The Innovation

Ambient particulate matter (PM) is a well-established environmental risk factor for non-communicable diseases, yet its influence on mitochondrial function remains poorly defined. Mitochondrial DNA copy number (mtDNA-CN) serves as a biomarker of mitochondrial biogenesis, making it a candidate exposure biomarker. We conducted the study per PRISMA guidelines (PROSPERO-CRD420261320957) and examined the association between ambient PM exposure and mtDNA-CN. Risk of bias was assessed using Joanna Briggs Institute tools, and relative and absolute changes in mtDNA-CN were pooled using random-effects models, with subgroup analyses by pollutant type and descriptive synthesis of mechanistic evidence. Of 1,224 records identified, 24 studies met inclusion criteria for quantitative analysis, with 12 reporting percentage change and 12 reporting absolute values, covering 13,092 participants. PM exposure was significantly associated with decreased percentage mtDNA-CN (ES: -4.90; 95% CI: -7.97 to -1.82; p = 0.002), while absolute mtDNA-CN levels increased significantly (ES = 0.55; 95% CI: 0.05 to 1.04; p = 0.030). Mechanistic pathways contributing included mtDNA hypermethylation, impaired mitochondrial biogenesis and dynamics. Our findings show ambient PM exposure alters mtDNA-CN, though directionality differs by metric, pointing to the need for larger prospective studies to validate mtDNA-CN as a reliable biomarker of airborne PM and nanoparticulate exposure.

Background Wildfire activity and smoke exposure are increasing worldwide because of climate and land-use change. Although fine particulate matter (PM2.5) may impair pulmonary immune defences against tuberculosis (TB), population-level evidence remains limited. We estimated the effect of wildfire-related PM2.5 exposure on TB notification rates in Brazil. Methods We conducted a nationwide panel study linking municipality-level monthly TB notifications from Brazil's SINAN system with wildfire-related PM2.5 estimates from GEOS-Chem simulations across 5,545 municipalities (2003-2023). We estimated the impact of high-exposure days (PM2.5 > 25 g/m3) on monthly TB notifications using Poisson regression with fixed effects for municipalities, state-by-year, and state-by-month, controlling for time-invariant differences, secular trends, and seasonality. Distributed lag effects were estimated over 1-24 months before notification. Models accounted for meteorological conditions, GeneXpert diagnostic coverage, and spatial correlation using Conley standard errors. We computed attributable fractions among exposed municipality-months (AFE). Sensitivity analyses evaluated alternative PM2.5 thresholds (15 and 35 g/m3), co-pollutants, and agricultural expansion. Findings From Jan 1, 2003 to Dec 1, 2023, 1,758,982 TB cases were reported. Of these, 353,319 (20.1%) had at least one high-exposure day (PM2.5 > 25 g/m3) 1-24 months before notification. An additional 14 high-exposure days over the 24-month lag period was associated with an average monthly increase of 2.9% [95% CI: 0.9-4.9%] in TB notification rates. Effects peaked at 13 months (IQR: 11-14) prior to notification. Results showed a dose-response relationship across PM2.5 thresholds and were robust to controlling for NO2, O3, and agricultural expansion. Overall, wildfire-related PM2.5 exposure accounted for 2.1% [0.7-3.5%] of TB notifications in exposed municipality-months, corresponding to 7,802 [2,612-12,544] attributable cases. The AFE reached 10.7% [7.1-14.0%] in Pantanal and 7.3% [6.1-8.5%] in Amazonia, areas most impacted by wildfires. Interpretation Wildfire-related PM2.5 exposure may represent an increasingly important and modifiable risk factor for TB. As wildfire activity increases across many regions of the world, these findings highlight the need for integrating air quality into climate adaptation and TB control strategies.

