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Carbon dots-enhanced pH-responsive lubricating hydrogel based on reversible dynamic covalent bondings

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Chinese Chemical Letters 2024年第5期35卷 232-237页

作者： Jianye Kang xinyu yang Xuhao yang Jiahui Sun Yuhang Liu Shutao Wang Wenlong Song State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012China CAS Key Laboratory of Bio-inspired Materials and Interfacial Science CAS Center for Excellence in NanoscienceTechnical Institute of Physics and ChemistryChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Due to the various pH liquid environment in nature,the pH-responsive lubricating hydrogel is widely investigated and developed for tissue interface ***,the applied liquid environment will lead to poor mechanical property and weaken the pH-responsive *** this work,a carbon dotsenhanced pH-responsive lubricating hydrogel is developed by combining a pH-responsive section of dynamic PVA-borax network into a PAAm covalent polymer *** formed hydrogel presents a partial gel-sol transition under controlled pH *** low pH environments(<6.0),the formed lubricating layer originated from dynamic disassembly of PVA-borax hydrogel,and brings the lubricating properties on the hydrogel ***,the mechanical strength and lubrication properties are well promoted by introducing the carbon dots into the hydrogel,the blue sol layer can be observed more visually under the fluorescence *** pH-response also exhibits well *** prepared hydrogel broadens the idea for designing pH-responsive soft materials for soft lubricating actuator or robot.

关键词： pH-responsive Carbon dots Dynamic covalent bonding Lubrication

Coordinate-wise monotonic transformations enable privacy-preserving age estimation with 3D face point cloud

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Science China(Life Sciences) 2024年第7期67卷 1489-1501页

作者： xinyu yang Runhan Li Xindi yang Yong Zhou Yi Liu Jing-Dong J.Han School of Life Sciences Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking UniversityBeijing 100871China Beijing Key Lab of Traffic Data Analysis and Mining School of Computer and Information TechnologyBeijing Jiaotong UniversityBeijing 100044China Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy *** we present an approach for facial data masking that preserves age-related features using coordinate-wise monotonic *** first develop a deep learning model that estimates age directly from non-registered face point clouds with high accuracy and *** show that the model learns a highly indistinguishable mapping using faces treated with coordinate-wise monotonic transformations,indicating that the relative positioning of facial information is a low-level biomarker of facial *** visual perception tests and computational3D face verification experiments,we demonstrate that transformed faces are significantly more difficult to perceive for human but not for machines,except when only the face shape information is *** study leads to a facial data protection guideline that has the potential to broaden public access to face datasets with minimized privacy risks.

关键词： face point cloud age estimation face verification privacy coordinate-wise monotonic transformation

Tumor biomarkers for diagnosis,prognosis and targeted therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2391-2476页

作者： Yue Zhou Lei Tao Jiahao Qiu Jing Xu xinyu yang Yu Zhang xinyu Tian Xinqi Guan Xiaobo Cen Yinglan Zhao Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China School of Pharmacy Sichuan UniversityChengdu 610041China School of Medicine Tibet UniversityLhasa 850000China National Chengdu Center for Safety Evaluation of Drugs State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Tumor biomarkers,the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression,have been demonstrated to possess critical and encouraging value in screening and early diagnosis,prognosis prediction,recurrence detection,and therapeutic efficacy monitoring of *** the past decades,continuous progress has been made in exploring and discovering novel,sensitive,specific,and accurate tumor biomarkers,which has significantly promoted personalized medicine and improved the outcomes of cancer patients,especially advances in molecular biology technologies developed for the detection of tumor ***,we summarize the discovery and development of tumor biomarkers,including the history of tumor biomarkers,the conventional and innovative technologies used for biomarker discovery and detection,the classification of tumor biomarkers based on tissue origins,and the application of tumor biomarkers in clinical cancer *** particular,we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic *** also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this ***,the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine,broaden horizons in future research directions,and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

关键词： diagnosis breakthrough biomarkers

Current status and challenges in the application of microbial PHA particles

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Particuology 2024年第4期87卷 286-302页

作者： Jiaxuan Liu Ziqi Zhou Haoru Li xinyu yang Zeyu Wang jian Xiao Dai-Xu Wei Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineDepartment of Life Sciences and MedicineNorthwest UniversityXi'an710069China School of Clinical Medicine Qujing Medical CollegeQujing655000China School of Physics and Electronic Information Shangrao Normal UniversityShangrao334001China Zigong Affiliated Hospital of Southwest Medical University Zigong Psychiatric Research CenterZigong Institute of Brain ScienceZigong643002China

Polyhydroxyalkanoates(PHAs)are diversiform biopolyesters with a similar structure and different side chain groups,synthesized by a variety of *** to their excellent biodegradability and biocompatibility,PHAs have been used for many applications,including medical implants,antibacterial agents and ***-architecture is an emerging area for the use of *** review summarizes the current status and challenges of PHAs-based particles on the micro-and nano-scale,including their production,degradation,biological safety,and surface *** also focus on the applications of PHA particles in drug delivery systems,environment protection,tissue engi-neering,vaccine engineering,food science,biotechnology and ***,the future development trends of PHAs-based particles are prospected.

