Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis.

BACKGROUND: Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM: To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS: 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS: Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION: Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

Current state of research on exercise for the treatment of myasthenia gravis: A scoping review.

OBJECTIVE: To provide a comprehensive overview of existing evidence, research gaps, and future research priorities concerning the treatment of myasthenia gravis (MG) using exercise therapies. METHOD: Clinical studies on exercise treatment for MG were searched in nine databases to conduct a scoping review. Two independent researchers screened the literature and comprehensively analyzed the characteristics and limitations of the included articles. RESULTS: A total of 5725 studies were retrieved, of which 24 were included. The included studies were conducted in 16 different countries/regions and 456 patients were enrolled. Study designs included both interventional and observational studies. Exercise interventions included aerobic exercise, resistance exercise, balance training, and stretch training, and are typically administered in conjunction with medication, usual care, or some other interventions. The intensity, frequency, and duration of exercise interventions varied hugely among studies. Six-minute walk test, adverse events, muscle strength, MG quality of life-15 scale, forced vital capacity, quantitative MG scale, and MG activities of daily living scale were the most frequently used outcomes. All studies reported results in favor of the efficacy and safety of exercise in MG, and exercise-related adverse events were reported in two studies. CONCLUSION: This scoping review provides an overview of the evidence concerning exercise treatment for MG. Key gaps in evidence include a limited number of participants, complex interventions, variability in outcome selection, and insufficient reporting in publications. The promotion of exercise treatment for MG still encounters several obstacles. A larger population, rigorous study design and conduction, standardized interventions and outcomes, and standardized reporting are essential.

Integrated Analysis of Per- and Polyfluoroalkyl Substance Exposure and Metabolic Profiling of Elderly Residents Living near Industrial Plants.

Per- and polyfluoroalkyl substances (PFASs) are widely used in industrial production, causing potential health risks to the residents living around chemical industrial plants; however, the lack of data on population exposure and adverse effects impedes our understanding and ability to prevent risks. In this study, we performed screening and association analysis on exogenous PFAS pollutants and endogenous small-molecule metabolites in the serum of elderly residents living near industrial plants. Exposure levels of 11 legacy and novel PFASs were determined. PFOA and PFOS were major contributors, and PFNA, PFHxS, and 6:2 Cl-PFESA also showed high detection frequencies. Association analysis among PFASs and 287 metabolites identified via non-target screening was performed with adjustments of covariates and false discovery rate. Strongly associated metabolites were predominantly lipid and lipid-like molecules. Steroid hormone biosynthesis, primary bile acid biosynthesis, and fatty-acid-related pathways, including biosynthesis of unsaturated fatty acids, linoleic acid metabolism, α-linolenic acid metabolism, and fatty acid biosynthesis, were enriched as the metabolic pathways associated with mixed exposure to multiple PFASs, providing metabolic explanation and evidence for the potential mediating role of adverse health effects as a result of PFAS exposure. Our study achieved a comprehensive screening of PFAS exposure and associated metabolic profiling, demonstrating the promising application for integrated analysis of exposome and metabolome.

Photoinduced deformation behavior of poly(aryl ether)s with different azobenzene groups in the side chain.

Azobenzene-containing poly(aryl ether)s are a potential type of photoinduced deformable high-performance polymer. However, research on photoinduced deformation of azobenzene-containing poly(aryl ether)s focuses mainly on poly(aryl ether)s containing azobenzene groups in the main chain. In this paper, the photoinduced deformation of poly(aryl ether)s containing azobenzene groups in the side chain was studied for the first time. Two novel poly(aryl ether)s containing azobenzene groups in the side chain were synthesized, and their photoinduced isomerization behavior and photoinduced deformation behavior were studied. It could be seen that the match of the excitation luminescence to the maximum absorption peak of the azobenzene groups was more compatible, and the photoinduced motion of the polymers was faster. In addition, poly(aryl ether)s containing azobenzene groups in the side chain showed highly stable photoinduced deformation. The results of this work will be helpful for designing polymers which could be controlled by lasers of different wavelengths.

Scleral remodeling during myopia development in mice eyes: a potential role of thrombospondin-1.

