Vaccination during pregnancy to protect infants against respiratory syncytial virus (RSV) disease relies on transplacental transfer of RSV neutralizing antibodies. Observational natural history studies on correlations between RSV-specific antibody levels and infant protection have, however, had variable results.

This observational natural history study characterized RSV-specific neutralizing antibody levels and described infant RSV disease dynamics in South African and United States (US) maternal-infant pairs. Naturally acquired RSV serum neutralizing titers were determined from 726 pregnant individuals and their infants at birth and assessed in relationship to serum neutralizing titers conferred by serum palivizumab protective levels.

In the absence of vaccination, we found no correlation between RSV neutralizing titers and infant protection against RSV-associated lower respiratory tract illness. South Africa versus US comparison revealed similar, broad distributions of maternal serum RSV neutralizing titers but lower transplacental transfer rates in South Africa (0.6 [95% confidence interval {CI}, .6-.7]) than the US (1.3 [95% CI, 1.1-1.4]) and high rates of community spread of infant asymptomatic RSV infection in South Africa versus the US.

These findings suggest that the effectiveness of maternal immunization against infant RSV relies on immunization shifting natural distribution of maternal RSV neutralizing titers into the protective range for infants, which is supported by efficacy demonstrated with RSV maternal immunization.

Acute respiratory tract infections (ARTIs) may be misdiagnosed due to bottlenecks in conventional diagnostics. The primary objective was to identify viral pathogens using reverse transcription real-time polymerase chain reaction (RT-PCR).

Cross-sectional study was conducted between 2022 and 2024 at Tanzanian referral hospitals. Viral RNA was extracted from oral-nasopharyngeal swabs and amplified using multiplex and singleplex RT-PCR. Cycle threshold values ≤40 and ≤35 were considered positive for multiplex and singleplex RT-PCR, respectively.

We recruited 183 participants with median age of 52 years (interquartile range, 32-69). Of these, 119 (65%) were females. The majority (167 of 183, 91.3%) had no COVID-19 vaccination. Over one-third (67 of 183, 36.61%) were PCR-positive for viral pathogens. Seven viral pathogens were identified, and the more prevalent were influenza A virus (Flu A) (n = 27), SARS-CoV-2 (n = 10), and respiratory syncytial virus (n = 7). The most common co-infecting viruses were FluA + respiratory syncytial virus (n = 6), Flu A + influenza B virus + SARS-CoV-2 (n = 4), and SARS-CoV-2 + Flu A (n = 3). Elderly people (aged >65 years) were commonly infected with Flu A (n = 9) and SARS-CoV-2 (n = 5).

Viral pathogens are common in people with ARTIs. This study emphasizes consideration of RT-PCR in addition to conventional diagnostic approaches for identifying viral pathogens in patients with ARTIs.

Despite growing interest in acupuncture as a complementary therapy for chronic obstructive pulmonary disease (COPD), comprehensive analyses of its global research trajectory, disciplinary convergence patterns, and geopolitical contributions remain unexplored. This study addresses this gap by mapping the intellectual and geopolitical architecture of acupuncture-COPD research over nearly four decades, a period chosen to capture the significant developments in acupuncture's global recognition since the late 1980s, when traditional medicine began to gain more global attention.

We conducted a longitudinal bibliometric analysis of 299 publications indexed in the Web of Science Core Collection (1986-2024). Employing Bradford's and Lotka's laws, co-citation networks, and keyword co-occurrence clustering, we systematically evaluated temporal productivity trends, institutional/country contributions, citation dynamics, and thematic evolution using SciMAT, VOSviewer, and bibliometrix R-package. (Response to Editor's Comment 1).

Research productivity followed a triphasic trajectory: a dormant phase (1986-2000, ≤2 articles/year), a stabilization phase (2001-2014, +4% annual growth), and an exponential growth phase (2015-2024, 13 articles/year), closely aligned with global policy shifts in traditional medicine. China emerged as the dominant contributor (338 articles, 64.2% global output), yet Canada demonstrated superior research impact (108 citations/article), highlighting a productivity-impact paradox. Mechanistic investigations into neuroimmunological pathways, particularly μ-opioid receptor modulation (centrality 0.74), became central research pillars, reinforced by biomarker-correlated clinical trials showing β-endorphin-FEV1 interactions (r = 0.526, p = 0.008). Persistent translational gaps were evident, with 63% of RCTs relying on subjective "deqi" assessments despite technological advances in objective acupuncture monitoring.

