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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo yuan Qin qian yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao qian Yang Department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University Department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken togeth

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

Revealing Al-O/Al-F reaction dynamic effects on the combustion of aluminum nanoparticles in oxygen/fluorine containing environments:A reactive molecular dynamics study meshing together experimental validation

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Defence Technology（防务技术） 2024年第4期34卷 313-327页

作者： Gang Li Chuande Zhao qian yu Fang Yang Jie Chen Institute of Chemical Materials China Academy of Engineering Physics(CAEP)P.O.Box 919-311Mianyang 621900SichuanChina

Improving the energy conversion efficiency in metallic fuel(e.g.,Al)combustion is always desirable but challenging,which often involves redox reactions of aluminum(Al)with various mixed oxidizing environments.For instance,Al-O reaction is the most common pathway to release limited energy while Al-F reaction has received much attentions to enhance Al combustion efficiency.However,microscopic understanding of the Al-O/Al-F reaction dynamics remains unsolved,which is fundamentally necessary to further improve Al combustion efficiency.In this work,for the first time,Al-O/Al-F reaction dynamic effects on the combustion of aluminum nanoparticles(n-Al)in oxygen/fluorine containing environments have been revealed via reactive molecular dynamics(RMD)simulations meshing together combustion experiments.Three RMD simulation systems of Al core/O_(2)/HF,n-Al/O_(2)/HF,and n-Al/O_(2)/CF4 with oxygen percentage ranging from 0%to 100%have been performed.The n-Al combustion in mixed O_(2)/CF_4 environments have been conducted by constant volume combustion experiments.RMD results show that Al-O reaction exhibits kinetic benefits while Al-F reaction owns thermodynamic benefits for n-Al combustion.In n-Al/O_(2)/HF,Al-O reaction gives faster energy release rate than Al-F reaction(1.1 times).The optimal energy release efficiency can be achieved with suitable oxygen percentage of 10%and 50%for n-Al/O_(2)/HF and n-Al/O_(2)/CF_4,respectively.In combustion experiments,90%of oxygen percentage can optimally enhance the peak pressure,pressurization rate and combustion heat.Importantly,Al-O reaction prefers to occur on the surface regions while Al-F reaction prefers to proceed in the interior regions of n-Al,confirming the kinetic/thermodynamic benefits of Al-O/Al-F reactions.The synergistic effect of Al-O/Al-F reaction for greatly enhancing n-Al combustion efficiency is demonstrated at atomicscale,which is beneficial for optimizing the combustion performance of metallic fuel.

关键词： Al-O/Al—F reaction Kinetic benefits Thermodynamic benefits Molecular dynamics Combustion

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua qian-qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi yu Man Liu Zheng-Rui Bian Bei-Bei Zhang qian yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina Department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

Potassium isotopic signatures of modern offshore detrital sediments from different climatic regimes and the implications

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Science China Earth Sciences 2024年第2期67卷 405-419页

作者： Jun MU Tianyu CHEN qian yu Shichao AN Jianfang CHEN Xuefa SHI Weiqiang LI State Key Laboratory for Mineral Deposits Research School of Earth Sciences and EngineeringNanjing UniversityNanjing210023China Ministry of Education Key Laboratory for Coast and Island Development School of Geography and Ocean ScienceNanjing UniversityNanjing210023China State Key Laboratory of Satellite Ocean Environment Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou310012China Key Laboratory of Marine Geology and Metallogeny First Institute of OceanographyMinistry of Natural ResourcesQingdao266061China

Potassium isotopes are a novel tracer for continental weathering.Previous K isotope studies on chemical weathering generally targeted weathering profiles under a particular climate region,yet the effects of chemical weathering on K isotopes under different climatic backgrounds remain unclear.Moreover,little is known about the K isotope signatures of modern unconsolidated detrital sediments.Here,we report K isotopic data of surficial seafloor sediments from continental shelves along the east coast of China(ECC),as well as those around the tropical Hainan island in the northern South China Sea.The ECC sediments have a relatively narrow distribution ofδ^(41)K(with reference to NIST3141a)values,which range from(-0.40±0.01)‰to(-0.57±0.04)‰,with an average of(-0.51±0.09)‰.By contrast,δ^(41)K values of Hainan offshore sediments display a larger variation,ranging from(-0.28±0.07)‰to(-0.67±0.02)‰.Theδ^(41)K values of Hainan offshore sediments exhibit negative correlations with the chemical index of alteration(CIA),Al/K,Ti/K,and total iron(FeT),which underlines the control of chemical weathering on K isotopic signatures of detritus inputs into oceans.We also measured Mg isotope compositions for the same samples;interestingly,the variability inδ^(26)Mg of the samples is small(~0.24‰)for all ECC and Hainan offshore sediments,andδ^(26)Mg values do not show clear correlations with indexes of chemical weathering.Our study demonstrates the link between K isotopic variability of detrital sediments and climatic conditions including rainfall intensity,which indicates that K isotopes of the detrital component of marine sediments could be applied to study Earth’s climate in deep time.Theδ^(41)K values of the offshore detrital sediments are significantly less variable than those of pelagic marine sediments,highlighting the importance of distinguishing the effects of diagenesis and neoformation of clay minerals from continental weathering in attempts to study deep-time climate-weathering link by K isotopes in detrital sedimentary recor

