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Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.king Department of Neurology and Center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SO

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

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Prey decline leads to diet shift in the largest population of Indo-Pacific humpback dolphins?

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Integrative Zoology 2021年第4期16卷 548-574页

作者： Wenzhi LIN Leszek KARCZMARSKI Ruilian ZHOU Yaqian MO Lang GUO sam king Fung YIU Xi NING Tak-Cheung WAI Yuping WU School of Marine Sciences Zhuhai Key Laboratory of Marine Bioresources and EnvironmentGuangdong Provincial Key Laboratory of Marine Resources and Coastal EngineeringSouthern Marine Science and Engineering Guangdong LaboratorySun Yat-Sen UniversityZhuhaiChina Division of Cetacean Ecology Cetacea Research InstituteLantauHong Kong SARChina Marine Mammal and Marine Bioacoustics Laboratory Institute of Deep-sea Science and EngineeringChinese Academy of SciencesSanyaChina School of Biological Sciences University of Hong KongPokfulamHong Kong SARChina State Key Laboratory of Marine Pollution City University of Hong KongHong Kong SARChina

The Pearl River Delta(PRD)region on the southeast coast of China has long been known as a highly productive fishing ground.Since the late 1980s,fishing pressure in the PRD has been intense,which warrants concerns of potential fishery-related impacts on the food resources and foraging ecology of apex marine predators in this region,such as the Indo-Pacific humpback dolphin(Sousa chinensis).In this study,we examined 54 stomachs with food remains,collected from beached carcasses of humpback dolphins recovered during fifteen years between 2003 and 2017.The 6043 identified prey items represent 62 teleost taxa,primarily small estuarine fish,but also larger reef fish.The dolphins appear to be opportunistic foragers,hunting across the water-column,with preference for shoaling and meaty fishes(e.g.Collichthys lucidus IRI%=38.6%,Johnius belangerii IRI%=23.1%,Mugil cephalus IRI%=14.0%).Our findings suggest a dietary shift in recent years,from primarily demersal(as previously reported)to greater intake of neritic and pelagic fish.Dolphin foraging group size has decreased in recent years,which corresponds with declining size and numbers of prey items retrieved from dolphin stomachs.We suggest that these are indicators of declining food resources.Faced with a shortage of preferred prey,humpback dolphins may have broadened their dietary spectrum to maintain their daily energy intake,while their foraging group size decreased in response to the altered tradeoff between the costs and benefits of group foraging.

关键词： feeding ecology Pearl River Delta prey decline Sousa chinensis stomach content analysis

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Resilience conferred by APOE-R136S:a defense bestowed by nature to combat Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 831-832页

作者： Bin Xiao Joshua Kuruvilla Eng-king Tan Department of Neurology National Neuroscience InstituteSingaporeSingapore Neuroscience Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore Neuroscience and Behavioural Disorders Program Duke-NUS Medical SchoolSingaporeSingapore

In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune responses.Nelson et al.and Chen et al.have provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.

关键词： protective al. Alzheimer

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Population Dynamics in an Advective Environment

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Communications on Applied Mathematics and Computation 2024年第1期6卷 399-430页

作者： king-Yeung Lam Ray Lee Yuan Lou Department of Mathematics The Ohio State UniversityColumbusOH43210USA School of Mathematical Sciences CMA-Shanghai and MOE-LSCShanghai Jiao Tong UniversityShanghai200240China

We consider a one-dimensional reaction-diffusion equation describing single-and two-species population dynamics in an advective environment,based on the modeling frameworks proposed by Lutscher et al.in 2006.We analyze the effect of rate of loss of individuals at both the upstream and downstream boundaries.In the single-species case,we prove the existence of the critical domain size and provide explicit formulas in terms of model parameters.We further derive qualitative properties of the critical domain size and show that,in some cases,the critical domain size is either strictly decreasing over all diffusion rates,or monotonically increasing after first decreasing to a minimum.We also consider competition between species differing only in their diffusion rates.For two species having large diffusion rates,we give a sufficient condition to determine whether the faster or slower diffuser wins the competition.We also briefly discuss applications of these results to competition in species whose spatial niche is affected by shifting isotherms caused by climate change.