BACKGROUND: Scleral extracellular matrix (ECM) remodeling plays a crucial role in the development of myopia, particularly in ocular axial elongation. Thrombospondin-1 (THBS1), also known as TSP-1, is a significant cellular protein involved in matrix remodeling in various tissues. However, the specific role of THBS1 in myopia development remains unclear. METHOD: We employed the HumanNet database to predict genes related to myopic sclera remodeling, followed by screening and visualization of the predicted genes using bioinformatics tools. To investigate the potential target gene Thbs1, we utilized lens-induced myopia models in male C57BL/6J mice and performed Western blot analysis to detect the expression level of scleral THBS1 during myopia development. Additionally, we evaluated the effects of scleral THBS1 knockdown on myopia development through AAV sub-Tenon's injection. The refractive status and axial length were measured using a refractometer and SD-OCT system. RESULTS: During lens-induced myopia, THBS1 protein expression in the sclera was downregulated, particularly in the early stages of myopia induction. Moreover, the mice in the THBS1 knockdown group exhibited alterations in myopia development in both refraction and axial length changed compared to the control group. Western blotting analysis confirmed the effectiveness of AAV-mediated knockdown, demonstrating a decrease in COLA1 expression and an increase in MMP9 levels in the sclera. CONCLUSION: Our findings indicate that sclera THBS1 levels decreased during myopia development and subsequent THBS1 knockdown showed a decrease in scleral COLA1 expression. Taken together, these results suggest that THBS1 plays a role in maintaining the homeostasis of scleral extracellular matrix, and the reduction of THBS1 may promote the remodeling process and then affect ocular axial elongation during myopia progression.

Establishment of a novel ER-stress induced myopia model in mice.

BACKGROUND: Recent studies have indicated a strong correlation between endoplasmic reticulum (ER) stress and myopia and that eyedrops containing the ER stress inducer tunicamycin (Tm) can induce myopic changes in C57BL/6 J mice. Therefore, this study aimed to create a new myopia model using Tm eyedrops and to explore the mechanism of ER stress-mediated myopia development. METHODS: Three-week-old C57BL/6 J mice were treated with different concentrations (0, 25, 50, and 100 µg/mL) and/or number of applications (zero, one, three, and seven) of Tm eyedrops. Refraction and axial length (AL) were measured before and one week after Tm treatment. Scleral collagen alterations were evaluated under polarised light after picrosirius red staining. ER stress-related indicators, such as the expression of collagen I and cleaved collagen were detected using Western blotting. RESULTS: Compared with the control group, mice administered eyedrops with 50 µg/mL Tm only once showed the greatest myopic shifts in refraction and AL elongation and reduced scleral expression of collagen I. Picrosirius red staining showed a lower percentage of bundled collagen in the Tm group. Expression of ER-stress indicators increased in the Tm groups. Furthermore, optimised administration of Tm induced matrix metalloproteinase-2 (MMP2) expression in the sclera, which plays a major role in collagen degradation. CONCLUSIONS: We have demonstrated that ER stress in the sclera is involved in myopia progression. Tm eyedrops induced myopic changes, loosening of the scleral collagen and decreased expression of collagen I. This process may be associated with ER stress in the sclera, which upregulates the expression of MMP2 leading to collagen degradation.

Effect of High-Hydrostatic-Pressure Treatment on the Physicochemical Properties of Kafirin.

The kafirin derived from Jin Nuo 3 sorghum underwent a high-hydrostatic-pressure (HHP) treatment of 100, 300, and 600 MPa for 10 min to investigate alterations in its physicochemical attributes. The findings exhibited a reduction in protein solubility, declining from 83% to 62%, consequent to the application of the HHP treatment. However, this treatment did not lead to subunit-specific aggregation. The absorption intensity of UV light diminished, and the peak fluorescence absorption wavelength exhibited a shift from 342 nm to 344 nm, indicating an increased polarity within the amino acid microenvironment. In an aqueous solution, the specific surface area expanded from 294.2 m2/kg to 304.5 m2/kg, while the average particle-size value in a 70% ethanol solution rose to 26.3 nm. Conversely, the zeta-potential value decreased from 3.4 mV to 1.3 mV, suggesting a propensity for aggregation in ethanol solutions. A notable rise in the intermolecular ß-sheet content to 21.06% was observed, along with a shift in the peak denaturation temperature from 76.33 °C to 86.33 °C. Additionally, the content of disulfide bonds increased to 14.5 µmol/g. Collectively, the application of the HHP treatment not only enhanced the thermal stability but also induced a more ordered secondary structure within the kafirin.

Characteristics of corneal microcysts in Hong Kong children wearing orthokeratology.

