Pathogenicity and molecular characterization of a GI-19 infectious bronchitis virus isolated from East China.

Infectious bronchitis virus (IBV) is responsible for avian infectious bronchitis, a disease prevalent in countries with intensive poultry farming practices. Given the presence of multiple genotypic strains in China, identifying the regionally dominant genotypes is crucial for the implementation of effective prevention and control measures. This study focuses on the IBV strain CK/CH/WJ/215, isolated from a diseased commercial chicken flock in China in 2021. The CK/CH/WJ/215 isolate was genetically characterized through complete S1 sequence analysis. Phylogenetic comparisons were made with prevalent vaccine strains (H120, LDT3-A, and 4/91). Glycosylation patterns in the S1 protein were also analyzed. Pathogenicity was assessed in 7-day-old specific-pathogen-free chicks, monitoring morbidity, mortality, and tissue tropisms. Phylogenetic analysis clustered the CK/CH/WJ/215 isolate within the GI-19 lineage. Identity with the vaccination strains H120, LDT3-A, and 4/91 was low (75.7%, 78.6%, and 77.5% respectively). Novel glycosylation sites at positions 138 and 530 were identified compared to H120 and LDT-A. The isolate demonstrated nephropathogenic characteristics, causing 100% morbidity and 73.3% mortality in SPF chicks, with broader tropisms in tissues including trachea, lungs, kidneys, and bursa of Fabricius. Comprehensive genetic and pathological investigations revealed significant differences between the CK/CH/WJ/215 isolate and common vaccine strains, including novel glycosylation sites and a strong multiorgan infective capability. These findings are crucial for understanding the evolutionary dynamics of IBV and developing more effective prevention and control strategies.

A crucial role of neutrophil extracellular traps in pulmonary infectious diseases.

Neutrophil extracellular traps (NETs), extrusions of intracellular DNA with attached granular material that exert an antibacterial effect through entangling, isolating, and immobilizing microorganisms, have been extensively studied in recent decades. The primary role of NETs is to entrap and facilitate the killing of bacteria, fungi, viruses, and parasites, preventing bacterial and fungal dissemination. NET formation has been described in many pulmonary diseases, including both infectious and non-infectious. NETs are considered a double-edged sword. As innate immune cells, neutrophils release NETs to kill pathogens and remove cellular debris. However, the deleterious effects of excessive NET release in lung disease are particularly important because NETs and by-products of NETosis can directly induce epithelial and endothelial cell death while simultaneously inducing inflammatory cytokine secretion and immune-mediated thrombosis. Thus, NET formation must be tightly regulated to preserve the anti-microbial capability of NETs while minimizing damage to the host. In this review, we summarized the recent updates on the mechanism of NETs formation and pathophysiology associated with excessive NETs, aiming to provide insights for research and treatment of pulmonary infectious diseases.

Management of Tuberculosis of the Hip With Antitubercular Therapy and Single-Stage Total Hip Replacement: A Case Report.

Hip tuberculosis (TB) is not a common disease, and this devastating illness requires complete treatment. This case study describes the treatment of a 25-year-old female who suffered from hip TB. She came with right hip discomfort, limping, and a restricted range of movement. The clinical examination showed a fixed flexion deformity, adduction, internal rotation, and leg shortening. Radiographic imaging showed arthritis with hip joint space narrowing, bone erosion, and bone disintegration. Laboratory testing revealed increased inflammatory markers, and a synovial fluid investigation showed tuberculous arthritis. The initial treatment consisted of a regular four-drug antitubercular therapy (ATT) regime for six months and then an additional four months of isoniazid and rifampicin. This therapy resulted in improved clinical symptoms and decreased inflammatory markers. However, the level of joint degeneration required surgical intervention. Due to substantial joint damage, the patient received a hybrid total hip replacement (THR) after completing ATT, confirming that the infection had been cured. Intraoperative observations included synovial enlargement, bone erosions, and significant cartilage damage. The patient underwent a rehabilitation program following surgery to regain mobility and hip joint range of motion. The patient reported substantial pain relief and functional improvement at the one-year follow-up with no signs of implant loosening or infection recurrence.

