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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi su Kun Chen Qing Wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

Carrimycin ameliorates lipopolysaccharide and cecal ligation and puncture-induced sepsis in mice

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Chinese Journal of Natural Medicines 2024年第3期22卷 235-248页

作者： LAI Junzhong LIANG Jiadi CHEN Kunsen GUAN Biyun CHEN Zhirong CHEN Linqin FAN Jiqiang ZHANG Yong LI Qiumei su Jingqian CHEN Qi LIN Jizhen The Cancer Center Fujian Medical University Union HospitalFuzhou 350001China Fujian Key Laboratory of Innate Immune Biology Biomedical Research Center of South ChinaFujian Normal UniversityFuzhou 350117China The Department of Otolaryngology Head&Neck SurgeryUniversity of Minnesota Medical SchoolMinneapolisMN 55455USA

Carrimycin(CA),sanctioned by China’s National Medical Products Administration(NMPA)in 2019 for treating acute bronchitis and sinusitis,has recently been observed to exhibit multifaceted biological activities,encompassing anti-inflammatory,antiviral,and anti-tumor *** these applications,its efficacy in sepsis treatment remains *** study introduces a novel function of CA,demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide(LPS)and cecal ligation and puncture(CLP)in mice *** research employed in vitro assays,real-time quantitative polymerase chain reaction(RT-qPCR),and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines,namely tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),in response to LPS ***,Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B(NF-κB)activation in LPS-stimulated RAW264.7 *** these findings,in vivo experiments demonstrated that CA effectively alleviates LPS-and CLP-triggered organ inflammation in C57BL/6 *** insights were gained through 16S sequencing,highlighting CA’s pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways,particularly by augmenting the production of short-chain fatty acids in mice subjected to ***,a comparative analysis revealed that CA’s anti-inflammatory efficacy surpasses that of equivalent doses of aspirin(ASP)and ***,these findings suggest that CA exhibits significant therapeutic potential in sepsis *** discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.

关键词： Carrimycin Inflammation Lipopolysaccharide Cecal ligation and puncture Sepsis Gut microbiota

Unification of Gravitational and Strong Interaction Fields Using Partial Gauge Symmetry

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第2期10卷 515-533页

作者： young Hwan Yun Kiho Jang Zero Theoretical Physics Lab Seoul Republic of Korea

We propose the new field potential by maintaining both the symmetry of the scalar gauge and the conservation law keeping N?ether’s theorem, while disregarding the symmetry of the vector gauge. The new potential forms like the well-type potential where a particle behaves almost freely but is very hard to escape without external energy, which can be interpreted as local confinement and asymptotic freedom. By assuming a 2-dimensional metric tensor in 4-dimensional space-time, we suggest the existence of 3 kinds of particles that resemble QCD with 3 color charges. We also show that the mass term exists but comes to zero and derive the charge and spin values. We can regard the particle with this new potential as a gluon, and the interaction in this well-type potential as a strong interaction for the properties of mass, charge, spin, and its behavior. We suggest the eight-fold way with this new particle, which is similar to the existing method based on su (3) symmetry. Even though the strong interaction has been analyzed in the standard model and string theory, we build a new consistent model based on the theory of relativity including Riemann geometry, and show the unification of gravitational and strong interactional field.

关键词： Strong Interaction Gauge Symmetry Relativity QCD Confinement Asymptotic Freedom

Annual Energy Production Estimation for Variable-speed Wind Turbine at High-altitude Site

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Journal of Modern Power Systems and Clean Energy 2021年第3期9卷 684-687页

作者： Dongran Song Songyue Zheng Sheng yang Jian yang Mi Dong Mei su young Hoon Joo the School of Automation Central South UniversityChangsha 410083China the School of Energy Science and Engineering Central South UniversityChangsha 410083China the School of IT Information and Control Engineering Kunsan National UniversityKunsan 573701Korea

This letter presents a systematic approach to estimate the annual energy production(AEP) of variable-speed wind turbines erected at high-altitude sites. Compared with the existing empirical-model based approaches, the proposed approach models the influence of the air density on the power production while employing the theoretical power curve. Consequently, the proposed approach provides a precise estimation of AEP, which can serve as a foundation of the optimum turbinesite matching design at different-altitude sites.

关键词： Variable-speed wind turbine annual energy production high-altitude site turbine-site matching

COP 28: Challenge of coping with climate crisis

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The Innovation 2024年第1期5卷 21-22页

作者： Tong Jiang Xiaojia He Buda su Peni Hausia Havea Ke Wei Zbigniew W.Kundzewicz Dong Liu Research Institute of Climatic and Environmental Governance/Institute for Disaster Risk Management School of Geographical ScienceNanjing University of Information Science&TechnologyNanjing 210044China The Administrative Center for China’s Agenda 21 Beijing 100038China Pacific Global Solution Nuku’alofaTongatapu 000676Tonga Centre for Monsoon System Research Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Department of Environmental Engineering and Mechanical Engineering Poznan University of Life Sciences60-637 PoznanPoland The Paper Shanghai United Media GroupShanghai 200040China

The 28th Conference of Parties(COP 28)of the United Nations Framework Convention on Climate Change(UNFCCC)is being held in Dubai,United Arab Emirates,from November 30 to December 12,2023,with the participation of over 160 world leaders(Figure 1).The tone of the COP 28 is set by the observation that,clearly,the nationally determined contributions related to CO_(2) emission reduction are not on track to curb the temperature rise as per the Paris *** order to hold the increase in global mean temperature to well below 2℃ above the pre-industrial level and to pursue efforts to limit the warming to 1.5℃,there is a need for ratcheting up ambition for near-term climate action.

