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.

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.

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.

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.

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.

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.

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.

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.

Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK‑PGC‑1α signaling pathway and alters the muscle fiber composition of sheep

Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1αmRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type I myofibers with RA treatment was significantly increased,and type IIx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1αto inhibit PGC-1αexpression and found that si-PGC-1αsignificantly abrogated RA-induced the formation of type I myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type IIx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1αexpression,and increased type I myofibers.In order to prove that the effect of RA on the level of PGC-1αis caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1αand MyHC I levels.Conclusion VA promoted PGC-1αexpression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.

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.

Low skeletal muscle mass and high visceral adiposity are associated with recurrence of acute cholecystitis after conservative management:A propensity score-matched cohort study

Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.

Catalpa bignonioides extract improves exercise performance through regulation of growth and metabolism in skeletal muscles

Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.

Automated body composition analysis system based on chest CT for evaluating content of muscle and adipose

Objective To establish a body composition analysis system based on chest CT,and to observe its value for evaluating content of chest muscle and adipose.Methods T7—T8 layer CT images of 108 pneumonia patients were collected(segmented dataset),and chest CT data of 984 patients were screened from the COVID 19-CT dataset(10 cases were randomly selected as whole test dataset,the remaining 974 cases were selected as layer selection dataset).T7—T8 layer was classified based on convolutional neural network(CNN)derived networks,including ResNet,ResNeXt,MobileNet,ShuffleNet,DenseNet,EfficientNet and ConvNeXt,then the accuracy,precision,recall and specificity were used to evaluate the performance of layer selection dataset.The skeletal muscle(SM),subcutaneous adipose tissue(SAT),intermuscular adipose tissue(IMAT)and visceral adipose tissue(VAT)were segmented using classical fully CNN(FCN)derived network,including FCN,SegNet,UNet,Attention UNet,UNET++,nnUNet,UNeXt and CMUNeXt,then Dice similarity coefficient(DSC),intersection over union(IoU)and 95 Hausdorff distance(HD)were used to evaluate the performance of segmented dataset.The automatic body composition analysis system was constructed based on optimal layer selection network and segmentation network,the mean absolute error(MAE),root mean squared error(RMSE)and standard deviation(SD)of MAE were used to evaluate the performance of automatic system for testing the whole test dataset.Results The accuracy,precision,recall and specificity of DenseNet network for automatically classifying T7—T8 layer from chest CT images was 95.06%,84.83%,92.27%and 95.78%,respectively,which were all higher than those of the other layer selection networks.In segmentation of SM,SAT,IMAT and overall,DSC and IoU of UNet++network were all higher,while 95HD of UNet++network were all lower than those of the other segmentation networks.Using DenseNet as the layer selection network and UNet++as the segmentation network,MAE of the automatic body composition analysis system for predicting SM,SAT,IMAT,VAT and MAE was 27.09,6.95,6.65 and 3.35 cm 2,respectively.Conclusion The body composition analysis system based on chest CT could be used to assess content of chest muscle and adipose.Among them,the UNet++network had better segmentation performance in adipose tissue than SM.

Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

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.

Metabolic dysfunction-associated fatty liver disease and low muscle strength: A comment

The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.