AI-based epidemic and pandemic early warning systems: A systematic scoping review.

Background: Timely detection of disease outbreaks is critical in public health. Artificial Intelligence (AI) can identify patterns in data that signal the onset of epidemics and pandemics. This scoping review examines the effectiveness of AI in epidemic and pandemic early warning systems (EWS). Objective: To assess the capability of AI-based systems in predicting epidemics and pandemics and to identify challenges and strategies for improvement. Methods: A systematic scoping review was conducted. The review included studies from the last 5 years, focusing on AI and machine learning applications in EWS. After screening 1087 articles, 33 were selected for thematic analysis. Results: The review found that AI-based EWS have been effectively implemented in various contexts, using a range of algorithms. Key challenges identified include data quality, model explainability, bias, data volume, velocity, variety, availability, and granularity. Strategies for mitigating AI bias and improving system adaptability were also discussed. Conclusion: AI has shown promise in enhancing the speed and accuracy of epidemic detection. However, challenges related to data quality, bias, and model transparency need to be addressed to improve the reliability and generalizability of AI-based EWS. Continuous monitoring and improvement, as well as incorporating social and environmental data, are essential for future development.

Systematic review of knowledge, attitudes, and practices of dairy farmers and consumers towards bovine tuberculosis in low- and middle-income countries.

Bovine Tuberculosis (bTB), caused by Mycobacterium bovis, is a neglected zoonotic disease primarily associated with cattle. The incidence of bTB is highest in low-income settings with high cattle density and unpasteurised dairy consumption. Smallholder dairy farming has steadily grown in low- and middle-income countries (LMICs) with limited professional support for adequate bTB surveillance and risk mitigation. Several studies have explored the knowledge, attitudes, and practices (KAP) of milk value chain stakeholders towards bTB in LMICs, but this evidence has not been collated and synthesised. We conducted a systematic review to determine what is known, believed, and done in relation to bTB among dairy producers and consumers in LMICs. We performed a systematic search of studies in OVID Medline, Scopus and CABI on 11 September 2023. KAP data were summarised using narrative synthesis and forest plots. We retrieved 2763 articles, retaining 51 for the review. Only studies from Africa (n = 38) and Asia (n = 13) met the eligibility criteria. Most populations reported awareness of human tuberculosis and knew it could be treated, but there was limited awareness of bTB and its zoonotic potential. Knowledge of bTB transmission routes and bTB mitigation varied across populations, and risky practices were also variable. Inconsistencies in study design and survey tools suggest some results may have a mid- to high-risk of bias. Awareness of bTB is surprisingly low among African and Asian populations with high bTB exposure risk, possibly due to the long-standing divide between animal and human health messages that has obscured the One Health implications of bTB. Addressing bTB in LMICs requires a structural One Health approach and standard KAP survey tools to adequately explore the socio-cultural, political, and economic processes and drivers favouring bTB spread and persistence.

Clinical Features and Visual Outcome of Infectious Keratitis Associated with Orthokeratology Lens in Korean Pediatric Patients.

Purpose: To investigate the clinical features and visual outcome of infectious keratitis associated with Orthokeratology (Ortho-K) lens in Korean pediatric patients. Methods: We retrospectively reviewed medical records of patients diagnosed with Ortho-K lens-associated infectious keratitis from June 2005 to April 2020 at a tertiary referral hospital. Patients' demographics, clinical features, microbiological evaluation, and treatment methods were assessed and factors related to final visual outcomes were analyzed. Results: The study included 26 eyes of 26 patients (19 female, 7 male; mean age: 11.9 years), with an average Ortho-K lens wear duration of 33.7 ± 21.2 months. The highest number of cases occurred in summer (42.3%, 11/26). Central or paracentral corneal lesions were observed in 96.2% (25/26) of cases, with a mean corneal epithelial defect size of 5.13 mm². Pseudomonas aeruginosa was the most commonly isolated organism (n = 5), followed by Serratia marcescens (n = 4). All patients responded to medical treatment without needing surgical intervention. 72% of cases achieved favorable visual outcomes (Snellen BCVA > 6/12), while 8% experienced severe visual impairment (Snellen BCVA ≤ 6/60) due to residual central corneal opacities. Multivariable analysis showed that non-summer seasons, duration from symptom onset to presentation, and corneal epithelial defect size were significantly associated with final logMAR BCVA (p = 0.043, p = 0.040, and p = 0.002, respectively). Failed autorefraction at presentation due to an Ortho-K-related infectious keratitis lesion was a significant predictor of poor final visual outcome (Snellen BCVA ≤ 6/12) (OR = 38.995, p = 0.030). Conclusions: Ortho-K lens-related infectious keratitis can lead to permanent corneal opacities and potentially devastating visual outcomes in children. Delayed time to presentation, large corneal lesions, failure of autorefraction, and non-summer seasons were associated with poorer outcomes. Proper education and early detection would be key to safe use of orthokeratology lenses in pediatric patients.

A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study.

BACKGROUND: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322-5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy. METHODS: This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT. DISCUSSION: We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. TRIAL REGISTRATION: NCT, NCT05110001 , Registered on November 5, 2021.

Machine learning prediction and explanatory models of serious infections in patients with rheumatoid arthritis treated with tofacitinib.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program. METHODS: This analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model. RESULTS: A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only. CONCLUSIONS: Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.

The Association of Chronic Pulmonary Aspergillosis and Chronic Pulmonary Histoplasmosis with MDR-TB Patients in Indonesia.

In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56-7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594-203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis.

Recent Advances in Oral Vaccines for Animals.

Compared to traditional injected vaccines, oral vaccines offer significant advantages for the immunization of livestock and wildlife due to their ease of use, high compliance, improved safety, and potential to stimulate mucosal immune responses and induce systemic immunity against pathogens. This review provides an overview of the delivery methods for oral vaccines, and the factors that influence their immunogenicity. We also highlight the global progress and achievements in the development and use of oral vaccines for animals, shedding light on potential future applications in this field.

Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus.

Congenital post-infectious hydrocephalus (PIH) is a condition characterized by enlargement of the ventricular system, consequently imposing a burden on the associated stem cell niche, the ventricular-subventricular zone (V-SVZ). To investigate how the V-SVZ adapts in PIH, we developed a mouse model of influenza virus-induced PIH based on direct intracerebroventricular injection of mouse-adapted influenza virus at two distinct time points: embryonic day 16 (E16), when stem cells line the ventricle, and postnatal day 4 (P4), when an ependymal monolayer covers the ventricle surface and stem cells retain only a thin ventricle-contacting process. Global hydrocephalus with associated regions of astrogliosis along the lateral ventricle was found in 82% of the mice infected at P4. Increased ependymogenesis was observed at gliotic borders and throughout areas exhibiting intact ependyma based on tracking of newly divided cells. Additionally, in areas of intact ependyma, stem cell numbers were reduced; however, we found no significant reduction in new neurons reaching the olfactory bulb following onset of ventriculomegaly. At P4, injection of only the non-infectious viral component neuraminidase resulted in limited, region-specific ventriculomegaly due to absence of cell-to-cell transmission. In contrast, at E16 intracerebroventricular injection of influenza virus resulted in death at birth due to hypoxia and multiorgan hemorrhage, suggesting an age-dependent advantage in neonates, while the viral component neuraminidase resulted in minimal, or no, ventriculomegaly. In summary, we tracked acute adaptations of the V-SVZ stem cell niche following onset of ventriculomegaly and describe developmental changes that help mitigate the severity of congenital PIH.

Bat humoral immunity and its role in viral pathogenesis, transmission, and zoonosis.

