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Temporal changes in inflammatory mitochondria-enriched microRNAs following traumatic brain injury and effects of miR-146a nanoparticle delivery

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Neural Regeneration Research 2021年第3期16卷 514-522页

作者： wang-xia wang Paresh Prajapati Hemendra J.Vekaria Malinda Spry Amber L.Cloud Patrick G.Sullivan Joe E.Springer Sanders Brown Center on Aging University of KentuckyLexingtonKYUSA Spinal Cord and Brain Injury Research Center University of KentuckyLexingtonKYUSA Department of Pathology&Laboratory Medicine University of KentuckyLexingtonKYUSA Department of Neuroscience University of KentuckyLexingtonKYUSA

MicroRNAs(miRNAs)are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function.We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation(i.e.,miR-142-3p,miR-142-5p,and miR-146a)are altered in the hippocampus at 3–12 hours following a severe traumatic brain injury.In the present study,we investigated the temporal expression profile of these inflammatory miRNAs in mitochondria and cytosol fractions at more chronic post-injury times following severe controlled cortical impact injury in rats.In addition,several inflammatory genes were analyzed in the cytosol fractions.The analysis showed that while elevated levels were observed in cytoplasm,the mitochondria-enriched miRNAs,miR-142-3p and miR-142-5p continued to be significantly reduced in mitochondria from injured hippocampi for at least 3 days and returned to near normal levels at 7 days post-injury.Although not statistically significant,miR-146a also remained at reduced levels for up to 3 days following controlled cortical impact injury,and recovered by 7 days.In contrast,miRNAs that are not enriched in mitochondria,including miR-124a,miR-150,miR-19b,miR-155,and miR-223 were either increased or demonstrated no change in their levels in mitochondrial fractions for 7 days.The one exception was that miR-223 levels were reduced in mitochondria at 1 day following injury.No major alterations were observed in sham operated animals.This temporal pattern was unique to mitochondria-enriched miRNAs and correlated with injury-induced changes in mitochondrial bioenergetics as well as expression levels of several inflammatory markers.These observations suggested a potential compartmental re-distribution of the mitochondria-enriched inflammatory miRNAs and may reflect an intracellular mechanism by which specific miRNAs regulate injury-induced inflammatory signaling.To test this,we utilized a novel peptide-based nanoparticle strategy for in vitro and in vivo

关键词： cell permeable peptide-delivery controlled cortical impact inflammatory pathway mitochondria-associated microRNA nanoparticle nuclear factor-kappa B traumatic brain injury

Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells

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Genomics, Proteomics & Bioinformatics 2014年第1期12卷 19-30页

作者： wang-xia wang Robert J.Danaher Craig S.Miller Joseph R.Berger Vega G.Nubia Bernard S.Wilfred Janna H.Neltner Christopher M.Norris Peter T.Nelson Sanders-Brown Center on Aging University of KentuckyLexingtonKY 40536USA College of Dentistry University of KentuckyLexingtonKY 40536USA Department of Neurology University of KentuckyLexingtonKY 40536USA Department of Pathology University of KentuckyLexingtonKY 40536USA Department of Molecular and Biomedical Pharmacology University of KentuckyLexingtonKY 40536USA

The miR-15/107 family comprises a group of 10 paralogous microRNAs （miRNAs）,sharing a 5＇ AGCAGC sequence.These miRNAs have overlapping targets.In order to characterize the expression of miR-15/107 family miRNAs,we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members,and other selected miRNAs,in 11 human tissues obtained at autopsy including the cerebral cortex,frontal cortex,primary visual cortex,thalamus,heart,lung,liver,kidney,spleen,stomach and skeletal muscle.miR-103,miR-195 and miR-497 were expressed at similar levels across various tissues,whereas miR-107 is enriched in brain samples.We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations （enriched for cortical neurons,astrocytes and microglia,respectively）.In primary cultures of rat brain cells,several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system （CNS）.In addition to mature miRNAs,we also examined the expression of precursors （pri-miRNAs）.Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors.In summary,we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