关键词： Potassium isotopes Magnesium isotopes Chemical weathering Detrital sediments Climatic regimes Mean annual precipitation

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Alignment error modeling and control of a double-sided microlens array during precision glass molding

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Microsystems & Nanoengineering 2024年第2期10卷 311-322页

作者： Zihao Zeng Tianfeng Zhou qian yu Jia Zhou Gang Wang Qiuchen Xie Zifan Wang Xiaoqiang Yao yubing Guo School of Medical Technology Beijing Institute of TechnologyNo.5 Zhongguancun South StreetHaidian DistrictBeijing100081China School of Mechanical Engineering Beijing Institute of TechnologyNo.5 Zhongguancun South StreetHaidian DistrictBeijing100081China

Double-sided microlens arrays(DSMLAs)include combinations of two single-sided MLAs to overcome positioning errors and greatly improve light transmissivity compared to other types of lenses.Precision glass molding(PGM)is used to fabricate DSMLAs,but controlling alignment errors during this process is challenging.In this paper,a mold assembly was manufactured with a novel combination of materials to improve the alignment accuracy of mold cores during PGM by using the nonlinear thermal expansion characteristics of the various materials to improve the DSMLA alignment accuracy.By establishing a mathematical model of the DSMLA alignment error and a thermal expansion model of the mold-sleeve pair,the relationship between the maximum alignment error of the DSMLA and the mold-sleeve gap was determined.This research provides a method to optimize the mold-sleeve gap and minimize the alignment error of the DSMLA.The measured DSMLA alignment error was 10.56μm,which is similar to the predicted maximum alignment error.Optical measurements showed that the uniformity of the homogenized beam spot was 97.81%,and the effective homogeneous area accounted for 91.66%of the total area.This proposed method provides a novel strategy to improve the performance of DSMLAs.

关键词： sided alignment error

A nanoplatform with oxygen self-supplying and heat-sensitizing capabilities enhances the efficacy of photodynamic therapy in eradicating multidrug-resistant biofilms

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Journal of Materials Science & Technology 2024年第2期169卷 209-219页

作者： Haixin Zhang Yi Zou Kunyan Lu Yan Wu yuancheng Lin Jingjing Cheng Chunxia Liu Hong Chen Yanxia Zhang qian yu State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215007China

Bacterial biofilms,especially those caused by multidrug-resistant bacteria,have emerged as one of the greatest dangers to global public health.The acceleration of antimicrobial resistance to conventional an-tibiotics and the severe lack of new drugs necessitates the development of novel agents for biofilm eradication.Photodynamic therapy(PDT)is a promising non-antibiotic method for treating bacterial infections.However,its application in biofilm eradication is hampered by the hypoxic microenvironment of biofilms and the physical protection of extracellular polymeric substances.In this study,we develop a composite nanoplatform with oxygen(O_(2))self-supplying and heat-sensitizing capabilities to improve the PDT efficacy against biofilms.CaO_(2)/ICG@PDA nanoparticles(CIP NPs)are fabricated by combining calcium peroxide(CaO_(2))with the photosensitizer indocyanine green(ICG)via electrostatic interactions,followed by coating with polydopamine(PDA).The CIP NPs can gradually generate O_(2)in response to the acidic microenvironment of the biofilm,thereby alleviating its hypoxic state.Under near-infrared(NIR)irradiation,the nanoplatform converts O_(2)into a significant amount of singlet oxygen(^(1)O_(2))and heat to eradicate biofilm.The generated heat enhances the release of O_(2),accelerates the generation of^(1)O_(2)in PDT,increases cell membrane permeability,and increases bacterial sensitivity to^(1)O_(2).This nanoplatform significantly improves the efficacy of PDT in eradicating biofilm-dwelling bacteria without fostering drug resistance.Experiments on biofilm eradication demonstrate that this nanoplatform can eradicate over 99.9999%of methicillin-resistant Staphylococcus aureus(MRSA)biofilms under 5-min NIR irradiation.Notably,these integrated advantages enable the system to promote the healing of MRSA biofilm-infected wounds with negligible toxicity in vivo,indicating great promise for overcoming the obstacles associated with bacterial biofilm eradication.