This analysis reveals critical asymmetries between Eastern research productivity and Western methodological innovation in acupuncture-COPD research. This analysis suggests a need for a threefold strategy integrating multiscale neuroimaging validation, globalized trial standardization through CONSORT-Acupuncture frameworks, and equitable North-South knowledge exchange to address the growing burden of COPD-related dyspnea in aging populations.

Exosomes, known as small membrane vesicles of endocytic origin produced by most cell types, exist in a variety of body fluids including plasma. The roles of exosomes in immune responses against Mycobacteria tuberculosis (Mtb) infection remain poorly characterized. Here, we found that miR-107 highly expressed in exosomes from plasma of TB patients but not healthy control (HC) subjects. Consistently, such miR-107-high exosomes were also detected in both the extracellular fluid released by mycobacterial-infected macrophages and the plasma of mycobacterial-infected mice. Interestingly, adding the miR-107-high plasma exosomes or the miR-107 mimics to infected THP-1 macrophages inhibited intracellular mycobacterial growth. Consistently, while nanoscale and fluorescence imaging revealed that miR-107 could be transferred inter-cellularly via exosomes, miR-107-enriched exosomes from miR-107 overexpressing cells also inhibited mycobacterial growth in THP-1 macrophages and primary monocytes/peripheral blood mononuclear cells (PBMC). Mechanistically, miR-107-high exosomes increased ROS production; miR-107 regulated Wnt pathway by targeting Wnt16 and promoted autophagy in THP-1 macrophages. Furthermore, treatment of infected mice with miR-107-enriched exosomes reduced mycobacterial infection in lung tissues. Our results raise a possibility to explore miR-107-high plasma exosomes for a potential surrogate marker for TB. Findings suggest that exosomes enriched with miR-107 or other bio-active molecules may potentially serve as an attractive approach for treatment of infection.

Chronic obstructive pulmonary disease (COPD), as the third leading cause of global mortality, presents complex pathological mechanisms and imposes a substantial health burden. Emerging evidence reveals that olfactory receptors (ORs), traditionally associated with odor detection, exhibit non-canonical regulatory functions in COPD pathogenesis. This review systematically explores ORs' multidimensional roles: environmental triggers activate specific ORs in specific cells, initiating chronic inflammatory cascades. Persistent inflammation drives irreversible airway remodeling through smooth muscle proliferation and extracellular matrix reorganization. Preclinical and clinical studies demonstrate that OR agonists/antagonists modulate the inflammation-remodeling axis to influence pulmonary function, though their pleiotropic effects complicate therapeutic targeting. The cell type-specific expression patterns and diverse ligand profiles of ORs create unique opportunities for precision interventions, while posing challenges in tissue delivery and receptor efficacy optimization. Future investigations should integrate single-cell omics and artificial intelligence to elucidate OR-mediated dynamic networks, downstream signaling pathways, and their interplay with microbiome-gut-lung axis regulation. This review not only advances our understanding of OR biology in respiratory diseases but also proposes a novel theoretical framework for developing OR-based diagnostic and therapeutic strategies in the early management of COPD.

Patient demand often drives inappropriate antibiotic prescribing for acute respiratory tract infections (ARTI). This study aimed to develop novel culturally- and linguistically-tailored patient education material regarding appropriate ARTI care.

This qualitative study used a four-phase approach to develop single-page English, Spanish, and Haitian Creole patient education materials for appropriate ARTI treatment designed for clinical use: 1) material development informed by pre-existing materials, 2) learner verification, 3) revision, and 4) transcreation. Patient and provider focus groups and interviews were conducted at three Massachusetts health systems. Transcripts were coded and analyzed using a framework informed by the Patient Education Materials Assessment Tool.

