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Prenatal ozone (O3) exposure may disrupt normal offspring growth. However, epidemiological evidence that prenatal O3 exposure affects the physical development of offspring early in life is far from adequate. A total of 4909 maternal–child pairs from the Shanghai Maternal–Child Pairs Cohort were included. A high-resolution random forest model was utilized to evaluate prenatal exposure levels of O3 based on the home addresses of pregnant women. Group-based trajectory and mixed-effects models were used to assess associations between prenatal O3 exposure and physical parameters. Each 10 μg/m³ increase in O3 concentration was associated with 0.084, 0.048, and 0.082-unit increases in body mass index (BMI) for age Z score (BAZ), weight for age Z score (WAZ), and weight for length Z score (WLZ), respectively. Specifically, a 10 μg/m³ increase in O3 concentration was linked to a 1.208-fold and 1.209-fold increase in the elevated-increasing group for the BAZ and WLZ trajectories, respectively. Moreover, each 10 μg/m³ increases in prenatal O3 was associated with a 1.396-fold and 0.786-fold increase in the risk of BAZ and length for age Z score (LAZ) accelerated growth, respectively. Furthermore, a 10 μg/m³ increase in prenatal O3 was linked to a 1.355-fold increase in the risk of overweight and obesity (OAO). Our study revealed that prenatal O3 exposure is associated with accelerated BMI gain or decelerated body length gain in the early life of children. Prenatal O3 may also increase the risk of OAO in children for the first two years.

Abstract Objective To understand the hospitalization expenditures and the composition of hospitalized patients with chronic obstructive pulmonary disease (COPD) in Yunnan Province from 2016 to 2022 and to identify the factors that influence them. The study aims to provide evidence-based information to health administration, hospitals, health insurance offices, and other related departments to help them formulate relevant policies. Methods This study analyzed data from 728,980 COPD patients in Yunnan Province between 2016 and 2022. This study described trends in hospitalization expenditures and their components over a 7-year period. Path analysis was used to investigate the factors that affect hospitalization expenditures. Results The average hospitalization expenditures for 2016–2022 were 7828 CNY. The total hospitalization expenditures were continuously increasing, from 828 million CNY to 967 million CNY, which is a 16.84% increase. However, the average expenditure per hospitalization decreased from 9185 CNY to 7261 CNY, which is a decrease of 20.95%. The main components of hospitalization expenditures were diagnostic fees, medication fees, and comprehensive medical service fees. The proportion of medication fees is decreasing, while the proportion of diagnostic fees and comprehensive medical services fees are increasing. The results of the path analysis indicate that age, gender, ethnicity, hospital level, admission route, medical payment method, COPD with acute lower respiratory tract infection, non-acute exacerbation of COPD, rehabilitation treatment experience, and comorbidity have both direct and indirect effects on hospitalization expenditures through length of stay (LOS). Additionally, marital status indirectly affects hospitalization expenditures through LOS. Conclusion Shortening the average LOS is crucial for hospitals to improve efficiency and reduce unnecessary expenses for patients. To achieve this, it is necessary to actively implement clinical pathway management and establish a standardized diagnosis and treatment system.

BackgroundAnimal studies have shown that exposure to organophosphate esters (OPEs) disturbs the composition of gut microbiome in rodents and zebrafish. However, current associated evidence in humans is limited. Considering the importance of gut microbiome in neonatal development, we need to investigate the impact of OPEs exposure on the early development stage of neonatal microbiome. ObjectiveTo investigate the associations between umbilical OPEs exposure and the diversity and composition of gut microbiome in newborns. MethodsBased on the Shanghai Maternal-Child Pairs Cohort (MCPC), 391 mother-infant pairs with comprehensive follow-up information and bio-samples were enrolled in this study. Concentrations of OPEs in neonatal cord blood were quantified using ultra performance liquid chromatography-tandem mass spectrometry. Meconium samples were collected after delivery and measured through 16S rRNA sequencing on the Illumina Miseq platform. Multiple linear regression models were used to assess the effects of OPEs exposure on the alpha diversity of meconium microbiome. Principal coordinate analysis and permutational multivariate analysis of variance based on unweighted UniFrac distance were used to compare the beta diversity differences between high and low exposure groups of OPEs. Linear discriminant analysis effect size (LEfSe) was utilized to analyze the differential gut microbiome taxa between high and low OPEs exposure groups. The functional pathways involved in the meconium microbiome were predicted based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and multivariate analysis by linear models (MaAsLin2) were conducted to explore the effects of OPEs exposure on gut microbiome pathways. ResultsSeven OPEs were detectable in the neonatal cord blood samples, of which four were detected higher than 50% including tributyl phosphate (TBP), tris (2-butoxyethyl) phosphate (TBEP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tris (2-chloro-1 (chloromethyl) ethyl) phosphate (TDCPP), and the median concentrations of these four congeners were as follows: 0.52 μg·L−1 for TBP, 2.41 μg·L−1 for TBEP, 0.13 μg·L−1 for EHDPP, and 2.23 μg·L−1 for TDCPP. A significant association was observed between umbilical TBEP and TDCPP exposure and alpha diversity indices in neonatal meconium microbiome. Beta diversity significantly differed across varied high and low OPEs exposure groups. The results of LEfSe analysis indicated a significant correlation between umbilical OPEs exposure and 27 genera, including Streptococcus, Corynebacterium, Neisseria, Haemophilus, and Parabacteroides. The MaAsLin2 analysis identified associations between OPEs exposure and upregulation of pathways related to linoleic acid metabolism, steroid biosynthesis, Toll and Imd signaling pathway, retinol metabolism, NOD like receptor signaling pathway, and fatty acid biosynthesis . ConclusionUmbilical OPEs exposure is associated increased alpha diversity indices, increased relative abundances of Neisseria, Streptococcus, Parabacteroides, and Corynebacterium in the gut microbiome, as well as predicted metabolic pathway alterations in linoleic acid metabolism, fatty acid biosynthesis, etc. These findings indicate that umbilical OPEs exposure may disrupt meconium microbiome equilibrium.