Hydroclimate whiplash, defined as the rapid transition between unusually wet and dry conditions, is expected to intensify under climate change, yet its population health impacts remain largely unknown. Here we quantified the association between hydroclimate whiplash and mortality across the contiguous United States from 2003 to 2023 using monthly county-level mortality records, standardized precipitation evapotranspiration index data, and two-stage time-series models. We identified overall and direction-specific dry-to-wet and wet-to-dry whiplash events at seasonal and sub-annual timescales and across 5-, 10-, and 20-year recurrence intervals. More severe whiplash events were associated with higher all-cause mortality risk; 5-, 10-, and 20-year sub-annual overall whiplash events increased mortality risk over five months by 3.4%, 4.5%, and 5.7%, respectively. Elevated risks were observed across cause-specific mortality outcomes, with the strongest association for infectious diseases. We estimated that 103,471 deaths were attributable to overall whiplash during the study period. These findings identify hydroclimate whiplash as an emerging climate-related public health threat and suggest that adaptation strategies focused on single hazards may underestimate the health burden of rapid, sequential hydroclimatic extremes.

Socioeconomic inequality in exposure to air pollution possess a significant public health challenge, yet little is known about how the disparities vary across the various economic status areas in Nairobi. Globally, studies have shown that exposure to air pollution is unequal across communities hence disparities in harm to human health. This study examined the association between socioeconomic characteristics and perceived air quality among residents of low- and high-socioeconomic status areas in Nairobi, Kenya. Two regions within Nairobi County were selected for this study: Mukuru kwa Njenga (representing the Low Socioeconomic Status) and Langata (representing the High Socioeconomic Status) with a sample size of 384 in HSES areas and 368 in LSES areas. A cross-sectional study was conducted among 752 respondents residing in selected LSES and HSES areas of Nairobi. Data was collected using a structured questionnaire assessing sociodemographic characteristics, income, education, employment, perceived air quality, and self-reported health outcomes associated with air pollution exposure. Descriptive statistics were used to summarize participant characteristics and perceived air quality. Chi-square tests were used to examine associations between residential area and categorical health outcomes, while ordinal logistic regression was used to assess the association between socioeconomic characteristics and perceived air-quality ratings. Perceived air quality differed significantly between residential socioeconomic groups. Respondents in LSES areas were more likely to rate air quality as poor or very poor, with 45.4% rating it as very poor, compared with only 1.6% of respondents in HSES areas. In contrast, 12.2% of HSES respondents rated air quality as good compared with 0.3% in LSES areas. The association between area of residence and perceived air-quality rating was statistically significant, {chi}2(3) = 282.672, p < 0.001. In the ordinal logistic regression model, HSES residence was associated with significantly lower odds of reporting poorer perceived air quality compared with LSES residence (OR = 0.135, 95% CI: 0.095-0.190, p < 0.001). Income was also significantly associated with perceived air quality, while respondents with no formal education had higher odds of reporting poorer perceived air quality compared with those with secondary education (OR = 3.254, 95% CI: 1.388-7.638, p = 0.007). Significant differences were also observed for several self-reported health outcomes. Respiratory problems were more prevalent among respondents in LSES areas than HSES areas (72.7% versus 50.4%; {chi}2(1) = 29.081, p < 0.001; Cramer's V = 0.224). However, allergies, eye irritation, and headaches were reported more frequently in HSES areas than in LSES areas, with significant associations observed for allergies ({chi}2(1) = 106.479, p < 0.001; Cramer's V = 0.429), eye irritation ({chi}2(1) = 136.577, p < 0.001; Cramer's V = 0.486), and headaches ({chi}2(1) = 149.180, p < 0.001; Cramer's V = 0.508). No statistically significant association was observed for cardiovascular problems, likely reflecting the very low number of reported cases. Substantial socioeconomic disparities in perceived air quality and self-reported respiratory health outcomes were observed. Residents of low-socioeconomic status areas consistently perceived poorer air quality and reported a higher burden of respiratory problems, highlighting the need for targeted interventions to reduce environmental health inequalities.

