Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure.

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

A high-performance deep-learning-based pipeline for whole-brain vasculature segmentation at the capillary resolution.

MOTIVATION: Reconstructing and analyzing all blood vessels throughout the brain is significant for understanding brain function, revealing the mechanisms of brain disease, and mapping the whole-brain vascular atlas. Vessel segmentation is a fundamental step in reconstruction and analysis. The whole-brain optical microscopic imaging method enables the acquisition of whole-brain vessel images at the capillary resolution. Due to the massive amount of data and the complex vascular features generated by high-resolution whole-brain imaging, achieving rapid and accurate segmentation of whole-brain vasculature becomes a challenge. RESULTS: We introduce HP-VSP, a high-performance vessel segmentation pipeline based on deep learning. The pipeline consists of three processes: data blocking, block prediction, and block fusion. We used parallel computing to parallelize this pipeline to improve the efficiency of whole-brain vessel segmentation. We also designed a lightweight deep neural network based on multi-resolution vessel feature extraction to segment vessels at different scales throughout the brain accurately. We validated our approach on whole-brain vascular data from three transgenic mice collected by HD-fMOST. The results show that our proposed segmentation network achieves the state-of-the-art level under various evaluation metrics. In contrast, the parameters of the network are only 1% of those of similar networks. The established segmentation pipeline could be used on various computing platforms and complete the whole-brain vessel segmentation in 3 h. We also demonstrated that our pipeline could be applied to the vascular analysis. AVAILABILITY AND IMPLEMENTATION: The dataset is available at http://atlas.brainsmatics.org/a/li2301. The source code is freely available at https://github.com/visionlyx/HP-VSP.

LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

Exploring the impact of prenatal perfluoroalkyl and polyfluoroalkyl substances exposure on blood pressure in early childhood: A longitudinal analysis.

Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP [first trimester:ß=3.03, 95%CI: (1.01,5.05); second trimester: ß=2.35, 95%CI: (0.94,3.75); third trimester: ß=2.57, 95%CI:(0.80,4.34)]; MAP [first trimester:ß=2.55, 95%CI: (0.64,4.45); second trimester: ß=2.28, 95%CI: (0.95,3.61); third trimester: ß=2.35, 95%CI:(0.68,4.01)]). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters [first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79)]. A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (ß=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.

Paraben exposure and couple fecundity: a preconception cohort study.

STUDY QUESTION: Is pre-conception exposure to parabens associated with fecundity in couples of childbearing age? SUMMARY ANSWER: Paraben exposure in female partners was associated with reduced couple fecundity and anti-Müllerian hormone (AMH) might be one of the possible mediators. WHAT IS KNOWN ALREADY: The reproductive toxicity of parabens, a class of widely used preservatives, has been suggested but evidence regarding their effects on couple fecundity is scarce. STUDY DESIGN, SIZE, DURATION: In this couple-based prospective cohort study, a total of 884 pre-conception couples who participated in the Shanghai Birth Cohort between 2013 and 2015 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Concentrations of six parabens were measured in urine samples collected from couples. Malondialdehyde, C-reactive protein, and AMH were assessed in female partners. The outcomes included couple fecundability (time-to-pregnancy, TTP) and infertility (TTP > 12 menstrual cycles). Partner-specific and couple-based models were applied to estimate the associations. The joint effect of paraben mixture on couple fecundity was estimated by quantile-based g-computation (q-gcomp). Mediation analysis was used to assess the mediating roles of oxidative stress, inflammation and ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 525 couples (59.4%) conceived spontaneously. In the partner-specific model, propyl paraben (PrP), butyl paraben (BuP), and heptyl paraben (HeP) in female partners were associated with reduced fecundability (fecundability odds ratio (95% CI): 0.96 (0.94-0.98) for PrP; 0.90 (0.87-0.94) for BuP; 0.42 (0.28-0.65) for HeP) and increased risk of infertility (rate ratio (95% CI): 1.06 (1.03-1.10) for PrP; 1.14 (1.08-1.21) for BuP; 1.89 (1.26-2.83) for HeP). Similar associations were observed in the couple-based model. AMH played a significant mediation role in the association (average causal mediation effect (95% CI): 0.001 (0.0001-0.003)). Paraben exposure in male partners was not associated with couple fecundity. The joint effect of paraben mixture on couple fecundity was non-significant. LIMITATIONS, REASONS FOR CAUTION: Self-reported pregnancy and single urine sample may lead to misclassification. The mediation analysis is limited in that levels of sex hormones were not measured. The inclusion of women with irregular menstrual cycles might affect the results. It is possible that the observed association was due to reverse causation. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to assess the effects of paraben exposure on couple fecundity in Asians. Given the widespread exposure to parabens in couples of childbearing age, the present findings may have important public health implications. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by the National Natural Science Foundation of China (41991314), the Shanghai Science and Technology Development Foundation (22YF1426700), the Science and Technology Commission of Shanghai Municipality (21410713500), and the Shanghai Municipal Health Commission (2020CXJQ01). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