PURPOSE: To report the characteristics (prevalence, severity, and location) of corneal epithelial microcysts and investigate associated risk factors in children wearing orthokeratology (ortho-k) lenses. METHOD: Ninety-five myopic children wearing ortho-k lenses (examined by one of three independent investigators from March to September 2020) were included in this retrospective cross-sectional study. Pertinent data at baseline before ortho-k treatment and at the aftercare visits (the first visit when the microcysts were observed for children with microcysts, and the last visit before October 2020 for children without microcysts) were retrieved and analysed. RESULTS: A microcystic response was observed in 52.6% of children wearing ortho-k lenses. Children with high myopia (≥ 5.00 D) had a higher prevalence (100.0%, 23/23) and severity (69.5% (16/23) > grade 2 Efron scale) compared to children with low myopia (≤ 4.00 D) (prevalence of 37.5% (27/72) and 7.0% (5/72) > grade 2, p < 0.001). Microcysts were predominantly (86.0%) observed in the region of the inferior pigmented arc, typically originating in the inferior mid-peripheral cornea, and expanding over time into a semi- or whole annulus. Baseline myopia and topographical change at the treatment zone centre were significantly greater (p < 0.05) in low myopic children with microcysts (univariate analyses). CONCLUSIONS: During the COVID-19 pandemic, probably due to lifestyle changes, microcysts were frequently observed in children wearing ortho-k lenses and were associated with higher baseline myopia. Practitioners should examine ortho-k wearers with caution using a slit lamp with high magnification and illumination, especially the mid-peripheral cornea. The use of highly oxygen permeable lenses and frequent aftercare are necessary for ortho-k wearers, especially those with higher myopia.

Salvage lenvatinib/everolimus combination therapy after immune checkpoint inhibitor and VEGFR tyrosine kinase inhibitor for metastatic renal cell carcinoma.

Background: The optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking. Methods: We retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan-Meier method. Results: The median age was 64 (range 31-84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5-7.6) and the median OS was 9 months (95% CI, 7.6-12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18-7.79), as was ≥4L treatment vs. 2L/3L treatment (HR, 2.02, 95% CI, 1.08-3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance. Conclusions: LE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies.

TET2 is required to suppress mTORC1 signaling through urea cycle with therapeutic potential.

Tumor development, involving both cell growth (mass accumulation) and cell proliferation, is a complex process governed by the interplay of multiple signaling pathways. TET2 mainly functions as a DNA dioxygenase, which modulates gene expression and biological functions via oxidation of 5mC in DNA, yet whether it plays a role in regulating cell growth remains unknown. Here we show that TET2 suppresses mTORC1 signaling, a major growth controller, to inhibit cell growth and promote autophagy. Mechanistically, TET2 functions as a 5mC "eraser" by mRNA oxidation, abolishes YBX1-HuR binding and promotes decay of urea cycle enzyme mRNAs, thus negatively regulating urea cycle and arginine production, which suppresses mTORC1 signaling. Therefore, TET2-deficient tumor cells are more sensitive to mTORC1 inhibition. Our results uncover a novel function for TET2 in suppressing mTORC1 signaling and inhibiting cell growth, linking TET2-mediated mRNA oxidation to cell metabolism and cell growth control. These findings demonstrate the potential of mTORC1 inhibition as a possible treatment for TET2-deficient tumors.

ALDH1A1 promotes PARP inhibitor resistance by enhancing retinoic acid receptor-mediated DNA polymerase θ expression.

Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPi) have been approved for both frontline and recurrent setting in ovarian cancer with homologous recombination (HR) repair deficiency. However, more than 40% of BRCA1/2-mutated ovarian cancer lack the initial response to PARPi treatment, and the majority of those that initially respond eventually develop resistance. Our previous study has demonstrated that increased expression of aldehyde dehydrogenase 1A1 (ALDH1A1) contributes to PARPi resistance in BRCA2-mutated ovarian cancer cells by enhancing microhomology-mediated end joining (MMEJ) but the mechanism remains unknown. Here, we find that ALDH1A1 enhances the expression of DNA polymerase θ (Polθ, encoded by the POLQ gene) in ovarian cancer cells. Furthermore, we demonstrate that the retinoic acid (RA) pathway is involved in the transcription activation of the POLQ gene. The RA receptor (RAR) can bind to the retinoic acid response element (RARE) located in the promoter of the POLQ gene, promoting transcription activation-related histone modification in the presence of RA. Given that ALDH1A1 catalyzes the biosynthesis of RA, we conclude that ALDH1A1 promotes POLQ expression via the activation of the RA signaling pathway. Finally, using a clinically-relevant patient-derived organoid (PDO) model, we find that ALDH1A1 inhibition by the pharmacological inhibitor NCT-505 in combination with the PARP inhibitor olaparib synergistically reduce the cell viability of PDOs carrying BRCA1/2 mutation and positive ALDH1A1 expression. In summary, our study elucidates a new mechanism contributing to PARPi resistance in HR-deficient ovarian cancer and shows the therapeutic potential of combining PARPi and ALDH1A1 inhibition in treating these patients.