Background: Environmental noise and air pollution are both shaped by road traffic and the built environment, and exposure assessment increasingly folds them into composite indices or proxies both by traffic exposure. Whether the two share a social distribution has rarely been tested against direct measurement of several exposures in the same communities, and community noise is almost always characterized by A-weighted levels alone, which discount low-frequency energy. Methods: At 176 sites across Rhode Island, spanning the contiguous urban area of Providence, Central Falls, and Pawtucket together with four rural municipalities, we measured the acoustic environment under A- and C-weighting (LAeq, LCeq), fine particulate matter (PM2.5), night-time illuminance, and relative humidity across four session types over roughly one year (704 site-sessions). Exposures were linked to census-tract composition (American Community Survey), and mixed-effects models were fitted for each of eight area-level markers of disadvantage, adjusting for campaign and session. Relative humidity was carried through the identical model as a negative control. Results: A-weighted noise was consistently higher in more disadvantaged tracts, rising with non-White, poverty, renter, and no-vehicle shares and falling with income and older-resident share (six of eight markers significant; 1.3 to 1.8 dBA per standard deviation; 6.6 dBA between the least and most racially diverse neighborhoods). C-weighted levels followed the same gradient on every marker and exceeded their A-weighted counterparts at block-group scale for renter occupancy and vehicle absence. Night-time illuminance was also socially patterned, whereas short-term PM2.5 was roughly an order of magnitude weaker and relative humidity showed no gradient. The acoustic gradient persisted within the urban core alone. Conclusions: Measured burden was carried by the acoustic environment, including its low-frequency component, and by night-time light, not by short-term particulates. The exposure metric and the averaging time determine which disparities are visible at all.

Wildfire smoke has increasingly affected air quality across North America, raising concerns about the health effects of fine particulate matter (PM2.5) exposure, including potential impacts on brain health. However, relatively few studies have characterized personal PM2.5 exposure during these events using wearable monitoring. We examined daily personal PM2.5 concentrations during wildfire smoke episodes in southeast Michigan alongside neighborhood outdoor PM2.5 estimates. Four participants (one adolescent and three adults) wore AirBeam3 personal monitors during ongoing studies. Neighborhood outdoor PM2.5 was estimated using the average of three nearest PurpleAir outdoor air quality sensors, and wildfire smoke days were identified using state air quality advisories. Group-level descriptive statistics summarized personal and neighborhood outdoor PM2.5 and self-reported time spent outdoors. Exploratory within-participant analyses quantified associations between neighborhood outdoor and personal PM2.5 concentrations on smoke and non-smoke days. Neighborhood outdoor daily PM2.5 concentrations were higher during wildfire smoke days than non-smoke days (87.6 + 80.2 vs. 12.3 + 7.0 {micro}g/m3). Personal PM2.5 concentrations were more than five times higher during wildfire smoke days (28.2 + 20.0 vs. 5.1 + 4.7 {micro}g/m3) than non-smoke days. Within participants, every 10 {micro}g/m3 increase in neighborhood PM2.5 was associated with 2.3 {micro}g/m3 increase in personal PM2.5 concentrations. Wearable PM2.5 monitoring captured elevated personal exposures while providing individual-level exposure information beyond neighborhood outdoor air quality estimates. These findings demonstrate that wearable monitoring complements neighborhood air quality measurements by capturing individual-level exposure, providing a more comprehensive assessment of real-world wildfire smoke exposure for future studies examining the effects on brain health.

Viral phenotypes such as host and tissue tropism are critical determinants of viral infection and transmission. Inferring viral phenotypes presents unique challenges compared to cellular organisms, as viruses rely entirely on host machinery for replication and survival. Current methods for predicting viral phenotypes mainly rely on viral genomic data, often overlooking host-related information. Here, we evaluated the utility of predicted virus-human protein-protein interactions (PPIs) in inferring diverse viral phenotypes using machine-learning algorithms. For predicting human infectivity, a PPI-based machine learning model outperformed both virus genomic and protein sequence-based models that used large language model embeddings. It also surpassed previous methods that incorporated both viral and host genomic data. The human proteins identified by the model were significantly enriched in functions related to viral infection and immune response. In predicting various phenotypes of human RNA viruses, PPI-based models performed better than virus sequence-based models in forecasting virulence, human transmissibility and transmission routes, while showing comparable performance to genomic sequence-based models in predicting tissue tropism. Finally, we demonstrated that a PPI-based model could distinguish high-risk HPV genotypes from low-risk ones. Proteins associated with high-risk HPV were involved in apoptosis and immune regulation, whereas those linked to low-risk HPV were enriched in telomere maintenance and DNA repair. Collectively, this study is the first to demonstrate the value of predicted virus-human PPIs in inferring viral phenotypes, thereby enhancing our understanding of the molecular mechanisms underlying these phenotypes. It also provides effective tools for risk assessment of emerging viruses, contributing to improved pandemic preparedness.

