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 ...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.展开更多
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 hav...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.展开更多
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...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.展开更多
Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizi...Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.展开更多
BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during or...BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.展开更多
Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.Howev...Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.展开更多
Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal...Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.展开更多
The growth and development of skeletal muscle also determine the meat production of yak, ultimately affecting the economic benefits. Hence, improving growth performance is a top priority in the yak industry. Skeletal ...The growth and development of skeletal muscle also determine the meat production of yak, ultimately affecting the economic benefits. Hence, improving growth performance is a top priority in the yak industry. Skeletal muscle development is a complex process involving the regulation of several genes, including microRNAs(miRNAs). However,the transcription of miRNAs in yak skeletal muscle during prenatal to postnatal stages is unknown. We used small RNA sequencing(small RNA-Seq) to determine the global miRNAs of longissimus dorsi muscle from yak(the samples were collected from three fetuses and three adults). Totally 264 differently expressed miRNAs(|log2(fold change)|>1and P-value≤0.05) were detected between the two groups. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that differently expressed miRNAs-targeted genes participated in pathways associated with muscle development, such as MAPK, PI3K-Akt, and Hippo signaling pathways, etc. MiR-652, which was up-regulated in the fetal group, was transfected into C2C12 myoblasts to examine its role. miR-652 promoted(P≤0.05)proliferation and differentiation, but inhibited(P≤0.001) apoptosis at early period. Furthermore, miR-652 reduced(P≤0.001) the proportion of C2C12 myoblasts in the G1 phase while increasing(P≤0.01) the proportion of cells in the S and G2 phases. Dual-luciferase reporter assays indicated that ISL1 served as a target of miR-652. In general, these findings expand our understanding of yak skeletal muscle miRNAs, and suggested that miR-652 probably regulated myogenesis by regulating ISL1.展开更多
Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by diet...Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by dietary selenium(Se)level.Here,we developed the dietary oxidative stress(DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation.Results Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation,which is accompanied by mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and protein and lipid metabolism disorders.Supplementation with Se(0.3,0.6 or 0.9 mg Se/kg)in form of hydroxy selenomethionine(OH-SeMet)linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins,which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle,and the mitigation of mitochondrial dysfunction and ER stress.What’s more,selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle.However,several parameters such as the activity of GSH-Px and T-SOD,the protein abundance of JNK2,CLPP,SELENOS and SELENOF did not show dose-dependent changes.Notably,several key selenoproteins such as MSRB1,SELENOW,SELENOM,SELENON and SELENOS play the unique roles during this protection.Conclusions Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress,recover protein and lipid biosynthesis,thus alleviate skeletal muscle growth retardation.Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.展开更多
Skeletal muscle regeneration is a complex process where various cell types and cytokines are involved.Single-cell RNA-sequencing (scRNA-seq) provides the opportunity to deconvolute heterogeneous tissue into individual...Skeletal muscle regeneration is a complex process where various cell types and cytokines are involved.Single-cell RNA-sequencing (scRNA-seq) provides the opportunity to deconvolute heterogeneous tissue into individual cells based on their transcriptomic profiles.Recent scRNA-seq studies on mouse muscle regeneration have provided insights to understand the transcriptional dynamics that underpin muscle regeneration.However,a database to investigate gene expression profiling during skeletal muscle regeneration at the single-cell level is lacking.Here,we collected over 105 000 cells at 7 key regenerative time-points and non-injured muscles and developed a database,the Singlecell Skeletal Muscle Regeneration Database (SCSMRD).SCSMRD allows users to search the dynamic expression profiles of genes of interest across different cell types during the skeletal muscle regeneration process.It also provides a network to show the activity of regulons in different cell types at different time points.Pesudotime analysis showed the state changes trajectory of muscle stem cells (MuSCs) during skeletal muscle regeneration.This database is freely available at https://scsmrd.fengs-lab.com.展开更多
