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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui ling he Jing Wang Regenerative Medicine Program Ottawa Hospital Research InstituteOttawaONCanada Department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada Department of Pediatrics and Medicine Johns Hopkins Medical SchoolBaltimoreMDUSA Department of Cellular and Molecular Medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

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Horticultural Plant Journal 2024年第1期10卷 223-238页

作者： Xinyue Liu ling he Ze Wu Nianjun Teng Key Laboratory of Landscaping Agriculture Ministry of Agriculture and Rural AffairsCollege of HorticultureNanjing Agricultural UniversityNanjingJiangsu 210095China Key Laboratory of Biology of Ornamental Plants in East China National Forestry and Grassland AdministrationCollege of HorticultureNanjing Agricultural UniversityNanjingJiangsu 210095China Jiangsu Graduate Workstation of Nanjing Agricultural University and Nanjing Oriole Island Modern Agricultural Development Co. Ltd.NanjingJiangsu 210043China

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

关键词： Lily Anther development Pollen pollution GAMYB VIGS

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Numerical and experimental investigation on hydraulic-electric rock fragmentation of heterogeneous granite

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International Journal of Mining Science and Technology 2024年第1期34卷 15-29页

作者： Xiaohua Zhu ling he Weiji Liu Yunxu Luo Youjian Zhang Wuji Tang School of Mechatronic Engineering Southwest Petroleum UniversityChengdu 610500China School of Mechanical Engineering Sichuan University of Science and EngineeringYibin 643002China

Hydraulic-electric rock fragmentation(heRF)plays a significant role in improving the efficiency of high voltage pulse rock breaking.However,the underlying mechanism of heRF remains unclear.In this study,considering the heterogeneity of the rock,microscopic thermodynamic properties,and shockwave time domain waveforms,based on the shockwave model,digital imaging technology and the discrete element method,the cyclic loading numerical simulations of heRF is achieved by coupling electrical,thermal,and solid mechanics under different formation temperatures,confining pressure,initial peak voltage,electrode bit diameter,and loading times.Meanwhile,the heRF discharge system is conducive to the laboratory experiments with various electrical parameters and the resulting broken pits are numerically reconstructed to obtain the geometric parameters.The results show that,the completely broken area consists of powdery rock debris.In the pre-broken zone,the mineral cementation of the rock determines the transition of type CⅠcracks to type CⅡand type CⅢcracks.Furthermore,the peak pressure of the shockwave increased with initial peak voltage but decreased with electrode bit diameter,while the wave front time reduced.Moreover,increasing well depth,formation temperature and confining pressure augment and inhibit heRF,but once confining pressure surpassed the threshold of 60 MPa for 152.40,215.90,and 228.60 mm electrode bits,and 40 MPa for 309.88 mm electrode bits,heRF is promoted.Additionally,for the same kind of rock,the volume and width of the broken pit increase with higher initial peak voltage and rock fissures will promote heRF.Eventually,the electrode drill bit with a 215.90 mm diameter is more suitable for drilling pink granite.This research contributes to a better microscopic understanding of heRF and provides valuable insights for electrode bit selection,as well as the optimization of circuit parameters for heRF technology.

关键词： Hydraulic-electric rock fragmentation Shockwave Thermodynamics Microcracks Weak Linear Parallel Bond Model

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hepatitis B cure:Current situation and prospects

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World Journal of hepatology 2024年第6期16卷 900-911页

作者： Ya-Ping Li Chen-Rui Liu ling he Shuang-Suo Dang Department of Infectious Diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina

Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

关键词： Chronic hepatitis B Clinical cure Polyethylene glycol interferon Treatment strategies Research progress

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Application of total keratometry in ten intraocular lens power calculation formulas in highly myopic eyes

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Eye and Vision 2024年第2期10卷 22-30页

作者： ling Wei Kaiwen Cheng Wenwen he Xiangjia Zhu Yi Lu Department of Ophthalmology and Eye Institute Eye and ENT Hospital of Fudan UniversityShanghai 200031China Key Laboratory of Myopia(Fudan University)Key Laboratory of MyopiaShanghai Key Laboratory of Visual Impairment and Restoration National Health CommissionChinese Academy of Medical ScienceShanghai 200031China State Key Laboratory of Medical Neurobiology Fudan UniversityShanghai 200031China

Background:The accuracy of using total keratometry(TK)value in recent IOL power calculation formulas in highly myopic eyes remained unknown.Methods:Highly myopic patients who underwent uneventful cataract surgery were prospectively enrolled in this prospective comparative study.At one month postoperatively,standard deviation(SD)of the prediction errors(PEs),mean and median absolute error(MedAE)of 103 highly myopic eyes were back-calculated and compared among ten formulas,including XGboost,RBF 3.0,Kane,Barrett Universal II,Emmetropia Verifying Optical 2.0,Cooke K6,Haigis,SRK/T,and Wang-Koch modifications of Haigis and SRK/T formulas,using either TK or standard keratometry(K)value.Results:In highly myopic eyes,despite good agreement between TK and K(P>0.05),larger differences between the two were associated with smaller central corneal thickness(Phe refractive errors,TK method showed no differences compared to K method.The XGBoost,RBF 3.0 and Kane ranked top three when considering SDs of PEs.Using TK value,the XGboost calculator was comparable with the RBF 3.0 formula(P>0.05),which both presented smaller MedAEs than others(all Phe percentage of eyes within±0.50 D or±0.75 D of PE,the XGBoost TK showed comparable percentages with the RBF 3.0 TK formula(74.76%vs.66.99%,or 90.29%vs.87.38%,P>0.05),and statistically larger percentages than the other eight formulas(Phe XGboost enhancement calculator and RBF 3.0 formula using TK showed the most promising outcomes in highly myopic eyes.

关键词： High myopia Total keratometry Cataract surgery IOL power calculation

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Acute Bacillus cereus endophthalmitis caused by ocular perforation injury and occult intravitreal cilium implantation:a case report

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 976-978页

作者： ling Zhang Bin Chen Wei-Min he Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Ophthalmology the People’s Hospital of LeshanLeshan 614000Sichuan ProvinceChina

Dear Editor,We present a case of acute Bacillus cereus(B.cereus)endophthalmitis in a patient with an intraocular perforation injury combined with occult intravitreal cilium implantation.B.cereus endophthalmitis is a severe intraocular infection commonly caused by post-traumatic injuries.It often leads to significant vision loss or even eye loss within 12-48h[1].The presence of an intraocular foreign body(IOFB)increases the risk of infection,while early surgical removal of IOFBs can prevent endophthalmitis,some IOFBs are difficult to detect preoperatively.The Medical Ethics Review Board of West China Hospital of Sichuan University waived application for a clinical study because this was a retrospective report of a single patient based on imaging and because no human experimentation was involved.The patient provided written informed consent to use the imaging data for publication.

关键词： endophthalmitis ilium injuries

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Electrolyte effect on electrochemical behaviors of manganese fluoride material for aqueous asymmetric and symmetric supercapacitors

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Rare Metals 2024年第3期43卷 1048-1061页

作者： Zheng-Hua he Jian-Fei Gao ling-Bin Kong State Key Laboratory of Advanced Processing and Recycling of Non-Ferrous Metals Lanzhou University of TechnologyLanzhou730050China School of Materials Science and Engineering Lanzhou University of TechnologyLanzhou730050China

Exploring wide voltage window materials is not only an available measure to enhance the energy density of hybrid supercapacitor(HSCs),but also avoids the dynamic mismatch caused by different energy storage mechanisms of two electrodes in assembled symmetrical HSC.However,there are few reports about the wide potential window materials except Bi_(2)O_(3)and VO_(2).Therefore,the MnF_(2)synthesized by solvothermal reaction was served as the electrode for HSC.The MnF_(2)exhibited electrochemical activity in alkaline solution in three-electrode system,especially with a wide potential window from-0.8 to+0.5 V in 2 mol·L^(-1)NaOH.Furthermore,the assembled MnF_(2)//MnF_(2)symmetrical HSC had a potential window of 1.5 V,and it exhibited outstanding long-cycle capability.Meanwhile,when MnF_(2)was taken as the negative and positive respectively,the potential windows of asymmetric devices CoMoO_(4)//MnF_(2)and MnF_(2)//Activated Carbon(AC)could reach 1.3 and 1.45 V,respectively,showing excellent cycle stability.This work shows that MnF_(2)material has great research value in HSC,and provides a new research direction for developing high-performance devices.

关键词： Manganese fluoride Potential window Hybrid supercapacitors Electrochemical performance

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Immune checkpoint inhibitors break whose heart? Perspectives from cardio-immuno-oncology

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Genes & Diseases 2024年第2期11卷 807-818页

作者： Yingying he Hui Yu Shuang Dai Miao he ling Ma Zihan Xu Feng Luo Li Wang Oncology Department Deyang People's HospitalDeyangSichuan 618000China Department of Medical Oncology Lung Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610000China Cardiovascular Department Mianyang Central HospitalMianyangSichuan 621000China Department of Rheumatology and Immunology Deyang People's HospitalDeyangSichuan 618000China

Immune checkpoint inhibitors (ICIs) are monoclonal antibody antagonists,which can block cytotoxic T lymphocyte antigen-4 (CTLA-4),programmed death-1/ligand-1 (PD-1/PD-L1) pathways,and other molecules exploited by tumor cells to evade T cell-mediated immune response.ICIs have transformed the treatment landscape for various cancers due to their amazing efficacy.Many anti-tumor therapies,including targeted therapy,radiotherapy,and chemotherapy,combine ICIs to make the treatment more effective.However,the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ systems.Among irAEs,cardiotoxicity induced by ICIs,uncommon but fatal,has greatly offset survival benefits from ICIs,which is heartbreaking for both patients and clinicians.Consequently,such cardiotoxicity requires special vigilance,and it has become a common challenge both for patients and clinicians.This article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clinicians,elaborated on the underlying mechanisms in conjunction with animal studies,and then attempted to propose management strategies from a cardio-immuno-oncology multidisciplinary perspective.

关键词： Cancer management Cardio-immuno-oncology multidisciplinary Cardiotoxicity Immune checkpoint inhibitors Immune tolerance

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Nitric oxide assists nitrogen reduction reaction on 2D MBene: A theoretical study

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Chinese Chemical Letters 2024年第5期35卷 428-433页

作者： Chaozheng he Jia Wang ling Fu Wei Wei henan Engineering Center of New Energy Battery Materials College of Chemistry and Chemical EngineeringShangqiu Normal UniversityShangqiu 476000China School of Chemistry and Chemical Engineering Shandong Provincial Key Laboratory/Collaborative Innovation Center of Chemical Energy Storage&Novel Cell TechnologyLiaocheng UniversityLiaocheng 252059China Institute of Environment and Energy Catalysis Shaanxi Key Laboratory of Optoelectronic Functional Materials and DevicesSchool of Materials Science and Chemical EngineeringXi’an Technological UniversityXi’an 710021China College of Resources and Environmental Engineering Tianshui Normal UniversityTianshui 741001China

Electrocatalytic synthesis of ammonia as an environment-friendly and sustainable development method has received widespread attention in recent years.Two-dimensional(2D)materials are a promising catalyst for ammonia synthesis due to their large surface area.In this work,we have constructed a series of 2D metal borides(MBenes)with transition metal(TM)defects(TMd-MBenes)and comprehensively calculated the reactivity of electrocatalytic synthesis of ammonia-based on density functional theory.The results have demonstrated that the TMd-MBenes can effectively activate nitrogen oxide(NO)and nitrogen(N2)molecules thermodynamically.Particularly interesting,the co-chemisorption of O atoms,dissociated from NO,can facilitate the spilled of the inert N2 molecules into single N atoms,which can further hydrogenate into ammonia easily with an ultralow limiting potential of 0.59 V on TMd-MnB.Our research has not only provided clues for catalyst design for experimental study but also paved the way for the industrial application of electrocatalytic ammonia synthesis.

关键词： 2D mbenes Nitrogen electro-reduction DFT N_(2)activation Ammonia synthesis

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Numerical study on the effective thermal conductivity and thermal tortuosity of porous media with different morphologies

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Science China Technological Sciences 2024年第6期67卷 1685-1694页

作者： DU Shen LI Dong LI Meng-Jie he Ya-ling Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education School of Energy and Power Engineering Xi’an Jiaotong University

Effective thermal conductivity and thermal tortuosity are crucial parameters for evaluating the effectiveness of heat conduction within porous media. The direct pore-scale numerical simulation method is applied to investigate the heat conduction processes inside porous structures with different morphologies. The thermal conduction performances of idealized porous structures are directly compared with real foams across a wide range of porosity. Real foam structures are reconstructed using X-ray computed tomography and image processing techniques, while Kelvin and Weaire-Phelan structures are generated through periodic unit cell reconstruction. The detailed temperature fields inside the porous structures are determined by solving the heat conduction equation at the pore scale. The results present that the equivalent thermal conductivity of Kelvin and Weaire-Phelan structures is similar to and greater than that of the real foam structure with the same strut porosity. The thermal tortuosity of real foam structure is relatively larger and the heat conduction path becomes straighter by adopting the anisotropic design. The thermal tortuosity of the fluid channels for Kelvin, Weaire-Phelan, and real foam structures is close to one. The thermal conductivity of porous structures with heat transfer fluid increases as the thermal conductivity ratio of fluid to solid becomes larger. A small porosity of porous media leads to a larger equivalent thermal conductivity due to the dominant contribution of porous skeleton in the heat conduction process. Correlations derived from parallel and series models, as well as the Maxwell-Eucken models,provide decent predictions of effective thermal conductivity, with an average error of less than 8% in the entire range of thermal conductivity ratio.

关键词： volumetric solar receiver porous morphology direct pore-scale simulation equivalent thermal conductivity thermal tortuosity empirical correlation

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