关键词： Figure limit COP

Efficient and accurate simulation of vitrification in multicomponent metallic liquids with neural network potentials

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Science China Materials 2024年第10期67卷 3298-3308页

作者： Rui su Jieyi Yu Pengfei Guan Weihua Wang College of Materials&Environmental Engineering Hangzhou Dianzi UniversityHangzhou 310018China Beijing Computational Science Research Center Beijing 100193China Songshan Lake Materials Laboratory Dongguan 523808China

Constructing an accurate interatomic potential and overcoming the exponential growth of structural equilibration time are challenges for atomistic investigations of the composition-dependent structure and dynamics during the vitrification process of deeply supercooled multicomponent metallic *** this work,we describe a state-of-the-art strategy to address these challenges *** the case of the representative Zr–Cu–Al system,in combination with a general algorithm for effectively and accurately generating the neural network potentials(NNPs)of multicomponent metallic glasses,we propose a highly efficient atom-swapping hybrid Monte Carlo(SHMC)algorithm for accelerating the thermodynamic equilibration of deeply supercooled *** calculations demonstrate that the newly developed NNP faithfully reproduces the phase stabilities and structural characteristics obtained from ab initio calculations and *** the combined NNP-SHMC algorithm,the structure equilibration time at deeply supercooled temperatures is accelerated by at least five orders of magnitude,and the quenched glassy samples exhibit comparable stability to those prepared in the *** results pave the way for next-generation studies of the vitrification process and,thereby,the composition-dependent glass-forming ability and physical properties of multicomponent metallic glasses.

关键词： metallic glass computational methods glass transition

Effect of male HBV infection on the outcomes of IVF/ICSI cycles:a retrospective cohort study based on propensity score matching

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Asian Journal of Andrology 2024年第4期26卷 415-420页

作者： su-Qin Zhu Xiu-Hua Liao Wen-Wen Jiang Yan sun Hui-Ling Xu Xiao-Jing Chen Bei-Hong Zheng Fujian Provincial Reproductive Medicine Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics and Gynecology and PediatricsFujian Medical UniversityFuzhou 350001China Fujian Key Laboratory of Prenatal Diagnosis and Birth Defect Fuzhou 350001China Fujian Maternal-Fetal Clinical Medicine Research Center Fuzhou 350001China.

This study aimed to investigate the effects of male hepatitis B virus(HBV)infection on male fertility,embryonic development,and in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)*** performed a retrospective cohort study that included 3965 infertile couples who received fresh embryo transfer cycles for the first time at the Fujian Maternity and Child Health Hospital(Fuzhou,China)from January 2018 to January *** couples were categorized based on their HBV infection status into the HBV group(HBV-positive men and HBV-negative women)and the control group(HBV-negative couples).A 1:1 propensity score matching was performed with relatively balanced *** characteristics,semen parameters,laboratory outcomes,clinical outcomes,and obstetric and neonatal outcomes were compared between *** propensity score matching,821 couples were included in each *** groups had similar semen parameters and obstetric and neonatal *** HBV group showed a significantly lower live birth rate than the control group(P<0.05).The HBV group had a significantly higher abortion rate than the control group(P<0.05).The rates of high-quality embryos and blastocyst formation were significantly lower in the HBV group than those in the control group(both P<0.05).In conclusion,in couples who undergo IVF/ICSI,male HBV infection reduces the live birth rate and increases the risk of ***,the incidence of low birth weight in women with IVF/ICSI does not increase with male HBV infection.

关键词： hepatitis B virus in vitro fertilization intracytoplasmic sperm injection live birth rate propensity score matching

LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation

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Science China(Life Sciences) 2024年第3期67卷 488-503页

作者： Xiao Fan Fangzhou Liu Xiang Wang Ying Wang Yu Chen Chengyu Shi Xinwan su Manman Tan Qingfeng Yan Jinrong Peng Jianzhong Shao Yan Xiong Aifu Lin MOE Laboratory of Biosystem Homeostasis and Protection College of Life SciencesZhejiang UniversityHangzhou 310058China Key Laboratoryof Cancer Prevention and Intervention China National Ministry of EducationHangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China Key Laboratory for Cell and Gene Engineering of Zhejiang Province Hangzhou 310058China Department of Central Laboratory the First People's Hospital of HuzhouHuzhou 313000China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China MOE Key Laboratory for Molecular Animal Nutrition College of Animal SciencesZhejiang UniversityHangzhou 310058China Department of Orthopedic surgery the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310000China Breast Center of the First Affiliated Hospital School of MedicineZhejiang UniversityHangzhou 310003China International School of Medicine International Institutes of MedicineThe 4th Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China

