Background: Several individual studies from specific countries have reported rising numbers of pediatric COVID-19 cases with inconsistent reports on the clinical symptoms including respiratory and gastrointestinal symptoms as well as diverse reports on the mean age and household exposure in children. The epidemiological characteristics of COVID-19 in children are not fully understood, hence, comprehensive meta-analyses are needed to provide a better understanding of these characteristics. Methods: This review was conducted in Medline, Scopus, Cochrane library, Embase, Web of Science, and published reports on COVID-19 in children. Data were extracted by two independent researchers and a third researcher resolved disputes. STATA software and the random-effect model were used in the synthesis of our data. For each model, the heterogeneity between studies was estimated using the Q Cochrane test. Heterogeneity and publication bias were calculated using the I² statistic and Egger’s/Begg’s tests. Results: The qualitative systematic review was performed on 32 articles. Furthermore, the meta-analysis estimated an overall rate of involvement at 12% (95% CI: 9–15%) among children, with an I² of 98.36%. The proportion of household exposure was calculated to be 50.99% (95% CI: 20.80%–80.80%) and the proportion of admitted cases was calculated to be 45% (95% CI: 24%–67%). Additionally, the prevalence of cough, fatigue, fever and dyspnea was calculated to be 25% (95% CI: 0.16–0.36), 9% (95% CI: 0.03–0.18), 33% (95% CI: 0.21–0.47) and 9% (95% CI: 0.04–0.15), respectively. It is estimated that 4% (95% CI: 1–8%) of cases required intensive care unit admission. Conclusions: The pediatric clinical picture of COVID-19 is not simply a classic respiratory infection, but unusual presentations have been reported. Given the high incidence of household transmission and atypical clinical presentation in children, we strongly recommend their inclusion in research and population-based preventive measures like vaccination as well as clinical trials to ensure efficacy, safety, and tolerability in this age group.

Background: Osteoarthritis is a common and progressive degenerative joint disorder marked by cartilage degradation, subchondral bone remodeling, and chondrocyte apoptosis. Autophagy, a tightly regulated intracellular degradation process, is essential for maintaining chondrocyte homeostasis. Dysregulated autophagy can contribute to cartilage degeneration by disrupting the balance between cellular survival and death. The B-cell lymphoma 2 (BCL2) protein plays a dual role by inhibiting autophagy via its interaction with Beclin-1 while simultaneously suppressing apoptosis. This study aimed to investigate whether a therapeutic-grade purified exosome system derived from human plasma can modulate autophagy through regulation of BCL2 signaling, reduce chondrocyte apoptosis, and prevent osteoarthritis progression. Results: In vitro experiments demonstrated that exosome treatment increased autophagic activity and reduced apoptosis in both immortalized and osteoarthritic human chondrocytes. Mechanistic analysis revealed that exosomes downregulated BCL2 expression, disrupted the BCL2–Beclin-1 complex, and enhanced the expression of autophagy-related proteins LC3 and Beclin-1. Overexpression of BCL2 reversed these effects and led to impaired autophagic flux and elevated apoptosis, particularly in osteoarthritic chondrocytes. In a rat model of surgically induced osteoarthritis, intra-articular injection of the exosome product mixed with hyaluronic acid improved gait parameters, reduced mechanical pain sensitivity, and preserved cartilage architecture and subchondral bone structure. Histological and molecular analyses confirmed reduced chondrocyte apoptosis and elevated autophagic activity in exosome-treated joints, along with decreased BCL2 expression and complex formation with Beclin-1. Conclusions: This study demonstrates that a therapeutic-grade exosome formulation can alleviate osteoarthritis by restoring the balance between autophagy and apoptosis through modulation of the BCL2–Beclin-1 signaling axis. These findings highlight the potential of exosome-based nanotherapeutics as a novel disease-modifying treatment strategy for degenerative joint disorders. Graphical

Muscle stem cells (MuSCs) are essential for skeletal muscle regeneration, influenced by a complex interplay of mechanical, biochemical, and molecular cues. Properties of the extracellular matrix (ECM) such as stiffness and alignment guide stem cell fate through mechanosensitive pathways, where forces like shear stress translate into biochemical signals, affecting cell behavior. Aging introduces senescence which disrupts the MuSC niche, leading to reduced regenerative capacity via epigenetic alterations and metabolic shifts. Transplantation further challenges MuSC viability, often resulting in fibrosis driven by dysregulated fibro-adipogenic progenitors (FAPs). Addressing these issues, scaffold designs integrated with pharmacotherapy emulate ECM environments, providing cues that enhance graft functionality and endurance. These scaffolds facilitate the synergy between mechanotransduction and intracellular signaling, optimizing MuSC proliferation and differentiation. Innovations utilizing human pluripotent stem cell-derived myogenic progenitors and exosome-mediated delivery exploit bioactive properties for targeted repair. Additionally, 3D-printed and electrospun scaffolds with adjustable biomechanical traits tackle scalability in treating volumetric muscle loss. Advanced techniques like single-cell RNA sequencing and high-resolution imaging unravel muscle repair mechanisms, offering precise mapping of cellular interactions. Collectively, this interdisciplinary approach fortifies tissue graft durability and MuSC maintenance, propelling therapeutic strategies for muscle injuries and degenerative diseases.

