Search Results (1,881)

An abnormal increase in acne-causing bacteria is the main cause of acne. This study aimed to investigate Piper griffithii C.DC. as a new source of compounds for inhibiting acne-causing bacteria and to provide the first elucidation of the mechanism of action against these bacteria. The antibacterial efficacy of 27 Piper species was examined against acne-causing clindamycin-resistant bacterial strains. Antibacterial activity of various crude extracts derived from leaves or stems extracted using hexane, ethyl acetate, or ethanol was evaluated. Ethyl acetate leaf extract of P. griffithii exhibited the greatest antibacterial effect against all tested bacteria. Zeylenone, an antibacterial substance isolated, purified, and characterized from the ethyl acetate leaf extract of P. griffithii, disrupts cell walls and membranes. Minimum bactericidal concentration (MBC) values were 1.25, 2.5, and 7.5 mg/mL for Cutibacterium acnes, Staphylococcus aureus, and S. epidermidis, respectively. Zeylenone derived from P. griffithii leaves was nontoxic to human skin keratinocytes (HaCaT). A formulated anti-acne gel with zeylenone was effective in controlling acne-causing bacteria. These results suggest that zeylenone isolated from P. griffithii leaves can be further developed as a natural ingredient in anti-acne products. This is the first report of the use of zeylenone from P. griffithii for eliminating acne-causing bacteria. Full article

Erythropoietin-producing hepatocellular receptor A2 (EphA2) has emerged as a key mediator that promotes tumor malignant progression. EphA2 overexpression and its non-canonical signaling lead to oncogenic transformation, metabolic reprogramming, resistance to treatments, and metastasis. Therefore, strategies targeting EphA2 have been evaluated in clinical trials. However, the clinical effects were not sufficient. An anti-EphA2 monoclonal antibody (mAb), Ea₂Mab-7 (mouse IgG₁, κ), demonstrated high affinity and specificity among Eph receptors. In this study, we produced recombinant class-switched Ea₂Mab-7 variants, including Ea₂Mab-7-mG_2a (mouse IgG_2a) and Ea₂Mab-7-hG₁ (human IgG₁). Both Ea₂Mab-7-mG_2a and Ea₂Mab-7-hG₁ recognized human triple-negative breast cancer MDA-MB-231, pancreatic cancer MIA PaCa-2, and colorectal cancer HCT-15 in flow cytometry. Furthermore, both Ea₂Mab-7-mG_2a and Ea₂Mab-7-hG₁ exerted significant antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against these tumors. In mouse xenograft models of breast, pancreatic, and colorectal cancers, both mAbs demonstrated antitumor activity. These results indicate the potential of Ea₂Mab-7 variants for the treatment of EphA2-positive cancers. Full article

Background/Objectives: Drowning is a leading preventable cause of unintentional injury death, yet U.S. prevention efforts have largely focused on children. Despite international declines in pediatric drowning mortality, adult trends remain poorly characterized. We examined long-term trends and disparities in unintentional drowning mortality among U.S. adults aged ≥25 years from 1999 to 2024. Methods: Using CDC WONDER Multiple Cause of Death data, drowning deaths were identified using ICD-10 codes W65–W74, V90, and V92. Age-adjusted mortality rates (AAMRs) per 100,000 were computed by direct standardization to the 2000 U.S. standard population. Joinpoint regression estimated the annual percent change (APC) and average annual percent change (AAPC). Three sensitivity analyses assessed transport-related code exclusion, pandemic-era restriction, and multiple cause-of-death coding. Results: During 1999–2024, 101,743 unintentional drowning deaths occurred among U.S. adults aged ≥25 years (76,554 males; 25,201 females), with 58.09% in natural water or outdoor settings. The overall AAMR showed a non-significant increase (AAPC: 0.55%, p = 0.054); however, joinpoint analysis identified stable rates through 2013 followed by a significant sustained increase (APC: 1.32%, 95% CI: 0.32–2.32, p = 0.012). The male-to-female rate ratio narrowed significantly from 4.00 (1999) to 3.32 (2024) (ratio of rate ratios: 0.83, p = 0.0006), driven by a sustained female increase (AAPC: 1.27%, p < 0.001). Adults aged 65–85+ showed the steepest rise (AAPC: 1.15%, p < 0.001). Non-Hispanic AI/AN adults had the highest rates (3.47–5.44 per 100,000), and non-metropolitan areas consistently exceeded metropolitan rates. Conclusions: A significant upward trajectory has persisted since 2013, with marked disparities by age, sex, race/ethnicity, and geography. Adult-focused, equity-driven prevention strategies aligned with USNWSAP implementation are needed to address this underrecognized burden. Full article