A sensitive and robust method for the simultaneous determination of thirty-three legacy and emerging per- and polyfluoroalkyl substances in human plasma and serum.

Legacy and emerging per- and polyfluoroalkyl substances (PFAS) have attracted growing attention due to their potential adverse effects on humans. We developed a method to simultaneously determine thirty-three PFAS (legacy PFAS, precursors, and alternatives) in human plasma and serum using solid phase extraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The method yielded good linearity (>0.995) and excellent limits of detection (LODs) (0.0005~0.012 ng mL-1 in plasma and 0.002~0.016 ng mL-1 in serum). The relative recoveries ranged from 80.1 to 116%, with intra- and inter-day precision less than 14.3%. The robustness of this method has been tested continuously for 10 months (coefficients of variation <14.9%). Our method was successfully applied to the PFAS analysis of 42 real human plasma and serum samples collected from women. The proposed method is attractive for the biomonitoring of multi-class PFAS in human health risk assessment and epidemiological studies.

Prenatal exposure to fine particulate matter and newborn anogenital distance: a prospective cohort study.

BACKGROUND: Considerable attention has been paid to reproductive toxicity of fine particulate matter (PM2.5). However, the relationship between prenatal PM2.5 exposure and anogenital distance (AGD) has not been well studied. We aim to investigate the potential effects of prenatal exposure to PM2.5 on newborn AGD. METHODS: Prenatal PM2.5 exposure of 2332 participates in Shanghai (2013-2016) was estimated using high-performance machine learning models. Anoscrotal distance (AGDas) in male infants and anofourchette distance (AGDaf) in female infants were measured by well-trained examiners within 3 days after birth. We applied multiple linear regression models and multiple informant models to estimate the association between prenatal PM2.5 exposure and AGD. RESULTS: Multiple linear regression models showed that a 10 µg/m3 increase in PM2.5 exposure during full pregnancy, the second and third trimesters was inversely associated with AGDas (adjusted beta = - 1.76, 95% CI: - 2.21, - 1.31; - 0.73, 95% CI: - 1.06, - 0.40; and - 0.52; 95% CI: - 0.87, - 0.18, respectively) in males. A 10 µg/m3 increase in PM2.5 exposure during the full pregnancy, the first, second, and third trimesters was inversely associated with AGDaf (adjusted beta = - 4.55; 95% CI: - 5.18, - 3.92; - 0.78; 95% CI: - 1.10, - 0.46; - 1.11; 95% CI: - 1.46, - 0.77; - 1.45; 95% CI: - 1.78, - 1.12, respectively) in females after adjusting for potential confounders. Multiple informant models showed consistent but slightly attenuated associations. CONCLUSION: Our study observed a significant association between gestational PM2.5 exposure during pregnancy and shortened AGD in newborns, and provided new evidence on potential reproductive toxicity of prenatal PM2.5 exposure.

Perfluoroalkyl substances in umbilical cord blood and blood pressure in offspring: a prospective cohort study.

