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TRIM21-dependent ultrasmall chiral gold nanoparticles for preventing microglia senescence against Alzheimer's disease

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Science China Chemistry 2024年第4期67卷 1360-1372页

作者： Meiru Lu Changlong Hao Liguang Xu Feng Yu Jiwei Jiang Yanli Wang Jun Xu Hua Kuang Chuanlai Xu Maozhong Sun International Joint research laboratory for Biointerface and Biodetection State Key Laboratory of Food Science and ResourcesSchool of Food Science and TechnologyJiangnan UniversityWuxi 214122China Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China National clinical research center for Neurological Diseases Beijing 100070China

Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ***,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were *** conjugated with an NLR family pyrin domain-containing protein 3(NLRP3)antibody(D-NP-a NLRP3 or L-NP-a NLRP3),DNP-a NLRP3 showed effective delivery efficiency of the antibody into microglia and prevented Aβ-mediated microglia senescence,and p16^(ink4a),a marker of senescence,in the microglia was reduced by 90.3%±7.8% while L-NP-a NLRP3 decreased by 48.01%±3.1%.Mechanistic investigations revealed that the D-NP-a NLRP3((1.5±0.3)×10^(7)M^(-1))exhibited sixteen-fold larger binding affinity to transmembrane glycoprotein SLC3A2 than L-type((9.5±2.7)×10^(5)M^(-1)),which led to a high efficiency of antibody delivery and TRIM21-dependent NLRP3 ***,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in *** APP/PS1 Alzheimer's disease(AD)model mice experiments exhibited a reduction of 89.7%±6.8% for the NLRP3 protein and 84.2±7.5% for p16^(ink4a)following the intravenous administration of D-NP-a NLRP3 once a week for 60 ***,the levels of the AD markers Aβ and phosphorylatedTau in the brains were reduced by 86.2%±8.2% and 81.6%±9.1%;these were 2.1-fold and 1.9-fold higher than those treated with L-NP-a NLRP3,*** studies provide a method to rescue AD-like pathologies and prevent senescence.

关键词： chiral gold nanoparticles amyloid-β NLRP3 TRIM21 senescence Alzheimer's disease

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Single-cell transcriptomics systematically discloses the immune-inflammatory responses of peripheral blood mononuclear cells for diabetic nephropathy

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Genes & Diseases 2024年第4期11卷 82-85页

作者： Jiangpeng wu Nan Hu Baochun Guo Hualin Ma Lulin Xie Yisha Huang Siyu Xia Yuke Jiang Zhije Li Jigang Wang Xinzhou Zhang Zhen Liang Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China Department of Geriatrics and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China State Key laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China

Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes *** functional alterations of renal infiltrating immune cells have been reported as part of the pathological mechanism of DN,the understanding of the immune response underlying peripheral blood mononuclear cells(PBMCs)in DN remains ***,single-cell RNA sequencing(scRNA-seq)was used toprofile the transcriptomic signatures of PBMCs from DN patients.

关键词： nephropathy alterations mortality

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Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China medical research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer *** RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still *** bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and *** evidence suggests a connection between PBs dynamics and cancer *** the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in ***,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient *** MEX3A accelerates malignance and inhibits autophagy of CRC ***,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the ***,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs *** MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC ***,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall *** findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

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Adjuvant camrelizumab plus apatinib in resected hepatocellular carcinoma with microvascular invasion:a multi-center real world study

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 616-631,I0022-I0024页

作者： Jingzhong Ouyang Yi Yang Yanzhao Zhou Xu Chang Zhengzheng Wang Qingjun Li Yu Tang Jianqiang Cai Jinxue Zhou Zhen Huang Hong Zhao Department of Hepatobiliary and Pancreatic Surgery The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key laboratory of Gene Editing Screening and research and Development(R&D)of Digestive System Tumor Drugs Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Interventional Therapy II Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanChina clinical Trials center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background:It is well known that laparoscopic liver surgery can offer advantages over open liver surgery in selected ***,what type of procedures can benefit most from a laparoscopic approach has been investigated poorly thus *** aim of this study is thus to define the extent of advantages of laparoscopic over open liver surgery for lesions in the anterolateral(AL)and posterosuperior(PS)***:In this international multicentre retrospective cohort study,laparoscopic and open minor liver resections for lesions in the AL and PS segments were compared after propensity score *** differential benefit of laparoscopy over open liver surgery,calculated using bootstrap sampling,was compared between AL and PS resections and expressed as a Delta of the ***:After matching,3,040 AL and 2,336 PS resections were compared,encompassing open and laparoscopic procedures in a 1:1 *** and PS laparoscopic liver resections were more advantageous in comparison to open in terms of blood loss,transfusion rate,complications,and length of ***,AL resections benefitted more from laparoscopy than PS in terms of overall and severe complications(D-difference were 4.8%,P=0.046 and 3%,P=0.046)and blood loss(D-difference was 195 mL,P<0.001).Similar results were observed in the subset for high-volume centres,while in recent years no significant differences were found in the differential benefit between AL and PS ***:The advantage of laparoscopic over open liver surgery is greater in the AL segments than in the PS segments.

关键词： Liver neoplasms hepatectomy laparoscopic liver resection open liver resection

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Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

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Journal of Genetics and Genomics 2024年第2期51卷 222-229页

作者： Wenbin Huang Shiying Zhang Jiuxiang Lin Yi Ding Nan Jiang Jieni Zhang Huaxiang Zhao Feng Chen Department of Orthodontics Peking University School and Hospital of StomatologyBeijing100081China Key laboratory of Shaanxi Province for Craniofacial Precision Medicine research College of StomatologyXi’an Jiaotong UniversityXi’anShaanxi710004China Guangdong Provincial High-level clinical Key Specialty Guangdong Province Engineering Research Center of Oral Disease Diagnosis and TreatmentDepartment of OrthodonticsStomatological CenterPeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi'an Jiaotong UniversityXi'anShaanxi710049China National center for Stomatology National Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory for Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing100101China Central laboratory Peking University School and Hospital of StomatologyBeijing100081China

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.

关键词： Or ofacial clefts FLNB Loss-of-function mutati on Cleft palate Filamin B Actin flannent Knockout mouse

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Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell Therapy center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate *** a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury ***,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord *** neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury ***,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion *** of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the ***,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion ***-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China clinical research center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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research advances in the function and anti-aging effects of nicotinamide mononucleotide

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第9期25卷 723-735页

作者： Min WANG Yuan CAO Yun LI Lu WANG Yuyan LIU Zihui DENG Lianrong ZHU Hongjun KANG Chinese PLA medical School Beijing100853China Department of Critical Care Medicine the First Medical CentreChinese PLA General HospitalBeijing100853China Department of Emergency The Second Hospital of Hebei Medical UniversityShijiazhuang050004China Department of Biochemistry Chinese PLA Medical SchoolBeijing100853China Department of clinical Nutrition the First Medical CentreChinese PLA General HospitalBeijing100853China Nephrology Institute of the Chinese People’s Liberation Army State Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchDepartment of Nephrologythe First Medical CenterChinese PLA General HospitalBeijing100853China

Aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary *** these concerns is an imperative task,with the aims of postponing the aging process and finding effective treatments for age-related degenerative *** investigations have highlighted the significant roles of nicotinamide adenine dinucleotide(NAD+)in the realm of *** has been empirically evidenced that supplementation with nicotinamide mononucleotide(NMN)can elevate NAD+levels in the body,thereby ameliorating certain age-related degenerative *** principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism,inhibition of cell apoptosis,modulation of immune function,and preservation of genomic stability,which collectively contribute to the deferral of the aging *** paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN,elucidates the inherent limitations of current research,and proposes novel avenues for anti-aging investigations.

关键词： Nicotinamide mononucleotide(NMN) Anti-aging Energy metabolism Apoptosis DNA repair

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Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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Zoological research 2024年第3期45卷 663-678页

作者： Li-Rong Liang Bing Liu Shu-Hui Cao You-Yi Zhao Tian Zeng Mei-Ting Zhai Ze Fan Dan-Yi He San-Xin Ma Xiao-Tong Shi Yao Zhang Hui Zhang State Key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of AnesthesiologySchool of StomatologyAir Force Medical UniversityXi’anShaanxi 710032China Department of Anesthesiology 986th Air Force HospitalAir Force Medical UniversityXi’anShaanxi 710032China

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive ***,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive ***,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly *** this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal *** neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral *** indicated that ADNP was significantly down-regulated following developmental exposure to *** adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine ***,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane ***-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by *** analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic *** of Wnt signaling was restored in the davunetide-treated ***,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general *** study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity

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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key laboratory of Translational medical research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China center for medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National clinical research center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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