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Science China Life Sciences 2024年

作者： Xiaoyu Wang Chuchu Chen Chenggan Li Xiaochang Chen Rong Xu Meilin Chen Yongpeng Li Yihao Liu Xiaohong Liu Yaosheng Chen Delin Mo State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-Sen University Shaanxi Basic and Clinical translational research Team for Atherosclerotic Cardiovascular Disease Shaanxi Key Laboratory of Ischemic Cardiovascular Disease Institute of Basic and Translational MedicineXi'an Medical University

Intramuscular fat (IMF) is a complex adipose tissue within skeletal muscle, appearing specially tissue heterogeneous, and the factors influencing its formation remain unclear. In conditions such as diabetes, aging, and muscle wasting, IMF was deposited in abnormal locations in skeletal muscle, damaged the normal physiological functions of skeletal muscle. Here, we used Longissimus dorsi muscles from pigs with different IMF contents as samples and adopted a method combining spatial transcriptome (ST) and single-nucleus RNA-seq to identify the spatial heterogeneity of IMF. ST revealed that genes involved in TGF-β signaling pathways were specifically highly enriched in IMF. In lean pigs, IMF autocrine produces more TGF-β2, while in obese pigs, IMF received more endothelial-derived TGF-β1. In vitro experiments have proven that porcine endothelial cells in a simulated high-fat environment released more TGF-β1 than TGF-β2. Moreover,under obesity mice, the addition of TGF-β after muscle injury abolished IMF production and slowed muscle repair, whereas TGF-β inhibition accelerated muscle repair. Our findings demonstrate that the TGF-β pathway specifically regulates these processes, suggesting it as a potential therapeutic target for managing muscle atrophy in obese patients and enhancing muscle repair while reducing IMF deposition.

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Pichia pastoris composition expressed aerolysin mutant of Aeromonas veronii as an oral vaccine evaluated in zebrafish(Danio rerio)

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Marine Life Science & Technology 2024年第3期6卷 475-487页

作者： Yuan-Yuan Yao Qing-Shuang Zhang Shu-Bin Liu Hong-Wei Yang Xing-Yu Chen Ya-Lin Yang Chen-Chen Gao Chao Ran Tsegay Teame Zhen Zhang Zhi-Gang Zhou Key Laboratory for Feed Biotechnology of the Ministry of Agriculture Institute of Feed Research of Chinese Academy of Agricultural SciencesBeijing 100081China Sino-Norway Fish gastrointestinal Microbiota Joint Lab Institute of Feed Research of Chinese Academy of Agricultural SciencesBeijing 100081China Institute of Marine Sciences Shantou UniversityShantou 515063China Tigray Agricultural research Institute(TARI)Mekelle Center Tigray 7101Ethiopia

Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in *** this study,virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target *** pastoris constitutive secretory expression NTaer(GS115-NTaer)was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish *** result shows that vaccination of GS115-NTaer for four weeks did not affect the growth performance of the host,while eliciting an effective immune protective *** with the control group,the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α(TJP1α)gene,and significantly increased the contents of lysozyme(LYZ),complement C3 and C4 in the gut,indicating that the innate immune response of the fish was *** relative gene expression levels of macrophage-expressed gene 1(MPEG1)and T cell receptor(TCR-α)in the gut,and MPEG1,CD4,CD8,TCR-α,GATA3,and T-bet in the spleen were all increased significantly,indicating that the cellular immune response of the fish was ***,the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased,which showed that humoral immunity was also ***,inoculation with GS115-NTaer significantly changed the structure of gut *** particular,the relative ratio of(Firmicutes+Fusobacteriota+Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 ***,the vaccinated fish were challenged with ***,and the relative percent survival of GS115 and the GS115-NTear groups was 14.28%and 33.43%.This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish ***,this study provides information on the effectiveness of GS115-NTear

关键词： Aeromonas veronii Aerolysin mutant NTaer Oral vaccine Immune response Gut microbiota

Mental retardation,seizures and language delay caused by new SETD1B mutations:Three case reports

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World Journal of Clinical Cases 2024年第2期12卷 383-391页

作者： Le Ding Li-Wan Wei Tai-Song Li Jing Chen Department of Neurology Children’s Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina Chigene(Beijing)translational Medical research Center Co.Ltd.Beijing 101111China

BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve *** in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language *** SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B *** individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were *** article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment *** the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had *** treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat *** exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(***1825trp),c.4120C>T(***1374*,593),c.14_15insC(***5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language *** the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of ***,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.

