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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu key laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State key laboratory of pharmaceutical biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State key laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State key laboratory of Microbial Technology Shandong University National Health Commission (NHC) key laboratory of biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第1期 249-256页

作者： Qing-Yun Fang Chengyihan Gu Yinghan Chen Wencheng Yan Yong Liang Weipeng Li Chengjian Zhu Jie Han Jin Xie State key laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State key laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

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Tailor-made high elasticity and low-hysteresis hydrogels based on asymmetric H-bonding crosslinking for wearable applications

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Science China Chemistry 2025年

作者： Xiaofang Shi Nan Shi Miaomiao Dang Chengyu Ji Yingjie Li Peiyi Wu Zhiguo Hu Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials School of Chemistry and Chemical Engineering Henan Normal University State key laboratory for Modification of Chemical Fibers and Polymer Materials College of Chemistry Chemical Engineering and Biotechnology & Center for Advanced Low-dimension Materials Donghua University

The conventional method of fabricating hydrogels constantly confronts the conflict between elasticity and toughness, limiting their repetitive application. Achieving the desired elasticity through a simple and low-cost approach is a significant challenge for hydrogels, particularly through rational molecular design. Here, low-hysteresis and high-toughness hydrogels are developed from the design of a new feature monomer, N-acryloylethylsemicarbazide (NACE). Based on a concept of “asymmetric Hbonding design”, the unique double and triple H-bonding of NACE can result in a novel asymmetric crosslinking polymer with alternating strong and weak H-bonding regions. The NACE is copolymerized with acrylamide (AM) to regulate the mechanical properties of hydrogel via H-bonding density. The P(NACE-AM) ionic hydrogels are obtained simply and rapidly via one-step photopolymerization without a chemical cross-linking agent. The P(NACE-AM) hydrogels combine superb mechanical elasticity and toughness, and excellent ionic conductivity, showing great potential as durable ionic conductive devices for wearable utilization.

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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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Oncology research 2025年第1期33卷 225-234页

作者： Wei Zhang Weicheng Wang Rui Wang Xiao Han Lijun Zhu Wenjie Guo Yanhong Gu Department of Oncology The First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China. Department of Oncology The Affiliated Taizhou People's Hospital of Nanjing Medical University Taizhou 225300 China. State key laboratory of pharmaceutical biotechnology School of Life Sciences Nanjing University Nanjing 210023 China.

Background:As a novel blocker of vascular endothelial growth factor receptor (VEGFR), fruquintinib has been approved for treating colorectal cancer (CRC). However, its dosage and therapeutic efficacy are limited by its widespread adverse reactions. Venetoclax, recognized as the initial inhibitor of B-cell lymphoma protein 2 (BCL2), has shown potential in boosting the effectiveness of immunotherapy against CRC. This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax's efficacy against tumors. Then we employed various techniques to evaluate different aspects of the experimental outcomes. Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues. Western blot analysis was utilized to examine the occurrence of cell apoptosis, and flow cytometry to quantitate immune cells within the tumor tissues. Moreover, immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax, as opposed to individual drug use. Venetoclax was found to amplify the impact of fruquintinib, leading to decreased cancer cell proliferation, increased cancer cell apoptosis, lowered angiogenesis, better vascular structure normalization, and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment. Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC. Venetoclax holds promise in being assimilated into anticancer medications for CRC.

关键词： Anti-angiogenesis B-cell lymphoma protein 2 (BCL2) Colorectal cancer (CRC) Fruquintinib Immunotherapy Vascular endothelial growth factor receptor (VEGFR) Venetoclax

Small modifications of endo-functionalized cavities lead to large changes in molecular interaction in water

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Science China Chemistry 2025年第1期 369-376页

作者： Song-Meng Wang Hao Nian Yan-Fang Wang Li-Shuo Zheng Yu-Tao Zheng Yi-Wei Dong Liping Huang Xiaoping Wang Wei Jiang Liu-Pan Yang Department of Chemistry Southern University of Science and Technology School of Chemistry and pharmaceutical Sciences State Key Laboratory for Chemistry and Molecular Engineering of Medicinal ResourcesGuangxi Normal University School of pharmaceutical Science Hengyang Medical School University of South China

Studying molecular recognition in aqueous environments is crucial for understanding biological processes. Herein, we present a series of N-doped endo-functionalized anthracene-based cavities by introducing inward-directed pyridine units. The subtle modifications can significantly affect the binding properties of these receptors, which is similar to the mutations in biological systems. Combining theoretical calculations and molecular recognition experiments demonstrated that these “mutations” have an impact on the hydrophobicity and charge distribution of the hosts, consequently significantly influencing molecular *** is crucial for understanding the intricate mechanisms of molecular-level interactions in biological receptors.