This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship betw...This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship between protein synthesis and degradation rates,which determine muscle mass,the involvement of the satellite cells for continual muscle regeneration,and changes in myofiber calcium homeostasis linked to contractile dysfunction.We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment.Overall,HF causes multiple impairments related to autophagy,anabolic-catabolic signaling,satellite cell proliferation,and calcium homeostasis,which together promote fiber atrophy,contractile dysfunction,and impaired regeneration.Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF,the effects of satellite cell dynamics remain poorly explored.展开更多
Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor fo...Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor for developing T2D.Thus,the identifi cation of compounds that enhance the ability of SkM to take up glucose is a promising strategy for preventing T2D.Our previous work showed that kaempferol,a fl avonol present in many foods,improves insulin sensitivity in obese mice,however,the mechanism underlying this beneficial action remains unclear.Here,we show that kaempferol directly stimulates glucose uptake and prevents lipotoxicity-impaired glucose uptake in primary human SkM.Kaempferol stimulates Akt phosphorylation in a time-dependent manner in human SkM cells.The effect of kaempferol on glucose uptake was blunted by inhibition of glucose transporter 4,phosphoinositide 3-kinase(PI3K),or AMPK.In addition,kaempferol induced AMPK phosphorylation,and inhibition of AMPK prevented kaempferol-stimulated Akt phosphorylation.In vivo,kaempferol administration induced rapid glucose disposal accompanied with increased Akt and AMPK phosphorylation in SkM tissue of the mice.Taken together,these fi ndings suggest that kaempferol stimulates glucose uptake in SkM via an AMPK/Akt dependent mechanism,and it may be a viable therapeutic agent for insulin resistance.展开更多
A series of Ferrierite(FER)zeolites were prepared via hydrothermal synthesis in the absence of organic templates with the aid of sodium-type FER zeolite(NaFER)or NaFER suspensions(NaFERsus)acquired by NaOH solution tr...A series of Ferrierite(FER)zeolites were prepared via hydrothermal synthesis in the absence of organic templates with the aid of sodium-type FER zeolite(NaFER)or NaFER suspensions(NaFERsus)acquired by NaOH solution treatment as seeds.The differences in the structures and acid sites of the obtained FER zeolite catalysts arising from the choice of seed were investigated,and the catalytic performances of the obtained FER zeolites were evaluated in the skeletal isomerization of n-butene.The results indicate that the samples synthesized using NaFERsus feature more Br?nsted acid sites(BAS)in the 10-membered-ring(10-MR)at the expense of strong acid and Lewis acid sites(LAS),compared with samples derived from NaFER.Therefore,the FER samples synthesized using NaFERsus outperformed the NaFER counterparts as the BAS in 10-MR and LAS were the main active sites,while BAS in 8-MR and LAS were responsible for side reactions,such as polymerization,cracking,and carbon deposition in n-butene isomerization.The optimized FER catalyst was continuously used for 720 h at 350℃ at 0.1 MPa under an n-butene space velocity of 2.0 h^(-1),during which the n-butene conversion remained at>40%,and the isobutylene yield was>37.5%.展开更多
Objective:The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old.Methods:A total of 6669 healthy C...Objective:The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old.Methods:A total of 6669 healthy Chinese men and 4494 healthy Chinese women aged 30-92 years old were assessed for their skeletal muscle mass and visceral fat area.Results:The results showed age-dependent decreases in the total skeletal muscle mass indexes in both men and women aged 40-92 years old as well as age-dependent increases in the visceral fat area in men aged 30-92 years old and in women aged 30-80 years old.Multivariate regression models showed that the total skeletal muscle mass index was positively associated with the body mass index and negatively associated with the age and visceral fat area in both sexes.Conclusion:The loss of skeletal muscle mass becomes obvious at approximately 50 years of age,and the visceral fat area commences to increase at approximately 40 years of age in this Chinese population.展开更多
Mutations in SFRP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal fragility.The WNT signaling pathway plays important roles in determining skeletal architecture and SFRP4 is a secreted Frizzled...Mutations in SFRP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal fragility.The WNT signaling pathway plays important roles in determining skeletal architecture and SFRP4 is a secreted Frizzled decoy receptor that inhibits WNT signaling.Seven cohorts of male and female Sfrp4 gene knockout mice,examined through 2 years of age,had a normal lifespan but showed cortical and trabecular bone phenotypes.Mimicking human Erlenmeyer flask deformities,bone cross-sectional areas were elevated 2-fold in the distal femur and proximal tibia but only 30%in femur and tibia shafts.Reduced cortical bone thickness was observed in the vertebral body,midshaft femur and distal tibia.Elevated trabecular bone mass and numbers were observed in the vertebral body,distal femur metaphysis and proximal tibia metaphysis.Midshaft femurs retained extensive trabecular bone through 2 years of age.Vertebral bodies had increased compressive strength,but femur shafts had reduced bending strength.Trabecular,but not cortical,bone parameters in heterozygous Sfrp4mice were modestly affected.Ovariectomy resulted in similar declines in both cortical and trabecular bone mass in wild-type and Sfrp4 KO mice.SFRP4 is critical for metaphyseal bone modeling involved in determining bone width.Sfrp4 KO mice show similar skeletal architecture and bone fragility deficits observed in patients with Pyle’s disease with SFRP4 mutations.展开更多
Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underl...Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.展开更多
BACKGROUND Patient satisfaction with facial appearance at the end of orthodontic camouflage treatment is very important, especially for skeletal malocclusion. This case report highlights the importance of the treatmen...BACKGROUND Patient satisfaction with facial appearance at the end of orthodontic camouflage treatment is very important, especially for skeletal malocclusion. This case report highlights the importance of the treatment plan for a patient initially treated with four-premolar-extraction camouflage, despite indications for orthognathic surgery.CASE SUMMARY A 23-year-old male sought treatment complaining about his unsatisfactory facial appearance. His maxillary first premolars and mandibular second premolars had been extracted, and a fixed appliance had been used to retract his anterior teeth for two years without improvement. He had a convex profile, a gummy smile, lip incompetence, inadequate maxillary incisor inclination, and almost a class I molar relationship. Cephalometric analysis showed severe skeletal class Ⅱ malocclusion(A point-nasion-B point = 11.5°) with a retrognathic mandible(sella-nasion-B point = 75.9°), a protruded maxilla(sella-nasion-A point = 87.4°), and vertical maxillary excess(upper incisor to palatal plane = 33.2 mm). The excessive lingual inclination of the maxillary incisors(upper incisor to nasion-A point line =-5.5°)was due to previous treatment attempts to compensate for the skeletal class Ⅱ malocclusion. The patient was successfully retreated with decompensating orthodontic treatment combined with orthognathic surgery. The maxillary incisors were repositioned and proclined in the alveolar bone, the overjet was increased, and a space was created for orthognathic surgery, including maxillary impaction, anterior maxillary back-setting, and bilateral sagittal split ramus osteotomy to correct his skeletal anteroposterior discrepancy. Gingival display was reduced, and lip competence was restored. In addition, the results remained stable after 2 years. The patient was satisfied with his new profile as well as with the functional malocclusion at the end of treatment.CONCLUSION This case report provides orthodontists a good example of how to treat an adult with severe skeletal class Ⅱ malocclusion with vertical maxillary excess after an unsatisfactory orthodontic camouflage treatment. Orthodontic and orthognathic treatment can significantly correct a patient’s facial appearance.展开更多
BACKGROUND Diffuse idiopathic skeletal hyperostosis(DISH)is a disorder characterised by the calcification and ossification of ligaments and entheses.It is a frequent occurrence in elderly males,but rarely encountered ...BACKGROUND Diffuse idiopathic skeletal hyperostosis(DISH)is a disorder characterised by the calcification and ossification of ligaments and entheses.It is a frequent occurrence in elderly males,but rarely encountered in younger individuals.CASE SUMMARY A 24-year-old male was admitted to the hospital due to low back pain accompanied with numbness in both lower limbs for 10 d.Upon clinical examination and imaging tests,the patient was diagnosed with DISH with Scheuermann disease and thoracic spinal stenosis.Before the operation and medical treatment,the patient had hypoesthesia of the skin below the xiphoid process.Afterward,a standard laminectomy was conducted using ultrasonic bone curette and internal fixation was applied.Subsequently,the patient was given corticosteroids,neurotrophic drugs,hyperbaric oxygen and electric stimulation.As a result of the treatment,the patient’s sensory level decreased to the navel level and there was no major change in the muscle strength of the lower limbs.During follow-up,the patient’s skin sensation has returned to normal.CONCLUSION This case is a rare instance of DISH co-existing with Scheuermann’s disease in a young adult.This provides a valuable reference point for spine surgeons,as DISH is more commonly observed in middle-aged and elder adults.展开更多
