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World Journal of Clinical Cases 2024年第9期12卷 1634-1643页

作者： Dan shan Tao li Xi Tan Ya-Yi Hu Department of Obstetrics and Gynecology West China Second University HospitalSichuan UniversityChengdu 610000Sichuan ProvinceChina Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan UniversityMinistry of EducationChengdu 610000SichuanChina

BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during *** is considered to be the drug of choice due to its safety in not crossing *** the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a ***,the bleeding risk related with LMWH in preeclampsia patients has seldomly been *** current study aimed to identify the potential risks regarding LMWH application in patients with *** SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during *** the cases experienced catastrophic hemorrhagic *** reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems *** one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving *** studies reported minor bleeding risks,none of these were serious enough to stop LMWH *** of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be *** management of blood pressure even after delivery and homeostasis suture in surgery are *** Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

关键词： Pregnancy Preeclampsia Low-molecular-weight heparin Hemorrhage Case report

Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

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Chinese Journal of Natural Medicines 2024年第10期22卷 914-928页

作者： li Yichen HUANG liting li Jilang li Siyuan LV Jianzhen ZHONG Guoyue GAO Ming yang Shilin HAN shan HAO Wenhui life Sciences Institute Guangxi Medical University College of Pharmacy Guangxi University of Chinese Medicine National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal.Medicine Jiangxi University of Traditional Chinese Medicine Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases Department of Biochemistry and Molecular BiologySchool of Basic Medical Sciences Xinjiang Medical University

Acute lung injury（Ali） is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of Ali involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide（AG）, a bioactive compound derived from Andrographis, in mitigating lipopolysaccharide（LPS）-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced Ali. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced Ali mice. These protective effects are mediated via the modulation of the Toll-like receptor 4（TLR4）/Kelch-like ECH-associated protein 1（Keap1）/Nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol-1), and these interactions were further corroborated by Cellular Thermal Shift Assay（CETSA） and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced Ali by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG's potential as a therapeutic agent for Ali and provides new insights into its underlying mechanisms of action.

关键词： Acute lung injury Andrographolide Ferroptosis Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2 Toll-like receptor 4

DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli shan Zhou Xingfang Yu Kanaga Sabapathy Yong li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

Plant-based meat analogues aggravated lipid accumulation by regulating lipid metabolism homeostasis in mice

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Food Science and Human Wellness 2024年第2期13卷 946-960页

作者： Yunting Xie linlin Cai Zhiji Huang Kai shan Xinglian Xu Guanghong Zhou Chunbao li Key Laboratory of Meat Processing and Quality Control MOEKey Laboratory of Meat ProcessingMARAJiangsu Innovative Center of Meat ProductionProcessing and Quality ControlCollege of Food Science and TechnologyNanjing Agricultural UniversityNanjing 210095China

To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 *** with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in *** revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism *** PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose ***,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in *** specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters *** findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.

关键词： Meat analogues Metabolomics lipid metabolism Adipose tissue dysfunction Ectopic fat deposition

One-pot and One-step Cu(0)-mediated Reversible-Deactivation Radical Polymerization of N-Isopropylacrylamide(NIPAM) in Water

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Chinese Journal of Polymer Science 2024年第1期42卷 1-6,I0004页

作者： Zi-shan li Jing Lyu Bei Qiu Ying-Hao li Ruth Foley Ri-Jian Song Melissa Johnson Qiang Geng Wen-Xin Wang Institute of Precision Medicine(AUST-IPM) Anhui University of Science and TechnologyHuainan 232001China Charles Institute of Dermatology School of MedicineUniversity College DublinDublin D04 V1W8Ireland

Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.

关键词： Cu(0)-mediated RDRP N-isopropylacrylamide Propagation Deactivation Reaction parameters

Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2024年第3期19卷 619-628页

作者： Jun Chang Yujiao li Xiaoqian shan Xi Chen Xuhe Yan Jianwei liu Lan Zhao First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina Tianjin University of Traditional Chinese Medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s ***,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be *** to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to *** events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian ***,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative *** this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

关键词： Alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

lightweight foam-like nitrogen-doped carbon nanotube complex achieving highly efficient electromagnetic wave absorption

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Journal of Materials Science & Technology 2024年第1期168卷 114-123页

作者： Zongcheng li Jin liang Zhiheng Wei Xin Cao Jiahui shan Chunwei li Xiaoyi Chen Dong Zhou Ruizhe Xing Chunjia Luo Jie Kong MOE Key Lab of Materials Physics and Chemistry in Extraordinary Conditions Shaanxi Key Laboratory of Macromolecular Science and TechnologySchool of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China Key laboratory of Flexible Electronics of Zhejiang Province Ningbo Institute of Northwestern Polytechnical UniversityNingbo 315103China Polymer Materials and Engineering Department School of Materials Science and EngineeringChang’an UniversityXi’an 710064China