关键词： Bacterial biofilm Multidrug-resistant bacteria Photodynamic therapy Oxygen supplying Photothermal therapy

A probe into the acid deposition mitigation path in China over the last four decades and beyond

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National Science Review 2024年第4期11卷 84-92页

作者： qian yu Xiaodong Ge Haotian Zheng Jia Xing Lei Duan Dongwei Lv Dian Ding Zhaoxin Dong Yisheng Sun Posch Maximilian Danni Xie yu Zhao Bin Zhao Shuxiao Wang Jan Mulder Thorj?rn Larssen Jiming Hao State Key Laboratory of Environmental Simulation and Pollution Control School of EnvironmentTsinghua University State Key Laboratory of Pollution Control &Resource Reuse and School of the Environment Nanjing University State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex School of EnvironmentTsinghua University International Institute for Applied System Analysis(IIASA) School of Land Engineering Chang'an University Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life Sciences Norwegian Institute for Water Research

China currently has the highest acid deposition globally, yet research on its status, impacts, causes and controls is lacking. Here, we compiled data and calculated critical loads regarding acid deposition. The results showed that the abatement measures in China have achieved a sharp decline in the emissions of acidifying pollutants and a continuous recovery of precipitation p H, despite the drastic growth in the economy and energy consumption. However, the risk of ecological acidification and eutrophication showed no significant decrease. With similar emission reductions, the decline in areas at risk of acidification in China(7.0%) lags behind those in Europe(20%) or the USA(15%). This was because, unlike Europe and the USA, China's abatement strategies primarily target air quality improvement rather than mitigating ecological impacts. Given that the area with the risk of eutrophication induced by nitrogen deposition remained at 13%of the country even under the scenario of achieving the dual targets of air quality and carbon dioxide mitigation in 2035, we explored an enhanced ammonia abatement pathway. With a further 27% reduction in ammonia by 2035, China could largely eliminate the impacts of acid deposition. This research serves as a valuable reference for China's future acid deposition control and for other nations facing similar challenges.

关键词： acid deposition critical loads acidification eutrophication ammonia abatement

Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study

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中华神经外科杂志(英文) 2024年第2期10卷 1-10页

作者： Liu Tao Zhao Zhihao Huang Jinhao Zhu Xide Chen Weiliang Lin Kun yu yunhu Li Zhanying Fan Yibing Liu Mingqi Nie Meng Liu Xuanhui Gao Chuang Quan Wei qian yu Wu Chenrui yuan Jiangyuan Wu Di Lv Chuanxiang Dong Shiying Mi Liang Tian yu Tian Ye Zhang Jianning Jiang Rongcai Department of Neurosurgery Tianjin Medical University General Hospital Tianjin China Ministry of Education Tianjin Neurological Institute Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System Tianjin Medical University General Hospital Tianjin China Department of Neurosurgery Linyi People’s Hospital Shandong China Department of Neurosurgery Haining People’s Hospital Zhejiang China Department of Neurosurgery Fujian Provincial Hospital Fujian China Department of Clinical Research Center for Neurological Disease the People’s Hospital of HongHuaGang District of ZunYi Guizhou China Department of Neurosurgery Kailuan General Hospital Hebei China Department of Neurosurgery Tianjin First Central Hospital Tianjin China Department of Neurosurgery The First Hospital of Jilin University Changchun China

Background Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population.Methods/design A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up.Result Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%.Conclusion This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition.Trial registration ChiCTR2200057179

关键词： Chronic subdural hematoma Multimodality therapy Outcome Recurrence

Improved RF power performance via electrostatic shielding effect using AlGaN/GaN/graded-AlGaN/GaN double-channel structure

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Science China(Information Sciences) 2024年第4期67卷 341-342页

作者： Chunzhou SHI Ling YANG Meng ZHANG Hao LU Mei WU Bin HOU Xuerui NIU qian yu Wenliang LIU Wenze GAO Xiaohua MA yue HAO School of Advanced Materials and Nanotechnology Xidian University State Key Discipline Laboratory of Wide Bandgap Semiconductor Technology Xidian University

GaN-based high-electric-mobility transistors(HEMTs) have been investigated thoroughly because of their promising applications in high-frequency,-voltage, and-power applications. However, the theoretical material limit prevents conventional single-heterostructure GaN HEMTs from achieving high performance despite numerous efforts [1–3].

关键词： Drain current