Background: Anemia is a major public health issue, particularly among women of reproductive age (WRA) in low- and middle-income countries (LMICs). Pakistan’s National Nutrition Survey (NNS) 2011 showed a high prevalence of vitamin B₁₂ (B₁₂) and folate deficiency among WRA, necessitating further investigation in subsequent surveys. Methods: Blood samples from 31,828 WRA (15–49 years old) were collected using a stratified multi-stage sampling technique in NNS-2018. We conducted a secondary analysis using population-weighted logistic regression to assess the association of potential factors with B₁₂ and folate deficiency. B₁₂ (n = 4442) and folate (n = 12,662) samples were measured using an electrochemiluminescence immunoassay and a Centers for Disease Control and Prevention, USA (CDC)-approved microbiologic assay, respectively. Results: Folate deficiency was present in 44.7% WRA, and 20.2% had B₁₂ deficiency. Provincial distribution was associated with folate deficiency, i.e., Sindh (OR = 1.140, 95% CI 1.018, 1.285), Baluchistan (OR = 1.237, 95% CI 1.052, 1.453), and Islamabad (OR = 1.524, 95% CI 1.109, 2.092), while B₁₂ deficiency was prevalent in Islamabad (OR = 1.673, 95% CI 1.122, 2.497), Gilgit Baltistan (OR = 2.472, 95% CI 1.197, 5.106), and newly merged districts of KPK (OR = 1.584, 95% CI 0.977, 2.570). Rural residence (OR = 1.407, 95% CI 1.125, 1.760), obesity (OR = 1.649, 95% CI 1.282, 2.122), and overweight (OR = 1.560, 95% CI 1.262, 1.928) were associated with B₁₂ deficiency. Conclusions: Our results show regional and demographic differences in the prevalence of folate and B₁₂ deficiencies among WRA. This underscores the need for targeted nutritional interventions and further longitudinal studies to identify potentially associated factors. Full article

Remote sensing image change captioning (RSICC) aims to generate semantic textual descriptions characterizing changes between bi-temporal remote sensing images, with wide applications in disaster assessment and urban planning. However, existing methods face specific drawbacks: CNN-based models have limited ability to capture long-range spatial correlations due to local receptive fields, and Transformer-based models suffer from quadratic complexity while distributing attention uniformly across all spatial positions, resulting in weak perception of salient changes in background-dominated scenes. In this paper, we present PM3Net (Progressive Mask-guided Multigranular Mamba Network), which leverages Mamba state space models with linear complexity for efficient spatiotemporal change modeling. The Progressive Mask-guided Encoder (PME) creates dual-source change masks combining L2 norm spatial differences with cosine distance semantic differences for progressive change feature extraction from detailed structures to high-level semantics. The Mask-guided Feature Enhancement (MFE) module applies mask-weighted refinement and cross-layer fusion to emphasize salient change regions while suppressing background interference, producing multigranular visual representations. Experiments on LEVIR-MCI and WHU-CDC datasets show PM3Net achieves superior results compared to existing methods, with BLEU-4 scores of 66.89 and 73.05, respectively. The results confirm PM3Net’s ability to solve the RSICC task while demonstrating how Mamba models can succeed in this specific field. Full article