Timely identification and treatment of medical conditions could facilitate faster recovery and better health.Existing systems address this issue using custom-built sensors,which are invasive and difficult to generaliz...Timely identification and treatment of medical conditions could facilitate faster recovery and better health.Existing systems address this issue using custom-built sensors,which are invasive and difficult to generalize.A low-complexity scalable process is proposed to detect and identify medical conditions from 2D skeletal movements on video feed data.Minimal set of features relevant to distinguish medical conditions:AMF,PVF and GDF are derived from skeletal data on sampled frames across the entire action.The AMF(angular motion features)are derived to capture the angular motion of limbs during a specific action.The relative position of joints is represented by PVF(positional variation features).GDF(global displacement features)identifies the direction of overall skeletal movement.The discriminative capability of these features is illustrated by their variance across time for different actions.The classification of medical conditions is approached in two stages.In the first stage,a low-complexity binary LSTM classifier is trained to distinguish visual medical conditions from general human actions.As part of stage 2,a multi-class LSTM classifier is trained to identify the exact medical condition from a given set of visually interpretable medical conditions.The proposed features are extracted from the 2D skeletal data of NTU RGB+D and then used to train the binary and multi-class LSTM classifiers.The binary and multi-class classifiers observed average F1 scores of 77%and 73%,respectively,while the overall system produced an average F1 score of 69%and a weighted average F1 score of 80%.The multi-class classifier is found to utilize 10 to 100 times fewer parameters than existing 2D CNN-based models while producing similar levels of accuracy.展开更多
BACKGROUND Mesenchymal stromal cells(MSCs)are multipotent cell populations obtained from fetal and adult tissues.They share some characteristics with limb bud mesodermal cells such as differentiation potential into os...BACKGROUND Mesenchymal stromal cells(MSCs)are multipotent cell populations obtained from fetal and adult tissues.They share some characteristics with limb bud mesodermal cells such as differentiation potential into osteogenic,chondrogenic,and tenogenic lineages and an embryonic mesodermal origin.Although MSCs differentiate into skeletal-related lineages in vitro,they have not been shown to selforganize into complex skeletal structures or connective tissues,as in the limb.In this work,we demonstrate that the expression of molecular markers to commit MSCs to skeletal lineages is not sufficient to generate skeletal elements in vivo.AIM To evaluate the potential of MSCs to differentiate into skeletal lineages and generate complex skeletal structures using the recombinant limb(RL)system.METHODS We used the experimental system of RLs from dissociated-reaggregated human placenta(PL)and umbilical cord blood(UCB)MSCs.After being harvested and reaggregated in a pellet,cultured cells were introduced into an ectodermal cover obtained from an early chicken limb bud.Next,this filled ectoderm was grafted into the back of a donor chick embryo.Under these conditions,the cells received and responded to the ectoderm’s embryonic signals in a spatiotemporal manner to differentiate and pattern into skeletal elements.Their response to differentiation and morphogenetic signals was evaluated by quantitative poly-merase chain reaction,histology,immunofluorescence,scanning electron microscopy,and in situ hybridization.RESULTS We found that human PL-MSCs and UCB-MSCs constituting the RLs expressed chondrogenic,osteogenic,and tenogenic molecular markers while differentially committing into limb lineages but could not generate complex structures in vivo.MSCs-RL from PL or UCB were committed early to chondrogenic lineage.Nevertheless,the UCB-RL osteogenic commitment was favored,although preferentially to a tenogenic cell fate.These findings suggest that the commitment of MSCs to differentiate into skeletal lineages differs according to the source and is independent of their capacity to generate skeletal elements or connective tissue in vivo.Our results suggest that the failure to form skeletal structures may be due to the intrinsic characteristics of MSCs.Thus,it is necessary to thoroughly evaluate the biological aspects of MSCs and how they respond to morphogenetic signals in an in vivo context.CONCLUSION PL-MSCs and UCB-MSCs express molecular markers of differentiation into skeletal lineages,but they are not sufficient to generate complex skeletal structures in vivo.展开更多
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘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.
基金This study was approved by the Ethics Committee of Kyushu Rosai Hospital Moji Medical Center(No:04-01,date of approval:June 2,2022).This study was conducted in compliance with the principles of the Declaration of Helsinki.
文摘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.
基金supported by Korea Environment Industry&Technology Institute through Project to make multi-ministerial national biological research resources more advanced Project,funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘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.
文摘Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.
基金Natural Science Foundation of Jiangsu Province, No. SBK2021021787the Major Project of the Health Commission ofJiangsu Province, No. ZD2022025and the Key Project of the Nanjing Health Commission, No. ZKX20048.
文摘BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.
基金the Foundation of State Key Laboratory of Component-based Chinese Medicine,No.CBCM2023107National Natural Science Foundation of China,No.81901853Specially Funded Scientific Research Project of the Fourth Affiliated Hospital of Harbin Medical University,No.HYDSYTB202126.
文摘Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.
