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Investigating the Head Impact Force-Induced Evolution of Hyperphosphorylated Tau Proteins in Brain Tissue Through Mechanical Mesoscale Finite Element Simulation

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Acta Mechanica Solida Sinica 2022年第4期35卷 705-715页

作者： Ge He Lei Fan Shanghai Key Laboratory of Mechanics in Energy Enginering Shanghai Institute of Applied Mathematics and MechanicsSchool of Mechanics and Engineering ScienceShanghai UniversityShanghai 200444China Department of Mechanical Engineering Michigan State UniversityEast LansingMI 48824USA

For human heads that experienced repetitive subconcussive impacts,abnormal accumulation of hyperphosphorylated tau(p-tau)proteins was found in the postmortem brain tissue.To numerically understand the cause–effect relationship between the external force and the microscopic volume change of the p-tau protein,we created a mesoscale finite element model of the multilayer brain tissue containing microscopic voids representing the p-tau proteins.The model was applied under the loading boundary conditions obtained from a larger length scale simulation.A formerly developed internal state variable elastoplasticity model was implemented to describe the constitutive behaviors of gray and white matters,while the cerebrospinal fluid was assumed to be purely elastic.The effects of the initial sizes and distances of p-tau proteins located at four different brain regions(frontal,parietal,temporal and occipital lobes)on their volumetric evolutions were studied.It is concluded that both the initial sizes and distances of the proteins have more or less(depending on the specific brain region)influential effects on the growth or contraction rate of the p-tau protein.The p-tau proteins located within the brain tissue at the frontal and occipital lobes are more heavily affected by the frontal impact load compared with those at the parietal and temporal lobes.In summary,the modeling approach presented in this paper provides a strategy for mechanically studying the evolution of p-tau proteins in the brain tissue and gives insight into understanding the correlation between macroscopic force and microstructure change of the brain tissue.

关键词： Traumatic head injury Hyperphosphorylated tau(p-tau)protein Internal state variable Brain tissue

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Phase Ⅰ study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients

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Frontiers of Medicine 2022年第2期16卷 285-294,F0004页

作者： Lei Fan Li Wang lei Cao Huayuan Zhu Wei Xu Jianyong Li Department of Hematology Pukou CLL CenterJiangsu Province HospitalThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

Anti-CD 19 chimeric antigen receptor(CAR)T cell therapy has shown impressive efficacy in treating B-cell malignancies.A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR,a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule,for the treatment of patients with refractory diffuse large B-cell lymphoma(DLBCL).Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell(C-CAR011)treatment.The overall response rate was 20%and 50%at 4 and 12 weeks after the infusion of C-CAR011,respectively,and the disease control rate was 60%at 12 weeks after infusion.Treatment-emergent adverse events occurred in all patients.The incidence of cytokine release syndrome in all grades and grade^3 was 90%and 0,respectively,which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel.Neurotoxicity or other dose-limiting toxicides was not observed in any dose cohort of C-CAR011 therapy.Antitumor efficacy was apparent across dose cohorts.Therefore,C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL,and further large-scale clinical trials are warranted.

关键词： CAR-T cell therapy refractory diffuse large B-cell lymphoma cytokine release syndrome dose-limiting toxicity

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Seed dormancy,germination and storage behavior of Magnolia sinica,a plant species with extremely small populations of Magnoliaceae

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Plant Diversity 2022年第1期44卷 94-100页

作者： Liang Lin lei Cai Lei Fan Jun-Chao Ma Xiang-Yun Yang Xiao-Jian Hu The Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Yunnan Key Laboratory for Integrative Conservation of Plant Species with Extremely Small Populations Key Laboratory far Plant Diversity and Biogeography of East AsiaKunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina

Magnolia sinica is one of the most endangered Magnoliaceae species in China.Seed biology information concerning its long-term ex situ conservation and utilization is insufficient.This study investigated dormancy status,germination requirements and storage behavior of M.sinica.Freshly matured seeds germinated to ca.86.5%at 25/15℃but poorly at 30℃;GA3 and moist chilling promoted germination significantly at 20℃.Embryos grew at temperatures(alternating or constant)between 20℃and 25℃,but not at 5℃or 30℃.Our results indicate that M.sinica seeds possibly have non-deep simple mor-phophysiological dormancy(MPD).Seeds survived desiccation to 9.27%and 4.85%moisture content(MC)as well as a further 6-month storage at-20℃and in liquid nitrogen,including recovery in vitro as excised embryos.The established protocol ensured that at least 58%of seedlings were obtained after both cold storage and cryopreservation.These results indicate that both conventional seed banking and cryopreservation have potential as long-term ex situ conservation methods,although further optimized approaches are recommended for this critically endangered magnolia species.

