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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Developing a new agenda for increased food and climate security

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Frontiers of Agricultural Science and Engineering 2024年第1期11卷 35-54页

作者： william J.DAVIES Lancaster Environment Centre Lancaster UniversityLancasterLA14YQUK

In many countries, political and environmental pressures are currently combining to generate a perfect storm of circumstances that is reducing food availability, increasing food costs and thereby reducing the availability of food to many. The UK is currently considering new national food and land management policies, and attention is also being given to legislation to address diet-related health issues. Many now argue for a revolution in UK farming practices to reduce their impact on the natural environment. The UK is not alone in facing these and other challenges. Both the contribution of agriculture to greenhouse gas(GHG) emissions and the effects of climate change on food production are issues receiving worldwide attention.Regenerative agricultural practices can result in greater C capture, reduced GHG emissions, enhanced soil quality and enhanced biodiversity. However, it is questioned if such farming systems will be productive enough to feed a growing population with the food required for social and health benefits. To fully exploit the impact of new plant science in farmer fields, it is imperative to effectively link science to farming practices and conduct a broader conversation around the food revolution with social scientists and with the general public.

关键词： Climate resilience food security human health planetary health regenerative agriculture

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Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

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World Journal of Orthopedics 2024年第5期15卷 444-456页

作者： Frederick william Wyatt Oday Al-Dadah Translational and Clinical Research Institute Faculty of Medical SciencesNewcastle UniversityNewcastle Upon Tyne NE24HHUnited Kingdom Department of Trauma and Orthopaedic Surgery South Tyneside District HospitalSouth Shields NE340PLUnited Kingdom

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients wi

关键词： Arthroplasty Osteotomy Medial compartment Osteoarthritis Knee alignment Patient reported outcome measures

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Anatomic location of the first dorsal extensor compartment for surgical De-Quervain’s tenosynovitis release:A cadaveric study

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World Journal of Orthopedics 2024年第4期15卷 379-385页

作者： Aditya Thandoni william Nicholas Yetter Steven Michael Regal Department of Orthopaedic Surgery Allegheny Health NetworkPittsburghPA 15212United States

BACKGROUND De-Quervain’s tenosynovitis is a disorder arising from the compression and irritation of the first dorsal extensor compartment of the wrist.Patients who fail conservative treatment modalities are candidates for surgical release.However,risks with surgery include damage to the superficial radial nerve and an incomplete release due to inadequate dissection.Currently,there is a paucity of literature demonstrating the exact anatomic location of the first dorsal extensor compartment in reference to surface anatomy.Thus,this cadaveric study was performed to determine the exact location of the first extensor compartment and to devise a reliable surgical incision to prevent complications.AIM To describe the location of the first dorsal compartment in relation to bony surface landmarks to create replicable surgical incisions.METHODS Six cadaveric forearms,including four left and two right forearm specimens were dissected.Dissections were performed by a single fellowship trained upper extremity orthopaedic surgeon.Distance of the first dorsal compartment from landmarks such as Lister’s tubercle,the wrist crease,and the radial styloid were calculated.Other variables studied included the presence of the superficial radial nerve overlying the first dorsal compartment,additional compartment subsheaths,number of abductor pollicis longus(APL)tendon slips,and the presence of a pseudo-retinaculum.RESULTS Distance from the radial most aspect of the wrist crease to the extensor retinaculum was 5.14 mm±0.80 mm.The distance from Lister’s tubercle to the distal aspect of the extensor retinaculum was 13.37 mm±2.94 mm.Lister’s tubercle to the start of the first dorsal compartment was 18.43 mm±2.01 mm.The radial styloid to the initial aspect of the extensor retinaculum measured 2.98 mm±0.99 mm.The retinaculum length longitudinally on average was 26.82 mm±3.34 mm.Four cadaveric forearms had separate extensor pollicis brevis compartments.The average number of APL tendon slips was three.A pseudo-retinaculum was present in four cad

关键词： De-Quervain’s tenosynovitis First extensor compartment Cadaveric study Superficial radial nerve Radial styloid Lister’s tubercle

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Human-induced changes in recent sedimentation rates in Bohai Bay, China： Implications for coastal development