Background: Exercise training is a cornerstone intervention for cardiovascular disease, yet large cohort studies have reported attenuation of physical activity benefits at elevated air pollution concentrations, creating uncertainty around exercise prescription in polluted settings where cardiovascular disease burden is greatest. Objectives: To determine whether ambient PM2.5 concentration modifies the cardiovascular benefits of structured exercise training, using a global sample of trials spanning a >100-fold pollution gradient. Methods: We conducted a systematic review and multilevel meta-analysis of exercise training interventions reporting pre-post changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), peak oxygen uptake (VO2Max), or resting heart rate (HR) in adults. Annual ambient PM2.5 concentrations (3.5-283 g/m3) were assigned to each study location from CAMS ERA5 reanalysis data. Three-level random-effects models with cluster-robust variance estimation accounted for arms nested within studies. PM2.5 meta-regression was conducted unadjusted and adjusted for world region, exercise mode, trial duration, and health condition, with subgroup analyses by exercise mode and hypertension status. Results: Across 465 studies (27,629 participants), exercise training produced clinically meaningful benefits for all outcomes (SBP - mmHg, DBP - mmHg, VO2Max +3.2 ml/kg/min, HR - bpm; all p < 0.001), with benefits consistently larger in higher-pollution settings. Hypertensive participants showed the greatest improvements, particularly from aerobic exercise (SBP standardised mean difference 0.396 in the Low vs 1.020 in the High PM2.5 stratum). Although aerobic and resistance training participants experience similar chronic ambient PM2.5 exposure, only aerobic exercise showed a stratum gradient (interaction p = 0.074). Discussion: Exercise training delivers clinically meaningful cardiovascular benefits at every pollution level tested. The larger benefits observed in higher-pollution settings reflect the greater cardiovascular risk burden of those populations, and hypertensive patients stand to gain the most, particularly from aerobic exercise.

Background Alcohol-associated liver disease (ALD) has emerged as a major cause of chronic liver disease and liver-related mortality in China. This study aimed to project the future burden of ALD in Chinese adults from 2020 to 2050, including prevalence of ALD, number of alcoholic steatohepatitis (ASH) cases, incident hepatocellular carcinoma (HCC) cases, liver transplantation (LT) demand, liver-related deaths, and disability-adjusted life years (DALYs). Methods We developed an agent-based state-transition microsimulation model with yearly cycles and a lifetime horizon. The model simulated 5,678,912 representative Chinese adults (mean age 36.2 years, 51.2% male). Health states included no steatosis, alcohol-associated steatotic liver, ASH, fibrosis stages F0-F4, decompensated cirrhosis, HCC, LT, and liver-related death. Model inputs were derived from the China Kadoorie Biobank, Global Burden of Disease Study 2021, China's national surveys, published meta-analyses, and transplant registry data. Projections incorporated demographic shifts, alcohol consumption trends, and calibrated transition probabilities. Uncertainty was assessed via 1,000 Monte Carlo simulations generating 95% uncertainty intervals. Results ALD prevalence was projected to increase from 4.8% (55 million individuals) in 2020 to 8.5% (94 million individuals) by 2050. ASH cases rose from approximately 18 million to 20 million. Annual incident HCC cases nearly doubled from 20,500 in 2020-2025 to 45,200 by 2046-2050. LT demand quadrupled from 2,300 to 9,800 cases. Liver-related deaths increased from 50,000 in 2020 to 85,000 in 2050, while DALYs rose from 1.5 million to 2.6 million. Conclusions In the absence of strengthened alcohol control policies, ALD will impose a substantial and growing burden on China's health system by 2050, with marked increases in HCC incidence, LT demand, and liver-related mortality.