Scientific document processing: challenges for modern learning methods.

Neural network models enjoy success on language tasks related to Web documents, including news and Wikipedia articles. However, the characteristics of scientific publications pose specific challenges that have yet to be satisfactorily addressed: the discourse structure of scientific documents crucial in scholarly document processing (SDP) tasks, the interconnected nature of scientific documents, and their multimodal nature. We survey modern neural network learning methods that tackle these challenges: those that can model discourse structure and their interconnectivity and use their multimodal nature. We also highlight efforts to collect large-scale datasets and tools developed to enable effective deep learning deployment for SDP. We conclude with a discussion on upcoming trends and recommend future directions for pursuing neural natural language processing approaches for SDP.

Contralateral effect in progression and recovery of lens-induced myopia in mice.

PURPOSE: Apart from genetic factors, recent animal studies on myopia have focused on localised mechanisms. In this study, we aimed to examine the contralateral effects of monocular experimental myopia and recovery, which cannot be explained by a mere local mechanism. METHODS: One eye of 3-week-old C57BL/6 male mice was fitted with a -30 dioptre (D) lens. The mice were distributed into two groups based on different conditions in the contralateral eye: either no lens (NLC) (n = 10) or a Plano lens on the contralateral eye (PLC) group (n = 6). Mice receiving no treatment on either eye were set as a control group (n = 6). Lenses were removed after 3 weeks of myopia induction. All mice were allowed to recover for 1 week in the same environment. Refractive status, axial length (AL) and choroidal thickness were measured before myopia induction, after 1 and 3 weeks of lens wear and after 1 week of recovery. RESULTS: One week after removing the lenses, complete recovery was observed in the eyes that wore the -30 D lenses. In both the PLC and NLC groups, the refractive status showed a myopic shift after lens removal. Additionally, the choroid was significantly thinned in these eyes. The -30 D wearing eye showed a significant increase in AL after 3 weeks of lens wear. While the AL of the -30 D wearing eye ceased to grow after the lens was removed, the AL in the PLC and NLC contralateral eyes increased, and the binocular ALs gradually converged. CONCLUSIONS: Recovery of lens-induced myopia was observed in mouse models. In the fellow eyes, the effects, including thinning of the choroid and changes in refractive status, were triggered by contralateral visual cues.

Anticoagulant Property of a Sulfated Polysaccharide with Unique Structural Characteristics from the Green Alga Chaetomorpha aerea.

Sulfated polysaccharides from marine algae have attracted a great amount of attentions for the development of marine drugs due to their unique structural features, and they are great potential sources of naturally occurring anticoagulant agents. The genus Chaetomorpha is one of the largest genera in green algae and has a worldwide distribution. In the present study, a homogeneous polysaccharide from Chaetomorpha aerea, designated as PCA, was obtained by alkali extraction, anion-exchange and size-exclusion chromatography. Based on the results of chemical and spectroscopic analyses, PCA was a sulfated galactoarabinan which was mainly constituted of a backbone of →4)-ß-l-Arap-(1→ unit, partially sulfated at C-3 of →4)-ß-l-Arap-(1→ and C-4 of →6)-α-d-Galp-(1→. The side chains consisting of →6)-α-d-Galp-(1→ and →5)-α-l-Araf-(1→ residues were in C-2 of →4)-ß-l-Arap-(1→ unit. PCA had a strong anticoagulant activity in vitro as evaluated by the assays of activated partial thromboplastin time, thrombin time and fibrinogen level. The obvious anticoagulant activity in vivo of PCA was also found. PCA significantly inhibited the activities of the intrinsic coagulation factors XII, XI, IX and VIII, and exhibited weak inhibition effects on the common coagulation factors II and X. The anticoagulant mechanism of PCA was attributed to strong thrombin inhibition potentiated by heparin cofactor II or antithrombin III, and it also possessed an apparent inhibition effect on coagulation factor Xa mediated by antithrombin III. The investigation demonstrated that PCA could be a promising anticoagulant agent for health promotion and the treatment of thrombotic diseases.