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Science China Earth Sciences 2018年第10期61卷 1510-1522页

作者： Fu WANG Lizhu TIAN Xingyu JIANG william marshall Hong WANG Tianjin Center China Geological Survey (CGS) Tianjin 300170 China Key Laboratory of Muddy Coast Geo-Environment China Geological Survey Tianjin 300170 China Plymouth University Plymouth Devon PL4 8AA United Kingdom

In many countries, coastal planners strive to balance the demands between civil, commercial strategy and environmental conversation interests for future development, particularly given the sea level rise in the 21 st century. Achieving a sustainable balance is often a dilemma, especially in low-lying coastal areas where dams in inland river basin are trapping significant amounts of fluvial sediments. We recently investigated the shore of Bohai Bay in northern China where there has been a severe increase in sea level following a program of large-scale coastal reclamation and infrastructure development over the last five decades. To investigate this trend, we obtained sediment cores from near-shore in Bohai Bay, which were dated by ^(137)Cs and ^(210)Pb radionuclides to determine the sedimentation rates for the last 50 years. The average sedimentation rates of Bohai Bay exceeded 10 mm yr^(-1) before 1963, which was much higher than the rate of local sea-level rise. However, our results showed an overall decreasing sedimentation rate after 1963, which was not able to compensate for the increasing relative sea-level rise in that period. In addition, our results revealed that erosion occurred after the 1980 s in the shallow sea area of Bohai Bay. We suggest that this situation places the Bohai Bay coast at a greater risk of inundation and erosion within the next few decades than previously thought, especially in the large new reclamation area. This study may be a case study for many other shallow sea areas of the muddy coast if the sea level continues to rise rapidly and the sediment delivered by rivers continues to decrease.

关键词：沉积率海湾沿海开发中国相对海平面 137Cs 放射性核种

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william Morris,Establishing the Foundation for the Advancement of TCM in the US

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Chinese Medicine and Culture 2024年第1期7卷 29-40页

作者： Ioannis Solos Charles Buck william Morris Saint George Clinic and Research Institute Scottsdale 85251the United States of America Northern College of Acupuncture Micklegate YO16LJthe United Kingdom AOMA Graduate School of Integrative Medicine Austin 78745the United States of America

The interview was conducted on March 2nd, 2023 by Ioannis Solos and Charles Buck. william Morris has sustained practice since 1980. He has served on the California, Texas and Massachusetts Professional Associations, as well as the National Association. He has tendered 20 years of service to the field through academic medicine, earning a master’s degree in medical education to assist in developing Chinese medical doctoral programs and institutional review boards. He earned an OM.D. in 1988, a DAOM in 2002, and a Ph.D. focused on pulse diagnosis as clinical epistemology in 2009. He has published five books, including TCM Case Studies Dermatology, Li Shi-zhen Pulse Studies: An Illustrated Guide, Neoclassical Pulse Diagnosis, Cycles in Medical Astrology, and Transformation: Treating Trauma with Acupuncture and Herbs.

关键词： Acupuncture sustained diagnosis

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Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

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International Journal of Extreme Manufacturing 2024年第1期6卷 353-374页

作者： Amit Bandyopadhyay Indranath Mitra Sushant Ciliveri Jose D Avila william Dernell Stuart B Goodman Susmita Bose W.M.Keck Biomedical Materials Research Laboratory School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America Veterinary Clinical Sciences College of Veterinary MedicineWashington State UniversityPullmanWA 99164United States of America Department of Orthopedic Surgery Stanford University Medical CenterRedwood CityCA 94063United States of America

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. Mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

关键词： Ti6Al4V load-bearing implants additive manufacturing 3D printing antibacterial performance

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Flame Structure of Methane and Kerosene Combustion with a Compact Concave Flame-Holder using the LES-pdf Method

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Journal of Thermal Science 2024年第1期33卷 222-234页

作者： WANG Fang WANG Yunfan WEI Guanyi LIU Denghuan JIN Jie JONES P.william School of Energy and Power Engineering Beihang UniversityBeijingBeijing 100191China Department of Mechanical Engineering Imperial College LondonLondon SW72AZUK