关键词： Neurodevelopmental disorder Seizure SETD1B gene Whole-exome sequencing New mutation Case report

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia

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Neuroscience Bulletin 2024年第8期40卷 1127-1140页

作者： Lin Wu Donghang Zhang Yujie Wu Jin Liu Jingyao Jiang Cheng Zhou Department of Anesthesiology West China HospitalSichuan UniversityChengdu 610041China Laboratory of Anesthesia and Critical Care Medicine National-Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengdu 610041China

The lateral parabrachial nucleus(PBL)is implicated in the regulation of respiratory *** leak channel(NALCN)mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and ***,we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general *** results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency(RF)in mice;whereas chemogenetic inhibition suppressed *** knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane *** knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or *** sevoflurane anesthesia,painful stimuli rapidly increased the RF,which was not affected by NALCN knockdown in PBL glutamatergic *** study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

关键词： Glutamatergic neurons Lateral parabrachial nucleus NALCN Respiration General anesthesia

Estrogen restores disordered lipid metabolism in visceral fat of prediabetic mice

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World Journal of Diabetes 2024年第5期15卷 988-1000页

作者： Su-Huan Liu Zhao-Shui Shangguan Paiziliya Maitiaximu Zhi-Peng Li Xin-Xin Chen Can-Dong Li research Base of Chinese Medicine Syndrome Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina research Center for translational Medicine The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361003Fujian ProvinceChina

BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 ***[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully *** To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of *** Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body *** gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction *** and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,*** Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous ***,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 ***,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 *** study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene *** In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and thera

关键词： Estrogen Obesity,Visceral adiposity Energy metabolism Type 2 diabetes

Hodgkin's lymphoma:2023 update on treatment

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Cancer Biology & Medicine 2024年第4期21卷 269-273页

作者： Sicong Zhang Xianming Liu Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Xianhuo Wang Huilai Zhang Department of Lymphoma Tianjin Medical University Cancer Institute&HospitalNational Key Laboratory of Druggability Evaluation and Systematic Translational MedicineNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China

Hodgkin's lymphoma(HL)is a common,malignant hematological tumor of the lymph nodes and lymphatic system,accounting for 10%of all *** comprises 2 main subtypes:classical HL(cHL)and nodular lymphocyte predominant HL.

关键词： lymphoma treatment predominant

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DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & Medicine 2024年第3期21卷 252-266页

作者： Junya Yan Shibo Wang Jing Zhang Qiangqiang Yuan Xianchun Gao Nannan Zhang Yan Pan Haohao Zhang Kun Liu Jun Yu Linbin Lu Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila Yu Qi Qiujin Zhang Shundong Cang Yuanyuan Lu Yanglin Pan Yan Kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China unit 73211 of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese Medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and translational research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) ***: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published ***: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and ***: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

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Approaching the Sarcopenic Patient with Nonalcoholic Steatohepatitis-related Cirrhosis

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Journal of Clinical and translational Hepatology 2024年第3期12卷 278-286页

作者： Paolo Gallo Valentina Flagiello Andrea Falcomatà Giulia Di Pasquale Giorgio D’Avanzo Francesca Terracciani Antonio Picardi Umberto Vespasiani-Gentilucci Operative research unit of Clinical Medicine and Hepatology Fondazione Policlinico Universitario Campus Bio-MedicoVia Alvaro del PortilloRomaItaly research unit of Hepatology Department of Medicine and SurgeryUniversitàCampus Bio-Medico di RomaVia Alvaro del PortilloRomaItaly

Sarcopenia is a well-known complication of chronic liver disease(CLD),and it is almost always observed in patients with cirrhosis,at least in those with decompensated *** nonalcoholic fatty liver disease(NAFLD),recently renamed metabolic dysfunction-associated steatotic liver disease(MASLD),is becoming the leading cause of end-stage liver disease,a new scenario characterized by the frequent coexistence of NAFLD,obesity,and sarcopenia is *** it is not yet resolved whether the bidirectional relationship between sarcopenia and NAFLD subtends causal determinants,it is clear that the interaction of these two conditions is associated with an increased risk of poor ***,during the course of CLD,deregulation of the liver-muscle-adipose tissue axis has been ***,owing to the lack of properly designed studies,specific therapeutic guidelines for patients with sarcopenia in the context of NAFLD-related CLD have not yet been *** aimed to induce the loss of fat mass together with the maintenance of lean body mass seem most *** can be achieved by properly designed diets integrated with specific nutritional supplementations and accompanied by adequate physical *** studies aiming to add to the knowledge of the correct assessment and approach to sarcopenia in the context of NAFLD-related CLD are eagerly awaited.

关键词： NAFLD MASLD Cirrhosis Sarcopenia Sarcopenic obesity

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration research 2025年第2期20卷 481-482页

作者： Khaled Alok Timothy G.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA translational Brain research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

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Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan Hao-Xiang Wu Qi Meng Rui-Hua Xu Department of Clinical research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China research unit of Precision Diagnosis and Treatment for gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past *** substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of ***,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of *** ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and ***,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side *** this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload