Independent and joint effects of neighborhood-level environmental and socioeconomic exposures on body mass index in early childhood: The environmental influences on child health outcomes (ECHO) cohort.

Past studies support the hypothesis that the prenatal period influences childhood growth. However, few studies explore the joint effects of exposures that occur simultaneously during pregnancy. To explore the feasibility of using mixtures methods with neighborhood-level environmental exposures, we assessed the effects of multiple prenatal exposures on body mass index (BMI) from birth to age 24 months. We used data from two cohorts: Healthy Start (n = 977) and Maternal and Developmental Risks from Environmental and Social Stressors (MADRES; n = 303). BMI was measured at delivery and 6, 12, and 24 months and standardized as z-scores. We included variables for air pollutants, built and natural environments, food access, and neighborhood socioeconomic status (SES). We used two complementary statistical approaches: single-exposure linear regression and quantile-based g-computation. Models were fit separately for each cohort and time point and were adjusted for relevant covariates. Single-exposure models identified negative associations between NO2 and distance to parks and positive associations between low neighborhood SES and BMI z-scores for Healthy Start participants; for MADRES participants, we observed negative associations between O3 and distance to parks and BMI z-scores. G-computations models produced comparable results for each cohort: higher exposures were generally associated with lower BMI, although results were not significant. Results from the g-computation models, which do not require a priori knowledge of the direction of associations, indicated that the direction of associations between mixture components and BMI varied by cohort and time point. Our study highlights challenges in assessing mixtures effects at the neighborhood level and in harmonizing exposure data across cohorts. For example, geospatial data of neighborhood-level exposures may not fully capture the qualities that might influence health behavior. Studies aiming to harmonize geospatial data from different geographical regions should consider contextual factors when operationalizing exposure variables.

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months.

Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown. Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US. Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024. Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure. Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted. Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02). Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

Utility of gadoxetate disodium-enhanced magnetic resonance imaging in evaluating liver failure risk after major hepatic resection.

Background: Post-hepatectomy liver failure (PHLF) is still a predominant cause of hepatectomy-related mortality. However, it is difficult to evaluate the remnant liver functional reserve accurately before surgery to prevent PHLF. In this study, we aimed to explore the role of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in evaluating remnant liver functional reserve. Methods: For this cross-sectional study, the sample retrospectively included 56 patients undergoing liver resections of at least three segments between June 2019 and September 2022 at The General Hospital of the Western Theater Command. Pre-surgery assessments involved liver computer tomography (CT), an indocyanine green (ICG) clearance test, the Child-Pugh scoring system, and liver function serum biochemical indicators. Each patient underwent a gadoxetate disodium-enhanced MRI before the hepatectomy, and we measured the remnant hepatocellular uptake index (rHUI) as well as the standard remnant hepatocellular uptake index (SrHUI). We examined the diagnostic utility of rHUI, SrHUI, indocyanine green retention rate of 15 minutes (ICG R15), and Albumin for PHLF. Receiver operating characteristics (ROC) analyses were used to measure the preoperative liver function parameters (namely, rHUI, SrHUI, ICG R15, and Albumin) for predicting PHLF. The areas under the curve (AUCs) were calculated and compared between different preoperative liver function parameters using the Wilson/Brown method. The Pearson or Spearman correlation coefficient was used for correlation analysis between ICG R15, Albumin, and rHUI and between ICG R15, Albumin, and SrHUI, respectively. Results: Twelve patients (21.43%) had complications of PHLF. We found significant differences in rHUI, SrHUI, ICG R15, and Albumin between the non-PHLF and PHLF groups. The pooled r between ICG R15 and rHUI was -0.591 [95% confidence interval (CI): -0.740 to -0.389, P<0.001], and between ICG R15 and SrHUI was -0.534 (95% CI: -0.703 to -0.308, P<0.001). The area under the curve (AUC) values of rHUI, SrHUI, ICG R15, and Ablumin were 0.871 (sensitivity 81.82%; specificity 91.67%), 0.878 (sensitivity 79.55%; specificity 83.33%), 0.835 (sensitivity 99.73%; specificity 66.67%), and 0.782 (sensitivity 88.64%; specificity 58.33%), respectively. Conclusions: We found that the rHUI and SrHUI calculated using the gadoxetate disodium-enhanced MRI reflected a combination of remnant hepatocyte function and liver volume, and these were useful as a quantitative assessment indicator of remnant liver functional reserve and can be a better predictor of PHLF after major hepatic resection.

Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

Increased Risk of Gestational Hypertension by Periconceptional Exposure to Ambient Air Pollution and Effect Modification by Prenatal Depression.

BACKGROUND: Air pollution has been associated with gestational hypertension (GH) and preeclampsia, but susceptible windows of exposure and potential vulnerability by comorbidities, such as prenatal depression, remain unclear. METHODS: We ascertained GH and preeclampsia cases in a prospective pregnancy cohort in Los Angeles, CA. Daily levels of ambient particulate matters (with a diameter of ≤10 µm [PM10] or ≤2.5 µm [PM2.5]), nitrogen dioxide, and ozone were averaged for each week from 12 weeks preconception to 20 gestational weeks. We used distributed lag models to identify susceptible exposure windows, adjusting for potential confounders. Analyses were additionally stratified by probable prenatal depression to explore population vulnerability. RESULTS: Among 619 participants, 60 developed preeclampsia and 42 developed GH. We identified a susceptible window for exposure to PM2.5 from 1 week preconception to 11 weeks postconception: higher exposure (5 µg/m3) within this window was associated with an average of 8% (95% CI, 1%-15%) higher risk of GH. Among participants with probable prenatal depression (n=179; 32%), overlapping sensitive windows were observed for all pollutants from 8 weeks before to 10 weeks postconception with increased risk of GH (PM2.5, 16% [95% CI, 3%-31%]; PM10, 39% [95% CI, 13%-72%]; nitrogen dioxide, 65% [95% CI, 17%-134%]; and ozone, 45% [95% CI, 9%-93%]), while the associations were close to null among those without prenatal depression. Air pollutants were not associated with preeclampsia in any analyses. CONCLUSIONS: We identified periconception through early pregnancy as a susceptible window of air pollution exposure with an increased risk of GH. Prenatal depression increases vulnerability to air pollution exposure and GH.

Electronic Structure Modulation of Oxygen-Enriched Defective CdS for Efficient Photocatalytic H2 O2 Production.

Artificial photosynthesis for hydrogen peroxide (H2 O2 ) presents a sustainable and environmentally friendly approach to generate clean fuel and chemicals. However, the catalytic activity is hindered by challenges such as severe charge recombination, insufficient active sites, and poor selectivity. Here, a robust strategy is proposed to regulate the electronic structure of catalyst by the collaborative effect of defect engineering and dopant. The well designed oxygen-doped CdS nanorods with S2- defects and Cd2+ 4d10 electron configuration (CdS-O,Sv ) is successfully synthesized, and the Cd2+ active sites around S defects or oxygen atoms exhibit rapid charge separation, suppressed carrier recombination, and enhanced charge utilization. Consequently, a remarkable H2 O2 production rate of 1.62 mmol g-1  h-1 under air conditions is acquired, with an apparent quantum yield (AQY) of 9.96% at a single wavelength of 450 nm. This work provides valuable insights into the synergistic effect between defect and doping on catalytic activity.

Abnormal theta and alpha oscillations in children and adolescents with first-episode psychosis and clinical high-risk psychosis.

BACKGROUND: Cognitive control deficits are one of the main symptoms of psychosis. The basic neural oscillation patterns associated with cognitive control are already present in early adolescence. However, as previous studies have focused on adults with psychosis, it is unclear whether neurobiological impairments in cognitive control are present in children and adolescents with first-episode psychosis (FEP) or clinical high-risk (CHR) state for psychosis. AIMS: To explore the deficits of electroencephalogram related to cognitive control tasks in children and adolescents with FEP and CHR. METHOD: Electroencephalogram was recorded in untreated 48 patients with FEP, 24 patients with CHR and 42 healthy controls aged 10-17 years, while performing the visual oddball task. The N2 amplitude, theta and alpha oscillations were then analysed and compared between groups. RESULTS: There was no significant group difference in N2 amplitude (P = 0.099). All groups showed increased theta and alpha oscillations relative to baseline before the stimulus in the frontal, central, left fronto-central and right fronto-central areas. These changes differed significantly between groups, with the FEP group showing significantly smaller theta (P < 0.001) and alpha (P < 0.01) oscillation than healthy controls. Theta and alpha oscillations in the CHR group did not differ significantly from the FEP group and healthy controls. CONCLUSIONS: These results suggest that neural damage has already occurred in the early stage of psychosis, and that abnormal rhythmic activity of neurons may constitute the pathophysiological mechanism of cognitive dysfunction related to early-onset psychosis.

18F-Labeled PET Tracers Specific for Adenosine A2A Receptor: Design, Synthesis, and Biological Evaluation.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

Prenatal air pollution exposure is associated with inflammatory, cardiovascular, and metabolic biomarkers in mothers and newborns.

BACKGROUND: Prenatal air pollution exposure has been associated with individual inflammatory, cardiovascular, and metabolic biomarkers in mothers and neonates. However, studies of air pollution and a comprehensive panel of biomarkers across maternal and cord blood samples remain limited. Few studies used data-driven methods to identify biomarker groupings that converge biomarkers from multiple biological pathways. This study aims to investigate the impacts of prenatal air pollution on groups of biomarkers in maternal and cord blood samples. METHODS: In the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort, 87 biomarkers were quantified from 45 trimester 1 maternal blood and 55 cord blood samples. Pregnancy and trimester 1-averaged concentrations of particulate matter ≤2.5 µm and ≤10 µm in diameter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated, using inverse distance squared weighted spatial interpolation from regulatory air monitoring stations. Traffic-related NOx was assessed using California Line Source Dispersion Model: freeway/highway roads, non-freeway major roads, non-freeway minor roads, and their sum as total NOx. Elastic Net (EN) regression within the rexposome R package was used to group biomarkers and assess their associations with air pollution. RESULTS: In maternal samples, trimester 1-averaged PM10 was associated with elevated inflammation biomarkers and lowered cardiovascular biomarkers. NO2 exhibited positive associations with cardiovascular and inflammation markers. O3 was inversely associated with inflammation, metabolic, and cardiovascular biomarkers. In cord blood, pregnancy-averaged PM2.5 was associated with higher cardiovascular biomarkers and lower metabolic biomarkers. PM10 was associated with lower inflammation and higher cardiovascular biomarkers. Total and major road NOx was associated with lower cardiovascular biomarkers. CONCLUSION: Prenatal air pollution exposure was associated with changes in biomarkers related to inflammation, cardiovascular, metabolic, cancer, and neurological function in both mothers and neonates. This study shed light on mechanisms by which air pollution can influence biological function during pregnancy.

Recent advances in ambient-stable black phosphorus materials for artificial catalytic nitrogen cycle in environment and energy.

Nitrogen cycle is crucial for the Earth's ecosystem and human-nature coexistence. However, excessive fertilizer use and industrial contamination disrupt this balance. Semiconductor-based artificial nitrogen cycle strategies are being actively researched to address this issue. Black phosphorus (BP) exhibits remarkable performance and significant potential in this area due to its unique physical and chemical properties. Nevertheless, its practical application is hindered by ambient instability. This review covers the synthesis methods of BP materials, analyzes their instability factors under environmental conditions, discusses stability improvement strategies, and provides an overview of the applications of ambient-stable BP materials in nitrogen cycle, including N2 fixation, NO3- reduction, NOx removal and nitrides sensing. The review concludes by summarizing the challenges and prospects of BP materials in the nitrogen cycle, offering valuable guidance to researchers.

Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort.

BACKGROUND: Diet during pregnancy may be a potential intervention for preventing hypertensive disorders of pregnancy that disproportionally burdens Hispanic/Latina women. METHODS AND RESULTS: The MADRES (Maternal And Developmental Risks from Environmental and Social stressors) study (n=451) is a prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles, California, who completed up to 2 staff-administered 24-hour dietary recalls in the third trimester of pregnancy. Hypertensive disorders of pregnancy were abstracted from medical records and based on a physician's diagnosis or systolic or diastolic blood pressure (≥140 or ≥90 mm Hg, respectively) at ≥2 consecutive prenatal visits. Using multivariable logistic regression, we evaluated associations of 2 previously derived dietary patterns in this population (solid fats, refined grains, and cheese and vegetables, oils, and fruit) and the Healthy Eating Index 2015 with (1) gestational hypertension, (2) preeclampsia, and (3) any hypertensive disorder of pregnancy (either gestational hypertension or preeclampsia). In separate models, we additionally tested interactions with prepregnancy body mass index. Comparing highest-to-lowest quartiles, the solid fats, refined grains, and cheese dietary pattern was associated with an increased odds of any hypertensive disorder of pregnancy (odds ratio [OR], 3.99 [95% CI, 1.44-11.0]; Ptrend=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25-13.5]; Ptrend=0.036), whereas the vegetables, oils, and fruit pattern was associated with reduced odds of preeclampsia (OR, 0.32 [95% CI, 0.10-0.99]; Ptrend=0.041). Among the overweight prepregnancy body mass index category, inverse associations of vegetables, oils, and fruit and Healthy Eating Index 2015 with preeclampsia were more pronounced (both Pinteractions=0.017). Healthy Eating Index 2015 findings were generally nonsignificant. CONCLUSIONS: While the solid fats, refined grains, and cheese diet was strongly associated with preeclampsia during pregnancy, findings suggest the vegetables, oils, and fruit diet may be more relevant than Healthy Eating Index 2015 for preventing preeclampsia among low-income Hispanic/Latina women.

Sources of personal PM2.5 exposure during pregnancy in the MADRES cohort.

BACKGROUND: Personal exposure to fine particulate matter (PM2.5) is impacted by different sources each with different chemical composition. Determining these sources is important for reducing personal exposure and its health risks especially during pregnancy. OBJECTIVE: Identify main sources and their contributions to the personal PM2.5 exposure in 213 women in the 3rd trimester of pregnancy in Los Angeles, CA. METHODS: We measured 48-hr integrated personal PM2.5 exposure and analyzed filters for PM2.5 mass, elemental composition, and optical carbon fractions. We used the EPA Positive Matrix Factorization (PMF) model to resolve and quantify the major sources of personal PM2.5 exposure. We then investigated bivariate relationships between sources, time-activity patterns, and environmental exposures in activity spaces and residential neighborhoods to further understand sources. RESULTS: Mean personal PM2.5 mass concentration was 22.3 (SD = 16.6) µg/m3. Twenty-five species and PM2.5 mass were used in PMF with a final R2 of 0.48. We identified six sources (with major species in profiles and % contribution to PM2.5 mass) as follows: secondhand smoking (SHS) (brown carbon, environmental tobacco smoke; 65.3%), fuel oil (nickel, vanadium; 11.7%), crustal (aluminum, calcium, silicon; 11.5%), fresh sea salt (sodium, chlorine; 4.7%), aged sea salt (sodium, magnesium, sulfur; 4.3%), and traffic (black carbon, zinc; 2.6%). SHS was significantly greater in apartments compared to houses. Crustal source was correlated with more occupants in the household. Aged sea salt increased with temperature and outdoor ozone, while fresh sea salt was highest on days with westerly winds from the Pacific Ocean. Traffic was positively correlated with ambient NO2 and traffic-related NOx at residence. Overall, 76.8% of personal PM2.5 mass came from indoor or personal compared to outdoor sources. IMPACT: We conducted source apportionment of personal PM2.5 samples in pregnancy in Los Angeles, CA. Among identified sources, secondhand smoking contributed the most to the personal exposure. In addition, traffic, crustal, fuel oil, fresh and aged sea salt sources were also identified as main sources. Traffic sources contained markers of combustion and non-exhaust wear emissions. Crustal source was correlated with more occupants in the household. Aged sea salt source increased with temperature and outdoor ozone and fresh sea salt source was highest on days with westerly winds from the Pacific Ocean.

Multi-omics analysis reveals overactive inflammation and dysregulated metabolism in severe community-acquired pneumonia patients.

BACKGROUND: Severe community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity. METHODS: Here, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients. RESULTS: There were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases. CONCLUSION: The plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort.

Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (ORfine = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (pinteraction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (pinteraction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males ORgross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males ORfine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.

The Role of Social Support and Acculturation Factors on Postpartum Mental Health Among Latinas in the MADRES Pregnancy Cohort.

We examined the associations between social support and postpartum mental health in 137 U.S. and foreign-born Latinas in the MADRES pregnancy cohort. We also examined whether language, years in the U.S., and country of birth moderates these relationships. Participants were administered PROMIS support measures 1 month postpartum; the Perceived Stress and Postpartum Distress Measure 3, 6, and 12 months postpartum; and the CESD scale 12 months postpartum. Perceived stress was lower at 6 months postpartum for women reporting higher emotional (p = 0.01), informational (p = 0.03), and instrumental support (p < 0.001); and lower at 12 months postpartum for women reporting higher emotional support (p = 0.01). Distress at 6 months was lower in women reporting higher emotional support (p = 0.03). Interactions suggest that associations were stronger for mothers that speak Spanish, spent fewer years in the U.S., and were born in Central America.

A facile boronophenylalanine modified polydopamine dual drug-loaded nanoparticles for enhanced anti-tumor immune response in hepatocellular carcinoma comprehensive treatment.

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

Effects of in-utero personal exposure to PM2.5 sources and components on birthweight.

In-utero exposure to fine particulate matter (PM2.5) and specific sources and components of PM2.5 have been linked with lower birthweight. However, previous results have been mixed, likely due to heterogeneity in sources impacting PM2.5 and due to measurement error from using ambient data. Therefore, we investigated the effect of PM2.5 sources and their high-loading components on birthweight using data from 198 women in the 3rd trimester from the MADRES cohort 48-h personal PM2.5 exposure monitoring sub-study. The mass contributions of six major sources of personal PM2.5 exposure were estimated for 198 pregnant women in the 3rd trimester using the EPA Positive Matrix Factorization v5.0 model, along with their 17 high-loading chemical components using optical carbon and X-ray fluorescence approaches. Single- and multi-pollutant linear regressions evaluated the association between personal PM2.5 sources/components and birthweight, adjusting for gestational age, maternal age, race, infant sex, parity, diabetes status, temperature, maternal education, and smoking history. Participants were predominately Hispanic (81%), with a mean (SD) gestational age of 39.1 (1.5) weeks and age of 28.2 (6.0) years. Mean birthweight was 3295.8 g (484.1) and mean PM2.5 exposure was 21.3 (14.4) µg/m3. A 1 SD increase in the mass contribution of the fresh sea salt source was associated with a 99.2 g decrease in birthweight (95% CI - 197.7, - 0.6), and aged sea salt was associated with a 70.1 g decrease in birthweight (95% CI - 141.7, 1.4). Magnesium, sodium, and chlorine were associated with lower birthweight, which remained after adjusting for PM2.5 mass. This study found evidence that major sources of personal PM2.5 including fresh and aged sea salt were negatively associated with birthweight, with the strongest effect on birthweight from Na and Mg. The effect of crustal and fuel oil sources differed by infant sex with negative associations seen in boys compared to positive associations in girls.

Experience in the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma.

OBJECTIVE: To discuss the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma. METHODS: We retrospectively analyzed all cases of sigmoid sinus thrombophlebitis caused by middle ear cholesteatoma over a period of 7 years. 7 male and 2 female patients, ranging in age from 9 to 66 years, were diagnosed with sigmoid sinus thrombophlebitis by clinical presentation and radiological examination. By executing a modified mastoidectomy and tympanoplasty (canal wall-down tympanoplasty) to entirely remove the cholesteatoma-like mastoid epithelium, all patients were effectively treated surgically without opening the sigmoid sinus. All patients were treated with broad-spectrum antibiotics, but no anticoagulants were used. RESULTS: 9 patients had otogenic symptoms such as ear pus, tympanic membrane perforation, and hearing loss. In the initial stage of the surgery, modified mastoidectomy and tympanoplasty were performed on 8 of the 9 patients. 1 patient with a brain abscess underwent puncturing (drainage of the abscess) to relieve cranial pressure, and 4 months later, a modified mastoidectomy and tympanoplasty were carried out. Following surgery and medication, the clinical symptoms of every patient improved. After the follow-up of 6 months to 7 years, 3 patients were re-examined for MRV and showed partial sigmoid sinus recovery with recanalization. 4 months following middle ear surgery, the extent of a patient's brain abscess lesions was significantly reduced. 1 patient experienced facial paralysis after surgery and recovered in 3 months. None of the patients had a secondary illness, an infection, or an abscess in a distant organ. CONCLUSION: The key to a better prognosis is an adequate course of perioperative antibiotic medication coupled with surgical treatment. A stable sigmoid sinus thrombus can remain for a long time after middle ear lesions have been removed, and it is less likely to cause infection and abscesses in the distant organs. The restoration of middle ear ventilation is facilitated by tympanoplasty. It is important to work more closely with multidisciplinary teams such as neurology and neurosurgery when deciding whether to perform lateral sinusotomies to remove thrombus or whether to administer anticoagulation.

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia.

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.