BACKGROUND: Humans are widely exposed to perfluoroalkyl substances (PFAS), which have been found to be associated with various adverse birth outcomes. As blood pressure (BP) is an important parameter reflecting cardiovascular health in early life, it is necessary to investigate the association of PFAS exposure during early lifetime and BP in childhood. Therefore, we investigated the potential association between PFAS levels in umbilical cord blood and BP of the offspring at 4 years of age in a prospective cohort study. METHODS: PFAS in umbilical cord blood samples after birth were measured with high-performance liquid chromatography/tandem mass spectrometry in the Shanghai Birth Cohort. BP was measured at 4 years of age in the offspring. Multiple linear regression model was used to investigate the association between individual PFAS level and BP of the offspring. Bayesian kernel machine regression (BKMR) was used to analyze the relationship between the PFAS mixture and BP of the offspring, while weighted quantile sum (WQS) regression was utilized for sensitivity analysis. RESULTS: A total of 129 mother-child pairs were included in our analysis. In multiple linear regressions, we observed that long-chain PFAS, mainly including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUA), was negatively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). BKMR showed that an increase in umbilical cord blood PFAS mixture levels was significantly associated with a decrease in SBP, DBP and MAP [Estimated differences (SD): -0.433 (0.161); -0.437 (0.176); -0.382 (0.179), respectively]. The most important component in the association with SBP, DBP, and MAP was PFUA. PFDoA was found to be positively associated with SBP, DBP and MAP in both models. Sensitivity analysis with WQS regression showed consistent results. CONCLUSION: Our findings suggested that umbilical blood PFAS exposure was negatively associated with BP in offspring at 4 years of age, including SBP, DBP, and MAP.

Meta-Analysis of Estrogen in Osteoarthritis: Clinical Status and Protective Effects.

Context: Osteoarthritis (OA) impacted over 5-million people worldwide in 2018, with an incidence second only to diabetes and hypertension. Clinical research has had difficulty in finding methods to treat OA quickly and effectively. More and more researchers have begun to explore the effects of estrogen (ER) on OA. Objective: The study intended to conduct a meta-analysis of studies using ER in OA, aiming to confirm the potential value of ER, laying a foundation for follow-up research, and providing new choices for the treatment of OA. Design: The research team performed a literature review searching PubMed for clinical studies on the application of ER for the OA treatment or on the improvement of joint pain that: (1) were published after the year 2000, and (2) had participants who used ER compared to other treatment methods. The research team selected studies for analysis after independent screening by two members of the team, based on inclusion and exclusion criteria and a methodological quality evaluation. The meta-analysis used RevMan V5.3 software. Intervention: The research team included eight studies with 11 689 participants, with 5776 participants who received ER treatments becoming the intervention group, and with 5913 participants who received other treatments becoming the control group. Outcome Measures: The outcome measures included the selected studies' results related: (1) to changes in the bone marker, collagen cross-linked C-telopeptide type I (CTX-1); (2) to the levels of bone Gla protein (BGP); (3) to joint-pain relief, and (4) to subjective scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a visual analogue scale (VAS) for pain, and the Short-Form 36 (SF-36). Results: The meta-analysis found that the CTX-II level was significantly lower (P < .0001) and the BGP level was significantly higher (P = .07) in the EG group than the levels in the control group. Similarly, the number of participants with joint pain in the ER group was significantly lower than that of the control group (P = .01), and a significant difference existed between the groups in the subjective scores (P = .02). Conclusion: ER can exert varying degrees of positive effects on OA and can effectively ameliorate the pathological process in OA patients, and it may become an alternative for OA treatment in the future, providing patients with better health and life quality.

Exposure to parabens and semen quality in reproductive-aged men.

BACKGROUND: Parabens are common preservatives in personal care products, cosmetics, and medical goods. In the past few years, animal studies showed the male reproductive toxicity associated with some parabens. Yet, epidemiological studies have generated inconsistent findings and research rarely has focused on the mixture effects of the parabens. We aimed to explore the associations between individual paraben exposure as well as the mixture and semen quality parameters. METHODS: A total of 795 male partners from preconception couples were included in the study. Their urine samples were analyzed for the concentrations of six parabens, namely methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben (BuP), benzyl paraben (BzP) and heptyl paraben (HeP). Multiple linear regression models and weighted quantile sum regression (WQS) models were utilized to assess the relationships between individual paraben exposure and paraben mixture with semen quality parameters, respectively. RESULTS: After adjusting for covariates, exposure to a paraben mixture was significantly associated with declining sperm concentration, total sperm count, and progressive motility, among which BuP was identified as the main contributor to sperm concentration and total sperm count while MeP to progressive motility. Results from multiple linear regression models were generally in line with the WQS analysis. CONCLUSIONS: Our results suggest negative associations between paraben mixture and sperm concentration, total sperm count, and sperm motility among reproductive-aged men.

