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Chiral phosphoramidite ligand-modulated palladium auto-tandem catalysis for asymmetric dehydrogenative dienylation of imines with α-alkenes

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Science China Chemistry 2025年

作者： Zhong-Sheng Nong Hao-Fan Qian Ying-Chun Chen Pu-Sheng Wang Liu-Zhu Gong Hefei National research center for Physical Sciences at the Microscale and Department of Chemistry University of Science and Technology of China Key Laboratory of drug Targeting and drug Delivery System (Sichuan University) Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University School of Materials and Chemistry Southwest University of Science and Technology

The development of efficient processes allowing rapid access to complex chiral molecules from easily available alkenes is a long-term pursuit in the synthetic chemistry community. Transition metal-catalyzed asymmetric functionalization of allylic C–H bond represents a unique alternative toward this goal. However, enantioselective dehydrogenative transformation of olefins to value-added optically enriched molecules remains yet to be discovered. Here, we report a highly enantioselective dehydrogenative dienylation of imines with unactivated α-alkenes driven by the synergistic action of palladium complex and carboxylic acid. Chiral phosphoramidite ligands turned out to be superior in modulating the performance of palladium autotandem catalysis and allowed a broad range of α-alkenes and imines to be transformed into chiral dienylamines. Mechanistic studies suggest that the dienes could be in situ generated from α-alkenes through a palladium(0)-mediated dehydrogenative process in the presence of excess benzoquinone oxidants, and then participated in the Pd-chiral phosphoramidite-catalyzed intermolecular vinylogous-type addition to the imines activated by the carboxylic acid co-catalyst. Notably, the second β-H elimination occurring in the dienylation event might be the turnover-limiting step.

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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for research of Acupuncture Treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei College of Pharmacy and First clinical Medical College Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National drug clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and clinical research center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期68卷 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionclinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

关键词： non-squamous NSCLC squamous NSCLC LRP1B deleterious mutations predictive biomarker immune checkpoint inhibitor

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Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China Life Sciences 2025年第1期68卷 300-302页

作者： Ze-Min Lin Mai Xiang Wen-Hui Wei Shu-Hui Fan Li Chen Jie Wang Xiao-Qian Yang Chun-Hao Yang Shi-Jun He Jian-Ping Zuo Laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of drug research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期68卷 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer Hospital center for Disease Control and Prevention of Sheyang County Department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan center for Disease Control and Prevention Office for Cancer Control and research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

关键词： stomach neoplasms precancerous conditions cancer screening cumulative incidence risk stratification

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Sex differences in aging and injured brain

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Neural Regeneration research 2025年第10期20卷 2901-2902页

作者： Jordan N.Williamson Yuan Yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA Northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering research center of Stem Cells Translational Medicine ShanghaiChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National clinical research center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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