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Hepatic NAD^+ deficiency as a therapeutic target for NAFLD in aging

中国药理学与毒理学杂志 2016年第10期30卷 1055-1056页

作者： WANG Pei miao chao-yu Department of Pharmacology Second Military Medical University

OBJECTIVE Aging is an important risk factor of nonalcoholic fatty liver disease(NAFLD).Here,we investigated whether the deficiency of nicotinamide adenine dinucleotide(NAD+),a ubiquitous coenzyme,links aging with NAFLD.METHODS Hepatic NAD+concentration,together with the protein levels of nicotinamide phosphoribosyltransferase(NAMPT)and several other critical enzymes regulating NAD+biosynthesis,were compared between middle-aged and aged mice or patients.The influences of NAD+decline on the steatosis and steatohepatitis was evaluated in wild-type(WT)and H247A dominant-negative enzymatic-dead NAMPT transgenic mice(DN-NAMPT)under normal and high-fat diet(HFD).RESULTS Hepatic NAD+level decreased in aged mice and people.NAMPT-controlled NAD+salvage,but not de novo biosynthesis pathway,was compromised in liver of elderly mice and human.Under normal chow,middle-age DN-NAMPT mice displayed systemic NAD+reduction,and had moderate NAFLD phenotypes,including lipid accumulation,enhanced oxidative stress,triggered inflammation and impaired insulin sensitivity in liver.Allthese NAFLD phenotypes,especial y the pro-inflammatory factors release,Kupffer cell accumulation,monocytes infiltration,NLRP3 inflammasome pathway,and hepatic fibrosis(Masson’s staining and a-SMA staining),were further deteriorated under HFD challenge.Orally administration of nicotinamide riboside,a natural NAD+precursor,completely corrected these NAFLD phenotypes induced by NAD+deficiency alone or HFD,whereas adenovirusmediated SIRT1 overexpression only partially rescued these phenotypes.CONCLUSION These results provide the first evidence that aging-associated NAD+deficiency is a critical risk factor for NAFLD,and suggest that supplement of NAD+substrates may be a promising therapeutic strategy to prevent and treat NAFLD.

关键词： NAD liver NAFLD NLRP3

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Cerebral organoids repair ischemic stroke brain injury

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中国药理学与毒理学杂志 2019年第10期 849-850页

作者： WANG Shu-na WANG Zhi XU Tian-ying CHENG Ming-he LI Wen-lin miao chao-yu Department of Pharmacology Second Military Medical University Department of Cell Biology Second Military Medical University

OBJECTIVE Stroke is the second leading cause of death and main cause of disability worldwide,but with few effective therapies. Although stem cellbased therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids(COs) represent a promising transplantation source for stroke therapy that remains to be answered. METHODS Rat stroke model was prepared by middle cerebral artery occlusion(MCAO).COs at 55 d were transplanted into infarct periphery at 6,24 h or 7 d after MCAO to explore the therapeutic feasibility and underlying mechanisms. RESULTS COs transplantation at 6 h or even 24 h after MCAO significantly reduced brain infarct volume and improved neurological motor function. Transplanted COs exhibited the potential of multilineage differentiation to mimic in vivo cortical development, support motor cortex region-specific reconstruction, form neurotransmitter related neurons and achieve synaptic connection with host brain via in situ differentiation and cell replacement in stroke. Cells from transplanted COs showed extensive migration and integration into different brain regions along corpus callosum. The mechanisms underlying COs transplantation therapy were also associated with enhanced neurogenesis,synaptic reconstruction and angiogenesis, and decreased neural apoptosis with more survival neurons after stroke.Moreover, COs transplantation promoted predominantly exogenous neurogenesis in the transplantation periphery of ipsilateral cortex and predominantly endogenous neurogenesis in the hippocampus and subventricular zone.CONCLUSION This study demonstrates the efficacy and underlying mechanisms of COs transplantation in stroke, and provides first-hand preclinical evidence for COs transplantation as a potential and effective intervention for stroke treatment.

关键词： cerebral organoids brain damage repair functional recovery stroke transplantation

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Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2429-2438页

作者： Peng-Fei Jing Jin Chen En-Da yu chao-yu miao Department of Colorectal Surgery Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China Department of Endocrinology and Metabolism Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China Department of Pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been increasing.With the popularization of endoscopic technology,a number of early CRC has been diagnosed.However,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and metastasis.AIM To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations.METHODS A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study.Results of blood routine test,liver and kidney function tests and tumor markers were collected before surgery.Patients were followed up through disease-specific database and telephone interviews.Tumor recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis.RESULTS We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of CRC.Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for OS.The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL.Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for OS.Given that these measures are easier to detect and more acceptable to patients,they may have broader applications.

关键词： Colorectal cancer Platelet count Serum carcinoembryonic antigen Total cholesterol level Overall survival Disease-free survival

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What factors control plant height?