Boule is the ancestral member of the Deleted in Azoospermia (DAZ) family and is pivotal for gametogenesis and male fertility in most animals. However, there is a dearth of information on molluscan boule. Here, we identified a counterpart (Pcbol) from the genome of Pomacea canaliculata, which has emerged as a cosmopolitan alien species and notorious pest that causes devastating damage to aquatic biodiversity, freshwater ecosystems and crop production in invaded ranges. This study aimed to investigate the biological roles of Pcbol in male reproduction and to decipher the molecular mechanisms underpinning its modulation via dsRNA-delivered RNA interference (RNAi). The bioinformatic analysis showed that the Pcbol genomic sequence is 12,934 nt in length, harboring an open reading frame of 294 nt that encodes 97 aa residues, with an RRM domain evolutionarily conserved among molluscan orthologues. Spatiotemporal expression profiling indicated the predominant abundance of Pcbol in adult males and testis tissues. dsPcbol, injected at a dose of 4 μg/per snail for 5 days, yielded optimal silencing at both transcript and translation levels of Pcbol, as revealed by qRT-PCR and Western blotting. Immunofluorescence echoed a pronounced reduction in Pcbol signal intensity following RNAi. In addition to the arrested reproductive gland phenotype, the number of sperm cells substantially dwindled upon dsPcbol treatment relative to the dsGFP control. In biochemical and fecundity assays, Pcbol depletion triggered a significant decrease in Te/SP/Arg content and suppressed the number of deposited eggs and hatchability. Furthermore, spermatogenic genes like CDC25/TSSK1/SPATA17/DDX4/Dmrt2/Sox2/Kelch10/SPO11 displayed considerable downregulation post Pcbol silencing, with molecular docking predicting a strong affinity between CDC25 and Pcbol. These molecular modules may interact with Pcbol to mediate knockdown effects on spermatogenesis dysfunction. Collectively, our findings not only confirmed that boule was indispensable for spermatogenesis and male fertility in a mollusk, but also highlighted the Pcbol-based male sterile technique (MST), which can be incorporated into precision pest management (PPM) strategies for sustainable control of P. canaliculata. Full article

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant pathogenic fungus with an increased ability to cause outbreaks in healthcare facilities, leading to poor patient outcomes. Since its initial discovery in 2009, C. auris has spread rapidly across continents and is now classified by both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) as a critical-priority pathogen. This review summarizes current knowledge on the origin, taxonomy, microbiology, and virulence mechanisms of C. auris, emphasizing its thermotolerance, osmotolerance, and biofilm-forming capacity on biotic and abiotic surfaces, as well as aspects related to its antifungal drug resistance and management. These features, together with its genomic plasticity, contribute to persistence, transmission, and drug resistance. Emerging evidence also supports a potential link between climate change and C. auris evolution, highlighting environmental adaptation as a driver of pathogenicity. Combating C. auris will require multidisciplinary efforts to mitigate its expanding global impact. Full article

Non-albicans Candida (NAC) species have emerged as significant opportunistic pathogens due to their reduced susceptibility to antifungal agents combined with their strong ability to form biofilms. The severity of systemic candidiasis caused by NAC species highlights the need for novel antifungal strategies. Retinoids, a group of compounds derived from vitamin A, have been demonstrated to possess significant antifungal activity against the reference strain C. albicans ATCC 2091. This study aimed to assess the antifungal potential of three retinoids, all-trans retinoic acid (ATRA), trifarotene, and tazarotene, against NAC clinical isolates. Various concentrations of the retinoids (from 1 mM to 0.06 mM) were tested in vitro against the growth, adhesion, and biofilm development of NAC species, including Candida glabrata, Candida krusei, and Candida tropicalis, as well as a reference strain of C. auris (CDC B11903). At 1 mM, all three compounds maximally inhibited the growth, adhesion, and biofilm formation of all tested NAC species. At lower concentrations (0.5–0.06 mM), C. krusei remained the most susceptible, especially to tazarotene. Tazarotene also showed a strong inhibitory effect on C. auris and C. glabrata at 0.5–0.25 mM; however, this effect was weaker than that observed against C. krusei. At low concentrations (0.12–0.06 mM), only trifarotene induced a mild but statistically significant inhibition of C. tropicalis growth. Trifarotene at 0.5 mM was also the most effective retinoid in inhibiting C. glabrata and C. tropicalis adherence and biofilm formation, with inhibitory activity maintained even at sub-0.5 mM concentrations (0.25–0.12 mM). Overall, the results suggest that all three retinoids exhibited dose-dependent and species-specific antifungal activity against NAC species, supporting their potential as novel, tailored antifungal agents against drug-resistant Candida strains. Full article