Bats harbor viruses that can cause severe disease and death in humans including filoviruses (e.g., Ebola virus), henipaviruses (e.g., Hendra virus), and coronaviruses (e.g., SARS-CoV). Bats often tolerate these viruses without noticeable adverse immunological effects or succumbing to disease. Previous studies have largely focused on the role of the bat's innate immune response to control viral pathogenesis, but little is known about bat adaptive immunity. A key component of adaptive immunity is the humoral response, comprised of antibodies that can specifically recognize viral antigens with high affinity. The antibody genes within the 1,400 known bat species are highly diverse, and these genetic differences help shape fundamental aspects of the antibody repertoire, including starting diversity and viral antigen recognition. Whether antibodies in bats protect, mediate viral clearance, and prevent transmission within bat populations is poorly defined. Furthermore, it is unclear how neutralizing activity and Fc-mediated effector functions contribute to bat immunity. Although bats have canonical Fc genes (e.g., mu, gamma, alpha, and epsilon), the copy number and sequences of their Fc genes differ from those of humans and mice. The function of bat antibodies targeting viral antigens has been speculated based on sequencing data and polyclonal sera, but functional and biochemical data of monoclonal antibodies are lacking. In this review, we summarize current knowledge of bat humoral immunity, including variation between species, their potential protective role(s) against viral transmission and replication, and address how these antibodies may contribute to population dynamics within bats communities. A deeper understanding of bat adaptive immunity will provide insight into immune control of transmission and replication for emerging viruses with the potential for zoonotic spillover.

The Mediating Role of Human Mobility in Temporal-Lagged Relationships Between Risk Perception and COVID-19 Dynamics in Taiwan: Statistical Modeling for Comparing the Pre-Omicron and Omicron Eras.

Background: The COVID-19 pandemic has profoundly impacted all aspects of human life for over 3 years. Understanding the evolution of public risk perception during these periods is crucial. Few studies explore the mechanisms for reducing disease transmission due to risk perception. Thus, we hypothesize that changes in human mobility play a mediating role between risk perception and the progression of the pandemic. Objective: The study aims to explore how various forms of human mobility, including essential, nonessential, and job-related behaviors, mediate the temporal relationships between risk perception and pandemic dynamics. Methods: We used distributed-lag linear structural equation models to compare the mediating impact of human mobility across different virus variant periods. These models examined the temporal dynamics and time-lagged effects among risk perception, changes in mobility, and virus transmission in Taiwan, focusing on two distinct periods: (1) April-August 2021 (pre-Omicron era) and (2) February-September 2022 (Omicron era). Results: In the pre-Omicron era, our findings showed that an increase in public risk perception correlated with significant reductions in COVID-19 cases across various types of mobility within specific time frames. Specifically, we observed a decrease of 5.59 (95% CI -4.35 to -6.83) COVID-19 cases per million individuals after 7 weeks in nonessential mobility, while essential mobility demonstrated a reduction of 10.73 (95% CI -9.6030 to -11.8615) cases after 8 weeks. Additionally, job-related mobility resulted in a decrease of 3.96 (95% CI -3.5039 to -4.4254) cases after 11 weeks. However, during the Omicron era, these effects notably diminished. A reduction of 0.85 (95% CI -1.0046 to -0.6953) cases through nonessential mobility after 10 weeks and a decrease of 0.69 (95% CI -0.7827 to -0.6054) cases through essential mobility after 12 weeks were observed. Conclusions: This study confirms that changes in mobility serve as a mediating factor between heightened risk perception and pandemic mitigation in both pre-Omicron and Omicron periods. This suggests that elevating risk perception is notably effective in impeding virus progression, especially when vaccines are unavailable or their coverage remains limited. Our findings provide significant value for health authorities in devising policies to address the global threats posed by emerging infectious diseases.

Influence of HIV status on outcomes of children admitted with sepsis at a paediatric hospital in Zambia: protocol for a prospective longitudinal study.