Fine particulate matter (PM2.5) was found to be associated with elevated blood lipids, but fewer studies have examined the associations with specific constituents of PM2.5. We studied the associations between exposure to annual PM2.5 and its 14 constituents, and repeated blood lipid measurements among general responders enrolled in the World Trade Center Health Program between 2003 and 2019 (n = 44,876). We used generalized additive mixed effect models to investigate the single-pollutant associations with repeated measures of blood total cholesterol (TC), high and low-density lipoprotein (HDL-C and LDL-C) levels. We then used linear generalized weighted quantile sum regression with a random intercept for participant ID to account for the clustering of repeated measures and evaluate the combined associations with the component mixture. A decile increase in the mixture of 14 PM2.5 chemical components was associated with 0.375 mg/dL increase in TC levels (95% confidence Interval (CI): 0.174-0.577) and 0.302 mg/dL increase in LDL-C (95% CI: 0.063, 0.540). Lead, organic carbon, and iron were major drivers of both associations. Component-specific models also show higher TC and LDL levels associated with interquartile range increases in organic carbon (0.472, 95% CI [0.027, 0.918] and 0.648 95% CI [0.136, 1.160]) and iron exposure (1.081, 95% CI [0.630, 1.532] and 0.748, 95% CI [0.318, 1.178]). In conclusion, we found PM2.5 exposure to be associated with elevated lipid levels. The associations differed by PM2.5 composition, highlighting organic carbon, lead, and iron and major drivers. These findings are highly significant for a population exposed to extreme air pollution event and susceptible to lipid alterations that might trigger cardiovascular events.

While exposure to volatile organic compounds such as ethylene dichloride and vinyl chloride monomer is a well-established cause of liver disease, particularly hepatic hemangiosarcoma, characterizing real-world exposure profiles in communities surrounding industrial centers remains challenging. Calvert City, Kentucky (population ~2,500), provides a unique setting characterized by both active industrial emissions and legacy sources of air toxics. To address these complexities, this method paper describes the framework for the Biomonitoring and Environmental Assessment for Community Outreach and Neighborhood Safety (BEACON) study. By utilizing a novel, multi-dimensional exposure assessment strategy, BEACON aims to characterize air toxic exposures and provide actionable data for community health and safety. For the BEACON study, we will leverage Kentucky Department of Air Quality measures of air toxics, analyze urine samples in a small cohort of community volunteers, analyze community urine via wastewater in an adjacent community, geocode citizen odor reporting, assess blood markers in wildlife, survey small and large animal veterinarians in the area for anomalies in morbidity and mortality, and work with the regional health system to enhance vigilance for health issues associated with toxicants present in the area. In addition, blood samples will be collected at three time points and biobanked for future analyses. Efforts will be made to link this study to additional large-scale long-term cohorts where possible. Throughout the project, community engagement will play a critical role by raising awareness, fostering collaboration, and ensuring that the voices of affected residents are heard.

Background: Children spend more than 90% of their time indoors, and early childhood education settings (ECEs) are an understudied, high-occupant-density indoor microenvironment where exposure to volatile organic compounds, particulate matter, and other toxicants has been documented. Limited knowledge exists on ECE-specific exposures affecting young children and how they compare to exposures in the home. Methods: This prospective, repeated-measures pilot study targeted enrollment of 44 preschool-aged children and 8 ECE staff across two geographically and sociodemographically distinct ECEs in metropolitan Atlanta, Georgia. Paired silicone wristbands, one home-designated and one ECE-designated, were exchanged between settings across three consecutive days and nights beginning at enrollment to characterize microenvironment-specific exposure. A single spot urine sample was also collected from each child. Continuous indoor air quality monitoring was conducted in two classrooms per site. Caregivers and ECE staff completed structured questionnaires assessing home and ECE environmental characteristics, child respiratory risk, and protocol feasibility and acceptability. Feasibility was evaluated using eight pre-specified indicators spanning recruitment and enrollment, wristband wear duration and loss by microenvironment, urine sample collection completeness, and survey completion by instrument and respondent group. Conclusion: This pilot will establish feasibility and acceptability parameters for a paired, multi-matrix silicone wristband protocol across home and ECE microenvironments. Findings will inform the design, sample size, and power calculations for a subsequent study testing indoor air interventions and pediatric respiratory outcomes in ECEs. Feasibility outcomes are reported in a companion manuscript.