Per- and polyfluoroalkyl substances (PFAS) can pass through the placenta and adversely affect fetal development. However, there is a lack of comparison of legacy and emerging PFAS levels among different biosamples in pregnant women and their offspring. This study, based on the Shanghai Maternal–Child Pairs Cohort, analyzed the concentrations of 16 PFAS in the maternal serum, cord serum, and breast milk samples from 1,076 mother-child pairs. The placental and breastfeeding transfer efficiencies of PFAS were determined in maternal-cord and maternal-milk pairs, respectively. The binding affinities of PFAS to five transporters were simulated using molecular docking. The results suggested that PFAS were frequently detected in different biosamples. The median concentration of perfluorooctane sulfonate (PFOS) was the highest at 8.85 ng/mL, followed by perfluorooctanoic acid (PFOA) at 7.13 ng/mL and 6:2 chlorinated polyfluorinated ether sulfonate at 5.59 ng/mL in maternal serum. The median concentrations of PFOA were highest in cord serum (4.23 ng/mL) and breast milk (1.08 ng/mL). PFAS demonstrated higher placental than breastfeeding transfer efficiencies. The transfer efficiencies and the binding affinities of most PFAS to proteins exhibited alkyl chain length-dependent patterns. Furthermore, we comprehensively assessed the estimated daily intakes (EDIs) of PFAS in breastfeeding infants of different age groups and used the hazard quotient (HQ) to characterize the potential health risk. EDIs decreased with infant age, and PFOS had higher HQs than PFOA. These findings highlight the significance of considering PFAS exposure, transfer mechanism, and health risks resulting from breast milk intake in early life.

Abstract 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 (β: − 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.

This study introduces a sophisticated intelligent predictive maintenance system for industrial conveyor belts powered by a random forest machine learning model. The random forest model was evaluated against established models such as logistic regression, neural networks, decision trees, and gradient boosting, demonstrating superior performance. The model achieved 100% accuracy in classifying gearbox lubricant levels and sprocket conditions, highlighting its potential for addressing critical challenges in predictive maintenance, such as avoiding unexpected downtime. However, further validation with larger datasets and varied operational environments is recommended to confirm robustness. This performance highlights its effectiveness in multiclass fault detection and overfitting mitigation, establishing a new standard in predictive maintenance technology. The system, enhanced by a comprehensive sensor array, not only adeptly captures but also intelligently analyzes critical operational data, providing proactive and data-driven insights for maintenance decision-making. This study not only affirms the dominance of the random forest model in predictive analytics but also underscores its pivotal role in optimizing maintenance strategies, enhancing operational efficiency, and ensuring the reliability of conveyor systems in industrial settings.

Study region: The Laochang Karst watershed (LCKW) is located in eastern Yunnan Province, southwestern China. It is the representative karst area affected by coal-mining activities in southwestern China. Study focus: Identifying hydrological processes of multi-layered aquifers in karst watersheds is challenging due to complex natural and anthropogenic processes. This study attempts to clarify the hydrological conceptual model of the LCKW using hydrochemistry and D, O, Sr, S, and C isotopes. New hydrological insights for the region: Surface water and multi-layered groundwater have the hydrochemical types of SO4-Ca·Mg, HCO3·SO4-Ca, and HCO3-Ca. Meteoric water and condensate were the major recharge sources. The main processes dominating hydrochemical compositions consist of sulfide oxidative dissolution, carbonate dissolution, positive cation exchange, and agricultural activities. Elevated SO42− concentration in the mine water, river water and shallow coalbed water mainly originated from the oxidation of pyrite in the coal-bearing strata of the Longtan Formation. whereas the deeper layers and groundwater away from the mines were hardly contaminated by SO42− due to the presence of aquiclude. HCO3− concentrations of surface water and multi-layered groundwater were mainly derived from carbonate dissolution and soil CO2, and mine water was also influenced by atmospheric CO2. Positive cation exchange contributed to increasing Na+ concentration. Agricultural activities contributed NO3−, Cl−, and K+ ions in aquifers, especially near large karst fallout caves. A hydrological model of multi-layered aquifers in the LCKW was built based on the above results. These findings will provide valuable guidance for understanding the hydrological processes of complex karst watersheds worldwide.

