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Therapeutic potential of TNFa inhibitors in chronic inflammatory disorders:Past and future

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Genes & Diseases 2021年第1期8卷 38-47页

作者： future Hongtao zhang Nelson Shi Zhuo Diao Youhai Chen yejia zhang Department of Pathology and Laboratory Medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Department of Orthopaedic Surgery Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Department of Physical Medicine&Rehabilitation Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Translational Musculoskeletal Research Center(TMRC) Corporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPAUSA

In the past 20 years,patients with rheumatoid arthritis(RA),Crohn’s disease(CD),and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFa *** 5 approved anti-TNFa biologics on the market and soon available biosimilars,patients have more treatment options and have benefited from understanding the biology of ***,many unmet needs remain for people living with TNFa-related diseases,namely some side effects and tolerance of current anti-TNFa biologics and resistance to ***,common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFa therapies at early onset of *** of new TNFa inhibitors focusing on TNFR1 specific inhibitors,preferably small molecules that can be delivered orally,is much needed.

关键词： Antibodies Receptors Small molecule inhibitors TNFa TNFR1

Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain

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Bone Research 2023年第2期11卷 316-327页

作者： Ke Lu Qingyun Wang Hua Jiang Jun Li Zhou Yao Yongcan Huang Jianquan Chen yejia zhang Guozhi Xiao Xueyu Hu Zhuojing Luo Liu Yang Liping Tong Di Chen Research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina Faculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina Division of Spine Surgery the First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina Department of Orthopedic Surgery Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Institute of Orthopedics Xijing Hospitalthe Fourth Military Medical UniversityXi’anChina Department of Spine Surgery Peking University Shenzhen HospitalShenzhenChina Department of Clinical Medicine School of MedicineZhejiang University City CollegeHangzhouZhejiangChina Departments of Physical Medicine&Rehabilitation Perelman School of MedicineUniversity of PennsylvaniaPAUSA School of Medicine Southern University of Science and TechnologyShenzhenChina

Spine degeneration is an aging-related disease,but its molecular mechanisms remain unknown,although elevatedβ-catenin signaling has been reported to be involved in intervertebral disc ***,we determined the role ofβ-catenin signaling in spinal degeneration and in the homeostasis of the functional spinal unit(FSU),which includes the intervertebral disc,vertebra and facet joint and is the smallest physiological motion unit of the *** showed that pain sensitivity in patients with spinal degeneration is highly correlated withβ-catenin protein *** then generated a mouse model of spinal degeneration by transgenic expression of constitutively activeβ-catenin in Col2^(+) *** found thatβ-catenin-TCF7 activated the transcription of CCL2,a known critical factor in osteoarthritic *** a lumbar spine instability model,we showed that aβ-catenin inhibitor relieved low back *** study indicates thatβ-catenin plays a critical role in maintaining spine tissue homeostasis,its abnormal upregulation leads to severe spinal degeneration,and its targeting could be an avenue to treat this condition.

关键词： degeneration smallest homeostasis

A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

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Bone Research 2015年第3期3卷 164-172页

作者： Tiao Lin Wei Tong Abhishek Chandra Shao-Yun Hsu Haoruo Jia Ji Zhu Wei-Ju Tseng Michael A Levine yejia zhang Shi-Gui Yan X Sherry Liu Dongming Sun Wise Young Ling Qin Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Department of Musculoskeletal Oncology The First Affiliated Hospital of Sun Yat-sen University Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology W.M.Keck Center for Collaborative Neuroscience Rutgers The State University of New Jersey Department of Orthopaedic Surgery School of Medicine Shihezi University Division of Endocrinology and Diabetes The Children’s Hospital of Philadelphia and Department of Pediatrics Perelman School of Medicine University of Pennsylvania Department of Physical Medicine & Rehabilitation Perelman School of Medicine University of Pennsylvania and Translational Musculoskeletal Research Center Philadelphia Veterans Affairs Medical Center Department of Orthopaedic Surgery 2nd Affiliated Hospital School of Medicine Zhejiang University

Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective *** animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical *** trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

关键词： SCI bone A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

A microwell-based impedance sensor on an insertable microneedle for real-time in vivo cytokine detection

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Microsystems & Nanoengineering 2021年第6期7卷 139-150页

作者： Naixin Song Pengfei Xie Wen Shen Hanju Oh yejia zhang Flavia Vitale Mehdi Javanmard Mark G.Allen Department of Electrical and Systems Engineering University of PennsylvaniaPhiladelphiaPAUSA Department of Electrical and Computer Engineering Rutgers UniversityPiscatawayNJUSA Department of Physical Medicine and Rehabilitation University of PennsylvaniaPhiladelphiaPAUSA Department of Orthopedic Surgery University of PennsylvaniaPhiladelphiaPAUSA Corporal Michael J.Crescenz Veterans Affairs Medical Center PhiladelphiaPAUSA Department of Bioengineering School of Engineering and Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Department of Neurology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA

Impedance-based protein detection sensors for point-of-care diagnostics require quantitative specificity,as well as rapid or real-time ***,microfabrication of these sensors can lead to the formation of factors suitable for in vivo ***,we present microfabricated needle-shaped microwell impedance sensors for rapid-sample-to-answer,label-free detection of cytokines,and other *** microneedle form factor allows sensors to be utilized in transcutaneous or transvascular sensing *** vitro,experimental characterization confirmed sensor specificity and sensitivity to multiple proteins of *** characterization demonstrated sufficient microneedle robustness for transcutaneous insertion,as well as preserved sensor function *** further utilized these sensors to carry out real-time in vivo quantification of human interleukin 8(hIL8)concentration levels in the blood of transgenic mice that endogenously express *** assess sensor functionality,hIL8 concentration levels in serum samples from the same mice were quantified by *** agreement between real-time in vivo sensor readings in blood and subsequent ELISA serum assays was observed over multiple transgenic mice expressing hIL8 concentrations from 62 pg/mL to 539 ng/mL.

关键词： needle utilized insertion

Intervertebral disc development and disease-related genetic polymorphisms

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Genes & Diseases 2016年第3期3卷 171-177页

作者： Jason W.Ashley Motomi Enomoto-Iwamoto Lachlan J.Smith Robert L.Mauck Danny Chan Joseph Lee Martin F.Heyworth Howard An yejia zhang Department of Orthopedic Surgery Perelman School of MedicineUniversity of PennsylvaniaUSA Department of Surgery Division of Orthopaedic SurgeryChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA School of Biomedical Sciences The University of Hong KongHong Kong Department of Orthopedic Surgery University of ChicagoChicagoILUSA Corporal Michael J.Crescenz Veterans Affairs Medical Center PhiladelphiaPAUSA Department of Medicine Perelman School of MedicineUniversity of PennsylvaniaUSA Department of Orthopedic Surgery Rush University Medical CenterChicagoILUSA Department of Physical Medicine&Rehabilitation Perelman School of MedicineUniversity of PennsylvaniaUSA

The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,can be traced back to the notochord in ontogenetic *** vertebrates,the notochord undergoes mucinoid changes,and had been considered vestigial until ***,observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical *** its mechanical contribution to development,the notochord is also an essential signaling center,which coordinates formation of the neural tube and *** pertinent signaling molecules,particularly TGF-b and bone morphogenetic proteins(BMPs),continue to play roles in the adult tissues and have been utilized for tissue *** factors are major determinants of who will develop IVD degeneration and related back pain,and seem to correlate better with disc degeneration and back pain than do external forces on the *** summary,the spinal column is a landmark development in *** directing the development of the IVD may also contribute to its maintenance,degeneration,and ***,structural genes as well as genes responsible for maintenance of the structure are related to IVD ***,genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context.

关键词： Back pain Development Intervertebral disc(IVD) Notochord Regeneration

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三维模型最优视角选择的粒子群优化方法

计算机辅助设计与图形学学报 2014年第12期26卷 2126-2135页

作者：张晔嘉孙正兴李晨曦宋沫飞南京大学计算机软件新技术国家重点实验室南京210093

三维模型最优视角选择是指选择符合人类主观倾向最大信息量的三维物体视角.文中在预分割模型的基础上,提出一种采用粒子群优化的三维模型最优视角选择方法.首先设计了一个对候选最优视角打分的权重函数,其中的特征选取不仅考虑了视角应... 详细信息

三维模型最优视角选择是指选择符合人类主观倾向最大信息量的三维物体视角.文中在预分割模型的基础上,提出一种采用粒子群优化的三维模型最优视角选择方法.首先设计了一个对候选最优视角打分的权重函数,其中的特征选取不仅考虑了视角应能够看到三维模型尽可能多的几何特征,同时也考虑了视角的舒适性;然后采用粒子群优化算法对模型进行分类别学习,获取最适合于该类模型的权重值,并获取权重函数中各个特征的权重配置.对比实验结果表明,该方法所选出的视角更加符合人类的主观倾向且不失几何信息量.

关键词：最优视角权重函数粒子群优化

Impacts of COVID-19 on Informal Workers and National Policies in China

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Journal of Business Administration Research 2021年第4期4卷 15-22页

作者： Kadiriya Kaimaier yejia zhang Insurance Southwestern University of Finance and EconomicsChengduSichuan611100China Accounting Tianfu college of Southwestern University of Finance and EconomicsChengduSichuan610052China

The impact of the epidemic on China's economy is *** analyzing the impact of the epidemic on the informal economy and consulting the measures taken by local governments in Sichuan to restore the stall economy in the post epidemic period,this paper classifies and refines the measures made by urban governments of different sizes of cities,puts forward relevant laws,and puts forward opinions and forecasts on the future trend of the stall economy and stall economy in the post epidemic *** to the impact of the epidemic,people's awareness of self-protection has increased,local governments have also strengthened prevention and control,and the business of vendors has been seriously *** Sichuan case shows that the government's encouragement is an important guarantee for the rapid recovery of the stall *** the same time,reasonable control is a necessary means to prevent the recurrence of the *** the future trend of the stall,it is a trend to set up permittedvending-places(shudaoqu).Selecting an address according to the nature of the commodity is the guarantee of sales.

