Grain Protein Content Phenotyping in Rice via Hyperspectral Imaging Technology and a Genome-Wide Association Study.

Efficient and accurate acquisition of the rice grain protein content (GPC) is important for selecting high-quality rice varieties, and remote sensing technology is an attractive potential method for this task. However, the majority of multispectral sensors are poor predictors of GPC due to their broad spectral bands. Hyperspectral technology provides a new analytical technology for bridging the gap between phenomics and genomics. However, the small size of typical datasets is a constraint for model construction for estimating GPC, limiting their accuracy and reducing their ability to generalize to a wide range of varieties. In this study, we used hyperspectral data of rice grains from 515 japonica varieties and deep convolution generative adversarial networks (DCGANs) to generate simulated data to improve the model accuracy. Features sensitive to GPC were extracted after applying a continuous wavelet transform (CWT), and the estimated GPC model was constructed by partial least squares regression (PLSR). Finally, a genome-wide association study (GWAS) was applied to the measured and generated datasets to detect GPC loci. The results demonstrated that the simulated GPC values generated after 8,000 epochs were closest to the measured values. The wavelet feature (WF1743, 2), obtained from the data with the addition of 200 simulated samples, exhibited the highest GPC estimation accuracy (R 2 = 0.58 and RRMSE = 6.70%). The GWAS analysis showed that the estimated values based on the simulated data detected the same loci as the measured values, including the OsmtSSB1L gene related to grain storage protein. This study provides a new technique for the efficient genetic study of phenotypic traits in rice based on hyperspectral technology.

Advances of long non-coding RNAs in osteoclast differentiation and osteoporosis.

INTRODUCTION: Osteoclasts, which are responsible for bone resorption, are specialized multinucleated cells generated from monocyte/macrophage progenitor cells or hematopoietic stem cells (HSCs). Physiological bone remodeling can become pathological, such as osteoporosis, when osteoclastogenesis is out of balance. Thousands of long noncoding RNAs (lncRNAs) influence important molecular and biological processes. Recent research has revealed gene expression regulation function that numerous lncRNAs regulate nuclear domain organization, genome stability. Furthermore, the research of lncRNAs has substantial clinical implications for the treatment of existing and new diseases. AREAS COVERED: In this review, we gather the most recent research on lncRNAs and their potential for basic research and clinical applications in osteoclast and osteoporosis. We also discuss the findings here in order to fully understand the role of lncRNAs in osteoclast differentiation and osteoporosis, as well as to provide a solid basis for future research exploring associated mechanisms and treatments. EXPERT OPINION: LncRNA has been considered as an important role in the regulation of osteoclast differentiation and osteoporosis. It is exciting to investigate pathophysiological processes in osteoporosis and the therapeutic potential of lncRNAs. We hope that this review will offer promising prospects for the development of precision and individualized approaches to treatment.

Prevalence of Chronic Obstructive Pulmonary Disease and Its Associated Risk Factors in Yunnan Province, China: A Population Based Cross-Sectional Study.

Purpose: Chronic obstructive pulmonary disease (COPD) is a significant disease impacting health and quality of life. Yunnan Province, a major tobacco producer, lacks comprehensive COPD studies. The purpose of this study is to describe the epidemic situation of COPD in Yunnan province and explore its influencing factors. Methods: This study is a cross-sectional research conducted in a representative sample of adults aged 20 and older from 13 prefectures and cities in Yunnan Province, China. COPD was diagnosed using post-bronchodilator pulmonary function tests. Demographics were analyzed with descriptive statistics. The influencing factors of COPD were examined by using the multivariate logistic regression models. Results: Our study found that high-risk individuals for COPD accounted for 20.30% of the screened population aged 20 and above, with a COPD prevalence of 27.18% among this high-risk group. Male had a higher prevalence (33.01%) than did female (16.35%; p<0.001 for sex difference). Additionally, the proportion of severe and extremely severe COPD cases in Yunnan Province was higher than the national average and other provinces. After considering the potential confounding variables, male (OR=2.291, 95% CI: 1.584-3.313), age (OR=1.501, 95% CI: 1.338-1.685), underweight (OR=1.747, 95% CI: 1.225-2.491), previous smoking (OR=1.712, 95% CI: 1.182-2.478), passive smoking (OR=1.444, 95% CI: 1.159-1.800), and a history of respiratory system diseases in childhood (OR=2.010, 95% CI: 1.346-3.001) were significantly associated with an increased risk of COPD. Conversely, being overweight (OR=0.636, 95% CI: 0.489-0.828), and residing in high-altitude counties (OR=0.445, 95% CI: 0.263-0.754) were negatively correlated with the risk of COPD. Conclusion: There is significant prevalence of COPD (27.18%) among high-risk population aged 20 and above in Yunnan Province, China. Apart from male, smoking, BMI and other known risk factors for COPD. We found that high-altitude residence had a lower prevalence of COPD. There is no significant difference in COPD prevalence between Han and ethnic minority populations.

