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Neural Regeneration research 2024年第8期19卷 1647-1648页

作者： Sven Marcel Stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of clinical Pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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Animal Models and experimental Medicine 2024年第3期7卷 324-336页

作者： Bowen Niu Lingling Liu Qian Gao Meng-Min Zhu Lixiang Chen Xiu-Hua Peng Boying Qin Xiaohui Zhou Feng Li Department of laboratory Animal Science Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Biology College of Life SciencesShanghai Normal UniversityShanghaiPeople's Republic of China

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic *** taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in ***:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the ***,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder *** real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste *** to taste substance was also studied using twobottle preference ***:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 *** results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant *** qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant *** two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of *** addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB ***:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

关键词： bitter taste receptor CRISPR/Cas9 genetic mutation two-bottle preference test type 2 taste receptors(Tas2rs)

RSPSSL:A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization

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Light(Science & Applications) 2024年第2期13卷 366-386页

作者： Jiaqi Hu Gina Jinna Chen Chenlong Xue Pei Liang Yanqun Xiang Chuanlun Zhang Xiaokeng Chi Guoying Liu Yanfang Ye Dongyu Cui De Zhang Xiaojun yu Hong Dang Wen Zhang Junfan Chen Quan Tang Penglai Guo Ho-Pui Ho Yuchao Li Longqing Cong Perry Ping Shum State Key laboratory of Optical Fiber and Cable Manufacture Technology Guangdong Key Laboratory of Integrated Optoelectronics IntellisenseDepartment of EEESouthern University of Science and TechnologyShenzhen 518055China College of Optical and Electronic Technology China Jiliang UniversityHangzhou 310018China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060China Department of Ocean Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Department of Nephrology Chaozhou People’s HospitalChaozhou 521011China clinical research Design Division Sun Yatsen Memorial HospitalGuangzhouGuangdong 510120China School of Automation Northwestern Polytechnical UniversityXi’anShaanxi 710072China Department of Biomedical Engineering The Chinese University of Hong KongHong KongChina Guangdong Provincial Key laboratory of Nanophotonic Manipulation Institute of NanophotonicsJinan UniversityGuangzhou 511443China

Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and *** is also an emerging omics technique for metabolic profiling to shape precision ***,precisely attributing vibration peaks coupled with specific environmental,instrumental,and specimen noise is *** Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information ***,we propose a novel Raman spectral preprocessing scheme based on self-supervised learning(RSPSSL)with high capacity and spectral *** can preprocess arbitrary Raman spectra without further training at a speed of~1900 spectra per second without human *** experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88%reduction in root mean square error and a 60%reduction in infinite norm(L__(∞))compared to established *** this advantage,it remarkably enhanced various biomedical applications with a 400%accuracy elevation(ΔAUC)in cancer diagnosis,an average 38%(few-shot)and 242%accuracy improvement in paraquat concentration prediction,and unsealed the chemical resolution of biomedical hyperspectral images,especially in the spectral fingerprint *** precisely preprocessed various Raman spectra from different spectroscopy devices,laboratories,and diverse *** scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput,cross-device,various analyte complexity,and diverse applications.

关键词： spectral scheme resolution

A Heterozygous Phospholamban Variant(p.R14del)Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy

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Phenomics 2024年第1期4卷 13-23页

作者： Han Mo Xiumeng Hua Mengni Bao Zhe Sun Xiao Chen Mengda Xu Jiangping Song Shenzhen Key laboratory of Cardiovascular Disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhen 518057China State Key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College167A Beilishi RoadXi Cheng DistrictBeijing 100037China Beijing Key laboratory of Preclinical research and Evaluation for Cardiovascular Implant Materials Animal Experimental CentreFuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy(ARVC)caused by pathogenic mutations in the Phospholamban(PLN)*** study included 170 patients who had a confrmed diagnosis of ARVC and underwent PLN genetic screening using next-generation *** fndings of this study provide valuable insights into the association between PLN mutations and ARVC,which can aid in the development of more efective diagnostic and treatment strategies for ARVC *** of the patients evaluated,six had a rare pathogenic mutation in PLN with the same p.R14del *** screening revealed that heterozygous carriers of p.R14del exhibited a defnite ARVC *** clinical studies,individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome *** adjusting for covariates,individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations(95%CI 1.08–6.82,p=0.035).The accumulation of left ventricular fat and fbers is a pathological marker for ARVC patients with p.R14del *** a cohort of 170 Chinese ARVC patients,three point fve percent of probands had the PLN pathogenic variant(p.R14del)and all were *** data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure,which requires clinical diferentiation from classic ***,carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients.