Association of circulating tumor cell-white blood cell clusters with survival outcomes in patients with colorectal cancer after curative intent surgery.

BACKGROUND: The analysis of circulating tumor cell-associated white blood cell (CTC-WBC) clusters represented the progress in the liquid biopsy of malignant tumors, however, related research in patients with colorectal cancer is still absent. METHODS: To explore associations between CTC-WBC clusters and the prognosis of these patients, we conducted an independent cohort of 329 colorectal cancer patients after curative intent surgery and pre-operative CTC detection in Nanfang Hospital, Southern Medical University, Guangzhou, China between January 1, 2017, and September 31, 2019. The primary cohort referred to patients with CTC-WBC clusters positive. The control cohort was defined as those with exclusively CTCs positive. CTCs were enriched and distinguished by The CanPatrol™ system (SurExam, China). The Kaplan-Meier curve was used to compare the progressive-free survival (PFS) and overall survival (OS) between two groups. The COX regression model was used to assess the predictive value of CTC-WBC clusters. RESULTS: Sixty three patients presented CTC-WBC clusters positive (CTC-WBC group) and 266 patients showed solely CTCs (CTC group). The number of CTCs was significantly different between two groups (P < 0.001) and the rest of clinical characteristics were not markedly associated with the presence of CTC-WBC clusters. Kaplan-Meier curves of PFS and OS exhibited that the CTC-WBC group had significantly shorter PFS (P = 0.011), while not for OS. The multivariate model further suggested that the CTC-WBC clusters (Hazard Ratio = 1.89, 95% Confidence Interval 1.02-3.51, P = 0.042) was an independent predictor for the PFS of in post-operation CRC patients. CONCLUSION: The CTC-WBC cluster is significantly associated with recurrence after operation in CRC patients. This finding facilitates the evaluation of this indicator in tumor progression.

Environmental Exposure to 6:2 Polyfluoroalkyl Phosphate Diester and Impaired Testicular Function in Men.

6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) has been demonstrated to disrupt reproductive endocrine functions using experimental studies. However, evidence from humans is not available yet. This cross-sectional study aims to assess the relationship between 6:2 diPAP exposure and the testicular function among adult men. A total of 902 men seeking preconception care were included. Plasma 6:2 diPAP concentrations were determined, while the testicular function was assessed via semen quality and reproductive hormones in serum. The association was assessed by multiple linear regression. Stratified analyses by age and body mass index (BMI) were conducted to assess the potential effect modification by these two variables. Regression analyses revealed that 6:2 diPAP exposure was significantly inversely associated with androgens [i.e., total testosterone (TT) and free androgen index (FAI)], markers of testosterone production potential [i.e., TT/luteinizing hormone (LH) and FAI/LH], estradiol, and insulin-like factor 3, a biomarker of Leydig cell function. These associations were robust in sensitivity analyses. However, age and BMI did not modify these associations, and no association was observed between 6:2 diPAP and semen quality. Our study suggests that exposure to 6:2 diPAP may inhibit androgen synthesis and impair Leydig cell function in adult men.

Association between triclosan exposure and obesity measures among 7-year-old children in northern China.

