),showed that 1%atropine(100%)>0.05%atropine(74.9%)>0.025%atropine(51.6%)>0.02%atropine(47.9%)>0.01%atropine(25.6%)>control in refraction change and 1%atropine(98.7%)>0.05%atropine(70.4%)>0.02%atropine(61.4%)>0.025%atropine(42%)>0.01%atropine(27.4%)>control in axial length(AL)***:In Chinese children and teenagers,the five various concentrations of atropine can reduce the progression of *** the network Meta-analysis showed that 1%atropine is the best one for controlling refraction and AL change,there is a high incidence of adverse effects with the use of 1%***,we suggest that 0.05%atropine is optimal for Chinese children to slow myopia progression.

关键词： atropine China children and adolescents myopia network Meta-analysis

Purple acid phosphatase promoted hydrolysis of organophosphate pesticides in microalgae

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Environmental Science and Ecotechnology 2024年第2期18卷 137-149页

作者： xiang Wang Guo-Hui He Zhen-Yao Wang Hui-Ying Xu Jin-Hua Mou Zi-Hao Qin Carol Sze Ki Lin Wei-Dong Yang Yalei Zhang hong-Ye Li Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes College of Life Science and TechnologyJinan UniversityGuangzhou510632China School of Energy and Environment City University of Hong KongTat Chee AvenueKowloonHong Kong Centre for Technology in Water and Wastewater School of Civil and Environmental EngineeringUniversity of Technology SydneyUltimoNSW2007Australia Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou510000China State Key Laboratory of Pollution Control and Resources Reuse College of Environmental Science and EngineeringTongji UniversityShanghai200092China

When organophosphate pesticides(OPs)are not used and handled in accordance with the current rules and standards,it results in serious threats to the aquatic environment and human *** tricornutum is a prospective microalgae-based system for pollutant removal and carbon *** engineered ***,designated as the OE line(endogenously expressing purple acid phosphatase 1[PAP1]),can utilize organic phosphorus for cellular ***,the competencies and mechanisms of the microalgae-based system(namely the OE line of ***)for metabolizing OPs remain to be *** this study,the OE line exhibited the effective biodegradation competencies of 72.12%and 68.2%for 30 mg L^(-1)of dichlorvos and 50 mg L^(-1)of glyphosate,accompanied by synergistic accumulations of biomass(0.91 and 0.95 g L^(-1))and lipids(32.71%and 32.08%),***,the biodiesel properties of the lipids from the OE line manifested a high potential as an alternative feedstock for microalgae-based biofuel production.A plausible mechanism of OPs biodegraded by overexpressed PAP1 is that sufficient inorganic P for adenosine triphosphate and concurrent carbon flux for the reduced form of nicotinamide adenine dinucleotide phosphate biosynthesis,which improved the OP tolerance and biodegradation competencies by regulating the antioxidant system,delaying programmed cell death and accumulating lipids via the upregulation of related *** sum up,this study demonstrates a potential strategy using a genetically engineered strain of *** to remove high concentrations of OPs with the simultaneous production of biomass and biofuels,which might provide novel insights for microalgae-based pollutant biodegradation.

关键词： Biodegradation Lipid accumulation Organophosphate pesticide Phaeodactylum tricornutum Purple acid phosphatase

奶水牛乳汁体细胞数与抗氧化指标的相关性分析

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南方农业学报 2014年第5期45卷 882-886页

作者：杜玉兰邓慧芳黄云飞杜向宏骆燕静何宝祥广西大学动物科学技术学院南宁530005

【目的】了解奶水牛乳汁体细胞计数(SCC)与抗氧化指标之间的相关性,为乳汁质量监控和奶水牛健康养殖提供科学依据。【方法】随机选取南宁某牛场奶水牛139头,同步采集乳样与血样,乳汁SCC采用FOSS体细胞仪测定,血浆和乳清的总抗氧化能力(T... 详细信息

【目的】了解奶水牛乳汁体细胞计数(SCC)与抗氧化指标之间的相关性,为乳汁质量监控和奶水牛健康养殖提供科学依据。【方法】随机选取南宁某牛场奶水牛139头,同步采集乳样与血样,乳汁SCC采用FOSS体细胞仪测定,血浆和乳清的总抗氧化能力(TAC)采用FRAP法(血浆铁还原力法)测定,丙二醛(MDA)含量采用TBA法(硫酸巴比妥法)测定。【结果】被检的139头奶水牛中,乳汁SCC≥50.00万/mL(隐性乳房炎诊断标准)的样本占被检总数的12.23%,乳汁SCC<50.00万/mL的样本占被检总数的87.77%;奶水牛血浆和乳清的TAC分别为2.44±1.04和3.78±1.68 U/mL,MDA含量分别为2.07±0.48和1.55±0.52 nmol/mL,其差异均达极显著水平(P<0.01)。乳清TAC随乳汁SCC的升高而呈下降趋势,二者间呈显著负相关(r=-0.168,P<0.05);血浆MDA与乳清MDA间呈显著正相关(r=0.189,P<0.05),而血浆MDA与血浆TAC(r=0.391)、乳清MDA与血浆TAC(r=0.315)间呈极显著正相关(P<0.01)。【结论】乳清TAC可作为检测奶水牛乳房健康及其乳汁质量的备选指标。

关键词：奶水牛乳汁体细胞计数(SCC) 总抗氧化能力(TAC) 丙二醛(MDA) 相关性

XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng xiang Xu Yi-Zhuo Li Yan Tang Wei-hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of Stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

LLM4CP:Adapting Large Language Models for Channel Prediction

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Journal of Communications and Information Networks 2024年第2期9卷 113-125页

作者： Boxun Liu Xuanyu Liu Shijian Gao xiang Cheng Liuqing Yang State Key Laboratory of Advanced Optical Communication Systems and Networks School of ElectronicsPeking UniversityBeijing 100871China Internet of Things Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Internet of Things Thrust and Intelligent Transportation Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Department of Electronic and Computer Engineering and Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyHong KongChina

Channel prediction is an effective approach for reducing the feedback or estimation overhead in massive multi-input multi-output (m-MIMO) systems. However, existing channel prediction methods lack precision due to model mismatch errors or network generalization issues. Large language models (LLMs) have demonstrated powerful modeling and generalization abilities, and have been successfully applied to cross-modal tasks, including the time series analysis. Leveraging the expressive power of LLMs, we propose a pre-trained LLM-empowered channel prediction(LLM4CP)method to predict the future downlink channel state information (CSI) sequence based on the historical uplink CSI sequence. We fine-tune the network while freezing most of the parameters of the pre-trained LLM for better cross-modality knowledge transfer. To bridge the gap between the channel data and the feature space of the LLM,preprocessor, embedding, and output modules are specifically tailored by taking into account unique channel characteristics. Simulations validate that the proposed method achieves state-of-the-art (SOTA) prediction performance on full-sample, few-shot, and generalization tests with low training and inference costs.

关键词： channel prediction massive multi-input multi-output(m-MIMO) large language models(LLMs) fine-tuning time-series

Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology ***,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical ***,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus ***,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in *** cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed *** also found expression of signaling pathways components that may increase the potential for chimera *** for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in *** engineered cells retained embryonic and extra-embryonic developmental ***,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living *** study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li xiang Chen Yongfeng Shao Yong Ji hongshan Chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical Medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military Medical Research 2024年第4期11卷 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei hong Department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB