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Biallelic variants in RBM42 cause a multisystem disorder with neurological,facial,cardiac,and musculoskeletal involvement

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Protein & Cell 2024年第1期15卷 52-68页

作者： Yiyao chen Bingxin Yang Xiaoyu Merlin Zhang Songchang chen Minhui Wang Liya Hu Nina Pan Shuyuan Li Weihui Shi Zhenhua Yang Li Wang Yajing Tan Jian Wang Yanlin Wang Qinghe xing Zhonghua Ma Jinsong Li He-Feng Huang Jinglan Zhang chenming Xu Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China bstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China Intermational Peace Matermity and Child Health Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China Shanghai Key Laboratory of Embryo Original Diseases Shanghai 200030China State Key Laboratory of Cell Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China State Key Laboratory of Rice Biology the Key Laboratory of Molecular Biology of Crop Pathogens and InsectsInstitute of BiotechnologyZhejiang UniversityHangzhou 310058China Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of MedicineHoustonTX 77030USA Children's hospital of Fudan University Shanghai 201102China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024ZhejiangChina Research Units of Embryo Original Diseases Chinese Academy of Medical Sciences(No.2019RU056)Shanghai 200011China

Here,we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 *** patient is a 2-year-old female with severe central nervous system(CNs)abnormalities,hypotonia,hearing loss,congenital heart defects,and dysmorphic facial *** whole-exome sequencing(WEs)reveals that the patient has two compound heterozygous variants,c.304C>T(p.R102*)and c.1312G>A(p.A438T),in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein *** p.A438T variant is in the RRM domain which impairs RBM42 pro-tein stability in ***,p.A438T disrupts the interaction of RBM42 with hnRNP K,which is the causa-tive gene for Au-Kline syndrome with overlapping disease characteristics seen in the index *** human R102*or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout△FgRbp1 in Fusarium while it was rescued by the wild-type(WT)human RBM42.a mouse model carying Rbm42 compound heterozygous variants,c.280C>T(p.Q94*)and c.1306_1308delinsACA(p.A436T),demonstrated gross fetal develop-mental defects and most of the double mutant animals died by ***-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing(As).Overall,we present clinical,genetic,and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

关键词： RBM42 gene RNA-binding protein neurodevelopmental disorder Au-Kline syndrome alternative splicing

Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain:A prospective,multicenter randomized trial

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Journal of Integrative Medicine 2024年第1期22卷 39-45页

作者： Jun-yan He Xiao-yu Tu Zi-fei Yin Hui Mu Ming-jun Luo xing-yu chen Wei-bin Cai Xue Zhao Can Peng Fan-fu Fang Can Lü Bai Li School of Traditional Chinese Medicine Naval Medical UniversityShanghai 200433China Department of Rehabilitation Medicine and Physiotherapy the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Department of Rehabilitation Medicine and Training PLA 458 HospitalGuangzhou 510602Guangdong ProvinceChina No.3 Ward of Acupuncture Rehabilitation Department Guangdong Second Traditional Chinese Medicine HospitalGuangzhou 510095Guangdong ProvinceChina

Background As one of the most common musculoskeletal ailments,chronic nonspecific low-back pain(CNLBP)causes persistent disability and substantial medical *** evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is *** guidelines indicate a reduced role for medicines in the management of *** The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm,compared to nonsteroidal anti-inflammatory drug(NSAID)with a capsaicin plaster,in the treatment of ***,setting,participants and interventions We designed a prospective multicenter randomized clinical trial enrolling patients from January 1,2022 to December 31,2022.a total of 156 patients with CNLBP were randomized into two parallel *** sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied *** in the test group were treated with cupping and scraping using a medical device and medicated *** outcome measures Primary outcome was pain recorded using the visual analogue scale(VAS).Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale(JOA)and the traditional Chinese medicine(TCM)syndrome integral scale(TCMS)as assessment *** Between baseline and postintervention,all changes in outcome metric scales were statistically significant(P<0.001).Compared to the control group,patients in the test group had a significantly greater treatment effect in all outcome variables,as indicated by lower VAS and TCMS scores and higher JOA scores,after the one-week intervention period(P<0.001).Further,according to the findings of multivariate linear regression analysis,the participants’pain(VAS score)was related to their marital status,age,smoking habits and body mass *** adverse r

关键词： Chronic nonspecific low-back pain Traditional Chinese medicine Cupping and scraping therapy

Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2.axis Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 115-124页

作者： LUO Zhi-yi TIAN Qi chenG Niang-mei LIU Wen-han YANG Ye chen Wei ZHANG Xiang-zhi ZHENG Xiao-yuan chen Ming-sheng ZHUANG Qiu-yu ZHAO Bi-xing LIU Cong-sheng LIU Xiao-long LI Qin WANG Ying-chao The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd.ZhangzhouFujian Province(363099)China College of Biological Science and Engineering and Mengchao Med-X Center Fuzhou UniversityFuzhou(350116)China Department of Internal Medicine Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China

Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular ***:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 ***,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),*** vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of ***-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail *** 8 mice were randomly divided into PZH and control groups,4 mice in each *** 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day *** analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of *** real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq *** reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylatio

关键词： PienTzeHuang hepatocellular carcinoma RNA-seq Hippo yes-associated protein

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang xing Yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng Bolun Li Junling Pang Wenjun Guo Ting Shu Jinqiu Li Jie Yang Qilong Mao Ya Luo Xianmei Qi Peiran Yang Chaoyang Liang Hongmei Zhao Wenhui chen Jing Wang chen Wang State Key Laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China Department of Lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The State Key Laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B Pulmonary hypertension Endothelial-to-mesenchymal transition

Screening of Chinese giant salamander meat hydrolysates with DPP-IV inhibitory activity and systematic elucidation of their hypoglycemic functions in mouse model

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Food Science and Human Wellness 2024年

作者： Shucheng Li Changge Guan Yi Wang Haihong chen Wei Li Songjun Wang Chong Zhang Xin-Hui xing Key Laboratory for Industrial Biocatalysis， Ministry of Education of China， Department of Chemical Engineering， Tsinghua University School of Life Science and Technology， Tokyo Institute of Technology Institute of Biopharmaceutical and Health Engineering， Tsinghua Shenzhen International Graduate School Henan Giant Salamander Protection and Development Association Center for Synthetic and Systems Biology， Tsinghua University Institute of Biomedical Health Technology and Engineering， Shenzhen Bay Laboratory

Type 2 diabetes (T2D) presents a significant health challenge， underscoring the need for functional foods and nutraceutical hypoglycemic bioactive peptides for its prevention. This study investigates the potential of proteolytic hydrolysate from artificially cultivated Chinese giant salamander (CGS) meat， a rich protein source， as a preventive strategy for T2D. We produced a CGS meat hydrolysate (CGSh) and demonstrated its ability to inhibit the T2D drug target DPP-IV through in vitro assays. We identified five peptides (WRPPDH， WAPPSKD， IPDSPF， IPEMIF， and VPIAVPT) with high DPP-IV inhibitory activity in CGSh， suggesting its potential antidiabetic effects. In vivo experiments showed that CGSh effectively reduced insulin resistance in mice induced with a high-fat diet， as evidenced by a slower increase in blood glucose levels and a decreased HOMA-IR index. 16S rRNA sequencing analysis revealed that CGSh improved gut microbial homeostasis， promoting beneficial microorganisms and reducing harmful bacteria. Metabolomic analyses identified an increase in valeric acid levels and highlighted nine potential biomarker metabolites. By inhibiting metabolic pathways such as AGE-RAGE， CGSh may also prevent diabetic complications and reduce inflammation. These findings suggest that CGSh has a promising hypoglycemic effect， making it a potential functional food ingredient for T2D prevention and treatment.

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Alterations of sleep deprivation on brain function:A coordinatebased resting-state functional magnetic resonance imaging metaanalysis

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World Journal of Psychiatry 2024年第2期14卷 315-329页

作者： Qin Zhang Yong-Zhe Hou Hui Ding Yan-Ping Shu Jing Li Xi-Zhao chen Jia-Lin Li Qin Lou Dai-xing Wang Department of Radiology The Second People’s Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology Guizhou Provincial People’s HospitalGuiyang 550000Guizhou ProvinceChina Department of Psychiatry of Women and Children The Second People’s Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Medical Humanities College Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive *** numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep *** To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging *** metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)*** A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,*** that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE *** Twenty-one studies,including 23 experiments and 498 subjects,were *** to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal *** revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right *** This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.

关键词： Sleep deprivation Resting-state-functional magnetic resonance imaging Activation likelihood estimation-meta Signed differential mapping-meta

Acupotomy ameliorates knee osteoarthritis-related collagen deposition and fibrosis in rabbit skeletal muscle through the TGF-β/Smad pathway

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Journal of Traditional Chinese Medical Sciences 2024年第3期11卷 376-385页

作者： Tingyao Hu Einar Khavaza Chuxi Liang Longfei xing Xilin chen Yue Xu Weiwei Ma Farid Mokhtari Juan Lu Changqing Guo School of Acupuncture Moxibustion and TuinaBeijing University of Chinese MedicineBeijing 102488China Department of Traditional Chinese Medicine Peking University People's HospitalBeijing 100044China The Fifth College of Clinical Medicine Guangzhou University of Traditional Chinese MedicineGuangzhou 511436China Department of Acupuncture and Rehabilitation Guangdong Second Hospital of Traditional Chinese MedicineGuangzhou 510260China Traditional Clinic Shahid Beheshti Medical UniversityTehran ***Iran Department of Traditional Chinese Medicine Shenzhen Hospital of Southern Medical UniversityShenzhen 510515China

Objective To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)*** Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 *** modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the *** behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron *** expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle *** blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P271).Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

关键词： Acupotomy Knee osteoarthritis Skeletal muscle Fibrosis Collagen deposition

Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DsS-inducedcolitis

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Precision Clinical Medicine 2024年第2期7卷 146-158页

作者： Jun-hua Li Yu chen Zheng-hao Ye Li-ping chen Jia-xin Xu Jian Han Lin Xie Shuai xing De-an Tian Ursula Seidler Jia-zhi Liao Fang Xiao Department of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolHannover 30625Germany

Background:Myeloid differentiation factor 88(MyD88)is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host ***,the role of MyD88 in the pathogenesis of inflammatory bowel disease is *** study aims to investigate the impact of MyD88 on intestinal inflammation and ***:MyD88 knockout(MyD88^(-/-))mice and the MyD88 inhibitor(TJ-M2010-5)were used to investigate the impact of MyD88 on acute dextran sodium sulfate(Dss)-induced *** activity index,colon length,histological score,and inflammatory cytokines were examined to evaluate the severity of *** transcriptome analysis and 16S rDNA sequencing were used to detect the potential ***:In an acute DSS-colitis model,the severity of colitis was not alleviated in MyD88^(-/-)mice and TJ-M2010-5-treated mice,despite significantly lower levels of NF-kB activation being exhibited compared to control ***,16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors(NLRs)signaling pathway in colitis mice following MyD88 *** blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DsS-induced colitis mice treated with TJ-M2010-5 ameiorated the disease severity,which was not improved solely by MyD88 *** treatment with broad-spectrum antibiotics,downregulation of the NLR signaling pathway was ***:Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota,leading to NLR-mediated immune activation and intestinal inflammation.

关键词： microbiota innate immunity myeloid differentiation factor 88,MyD88 inhibitor NOD-like receptor inflammatory bowel disease

Low palladium content CeO_(2)/ZnO composite for acetone sensor with sub-second response prepared by ultrasonic method

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Journal of Central South University 2024年第7期31卷 2137-2149页

作者： chen Xu-jie xing Qiao-ling TANG Xuan CAI Yong ZHANG Ming Hunan Provincial Key Laboratory of Low-dimensional Structural Physics&Devices School of Physics and ElectronicsHunan UniversityChangsha 410082China Changsha Semiconductor Technology and Application Innovation Research Institute College of Semiconductors(College of Integrated Circuits)Hunan UniversityChangsha 410082China School of Mechanical Engineering and Mechanics Xiangtan UniversityXiangtan 411105China Research Institute of Hunan University in Chongqing Chongqing 401120China Engineering Research Center of Advanced Semiconductor Technology and Application of Ministry of Education&Key Laboratory for Micro-/Nano-Optoelectronic Devices of Ministry of Education National Key Laboratory of Power Semiconductor and Integration TechnologyCollege of Semiconductors(College of Integrated Circuits)Hunan UniversityChangsha 410082China

In practical applications,noble metal doping is often used to prepare high performance gas sensors,but more noble metal doping will lead to higher preparation *** this study,CeO_(2)/ZnO-Pd with low palladium content was prepared by ultrasonic method with fast response and high selectivity for acetone *** the same amount of palladium added,the selectivity coefficient of CeO_(2)/ZnO-Pd is 1.88 times higher than that of the stirred *** with the pure PdO-doped CeO_(2)/ZnO-PdO material,the content of Pd in CeO_(2)/ZnO-PdO is about 30%of that in CeO_(2)/ZnO-PdO,but the selectivity coefficient for acetone is 2.56 times *** CeO_(2)/ZnO-Pd sensor has a higher response(22.54)to 50×10^(−6) acetone at 300℃and the selectivity coefficient is 2.57 times that of the CeO_(2)/ZnO *** sensor has a sub-second response time(0.6 s)and still has a 2.36 response to 330×10^(−9) of *** doping makes Pd particles smaller and increases the contact area with ***,the composition of n-p-n heterojunction and the synergistic effect of Pd/PdO improve the sensor *** shows that ultrasonic Pd doping provides a way to improve the utilization rate of doped metals and prepare highly selective gas sensors.

关键词： low palladium sub-second responce ultrasonic method acetone sensor heterojunction