关键词： Polyhydroxyalkanoates(PHAs) Particles Synthetic biology Tissue engineering

FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan yang Hao Chen Chiy He Huigang Li xinyu yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A_(2)receptors

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Science China(Life Sciences) 2024年第5期67卷 986-995页

作者： Yuan Weng xinyu yang Qiansen Zhang Ying Chen Yueming Xu Chenyu Zhu Qiong Xie Yonghui Wang Huaiyu yang Mingyao Liu Weiqiang Lu Gaojie Song Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China

The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy *** of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal ***,the precise mechanism underlying its dual-antagonistic properties remains ***,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist *** structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary *** contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)*** analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic *** disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)*** study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.

关键词： adenosine receptor A2AR A2BR inhibitor dual-antagonism drug discovery

Discovery of TK-642 as a highly potent,selective,orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3624-3642页

作者： Kai Tang Shu Wang Siqi Feng xinyu yang Yueyang Guo Xiangli Ren Linyue Bai Bin Yu Hong-Min Liu Yihui Song School of Pharmaceutical Sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Pingyuan LaboratoryState Key Laboratory of Antiviral DrugsZhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Src homology-2-containing protein tyrosine phosphatase 2(SHP2)is a promising therapeutic target for cancer *** this work,we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors,leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent,selective,orally bioavailable allosteric SHP2 inhibitor(SHP2WT IC_(50)=2.7 nmol/L)with favorable pharmacokinetic profiles(F=42.5%;t_(1/2)=2.47 h).Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the“tunnel”allosteric site of ***-642 could effectively suppress cell proliferation(KYSE-520 cells IC_(50)=5.73μmol/L)and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling ***,oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model,with a T/C value of 83.69%.Collectively,TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

关键词： Protein tyrosine phosphatase Pyrazolopyrazine SHP2 inhibitor Esophageal cancer

TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity

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Science China(Life Sciences) 2024年第9期67卷 1899-1914页

作者： Qi Wang Ping Rong Wen Zhang xinyu yang Liang Chen Ye Cao Minjun Liu Weikuan Feng Qian Ouyang Qiaoli Chen Hailong Li Hui Liang Fanguo Meng Hong-Yu Wang Shuai Chen State Key Laboratory of Pharmaceutical Biotechnology Department of CardiologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolModel Animal Research CenterSchool of MedicineNanjing UniversityNanjing 210061China MOE Key Laboratory of Model Animal for Disease Study Department of EndocrinologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolModel Animal Research CenterSchool of MedicineNanjing UniversityNanjing 210061China College of Life Science Anhui Medical UniversityHefei 230032China Redox Medical Center for Public Health Medical College of Soochow UniversitySuzhou 215123China Department of General Surgery First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Energy status is linked to the production of reactive oxygen species(ROS)in macrophages,which is elevated in ***,it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of ***,we show that the Rab-GTPase activating protein(Rab GAP)TBC1D1,a substrate of the energy sensor AMP-activated protein kinase(AMPK),is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity ***1D1 deletion decreases,whereas an energy overload-mimetic non-phosphorylatable TBC1D1^(S231A)Amutation increases,ROS production and M1-like polarization in ***,TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS *** of TBC1D1^(S231A)bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable Tt SOD for removal of ROS selectively in macrophages alleviates both TBC1D1~(S231A)mutation-and diet-induced *** findings therefore have implications for drug discovery to combat obesity.

关键词： TBC1D1 AMPK Rab8a NOX2 ROS inflammation macrophage obesity

Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

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Food Science and Human Wellness 2024年第5期13卷 2917-2936页

作者： Peng Ma Jie Xiao Biyu Hou Ping He xinyu yang Yisa Wang Zijing Wang Tianshu Xu Xiuying yang Xuan Zhu Shasha Xiang Song Li Guanhua Du Jian Ying Guifen Qiang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening ResearchBeijing 100050China COFCO Nutrition and Health Research Institute Beijing 102209China Department of Pharmacy The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China Faculty of Biology Medicine and Health SciencesThe University of ManchesterManchester M139PLUnited Kingdom Changchun University of Chinese Medicine Changchun 130117China School of Food Science and Biotechnology Zhejiang Gongshang UniversityHangzhou 310018China China Tea Technology(Beijing)Co. Ltd.Beijing 102209China Beijing Key Laboratory of Nutrition Health and Food SafetyBeijing 102209China

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as ***,drugs based on adipose tissue thermogenesis have not been successfully approved *** current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity ***,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning ***,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and *** gut microbiota regulation may prompt the CA2-dependent thermogenesis *** findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.

关键词： Obesity Black tea Thermogenesis Browning Adipose tissue