Ferroptosis, a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation, has a potential physiological function in tumor suppression, but its underlying mechanisms have not been fully elucidated. Here, we report that the long non-coding RNA(lncRNA) LncFASA increases the susceptibility of triple-negative breast cancer(TNBC) to ferroptosis. As a tumor suppressor, LncFASA drives the formation of droplets containing peroxiredoxin1(PRDX1), a member of the peroxidase family, resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis. Mechanistically, LncFASA directly binds to the Ahpc-TSA domain of PRDX1, inhibiting its peroxidase activity by driving liquid-liquid phase separation, which disrupts intracellular ROS homeostasis. Notably, high LncFASA expression indicates favorable overall survival in individuals with breast cancer, and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis. Together, our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.

关键词： long non-coding RNA peroxiredoxin liquid-liquid phase separation ferroptosis breast cancer

Polymer donors with hydrophilic side-chains enabling efficient and thermally-stable polymer solar cells by non-halogenated solvent processing

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Nano Research Energy 2024年第1期3卷 19-29页

作者： Soodeok Seo Jun-young Park Jin su Park Seungjin Lee Do-Yeong Choi Yun-Hi Kim Bumjoon J.Kim Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea Department of Materials Engineering and Convergence Technology and ERI Gyeongsang National UniversityJinju 52828Republic of Korea Advanced Energy Materials Research Center Korea Research Institute of Chemical Technology(KRICT)Daejeon 34114Republic of Korea Department of Chemistry and ERI Gyeongsang National UniversityJinju 52828Republic of Korea

Polymer solar cells(PSCs)with high power conversion efficiency(PCE)and environment-friendly fabrication are the main requirements enabling their production in industrial *** the use of non-halogenated solvent processing is inevitable for the PSC fabrication,it significantly reduces the processability of polymer donors(PDS)and small-molecule acceptors(SMAs).This often results in unoptimized blend morphology and limits the device *** address this issue,hydrophilic oligoethylene glycol(OEG)side-chains are introduced into a PD(2EG)to enhance the molecular compatibility between the PD and L8-BO *** 2EG PD induces higher crystallinity and alleviates phase separation with the SMA compared to the reference PD(PM7)with hydrocarbon ***,the 2EG-based PSCs exhibit a higher PCE(15.8%)than the PM7-based PSCs(PCE=14.4%)in the ortho-xylene based ***,benefitted from the reduced phase separation and increased crystallinity of 2EG PDS,the 2EG-based PSCs show enhanced thermal stability(84%of initial PCE after 120 h heating)compared to that of the PM7-based PSCs(60%of initial PCE after 120 h heating).This study demonstrates the potential of OEG side-chain-incorporated materials in developing efficient,stable,and eco-friendly PSCs.

关键词： polymer solar cell polymer donor OEG side-chain non-halogenated solvent process side-chain engineering

Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation

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Cancer Communications 2024年第9期44卷 1018-1041页

作者： Hailing Liu Lei Xu Shiwei Yue Hongfei su Xing Chen Qiumeng Liu Hui Li Huifang Liang Xiaoping Chen Jiefeng He Zeyang Ding Bixiang Zhang Hepatic surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Key Laboratory of Hepato‑Pancreatic‑Biliary Diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Hepatopancreatobiliary surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiangP.R.China Department of Hepatobiliary Pancreatic Tumor Center Chongqing University Cancer HospitalSchool of MedicineChongqing UniversityChongqingP.R.China Key Laboratory of Organ Transplantation Ministry of EducationWuhanHubeiP.R.China Department of Hepatobiliary surgery Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province(Preparatory)Shanxi Bethune HospitalShanxi Academy of Medical SciencesShanxi Medical UniversityTaiyuanShanxiP.R.China

Background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by regulating mRNA ***,its role in hepatocellular carcinoma(HCC)development and prognosis is largely *** study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic ***:The ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC *** expression of NAT10 was investigated using quantitative real-time polymerase chain reaction,western blotting,and immunohistochemical staining across 91 cohorts of HCC *** explore the underlying mechanisms of NAT10-ac4C in HCC,we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing,RNA sequencing and ribosome profiling analyses,along with RNA immunoprecipitation,RNA pulldown,mass spectrometry,and site-specific mutation *** drug affinity responsive targets stability,cellular thermal shift assay,and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and ***,the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCCmouse ***:Our investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in ***,elevated NAT10 expression was associated with poor outcomes in HCC ***,silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in ***,NAT10 stimulates the ac4C modification within the coding sequence(CDS)of high mobility group protein B2(HMGB2),which subsequently enhances HMGB2 translation by facilitating eukaryotic elongation factor 2(eEF2)binding to the ac4C sites on HMGB2 mRNA’s C

关键词： N4-acetylcytidine N-acetyltransferase 10 hepatocellular carcinoma mRNA translation targeted therapy