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Journal of Integrative Agriculture 2024年第6期23卷 1803-1824页

作者： Li miao Xiangyu Wang chao yu Chengyang Ye Yanyan Yan Huasen Wang College of Horticulture Qingdao Agricultural UniversityQingdao 266109China Key Laboratory for Quality and Safety Control of Subtropical Fruits and Vegetables College of Horticulture ScienceZhejiang Agriculture and Forestry UniversityHangzhou 311300China

Plant height(PH)is one of the most important components of the plant ideotype,and it affects plant biomass,yield,lodging resistance,and the ability to use mechanized harvesting.Since many complex pathways controlling plant growth and development remain poorly understood,we are still unable to obtain the most ideal plants solely through breeding efforts.PH can be influenced by genotype,plant hormonal regulation,environmental conditions,and interactions with other plants.Here,we comprehensively review the factors influencing PH,including the regulation of PH-related developmental processes,the genetics and QTLs contributing to PH,and the hormone-regulated molecular mechanisms for PH.Additionally,the symbiotic influence of grafting on PH is discussed,focusing on the molecular regulation of gene expression and genetics.Finally,we propose strategies for applying recent findings to breeding for better PH,highlight some knowledge gaps,and suggest potential directions for future studies.

关键词： dwarfism plant hormones interaction grafting QTLs phenotyping

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Dual-microcomb generation via a monochromatically pumped dual-mode microresonator

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Photonics Research 2024年第1期12卷 163-171页

作者： RUNLIN miao KE YIN chao ZHOU CHENXI ZHANG ZHUOPEI yu XIN ZHENG TIAN JIANG National Innovation Institute of Defense Technology Academy of Military Sciences PLA ChinaBeijing 100071China Beijing Institute for Advanced Study National University of Defense TechnologyBeijing 100000China College of Advanced Interdisciplinary Studies National University of Defense TechnologyChangsha 410073China College of Electronic Science and Technology National University of Defense TechnologyChangsha 410073China Institute for Quantum Science and Technology College of ScienceNational University of Defense TechnologyChangsha 410073China

Microcombs have enabled a host of cutting-edge applications from metrology to communications that have garnered significant attention in the last decade.Nevertheless,due to the thermal instability of the microresonator,additional control devices like auxiliary lasers are indispensable for single-soliton generation in some scenarios.Specifically,the increased system complexity would be too overwhelming for dual-microcomb generation.Here,we put forward a novel approach to mitigate the thermal instability and generate the dual-microcomb using a compact system.This process is akin to mode-division multiplexing,as the dual-microcombs are generated by pumping the dual-mode of a single Si_(3)N_(4) microresonator with a continuous-wave laser.Both numerical simulations and experimental measurements indicate that this innovative technique could offer a straightforward way to enlarge the soliton existence range,allowing entry into the multistability regime and triggering another microcomb alongside the main soliton pulse.This outcome not only shines new light on the interaction mechanism of microresonator modes but also provides an avenue for the development of dual-microcomb-based ranging and low phase noise microwave generation.

关键词： resonator pumped pumping

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How can technology and efficiency alleviate the dilemma of economic growth and carbon emissions in China's industrial economy? A metafrontier decoupling decomposition analysis

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Petroleum Science 2024年第2期21卷 1415-1428页

作者： miao Wang chao Feng School of Business Zhengzhou UniversityZhengzhou450001HenanChina School of Economics and Business Administration Chongqing UniversityChongqing400030China

This paper attempts to explore the decoupling relationship and its drivers between industrial economic increase and energy-related CO_(2) emissions(ICE). Firstly, the decoupling relationship was evaluated by Tapio index. Then, based on the DEA meta-frontier theory framework which taking into account the regional and industrial heterogeneity and index decomposition method, the driving factors of decoupling process were explored mainly from the view of technology and efficiency. The results show that during2000-2019, weak decoupling was the primary state. Investment scale expansion was the largest reason hindering decoupling process of industrial increase from ICE. Both energy saving and production technology achieved significant progress, which facilitated the decoupling process. Simultaneously, the energy technology gap and production technology gap among regions have been narrowed, and played a role in promoting decoupling process. On the contrary, both scale economy efficiency and pure technical efficiency have inhibiting effects on decoupling process. The former indicates that the scale economy of China's industry was not conducive to improve energy efficiency and production efficiency, while the latter indicates that resource misallocation problem may exist in both energy market and product market.

关键词： China's industrial sector Decoupling process Meta-frontier DEA Index decomposition method Driving factors

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Metrnl increases blood HDL-cholesterol and decreases blood triglyceride

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中国药理学与毒理学杂志 2019年第10期 799-799页

作者： QI Qi LI Zhi-yong miao chao-yu Department of Pharmacology Second Military Medical University