With the increased electromagnetic wave(EMW)threat to military and human health,the develop-ment of EMW-absorbing materials is ***-organic framework derivatives containing magnetic nanoparticles and a carbon matrix are potential candidates for designing efficient EMW-absorbing ***,a zeolitic imidazolate framework-67(ZIF-67)-embedded three-dimensional melamine foam is pyrolyzed to afford carbon foam-based nitrogen-doped carbon nanotube composites,named 3D foam-like CoO/Co/*** CoO/Co particles are confined in the dielectric carbon nanotube *** carbon nanotubes provide considerable conductive loss,while CoO/Co magnetic particles are con-ducive to providing magnetic loss and adjusting impedance ***,the numerous defect structures introduced by heteroatomic doping(nitrogen)cause dipole polarization and simultaneously adjust impedance ***,the unique porous nanotube structure promotes multiple re-flections and scattering of EMWs,further optimizing impedance ***/Co/N-CNTs composites exhibit a minimum reflection loss of−52.3 dB at a matching thickness of 2.0 mm,while the correspond-ing effective absorption bandwidth is 5.28 GHz at a matching thickness of 2.2 *** study reports a novel approach to fabricating a lightweight high-performance EMW-absorbing material.

关键词： lightweight porous carbon materials Carbon nanotubes CoO/Co magnetic particles Electromagnetic synergistic effect Impedance matching

New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第2期22卷 161-170页

作者： SUN Zeshi liN shan WU Zhi-li DONG Hong-Yuan XU Xi-Ke li Hui-liang WANG Jinxin School of Pharmacy Second Military Medical UniversityShanghai 200433China State Key Laboratory of New Drug and Pharmaceutical Process Shanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 201203China

Our continued works on the chemical constituents of Ginkgo biloba(***)leaves has led to the isolation of two novel phenylbutenoids(1,2),along with five previously unidentified terpene glycosides(3−7).Among them,compounds 1 and 2 represent unique(Z)-phenylbutenoids,3−6 are megastigmane glycosides,and 7 is identified as a rare bilobanone glycoside(Fig.1).This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from *** chemical structures of these compounds were elucidated through extensive spectroscopic analysis,including HR-ESI-MS and various 1D and 2D NMR ***,the absolute configurations of these molecules were determined using Mosher’s method,ECD experiments,and Cu-KαX-ray crystallographic analyses.

关键词： Ginkgo biloba Phenylbutenoid Megastigmane glycoside Bilobanone glycoside

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment:Several Unanswered Questions

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Journal of Clinical and Translational Hepatology 2024年第5期12卷 525-533页

作者： Le li Zhen-Zhen li li-Xin Pan Jia-Yong Su shan Huang liang Ma Jian-Hong Zhong Hepatobiliary Surgery Department Guangxi Medical University Cancer HospitalNanningGuangxiChina Guangxi Academy of Medical Sciences Emergency DepartmentThe People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxiChina Pathology Department Guangxi Medical University Cancer HospitalNanningGuangxiChina Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University) Ministry of EducationNanningGuangxiChina Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor NanningGuangxiChina

Most patients with hepatocellular carcinoma(HCC)have a poor *** and local ablation are the main curative treatments for ***,the recurrence rate after hepatectomy or ablation is up to 70%,which seriously affects patient *** adjuvant therapies have been explored to reduce postoperative ***,although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival,a standard consensus of national HCC guidelines for adjuvant treatment is ***,there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines.A variety of adjuvant treatment methods,such as antiviral therapy,transarterial chemoembolization or traditional Chinese medicine,are recommended by the Chinese HCC ***,Western guidelines make few recommendations other than antiviral *** immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of liver Diseases *** review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

关键词： Hepatocellular carcinoma Adjuvant therapy Curative hepatectomy Recurrence Overall survival Immune checkpoint inhibitor

Regioselective C-C bond cleavage/aminocarbonylation cascade under copper catalysis

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Science China Chemistry 2024年第11期67卷 3798-3806页

作者： Qi-Chao shan Yan Zhao Yong Wu Hong-Fei liu Xin-Hua Duan li-Na Guo Department of Chemistry School of Chemistry Energy Research Center of Energy Storage Materials and Devices Ministry of EducationXi'an Jiaotong University State Key Laboratory of Applied Organic Chemistry Lanzhou University

A regioselective C-C bond cleavage/aminocarbonylation cascade is presented. In recent years, tremendous progress has been made in the alkoxyl radical-mediated C-C bond cleavage of unstrained monocarbocycles. In contrast, the deconstruction and functionalization of bicyclic skeletons has been less developed and has mainly focused on the ring expansion process. Inspired by the aromatization-driven C-C bond cleavage, here we demonstrate a ring-opening/aminocarbonylation cascade under copper catalysis, in which the formation of a stable γ-lactam or succinimide skeleton reverses the selectivity of C-C cleavage. Remarkably, the photo and thermal assistance is not required when the succinimide skeleton is formed during the ring opening process. DFT calculations revealed that this unexpected ring-opening process is thermodynamically and kinetically favourable.

关键词： C-C bond cleavage controllable regioselectivity aminocarbonylation bicyclic alkoxy radical