Background: Loss of finger motion after zone II flexor tendon repair remains common and is largely caused by adhesion formation. Although intrinsic vascular and cellular contributions to tendon healing have been examined in canine, avian, and primate models, prior studies have emphasized biochemical or perfusion-based endpoints without comprehensive assessment of functional and mechanical outcomes after clinically relevant repair. Consequently, the influence of intrinsic healing elements on early postoperative function remains unclear. In this study, we employed a novel avian model of intrasynovial (zone II) tendon injury, which enables clinically relevant operative repair, postoperative rehabilitation, and quantitative assessment of tendon function and biomechanics, to investigate the contribution of intrinsic healing elements to tendon repair. Questions/purposes: (1) Does operative ablation of intrinsic healing elements worsen early ROM after zone II flexor tendon repair? (2) Does disruption of intrinsic pathways increase adhesion formation, as measured by normalized work of flexion and gross adhesion scores? (3) Does intrinsic tendon component ablation compromise mechanical properties, including ultimate load to failure and stiffness? (4) Does removal of intrinsic elements alter the expression of fibrotic and matrix-related genes during early healing? Methods: Using a clinically relevant, large-animal avian ( Meleagris gallopavo ) model of zone II flexor tendon repair, flexor digitorum longus (FDL) tendons underwent sharp transection and primary repair and were assigned to one of four groups: (1) control repair with intact intrinsic elements (3 weeks postinjury, n = 11; 6 weeks postinjury, n = 18), (2) vincular ligation and transection (3 weeks postinjury, n = 12; 6 weeks postinjury, n = 16), (3) tenocyte cryoablation via intraoperative freeze-thaw devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 13), or (4) complete tendon devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 16). A total of 112 male and female birds were used for this study. Harvested tendons were evaluated at 3 and 6 weeks postoperatively. Outcomes included interphalangeal ROM, normalized work of flexion, semiquantitative gross adhesion scoring, ultimate load to failure, stiffness, qualitative histologic assessment, qualitative immunofluorescence, and quantitative PCR for fibrotic and matrix-related genes. Results: Operative ablation of the intrinsic healing elements did not worsen total ROM and/or increase normalized work of flexion. All experimental groups demonstrated reduced total ROM of the operative digit at 3 weeks postoperatively compared with the contralateral nonoperative digit: mean ± SD control repair with intact intrinsic healing elements (50° ± 10° versus 14° ± 6°, mean difference 36.41° [95% confidence interval (CI) 26.87° to 45.94°]; p < 0.001), vincular disruption group (50° ± 10° versus 14° ± 7°, mean difference 35.97° [95% CI 21.44° to 45.51°]; p < 0.001), tenocyte cryoablation group (50° ± 10° versus 15° ± 8°, mean difference 35.27° [95% CI 25.99° to 44.55°]; p < 0.001), and complete tendon devitalization group (50° ± 10° versus 11° ± 4°, mean difference 38.97° [95% CI 29.44° to 48.50°]; p < 0.001). However, no differences between the groups were detected. Similarly, the total ROM was impaired at 6 weeks postinjury compared with the nonoperative digit in all groups. We did not detect any differences between the groups, and results did not demonstrate time-dependent differences between the two time points. Furthermore, normalized work of flexion, a proxy for peritendinous adhesion severity, was increased in all experimental groups at 3 weeks postinjury: mean ± SD control repair with intact intrinsic healing elements (0 ± 0 N mm/° versus 4 ± 3 N mm/°, mean difference -3.33 [95% CI -5.73 to -0.93]; p = 0.003), vincular disruption group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.09 [95% CI -5.49 to -0.69]; p = 0.006), tenocyte cryoablation group (0 ± 0 N mm/° versus 3 ± 2 N mm/°, mean difference -2.99 [95% CI -5.33 to -0.66]; p = 0.006), and complete tendon devitalization group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.31 [95% CI -5.70 to -0.91]; p = 0.003). However, no group differences were detected. At the 6-week follow-up, the normalized work of flexion was also elevated in all groups without any differences between the treatments. Furthermore, the integrity of the tendon intrinsic components has been presumed to be a major determinant of flexor tendon healing strength after zone II tendon repair. However, our results do not support this assumption. At both time points, there were no differences in ultimate load and stiffness between the experimental groups, and there were no group × time interaction effects. Additionally, structural removal of the intrinsic healing elements did not result in meaningful qualitative histologic differences in extrinsic fibrosis, neovascularization, or collagen fiber organization. The profibrotic gene, transforming growth factor beta induced (TGFBI), was upregulated in all experimental groups compared with the normal FDL tendon. Matrix remodeling, measured by matrix metalloproteinase 7 (MMP7) activity, was also activated in all groups relative to the normal FDL tendon. However, no differences were detected between the groups. Conclusion: Operative ablation of intrinsic healing elements, including the flexor vincular system and resident tenocytes, did not worsen early ROM, adhesion formation, or mechanical properties after zone II flexor tendon repair in a clinically relevant large-animal model. Early healing was characterized by a robust fibrovascular response across all groups, indicating that extrinsic mechanisms predominate during the early reparative phase. Paradigms that modulate the extrinsic tendon healing mechanisms could represent a more viable approach to flexor tendon healing outcomes than focusing on bolstering the intrinsic components. Clinical Relevance: Our findings suggest that early functional recovery in this model may depend more on modulation of the extrinsic fibrotic response than on preservation of intrinsic vascular or cellular elements, supporting the development of antiadhesion therapies. Additional preclinical studies are needed to identify the cellular niches that drive extrinsic fibrosis and adhesion formation, determine whether they can be selectively modulated without impairing tendon healing, and establish the translational relevance of these mechanisms across species before clinical application.