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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

Bone Research 2024年第1期12卷 199-214页

作者： Laura j.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer david j.beech Frank Timo Beil Michael Amling johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： david j.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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人血管内皮细胞特异性表达TMEM 16B

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空军医学杂志 2015年第3期31卷 151-153,157页

作者：付兆君刘红巾程军徐先荣 david j.beech 空军总医院全军临床航空医学中心北京100142 英国利兹大学生物医学系

目的探讨人血管内皮细胞上TMEM16A、TMEM16B蛋白的表达情况,并初步探讨后者的功能。方法采用实时PCR方法检测人脐带静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)中TMEM16A、TMEM16B的基因表达情况。采用Western-Blot... 详细信息

目的探讨人血管内皮细胞上TMEM16A、TMEM16B蛋白的表达情况,并初步探讨后者的功能。方法采用实时PCR方法检测人脐带静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)中TMEM16A、TMEM16B的基因表达情况。采用Western-Blot及免疫荧光染色方法进一步证实HUVECs中TMEM16B的表达情况。Fura-2am标记HUVECs后采用Flex-station检测细胞内钙变化情况。结果 HUVECs细胞表达TMEM16B,而未表达TMEM16A。Western-Blot及免疫荧光方法从蛋白水平证明HUVECs表达TMEM16B。在使用TMEM16B的si RNA干预HUVECs后,无论是有钙及无钙溶液,在50 n M血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)刺激下,钙浓度峰值均增大,而且峰值出现时间提前。结论人血管内皮细胞特异性表达TMEM16B,生理情况下TMEM16B对VEGF刺激引起的Ca2+的释放过程可能起着负向调节作用。

关键词：血管内皮细胞 TMEM16B 离子通道细胞内钙调节

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Single-atom Pt on carbon nanotubes for selective electrocatalysis

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Carbon Energy 2024年第1期6卷 63-71页

作者： Samuel S.Hardisty Xiaoqian Lin Anthony R.j.Kucernak david Zitoun Department of Chemistry Bar Ilan Institute of Nanotechnology and Advanced Materials(BINA)Bar Ilan UniversityRamat GanIsrael Department of Chemistry Molecular Science Research HubImperial College LondonLondonUK

Utilizing supported single atoms as catalysts presents an opportunity to reduce the usage of critical raw materials such as platinum,which are essential for electrochemical reactions such as hydrogen oxidation reaction(HOR).Herein,we describe the synthesis of a Pt single electrocatalyst inside single-walled carbon nanotubes(SWCNTs)via a redox *** via electron microscopy,X-ray photoelectron microscopy,and X-ray absorption spectroscopy show the single-atom nature of the *** electrochemical behavior of the sample to hydrogen and oxygen was investigated using the advanced floating electrode technique,which minimizes mass transport limitations and gives a thorough insight into the activity of the *** single-atom samples showed higher HOR activity than state-of-the-art 30%Pt/C while almost no oxygen reduction reaction activity in the proton exchange membrane fuel cell operating *** selective activity toward HOR arose as the main fingerprint of the catalyst confinement in the SWCNTs.

关键词： confinement electrocatalysis hydrogen platinum single atom catalysts

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex david j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

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World journal of Psychiatry 2024年第1期14卷 159-178页

作者： Renee j Dufault Katherine M Adler david O Carpenter Steven G Gilbert Raquel A Crider College of Graduate Health Studies A.T.Still UniversityKirksvilleMO 63501United States Department of Research Food Ingredient and Health Research InstituteNaalehuHI 96772United States Department of Health Sciences University of New HavenWest HavenCT 06516United States Institute for Health and the Environment School of Public HealthState University of New YorkAlbanyNY 12222United States Department of Research Institute of Neurotoxicology and Neurological DisordersSeattleWA 98105United States Department of Statistics Food Ingredient and Health Research InstituteNaalehuHI 96772United States

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their *** may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics *** To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food *** The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ***-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)*** test group participated in the six-week online nutritional epigenetics tutorial,while the control group did *** efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention *** intake scores were derived for both ultra-processed and whole/organic *** sample t-tests were conducted to determine any differences in mean diet scores within each *** There was a significant difference in the diet scores of the test group between the pre-and post-intervention *** parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the

关键词： Epigenomics Parenteral nutrition Autism Attention deficit/hyperactivity disorder Ultra-processed foods Heavy metals

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Error field penetration in j-TEXT tokamak based on two-fluid drift-MHD model

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Chinese Physics B 2024年第4期33卷 545-551页

作者：王文徐涛张仪 the j-TEXT team State Key Laboratory of Advanced Electromagnetic Technology International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma PhysicsSchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074China

An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant *** have studied the plasma responses using Fitzpatrick's improved two-fluid model and program *** calculated the error field penetration threshold for *** addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration ***,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the *** scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency ***,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.

关键词： plasma responses drift-MHD model error field penetration

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Enhancing diabetic retinopathy screening:Non-mydriatic fundus photography-assisted telemedicine for improved clinical management

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World journal of Diabetes 2024年第8期15卷 1820-1823页

作者： Kira j Szulborski david j Ramsey Department of Ophthalmology Tufts University School of MedicineBostonMA 02111United States Lahey Department of Surgery Division of OphthalmologyUMass Chan Medical SchoolUniversity of MassachusettsBurlingtonMA 01805United States Graduate Faculty New England College of OptometryBostonMA 02115United States

The utilization of non-mydriatic fundus photography-assisted telemedicine to screen patients with diabetes mellitus for diabetic retinopathy provides an accurate,efficient,and cost-effective method to improve early detection of *** has also been shown to correlate with increased participation of patients in other aspects of diabetes *** particular,patients who undergo teleretinal imaging are more likely to meet Comprehensive Diabetes Care Healthcare Effectiveness Data and Information Set metrics,which are linked to preservation of quality-adjusted life years and additional downstream healthcare savings.

关键词： Diabetes Diabetic retinopathy Telemedicine Tele-ophthalmology Nonmydriatic fundus photography-assisted telemedicine Vision screening Preventative health services Health policy

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Hydroxychloroquine in SARS-CoV-2 infection:Understanding the misadventure

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journal of Acute Disease 2024年第2期13卷 45-52页

作者： david Banji Otilia j F Banji Department of Pharmacology&Toxicology College of PharmacyJazan UniversitySaudi Arabia Department of Clinical Pharmacy College of PharmacyJazan UniversitySaudi Arabia

The widespread outbreak of SARS-CoV-2 was declared a public health emergency by the World Health Organization and various governments *** prompted the implementation of stringent infection control measures to curb the spread of the *** this,the medical community faced the challenge of treating the virus without specific therapies or a vaccine,leading to reliance on empirical treatment *** this context,hydroxychloroquine,an antimalarial and antirheumatic drug,gained attention as a potential treatment *** its theoretical benefits,such as inhibiting viral entry,reducing inflammation,and modulating immune responses,empirical studies yielded inconsistent *** indicated a potential for symptom relief,while others showed no significant improvement in patient *** initial enthusiasm waned as the lack of substantial evidence led to revoking its Emergency Use Authorization,and several clinical trials were prematurely *** review in question critically examines the factors contributing to the ineffectiveness of hydroxychloroquine in treating SARS-CoV-2 infection,highlighting the complexities of drug repurposing during a rapidly evolving pandemic.

关键词： SARS-CoV-2 Hydroxychloroquine Pharmacogenomics TLR signaling Cardiotoxicity

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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold jenifer Murphy-Smith Chee H.Ng david Mischoulon Gerard j.Byrne Chad A.Bousman Con Stough Michael Berk jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

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