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MAP4K inhibition as a potential therapy for amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第8期19卷 1639-1640页

作者： Shuaipeng Ma Chun-Li Zhang Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA

Amyotrophic lateral sclerosis(ALS)is a rare neurological disease,featuring gradual loss of muscle controls due to degeneration of motor ***,there is currently no cure for *** available therapies only offer a limited e... 详细信息

关键词： degeneration sclerosis MAP4

Apoer2/Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz Department of Molecular Genetics and Center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA Department of Neuroscience Department of Neurology university of texas southwestern Medical Center at Dallas DallasTXUSA

Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric *** this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

Impact of COVID-19-related lifestyle changes on diabetic macular edema

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 97-106页

作者： Bryce P.Johnson Yu-Guang He Zachary M.Robertson Angeline Wang Rafael L.Ufret-Vincenty Department of Ophthalmology UT Southwestern Medical CenterDallasTexas 75390-9057USA

AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office ***:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DME seen on 3 separate visits between January 2019 and July *** 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was March 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).Main outcome measures included visual acuity,body mass index(BMI),blood pressure(BP),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DME treatment(s)received at each *** facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT ***:There was no change of BMI,systolic BP,and diastolic BP between any of the time ***1c showed a very small increase from period 1(7.6%)to period 2(7.8%,P=0.015)and decreased back to 7.6%at period 3(P=0.12).Macular thickness decreased for 100%of macular *** central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(P=0.0045).After analysis of multiple variables including HbA1c,BMI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in ***:DME doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant *** identifying a mechanism behind our findings is beyond the scope of this study,potential explanat

关键词： COVID-19 diabetic macular edema diabetic retinopathy optical coherence tomography

Integrated analysis of plasma rotation effect on HL-3 hybrid scenario

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Chinese Physics B 2024年第8期33卷 329-336页

作者：薛淼郑国尧薛雷李佳鲜王硕杜海龙朱毅仁周月 southwestern Institute of Physics Chengdu 610000China

The hybrid scenario,which has good confinement and moderate MHD instabilities,is a proposed operation scenario for international thermonuclear experimental reactor(ITER).In this work,the effect of plasma rotation on the HL-3 hybrid scenario is analyzed with the integrated modeling framework *** results show that toroidal rotation has no obvious effect on confinement with a high line averaged density of n_(bar)~(7)×10^(19)m^(-3).In this case,the ion temperature only changes from 4.7 keV to 4.4 keV with the rotation decreasing from 10^(5) rad/s to 10^(3) rad/s,which means that the turbulent heat transport is not *** in the scenarios characterized by lower densities,such as n_(bar)~4×10^(19)m^(-3),turbulent transport becomes dominant in determining heat *** ion temperature rises from 3.8 keV to 6.1 keV in the core as the rotation velocity increases from 10^(3) rad/s to 10^(5) rad/*** the ion temperature rising,the rotation velocity does not obviously affect electron temperature or ***,it is noteworthy that the variation in rotation velocity does not significantly affect the global confinement of plasma in scenarios with low density or with high density.

关键词： HL-3 hybrid scenario toroidal rotation integrated modeling

Gyrokinetic simulation of magnetic-island-induced electric potential vortex mode

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Plasma Science and Technology 2024年第1期26卷 34-41页

作者：王丰李继全曲洪鹏彭晓东 southwestern Institute of Physics Chengdu 610041People’s Republic of China

Ion temperature gradient(ITG)-driven turbulence with embedded static magnetic islands is simulated by utilizing a gyrokinetic theory-based global turbulence transport code(GKNET)in this *** from the traditional equilibrium circular magnetic-surface average(EMSA)method,an advanced algorithm that calculates the perturbed magnetic-surface average(PMSA)of the electric potential has been developed to precisely deal with the zonal flow component in a non-circular magnetic surface perturbed by magnetic *** show that the electric potential vortex structure inside islands induced by the magnetic islands is usually of odd parity when using the EMSA *** is found that the odd symmetry vortex can transfer into an even one after a steep zonal flow gradient,*** flow shear has been built in the vicinity of the magnetic islands by adopting the PMSA *** phase of the potential vortex in the poloidal cross section is coupled with the zonal flow *** an electric potential vortex mode may be of essential importance in wide topics,such as the turbulence spreading across magnetic islands,neoclassical tearing mode physics,and also the interaction dynamics between the micro-turbulence and MHD activities.

关键词： magnetic islands electric vortex ITG perturbed magnetic flux surface average

Gyro-Landau-fluid simulations of impurity effects on ion temperature gradient driven turbulence transport

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Plasma Science and Technology 2024年第1期26卷 8-15页

作者：刘逸飞李继全 southwestern Institute of Physics Chengdu 610041People’s Republic of China

The effects of impurities on ion temperature gradient(ITG)driven turbulence transport in tokamak core plasmas are investigated numerically via global simulations of microturbulence with carbon impurities and adiabatic *** simulations use an extended fluid code(ExFC)based on a four-field gyro-Landau-fluid(GLF)*** multispecies form of the normalized GLF equations is presented,which guarantees the self-consistent evolution of both bulk ions and *** parametric profiles of the cyclone base case,well-benchmarked ExFC is employed to perform simulations focusing on different impurity density *** a fixed temperature profile,it is found that the turbulent heat diffusivity of bulk ions in a quasi-steady state is usually lower than that without impurities,which is contrary to the linear and quasilinear *** evolutions of the temperature gradient and heat diffusivity exhibit a fast relaxation process,indicating that the destabilization of the outwardly peaked impurity profile is a transient state ***,the impurity effects from different profiles can obviously influence the nonlinear critical temperature gradient,which is likely to be dominated by linear *** results suggest that the improvement in plasma confinement could be attributed to the impurities,most likely through adjusting both heat diffusivity and the critical temperature gradient.

关键词： gyro-Landau-fluid simulation impurity effects ion temperature gradient mode turbulence transport

The research progress of an E//B neutral particle analyzer

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Plasma Science and Technology 2024年第3期26卷 10-16页

作者：马龙屈玉凡罗圆谢德豪汪彦熹王硕曲国峰任培培罗小兵刘星泉韩纪锋 Roy WADA 林炜平臧临阁朱敬军 Key Laboratory of Radiation Physics and Technology of the Ministry of Education Institute of Nuclear Science and TechnologySichuan UniversityChengdu 610064People's Republic of China southwestern Institute of Physics Chengdu 610064People's Republic of China Cyclotron Institute Texas A&M UniversityCollege StationTexas 77843United States of America

An E//B neutral particle analyzer(NPA)has been designed and is under development at Sichuan university and southwestern Institute of *** main purpose of the E//B NPA is to measure the distribution function of fast ions in the HL-2A/3 *** E//B NPA contains three main units,*** stripping unit,the analyzing unit and the detection unit.A gas stripping chamber was adopted as the stripping *** results of the simulations and beam tests for the stripping chamber are *** electric and magnetic fields provided by a NdFeB permanent magnet and two parallel electric plates were designed and constructed for the analyzing *** calibration of the magnetic and electric fields was performed using a 50 kV electron cyclotron resonance ion source(ECRIS)*** detection unit consists of 32lutetium-yttrium oxyorthosilicate(LYSO)detector modules arranged in two *** response functions ofα,hydrogen ions(H^(+),H_(2)^(+)and H_(3)^(+))andγfor a detector module were measured with^(241)Am,^(137)Cs and^(152)Eu sources together with the 50 kV ECRIS *** overall results indicate that the designed E//B NPA device is capable of measuring the intensity of neutral hydrogen and deuteron atoms with energy higher than 20 keV.

关键词： E//B neutral particle analyzer gas stripping lutetium-yttrium oxyorthosilicate electron cyclotron resonance ion source platform

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James David Hudson Kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Comparison of thermal shock resistance capabilities of the rotary swaged pure tungsten,potassium-doped tungsten,and W-La2O3 alloys

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Tungsten 2024年第4期6卷 759-766页

作者： Tao Yang Hao Wang Fan Feng Xiang Liu Xue-Yu Gong You-Yun Lian Jian-Bao Wang School of Nuclear Science and Technology University of South China southwestern Institute of Physics

Tungsten-based materials are one of the most important candidates for the plasma facing materials（PFMs） of future fusion reactors,and it is necessary to study the properties of tungsten-based materials under the service conditions of fusion devices to ensure the long-term steady-state operation of future fusion *** this paper,different tungsten-based materials made by the same rotary swaging process are selected to simulate the transient thermal loads on the PFMs of a fusion reactor using an electron beam,and thermal load experiments are carried out by changing the power density of a loading pulse and the pulse *** is found that different tungsten-based materials made by the same process have large differences in thermal shock resistance,and the doped tungsten materials（W-K and W-La2O3） are significantly better than the pure tungsten materials with the increase in thermal shock power density and the number of cycles,especially the W-K materials,which have excellent performance.

关键词： Electron beam Rotary swaging Thermal shock Tungsten materials