关键词： Stall economy Post epidemic period Reasonable control Permitted-vending-place

N-doped graphene quantum dot-decorated N-TiO2/P-doped porous hollow g-C_(3)N_(4) nanotube composite photocatalysts for antibiotic photodegradation and H2 production

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 165-178页

作者： Jingshu Yuan Yao zhang Xiaoyan zhang Junjie zhang Shen’gen zhang Institute for Advanced Materials and Technology University of Science and Technology BeijingBeijing 100083China Xi’an Fanyi University Xi’an 710105China Shunde Graduate School of University of Science and Technology Beijing Foshan 528399China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao SAR 820000China

Exclusive responsiveness to ultraviolet light (~3.2 eV) and high photogenerated charge recombination rate are the two primary drawbacks of pure TiO_(2). We combined N-doped graphene quantum dots (N-GQDs), morphology regulation, and heterojunction construction strategies to synthesize N-GQD/N-doped TiO_(2)/P-doped porous hollow g-C_(3)N_(4) nanotube (PCN) composite photocatalysts (denoted as G-TPCN). The optimal sample (G-TPCN doped with 0.1wt% N-GQD, denoted as 0.1% G-TPCN) exhibits significantly enhanced photoabsorption, which is attributed to the change in bandgap caused by elemental doping (P and N), the improved light-harvesting resulting from the tube structure, and the upconversion effect of N-GQDs. In addition, the internal charge separation and transfer capability of0.1% G-TPCN are dramatically boosted, and its carrier concentration is 3.7, 2.3, and 1.9 times that of N-TiO_(2), PCN, and N-TiO_(2)/PCN(TPCN-1), respectively. This phenomenon is attributed to the formation of Z-scheme heterojunction between N-TiO_(2) and PCNs, the excellent electron conduction ability of N-GQDs, and the short transfer distance caused by the porous nanotube structure. Compared with those of N-TiO_(2), PCNs, and TPCN-1, the H2 production activity of 0.1%G-TPCN under visible light is enhanced by 12.4, 2.3, and 1.4times, respectively, and its ciprofloxacin (CIP) degradation rate is increased by 7.9, 5.7, and 2.9 times, respectively. The optimized performance benefits from excellent photoresponsiveness and improved carrier separation and migration efficiencies. Finally, the photocatalytic mechanism of 0.1% G-TPCN and five possible degradation pathways of CIP are proposed. This study clarifies the mechanism of multiple modification strategies to synergistically improve the photocatalytic performance of 0.1% G-TPCN and provides a potential strategy for rationally designing novel photocatalysts for environmental remediation and solar energy conversion.

关键词： N-doped TiO_(2) N-doped graphene quantum dots P-doped g-C_(3)N_(4) porous hollow nanotube heterojunction photocatalysis

Reversing free-electron transfer of sulfide cocatalyst for exceptional photocatalytic H_(2)evolution

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Journal of Materials Science & Technology 2024年第4期171卷 147-149页

作者： Yanfeng zhang Zhenyi zhang National Experimental Chemistry Teaching Center Hebei Key Laboratory of Inorganic Nano-materialsCollege of Chemistry and Materials ScienceHebei Normal UniversityShijiazhuang 050024China Key Laboratory of New Energy and Rare Earth Resource Utilization of State Ethnic Affairs Commission Key Laboratory of Photosensitive Materials and Devices of Liaoning ProvinceSchool of Physics and Materials EngineeringDalian Minzu UniversityDalian 116600China

Recently,Yu and co-workers deeply explore the potential impact of free electron transfer between co-catalysts and photocatalyst carriers on H_(2)evolution efficiency of active sites over MoS_(2+x).They pro-pose an electron-reversal tactics to evade the unexpected electron transfer and synchronously regulate the above transfer in a beneficial orientation for weakening hydrogen adsorption on S ***,this highlight not only discusses and summarizes the essences of electron reversal and the optimized H ad-sorption/desorption mechanism,but also emphasizes the significance of femtosecond transient absorp-tion spectroscopy(fs-TAS)and in-situ irradiated X-ray photoelectron spectroscopy(ISI-XPS)for revealing charge transfer dynamics and *** anticipate that this highlight can disseminate a new per-spective on the roles of photocatalyst carriers in improving cocatalytic H_(2)-production kinetics.

关键词： Photocatalysis Cocatalyst Electron reversal Antibonding-orbital occupancy S–H bonds