关键词： Magnolia sinica Seed Dormancy Storage behavior Cryopreservation Excised embryo

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High‑Performance Silicon‑Rich Microparticle Anodes for Lithium‑Ion Batteries Enabled by Internal Stress Mitigation

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纳微快报:英文版 2023年第12期15卷 99-114页

作者： Yao Gao Lei Fan Rui Zhou Xiaoqiong Du Zengbao Jiao Biao Zhang Department of Applied Physics The Hong Kong Polytechnic UniversityKowloonHong KongPeople’s Republic of China Department of Mechanical Engineering The Hong Kong Polytechnic UniversityKowloonHong KongPeople’s Republic of China Department of Physics The Chinese University of Hong KongNew TerritoriesHong KongPeople’s Republic of China

Si is a promising anode material for Li ion batteries because of its high specific capacity,abundant reserve,and low cost.However,its rate performance and cycling stability are poor due to the severe particle pulverization during the lithiation/delithiation process.The high stress induced by the Li concentration gradient and anisotropic deformation is the main reason for the fracture of Si particles.Here we present a new stress mitigation strategy by uniformly distributing small amounts of Sn and Sb in Si micron-sized particles,which reduces the Li concentration gradient and realizes an isotropic lithiation/delithiation process.The Si8.5Sn0.5Sb microparticles(mean particle size:8.22μm)show over 6000-fold and tenfold improvements in electronic conductivity and Li diffusivity than Si particles,respectively.The discharge capacities of the Si_(8.5)Sn_(0.5)Sb microparticle anode after 100 cycles at 1.0 and 3.0 A g^(-1)are 1.62 and 1.19 Ah g^(-1),respectively,corresponding to a retention rate of 94.2%and 99.6%,respectively,relative to the capacity of the first cycle after activation.Multicomponent microparticle anodes containing Si,Sn,Sb,Ge and Ag prepared using the same method yields an ultra-low capacity decay rate of 0.02%per cycle for 1000 cycles at 1 A g^(-1),corroborating the proposed mechanism.The stress regulation mechanism enabled by the industry-compatible fabrication methods opens up enormous opportunities for low-cost and high-energy-density Li-ion batteries.

关键词： Silicon anodes Silicon microparticles Lithium-ion batteries Internal stress

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Antibacterial hydrogel with pH-responsive microcarriers of slow-release VEGF for bacterial infected wounds repair

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Journal of Materials Science & Technology 2023年第13期144卷 198-212页

作者： Xiaofei Xie Huan lei Daidi fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi’an 710069China Shaanxi R&D Center of Biomaterials and Fermentation Engineering School of Chemical EngineeringNorthwest UniversityXi’an 710069China Biotech.&Biomed.Research Institute Northwest UniversityXi’an 710069China

Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor(VEGF)that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release.The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles(AgNPs)in situ,and dynamically crosslink with the polyacrylamide,which forms a stable slow-release system with different release behavior for the VEGF and AgNPs.The hydrogel inhib-ited bacterial formation and accelerated wound healing.With the hydrogel dressing,83.3%±4.29%of the wound heals at day 7,which is 40.9%±8.5%higher than the non-treatment group in defect infected model.The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines,and the release of VEGF in the middle and late phases of wound healing in response to pH changes pro-motes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine.The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microen-vironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases.Collectively,the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.

关键词： Antibacterial pH-responsive microcarriers Slow-release Infected wound repair

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The nanohertz stochastic gravitational wave background from cosmic string loops and the abundant high redshift massive galaxies

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Science China(Physics,Mechanics & Astronomy) 2023年第12期66卷 11-19页

作者： Ziwei Wang lei lei Hao Jiao lei Feng Yi-Zhong fan Key Laboratory of Dark Matter and Space Astronomy Purple Mountain ObservatoryChinese Academy of SciencesNanjing 210023China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China Department of Physics McGill UniversityMontreal H3A 2T8Canada

Recently,pulsar timing array(PTA)experiments have provided compelling evidence for the existence of the nanohertz stochastic gravitational wave background(SGWB).In this work,we demonstrated that cosmic string loops generated from cosmic global strings offer a viable explanation for the observed nanohertz SGWB data,requiring a cosmic string tension parameter of log(Gμ)~-12 and a loop number density of log N~4.Additionally,we revisited the impact of cosmic string loops on the abundance of massive galaxies at high redshifts.However,our analysis revealed challenges in identifying a consistent parameter space that can concurrently explain both the SGWB data and observations from the James Webb Space Telescope.This indicates the necessity for either extending the existing model employed in this research or acknowledging distinct physical origins for these two phenomena.