Fine particulate air pollution (PM2.5) in the United States has fallen by roughly half since 2000, yet linked health outcomes such as diabetes and childhood ADHD have not improved in parallel. One reconciling possibility is that pollution exposure in early life produces health effects that emerge only years or decades later, after pollution itself has declined. Using two decades of U.S. county-level data, we relate annual PM2.5 estimates to birth outcomes, diabetes prevalence, and small-area estimates of childhood attention-deficit/hyperactivity disorder (ADHD) across short and long time scales. Within counties, changes in low birth weight rates are associated with changes in PM2.5 during the same year and the year prior to birth. At longer time scales, cross-county comparisons show that PM2.5 exposure is associated with higher prevalence of adult diabetes and ADHD after approximately a decade. Together, these patterns suggest that population-level health risks from air pollution may persist over decades, even as pollution itself declines.

Despite significant advancements in microsurgical techniques in recent years, the treatment and prognosis of craniopharyngiomas remain unsatisfactory. As a central nervous system tumor located adjacent to important brain structures such as the hypothalamus-pituitary axis and accompanied by a highly inflammatory microenvironment, the tumor heterogeneity and tumor microenvironment characteristics of papillary craniopharyngiomas (PCPs) remain unclear. In this study, we integrated multimodal single-cell and spatial profiling from PCP tissue and peripheral blood mononuclear cells (PBMCs) to elucidate the tumor heterogeneity and microenvironment characteristics of PCP. Our single-cell and spatial analyses defined four specific tumor cell states in PCP, representing specific transcriptional regulatory programs and spatial heterogeneity characteristics during tumor progression. By constructing a spatial niche composed of tumor, immune, and stromal cells, we analyzed the cellular and spatial ecosystem of PCP at multiple levels to further assess the communication relationships between different tumor cell states and microenvironment cells. This study established a multidimensional molecular atlas of PCP from the perspectives of cell state, spatial structure, and microenvironment interactions, providing a foundation for understanding its biological behavior and exploring new intervention strategies.

This study aimed to clarify aerosol exposure risks throughout the workflow of a Biosafety Level 2 (BSL-2) polymerase chain reaction (PCR) laboratory, validate the suitability of the {Phi}X174 bacteriophage as an indicator virus, and provide evidence for biosafety control measures. The {Phi}X174 bacteriophage was used to simulate viral samples, and a concentration-bacteriophage plaque standard curve was constructed (R2=0.998). Five operational steps in a simulated PCR laboratory were quantitatively monitored for aerosol concentration using double-layer agar plates, with blank controls used to eliminate interference. Statistical analysis was employed to identify risk differences. Sample homogenization ((5.67 {+/-} 1.23) x 104 plaque-forming units (PFU)/m3) and nucleic acid extraction ((3.45 {+/-} 0.89) x 104 PFU/m3) were identified as high-/very high-risk steps. The viral load in the samples was strongly positively correlated with the aerosol concentration (r = 0.926, P <0.001), with aerosol levels linearly decreasing with increasing distance in high-risk steps. The {Phi}X174 bacteriophage demonstrated high detection sensitivity (101 PFU/ml) and demonstrated safety compatibility with BSL-2 laboratories. Aerosol risks in PCR laboratories exhibit step-specific differentiation, and {Phi}X174 serves as an ideal indicator virus. Proposed strategies such as equipment upgrades and personal protective equipment (PPE) grading can reduce exposure risks.