关键词： Arrhythmogenic right ventricular cardiomyopathy Phospholamban Left ventricular involvement Heart failure Risk stratifcation

LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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Animal Models and experimental Medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina National Center of Stomatology BeijingChina National clinical research Center for Oral Diseases BeijingChina Beijing Key laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina Peking University International Cancer Institute Peking University Health Science CenterPeking UniversityBeijingChina Central laboratory Peking University School and Hospital of StomatologyBeijingChina National Engineering research Center of Oral Biomaterials and Digital Medical Devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone ***,current anti-resorptive drugs carry a risk of various *** deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression *** study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone ***:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary ***-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also *** underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),***:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of *** BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting ***:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical research Centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)***-ing of disease pathogenesis remains limited and has prevented the development of effective *** an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully *** human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory *** review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis Epithelial-mesenchymal transition(EMT) Crosstalk

Mechanism of acupuncture in attenuating cerebral ischaemia-reperfusion injury based on nuclear receptor coactivator 4 mediated ferritinophagy

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Journal of Traditional Chinese Medicine 2024年第2期44卷 345-352页

作者： ZHANG Xinchang HUANG Zheng HUANG Peiyan YANG Mengning ZHANG Zhihui NI Guangxia College of Acupuncture-Moxibustion and Tuina Nanjing University of Chinese MedicineNanjing 210023China Key laboratory of Acupuncture and Medicine research of Ministry of Education Nanjing University of Chinese MedicineNanjing 210023China

OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ***:Sprague-Dawley male rats were divided into four groups:the sham group,model group,acupuncture group,and sham acupuncture *** 2 h of middle cerebral artery occlusion(MCAO),reperfusion was performed for 24 h to induce *** rats were treated with acupuncture at the Neiguan(PC6)and Shuigou(GV26)*** neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after *** chloride staining was applied to assess the cerebral infarct volume at 24 h after *** malondialdehyde(MDA)and ferrous iron(Fe^(2+))levels were observed after 24 h of reperfusion using an assay *** blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1(FTH1)at 24 h after ***,the colocalization of ferritin with neurons,NCOA4 with microtubule-associated protein 1 light chain 3(LC3),and NCOA4 with ferritin was visualized using immunofluorescence ***:Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture *** CIRI,the expression of NCOA4,LC3 and FTH1 was increased,which enhanced ferritinophagy and induced an inappropriate accumulation of Fe^(2+)and MDA in the ischaemic ***,acupuncture dramatically downregulated the expression of NCOA4,LC3 and FTH1,inhibited the overactivation of ferritinophagy,and decreased the levels of MDA and Fe^(2+).CONCLUSIONS:Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.

关键词： acupuncture ferritinophagy ferroptosis ferritin nuclear receptor coactivator 4 cerebral ischaemia-reperfusion injury

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A novel small-animal locomotor activity recording device for biological clock research

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Animal Models and experimental Medicine 2024年第1期7卷 71-76页

作者： Yi-Long Wu Ming Zhong Jun Yin Wei-Jie Ou Yu-Bin Zhuang Nan-Wen Zhang Su Lin Yue-Yong Zhu Endoscopy Center The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Endocrinology The First Affiliated HospitalFujian Medical UniversityFuzhouChina Chuangke Workshop Technology Co. LtdShenzhenChina Department of Digestive Nutrition Fujian Children's HospitalFuzhouChina experimental Animal Center Fujian Medical UniversityFuzhouChina Department of Pharmacology Fujian Medical UniversityFuzhouChina Department of Hepatology Hepatology Research InstituteClinical Research Center for Liver and Intestinal Diseases of Fujian ProvinceThe First Affiliated HospitalFujian Medical UniversityFuzhouChina

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian *** study demonstrated how to construct a simple and intelligent running-wheel recording *** running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's ***,the RJ25 adaptor relayed the running signal to the main control ***,the main control board was connected to the USB port of the computer with the USB *** were collected using the online-accessible,self-created software *** Magturning,generated data were saved and exported in real ***,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light *** conclusion,this new device can record circadian activity of *** device is appropriate for interdisciplinary investigations related to biological clock research.

关键词： biological clock circadian rhythm intelligent equipment locomotor activity running wheel

Investigation of the active ingredients and mechanism of Shuangling extract in dextran sulfate sodium salt induced ulcerative colitis mice based on network pharmacology and experimental verification

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Journal of Traditional Chinese Medicine 2024年第3期44卷 478-488页

作者： CHU Mengzhen WANG Yu LIN Zhijian Lyu Jintao ZHANG Xiaomeng ZHANG Bing Department of clinical Chinese Pharmacy School of Chinese Materia MedicaBeijing University of Chinese Medicine

OBJECTIVE: To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis(UC). METHODS: The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice. RESULTS: The Shuangling extract reduced the levels of seruminterleukin-1β(IL-1β), tumor necrosis factor-α(TNF-N), interleukin-6(IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways. CONCLUSION: The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.

关键词： Shuangling extract colitis, ulcerative molecular docking simulation network pharmacology pharmacodynamic study

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