Gestational Weight Gain and Small for Gestational Age in Obese Women: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis evaluates the relationship between gestational weight gain and the risk of small for gestational age in obese pregnant women. Methods: Studies were identified by searching the Web of Science, Embase, and PubMed databases up to June 30th, 2022. The meta-analysis was carried out to determine the risk of small for gestational age with gestational weight gain (GWG) below the 2009 Institute of Medicine (IOM) guidelines compared with within the guidelines in obese women. The Newcastle-Ottawa Scale was used to assess the methodological quality. The chi-squared test, Q test, and I2 test were used to evaluate statistical heterogeneity. Subgroup analyses were conducted, and publication bias was assessed by funnel plots and Egger's test. Sensitivity analyses were performed for three groups of obese people (I: BMI 30-34.9 kg/m2, II: BMI 35-39.9 kg/m2, and III: BMI ≥ 40 kg/m2) to examine the association of obesity and SGA. Results: A total of 788 references were screened, and 29 studies (n = 1242420 obese women) were included in the systematic review. Obese women who gained weight below the IOM guideline had a higher risk of SGA than those who gained weight within the guideline (OR = 1.27, 95% CI = 1.16-1.38, Z = 5.36). Both weight loss (<0 kg) and inadequate weight (0-4.9 kg) during pregnancy in obese women are associated with an increased risk of SGA (OR = 1.50, 95% CI = 1.37-1.64, Z = 8.82) (OR = 1.18, 95% CI = 1.14-1.23, Z = 8.06). The same conclusions were also confirmed for the three obesity classes (I: OR = 1.38, 95% CI = 1.29-1.47; II: OR = 1.39, 95% CI = 1.30-1.49; and III: OR = 1.26, 95% CI = 1.16-1.37). Subgroup analysis by country showed that GWG below guidelines in obese women of the USA and Europe was associated with risk for SGA (USA (OR = 1.30, 95% CI = 1.15-1.46), Europe (OR = 1.24, 95% CI = 1.11-1.40)) and not in Asia (OR = 1.17, 95% CI = 0.91-1.50). Conclusion: Our findings indicated that obese pregnant women who had weight loss or inadequate weight (0-4.9 kg) according to the IOM guideline had increased risks for SGA. Moreover, we also evaluated that gestational weight loss (<0 kg) in these pregnancies was associated with an increased risk for SGA compared with inadequate weight (0-4.9 kg) in these pregnancies. Therefore, the clinical focus should assist obese women to achieve GWG within the IOM guidelines to decrease the risk for SGA.

A sulfated polysaccharide from Dictyosphaeria cavernosa: Structural characterization and effect on immunosuppressive recovery.

A homogeneous sulfated polysaccharide DCS1 was obtained from Dictyosphaeria cavernosa by alkali extraction and chromatography purification. On the basis of chemical and spectroscopic analyses, DCS1 was a novel mannan-type sulfated polysaccharide and had a molecular weight of 15.48 kDa. DCS1 consisted of a main chain of (1 â†’ 4)-α-d-Manp units with partial sulfate substitution at C-2 and branches at C-2/C-6. DCS1 possessed a potent immune-enhancing effect in vitro evaluated by the assays of lymphocytes proliferation and macrophage phagocytosis. The immunomodulatory effect of DCS1 in vivo was further investigated using immunosuppressed mice induced by cyclophosphamide (Cy). The data showed that DCS1 markedly increased the spleen and thymus indexes, and ameliorated the Cy-induced damage to spleen and thymus. Moreover, DCS1 had a significant effect on hematopoietic function recovery, and promoted the secretion of the interleukin-2 and tumor necrosis factor-α. Notably, DCS1 reversed the reduction of CD4+ T cells, improved the disorder of CD4+/CD8+ T cells and enhanced the immune response. The investigation demonstrated that the sulfated polysaccharide DCS1 with novel structure could be a hopeful immunomodulatory agent.

Mapping current trends and hotspots in myasthenia gravis from 2003 to 2022: a bibliometric analysis.