Placental Transmogrification of the Lung Presenting as Cystic-Solid Mass: A Case Report.

The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.

Consensus for antifungal stewardship in China (2024 edition).

Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

Longitudinal association between maternal cardiovascular health in pregnancy and child birth outcomes.

The American Heart Association has updated its definition of cardiovascular health (CVH) with a new framework known as Life's Essential 8 (LE8). Although gestational CVH assessment has been recommended, its significance based on LE8 for birth outcomes is unknown. We thus evaluated the status of gestational CVH based on LE8 in 3036 pregnant women of the Shanghai Maternal-Child Pairs Cohort and the population of China Maternal Nutrition and Health Sciences Survey, and also examined the association between gestational CVH and child birth outcomes. We found that only a small proportion (12.84%) had high CVH, while 1.98% had low CVH in this cohort study. In adjusted models, a 10-point increase in the gestational CVH score, indicating a more favorable score, was associated with lower neonatal size such as birth weight (ß: - 37.05 [95% confidence interval: - 52.93, - 21.16]), birth length (- 0.12[- 0.22, - 0.01]), weight-for-height z-score (- 0.07[- 0.12, - 0.03]), body mass index z-score (- 0.09 [- 0.13, - 0.04]), length-for-age Z-score (- 0.03 [- 0.06, - 0.01]), and weight-for-age z-score (- 0.08 [- 0.12, - 0.05]). Also, a 10-point increase in the gestational CVH score was associated with the lower risk of large for gestational age (LGA) (0.82 [0.73, 0.92]) and macrosomia infant (0.75 [0.64, 0.88]). CVH categories showed similar results. That is, better maternal CVH status in pregnancy was associated with lower neonatal size and lower risks for LGA and macrosomia in newborns.

Prospective associations of maternal cardiometabolic health with children cardiometabolic health at ages 3 to 6 years.

OBJECTIVE: Maternal cardiometabolic health (MCMH) may have critical effects on offspring lifetime CMH, whereas evidence on the relationship between MCMH during pregnancy and children CMH (CCMH) at ages 3∼6 years remains unknown. METHOD: The study included 1478 mother-child dyads from the Shanghai Maternal-Child Pairs Cohort study. MCMH was examined at a mean of 27.8 (24-36) weeks' gestation based on 8 metrics of 'Life Essential 8' framework involving pre-pregnancy body mass index, total cholesterol, glucose level, blood pressure, physical activity, sleep, diet quality, and nicotine exposure. CCMH was examined at the age of 3 to 6 based on 5 metrics including body mass index, physical activity, sleep health, diet quality, and nicotine exposure. To validate the robustness of main analysis, 499 children were selected to reevaluate CCMH by six metrics (adding blood pressure) for sensitivity analysis. RESULTS: Among 1478 mother-child dyads, the mean (SD) MCMH during pregnancy and CCMH scores were 67.07 (SD 8.82) and 73.80 (SD 10.75), respectively. After adjusting important confounders, each 10 points increase in (more favorable) MCMH score was significantly associated with a higher CCMH score (ß: 0.85, [95% confidence interval (CI): 0.22, 1.47]). Subgroup analysis showed similar results in girls but not in boys. For cardiometabolic risks factors in children, the risk of overweight/obesity and hypertension in children decreased with increased MCMH score (overweight/obesity, Relative Risks [RRs]: 0.98, 95%CI: [0.96, 0.99]); hypertension, RRs: 0.66, 95%CI: [0.47, 0.92]). Sensitivity analysis showed similar result. CONCLUSIONS: Better MCMH in pregnancy was associated with better CCMH at ages 3∼6 years.