Background/Objectives: Healthy food incentive programs (HFIP), such as fruit and vegetable voucher incentives, can supplement other nutrition assistance programs to support food and nutrition security. However, little is known about the prevalence of HFIP, particularly at the municipal level. This study examines the prevalence of HFIP in a nationally representative sample of U.S. municipalities and the association between the availability of HFIP and municipal characteristics. Methods: Using data from the CDC’s 2021 National Survey of Community-Based Policy and Environmental Supports for Healthy and Active Living (n = 1982 municipalities), a weighted bivariate analysis and multivariable logistic regression analysis were conducted to estimate the prevalence of HFIP overall and by municipal characteristics, and to assess the relationship between municipal characteristics and HFIP. Results: Only 7.8% of municipalities reported offering HFIP in 2021. The odds of having an HFIP were higher in municipalities with a food policy council (aOR 2.8; 95%CI: 1.9, 3.9) compared to those without. Larger communities (size ≥ 50,000 reported 24.6%) and those with a higher prevalence of residents living in poverty were also more likely to offer HFIP. Conclusions: Few municipalities reported offering HFIP. Results suggested that engaging institutions and individuals (e.g., via food access coalitions) may be strategies that could support municipalities initiating and implementing HFIP to improve diet quality and reduce chronic disease risk. Full article

Dendritic cells (DCs) are key sentinels in the lung mucosa that interpret environmental signals to either promote tolerance or trigger inflammation, influencing the development of chronic lung diseases. This review highlights recent mechanistic insights showing that metabolic checkpoints serve as upstream regulators of DC fate and activity: inflammatory stimuli activate HIF-1α/mTOR-linked glycolytic pathways that drive maturation, cytokine secretion, antigen presentation, and migration. In contrast, AMPK-related oxidative and lipid metabolism pathways support tolerogenic states that encourage regulatory T-cell responses and inhibit checkpoints like PD-1/PD-L1. We also present evidence that DC subset specialization (cDC1 vs. cDC2) and their tissue location interact with these metabolic pathways to regulate lymphoid tissue formation, including the development and persistence of tertiary lymphoid structures in chronically inflamed lungs. These ectopic lymphoid tissues enhance local immune responses through DC–stromal interactions and ongoing T follicular helper–B cell communication, contributing to persistent inflammation and tissue remodeling in conditions such as COPD, asthma, pulmonary hypertension, and fibrotic interstitial lung disease. Finally, we discuss the translational potential of targeting this immunometabolic–lymphoid pathway, suggesting that modulating metabolic regulators, migratory circuits, and tolerogenic programs could restore immune balance while maintaining host defense—a promising framework for developing advanced therapies for chronic lung inflammation. Full article

Meningitis remains a significant cause of morbidity and mortality in the United States despite advances in vaccination, antimicrobial therapy, and critical care. However, long-term national mortality patterns across demographic and geographic subgroups remain incompletely characterized. This study evaluated temporal trends in meningitis-associated mortality among U.S. adults aged ≥25 years from 1999 to 2024 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database. Death certificates listing meningitis as either the underlying cause or a contributing cause of death were identified using ICD-10 codes to capture meningitis-associated mortality. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Across the study period, meningitis-associated mortality demonstrated an early decline followed by stabilization and more recent increases in several subgroups. AAMRs decreased significantly from 1999 to 2001 (APC: −14.09%; p = 0.0029) and from 2001 to 2013 (APC: −4.74%; p < 0.000001), followed by a significant increase from 2013 to 2024 (APC: 1.78%; p = 0.0059). Despite these later increases, the overall AAPC across the full study period remained significantly negative (AAPC: −2.73%; p < 0.000001). Earlier analyses using shorter observation windows did not demonstrate a statistically significant overall trend; the significance observed in the present analysis reflects the inclusion of extended mortality data through 2024. Mortality rates were consistently higher among males and adults aged ≥65 years. Non-Hispanic Black individuals experienced increasing mortality after 2013, while Hispanic individuals demonstrated a sustained increase across the entire study period. Regional analyses showed recent increases in the Northeast, South, and West, while non-metropolitan areas did not experience statistically significant improvement through 2020. In summary, meningitis-associated mortality among U.S. adults declined significantly during the early study years but has shown stabilization and recent increases in several demographic and geographic subgroups since approximately 2013. Although overall mortality across the full study period remains lower than baseline levels, these emerging disparities highlight the importance of continued surveillance and targeted public health interventions. Full article