关键词： miR-16 miR-424 miR-503 miR-15 Normalization Target prediction

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

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Chinese Journal of Integrative Medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min wang xia LIU xia ZHAO Juan Medical Examination Center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental Center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

Continuous-wave operation of 1550 nm low-threshold triple-lattice photonic-crystal surface-emitting lasers

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Light(Science & Applications) 2024年第3期13卷 446-453页

作者： Ziye wang xia Liu Pinyao wang Huanyu Lu Bo Meng Wei Zhang Lijie wang Yanjing wang Cunzhu Tong State Key Laboratory of Luminescence and Applications Changchun Institute of OpticsFine Mechanics and PhysicsChinese Academy of SciencesChangchun 130033China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Central Research Institute Planning Dept 2012 LabsHuawei Technologies Company Ltd.Shenzhen 518129China

Benefitting from narrow beam divergence,photonic crystal surface-emitting lasers are expected to play an essential role in the ever-growing fields of optical communication and light detection and ranging.Lasers operating with 1.55μm wavelengths have attracted particular attention due to their minimum fiber loss and high eye-safe threshold.However,high interband absorption significantly decreases their performance at this 1.55μm wavelength.Therefore,stronger optical feedback is needed to reduce their threshold and thus improve the output power.Toward this goal,photonic-crystal resonators with deep holes and high dielectric contrast are often used.Nevertheless,the relevant techniques for high-contrast photonic crystals inevitably complicate fabrication and reduce the final yield.In this paper,we demonstrate the first continuous-wave operation of 1.55μm photonic-crystal surface-emitting lasers by using a‘triple-lattice photonic-crystal resonator’,which superimposes three lattice point groups to increase the strength of in-plane optical feedback.Using this geometry,the in-plane 180°coupling can be enhanced threefold compared to the normal single-lattice structure.Detailed theoretical and experimental investigations demonstrate the much lower threshold current density of this structure compared to‘single-lattice’and‘double-lattice’photonic-crystal resonators,verifying our design principles.Our findings provide a new strategy for photonic crystal laser miniaturization,which is crucial for realizing their use in future high-speed applications.

关键词： resonator crystal lattice

In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & Vascular Neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing wang Yuesong Pan xia Meng Xingquan Zhao Liping Liu Yongjun wang Yilong wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina National Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method Data were obtained from the Third China National Stroke Registry study.We estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were explored.Sensitivity analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were conducted.Result Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were men.After adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild BG-EPVS.Patients with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild BG-EPVS.Sensitivity analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year follow-up.Conclusion BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 year.Therefore,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

Polarizable Additive with Intermediate Chelation Strength for Stable Aqueous Zinc‑Ion Batteries

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Nano-Micro Letters 2024年第5期16卷 41-55页

作者： Yuting xia Rongao Tong Jingxi Zhang Mingjie Xu Gang Shao Hailong wang Yanhao Dong Chang‑An wang State Key Lab of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084People’s Republic of China School of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450001HenanPeople’s Republic of China

Aqueous zinc-ion batteries are promising due to inherent safety,low cost,low toxicity,and high volumetric capacity.However,issues of dendrites and side reactions between zinc metal anode and the electrolyte need to be solved for extended storage and cycle life.Here,we proposed that an electrolyte additive with an intermediate chelation strength of zinc ion—strong enough to exclude water molecules from the zinc metal-electrolyte interface and not too strong to cause a significant energy barrier for zinc ion dissociation—can benefit the electrochemical stability by suppressing hydrogen evolution reaction,overpotential growth,and den-drite formation.Penta-sodium diethylene-triaminepentaacetic acid salt was selected for such a purpose.It has a suitable chelating ability in aqueous solutions to adjust solvation sheath and can be readily polarized under electrical loading conditions to further improve the passivation.Zn||Zn symmetric cells can be stably operated over 3500 h at 1 mA cm^(-2).Zn||NH4V4O10 full cells with the additive show great cycling stability with 84.6%capacity retention after 500 cycles at 1 A g^(-1).Since the additive not only reduces H2 evolution and corrosion but also modifies Zn2+diffusion and deposition,highlyreversible Zn electrodes can be achieved as verified by the experimental results.Our work offers a practical approach to the logical design of reliable electrolytes for high-performance aqueous batteries.

