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.

Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19.

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

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.

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.

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.

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.

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.

Organophosphate ester flame retardant chemicals and maternal depression during pregnancy.

BACKGROUND: Depression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy. METHODS: This study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR). RESULTS: Participants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP. CONCLUSIONS: Our findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression.

A Vegetable, Oil, and Fruit Dietary Pattern in Late Pregnancy is Linked to Reduced Risks of Adverse Birth Outcomes in a Predominantly Low-Income Hispanic and Latina Pregnancy Cohort.

BACKGROUND: Studies examining diet and its links to birth outcomes among socioeconomically disadvantaged populations in the United States are scarce. OBJECTIVES: We aimed to identify prenatal dietary patterns, examine their relationships with birth outcomes, and evaluate the variation of these associations by maternal diabetes status [no diabetes, gestational diabetes mellitus (GDM), preexisting diabetes]. METHODS: Women in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study (n = 465)-an ongoing, prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles-completed up to two 24-hour dietary recalls in the third trimester of pregnancy. We identified prenatal dietary patterns via factor analysis and evaluated their associations with infant birth weight and gestational age at birth (GA) z-scores, separately, using linear regression, as well as the associations of the dietary patterns with premature births, having an infant that was small for gestational age (SGA), and having an infant that was large for gestational age, using logistic regression and adjusting for relevant covariates. We additionally tested interaction terms between prenatal dietary patterns and maternal diabetes status in separate models. We adjusted for multiple comparisons using the false discovery rate. RESULTS: We identified 2 dietary patterns: 1) a dietary pattern of solid fats, refined grains, and cheese (SRC); and 2) a dietary pattern of vegetables, oils, and fruit (VOF). Comparing the highest to lowest quartiles, the VOF was significantly associated with a greater infant birth weight (ß = 0.40; 95% CIs: 0.10, 0.70; Ptrend = 0.011), a greater GA (ß = 0.32; 95% CIs: 0.03, 0.61; Ptrend = 0.036), lower odds of a premature birth (OR = 0.31; 95% CIs: 0.10, 0.95; Ptrend = 0.049), and lower odds of having an infant that was SGA (OR = 0.18; 95% CIs: 0.06, 0.58; Ptrend = 0.028). Only among women with GDM, a 1-SD score increase in the prenatal SRC was significantly associated with a lower infant birth weight (ß = -0.20; 95% CIs -0.39, -0.02; Pinteraction = 0.040). CONCLUSIONS: Among low-income Hispanic/Latina pregnant women, greater adherence to the prenatal VOF may lower the risk of a premature birth and having an infant that is SGA. Greater adherence to the SRC, however, may adversely affect newborn birth weight among mothers with GDM, but future research is needed to verify our findings.

Research progress of circRNA in malignant tumour metabolic reprogramming.

Cancer is a multi-factor systemic malignant disease, which has seriously threatened human health and created a heavy burden on the world economy. Metabolic reprogramming, one of the important signs of malignant tumours, provides necessary nutrition for tumorigenesis and cancer development; thus, it has recently become a research hot spot, even though the metabolic mechanism is quite intricate. Circular RNA (circRNA) affects cancer cell metabolism through various molecular mechanisms, playing an important role in promoting or suppressing cancer. Because of the structure characteristics, circRNA is quite stable, and can be utilized as biomarkers. In this review, we analysed and summarized the characteristics and biological functions of circRNA and comprehensively reviewed and discussed the important role of circRNA in cancer metabolic reprogramming. This review will provide new ideas for developing new anti-cancer therapeutic targets, mining cancer diagnostic and prognostic markers, and will provide guidance for other researchers to design circRNA-related experiments and develop anti-tumour drugs.

A Comparison of Measured Airborne and Self-Reported Secondhand Smoke Exposure in the MADRES Pregnancy Cohort Study.

INTRODUCTION: Secondhand smoke (SHS) exposure during pregnancy is linked to adverse birth outcomes, such as low birth weight and preterm birth. While questionnaires are commonly used to assess SHS exposure, their ability to capture true exposure can vary, making it difficult for researchers to harmonize SHS measures. This study aimed to compare self-reported SHS exposure with measurements of airborne SHS in personal samples of pregnant women. METHODS: SHS was measured on 48-hour integrated personal PM2.5 Teflon filters collected from 204 pregnant women, and self-reported SHS exposure measures were obtained via questionnaires. Descriptive statistics were calculated for airborne SHS measures, and analysis of variance tests assessed group differences in airborne SHS concentrations by self-reported SHS exposure. RESULTS: Participants were 81% Hispanic, with a mean (SD) age of 28.2 (6.0) years. Geometric mean (SD) personal airborne SHS concentrations were 0.14 (9.41) µg/m3. Participants reporting lower education have significantly higher airborne SHS exposure (p=0.015). Mean airborne SHS concentrations were greater in those reporting longer duration with windows open in the home. There was no association between airborne SHS and self-reported SHS exposure; however, asking about the number of smokers nearby in the 48-hour monitoring period was most correlated with measured airborne SHS (Two+ smokers: 0.30µg/m3 vs. One: 0.12µg/m3 and Zero: 0.15µg/m3; p=0.230). CONCLUSIONS: Self-reported SHS exposure was not associated with measured airborne SHS in personal PM2.5 samples. This suggests exposure misclassification using SHS questionnaires and the need for harmonized and validated questions to characterize this exposure in health studies. IMPLICATIONS: This study adds to the growing body of evidence that measurement error is a major concern in pregnancy research, particularly in studies that rely on self-report questionnaires to measure secondhand smoke (SHS) exposure. The study introduces an alternative method of SHS exposure assessment using objective optical measurements, which can help improve the accuracy of exposure assessment. The findings emphasize the importance of using harmonized and validated SHS questionnaires in pregnancy health research to avoid biased effect estimates. This study can inform future research, practice, and policy development to reduce SHS exposure and its adverse health effects.

Prenatal exposures to organophosphate ester metabolite mixtures and children's neurobehavioral outcomes in the MADRES pregnancy cohort.

BACKGROUND: Evidence suggests organophosphate esters (OPEs) are neurotoxic; however, the epidemiological literature remains scarce. We investigated whether prenatal exposures to OPEs were associated with child neurobehavior in the MADRES cohort. METHODS: We measured nine OPE metabolites in 204 maternal urine samples (gestational age at collection: 31.4 ± 1.8 weeks). Neurobehavior problems were assessed among 36-month-old children using the Child Behavior Checklist's (CBCL) three composite scales [internalizing, externalizing, and total problems]. We examined associations between tertiles of prenatal OPE metabolites (> 50% detection) and detect/non-detect categories (< 50% detection) and CBCL composite scales using linear regression and generalized additive models. We also examined mixtures for widely detected OPEs (n = 5) using Bayesian kernel machine regression. RESULTS: Maternal participants with detectable versus non-detectable levels of bis(2-methylphenyl) phosphate (BMPP) had children with 42% (95% CI: 4%, 96%) higher externalizing, 45% (-2%, 114%) higher internalizing, and 35% (3%, 78%) higher total problems. Participants in the second versus first tertile of bis(butoxethyl) phosphate (BBOEP) had children with 43% (-1%, 109%) higher externalizing scores. Bis(1-chloro-2-propyl) phosphate (BCIPP) and child sex had a statistically significant interaction in internalizing (p = 0.02) and total problems (p = 0.03) models, with 120% (23%, 295%) and 57% (6%, 134%) higher scores in the third versus first BCIPP tertile among males. Among females, detectable vs non-detectable levels of prenatal BMPP were associated with 69% higher externalizing scores (5%, 170%) while the third versus first tertile of prenatal BBOEP was associated with 45% lower total problems (-68%, -6%). Although the metabolite mixture and each CBCL outcome had null associations, we observed marginal associations between di-n-butyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and higher internalizing scores (0.15; 95% CrI: -0.02, 0.32), holding other metabolites at their median. CONCLUSIONS: Our results generally suggest adverse and sex-specific effects of prenatal exposure to previously understudied OPEs on neurobehavioral outcomes in 36-month children, providing evidence of potential OPE neurotoxicity.

Value of P300 amplitude in the diagnosis of untreated first-episode schizophrenia and psychosis risk syndrome in children and adolescents.