Utilizing Star Polycation Nanocarrier for the Delivery of miR-184 Agomir and Its Impact on the Life History Traits of the English Grain Aphid, Sitobion avenae.

The investigation of genetics-based biopesticides has become a central focus in pesticide studies due to their inherent advantages, including species specificity, environmental safety, and a wide range of target genes. In this study, a mixture of miR-184 agomir and nanomaterial star polycation (SPc) was used to treat the nymphs of the English grain aphid, Sitobion avenae (F.). The life parameters of the aphids at various developmental stages were analyzed using an age-stage two-sex life table to assess the effect of miR-184 agomir on the experimental population. The results indicated that miR-184 agomir had a significant negative effect on four key life parameters, including the intrinsic rate of increase, the finite rate of increase, the net rate of increase, and the mean generation time. The population prediction revealed a substantial reduction (91.81% and 95.88%) in the population size of S. avenae at 60 d after treatment with miR-184 agomir, compared to the control groups. Our findings suggest that the miR-184 agomir has the potential to reduce the survival rate and mean longevity of S. avenae, highlighting its potential as a promising candidate for the development of an effective genetics-based biopesticide.

The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

Microbial community diversity from nearshore to offshore in the East China Sea.

The Pollution Nagasaki (PN) section of the East China Sea (ECS) is a typical area for studying the complex hydrographic dynamics between Changjiang River discharge and Kuroshio, displaying intense variations of environmental gradients from nearshore to offshore. However, the temporal and spatial changes of microbial communities along the PN section have long been overlooked. In this study, we performed a comprehensive investigation into the abundance, diversity and ecology of free-living (FL) and particle-associated (PA) microbial communities in seawater samples along the PN section during both summer and winter. Distinct hydrological conditions and resulting environmental gradients were observed between summer and winter, with clear features of intrusive Kuroshio subsurface water in summer and strong vertical mixing of seawater in winter. Bacterial abundance along the PN section was higher in summer (1.11 × 108 copies·L-1 - 7.37 × 108 copies·L-1) than in winter (1.83 × 106 copies·L-1 - 1.34 × 108 copies·L-1). Microbial diversity, as indicated by α-diversity indices, remained at relatively stable levels in summer, while a clear decreasing trend was observed in winter along the PN section. Additionally, the winter communities exhibited a more evident spatial shift along the PN section compared to the summer communities. 16S rRNA gene amplicon sequencing showed that microbial community composition varied considerably between different seasons (summer and winter) and lifestyles (FL and PA), with a notable dominance of Ralstonia species. in winter. Regarding the assembly of microbial communities, the stochastic process represented by dispersal limitation was the dominant process in summer, while the deterministic homogeneous selection was the most important process in winter. Correspondingly, distinct topological properties of the microbial co-occurrence networks were shown between different seasons and along the PN section. These results enhance our understanding of how hydrological conditions influence dynamic changes of microbial communities along the PN section, providing new insights for the microbial community assembly and interactions in such a complex environment.

Effects of miR-306 Perturbation on Life Parameters in the English Grain Aphid, Sitobion avenae (Homoptera: Aphididae).

MicroRNAs (miRNA) play a vital role in insects' growth and development and have significant potential value in pest control. Previously, we identified miR-306 from small RNA libraries within the English grain aphid, Sitobion avenae, a devasting insect pest for wheat. miR-306 not only involves in wing morphogenesis, but also is critically important for aphid survival. Its specific impacts on the life history traits, however, remain unclear. Here, we evaluate the impact of miR-306 perturbation on S. avenae populations using a two-sex life table approach. This comprehensive analysis revealed that miR-306 perturbation significantly prolongs the developmental stages (9.64% and 8.20%) and adult longevity of S. avenae, while decreasing pre-adult survival rate (41.45% and 38.74%) and slightly reducing average fecundity (5.80% and 13.05%). Overall, miR-306 perturbation negatively affects the life table parameters of the aphid population. The population prediction models show a significant decline in the aphid population 60 days post interference, compared to the control groups (98.14% and 97.76%). Our findings highlight the detrimental effects of miR-306 perturbation on S. avenae population growth and suggest potential candidate genes for the development of RNAi-based biopesticides targeted specifically at this pest species.