Twenty-six providers and 48 patients (27 English, 10 Spanish, 11 Haitian Creole speaking) participated. Participants suggested improving readability by replacing text blocks with bulleted lists and usability by providing self-care solutions. The transcreation process resulted in literal translations that were unclear to Spanish and Haitian Creole speakers, who provided culturally-appropriate suggestions.

Patient education materials are co-created with diverse patient and provider populations to create culturally-tailored materials, available in multiple languages, for ARTI treatment.

Learner verification, revision, and transcreation can result in understandable and actionable materials for patients in multiple languages. Materials may help decrease demand for and rates of inappropriate antibiotic prescribing for ARTI.

We investigated statin-based peptidomimetic compounds as inhibitors of SARS-CoV-2 papain-like protease (PLpro) by in silico methods, including molecular docking/dynamic simulations and ADMET prediction, as well as enzymatic in vitro assays. Five compounds (LQMed 426, 428, 430, 431, and 432) were identified as having promising interactions with the active site and an allosteric site of PLpro. The docking poses in the active site revealed that the compounds interacted with the catalytic triad (Cys111, His272, and Asp286). Compound 426 stood out for forming significant hydrophobic interactions and hydrogen bonds. In molecular dynamic (MD) simulations, there was a tendency for the compounds to migrate to a pocket in the ubiquitin-like (Ubl) domain region, indicating possible allosteric inhibition. Principal component analysis (PCA) and free energy landscape (FEL) plot showed significant differences in the conformational stability of protein-ligand complexes. Complex 432 had the highest stability (PC1: 24.9%, PC2: 10.5%) with restricted movements, while complex 430 had the lowest stability and the highest PC1, indicating broader movements. Complexes 426 and 428 had intermediate stability. FEL analysis confirmed that complex 432 had multiple minimum energy clusters, suggesting a greater likelihood of stable enzyme-ligand complex. In vitro assays demonstrated that all compounds inhibited PLpro activity by at least 50%, with IC₅₀ values ranging from 0.85 µM to 4.06 µM. Compounds 426 and 432 were the most promising, with IC₅₀ of 0.85 µM and 1.46 µM, respectively, values comparable to the GRL-0617 reference inhibitor. Binding free energy analysis indicated that compounds 430 and 431 showed significant affinity for the allosteric site (-27 kcal/mol and - 14 kcal/mol, respectively), while compound 428 showed reduced stability. In addition, in silico pharmacokinetics and toxicity (ADMET) prediction revealed that statine-based compounds are promising compared to GRL-0617 due to the low potential of inhibition of CYP's family and toxicity risk. Overall, the tested compounds, especially 426 and 432, showed potential as inhibitors of SARS-CoV-2 PLpro and may act by non-competitive or mixed mechanisms, making them promising candidates for developing antivirals against CoViD-19.

Sepsis is a major cause of acute lung injury (ALI) characterized by inflammatory responses. Ubiquitination plays a critical role in the pathogenesis of ALI. This study aimed to investigate the role of USP50, a deubiquitinating enzyme, in sepsis-induced ALI and its underlying molecular mechanisms. THP-1 cells were differentiated into macrophages and exposed to lipopolysaccharide (LPS) to establish an in vitro injury model. Pyroptosis was assessed using immunoblotting, flow cytometry, and enzyme-linked immunosorbent assay. The regulation of USP50 on NLRP3 deubiquitination was analyzed through immunoprecipitation, immunoblotting, and protein stability assays. The in vivo function of USP50 was evaluated using a cecal ligation and puncture (CLP)-induced septic mouse model. Results demonstrated that USP50 expression was significantly upregulated in the blood of patients with sepsis-induced ARDS and in the lungs of CLP-treated mice. USP50 knockdown suppressed pyroptosis in LPS-stimulated macrophages and septic mice. Furthermore, USP50 inhibition enhanced NLRP3 degradation by facilitating K48-linked ubiquitination. Overexpression of NLRP3 reversed the anti-pyroptotic effects induced by USP50 depletion in macrophages. In conclusion, USP50 suppression attenuates macrophage pyroptosis through inhibition of NLRP3 deubiquitination, thereby reducing lung injury in sepsis-induced models. These findings identify USP50 as a potential therapeutic target for sepsis-associated acute lung injury.