BACKGROUND: Identifying the characteristic neurobiological changes of early psychosis is helpful for early clinical diagnosis. However, previous studies on the brain electrophysiology of children and adolescents with psychosis are rare. METHODS: This study compared P300 amplitude at multiple electrodes between children and adolescents with first-episode schizophrenia (FES, n = 48), children and adolescents with psychosis risk syndrome (PRS, n = 24), and healthy controls (HC, n = 30). Receiver operating characteristic (ROC) analysis was used to test the ability of P300 amplitude to distinguish FES, PRS and HC individuals. RESULTS: The P300 amplitude in the FES group were significantly lower than those in the HC at the Cz, Pz, and Oz electrodes. The P300 amplitude was also significantly lower in the prodromal group than in the HC at the Pz and Oz electrodes. ROC curve analysis showed that at the Pz electrode, the P300 amplitude evoked by the target and standard stimulus showed high sensitivity, specificity, accuracy, and area under the curve value for distinguishing FES from HC individuals. CONCLUSIONS: This study found early visual P300 deficits in children and adolescents with FES and PRS, with the exclusion of possible influence of medication and chronic medical conditions, suggesting the value of P300 amplitude for the identification of early psychosis.

Highly Selective and Efficient Solar-Light-Driven CO2 Conversion with an Ambient-Stable 2D/2D Co2 P@BP/g-C3 N4 Heterojunction.

Renewable solar-driven carbon dioxide (CO2 ) conversion to highly valuable fuels is an economical and prospective strategy for both the energy crisis and ecological environment disorder. However, the selectivity and activity of current photocatalysts have great room for improvement due to the diversification and complexity of products. Here, an ambient-stable 2D/2D Co2 P@BP/g-C3 N4 heterojunction is designed for highly selective and efficient photocatalytic CO2 reduction reaction. The resulting Co2 P@BP/g-C3 N4 material has a remarkable conversion of CO2 to carbon monoxide (CO) with an ≈96% selectivity, coupled with a dramatically increased CO generation rate of 16.21 µmol g-1 h-1 , which is 5.4 times higher than pristine graphitic carbon nitride (g-C3 N4 ). In addition, this photocatalyst exhibits good ambient stability of black phosphorus (BP) without oxidation even over 180 days. The excellent photocatalytic selectivity and activity of Co2 P@BP/g-C3 N4 heterojunction are attributed to its lower energy barriers of *COOH, *CO, and *+CO in the process of CO2 reduction, coupled with rapid charge transfer at the heterointerfaces of BP/g-C3 N4 and Co2 P/BP. This is solidly verified by both density functional theory calculation and mechanism experiments. Therefore, this work holds great promise for an ambient-stable efficient and high selectivity photocatalyst in solar-driven CO2 conversion.

Fecal metabolomic analysis of rabbits infected with Eimeria intestinalis and Eimeria magna based on LC-MS/MS technique.

Rabbit coccidiosis is a common parasitic disease leading to economic losses in the rabbit industry. The intestinal flora plays a key role in pathogenesis of coccidiosis, and fecal metabolome mediates host-microbiome interactions as a functional readout of the gut microbiome. In this study, the E. intestinalis-infected and E. magna-infected rabbit models were established to investigate metabolic alterations and metabolic pathways based on LC-MS/MS technique for the first time. Multivariate OPLS-DA analysis was performed to explore differential metabolites. In total, 288 metabolites were detected from infected and uninfected rabbits. The level of 33 metabolites increased and 4 decreased in rabbits infected with E. intestinalis. Eight pathways were significantly perturbed during E. intestinalis infection including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, etc. After rabbits infected with E. magna, 13 metabolites were altered and 7 metabolic pathways were dysregulated. These metabolites and metabolic pathways were mainly involved in tuberculosis, parathyroid hormone synthesis, etc. Besides, 25 metabolites differed in abundance between E. intestinalis infection group and E. magna infection group, the major perturbed metabolic pathways were lipid metabolism and endocrine system, respectively. In general, it is confirmed that E. intestinalis and E. magna infection destroyed the intestinal flora, which caused corresponding changes in metabolites, and provide novel insights into the molecular mechanisms of rabbit-parasite interactions.

