Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

A"messenger zone hypothesis"based on the visual three-dimensional spatial distribution of motoneurons innervating deep limb muscles

Coordinated contraction of skeletal muscles relies on selective connections between the muscles and multiple classes of the spinal motoneuro ns.Howeve r,current research on the spatial location of the spinal motoneurons innervating differe nt muscles is limited.In this study,we investigated the spatial distribution and relative position of different motoneurons that control the deep muscles of the mouse hindlimbs,which were innervated by the obturator nerve,femoral nerve,inferior gluteal nerve,deep pe roneal nerve,and tibial nerve.Locations were visualized by combining a multiplex retrograde tracking technique compatible with three-dimensional imaging of solvent-cleared o rgans(3DISCO)and 3-D imaging technology based on lightsheet fluorescence microscopy(LSFM).Additionally,we propose the hypothesis that"messenger zones"exist as interlaced areas between the motoneuron pools that dominate the synergistic or antagonist muscle groups.We hypothesize that these interlaced neurons may participate in muscle coordination as messenger neurons.Analysis revealed the precise mutual positional relationships among the many motoneurons that innervate different deep muscles of the mouse.Not only do these findings update and supplement our knowledge regarding the overall spatial layout of spinal motoneurons that control mouse limb muscles,but they also provide insights into the mechanisms through which muscle activity is coordinated and the architecture of motor circuits.

Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration

Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,differentiation,migration,and myotube fusion in primary myoblasts and C2C12 cells.To this end,we constructed TNFαmuscle-conditional knockout(TNFα-CKO)mice and compared them with flox mice to assess the effects of TNFαknockout on skeletal muscles.Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development,enhanced regenerative capacity,and improved exercise endurance compared to flox mice,with no significant differences observed in major visceral organs or skeletal structure.Using label-free proteomic analysis,we found that TNFα-CKO altered the distribution of several muscle development-related proteins,such as Hira,Casz1,Casp7,Arhgap10,Gas1,Diaph1,Map3k20,Cfl2,and Igf2,in the nucleus and cytoplasm.Gene set enrichment analysis(GSEA)further revealed that TNFαdeficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling.These findings suggest that TNFα-CKO positively regulates muscle growth and development,possibly via these newly identified targets and pathways.

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

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 SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.

Muscle satellite cells:one of the important factors in the occurrence and development of sarcopenia

Sarcopenia,or muscle loss,has been one of the hot topics in the medical field in recent years.Due to limited attention and effective treatments for sarcopenia in the past,many patients,especially the elderly,suffered irreversible damage to their motor function caused by sarcopenia.However,recent scientific studies have found that the occurrence and development of sarcopenia are closely related to the function and quantity of muscle satellite cells.This article briefly discusses the relationship between muscle satellite cells and sarcopenia.

Effect of external and internal cues on core muscle activation during the Sahrmann five-level core stability test

BACKGROUND Pain in the back or pelvis or fear of back pain may affect the timing or cocontraction of the core muscles.In both static and dynamic movements,the Sahrmann core stability test provides an assessment of core muscle activation and a person's ability to stabilize the lumbopelvic complex.Preparatory cues and images can be used to increase the activation of these muscles.To attain optimal movement patterns,it will be necessary to determine what cueing will give the most effective results for core stability.AIM To investigate the effects of external and internal cues on core muscle activation during the Sahrmann five-level core stability test.METHODS Total 68 participants(21.83±3.47 years)were randomly allocated to an external(n=35)or internal cue group(n=33).Participants performed the Sahrmann fivelevel core stability test without a cue as baseline and the five-level stability exercises with an internal or external cue.External cue group received a pressure biofeedback unit(PBU),and the internal cue group received an audio cue.A Delsys Trigno^(TM)surface electromyography unit was used for muscle activation from the rectus abdominis,external oblique,and transverse abdominis/internal oblique muscles.RESULTS Linear mixed effects model analysis showed that cueing had a significant effect on core muscle activation(P=0.001);however,there was no significant difference between cue types(internal or external)(P=0.130).CONCLUSION Both external and internal cueing have significant effects on core muscle activation during the Sahrmann five-level core stability test and the PBU does not create higher muscle activation than internal cueing.

Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

Cerebral and muscle tissue oxygenation during exercise in healthy adults: A systematic review

Background:Near-infrared spectroscopy(NIRS)technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise.Since this technology has been growing and is now successfully used in laboratory and sports settings,this systematic review aimed to synthesize the evidence and enhance an integrative understanding of bloodflow adjustments and oxygen(O_(2))changes(i.e.,the balance between O_(2) delivery and O_(2) consumption)within the cerebral and muscle systems during exercise.Methods:A systematic review was conducted using PubMed,Embase,Scopus,and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise.This review considered manuscripts written in English and available before February 9,2023.Each step of screening involved evaluation by 2 inde-pendent authors,with disagreements resolved by a third author.The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies.Results:Twenty studies were included,of which 80%had good methodological quality,and involved 290 young or middle-aged adults.Different types of exercises were used to assess cerebral and muscle hemodynamic changes,such as cycling(n=11),treadmill(n=1),knee extension(n=5),isometric contraction of biceps brachii(n=3),and duet swim routines(n=1).The cerebral hemodynamics anal-ysis was focused on the frontal cortex(n=20),while in the muscle,the analysis involved vastus lateralis(n=18),gastrocnemius(n=3),biceps brachii(n=5),deltoid(n=1),and intercostal muscle(n=1).Overall,muscle deoxygenation increases during exercise,reaching a plateau in voluntary exhaustion,while in the brain,oxyhemoglobin concentration increases with exercise intensity,reaching a plateau or declining at the exhaustion point.Conclusion:Muscle and cerebral oxygenation respond differently to exercise,with muscle increasing O_(2) utilization and cerebral tissue increasing O_(2) delivery during exercise.However,at the exhaustion point,both muscle and cerebral oxygenation become compromised.This is characterized by a reduction in bloodflow and a decrease in O_(2) extraction in the muscle,while in the brain,oxygenation reaches a plateau or decline,potentially resulting in motor failure during exercise.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

Magnetic resonance imaging of extraocular rectus muscles abnormalities in acute acquired concomitant esotropia

AIM:To investigate the difference of medial rectus(MR)and lateral rectus(LR)between acute acquired concomitant esotropia(AACE)and the healthy controls(HCs)detected by magnetic resonance imaging(MRI).METHODS:A case-control study.Eighteen subjects with AACE and eighteen HCs were enrolled.MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner.Extraocular muscles(EOMs)were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator.To form posterior partial volumes(PPVs),the LR and MR cross-sections in the image planes 8,10,12,and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness.The data were classified according to the right eye,left eye,dominant eye,and non-dominant eye,and the differences in mean cross-sectional area,maximum cross-sectional area,and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively.RESULTS:There were no significant differences between the two groups of demographic characteristics.The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes(P=0.028).The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group(P=0.009,P=0.016).For the dominant eye,the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group(P=0.013),but not in the MR muscle(P=0.698).CONCLUSION:The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia.The LR muscle become larger to compensate for the enhanced convergence in the AACE.

Exploring Passive Exoskeleton-Induced Changes in Lumbar Muscle Activity

Purpose: The purpose of this study was to evaluate the effect of using a passive exoskeleton on lumbar muscle activity during lifting movements, and to determine whether muscle activity remains altered after exoskeleton removal. This study sought to identify the potential risks and benefits associated with the use of passive exoskeletons for the prevention and treatment of low back pain. Methods: Eighteen healthy adult participants lifted a 10 kg suitcase while wearing a passive exoskeleton. Muscle activity and postures were measured during lifting and before, during, and after exoskeleton use. This study examined whether the reduced muscle activity observed during exoskeleton use persisted after exoskeleton removal. Muscle activity was assessed using electromyography and postures were recorded using reflective markers and a camera. Results: The study found that Lumbar muscle activity decreased significantly (approximately 40%) during exoskeleton use compared to that without exoskeleton use. Importantly, lumbar muscle activity remained low after exoskeleton removal, at levels similar to those observed during exoskeleton use. This suggests that individuals adapted to the exoskeleton support and maintained altered muscle control, even without the exoskeleton. Conclusion: This study demonstrates that passive exoskeletons significantly reduce lumbar muscle activity during lifting tasks, and that this altered muscle control persists after exoskeleton removal. These findings contribute to the understanding of the risks and benefits of passive exoskeletons, potentially aiding their development and informing their use in the prevention and treatment of low back pain.