Free chlorine reacts with viral proteins, but the protein structural determinants of viral resistance to chlorine treatment remain poorly understood. Here, we curated a dataset of 498 icosahedral virus structures, including intact virions and virus-like particles (VLPs), from the Protein Data Bank. Surprisingly, only 6.6% of these structures are associated with published viral chlorine inactivation rate constants (kobs). In these matched cases representing 12 virus families, total and maximum solvent accessible surface areas (SASA) of methionine residues within viral attachment and entry proteins correlated significantly with median kobs (Pearsons r = 0.83 and 0.45, respectively; p < 0.05), suggesting a critical role of methionine exposure in viral resistance phenotypes. Across the full curated dataset, fuzzy c-means clustering upon total and maximum SASA profiles of chlorine-reactive residues demonstrates that the common surrogate panel (MS2, PhiX174, Phi6, PRD1, and PR772) fails to represent the SASA diversity of human viruses. Instead, VLPs and novel phages may serve as better surrogates for chlorine treatment due to SASA profile similarities to human viruses. Our findings highlight that residue SASA features provide a quantitative baseline for screening viral resistance to chlorine and offer a data-driven strategy to select structurally representative virus surrogates for future disinfection studies. SYNOPSISSolvent accessibility of chlorine-reactive residues correlates strongly with viral chlorine resistance, providing a robust quantitative metric to compare chlorine resistance phenotypes across viral capsids. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/732355v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@dd6bd1org.highwire.dtl.DTLVardef@d17c53org.highwire.dtl.DTLVardef@1394528org.highwire.dtl.DTLVardef@eb6378_HPS_FORMAT_FIGEXP M_FIG C_FIG

Hepatocellular carcinoma (HCC) is particularly aggressive and difficult to treat. Due to the lack of early clinical diagnosis and the unsatisfactory clinical treatment effect, it is particularly important to identify novel markers that can predict tumor behavior in HCC. biogenesis of ribosomes BRX1 (BRIX1) is abundant in various tissues of the human body. However, the regulatory mechanisms and its role in various tissues are not fully understood. Here, we analyzed the expression pattern of BRIX1 in HCC from public gene expression databases and tissue samples from clinical HCC. We confirmed that BRIX1 was upregulated in both HCC cell lines and HCC paraffin section samples. BRIX1 depletion significantly dicreased the capacity of cells to grow and migrate in vitro, and knockdown BRIX1 suppressed tumor growth in xenograft tumor model. Mechanistically, BRIX1 depletion suppressed the MAPK/ERK pathway, as reflected by reduced phosphorylated ERK (p-ERK) levels. In summary, we provide a rational clue for the further investigation of BRIX1 as an invaluable biological marker for diagnosing and predicting prognosis of patients with HCC.

Many urban health outcomes are shaped by environmental stressors that occur together rather than in isolation, yet methods for measuring such co-occurrence at the neighbourhood scale remain underdeveloped. We developed a multi-metric framework for joint co-exposure assessment and applied it to characterise the joint spatial distribution of summer surface heat and fine particulate matter (PM2.5) across 42,304 census tracts in 48 large US metropolitan areas during summers 2015 to 2020, covering approximately 174.6 million residents. The framework combines a composite co-exposure index, a joint exceedance indicator, a conditional exceedance ratio that compares observed joint occurrence to within-group statistical independence, and an upper tail dependence parameter estimated using both the non-parametric Caperaa-Fougeres-Genest estimator and a Gumbel copula, with bias-corrected and accelerated (BCa) confidence intervals obtained from a 5,000-replicate metropolitan-area block bootstrap. Among residents of predominantly Black tracts, 13.21% lived in neighbourhoods that simultaneously exceeded the within-metropolitan-area 80th percentile for both heat and PM2.5, compared with 3.33% of residents of predominantly White tracts; the corresponding heat-only and PM2.5-only ratios were 2.88 and 2.48. Residents of Home Owners Loan Corporation grade D tracts had 3.97 times the odds (95% confidence interval 2.79 to 5.66) of joint hotspot residence compared with grade A residents after adjustment for contemporary tract racial composition, poverty, renter-occupancy, and pre-1960 housing. The within-group conditional exceedance ratio at the 80th percentile was 2.29 in predominantly White tracts (95% BCa CI 1.81 to 2.78), 1.27 in predominantly Black tracts (0.71 to 1.56), and 1.13 in predominantly Hispanic tracts (0.70 to 1.41); the White interval excluded one while the Black and Hispanic intervals included one, which we interpret as power-limited given fewer contributing CBSAs. Magnitudes attenuated under near-surface air temperature surfaces but the direction and statistical significance of the primary findings were preserved. The framework is portable to other compound-exposure questions and supports cumulative-impact assessment.