Novel 18F-Labeled PET Tracers Specific to Aromatase: Design, Synthesis, and Biological Evaluation.

The abnormal expression of aromatase is associated with the occurrence and development of a variety of neurological diseases and tumors. A series of 18F-labeled and 68Ga-labeled potential aromatase-binding candidate compounds were designed and synthesized based on the structures of aromatase inhibitors. Competitive inhibition experiments in vitro and molecular docking showed that BIBD-069 and BIBD-071 have high affinity for aromatase. The radiolabeling conditions of [18F]BIBD-069 and [18F]BIBD-071 were simple, and the yields were high. Biodistribution and in vivo inhibition experiments confirmed that [18F]BIBD-069 and [18F]BIBD-071 specifically bind to aromatase. [18F]BIBD-069 and [18F]BIBD-071 selectively imaged the amygdala and nucleus of the stria terminalis, which is similar to the imaging result of [11C]vorozole. Radiometabolites of [18F]BIBD-069 and [18F]BIBD-071 did not bind to aromatase and interfered with brain imaging. MicroPET-CT imaging further confirmed that [18F]BIBD-069 and [18F]BIBD-071 can specifically bind to aromatase and were not defluorinated in vivo. Given that [18F]BIBD-069 and [18F]BIBD-071 exhibit excellent aromatase binding affinities, mild radiolabeling conditions, and good pharmacokinetics, they can be important tools for the diagnosis and treatment of aromatase-related diseases.

[18F]BIBD-239: 18F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein.

[11C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited by the short half-life of 11C (20.38 min). To overcome the deficiency of [11C]ER176 and keep the pharmacophore features of ER176 to the maximum extent, we designed four fluorine-labeled ER176 derivatives using the deuterium method. In vitro competition binding confirmed that the designed compounds had high affinity for TSPO. Biodistribution experiments showed that tissues with high expression of TSPO had high uptake of these compounds, as well as that the compound showed high brain penetration and mild defluorination in vivo. Therefore, [18F]BIBD-239 with simple synthesis conditions was selected for further biological evaluation. Theoretical simulations showed that BIBD-239 and ER176 have similar binding modes and sites to Ala147-TSPO and Thr147-TSPO, which indicated that the tracers may have consistent sensitivity to the three affinity genotypes. In vitro autoradiography and in vivo PET studies of the ischemic rat brain showed dramatically higher uptake of [18F]BIBD-239 on the lesion site compared to the contralateral side with good brain kinetics. Additionally, [18F]BIBD-239 provided clear tumor PET images in a GL261 glioma model. Importantly, PET imaging and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) results showed that in vivo defluorination and other metabolites of [18F]BIBD-239 did not interfere with brain imaging. Conclusively, [18F]BIBD-239, similar to ER176 with low polymorphism sensitivity, has simple labeling conditions, high labeling yield, high affinity, and high specificity for TSPO, and it is planned for further evaluation in higher species.

Identifying pre-conception and pre-natal periods in which ambient air pollution exposure affects fetal growth in the predominately Hispanic MADRES cohort.

BACKGROUND: It is well documented that persons of color experience disproportionate exposure to environmental contaminants, including air pollution, and have poorer pregnancy outcomes. This study assessed the critical windows of exposure to ambient air pollution on in utero fetal growth among structurally marginalized populations in urban Los Angeles. METHODS: Participants (N = 281) from the larger ongoing MADRES pregnancy cohort study were included in this analysis. Fetal growth outcomes were measured on average at 32 [Formula: see text] 2 weeks of gestation by a certified sonographer and included estimated fetal weight, abdominal circumference, head circumference, biparietal diameter and femur length. Daily ambient air pollutant concentrations were estimated for four pollutants (particulate matter less than 2.5 µm (PM2.5) and less than 10 µm (PM10) in aerodynamic diameter, nitrogen dioxide (NO2), and 8-h maximum ozone (O3)) at participant residences using inverse-distance squared spatial interpolation from ambient monitoring data. Weekly gestational averages were calculated from 12 weeks prior to conception to 32 weeks of gestation (44 total weeks), and their associations with growth outcomes were modeled using adjusted distributed lag models (DLMs). RESULTS: Participants were on average 29 years [Formula: see text] 6 old and predominately Hispanic (82%). We identified a significant sensitive window of PM2.5 exposure (per IQR increase of 6 [Formula: see text]3) between gestational weeks 4-16 for lower estimated fetal weight [Formula: see text] averaged4-16 = -8.7 g; 95% CI -16.7, -0.8). Exposure to PM2.5 during gestational weeks 1-23 was also significantly associated with smaller fetal abdominal circumference ([Formula: see text] averaged1-23 = -0.6 mm; 95% CI -1.1, -0.2). Additionally, prenatal exposure to PM10 (per IQR increase of 13 [Formula: see text]3) between weeks 6-15 of pregnancy was significantly associated with smaller fetal abdominal circumference ([Formula: see text] averaged6-15 = -0.4 mm; 95% CI -0.8, -0.1). DISCUSSION: These results suggest that exposure to particulate matter in early to mid-pregnancy, but not preconception or late pregnancy, may have critical implications on fetal growth.