Acute lung injury (ALI) is closely associated with high mortality in severe acute pancreatitis (SAP). Nr4a3 is a nuclear receptor with proinflammatory effects. The role of Nr4a3 in SAP-associated ALI is unclear. Caerulein (CRE)-induced AP mice represented significant pancreatic and lung pathological injury, with high Nr4a3 expression in lung tissues. Nr4a3 expression in lung tissues of AP mice inhibited CD31 expression, suggesting lung microvascular injury. In vitro and in vivo experiments were performed to investigate the effect of Nr4a3 inhibition in mitigating SAP-associated ALI. Nr4a3 downregulation reduced permeability, increased trans-endothelial electrical resistance (TEER) and VE-cadherin expression in TNF-α-induced human pulmonary microvascular endothelial cells (hPMVECs), suggesting recovered endothelial barrier function. Nr4a3 knockdown attenuated lung injury in AP mice, as reflected by restored lung edema and endothelial barrier function. Reduced inflammatory cell counts and mediators indicated that Nr4a3 knockdown mitigated lung inflammation in AP mice. The up-regulation of Nr4a3 in TNF-α-induced hPMVECs was further elevated after Sirt1 (a deacetylase) inhibition. Mechanistically, Sirt1 deficiency increased the enrichment of CREB at the Nr4a3 promoter through acetylating H3K27, thereby promoting Nr4a3 expression. Rescue experiments in vivo demonstrated that Nr4a3 knockdown attenuated lung injury aggravated by Sirt1 inhibition. These results suggested that Sirt1 might prevent CREB enrichment by inhibiting histone acetylation in the Nr4a3 promoter, thereby suppressing Nr4a3 expression and ultimately attenuating ALI.

The COVID-19 pandemic has exposed the vulnerabilities of lower-income countries due to limited healthcare infrastructure and socioeconomic constraints, highlighting the need for effective containment measures that minimize socioeconomic costs and prepare for future pandemics alike, which are expected to become more frequent. Although prior studies have examined various strategies in these regions, a significant gap remains in quantitative research on affordable measures to combat the highly transmissible SARS-CoV-2 Omicron variant, which greatly challenges effective measures for previous strains. Studies on targeted containment measures for Omicron have dramatically declined even in higher-income regions, and their findings could be much less applicable in lower-income regions due to substantial socioeconomic disparities.

This study addresses this gap by focusing on South Africa. A spatial Susceptible-Exposed-Infected-Recovered (SEIR) model was developed to simulate the virus spread during the country's first Omicron wave from November 2021 to April 2022, integrating multisource statistics to overcome the typical scarcity of inter-city mobility data in lower-income countries. Three affordable containment measures were examined: (1) restricting inter-city mobility in epicenter provinces, while allowing nationwide intra-city movement for livelihood activities; (2) home isolation for positive cases, alongside quarantine for co-residents, accounting for high rates of asymptomatic cases, underreporting, and delays of self-isolation; and (3) prioritizing booster vaccinations for high-risk healthcare workers.

The findings indicate that restricting inter-city mobility in the epicenter Gauteng, which only accounted for 3.6% of national mobility, could reduce national infections by 15.0%. Quarantining households with positive cases could reduce infections by 10.9%, despite the high rates of asymptomatic cases and presymptomatic transmission. Prioritizing booster vaccinations was also effective when healthcare workers had a much higher infection risk than others. Meanwhile, these measures incurred minimal socioeconomic costs compared to earlier pandemic strategies. Additionally, the spatial variation of containment measure effectiveness suggests that timely implementation of these measures before the infection rate escalates is critical for ensuring their effectiveness.

This research provides essential insights for lower-income countries to manage current and future pandemics within their economic and healthcare constraints, especially regarding targeted mobility restriction, quarantine, prioritized vaccination, and timing of containment measures.