基金supported in part by funding from the Veterans Administration (1IOBX001262, 1I01 BX004269)South Carolina State Spinal Cord Injury Research Fund (SCIRF-2015P-01, SCIRF-2015P-04, SCIRF-2015-I-01, SCIRF#2016 I-03, and SCIRF#2018 I-01)(to AH)+1 种基金supported in part by funding from the National Institutes of Health (1R21NS118393-01)(to AH)a Research Career Scientist award (#IK6BX005964) from the Department of veterans Affairs。
文摘Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.
基金supported by the Agricultural Science and Technology Innovation Program, CAAS (25-LZIHPS-01)the China Agriculture Research System of MOF and MARA (CARS-37)the National Natural Science Foundation of China (32102500)。
文摘The growth and development of skeletal muscle also determine the meat production of yak, ultimately affecting the economic benefits. Hence, improving growth performance is a top priority in the yak industry. Skeletal muscle development is a complex process involving the regulation of several genes, including microRNAs(miRNAs). However,the transcription of miRNAs in yak skeletal muscle during prenatal to postnatal stages is unknown. We used small RNA sequencing(small RNA-Seq) to determine the global miRNAs of longissimus dorsi muscle from yak(the samples were collected from three fetuses and three adults). Totally 264 differently expressed miRNAs(|log2(fold change)|>1and P-value≤0.05) were detected between the two groups. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that differently expressed miRNAs-targeted genes participated in pathways associated with muscle development, such as MAPK, PI3K-Akt, and Hippo signaling pathways, etc. MiR-652, which was up-regulated in the fetal group, was transfected into C2C12 myoblasts to examine its role. miR-652 promoted(P≤0.05)proliferation and differentiation, but inhibited(P≤0.001) apoptosis at early period. Furthermore, miR-652 reduced(P≤0.001) the proportion of C2C12 myoblasts in the G1 phase while increasing(P≤0.01) the proportion of cells in the S and G2 phases. Dual-luciferase reporter assays indicated that ISL1 served as a target of miR-652. In general, these findings expand our understanding of yak skeletal muscle miRNAs, and suggested that miR-652 probably regulated myogenesis by regulating ISL1.
基金supported by the National Natural Science Foundation of China(No.31772643 and 31272468)the Special Research Funding for Discipline Construction in Sichuan Agricultural University(No.03570126)Adisseo France(18SES533).
文摘Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by dietary selenium(Se)level.Here,we developed the dietary oxidative stress(DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation.Results Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation,which is accompanied by mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and protein and lipid metabolism disorders.Supplementation with Se(0.3,0.6 or 0.9 mg Se/kg)in form of hydroxy selenomethionine(OH-SeMet)linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins,which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle,and the mitigation of mitochondrial dysfunction and ER stress.What’s more,selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle.However,several parameters such as the activity of GSH-Px and T-SOD,the protein abundance of JNK2,CLPP,SELENOS and SELENOF did not show dose-dependent changes.Notably,several key selenoproteins such as MSRB1,SELENOW,SELENOM,SELENON and SELENOS play the unique roles during this protection.Conclusions Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress,recover protein and lipid biosynthesis,thus alleviate skeletal muscle growth retardation.Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.
基金supported by the National Natural Science Foundation of China(31972539 and 32102513)the Science,Technology,and Innovation Commission of Shenzhen Municipality,China(JCYJ20180306173644635)+2 种基金the Fundamental Research Funds for the Central Universities,China(G2020KY05109)the Natural Science Basic Research Program of Shaanxi Province,China(2022JQ-644)the Basic Research Programs of Taicang,China(TC2021JC14)。
文摘Skeletal muscle regeneration is a complex process where various cell types and cytokines are involved.Single-cell RNA-sequencing (scRNA-seq) provides the opportunity to deconvolute heterogeneous tissue into individual cells based on their transcriptomic profiles.Recent scRNA-seq studies on mouse muscle regeneration have provided insights to understand the transcriptional dynamics that underpin muscle regeneration.However,a database to investigate gene expression profiling during skeletal muscle regeneration at the single-cell level is lacking.Here,we collected over 105 000 cells at 7 key regenerative time-points and non-injured muscles and developed a database,the Singlecell Skeletal Muscle Regeneration Database (SCSMRD).SCSMRD allows users to search the dynamic expression profiles of genes of interest across different cell types during the skeletal muscle regeneration process.It also provides a network to show the activity of regulons in different cell types at different time points.Pesudotime analysis showed the state changes trajectory of muscle stem cells (MuSCs) during skeletal muscle regeneration.This database is freely available at https://scsmrd.fengs-lab.com.