关键词： Reaction-diffusion-advection Critical domain size Competition Climate change

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Naturally Crosslinked Biocompatible Carbonaceous Liquid Metal Aqueous Ink Printing Wearable Electronics for Multi-Sensing and Energy Harvesting

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Nano-Micro Letters 2024年第8期16卷 148-168页

作者： king Yan Chung Bingang Xu Di Tan Qingjun Yang Zihua Li Hong Fu Nanotechnology Center School of Fashion and TextilesThe Hong Kong Polytechnic UniversityHong Kong 999077People’s Republic of China Department of Mathematics and Information Technology The Education University of Hong KongHong KongPeople’s Republic of China

Achieving flexible electronics with comfort and durability comparable to traditional textiles is one of the ultimate pursuits of smart wearables.Ink printing is desirable for e-textile development using a simple and inexpensive process.However,fabricating high-performance atop textiles with good dispersity,stability,biocompatibility,and wearability for high-resolution,large-scale manufacturing,and practical applications has remained challenging.Here,waterbased multi-walled carbon nanotubes(MWCNTs)-decorated liquid metal(LM)inks are proposed with carbonaceous gallium–indium micro-nanostructure.With the assistance of biopolymers,the sodium alginate-encapsulated LM droplets contain high carboxyl groups which non-covalently crosslink with silk sericin-mediated MWCNTs.E-textile can be prepared subsequently via printing technique and natural waterproof triboelectric coating,enabling good flexibility,hydrophilicity,breathability,wearability,biocompatibility,conductivity,stability,and excellent versatility,without any artificial chemicals.The obtained e-textile can be used in various applications with designable patterns and circuits.Multi-sensing applications of recognizing complex human motions,breathing,phonation,and pressure distribution are demonstrated with repeatable and reliable signals.Self-powered and energy-harvesting capabilities are also presented by driving electronic devices and lighting LEDs.As proof of concept,this work provides new opportunities in a scalable and sustainable way to develop novel wearable electronics and smart clothing for future commercial applications.

关键词： Biocompatible Conductive ink Biopolymer E-textile Carbonaceous liquid metal

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Contemplative neuroaesthetics and architecture:A sensorimotor exploration

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Frontiers of Architectural Research 2024年第1期13卷 97-111页

作者： Zakaria Djebbara Juliet king Amir Ebadi Yoshio Nakamura Julio Bermudez Department of Architecture DesignMediaand TechnologyAalborg UniversityAalborgDenmark Biopsychology und Neuroergonomy Technical University BerlinBerlinGermany Art Therapy Department The George Washington UniversityWashington DCUnited States Department of Neurology Indiana University School of MedicineIndianapolisUnited States Dellustration Washington DCUnited States Pain Research Center Division of Pain MedicineDepartment of AnesthesiologyUniversity of Utah School of MedicineUtahUnited States School of Architecture and Planning The Catholic University of AmericaWashington DCUnited States

This paper takes initial steps towards developing a theoretical framework of contemplative neuroaesthetics through sensorimotor dynamics.We first argue that this new area has been largely omitted from the contemporary research agenda in neuroaesthetics and thus remains a domain of untapped potential.We seek to define this domain to foster a clear and focused investigation of the capacity of the arts and architecture to induce phenomenological states of a contemplative kind.By proposing a sensorimotor account of the experience of architecture,we operationalize how being attuned to architecture can lead to contemplative states.In contrasting the externally-induced methods with internally-induced methods for eliciting a contemplative state of mind,we argue that architecture may spontaneously and effortlessly lead to such states as certain built features naturally resonate with our sensorimotor system.We suggest that becoming sensible of the resonance and attunement process between internal and external states is what creates an occasion for an externallyinduced contemplative state.Finally,we review neuroscientific studies of architecture,elaborate on the brain regions involved in such aesthetic contemplative responses,provide architectural examples,and point at the contributions that this new area of inquiry may have in fields such as the evidence-based design movement in architecture.

关键词： Neuropheno menology Neuroaesthetics Contemplative states Architectural experience Well-being

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Rumen microbial degradation of bromoform from red seaweed(Asparagopsis taxiformis)and the impact on rumen fermentation and methanogenic archaea

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Journal of Animal Science and Biotechnology 2024年第1期15卷 412-426页

作者： Pedro Romero Alejandro Belanche Elisabeth Jiménez Rafael Hueso Eva Ramos-Morales Joan king Salwen Ermias Kebreab David R.Yáñez-Ruiz Estacion Experimental del Zaidin Consejo Superior de Investigaciones Cientificas(CSIC)Profesor Albareda 1Granada 18008Spain Department of Animal Production and Food Sciences University of ZaragozaMiguel Servet 177Saragossa 50013Spain Blue Ocean Barns Inc. Redwood CityCAUSA Department of Animal Science University of CaliforniaDavisCA 95618USA

Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degradation process of CHBr3 from A taxiformis in the rumen and whether this process is diet-dependent.An in vitro batch culture system was used according to a 2×2 factorial design,assessing two A taxiformis inclusion rates[0(CTL)and 2%DM diet(AT)]and two diets[high-concentrate(HC)and high-forage diet(HF)].Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0,0.5,1,3,6,8,12,16,24,48 and 72 h to assess the pattern of degradation of CHBr_(3) into dibromomethane(CH_(2)Br_(2))and fermentation parameters.Additionally,an in vitro experiment with pure cultures of seven methanogens strains(Methanobrevibacter smithii,Methanobrevibacter ruminantium,Methanosphaera stadtmanae,Methanosarcina barkeri,Methanobrevibacter millerae,Methanorhermobacter wolfei and Methanobacterium mobile)was conducted to test the effects of increasing concentrations of CHBr3(0.4,2,10and 50μmol/L).Results The addition of AT significantly decreased CH_(4) production(P=0.002)and the acetate:propionate ratio(P=0.003)during a 72-h incubation.The concentrations of CHBr_(3) showed a rapid decrease with nearly 90%degraded within the first 3 h of incubation.On the contrary,CH_(2)Br_(2) concentration quickly increased during the first 6 h and then gradually decreased towards the end of the incubation.Neither CHBr_(3) degradation nor CH_(2)Br_(2) synthesis were affected by the type of diet used as substrate,suggesting that the fermentation rate is not a driving factor involved in CHBr_(3)degradation.The in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of M.smithii,M.ruminantium,M.stadtmanae,M.barkeri,M.millerae,M.wolfei,and M.mobile.Conclusions The present work demonstrated that CHBr_(3) from A.taxiformis is quickly degraded to CH_(2)Br_(2)in the rumen and that the ferm

关键词： Bromoform metabolism Dibromomethane metabolism Methane mitigation Methanogens Rumen microbiota Seaweed

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Evening Breeze

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The World of Chinese 2024年第1期 79-82页

作者：程惠子 Dylan Levi king

It is usually around Xiaoman, which is the eighth term in the traditional solar calendar, coming around the middle of May, that the rains assault the Lingnan region. Rain in that season is often overwhelming and violent.

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Manual Order Picking Route Optimization in Distribution Warehouse of Chain Furniture Retail Enterprise

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American Journal of Operations Research 2024年第3期14卷 105-136页

作者： Yongzhen Zeng Junkun Wang Ching-Kuei Kao king-Zoo Tang Department of Logistics Management Fujian University of Technology Fuzhou China Key Laboratory of LNG Industry Chain Fujian University of Technology Fuzhou China Department of Information Management National Chung Cheng University Chiayi China

Due to the effects of the COVID-19 pandemic and the rise of online shopping, the offline sales of IKEA Fuzhou have been declining since 2020. Because the cost of distribution warehouse is a major expense for offline chain furniture retailers, and the picking process is a key activity in distribution warehouse operations. To reduce the cost of distribution warehouse and alleviate the survival pressure of the offline chain furniture retailers, this paper focuses on optimizing the picking route of the IKEA Fuzhou distribution warehouse. It starts by creating a two-dimensional coordinate system for the storage location of the distribution warehouse using the traditional S-type picking strategy to calculate the distance and time of the sorting route. Then, the problem of optimizing the picking route is then transformed into the travelling salesman problem (TSP), and picking route optimization model is developed using a genetic algorithm to analyze the sorting efficiency and picking route optimization. Results show that the order-picking route using the genetic algorithm strategy is significantly better than the traditional S-type picking strategy, which can improve overall sorting efficiency and operations, reduce costs, and increase efficiency. Thus, this establishes an implementation process for the order-picking path based on genetic algorithm optimization to improve overall sorting efficiency and operations, reduce costs, increase efficiency, and alleviate the survival pressure of pandemic-affected enterprises.

关键词： S-Shaped Picking Strategy Picking Route Traveling Salesman Problem Genetic Algorithm

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Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo Ryan Potter Jacob P.Rose Joanna Bons Christina D.king Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly individuals.The molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by osteocytes.We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material properties.We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses PLR.The control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)bone.This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests.The effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

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