Human immunodeficiency virus (HIV) remains a major global health challenge, requiring accurate diagnostic testing for early detection. Chemiluminescent immunoassay screening, particularly the Architect HIV Ag/Ab Combo assay, followed by immunoblot confirmation using INNO-LIA™ has traditionally been used in many diagnostic workflows. To address these limitations, the U.S. Centers for Disease Control and Prevention (CDC) recommends the use of an HIV-1/2 antibody differentiation immunoassay, such as the Geenius HIV-1/2 Supplemental Assay, as part of the confirmatory testing algorithm. This study evaluates the performance of two rapid HIV-1/2 confirmatory assays—the Multisure HIV-1/2 Confirmatory Test and the Bio-Rad Geenius HIV-1/2 Supplemental Assay—within a CDC-aligned diagnostic framework, with the aim of assessing Multisure as a potential alternative differentiation assay. A total of 224 archived serum samples were analyzed, including true positives (n = 38), true negatives (n = 139), false positives (n = 20), and INNO-LIA™ indeterminate samples (n = 27), as defined by Architect HIV and INNO-LIA™ results. Samples were initially screened using the Architect HIV Ag/Ab Combo assay, confirmed by INNO-LIA™ and PCR, and subsequently re-tested using Multisure HIV-1/2 and Geenius HIV-1/2 assays. Diagnostic performance metrics were evaluated. Both rapid assays demonstrated 100% sensitivity and specificity when compared with INNO-LIA™. Among INNO-LIA™ indeterminate samples, Multisure HIV-1/2 classified 81.5% as negative compared with 55.6% using Geenius HIV-1/2. When compared with PCR, Multisure demonstrated higher specificity (89.2%) and positive predictive value (89.5%) than Geenius (82.9% and 84.6%). No confirmed HIV-2 infections were identified in the analyzed dataset, and HIV-1 subtype information was not available for the archived samples; therefore, conclusions regarding HIV-1/2 differentiation are based primarily on assay design and antigenic targets. Multisure HIV-1/2 demonstrated strong diagnostic performance comparable to established differentiation assays and may represent a practical alternative rapid confirmatory option within CDC-aligned HIV diagnostic workflows. Further studies including larger datasets and confirmed HIV-2 infections are warranted to further validate its clinical utility. Full article

Background/Objective: Dietary polysaccharides are increasingly recognized as functional nutritional components that support human health through modulation of immune function. However, clinical evidence linking their intake to site-specific upper respiratory mucosal immune health in humans remains limited. This study investigated whether dietary β-1,3/1,6-glucan (SC-BG) from baker’s yeast may support upper respiratory mucosal immune health in healthy adults. Methods: Following in vitro assays on human dendritic cells (DCs), a randomized, double-blind, placebo-controlled parallel-group trial was performed in healthy adults (18–69 years) who consumed either SC-BG or placebo capsules for 12 weeks in Japan. The primary outcome was circulating DC activation. Secondary outcomes were mucosal immune markers including secretory immunoglobulin A (s-IgA) and lysozymes from site-specific mucosal swabs (posterior oropharyngeal wall/nasopharynx) and salivar, and self-perceived upper respiratory tract symptoms. Results: SC-BG increased CD80 expression in DCs in vitro. In the clinical trial, 40 participants were randomized (n = 20 per group), and 39 (SC-BG: n = 19, placebo: n = 20) were analyzed. At week 8, the SC-BG group showed higher cDC1 CD80 expression than placebo. SC-BG intake also attenuated declines in s-IgA levels in the posterior oropharyngeal wall and nasopharynx and increased salivary lysozyme concentrations. Participants receiving SC-BG reported fewer cumulative days with upper respiratory tract-related local and systemic symptoms. No test food-related adverse events were observed. Conclusions: These findings provide preliminary clinical and mechanistic observations suggesting that dietary SC-BG may enhance circulating cDC1 activation and may help support upper respiratory local mucosal immune health in healthy adults, highlighting the potential of dietary polysaccharides as functional nutritional strategies for maintaining immune resilience. Full article