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Enhanced subacute ischemic stroke treatment via multistage drug delivery system design for combination therapy

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Science China Chemistry 2025年

作者： Xihan Xu Juan-Juan Li Jiamin Li Hui-Yan Zhang Yilin Qi Bing-Sen Shi Tianqi Li Shan-Shan Su Weitao Zhao Chang Chen Zhongying Gong Huiyu Liu Ke-Rang Wang Dong-Sheng Guo Xue Xue State key laboratory of Medicinal Chemical Biology College of Pharmacy Nankai University College of Chemistry State Key Laboratory of Elemento-Organic Chemistry Key Laboratory of Functional Polymer Materials (Ministry of Education) Frontiers Science Center for New Organic Matter Collaborative Innovation Center of Chemical Science and EngineeringNankai University College of Chemistry and Materials Science State Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education) Key Laboratory of Chemical Biology of Hebei Province Hebei Research Center of the Basic Discipline of Synthetic Chemistry Hebei University Department of Neurology Tianjin First Central Hospital School of Medicine Nankai University Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Organic-Inorganic Composites Beijing Laboratory of Biomedical Materials Bionanomaterials & Translational Engineering Laboratory Beijing Key Laboratory of BioprocessBeijing University of Chemical Technology

The management of acute ischemic stroke remains challenging due to its abrupt onset and the narrow treatment window,resulting in high rates of disability and *** therapy for neuroprotection and neurorepair strategies provided new hopes for subacute stroke *** we designed a multistage nanodelivery system that matches the unique microenvironment of the subacute phase of stroke,which utilizes calixarene as a building block to effectively load the neuroprotective drug *** calixarene is designed with glycosidic linkages targeting the glucose transporter 1 (GLUT1)on the blood-brain barrier (BBB) and azo bonds that are responsive to hypoxic ***,the decomposed calixarene molecules themselves possess intrinsic bio-activation to modulate inflammatory responses,achieving a multistage therapeutic approach that transitions from targeting to release and finally to *** approach combines anti-inflammation and neuroprotection,providing a multi-level treatment *** system was validated in a rat model of permanent middle cerebral artery occlusion (pMCAO),demonstrating that intravenous administration of the nanodelivery system repairs brain damage and improves motor function 24 h post-pMCAO *** work offers a precise and integrative strategy for stroke patients missing the acute therapy window to improve functional recovery and enhance the effect of comprehensive treatment.

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Enteromorpha prolifera polysaccharide-Fe(Ⅲ) complex promotes intestinal development as a new iron supplement

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Science China Life Sciences 2025年第1期 219-231页

作者： Yingying Feng Yuying Wu Jialu Wang Zhenglin Dong Qian Yu Shuangshuang Xia Chunxue Liu Haihua Wang Xin Wu Tianjin Institute of Industrial biotechnology Chinese Academy of Sciences CAS key laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of Sciences ANYOU biotechnology Group Co.Ltd Qingdao Seawin Biotech Group Co. LTD

Iron is a crucial micronutrient, and its deficiency can have detrimental effects on the health of infants. Dietary polysaccharide-iron(Ⅲ) complexes(PICs) are promising for addressing iron deficiency due to their minimal adverse reactions and high iron absorption rate. This study aimed to investigate the effects of dietary Enteromorpha prolifera polysaccharide-Fe(Ⅲ) complex(EP-Fe) on newborns, using 3-day weaned piglets as the iron-deficiency model. Results showed that EP-Fe improved iron levels and promoted intestinal development in piglets. Transcriptome sequencing revealed that EP-Fe increased the survival of intestinal epithelial cells under hypoxia by upregulating the expression of genes that promote the development of the vascular system. Additionally, EP-Fe enhanced the mucosal barrier functions by inhibiting myosin light chain kinase(MLCK)/phosphorylated myosin light chain(p-MLC) signaling pathway to increase the expression of intestinal tight junction proteins. Furthermore, the 16S r RNA gene sequencing of gut microbiota showed that EP-Fe promoted the enrichment of Bacteroides＿fragilis and other gut microbes that can metabolize carbohydrates. In conclusion, EP-Fe is an effective iron supplement for newborns, and it can be developed as a comprehensive nutritional supplement.

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State key laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina key laboratory of Hearing Science Ministry of EducationBeijingChina Beijing key laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina key laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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