关键词： nanohertz stochastic gravitational-wave background cosmic string loop JamesWebb Space Telescope galaxy formation

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Three‑Dimensional Numerical Study on the Metal Rotating Spray Transfer Process of High‑Current GMAW

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Chinese Journal of Mechanical Engineering 2022年第6期35卷 234-246页

作者： lei Xiao Ding fan Jiankang Huang School of Materials Science and Engineering Lanzhou Jiaotong UniversityLanzhou 730070China State Key Laboratory of Advanced Processing and Recycling of Non‑ferrous Metals Lanzhou University of TechnologyLanzhou 730050China School of Materials Science and Engineering Lanzhou University of TechnologyLanzhou 730050China

A three-dimensional numerical model based on the volume-of-fluid(VOF)method is typically preferred for studying high-current gas metal arc welding(GMAW)metal transfer mechanism and then controlling it.It is informed that the rotating spray transfer is extremely complicated,and some researchers have focused on simplified models without considering the energy conservation to make analysis manageable for the unstable metal transfer process.Using our created numerical model,the metal transfer of high-current GMAW with shielding gas of different conductivities has been studied by analyzing acting forces and fluid flows in the metal liquid column,especially for the contributions of the self-induced electromagnetic force,equivalent volume force of the capillary pressure of the surface tension(Named surface tension force in this work),static arc pressure.It is found that the unbalanced electromagnetic force greatly promotes the metal rotating motion in 500 A metal inert gas(MIG)welding with pure argon shielding gas and it pushes the metal liquid column to rotate.Considering the arc constricting effect in active shielding gas by simply changing the arc conductivity,it is found that the metal liquid column no longer rotates,it turns to swing since the unbalanced electromagnetic force is large enough to break the rotating motion.The calculated results of the metal liquid column deflected angle and rotating/swing frequency agree well with the experiment of high-speed camera observations.

关键词： Gas metal arc welding Rotating spray transfer Three-dimensional model Electromagnetic force Surface tension

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Influence of laser wavelength instability,polarization fading and phase fluctuation on local heterodyne detection wavelength scanning BOTDR

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Optoelectronics Letters 2023年第4期19卷 200-204页

作者： LI Yongqian WANG lei fan Haijun Department of Electronic and Communication Engineering North China Electric Power UniversityBaoding 071003China Hebei Key Laboratory of Power Internet of Things Technology North China Electric Power UniversityBaoding 071003China Baoding Key Laboratory of Optical Fiber Sensing and Optical Communication Technology North China Electric Power UniversityBaoding 071003China

In this paper,the influence of laser wavelength instability,polarization fading and phase fluctuation on local heterodyne detection wavelength scanning Brillouin optical time domain reflectometer(WS-BOTDR)is theoretically analyzed,and a local heterodyne detection WS-BOTDR system is built for experimental verification.The experimental results show that with the increase of sensing distance,the adverse effect of laser wavelength instability,polarization fading and phase fluctuation on local heterodyne detection WS-BOTDR is gradually aggravated,which will lead to the broadening and distortion of the wavelength power spectrum(WPS),resulting in large errors in demodulated Brillouin central wavelength(BCW)and temperature.The average temperature measurement errors at the positions of 1 km,5 km,9 km non-heating section and 9.45 km heating section are 1.76℃,3.42℃,3.89℃and 4.3℃,respectively.

关键词： polarization BOTDR local

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Photochemical Nitration of Protected Anilines by 5-Methyl-1,4-dinitroimidazole

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中国化学:英文版 2023年第13期41卷 1589-1593页

作者： Xinlong fan Yue Zhao lei Liu Huan Wang State Key Laboratory of Coordination Chemistry Chemistry and Biomedicine Innovation Center of Nanjing UniversityJiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjingJiangsu210023 China

Nitroanilines are important building blocks in pharmaceuticals,materials and dyes.Nitration methods for anilines under mild conditions are highly desired.Herein,we report a photochemical method for the nitration of anilines bearing various protecting groups by 5-methyl-1,4-dinitroimidazole as a new type of nitro source.This method is light-controlled and proceeds under mild reaction conditions with high efficiency.Fmoc-,Ts-and alkyl-protected anilines are all well nitrated with good functional group tolerance.

关键词： Aniline Nitration Photocatalysis Photochemistry Dinitroimidazole Nitroaniline Peptidomimetics Radical reactions

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Cancer metabolism and dietary interventions

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Cancer Biology & Medicine 2022年第2期19卷 163-174页

作者： Lin Qian fan Zhang Miao Yin Qunying lei Fudan University Shanghai Cancer Center&Institutes of Biomedical Sciences Cancer InstitutesKey Laboratory of Breast Cancer in ShanghaiShanghai Key Laboratory of Radiation OncologyShanghai Key Laboratory of Medical EpigeneticsShanghai Medical CollegeFudan UniversityShanghai 200030China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200030China State Key Laboratory of Medical Neurobiology Fudan UniversityShanghai 200030China Lead Contact Shanghai 200030China

Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant cells tend to modify cellular metabolism to favor specialized fermentation over the aerobic respiration usually used by most normal cells.Thus,targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice.In particular,the management of nutrient availability is becoming more attractive in cancer treatment.In this review,we discuss recent findings on tumor metabolism and potential dietary interventions based on the specific characteristics of tumor metabolism.First,we present a comprehensive overview of changes in macronutrient metabolism.Carbohydrates,amino acids,and lipids,are rewired in the cancer microenvironment individually or systematically.Second,we summarize recent progress in cancer interventions applying different types of diets and specific nutrient restrictions in pre-clinical research or clinical trials.

关键词： Cancer metabolism diet intervention carbohydrate amino acid lipid

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