BACKGROUND: Triclosan (TCS) is a widely used synthetic antibacterial compound with ubiquitous human exposure. Animal studies have suggested the obesogenic effect of TCS exposure, but knowledge regarding its impacts on childhood obesity was limited. OBJECTIVE: To investigate the associations of TCS exposure with childhood obesity in northern China. METHODS: This study included 423 children who participated in the 7-year-old follow-up visits of Laizhou Wan Birth Cohort in Shandong, northern China. Children's TCS exposure were determined in spot urine samples via high performance liquid chromatography-tandem mass. Their height, weight, waist circumference, body fat percentage, body mass index (BMI), and waist-to-height ratio (WHtR) were measured or calculated. BMI z-score ≥ 85th percentile was defined as overweight/obesity, and WHtR ≥ 0.5 was considered to be abdominal obesity. Multivariable linear regressions, generalized linear models (GLMs), and multivariable logistic regressions were performed to examine the associations between TCS exposure and obesity measures in children. RESULTS: Linear regressions showed that TCS concentrations, when treated as continuous variables, were positively associated with BMI z-score (ß = 0.12, 95% CI: 0.01, 0.24) and body fat percentage (ß = 0.82, 95% CI: 0.13, 1.52). When TCS concentrations were categorized as a four-level ordinal variable, the results of GLMs were similar those of continuous variables and both of the positive trends were significant (p-trend = 0.049 for BMI z-score; p-trend = 0.023 for body fat percentage). Moreover, the higher TCS levels versus reference group were associated with an approximate 2-3 fold increased risk of abdominal obesity (p-trend = 0.044). CONCLUSION: Exposure to TCS was positively associated with obesity measures among 7-year-old children in northern, China. Given to the cross-sectional study design, a large prospective study is warranted to confirm our findings.

OsHsfB4b Confers Enhanced Drought Tolerance in Transgenic Arabidopsis and Rice.

Heat shock factors (Hsfs) play pivotal roles in plant stress responses and confer stress tolerance. However, the functions of several Hsfs in rice (Oryza sativa L.) are not yet known. In this study, genome-wide analysis of the Hsf gene family in rice was performed. A total of 25 OsHsf genes were identified, which could be clearly clustered into three major groups, A, B, and C, based on the characteristics of the sequences. Bioinformatics analysis showed that tandem duplication and fragment replication were two important driving forces in the process of evolution and expansion of the OsHsf family genes. Both OsHsfB4b and OsHsfB4d showed strong responses to the stress treatment. The results of subcellular localization showed that the OsHsfB4b protein was in the nucleus whereas the OsHsfB4d protein was located in both the nucleus and cytoplasm. Over-expression of the OsHsfB4b gene in Arabidopsis and rice can increase the resistance to drought stress. This study provides a basis for understanding the function and evolutionary history of the OsHsf gene family, enriching our knowledge of understanding the biological functions of OsHsfB4b and OsHsfB4d genes involved in the stress response in rice, and also reveals the potential value of OsHsfB4b in rice environmental adaptation improvement.

Construction and application of the knowledge graph method in management of soil pollution in contaminated sites: A case study in South China.

Contaminated sites are a main cause of urban soil problems and have led to increasing pollution and public risk in China as a result of the rapid growth of industrial and urban land use. Because land pollution involves extensive multi-source heterogeneous information, identifying the risk of urban soil pollution efficiently and predicting pollution-related events are important for urban environmental management. Knowledge graphs (KGs) have unique advantages in dealing with massive amounts of information. This study attempts to construct a KG of contaminated sites in South China to explore its feasibility and effectiveness in urban soil environmental management. The results demonstrate that KGs have a favorable effect in information retrieval, knowledge reasoning, and visualization. Studied cases in this article demonstrate that the KG model can achieve many functions, including the display of global information of polluted sites, and discovery of regional distribution of characteristic pollutants and main pollutants of specific industries, based on special query syntax. However, this approach is limited by some technical difficulties, such as knowledge mining of natural resources, which must be overcome in future studies to improve the operability of KG technologies.

alpha1A-adrenoceptor is involved in norepinephrine-induced proliferation of pulmonary artery smooth muscle cells via CaMKII signaling.