INTRODUCTION: Sepsis, a condition of global public health concern, is a major cause of morbidity and mortality, especially in patients with underlying HIV infection. This study aims to determine outcomes, aetiology and antibiotic resistance patterns among children with HIV exposure or infection admitted with a clinical presentation suggestive of sepsis who have confirmed bloodstream infections at Arthur Davison Children's Hospital (ADCH) in Ndola, Zambia. METHODS AND ANALYSIS: This will be a prospective longitudinal study of 200 children aged <2 years admitted with sepsis at ADCH with two of the following conditions: temperature of 38.0°C, respiratory rate ≥20 breaths per minute and pulse rate ≥90 beats per minute. About 2-5 mL of blood collected from each participant will be inoculated into BACTEC culture bottles and incubated for 5-7 days. Positive cultures will be inoculated onto culture media for subculture followed by species identification followed by antibiotic susceptibility testing. Time-to-event outcomes such as hospital readmission and mortality will be analysed using Kaplan-Meier and Cox proportional hazards. Predictors will be identified using regression methods. All statistical tests will use a 5% significance level with a 95% confidence level. STATA V.16 will be used for statistical analysis. ETHICS AND DISSEMINATION: Ethical clearance and approval have been granted by the Tropical Diseases Research Centre Ethics Committee (TDRC-EC 092/07/23). Caregiver consent will be obtained verbally for participants presenting as medical emergencies, and written informed consent will be obtained once stable. Findings from this study will be shared with the Ministry of Health Zambia and will be disseminated to the scientific community through peer-reviewed scientific journals.

Development of a core outcome set for maternal and perinatal health research and surveillance in light of emerging and ongoing epidemic threats.

Background: Maternal and perinatal health is often directly and indirectly affected during infectious disease epidemics. Yet, a lack of evidence on epidemics' impact on women and their offspring delays informed decision-making for healthcare providers, pregnant women, women in the post-pregnancy period and policy-makers. To rapidly generate evidence in these circumstances, we aim to develop a Core Outcome Set (COS) for maternal and perinatal health research and surveillance in light of emerging and ongoing epidemic threats. Methods: We will conduct a Systematic Review and a four-stage modified Delphi expert consensus. The systematic literature will aim to inform experts on outcomes reported in maternal and perinatal research and surveillance during previous epidemics. The expert consensus will involve two individual, anonymous online surveys to rate outcomes' importance and suggest new ones, one virtual meeting to discuss disagreements, and one in-person meeting to agree on the final COS, outcomes definitions and measurement methods. Four panels will be established to participate in the modified Delphi with expertise in (a) maternal and perinatal health, (b) neonatal health, (c) public health and emergency response, and (d) representation of civil society. We will recruit at least 20 international experts for each stakeholder group, with diverse backgrounds and gender, professional, and geographic balance. Only highly-rated outcomes (with at least 80% of ratings being 7-9 on a 9-point Likert scale) and no more than 10% of low ratings (1-3) will be included in the final COS. Conclusions: Implementing this COS in future maternal and perinatal research and surveillance, especially in the context of emerging and ongoing epidemic threats, will facilitate the rapid and systematic generation of evidence. It will also enhance the ability of policy-makers, healthcare providers, pregnant women and women in the post-pregnancy period and their families to make well-informed choices in challenging circumstances.

Youthful small extracellular vesicles restore the function and reparative capacity of inflammatory-impaired periodontal ligament stem cells via delivering protein biglycan for bone regeneration.

Regenerating inflamed bone defects represents a severe clinical challenge due to the undesirable inflammatory microenvironment. The inflammatory stimulus poses a weighty threat to the regenerative capacity of endogenously derived mesenchymal stem cells (MSCs), which are mainly responsible for osteogenic differentiation, thereby resulting in compromised endogenous bone formation. Consequently, alleviating the biological characteristics of inflammatory-impaired MSCs is crucial for promoting inflamed bone regeneration. Nano-sized small extracellular vesicles (sEVs) have emerged as promising therapeutic tools to orchestrate MSCs fate due to their intrinsic biocompatibility and encapsulated bioactive contents. In the present study, we extracted sEVs from youthful and adult dental pulp MSCs and explored their ability to recover inflammation-compromised periodontal ligament stem cells (IPDLSCs). The results indicated that both types of sEVs were capable of facilitating IPDLSCs osteogenesis. However, young sEVs exhibited a more robust potential at a lower concentration compared to adult sEVs. Mechanically, young sEVs enhanced the expression of bone morphogenetic protein 4 (BMP4) via delivering the protein Biglycan, which correspondingly promoted the osteogenic capability of IPDLSCs. Collectively, our findings emphasized that young sEVs hold enormous potential to rescue the inherent function and regenerative competence of inflammation-impaired MSCs, shedding light on their promising therapeutic prospects for infected bone regeneration.