基金supported by Heart Research UK(Grant number 119191)British Heart Foundation(Grant number 124055)。
文摘This review highlights some established and some more contemporary mechanisms responsible for heart failure(HF)-induced skeletal muscle wasting and weakness.We first describe the effects of HF on the relationship between protein synthesis and degradation rates,which determine muscle mass,the involvement of the satellite cells for continual muscle regeneration,and changes in myofiber calcium homeostasis linked to contractile dysfunction.We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment.Overall,HF causes multiple impairments related to autophagy,anabolic-catabolic signaling,satellite cell proliferation,and calcium homeostasis,which together promote fiber atrophy,contractile dysfunction,and impaired regeneration.Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF,the effects of satellite cell dynamics remain poorly explored.
基金partially supported by grants from Diabetes Action Research and Education Foundation。
文摘Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor for developing T2D.Thus,the identifi cation of compounds that enhance the ability of SkM to take up glucose is a promising strategy for preventing T2D.Our previous work showed that kaempferol,a fl avonol present in many foods,improves insulin sensitivity in obese mice,however,the mechanism underlying this beneficial action remains unclear.Here,we show that kaempferol directly stimulates glucose uptake and prevents lipotoxicity-impaired glucose uptake in primary human SkM.Kaempferol stimulates Akt phosphorylation in a time-dependent manner in human SkM cells.The effect of kaempferol on glucose uptake was blunted by inhibition of glucose transporter 4,phosphoinositide 3-kinase(PI3K),or AMPK.In addition,kaempferol induced AMPK phosphorylation,and inhibition of AMPK prevented kaempferol-stimulated Akt phosphorylation.In vivo,kaempferol administration induced rapid glucose disposal accompanied with increased Akt and AMPK phosphorylation in SkM tissue of the mice.Taken together,these fi ndings suggest that kaempferol stimulates glucose uptake in SkM via an AMPK/Akt dependent mechanism,and it may be a viable therapeutic agent for insulin resistance.
基金the funding of the project by the CNPC Corporation (2018B-1907)。
文摘A series of Ferrierite(FER)zeolites were prepared via hydrothermal synthesis in the absence of organic templates with the aid of sodium-type FER zeolite(NaFER)or NaFER suspensions(NaFERsus)acquired by NaOH solution treatment as seeds.The differences in the structures and acid sites of the obtained FER zeolite catalysts arising from the choice of seed were investigated,and the catalytic performances of the obtained FER zeolites were evaluated in the skeletal isomerization of n-butene.The results indicate that the samples synthesized using NaFERsus feature more Br?nsted acid sites(BAS)in the 10-membered-ring(10-MR)at the expense of strong acid and Lewis acid sites(LAS),compared with samples derived from NaFER.Therefore,the FER samples synthesized using NaFERsus outperformed the NaFER counterparts as the BAS in 10-MR and LAS were the main active sites,while BAS in 8-MR and LAS were responsible for side reactions,such as polymerization,cracking,and carbon deposition in n-butene isomerization.The optimized FER catalyst was continuously used for 720 h at 350℃ at 0.1 MPa under an n-butene space velocity of 2.0 h^(-1),during which the n-butene conversion remained at>40%,and the isobutylene yield was>37.5%.
基金supported by the Basic Public Welfare Research Program of Zhejiang Province(No.LGF20H020009)a Taizhou Science and Technology Plan Project(No.22ywb105)。
文摘Objective:The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old.Methods:A total of 6669 healthy Chinese men and 4494 healthy Chinese women aged 30-92 years old were assessed for their skeletal muscle mass and visceral fat area.Results:The results showed age-dependent decreases in the total skeletal muscle mass indexes in both men and women aged 40-92 years old as well as age-dependent increases in the visceral fat area in men aged 30-92 years old and in women aged 30-80 years old.Multivariate regression models showed that the total skeletal muscle mass index was positively associated with the body mass index and negatively associated with the age and visceral fat area in both sexes.Conclusion:The loss of skeletal muscle mass becomes obvious at approximately 50 years of age,and the visceral fat area commences to increase at approximately 40 years of age in this Chinese population.