Recycling of wheat gluten wastewater: Recovery of arabinoxylan and application of its film in cherry and strawberry preservation.

This study investigated the effect of an edible water-extractable arabinoxylan (WEAX) coating on the postharvest preservation of strawberries and cherries. The WEAX film was prepared using carboxymethyl chitosan (CMCS) film as a control, with thorough characterization of its film properties. Subsequently, strawberry and cherry fruits were submerged in a solution containing edible film-forming materials and left to be stored at room temperature, followed by the analysis of their physicochemical parameters to assess their preservation efficacy. The results show that the WEAX film exhibited enhanced flexibility, superior water vapor permeability, thermal stability, and surface morphology. Furthermore, the implementation of WEAX film effectively mitigated weight loss, decay, color degradation, softening process, ascorbic acid decline, anthocyanin accumulation, and an increase in malondialdehyde content in fruits. Thus, the incorporation of WEAX coating demonstrates its capability in prolonging the shelf life of fruits post-harvest, underscoring its potential in fruit preservation practices.

Dual-role regulator of a novel miR-3040 in photoperiod-mediated wing dimorphism and wing development in green peach aphid.

Wing dimorphism is regarded as an important phenotypic plasticity involved in the migration and reproduction of aphids. However, the signal transduction and regulatory mechanism of wing dimorphism in aphids are still unclear. Herein, the optimal environmental conditions were first explored for inducing winged offspring of green peach aphid, and the short photoperiod was the most important environmental cue to regulate wing dimorphism. Compared to 16 L:8 D photoperiod, the proportion of winged offspring increased to 90% under 8 L:16 D photoperiod. Subsequently, 5 differentially expressed microRNAs (miRNAs) in aphids treated with long and short photoperiods were identified using small RNA sequencing, and a novel miR-3040 was identified as a vital miRNA involved in photoperiod-mediated wing dimorphism. More specifically, the inhibition of miR-3040 expression could reduce the proportion of winged offspring induced by short photoperiod, whereas its activation increased the proportion of winged offspring under long photoperiod. Meanwhile, the expression level of miR-3040 in winged aphids was about 2.5 times that of wingless aphids, and the activation or inhibition of miR-3040 expression could cause wing deformity, revealing the dual-role regulator of miR-3040 in wing dimorphism and wing development. In summary, the current study identified the key environmental cue for wing dimorphism in green peach aphid, and the first to demonstrate the dual-role regulator of miR-3040 in photoperiod-mediated wing dimorphism and wing development.

Groundwater suitability assessment for irrigation and drinking purposes by integrating spatial analysis, machine learning, water quality index, and health risk model.

An in-depth understanding of nitrate-contaminated surface water and groundwater quality and associated risks is important for groundwater management. Hydrochemical characteristics and driving forces of groundwater quality and non-carcinogenic risks of nitrate were revealed by the integrated approaches of self-organizing map analysis, spatial visualization by geography information system, entropy and irrigation water quality indices, and human health risk model. Groundwater samples were categorized into two clusters by SOM analysis. Cluster I including three samples were Ca-SO4 type and cluster II of remaining 136 samples were Ca-HCO3 type. Hydrochemical compositions of two cluster samples were dominated by water-rock interaction: (1) calcite and gypsum dissolution for cluster I samples and (2) calcite dissolution, silicate weathering, and positive cation exchange for cluster II samples. Nitrate contamination occurred in both cluster I and II samples, primarily induced by agricultural nitrogen fertilizer. The EWQI results showed that 90.97% in total groundwater samples were suitable for drinking purpose, while the IWQI results demonstrated that 65.03% in total groundwater samples were appropriate for irrigation purpose. The HHR model and Monte Carlo simulation indicated that the non-carcinogenic nitrated risk was highest in children. Exposure frequency was the most sensitive factor (86.33% in total) influencing the total non-carcinogenic risk, indicated by sensitivity analysis. Compared with the two clusters of groundwater, surface water has a shorter circulation cycle and lower ion concentrations resulting in better water quality. This study can provide scientific basis for groundwater quality evaluation in other parts of the world.

Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection.

The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

NLRP3-dependent pyroptosis exacerbates coxsackievirus A16 and coxsackievirus A10-induced inflammatory response and viral replication in SH-SY5Y cells.

Coxsackievirus A16 (CV-A16) and coxsackievirus A10 (CV-A10), more commonly etiological agents of hand, foot and mouth disease (HFMD), are capable of causing severe neurological syndromes with high fatalities, but their neuropathogenesis has rarely been studied. Mounting evidence indicated that pyroptosis is an inflammatory form of cell death that might be widely involved in the pathogenic mechanisms of neurotropic viruses. Our study was designed to examine the effects of NLRP3-mediated pyroptosis in CV-A16- and CV-A10-induced inflammatory neuropathologic formation. In this work, it was showed that SH-SY5Y cells were susceptible to CV-A16 and CV-A10, and meanwhile their infections could result in a decreasing cell viability and an increasing LDH release as well as Caspase1 activation. Moreover, CV-A16 and CV-A10 infections triggered NLRP3-mediated pyroptosis and promoted the release of inflammatory cytokines. Additionally, activated NLRP3 accelerated the pyroptosis formation and aggravated the inflammatory response, but inhibited NLRP3 had a dampening effect on the above situation. Finally, it was further revealed that NLRP3 agonist enhanced the viral replication, but NLRP3 inhibitor suppressed the viral replication, suggesting that NLRP3-driven pyroptosis might support CV-A16 and CV-A10 production in SH-SY5Y cells. Together, our findings demonstrated a mechanism by which CV-A16 and CV-A10 induce inflammatory responses by evoking NLRP3 inflammasome-regulated pyroptosis, which in turn further stimulated the viral replication, providing novel insights into the pathogenesis of CV-A16 and CV-A10 infections.

Prenatal maternal stress, sleep quality, and neonatal birth weight: A prospective cohort study.

To assess if the impacts of prenatal maternal stress (PNMS) on neonatal physical development including birth weight and body length vary by trimesters, and to explore the mediating effect of sleep quality in the relationships. A total of 2778 pregnant women were included from the Shanghai Maternal-Child Pairs Cohort. PNMS and sleep quality were measured in the first trimester (12-16 gestational weeks) and third trimester (32-36 gestational weeks) using the Life Event Scale for Pregnant Women (LESPW) and Pittsburgh Sleep Quality Index, respectively. And total LESPW scores were classified into three groups: high stress (≥75th percentile), medium stress (≥25th and <75th percentile), and low stress (<25th percentile). Multiple linear and logistic regressions were employed to examine the associations between PNMS and birth weight, and bootstrap were utilized to explore the mediating effects of maternal sleep. Higher (adjusted odds ratio, aOR = 1.521; 95% confidence interval (CI), 1.104-2.096) and medium (aOR = 1.421; 95% CI, 1.071-1.885) PNMS and stress from subjective events (aOR = 1.334; 95% CI, 1.076-1.654) in the first trimester were significantly associated with elevated risk for large for gestational age. Maternal severe negative objective events stress (OE3) in the third trimester were negatively associated with birth weight (ß = -0.667; 95% CI, -1.047∼-0.287), and maternal sleep latency during this period acted as a mediator in the association (indirect effect: ß = -0.0144; 95% CI, -0.0427∼-0.0003). Besides, a significant negative correlation between total LESPW score (ß = -0.022; 95% CI, -0.038∼-0.006; per 100 score) and body length in the third trimester was also observed. The impact of PNMS on neonatal birth weight varies by stress types and exposure timing. Prolonged maternal sleep latency in the third trimester correlated with lower birth weight, and mediating the link of OE3 and birth weight, which might indicate a critical period of vulnerability to the effects of PNMS on neonatal physical development.

PM2.5-induced cellular senescence drives brown adipose tissue impairment in middle-aged mice.