关键词： Aqueous zinc-ion batteries Electrolyte additives DTPA-Na Chelation strength

A synergetic strategy of NIR-Ⅱ squaraine dyes with ultrahigh photothermal conversion efficiency for photothermal therapy

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Science China Chemistry 2024年第2期67卷 612-621页

作者： Yigang wang Guomin xia Junhui wang Mingda wang Weihan Guo Manman Tan Leilei Si Yang Yang Hua wang Hongming wang Institute for Advanced Study and School of Chemistry and Chemical Engineering Nanchang UniversityNanchang330031China State Key Laboratory of Molecular Reaction Dynamics and Dynamics Research Center for Energy and Environmental Materials Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023China The Second Affiliated Hospital of Nanchang University Nanchang330031China

Recent research on photothermal therapy(PTT) has sparked significant interest in the development of new organic photothermal agents(PTAs),ranging from single-molecule to aggregated levels.However,controlling aggregation pathways for PTAs with ultrahigh photothermal conversion efficiency(PCE) remains a major challenge.Herein,a two-pronged approach utilizing “Haggregation” and “intramolecular motion” was employed to enhance the PCE of an acceptor-substituted squaraine dye(NSQs).The C2vmolecular symmetry of the NSQs,which possess a ground state dipole moment(μg),promotes H-dimeric aggregates through dipole-dipole counteraction.Peripheral triphenylethylene or diphenylamine groups were added to this H-dimeric nanoplatform.This was done to enhance intramolecular motions for heat generation and also to extend conjugation,which redshifted the optical absorption and balanced the blue-shift induced by H-aggregation.With this technique,an organic PTA with NIR-II absorption was developed,and its nanoparticle achieved a remarkable PCE of 86.3% under 1,064 nm laser excitation.Femtosecond transient absorption spectroscopy and quantum mechanical calculations demonstrated the accelerated internal conversion process in NIR-II PTAs for rapid heat generation.The NSQs nanoparticles exhibit superior photothermal therapeutic properties for in vivo photoacoustic imaging-guided PTT,demonstrating the potential of bottom-up design to enable synergistic engineering strategies towards efficient phototheranostic agents.

关键词： squaraine dyes second near-infrared window H-aggregation intramolecular motion photothermal therapy

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

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Current Medical Science 2024年第2期44卷 261-272页

作者： Meng-jie wang Yu xia Qing-lei GAO Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Cancer Invasion and Metastasis(Ministry of Education) Hubei Key Laboratory of Tumor Invasion and MetastasisTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

关键词： DNA damage tumor immune microenvironment inflammatory cytokines cancer therapy

Numerical insight into heat transfer enhancement by granules inner-migration in a moving bed:A performance comparison between slanted-stick and plow-shaped agitator

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Particuology 2024年第6期89卷 109-116页

作者： Binfan Jiang Hao Pei Dehong xia Haiyang wang School of Energy and Environmental Engineering University of Science and Technology BeijingBeijing 100083China Shunde Graduate School of University of Science and Technology Beijing Guangdong 528399China Jianlong Group&USTB Joint Laboratory Beijing 100083China

Waste heat recovery of high-temperature granules is one of the most promising sustainable energy supply and carbon reduction ways for industry.A moving bed indirect heat exchanger(MBIHE)with inner-migration was proposed for granular heat recovery.Granule migration and the enhanced heat transfer induced by two types of agitators(i.e.,agitator with slanted stick A_(s)and with plow-shaped surface A_(p))in the MBIHE are analyzed based on DEM coupled with CFD.Owing to the effective agitation,the average heat transfer coefficient in the granule side is enhanced to∼3 times compared to that without agitation.The heat recovery efficiency in the moving bed reached more than 70%with the agitations of either A_(s)or A_(p).The heat efficiency of A_(s)is∼7%higher than that of A_(p),but with at least 60%greater rotational torque.To ensure reliable agitation,the A_(p)is suggested to be adopted in the MBIHE to induce granule migration.

关键词： Waste heat recovery High-temperature granule Granule migration Heat transfer enhancement Industry energy saving