Rational design of carbon skeleton interfaces for highly reversible sodium metal battery anodes

Sodium metal batteries(SMBs)have attracted increasing attention over time due to their abundance of sodium resources and low cost.However,the widespread application of SMBs as a viable technology remains a great challenge,such as uneven metallic deposition and dendrite formation during cycling.Carbon skeletons as sodiophilic hosts can alleviate the dendrite formation during the plating/stripping.For the carbon skeleton,how to rationalize the design sodiophilic interfaces between the sodium metal and carbon species remains key to developing desirable Na anodes.Herein,we fabricated four kinds of structural features for carbon skeletons using conventional calcination and flash Joule heating.The roles of conductivity,defects,oxygen content,and the distribution of graphite for the deposition of metallic sodium were discussed in detail.Based on interface engineering,the J1600 electrode,which has abundant Na-C species on its surface,showed the highest sodiophilic.There are uniform and rich F-Na species distributed in the inner solid electrolyte interface layer.This study investigated the different Na-deposition behavior in carbon hosts with distinct graphitic arrangements to pave the way for designing and optimizing advanced electrode materials.

Vacancy defect MoSeTe embedded in N and F co-doped carbon skeleton for high performance sodium ion batteries and hybrid capacitors

Sodium-ion batteries(SIBs) and hybrid capacitors(SIHCs) have garnered significant attention in energy storage due to their inherent advantages,including high energy density,cost-effectiveness,and enhanced safety.However,developing high-performance anode materials to improve sodium storage performa nce still remains a major challenge.Here,a facile one-pot method has been developed to fabricate a hybrid of MoSeTe nanosheets implanted within the N,F co-doped honeycomb carbon skeleton(MoSeTe/N,F@C).Experimental results demonstrate that the incorporation of large-sized Te atoms into MoSeTe nanosheets enlarges the layer spacing and creates abundant anion vacancies,which effectively facilitate the insertion/extraction of Na^(+) and provide numerous ion adsorption sites for rapid surface capacitive behavior.Additionally,the heteroatoms N,F co-doped honeycomb carbon skeleton with a highly conductive network can restrain the volume expansion and boost reaction kinetics within the electrode.As anticipated,the MoSeTe/N,F@C anode exhibits high reversible capacities along with exceptional cycle stability.When coupled with Na_(3)V_(2)(PO_(4))_(3)@C(NVPF@C) to form SIB full cells,the anode delivers a reversible specific capacity of 126 mA h g^(-1) after 100 cycles at 0.1 A g^(-1).Furthermore,when combined with AC to form SIHC full cells,the anode demonstrates excellent cycling stability with a reversible specific capacity of50 mA h g^(-1) keeping over 3700 cycles at 1.0 A g^(-1).In situ XRD,ex situ TEM characterization,and theoretical calculations(DFT) further confirm the reversibility of sodium storage in MoSeTe/N,F@C anode materials during electrochemical reactions,highlighting their potential for widespread practical application.This work provides new insights into the promising utilization of advanced transition metal dichalcogenides as anode materials for Na^(+)-based energy storage devices.

Clinical Study of Shentong Zhuyu Decoction Combined with Massage Therapy in the Treatment of Exertional Chronic Lumbar Muscle Strain

[Objectives]To explore the effects of Shentong Zhuyu decoction combined with massage therapy in the treatment of exertional chronic lumbar muscle strain.[Methods]Sixty-four cases of exertional chronic lumbar muscle strain were randomly divided into two groups(32 cases each group).The patients in the control group only took celecoxib capsules,and those in the treatment group additionally took Shentong Zhuyu decoction combined with massage therapy.TCM syndrome score,lumbar function,hemorrheology index and clinical effect were compared between the two groups before and after treatment.[Results]After treatment,the TCM syndrome scores of lumbar distension/dull pain,tingling-like lumbago,adverse lateral turn,body weight loss,dark purple tongue,slow or astringent pulse,and Oswestry disability index(ODI)score in the treatment group were lower than those in the control group,and the levels of plasma viscosity,red blood cell aggregation index,platelet aggregation rate(PAG)and fibrinogen(Fib)were lower than those in the control group,showing statistical significance(P<0.05).The overall clinical effect distribution of the treatment group was better than that of the control group,and the difference was statistically significant(P<0.05).[Conclusions]Shentong Zhuyu decoction combined with massage therapy can effectively relieve the symptoms of patients with lumbago and improve the lumbar mobility function and hemorrheology,with obvious therapeutic effects in the treatment of exertional chronic lumbar muscle strain.

