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LncRNA CCRR maintains Ca^(2+)homeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China(Life Sciences) 2024年第8期67卷 1601-1619页

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun Department of pharmacology Harbin Medical University(State Key Laboratory of Frigid Zone Cardiovascular Diseasethe State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of EducationJoint International Research Laboratory of Cardiovascular Medicine ResearchMinistry of EducationChina)College of PharmacyHarbin Medical UniversityHarbin 150081China

Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier *** study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following *** effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full ***,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of *** increased SERCA2a protein stability by upregulating FTO *** direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown *** of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in *** study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in ***,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

关键词： CCRR calcium homeostasis FTO myocardial infarction SERCA2a

In situ embedded bismuth nanoparticles among highly porous carbon fibers for efficient carbon dioxide reduction

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Rare Metals 2024年第9期43卷 4312-4320页

作者： Wei-Jian Guo Ao Zhou Wen-Wen Cai Jin-Tao Zhang key laboratory for Colloid and Interface Chemistry (ministry of education) School of Chemistry and Chemical EngineeringShandong University

Electrocatalysis provides an optimal approach for the conversion of carbon dioxide(CO2) into high-value chemicals, thereby presenting a promising avenue toward achieve carbon neutrality. However, addressing the selectivity and stability challenges of metal catalysts in electrolytic reduction remains a daunting task. In this study, the electrospinning method is employed to fabricate porous carbon nanofibers loaded with bismuth nanoparticles with the help of in situ pyrolysis. The porous carbon nanofibers as conductive support would facilitate the dispersion of bismuth active sites while inhibiting their aggregation and promoting the mass transfer, thus enhancing their electrocatalytic activity and stability. Additionally, nitrogen doping induces electron delocalization in bismuth atoms through metal-support interactions, thus enabling efficient adsorption of intermediates for improving selectivity based on the theoretical calculation. Consequently, Bi@PCNF-500 exhibits the exceptional selectivity and stability across a wide range of potential windows. Notably, its faradaic efficiency(FE) of formate reaches 92.7% in H-cell and94.9% in flow cell, respectively, with good electrocatalytic stability. The in situ characterization and theoretical calculations elucidate the plausible reaction mechanism to obtain basic rules for designing efficient electrocatalyst.

关键词： Carbon dioxide reduction Electron delocalization N-doping Porous carbon nanofiber

Formation estimation and evolution mechanism of the pressure arch for non-circular tunnels under asymmetrical stress field

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Science China(Technological Sciences) 2024年第9期67卷 2919-2938页

作者： SUN ZhenYu ZHANG DingLi XU Tong CHEN Xu key laboratory for Urban Underground Engineering of ministry of education Beijing Jiaotong UniversityBeijing 100044China

The tunneling-induced stress redistribution is dependent on the tunnel shape and the in-situ stress field, and the previous arch characterization method based on the circumferential or maximum principal stresses is only suitable for the circular tunnels under the hydrostatic stress field. In this study, a unified characterization method of the pressure arch for non-circular tunnels under the arbitrary stress field is proposed. By comparing the variations of compressive stress in different directions due to excavation, the ratio of the most significant increase in compressive stress is presented to characterize the arch effect, and the corresponding numerical algorithm is given. Since the proposed method takes the stress element as the basic analytical model, it can be easily applied to various complex excavation situations. Thereafter, combined with the established folding catastrophic model, an objective and unified quantitative method of the pressure arch boundaries is given. Using the proposed method, the longitudinal evolution of the pressure arch is analyzed. According to the expansion rate of the arch boundaries, three evolution stages including the initial formation, rapid expansion and stabilization are categorized. Parametric studies are conducted to illustrate the effect of ground properties and support stiffness on the pressure arch formation. It is found that the ground strength parameters and burial depth affect the arch range at a decreasing rate, while they have little effect on the arch shape. The lateral pressure coefficient has a significant effect on both the shape and range of the pressure arch. Increasing the support stiffness helps reduce the pressure arch range with a decreasing rate, while the synchronous variation of the elastic moduli of the surrounding rock and support does not affect the arch range under a certain relative elastic modulus. Finally, field monitoring is conducted to validate the proposed method in actual support design.

关键词： pressure arch stress redistribution numerical simulation quantitative characterization longitudinal evolution parametric study

Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI key laboratory of Fertility Preservation and Maintenance of ministry of education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China key laboratory of Reproduction and Genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

m^(6)A reader YTHDF1 promotes cardiac fibrosis by enhancing AXL translation

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Frontiers of Medicine 2024年第3期18卷 499-515页

作者： Han Wu Weitao Jiang Ping Pang Wei Si Xue Kong Xinyue Zhang Yuting Xiong Chunlei Wang Feng Zhang Jinglun Song Yang Yang Linghua Zeng Kuiwu Liu Yingqiong Jia Zhuo Wang Jiaming Ju Hongtao Diao Yu Bian Baofeng Yang Department of pharmacology(National key laboratory of Frigid Zone Cardiovascular Diseases the State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin150081China

Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction(MI)can lead to heart *** N6-methyladenosine(m^(6)A)methylation has been shown to play a pivotal role in the occurrence and development of many *** investigating the biological function of the m^(6)A reader YTHDF1 in cardiac fibrosis,adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts,and MI surgery in vivo and transforming growth factor-β(TGF-β)-activated cardiac fibroblasts in vitro were performed to establish fibrosis *** results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis,whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic ***,zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene ***1 augmented AXL translation and activated the TGF-β-Smad2/3 signaling pathway,thereby aggravating the occurrence and development of cardiac dysfunction and myocardial ***,our data indicated that YTHDF1 was involved in activation,proliferation,and migration to participate in cardiac fibrosis in *** results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.

