PLoS ONE最新文献

Chronic exposure to air pollution is associated with an increased cardiovascular disease (CVD) risk, and inflammation induced by fine particulate matter (PM2.5) exposure is a key driver in CVD development. However, the mechanism by which PM2.5 causes cardiacovescular damage remains unclear. Here, Balb/c mice were intratracheally instilled with PM2.5 suspension at doses of 2.0 mg/kg or 4.0 mg/kg body weight for 7 consecutive days to establish an aortic injury model. Pathological changes were assessed by hematoxylin and eosin (H&E), elastic Van Gieson, and Masson's trichrome staining. Potential pathways were identified through GeneCards database analysis, R language, and Metascape pathway enrichment analysis. Immune cell profiles in the blood were analyzed by flow cytometry, and serum inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Confocal microscopy was used to evaluate inflammatory cell infiltration in the aorta. Intestinal barrier integrity was assessed by transmission electron microscopy; H&E, and immunofluorescence staining; and western blotting. We found that high-dose PM2.5 exposure led to inflammatory cell infiltration, disorganization of elastic fiber layers, and aortic tissue fibrosis. Pathway enrichment analyses indicated the involvement of pathways related to the regulation of inflammatory responses and responses to bacterial molecules. Increased inflammatory cells and pro-inflammatory cytokines were detected in the blood, accompanied by an increase in circulating lipopolysaccharide. PM2.5 exposure disrupted the intestinal mucosal barrier, leading to reduced claudin-1 and occludin (tight junction protein) expression, which exacerbated systemic inflammation and induced aortic injury. In conclusion, PM2.5 exposure caused pathological aortic damage and exacerbated systemic inflammation, potentially mediated by compromised intestinal barrier integrity.

Background: Mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs) are an attractive cell source for regenerative medicine due to high proliferative capacity, non-invasive accessibility, and minimal ethical constraints. However, their therapeutic efficacy may vary with isolation technique and culture conditions.

Methods: We compared three WJ-MSC isolation methods; two explant approaches (non-scraped and scraped) and one enzymatic method - each cultured with or without basic fibroblast growth factor (bFGF). WJ-MSCs were obtained from three full-term umbilical cords, and subsequently evaluated for cell viability, proliferation kinetics, immunophenotypic surface marker expression, multilineage differentiation potential, and proteomic profiles through mass spectrometry coupled with bioinformatics analyses.

Results: All methods produced viable WJ-MSCs, although enzymatic isolation without bFGF resulted in early culture failure in 2/3 donors and was excluded from downstream analyses. Highest viability was observed with the non-scraped explant method supplemented with bFGF, and bFGF significantly enhanced proliferation by reducing cell doubling time. All groups consistently expressed canonical MSC markers, along with WJ-MSC-specific surface proteins. Osteogenic differentiation was robust across all groups, whereas adipogenic differentiation was limited. Proteomic profiling revealed 2,372 proteins commonly expressed across all groups, indicating a largely stable core proteome, with isolation- and bFGF-dependent modulation observed primarily at the pathway level. Gene set enrichment analysis showed that bFGF-treated cultures were enriched for metabolic pathways, including oxidative phosphorylation and fatty acid metabolism, whereas bFGF-free and enzymatic isolation methods showed increased inflammatory and stress-related signatures. Differential expression analysis further identified 36 proteins uniquely regulated by isolation method and bFGF treatment, associated with cell adhesion, tissue morphogenesis, and immunomodulatory functions.

Conclusion: This study clarifies how isolation- and growth factor-driven effects shape the functional properties and paracrine identity of WJ-MSCs. The non-scraped explant method with bFGF emerges as a robust, reproducible approach, yielding high-viability, phenotypically stable, and metabolically resilient MSCs. These findings provide a framework for standardized WJ-MSC production optimized for regenerative and immunomodulatory applications.

Objective: This study investigates how Saudi parents of children with autism perceive the roles and responsibilities of school staff and families in implementing transition plans. It looks at how these duties are shared between home and school during the planning phase.

Methods: A cross-sectional, quantitative approach was employed. A total of 469 parents of students with autism from the Riyadh (n = 243) and Makkah (n = 226) regions completed a structured survey. The instrument, developed from validated measures and based on the National Technical Assistance Center on Transition (NTACT) practices, used a 5-point Likert scale. Descriptive and inferential statistics (t-tests and cross-tabulations) were applied to compare perceptions across demographic variables such as gender, education level, and region.

Results: Parents viewed schools as more responsible than homes for most transitional skills, especially in areas like self-advocacy, vocational preparation, and study skills. Conversely, daily living and independent living skills were more often considered the family's responsibility. Perceptions did not significantly differ based on gender, education, or location.

Conclusion: The results indicate a collaborative responsibility between families and schools, with schools being considered the primary partner in most skill areas. To support smooth transitions for individuals with autism, increased collaboration between educators and families and parent-led training are essential.