Introduction: Research on myasthenia gravis (MG) has undergone rapid development in recent years. This article aimed to elucidate the characteristics of MG publications over the past 20 years and analyze emerging trends using bibliometric methods. Methods: Information on MG articles was obtained from the Web of Science Core Collection and stored in Excel for quantitative analyses. Bibliometric analyses were performed using CiteSpace and VOSviewer to visualize publications according to countries/regions, institutions, journals, and authors. Results: A total of 3,610 publications were included in the analysis. The USA had the highest number of publications (NP) and H-index. Among the institutions, the University of Oxford had the highest NP, followed by the University of Toronto and Duke University. Close cooperation was observed among countries and institutions. The most productive author was Renato Mantegazza, followed by Jan J. Verschuuren, and Amelia Evoli. Muscle & Nerve published the most articles on MG, followed by the Journal of Neuroimmunology and Neuromuscular Disorders. The keyword with the highest strength is "neuromuscular transmission," followed by "safety" and "rituximab." Co-citation analysis includes 103 publications cited at least 65 times, categorized into four clusters. Additionally, 123 keywords cited more than 40 times were analyzed and divided into five clusters. Conclusion: This bibliometric analysis shows the framework of research over the past 20 years by mapping the scholarly contributions of various countries or regions, institutions, journals, and authors in MG. The analysis also explores future trends and prospective directions, emphasizing individualized treatment based on subtypes, novel immunotherapeutic approaches, and thymectomy.

Application and Molecular Mechanisms of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Osteoporosis.

Osteoporosis (OP) is a chronic bone disease characterized by decreased bone mass, destroyed bone microstructure, and increased bone fragility. Accumulative evidence shows that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes (Exos), exhibit great potential in the treatment of OP. However, the research on MSC-EVs in the treatment of OP is still in the initial stage. The potential mechanism has not been fully clarified. Therefore, by reviewing the relevant literature of MSC-EVs and OP in recent years, we summarized the latest application of bone targeted MSC-EVs in the treatment of OP and further elaborated the potential mechanism of MSC-EVs in regulating bone formation, bone resorption, bone angiogenesis, and immune regulation through internal bioactive molecules to alleviate OP, providing a theoretical basis for the related research of MSC-EVs in the treatment of OP.

Current state of research on acupuncture for the treatment of amyotrophic lateral sclerosis: A scoping review.

Objective: To provide an overview of the range and characteristics of existing evidence, research gaps, and future research priorities in treating amyotrophic lateral sclerosis (ALS) with acupuncture. Method: Clinical studies on acupuncture treatment for ALS were searched in 9 databases and two websites. Two independent researchers screened the literature according to the inclusion and exclusion criteria; extracted the demographic data, interventions, and significant findings of the studies; and comprehensively analyzed the characteristics and limitations of the included articles. Results: A total of 2,326 studies were retrieved, of which 92 were included. Most of the studies were conducted in China, with the number increasing over time. Study designs included case reports, case series, randomized controlled trials (RCTs), and before-and-after studies, among which case reports were the most frequently used. A total of 1,388 patients were enrolled, of whom 1,031 had ALS, 274 had progressive bulbar palsy (PBP), 60 had progressive muscle atrophy (PMA), and 23 had primary lateral sclerosis (PLS). Acupuncture interventions included body acupuncture, electroacupuncture, acupoint injection, scalp acupuncture, acupoint massage, Sa-am acupuncture, needle-embedding therapy, auricular acupuncture, venom pharmacopuncture therapy, plum blossom needling, acupoint paste, electroacupuncture, and needle warming through moxibustion. The most frequently used acupoints were ST36, LI4, SP6, and LI11. Acupuncture is often applied in combination with other treatments, such as herbal or Western medicine. The frequency of treatment ranged from once a month to three times a day, and the duration of treatment ranged from 5 days to 3 years. Clinical symptoms, muscle strength, and effective rates were the most frequently used outcomes. Most studies reported significant efficacy, and only a few studies reported adverse events explicitly. Conclusion: Evidence gaps include poor study design, complex interventions, limited significance of the selected outcomes, and limited study reporting. The promotion of acupuncture treatment for ALS still faces several obstacles. Rigorous study design and conduct, standardized intervention and outcome measurements, and normative reporting are needed to investigate the efficacy and safety of acupuncture treatment for ALS.