Objective: Over the past decades, US policies intended to reduce air pollution emissions from electric generating units (EGUs), mobile sources (e.g., cars and trucks), and port activities have been implemented to improve air quality. This study aimed to estimate and compare counterfactual air pollution concentrations (i.e., concentrations that would have occurred without these policies) to observed concentrations, and then evaluate the health impacts of such policies in New York City, Los Angeles, and Atlanta from 2005 to 2019. Materials and Methods: We obtained data on respiratory emergency department (ED) visits and cardiovascular disease ED visits that result in hospitalizations for the three cities from 2005-2019. Daily concentrations of fine particulate matter (PM2.5), criteria gases [carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3)], and 1-in-3-day measured concentrations of PM2.5 components and PM sources estimated using positive matrix factorization were acquired from six monitoring sites in the three cities. To estimate health impacts of selected EGU, mobile, and port policies we estimated: 1) counterfactual daily pollutant concentrations at each of the 6 city-sites; 2) associations between daily pollutant concentrations and rates of cardiorespiratory visits using city-site specific multi-pollutant Poisson models; and 3) the percent of cardiorespiratory visits prevented by the implementation of the selected policies, through applying observed and counterfactual concentrations to the fitted health models. Results: Air quality policies were estimated to reduce ambient pollutant concentrations across the three cities, with median PM2.5 reductions of 27%-62% due to all policies combined during 2005-2019. Changes in criteria-pollutant concentrations associated with the selected policies were estimated to avert 7.1% (95% UI: 5.4%, 8.9%) of respiratory visits in New York City, 2.4% (95% UI: 1.4%, 3.4%) in Los Angeles, and 4.5% (95% UI: 0.8%, 8.2%) in Atlanta. In addition, 2.6% (95% UI: 0.9%, 4.2%) and 1.2% (95% UI: 0.3%, 2.1%) of cardiovascular visits were averted in New York City and Los Angeles, while the estimate in Atlanta did not indicate cardiovascular visits averted. Conclusion: The selected EGU, mobile-source, and port policies evaluated during 2005-2019 were estimated to reduce ambient pollutant concentrations and avert respiratory visits in all three cities and cardiovascular visits in New York City and Los Angeles.

Background Childhood respiratory mortality in China has fallen by over 90% in three decades alongside sustained national warming, yet national long-run evidence on temperature and child respiratory mortality is lacking. Methods We linked Global Burden of Disease (GBD) 2021 mortality estimates for China - lower respiratory infections (LRI), ages 0-19, and asthma, ages 0-24, 1990-2021 - with C-LSAT 0.5 deg gridded temperature data (1990-2019), aggregated nationally and to five climate zones. Four annual indicators (mean temperature, diurnal temperature range, seasonal amplitude, interannual variability) entered regressions of log mortality rates with Newey-West standard errors. A bootstrapped (500 resamples) quadratic model probed the minimum mortality temperature (MMT), with PM2.5-adjusted analyses and future-exposure, permutation, and detrended falsification tests. Results LRI deaths fell by 96.3% (330,194 in 1990 to 12,098 in 2021; 95% uncertainty interval 9,669-14,891) and asthma deaths by 94.9% (3,287 to 167), while mean temperature rose 0.364 deg C per decade and diurnal temperature range narrowed 0.092 deg C per decade. Baseline coefficients were large (mean temperature -1.696, SE 0.174; diurnal temperature range +2.408, SE 0.336; seasonal amplitude -0.162, SE 0.082; interannual variability +2.924, SE 1.514, per 1 deg C in log rate), but the future-exposure test failed and detrending nullified every coefficient: the associations are trend-level, and short-cycle causal effects are not identifiable. Nor was the national MMT identifiable - observed temperature support spans only 6.66-8.13 deg C, and the nominal turning point of 35.84 deg C is an extrapolation artifact (quadratic term p = 0.963). Within the observed range, warming and declining mortality moved in the same direction. Conclusions The 96% decline in childhood respiratory mortality cannot be attributed to warming. China sits on the low-temperature side of the optimum, and the marginal direction of future warming requires stronger designs to establish. The falsification framework offers a discipline for climate-health inference in China.