Oropouche fever (OF), caused by Oropouche virus (OROV), has expanded beyond its Amazonian range into Minas Gerais (MG), Brazil, raising concern about transmission in extra-Amazonian Atlantic Forest landscapes. Critical gaps persist regarding Culicoides vector communities, anthropophily, and climate-sensitive transmission risk in these newly affected regions. We conducted targeted entomological surveys outbreak-driven by human OF cases, standardized across five MG communities using CDC light traps and Protected Human Attraction (PHA) to characterize Culicoides composition. Females of Culicoides underwent RT-qPCR for OROV (n = 819) and physiological assessment (n = 312). We developed an entomological alert framework that integrates blood-fed abundance, minimum infection rate (MIR) upper confidence bounds, and environmental drivers (i.e., mean temperature, relative humidity and precipitation) via generalized additive mixed models, which explained 68% of the variability in Culicoides abundance and the alert index across communities. We collected 1171 Culicoides individuals representing five species (C. leopoldoi, C. paraensis, C. pusillus, C. foxi, and C. limai). C. leopoldoi (79.1%) and C. paraensis (20.3%) were the predominant species; notably, C. paraensis is recognized as the primary vector of OROV in the Americas. C. paraensis was documented for the first time in all five outbreak areas and dominated PHA captures (90%), suggesting anthropophily. Although no specimens tested OROV-positive (consistent with expected field infection rates of 0.01–1%), MIR upper bounds reached 132/1000 in low-sample settings and humidity and temperature strongly modulated abundance. This operational baseline and alert index transform virologically negative, sparse surveillance data into prioritized targets for intensified sampling and vector control during early, low-prevalence phases, when containment of OROV’s extra-Amazonian spread is still achievable. Full article

Background: Human granulocytic anaplasmosis (HGA) is a tick-borne zoonotic infection caused by Anaplasma phagocytophilum and transmitted by Ixodes species. In temperate regions, HGA is considered seasonal, with most cases occurring during late spring and summer. We describe two cases of HGA diagnosed in January during a winter period with episodic temperatures exceeding thresholds for tick activity, highlighting atypical seasonal presentation and diagnostic challenges. Methods: This report details the clinical course, diagnostic reasoning, and management of two patients evaluated at a tertiary care hospital in Suffolk County, New York. Data were derived from direct clinical care and the electronic health record. The institutional review board determined this work did not constitute human subject research. Written informed consent was obtained from both patients. Results: Both patients presented with acute febrile illness and characteristic laboratory abnormalities. Due to winter season, tick-borne infection was not initially suspected, resulting in delayed consideration. PCR testing confirmed A. phagocytophilum infection in Case 1, meeting CDC criteria for confirmed HGA. Case 2 met CDC criteria for probable HGA based on serologic testing showing elevated IgG (1:320) in the appropriate clinical context. Treatment with doxycycline led to rapid clinical improvement and complete recovery. Conclusions: These cases demonstrate that HGA can be diagnosed during winter months in endemic regions. Although the precise timing of infection cannot be determined, these observations occurred during a period when episodic temperatures exceeded thresholds for tick activity. The cases highlight limitations of season-based diagnostic assumptions and suggest maintaining clinical suspicion for anaplasmosis year-round in endemic areas. Full article