This study investigates the impact of different attachment shapes and configurations on the displacement, stress, and strain profiles of maxillary first molar during clear aligner-based orthodontic treatment. A subject-specific 3D maxillary model was developed from CBCT imaging, incorporating cortical and trabecular bone, periodontal ligament (PDL), teeth, attachments, and aligner geometry. Five attachment shapes square, rectangle, trapezoid, ellipse, and semicircle were analyzed in single and dual (buccal-lingual) configurations across four clinically relevant movements: mesialization, intrusion, extrusion, and rotation. Finite-element simulation results indicated that flat-shaped attachments (rectangular and trapezoidal) generated the greatest crown displacement but induced higher PDL strain (up to 0.390 mm/mm) and localized bone stress (7.11 MPa), particularly at the root apex and alveolar crest. Curved attachments provided more diffused load distribution but significantly reduced movement efficiency. Dual attachments improved root engagement and bodily displacement in all movement types, mitigating undesired tipping and enhancing force symmetry, albeit with elevated strain. Rotational control was most influenced by attachment geometry, with flat designs producing greater angular movement. Overall, attachment shape and placement exert a substantial influence on orthodontic biomechanics during aligner therapy. The findings underscore the need for evidence-based attachment protocols tailored to specific movement goals and patient risk profiles. These insights can guide clinicians toward optimizing clear aligner treatments for improved movement precision, minimized biological risk, and enhanced treatment outcomes in complex orthodontic cases.

Background: Mental health issues are commonly faced by the elderly population aged 60 and above, who are influenced by various risk factors, i.e., financial, family, social, and others that impact their quality of life. This study intends to identify the prevalence of depression, anxiety, and stress among the elderly population of Bangladesh and their associated factors.

Method: This cross-sectional study collected primary data from a sample of 400 elderly individuals aged 60 and above across four districts in Bangladesh. Depression, anxiety, and stress levels were measured using the PHQ-9, GAD-7, and PSS-10 scales, respectively. The ordinal logistic regression model is fitted to evaluate the effects of socio-demographic factors, and a confirmatory factor analysis is used to identify risk factors via a structural equation model.

Result: Findings revealed that 5.3% of elderly people have severe depression, 9.3% severe anxiety, and 4.75% high perceived stress. Older adults with poor health status were more likely to suffer from severe depression and anxiety. Social isolation and loneliness influence depression in old age. Significant risk factors include poor medical support from family and inadequate family relationships as age progresses, social discrimination and prejudice, and perceived social status. These factors were significantly associated with mental health problems (depression, anxiety, and stress) among the elderly population aged 60 and above.

Conclusion: Depression, anxiety, and stress are significant mental health issues among older people in Bangladesh. To ensure their quality of life, it is essential to diagnose and address these mental health problems to establish effective policies.

The global incidence of thyroid cancer (TC) has risen markedly, ranking as the tenth most common malignancy in 2020. Simultaneously, obesity now affects over one billion individuals worldwide, with its prevalence more than doubling since 1990. Emerging evidence suggests a significant association between high body mass index (BMI) and elevated TC risk, potentially mediated by mechanisms such as chronic inflammation and insulin resistance. This study aims to evaluate the global burden of thyroid cancer attributable to high BMI (TC-HBMI) from 1990 to 2021, examine temporal trends, and project future burden through 2036. We utilized data from the Global Burden of Disease Study 2021 to assess deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs). Temporal trends were examined using estimated annual percentage change (EAPC), joinpoint regression, and decomposition analysis. Inequality and future burden assessments were conducted through slope and concentration indices, frontier analysis, and Bayesian age-period-cohort modeling.

Due to the constantly evolving threat of antibiotic resistance, there is a dire need for novel antibacterial agents. Dihydropteroate synthase (DHPS) is a key bacterial enzyme which has been targeted for nearly a century as a means of selective treatment of microbial infections and exhibits two orthosteric binding sites - the p-aminobenzoic acid (pABA) site and the pterin site. The former is the target of sulfonamides, the earliest class of synthetic antibiotics, and its mutant forms have conferred resistance to this drug class, diminishing its utility in the clinic. Conversely, the pterin site, which is highly conserved across bacterial species, is purported to be less tolerant of mutations, rendering it an attractive target for novel antibiotics. Inspired by this, we conducted a large virtual screen of more than 450,000 compounds from commercial databases, identifying compounds 8802 and 7034 as potential pterin-site inhibitors. Compound 8802 was quite attractive as a hit due to the ease of generating analogues, leading to the synthesis of novel compounds LST-1 and LST-2. Rigid docking and molecular dynamics suggested favorable binding of these compounds to the pterin site of DHPS, and compound 8802 exhibited superior antibacterial activity compared to its analogues and 7034. Fluorescence polarization assays did not indicate competitive inhibition of pterin-derived probe binding, and surface plasmon resonance (SPR) suggested these compounds bind very weakly to DHPS, in a nonspecific manner. The in silico assessment of the physicochemical and pharmacological properties predicted a favorable overall profile, indicating that these are suitable leads for further study to improve their activity and determine their precise mode of action.