文摘Mutations in SFRP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal fragility.The WNT signaling pathway plays important roles in determining skeletal architecture and SFRP4 is a secreted Frizzled decoy receptor that inhibits WNT signaling.Seven cohorts of male and female Sfrp4 gene knockout mice,examined through 2 years of age,had a normal lifespan but showed cortical and trabecular bone phenotypes.Mimicking human Erlenmeyer flask deformities,bone cross-sectional areas were elevated 2-fold in the distal femur and proximal tibia but only 30%in femur and tibia shafts.Reduced cortical bone thickness was observed in the vertebral body,midshaft femur and distal tibia.Elevated trabecular bone mass and numbers were observed in the vertebral body,distal femur metaphysis and proximal tibia metaphysis.Midshaft femurs retained extensive trabecular bone through 2 years of age.Vertebral bodies had increased compressive strength,but femur shafts had reduced bending strength.Trabecular,but not cortical,bone parameters in heterozygous Sfrp4mice were modestly affected.Ovariectomy resulted in similar declines in both cortical and trabecular bone mass in wild-type and Sfrp4 KO mice.SFRP4 is critical for metaphyseal bone modeling involved in determining bone width.Sfrp4 KO mice show similar skeletal architecture and bone fragility deficits observed in patients with Pyle’s disease with SFRP4 mutations.
基金supported by a K08AR069099 (P.L.) from the National Institutes of Health/ National Institute of Arthritis and Musculoskeletal and Skinsupported by an R01AG056169 and a gift by the Patricia and Frank Zarb Family+5 种基金supported by an F30AG072834 from the National Institutes of Health/National Institute on Agingfunded through NIH Grant S10OD010751 and the Preclinical Imaging Laboratorypartially supported by the Laura and Isaac Perlmutter Cancer Center Support Grant NIH/NCI 5P30CA016087NIBIB Biomedical Technology Resource Center Grant NIH P41 EB017183supported in part by grant P30CA016087 from the National Institutes of Health/National Cancer Institutepartially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center。
文摘Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.
文摘BACKGROUND Patient satisfaction with facial appearance at the end of orthodontic camouflage treatment is very important, especially for skeletal malocclusion. This case report highlights the importance of the treatment plan for a patient initially treated with four-premolar-extraction camouflage, despite indications for orthognathic surgery.CASE SUMMARY A 23-year-old male sought treatment complaining about his unsatisfactory facial appearance. His maxillary first premolars and mandibular second premolars had been extracted, and a fixed appliance had been used to retract his anterior teeth for two years without improvement. He had a convex profile, a gummy smile, lip incompetence, inadequate maxillary incisor inclination, and almost a class I molar relationship. Cephalometric analysis showed severe skeletal class Ⅱ malocclusion(A point-nasion-B point = 11.5°) with a retrognathic mandible(sella-nasion-B point = 75.9°), a protruded maxilla(sella-nasion-A point = 87.4°), and vertical maxillary excess(upper incisor to palatal plane = 33.2 mm). The excessive lingual inclination of the maxillary incisors(upper incisor to nasion-A point line =-5.5°)was due to previous treatment attempts to compensate for the skeletal class Ⅱ malocclusion. The patient was successfully retreated with decompensating orthodontic treatment combined with orthognathic surgery. The maxillary incisors were repositioned and proclined in the alveolar bone, the overjet was increased, and a space was created for orthognathic surgery, including maxillary impaction, anterior maxillary back-setting, and bilateral sagittal split ramus osteotomy to correct his skeletal anteroposterior discrepancy. Gingival display was reduced, and lip competence was restored. In addition, the results remained stable after 2 years. The patient was satisfied with his new profile as well as with the functional malocclusion at the end of treatment.CONCLUSION This case report provides orthodontists a good example of how to treat an adult with severe skeletal class Ⅱ malocclusion with vertical maxillary excess after an unsatisfactory orthodontic camouflage treatment. Orthodontic and orthognathic treatment can significantly correct a patient’s facial appearance.
文摘BACKGROUND Diffuse idiopathic skeletal hyperostosis(DISH)is a disorder characterised by the calcification and ossification of ligaments and entheses.It is a frequent occurrence in elderly males,but rarely encountered in younger individuals.CASE SUMMARY A 24-year-old male was admitted to the hospital due to low back pain accompanied with numbness in both lower limbs for 10 d.Upon clinical examination and imaging tests,the patient was diagnosed with DISH with Scheuermann disease and thoracic spinal stenosis.Before the operation and medical treatment,the patient had hypoesthesia of the skin below the xiphoid process.Afterward,a standard laminectomy was conducted using ultrasonic bone curette and internal fixation was applied.Subsequently,the patient was given corticosteroids,neurotrophic drugs,hyperbaric oxygen and electric stimulation.As a result of the treatment,the patient’s sensory level decreased to the navel level and there was no major change in the muscle strength of the lower limbs.During follow-up,the patient’s skin sensation has returned to normal.CONCLUSION This case is a rare instance of DISH co-existing with Scheuermann’s disease in a young adult.This provides a valuable reference point for spine surgeons,as DISH is more commonly observed in middle-aged and elder adults.