Evidence for rate-dependent filtering of global extrinsic noise by biochemical reactions in mammalian cells.

Recent studies have revealed that global extrinsic noise arising from stochasticity in the intracellular biochemical environment plays a critical role in heterogeneous cell physiologies. However, it remains largely unclear how such extrinsic noise dynamically influences downstream reactions and whether it could be neutralized by cellular reactions. Here, using fluorescent protein (FP) maturation as a model biochemical reaction, we explored how cellular reactions might combat global extrinsic noise in mammalian cells. We developed a novel single-cell assay to systematically quantify the maturation rate and the associated noise for over a dozen FPs. By exploiting the variation in the maturation rate for different FPs, we inferred that global extrinsic noise could be temporally filtered by maturation reactions, and as a result, the noise levels for slow-maturing FPs are lower compared to fast-maturing FPs. This mechanism is validated by directly perturbing the maturation rates of specific FPs and measuring the resulting noise levels. Together, our results revealed a potentially general principle governing extrinsic noise propagation, where timescale separation allows cellular reactions to cope with dynamic global extrinsic noise.

Rabbit microbiota across the whole body revealed by 16S rRNA gene amplicon sequencing.

BACKGROUND: Rabbit can produce meat, fur and leather, and serves as an important biomedical animal model. Understanding the microbial community of rabbits helps to raise rabbits healthily and better support their application as animal models. RESULTS: In this study, we selected 4 healthy Belgium gray rabbits to collect the microbial samples from 12 body sites, including skin, lung, uterus, mouth, stomach, duodenum, ileum, jejunum, colon, cecum, cecal appendix and rectum. The microbiota across rabbit whole body was investigated via 16S rRNA gene amplicon sequencing. After quality control, 46 samples were retained, and 3,148 qualified ASVs were obtained, representing 23 phyla and 264 genera. Based on the weighted UniFrac distances, these samples were divided into the large intestine (Lin), stomach and small intestine (SSin), uterus (Uter), and skin, mouth and lung (SML) groups. The diversity of Lin microbiota was the highest, followed by those of the SSin, Uter and SML groups. In the whole body, Firmicutes (62.37%), Proteobacteria (13.44%) and Bacteroidota (11.84%) were the most predominant phyla. The relative abundance of Firmicutes in the intestinal tract was significantly higher than that in the non-intestinal site, while Proteobacteria was significantly higher in the non-intestinal site. Among the 264 genera, 35 were the core microbiota distributed in all body sites. Sixty-one genera were specific in the SML group, while 13, 8 and 1 were specifically found in the Lin, SSin and Uter groups, respectively. The Lin group had the most difference with other groups, there were average 72 differential genera between the Lin and other groups. The functional prediction analysis showed that microbial function within each group was similar, but there was a big difference between the intestinal tracts and the non-intestinal group. Notably, the function of microorganism in uterus and mouth were the most different from those in the gastrointestinal sites; rabbit's coprophagy of consuming soft feces possibly resulted in little differences of microbial function between stomach and large intestinal sites. CONCLUSION: Our findings improve the knowledge about rabbit microbial communities throughout whole body and give insights into the relationship of microbial communities among different body sites in health rabbits.