Compact flame-holders for afterburners are an increasing requirement for modern aero engines.However,flame-holder design is non-trivial since high inlet temperatures,velocities,and elaborate structures induce complex turbulence,combustion,and spray coupling in modern afterburners.In this work,the LES-pdf and stochastic fields-Lagrangian particle spray methods are used to investigate methane and aviation kerosene combustion structures formed by new-type concave flame-holders.The flow pattern,combustion mode,and flame structure of gaseous and liquid fuel around a concave flame-holder are analyzed,discussed,and compared with experimental results.Results reveal that the flame stability of a concave flame-holder is better than that of the non-concave one.Furthermore,when using liquid fuel,the concave flame-holder forms a stable and compact flame.These results suggest concave flame-holders are a promising design for compact afterburners.

关键词： concave structure flame-holder LES-pdf spray combustion flame structure AECSC

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A cross-sectional study of breastfed infants referred for tongue tie assessment and frenotomy in one Canadian health region

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儿科学研究(英文) 2024年第1期8卷 53-60页

作者： Lee Tiffany A. Bishop Jessica Drover Anne Midodzi william K. Twells Laurie K. School of Pharmacy Memorial University of Newfoundland (MUN) St. John’s Canada Faculty of Medicine Memorial University of Newfoundland (MUN) St. John’s Canada

Importance: Tongue tie (TT) is a condition that can cause infant feeding difficulties due to restricted tongue movement. When TT presents as a significant barrier to breastfeeding, a frenotomy may be recommended. Universally accepted diagnostic criteria for TT are lacking and wide prevalence estimates are reported. New referral processes and a Frenotomy Assessment Tool were implemented in one Canadian health region to connect breastfeeding dyads with a provider for TT evaluation and frenotomy.Objective: To determine the proportion of babies with TT as well as the frequency of frenotomy.Methods: This cross-sectional study included infants who initiated breastfeeding at birth and were referred for TT evaluation over a 14-month period. Data were collected retrospectively by chart review and analyzed using SPSS. Factors associated with frenotomy were examined using logistic regression.Results: Two hundred and forty-one babies were referred. Ninety-two percent (n = 222) were diagnosed with TT and 66.0% (n = 159) underwent frenotomy. In the multivariate model, nipple pain/trauma, inability to latch, inability to elevate tongue, and dimpling of tongue on extension were associated with frenotomy (P < 0.05). Most referrals in our region resulted in a diagnosis of TT; however, the number of referrals was lower than expected, and of these two-thirds underwent frenotomy.Interpretation: TT is a relatively common finding among breastfed infants. Future research should examine whether a simplified assessment tool containing the four items associated with frenotomy in our multivariate model can identify breastfed infants with TT who require frenotomy.

关键词： Breastfeeding Nutrition Community health services Pediatrics

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Isolating higher yielding and more stable rice genotypes in stress environments: fine-tuning a selection method using production and resilience score indices

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Frontiers of Agricultural Science and Engineering 2024年第1期11卷 169-185页

作者： Arnauld THIRY william J.DAVIES Ian C.DODD Lancaster Environment Centre Lancaster UniversityLancasterLancashire LA14YWUK

In Asia, the rice crop sustains millions of people. However, growing demand for this crop needs to be met while simultaneously reducing its water consumption to cope with the effects of climate change. Lowland cropping systems are the most common and productive but have particularly high water requirements. High-yielding rice genotypes adapted to drier environments(such as rainfed or aerobic rice ecosystems) are needed to increase the water use efficiency of cropping. Identifying these genotypes requires fast and more accurate selection methods. It is hypothesized that applying a new quantitative selection method(the score index selection method), can usefully compare rice yield responses over different years and stress intensities to select genotypes more rapidly and efficiently. Applying the score index to previously published rice yield data for 39 genotypes grown in no-stress and two stress environments, identified three genotypes(ARB 8, IR55419-04 and ARB 7) with higher and stable yield under moderate to severe stress conditions. These genotypes are postulated to be better adapted to stress environment such as upland and aerobic environments. Importantly, the score index selection method offers improved precision than the conventional breeding selection method in identifying genotypes that are well-suited to a range of stress levels within the target environment.

关键词： Aerobic rice breeding selection drought resilience production capacity index resilience capacity index stress score index upland

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