Airborne fine particulate matter (PM2.5) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function. Transcriptomics was performed to determine the differentially expressed genes in BAT. Quantitative RT-PCR, immunohistochemistry staining, and immunoblots were performed to verify the transcriptomics and explore the mechanism for BAT mitochondrial dysfunction. Firstly, PM2.5 exposure caused altered BAT morphology and mitochondrial dysfunction in middle-aged but not young or adult mice. Furthermore, PM2.5 exposure increased cellular senescence in BAT of middle-aged mice, accompanied by cell cycle arrest, impaired DNA replication, and inhibited AKT signaling pathway. Moreover, PM2.5 exposure disrupted apoptosis and autophagy homeostasis in BAT of middle-aged mice. Therefore, BAT in middle-aged mice was more vulnerable to PM2.5 exposure, and the cellular senescence-initiated apoptosis, autophagy, and mitochondrial dysfunction may be the mechanism of PM2.5 exposure-induced BAT impairment.

Natural background levels, source apportionment and health risks of potentially toxic elements in groundwater of highly urbanized area.

Identifying the natural background levels (NBLs), threshold values (TVs), sources and health risks of potentially toxic elements in groundwater is crucial for ensuring the water security of residents in highly urbanized areas. In this study, 96 groundwater samples were collected in urban area of Sichuan Basin, SW China. The concentrations of potentially toxic elements (Li, Fe, Cu, Zn, Al, Pb, B, Ba and Ni) were analyzed for investigating the NBLs, TVs, sources and health risks. The potentially toxic elements followed the concentration order of Fe > Ba > B > Al > Zn > Li > Cu > Ni > Pb. The NBLs and TVs indicated the contamination of potentially toxic elements mainly occurred in the northern and central parts of the study area. The Positive Matrix Factorization (PMF) model identified elevated concentrations of Fe, Al, Li, and B were found to determine groundwater quality. The primary sources of Fe, Al, Pb, and Ni were attributed to the dissolution of oxidation products, with Fe additionally affected by anthropogenic reduction environments. Li and B were determined to be originated from the weathering of tourmaline. High levels of Ni and Cu concentrations were derived from electronic waste leakage, while excessive Ba and Zn were linked to factory emissions and tire wear. The reasonable maximum exposure (RME) of hazard index (HI) was higher than safety standard and reveal the potential health risks in the southwestern study area. Sensitivity analysis demonstrated the Li concentrations possessed the highest weight contributing to health risk. This study provides a valuable information for source-specific risk assessments of potentially toxic elements in groundwater associated with urban areas.

MST1/2 exerts a pivotal role in inducing neuroinflammation and Coxsackievirus-A10 replication by interacting with innate immunity.

Coxsackievirus-A10 (CV-A10), responsible for the hand, foot and mouth disease (HFMD) pandemic, could cause serious central nervous system (CNS) complications. The underlying molecular basis of CV-A10 and host interactions inducing neuropathogenesis is still unclear. The Hippo signaling pathway, historically known for a dominator of organ development and homeostasis, has recently been implicated as an immune regulator. However, its role in host defense against CV-A10 has not been investigated. Herein, it was found that CV-A10 proliferated in HMC3 cells and promoted the release of inflammatory cytokines. Moreover, pattern recognition receptors (PRRs)-mediated pathways, including TLR3-TRIF-TRAF3-TBK1-NF-κB axis, RIG-I/MDA5-MAVS-TRAF3-TBK1-NF-κB axis and TLR7-MyD88-IRAK1/IRAK4-TRAF6-TAK1-NF-κB axis, were examined to be elevated under CV-A10 infection. Meanwhile, it was further uncovered that Hippo signaling pathway was inhibited in HMC3 cells with CV-A10 infection. Previous studies have been reported that there exist complex relations between innate immune and Hippo signaling pathway. Then, plasmids of knockdown and overexpression of MST1/2 were transfected into HMC3 cells. Our results showed that MST1/2 suppressed the levels of inflammatory cytokines via interacting with TBK1 and IRAK1, and also enhanced virus production via restricting IRF3 and IFN-ß expressions. Overall, these data obviously pointed out that CV-A10 accelerated the formation of neuroinflammation by the effect of the Hippo pathway on the PRRs-mediated pathway, which delineates a negative immunoregulatory role for MST1/2 in CV-A10 infection and the potential for this pathway to be pharmacologically targeted to treat CV-A10.