OBJECTIVE Dyslipidemias are risk factors for both cardiovascular diseases and type 2 diabetes.Many adipose-derived proteins/adipokines participate in modulation of blood lipids. As a new identified adipokine,metrnlin adipose is involved in regulation of blood triglyceride, suggesting metrnl may play extensive roles in regulation of blood lipid. However, the exact effects and the underling mechanisms of Metrnl on regulation of blood lipid remain unexplored. METHODS Metrnl global knockout mice were generated and fed with normal chow diet or high fat diet. Major clinical lipid parameters including blood triglyceride(TG), total cholesterol(TC), high density lipoprotein(HDL) cholesterol, low density lipoprotein(LDL) cholesterol, and non-esterified fatty acid(NEFA)were detected with automatic biochemistry analyzer. Further,intestine and liver specific knockout mice were generated and the major clinical lipid parameters were detected to clarify which tissue contributes to metrnl regulated alterations of clinical lipid parameters. RESULTS Global knockout of metrnl had no effects on clinical parameters under normal chow diet, but increased blood triglyceride by 14%,which was consistent with our previous findings in metrnl adipose specific knockout mice, and decreased total cholesterol by 16% and HDL-cholesterol by 24% under high fat diet. Intestine specific knockout of metrnl failed to alter any of the clinical lipid parameters under both normal chow diet and high fat diet. Notably, liver specific knockout of metrnl downregulated HDL-cholesterol by 24%, TC by20% and LDL-cholesterol by 16% without alterations of blood TG and NEFA under high fat diet. CONCLUSION Global deficiency of metrnl downregulates blood HDLcholesterol and upregulates blood TG, and liver participates in the former and adipose tissue the latter.

关键词： dyslipidemia HDL-cholesterol metrnl triglyceride

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Editorial Commentary:Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis:Current Knowledge and Future Perspectives

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Current Medical Science 2024年第1期44卷 241-243页

作者： miao yu Xiang CHENG Department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Key Laboratory of Biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Atherosclerosis(AS)is the main underlyingpathology of atherosclerotic cardiovascular disease(ASCVD),which is the leading cause of mortality inthe worldwide[1,2].Since the 19th century,Virchowhas already stated that AS is a chronic inflammatorystate induced by cholesterol.After that,it took at leastthree decades’worth of study to establish the multipleinflammatory pathways related to AS.

关键词： Virchow mortality cardiovascular

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Intestine metrnl acts as a local regulator released into gut lumen and maintaining gut antimicrobial peptides

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中国药理学与毒理学杂志 2016年第10期30卷 1092-1092页

作者： LI Zhi-yong FAN Mao-bing QU Yi ZHENG Si-li SONG Jie miao chao-yu Department of Pharmacology Second Military Medical University

OBJECTIVE Metrnl is a novel secreted protein with limited researches.In this study,we investigated metrnl tissue expression pattern in humans,and exploredthe possible role of its highest expression using animal models.METHODS We examined metrnl tissue expression pattern in a human tissue microarray containing 19types of tissues from 69 donors,and verified the highest expression in fresh human and mouse tissues.We then created an animal model of cell-specific knockout mice to study the role of metrnl.RESULTS Metrnl was the highest expressed in human gastrointestinal tract,and specifical y expressed in the intestinal epithelium.Consistently,Metrnl expression was also the highest expressed in mouse gastrointestinal tract among the detected tissues of 14 types.We developed intestinal epithelial cellspecific metrnl knockout mice with Vil in-Cre.In this animal model,metrnl levels displayed a statistically significant reduction in gut fluid,but not in blood serum.This cell specific deletion of metrnl did not affect body weight,food intake,blood glucose,colon length and histology,intestinal permeability,mucus production and mucin 2 expression under physiological conditions,but markedly reduced the expression of antimicrobial peptides,such as regenerating islet-derived 3 gamma and lactotransferrin.CONCLUSION Metrnl is rich in intestinal epithelial cells of humans and mice,mainly contributing to local gut metrnl level,and less affecting systemic circulating metrnl level.Metrnl plays a role in maintaining gut antimicrobial peptides.

关键词： metrnl secreted protein human expression pattern intestine epithelial cel antimicrobial peptide

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Heat Transfer Characteristics of a Microchannel Heat Sink with Highly-Dense Micro-Jet Arrays

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Journal of Thermal Science 2024年第3期33卷 1148-1160页

作者： ZHANG yu CHEN Xiaoyan miao Lin CHEN Liang HOU yu State Key Laboratory of Multiphase Flow in Power Engineering Xi’an Jiaotong UniversityXi’an710049China Beijing Aerospace Technology Institute Beijing100083China

This paper proposed a new structure of highly-dense micro-jet arrays for hybrid jet-impingement/microchannel heat sinks(~120 jet per cm^(2) with jet width of 0.35 mm).Parametric study is performed to investigate the influence of structure and flow parameters on the convective heat transfer of water jet cooling in confined space.The simulation results show that the optimal jet width,jet spacing and impingement distance are around 0.2 mm,0.2 mm and 0.3 mm,respectively,which can achieve a low thermal resistance as well as a relatively low pressure drop.The analysis of the heat transfer pathways shows that the micro-fin jet structures can extend the impinging heat transfer area and conduct a considerable proportion of heat,which can reach up to 38.9%with the Reynolds number ranging from 797.1 to 5602.2.The heat transfer characteristics in the heat sink will shift from impingement dominated heat transfer to the channel-convection dominated heat transfer as the jet impingement distance increases.A correlation is proposed to predict the average Nusselt number on the stagnation area for the heat sink with different structure parameters,and the deviations of predictions from the numerical results are less than 10%.

关键词： hybrid heat sink impingement microchannel thermal management high heat flux

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