Objective: To investigate the association between vapor pressure deficit (VPD) and arthritis in middle-aged and older Chinese adults.

Methods: This study utilized data from the China Health and Retirement Longitudinal Survey (CHARLS) spanning the years 2011-2020. Participants without arthritis in 2011 were selected as the study population, with VPD designated as the primary exposure factor and newly diagnosed arthritis cases as the outcome variable. Logistic regression models were used to estimate the association between VPD and incident arthritis. Restricted cubic spline (RCS) analyses were conducted to assess potential nonlinearity. Subgroup analyses were performed to examine effect heterogeneity across population subgroups.

Results: A total of 4615 subjects were included, and a total of 1317 subjects were reported to be diagnosed with arthritis during approximately 10 years of follow-up (2011-2020). The VPD level in the arthritis group was lower than that in the non-arthritis group (5.184 ± 0.828 vs 5.291 ± 0.818, p < 0.001). All logistic regression models showed that VPD was linearly related to the incidence of arthritis, and the relationship remained consistent even when VPD was categorized. RCS analysis showed that the incidence of arthritis decreased significantly with increasing VPD (p < 0.05), especially when VPD was lower than 5.28. Subgroup analysis indicated that VPD exerted a stronger protective effect against arthritis among rural residents (p for interaction = 0.006).

Conclusion: VPD was found to be negatively associated with the incidence of arthritis among middle-aged and elderly populations, with a particularly stronger effect observed in rural residents. These findings highlight VPD as an environmental factor associated with arthritis and may help improve understanding of environmental influences on arthritis development.

Introduction: This study aims to construct a dynamic network by collecting longitudinal data, which will assist medical professionals in identifying bridging symptoms associated with disease progression and causal mechanisms.

Methods: A longitudinal observational study was conducted from March to June 2024, recruiting an initial cohort of people with HIV (PWH) from three designated AIDS medical institutions in Beijing, China. Symptom data were collected at two time points, three months apart, using the Chinese version of the Self-Report Symptom Scale (SRSS) alongside a demographic questionnaire. The data were analyzed using cross-lagged panel network analysis to explore symptom dynamics over time.

Results: A total of 791 PWH were recruited and 706 participants (89.25%) continued to the 3-month follow-up, with a mean age of 38.37 ± 10.03 years. There were no significant differences in demographic variables between those who missed and those who completed the study, except for clinical indices such as CD4 + cell count, ART duration, and comorbidity. Psychological symptoms, such as feeling helpless, feeling uneasy, and feeling fearful, also appear frequently. The most significant association identified was between becoming confusing and having difficulty in reasoning (COGS5 → COGS4, OR = 1.20). Notable bridging symptoms across two distinct domains included becoming confusing, leading to hardly focusing on anything (COGS5 → PSYS2, OR = 1.12), feeling hopeless, leading to rash (PSYS8 → PHYS8, OR = 1.11), and worry overwhelming leading to sleep disturbance (PSYS3 → PHYS6, OR = 1.11), among others.

Conclusions: There is an urgent need to enhance the assessment and early monitoring of cognitive status for PWH.

Marine calcifiers incorporate magnesium into their calcium carbonate skeletons through processes influenced by both ambient environmental conditions and species-specific physiological regulation. As a result, their carbonate structures can serve as valuable archives of past and present oceanic conditions, provided that biological controls are explicitly considered. This study investigated how skeletal magnesium-to-calcium (Mg/Ca) ratios vary in space and time among three Arctic benthic invertebrates differing in phylogeny, evolutionary history, and biomineralization strategy: the barnacle Semibalanus balanoides, the spirorbid Paradexiospira violacea, and the bryozoan Harmeria scutulata. Mg/Ca ratios were quantified using inductively coupled plasma atomic emission spectroscopy (ICP-AES) across three Svalbard fjords and over a four-year temporal interval (2006-2009). Kruskal-Wallis analyses revealed that species identity was the dominant factor controlling Mg/Ca ratios among the studied taxa. S. balanoides exhibited the lowest values of mean Mg/Ca ratios but highly variable (mean = 35.2 mmol/mol ± 16.8 SD), whereas P. violacea (62.5 mmol/mol ± 14.3) and H. scutulata (65.3 mmol/mol ± 14.1) showed higher and more consistent Mg/Ca ratio. Significant differences in Mg/Ca ratios were observed among sites for all species, following a consistent Hornsund < Kongsfjorden < Isfjorden pattern. However, the magnitude of site-level variability in Mg/Ca differed among species, confirming that species-specific physiological controls exert a stronger influence on skeletal Mg incorporation than external, site-specific environmental conditions. In Isfjorden, interannual trends in Mg/Ca between 2006 and 2009 were found to be species-specific but non-significant for all species. Weak, negative, and statistically significant relationships with bottom-water temperatures in Isfjorden was found only in P. violacea. Overall, these results highlight the predominant role of intrinsic biological controls over ambient environmental conditions in shaping skeletal Mg/Ca ratios and underscore the importance of species-resolved approaches when applying geochemical proxies in rapidly changing Arctic ecosystems.