Transcriptomic and epigenomic landscapes of muscle growth during the postnatal period of broilers

Background Broilers stand out as one of the fastest-growing livestock globally,making a substantial contribution to animal meat production.However,the molecular and epigenetic mechanisms underlying the rapid growth and development of broiler chickens are still unclear.This study aims to explore muscle development patterns and regulatory networks during the postnatal rapid growth phase of fast-growing broilers.We measured the growth performance of Cornish(CC)and White Plymouth Rock(RR)over a 42-d period.Pectoral muscle samples from both CC and RR were randomly collected at day 21 after hatching(D21)and D42 for RNA-seq and ATAC-seq library construction.Results The consistent increase in body weight and pectoral muscle weight across both breeds was observed as they matured,with CC outpacing RR in terms of weight at each stage of development.Differential expression analysis identified 398 and 1,129 genes in the two dimensions of breeds and ages,respectively.A total of 75,149 ATAC-seq peaks were annotated in promoter,exon,intron and intergenic regions,with a higher number of peaks in the promoter and intronic regions.The age-biased genes and breed-biased genes of RNA-seq were combined with the ATAC-seq data for subsequent analysis.The results spotlighted the upregulation of ACTC1 and FDPS at D21,which were primarily associated with muscle structure development by gene cluster enrichment.Additionally,a noteworthy upregulation of MUSTN1,FOS and TGFB3 was spotted in broiler chickens at D42,which were involved in cell differentiation and muscle regeneration after injury,suggesting a regulatory role of muscle growth and repair.Conclusions This work provided a regulatory network of postnatal broiler chickens and revealed ACTC1 and MUSTN1 as the key responsible for muscle development and regeneration.Our findings highlight that rapid growth in broiler chickens triggers ongoing muscle damage and subsequent regeneration.These findings provide a foundation for future research to investigate the functional aspects of muscle development.

SWIR FluorescenceImaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.

Temporal and spatial regulation of biomimetic vascularization in 3D-printed skeletal muscles

In the intricate skeletal muscle tissue,the symbiotic relationship between myotubes and their supporting vasculature is pivotal in delivering essential oxygen and nutrients.This study explored the complex interplay between skeletal muscle and endothelial cells in the vascularization ofmuscle tissue.By harnessing the capabilities of three-dimensional(3D)bioprinting and modeling,we developed a novel approach involving the co-construction of endothelial and muscle cells,followed by their subsequent differentiation.Our findings highlight the importance of the interaction dynamics between these two cell types.Notably,introducing endothelial cells during the advanced phases of muscle differentiation enhanced myotube assembly.Moreover,it stimulated the development of the vascular network,paving the way for the early stages of vascularized skeletal muscle development.The methodology proposed in this study indicates the potential for constructing large-scale,physiologically aligned skeletal muscle.Additionally,it highlights the need for exploring the delicate equilibrium and mutual interactions between muscle and endothelial cells.Based on the multicell-type interaction model,we can predict promising pathways for constructing even more intricate tissues or organs.

In vivo measurement of NADH fluorescence lifetime in skeletal muscle via -ber-coupled time-correlated single photon counting

Nicotinamide adenine dinucleotide(NADH)is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis,the tricarboxylic acid cycle,and oxidative phosphorylation(OXPHOS).NADH is autofluorescent,and itsfluorescence lifetime can be used to infer metabolic dynamics in living cells.Fiber-coupled time-correlated single photon counting(TCSPC)equipped with an implantable needle probe can be used to measure NADH lifetime in vivo,enabling investigation of changing metabolic demand during muscle contraction or tissue regeneration.This study illustrates a proof of concept for point-based,minimally-invasive NADHfluorescence lifetime measurement in vivo.Volumetric muscle loss(VML)injuries were created in the left tibialis anterior(TA)muscle of male Sprague Dawley rats.NADH lifetime measurements were collected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscles,which was subsequently-t to a biexponential decay model to yield a metric of NADH utilization(cytoplasmic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscle compared to muscle at rest,suggesting higher levels of free NADH in contracting and recovering muscle,indicating increased rates of glycolysis.In injured muscle,this ratio was higher than uninjured muscle overall but decreased over time,which is consistent with current knowledge of inflammatory response to injury,suggesting tissue regeneration has occurred.These data suggest that-ber-coupled TCSPC has the potential to measure changes in NADH binding in vivo in a minimally invasive manner that requires further investigation.

Biology of Hippo signaling pathway:Skeletal muscle development and beyond

Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving meat production and muscle deposition and developing new molecular breeding technologies for livestock and poultry,which will be helpful for the development of animal molecular breeding.

Acupotomy ameliorates knee osteoarthritis-related collagen deposition and fibrosis in rabbit skeletal muscle through the TGF-β/Smad pathway

Objective:To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods: Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion: Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.