文摘Timely identification and treatment of medical conditions could facilitate faster recovery and better health.Existing systems address this issue using custom-built sensors,which are invasive and difficult to generalize.A low-complexity scalable process is proposed to detect and identify medical conditions from 2D skeletal movements on video feed data.Minimal set of features relevant to distinguish medical conditions:AMF,PVF and GDF are derived from skeletal data on sampled frames across the entire action.The AMF(angular motion features)are derived to capture the angular motion of limbs during a specific action.The relative position of joints is represented by PVF(positional variation features).GDF(global displacement features)identifies the direction of overall skeletal movement.The discriminative capability of these features is illustrated by their variance across time for different actions.The classification of medical conditions is approached in two stages.In the first stage,a low-complexity binary LSTM classifier is trained to distinguish visual medical conditions from general human actions.As part of stage 2,a multi-class LSTM classifier is trained to identify the exact medical condition from a given set of visually interpretable medical conditions.The proposed features are extracted from the 2D skeletal data of NTU RGB+D and then used to train the binary and multi-class LSTM classifiers.The binary and multi-class classifiers observed average F1 scores of 77%and 73%,respectively,while the overall system produced an average F1 score of 69%and a weighted average F1 score of 80%.The multi-class classifier is found to utilize 10 to 100 times fewer parameters than existing 2D CNN-based models while producing similar levels of accuracy.
基金Supported by the Dirección General de Asuntos del Personal Académico(DGAPA)-Universidad Nacional Autónoma de México,No.IN211117Consejo Nacional de Ciencia y Tecnología(CONACyT),No.1887 CONACyT-Fronteras de la Ciencia awarded to Chimal-Monroy J+1 种基金García-García RD and Garay-Pacheco E received an undergraduate scholarshipMarin-Llera JC a postdoctoral fellowship from the Consejo Nacional de Ciencia y Tecnología,No.CONACyT-Fronteras de la Ciencia-1887.
文摘BACKGROUND Mesenchymal stromal cells(MSCs)are multipotent cell populations obtained from fetal and adult tissues.They share some characteristics with limb bud mesodermal cells such as differentiation potential into osteogenic,chondrogenic,and tenogenic lineages and an embryonic mesodermal origin.Although MSCs differentiate into skeletal-related lineages in vitro,they have not been shown to selforganize into complex skeletal structures or connective tissues,as in the limb.In this work,we demonstrate that the expression of molecular markers to commit MSCs to skeletal lineages is not sufficient to generate skeletal elements in vivo.AIM To evaluate the potential of MSCs to differentiate into skeletal lineages and generate complex skeletal structures using the recombinant limb(RL)system.METHODS We used the experimental system of RLs from dissociated-reaggregated human placenta(PL)and umbilical cord blood(UCB)MSCs.After being harvested and reaggregated in a pellet,cultured cells were introduced into an ectodermal cover obtained from an early chicken limb bud.Next,this filled ectoderm was grafted into the back of a donor chick embryo.Under these conditions,the cells received and responded to the ectoderm’s embryonic signals in a spatiotemporal manner to differentiate and pattern into skeletal elements.Their response to differentiation and morphogenetic signals was evaluated by quantitative poly-merase chain reaction,histology,immunofluorescence,scanning electron microscopy,and in situ hybridization.RESULTS We found that human PL-MSCs and UCB-MSCs constituting the RLs expressed chondrogenic,osteogenic,and tenogenic molecular markers while differentially committing into limb lineages but could not generate complex structures in vivo.MSCs-RL from PL or UCB were committed early to chondrogenic lineage.Nevertheless,the UCB-RL osteogenic commitment was favored,although preferentially to a tenogenic cell fate.These findings suggest that the commitment of MSCs to differentiate into skeletal lineages differs according to the source and is independent of their capacity to generate skeletal elements or connective tissue in vivo.Our results suggest that the failure to form skeletal structures may be due to the intrinsic characteristics of MSCs.Thus,it is necessary to thoroughly evaluate the biological aspects of MSCs and how they respond to morphogenetic signals in an in vivo context.CONCLUSION PL-MSCs and UCB-MSCs express molecular markers of differentiation into skeletal lineages,but they are not sufficient to generate complex skeletal structures in vivo.