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Some studies have demonstrated the sympathetic nervous system is activated in PAH and norepinephrine (NE) released is closely linked with its activation. However, the subtypes of adrenoreceptor (AR) and the downstream molecular cascades which are involved in the proliferation of PASMCs are still unclear. In this study, adult male Wistar rats were exposed to chronic hypoxia and PASMCs were cultured in hypoxic condition. Significant upregulation of α1A -AR was identified by Western blot analysis or immunofluorescence in all of the pulmonary arteries, lung tissues, and cell hypoxic models. Western blot analysis, flow cytometry, and immunofluorescence were applied to detect the roles of α1A -AR in NE mediated proliferation of PASMCs. We revealed 5-methylurapidil (5-MU) reversed NE-induced upregulation of PCNA, CyclinA and CyclinE, more cells from G0 /G1 phase to G2 /M+S phase, enhancement of the microtubule formation. In addition, we found calcium/calmodulin(CaM)-dependent protein kinase type II (CaMKII) pathway was involved in α1A -AR-mediated cell proliferation. [Ca2+ ]i measurements showed that an increase of [Ca2+ ]i caused by NE or/and hypoxia could be blocked by 5-MU in PASMCs. Western blot analysis results demonstrated the augmentation of CaMKII phosphorylation level was caused by hypoxia or NE in pulmonary arteries, lung tissues, and PASMCs. KN62 attenuated NE-induced proliferation of PASMCs under normoxia and hypoxia. In conclusion, those results suggested NE which stimulated α1A -AR-mediated the proliferation of PASMCs, which may be via the CaMKII pathway, and it could be used as a novel treatment strategy in PAH.

15-Lipoxygenase promotes chronic hypoxia-induced pulmonary artery inflammation via positive interaction with nuclear factor-κB.

OBJECTIVE: Our laboratory has previously demonstrated that 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) is involved in hypoxic pulmonary arterial hypertension. Chronic hypoxia-induced vascular inflammation has been considered as an important stage in the development of pulmonary arterial hypertension. Here, we determined the contribution of 15-HETE in the hypoxia-induced pulmonary vascular inflammation. APPROACH AND RESULTS: Chronic hypoxia-induced monocyte/macrophage infiltration and the expressions of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed in hypoxic rat model and cultured pulmonary arterial endothelium cells using immunochemistry methods. We found that monocyte/macrophage infiltration and the expressions of intercellular adhesion molecules under hypoxia were markedly inhibited by 15-HETE inhibitors or 15-LO1/2 small interfering RNA. In addition, exogenous 15-HETE enhanced the expression of both adhesion molecules in pulmonary arterial endothelium cells in a time-dependent manner. Hypoxia-induced 15-LO1/2 expression in rat pulmonary arterial endothelium cells was significantly abolished by nuclear factor-κB inhibitors. Meanwhile, nuclear factor-κB activity was enhanced prominently by the 15-LO1/2 product, 15-HETE, suggesting a positive feedback mechanism. CONCLUSIONS: Taken together, our results suggest that chronic hypoxia promotes monocyte infiltration into the vasculature and adhesion molecules upregulation in pulmonary arterial endothelium cells via a positive interaction between 15-LO/15-HETE and nuclear factor-κB. Our study revealed a novel mechanism underlying hypoxia-induced pulmonary arterial inflammation and suggested new therapeutic strategies targeting 15-LO/15-HETE and nuclear factor-κB in the treatment of pulmonary arterial hypertension.

Polyfluoroalkyl phosphate esters (PAPs) as PFAS substitutes and precursors: An overview.

Polyfluoroalkyl phosphate esters (PAPs) are emerging substitutes for legacy per- and polyfluoroalkyl substances (PFAS), which are widely applied in consumer products and closely related to people's daily lives. Increasing concern has been raised about the safety of PAPs due to their metabolism into perfluorooctanoic acid (PFOA) and other perfluorinated carboxylates (PFCAs) in vivo. This review summarizes the current knowledge on PAPs and highlights the knowledge gaps. PAPs dominated the PFAS profiles in wastewater, sludge, household dust, food-contact materials, paper products, paints, and cosmetics. They exhibit biomagnification due to their higher levels in top predators. PAPs have been detected in human blood worldwide, with the highest mean levels being found in the United States (1.9 ng/mL) and China (0.4 ng/mL). 6:2 diPAP is the predominant PAP among all identified matrices, followed by 8:2 diPAP. Toxicokinetic studies suggest that after entering the body, most PAPs undergo biotransformation, generating phase Ⅰ (i.e., PFCAs), phase II, and intermediate products with toxicity to be verified. Several epidemiological and toxicological studies have reported the antiandrogenic effect, estrogenic effect, thyroid disruption, oxidative damage, and reproductive toxicity of PAPs. More research is urgently needed on the source and fate of PAPs, human exposure pathways, toxicity other than reproductive and endocrine systems, toxic effects of metabolites, and mixed exposure effects.