关键词： cardiac fibrosis YTHDF1 AXL ZBED6 heart failure

Polyoxometalates-Modulated Hydrophilic-Hydrophobic Composite Interfacial Material for Efficient Solar Water Evaporation and Salt Harvesting in High-Salinity Brine

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Energy & Environmental Materials 2024年第3期7卷 223-231页

作者： Sihang Cheng Cuimei Liu Yingqi Li Huaqiao Tan Yonghui Wang Yangguang Li key laboratory of Polyoxometalate and Reticular Material Chemistry of ministry of education Faculty of ChemistryNortheast Normal University

Solar vapor generation （SVC） represents a promising technique for seawater desalination to alleviate the global water crisis and energy *** of its main bottleneck problems is that the evaporation efficiency and stability are limited by salt crystallization under high-salinity ***,we demonstrate that the 3D porous melamine-foam （MF） wrapped by a type of self-assembling composite materials based on reduced polyoxometalates （*** blue,HPB）,oleic acid （OA）,and polypyrrole （PPy）(labeled with MF@HPB-PPy_n-OA) can serve as efficient and stable SVC material at high *** characterizations of MF@HPB-PPy_n-OA indicate that both hydrophilic region of HPBs and hydrophobic region of OA co-exist on the surface of composite materials,optimizing the hydrophilic and hydrophobic interfaces of the SVC materials,and fully exerting its functionality for ultrahigh water-evaporation and anti-salt *** optimal MF@HPBPPy10-OA operates continuously and stably for over 100 h in 10wt%***,MF@HPB-PPy10-OA accomplishes complete salt-water separation of 10wt%brine with 3.3kgm-2h-1under 1-sun irradiation,yielding salt harvesting efficiency of 96.5%,which belongs to the record high of high-salinity systems reported so far and is close to achieving zero liquid ***,the low cost of MF@HPB-PPy10-OA (2.56$m-2)suggests its potential application in the practical SVC technique.

关键词： heteropoly blue (HPB) hydrophilic-hydrophobic interface polyoxometalates (POM) salt-water separation solar vapor generation (SVG)

Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3605-3623页

作者： Zehui Tan Ning Guo Zhi Cao Shuyu Liu Jiayu Zhang Deyi Ma Jiahao Zhang Wencai Lv Nan Jiang Linghe Zang Lihui Wang Xin Zhai key laboratory of Structure-Based Drug Design and Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Department of pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung ***,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q *** most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar *** cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS *** the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in *** study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling ***,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.

关键词： DOT1L R231Q mutation Lung cancer Adenosine-containing inhibitors Epigenetics

Ultrafast pulse-dilation framing camera and its application for time-resolved X-ray diagnostic

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Nuclear Science and Techniques 2024年第7期35卷 101-114页

作者： Hou-Zhi Cai Qiu-Yan Luo Kai-Xuan Lin Xuan Deng Jun-Kai Liu Kai-Zhi Yang Dong Wang Jia-Jie Chen Jia-Heng Wang Jing-Hua Long Li-Hong Niu Yun-Fei Lei Jin-Yuan Liu key laboratory of Optoelectronic Devices and Systems of ministry of education and Guangdong Province Shenzhen Key Laboratory of Photonics and BiophotonicsCollege of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen518060China

An ultrafast framing camera with a pulse-dilation device,a microchannel plate(MCP)imager,and an electronic imaging system were *** camera achieved a temporal resolution of 10 ps by using a pulse-dilation device and gated MCP imager,and a spatial resolution of 100μm by using an electronic imaging system comprising combined magnetic *** spatial resolution characteristics of the camera were studied both theoretically and *** results showed that the camera with combined magnetic lenses reduced the field curvature and acquired a larger working area.A working area with a diameter of 53 mm was created by applying four magnetic lenses to the ***,the camera was used to detect the X-rays produced by the laser-targeting *** diagnostic results indicated that the width of the X-ray pulse was approximately 18 ps.

关键词： Inertial confinement fusion Plasma diagnostics Framing camera Combined lenses Pulse-dilation

Unraveling the nexus between cellular senescence and malignant transformation:a paradigm shift in cancer research

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Cancer Biology & Medicine 2024年第7期21卷 541-546页

作者： Xiaoyu Song Xiyan Liu Qiqiang Guo Hongde Xu Liu Cao The College of basic Medical Science Health Sciences InstituteChina Medical UniversityShenyang 110122China key laboratory of Cell Biology of ministry of Public Health Key Laboratory of Medical Cell Biology of Ministry of EducationKey Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors of Ministry of EducationLiaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and PreventionChina Medical UniversityShenyang 110122China

Cellular senescence, a natural process wherein cells cease division and undergo irreversible growth arrest, has long captivated the curiosity of scientists because of its many implications in aging and disease. Recent research has shed light on the nexus between cellular senescence and malignant transformation, thus leading to a paradigm shift in understanding cancer development and progression.

关键词： malignant cancer transformation