The mechanisms underlying pathological changes in the central nervous system (CNS) following Coxsackievirus A16 (CV-A16) infection have not yet been elucidated. IFN-γ-inducible protein-10 (IP-10) is often used as a predictive factor to monitor early virus infection. It has also been reported that IP-10 plays a pivotal role in neuroinflammation. In this study, we aimed to explore the role of IP-10 in the neuropathogenesis of CV-A16 infection. We observed that the level of IP-10, as well as the TLR3-TRIF-TRAF3-TBK1-NF-κB and RIG-I/MDA5-MAVS-TRAFS-TBK1-NF-κB pathways, which are the upstream of IP-10, were significantly elevated during the course of CV-A16 infection. This increase was accompanied by an increase in a series of inflammatory cytokines at different time-points during CV-A16 infection. To determine whether IP-10 influences BBB integrity, we examined junctional complexes. Our results revealed that the expression levels of Claudin5, Occludin, ZO-1 and VE-Cadherin were notably decreased in CV-A16-infected HUVECs, but these indicators were restored in CV-A16-infected HUVECs with Eldelumab treatment. Nevertheless, IP-10 is only a chemokine that primarily traffics CXCR3-positive immune cells to inflammatory sites or promotes the production of inflammatory cytokines. Therefore, the interactions between IP-10 and inflammatory cytokines were evaluated. Our data revealed that IP-10 mediated the production of TNF-α, which was also observed to change the junctional complexes. Moreover, in a suckling mouse model, IP-10 and TNF-α treatments exacerbated clinical symptoms, mortality and pathological changes in the brain of CV-A16-infected mice, but Anti-IP-10 and Anti-TNF-α treatments alleviated these changes. Our data also revealed that IP-10 may be detected early in CV-A16 infection, whereas TNF-α was detected late in CV-A16 infection, and the production of TNF-α was also found to be positively correlated with IP-10. In addition, IP-10 and TNF-α were observed to reduce junctional complexes and enhance virus entry into the CNS. Taken together, this study provides the first evidence that CV-A16 activates the IP-10/TNF-α regulatory axis to cause BBB damage and accelerate the formation of neuroinflammation in infected hosts, which not only provides a new understanding of the neuropathogenesis caused by CV-A16, but also offers a promising target for the development of CV-A16 antiviral drugs.

Abstract The aim of this study was to evaluate the effects of different types of inulin on acute alcoholic intoxication (AAI) in mice and prepare its hangover beverage. Basic physical and chemical properties of different types of inulin (short‐chain inulin, long‐chain inulin, and phosphorylated long‐chain inulin) were analyzed and given by gavage at a dose of 400 mg kg−1 day−1 for a continuous period of 7 days through animal behavior experiments, and the inebriation percentage, mortality rate, duration of inebriation, and sobering time were recorded with the righting reflex as the judgment criterion. The results showed that, compared with the control group, the drunkenness and mortality rates of short‐chain inulin decreased by 12% and 100%, respectively, and the sober time decreased by 18%, while alcohol tolerance was also improved. The best formula for a short‐chain inulin hangover drink was determined to be: 0.4% granulated sugar, 0.5% citric acid, and 0.5% pectin. These suggest that short‐chain inulin may have potential in preventing AAI.

Abstract 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.

Abstract 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.

Abstract 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-β 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.

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.

ABSTRACT 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.

Introduction: Cadonilimab (AK104) is an innovative human programmed cell death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody. Compared with the combination therapy of PD-1 and CTLA-4 blockers, less cellular toxicity of cadonilimab was significantly manifested. As one of the characteristic adverse effects of cadonilimab, infusion-related reactions (IRRs) represent fever, chills, rash, decreased blood pressure, and other symptoms. Case Presentation: Here, we documented seven cases of IRRs after the administration of cadonilimab. The symptoms of IRRs were relieved after the discontinuation of cadonilimab and the administration of diphenhydramine, dexamethasone, and cimetidine. Notably, 3 patients were able to tolerate the subsequent cadonilimab therapy under the pretreatment. Conclusion: In this study, we discovered that cadonilimab-related IRRs might be lessened or prevented by administering medication and the proper pretreatment and lowering the infusion rate.

Three-dimensional path planning refers to determining an optimal path in a three-dimensional space with obstacles, so that the path is as close to the target location as possible, while meeting some other constraints, including distance, altitude, threat area, flight time, energy consumption, and so on. Although the bald eagle search algorithm has the characteristics of simplicity, few control parameters, and strong global search capabilities, it has not yet been applied to complex three-dimensional path planning problems. In order to broaden the application scenarios and scope of the algorithm and solve the path planning problem in three-dimensional space, we present a study where five three-dimensional geographical environments are simulated to represent real-life unmanned aerial vehicles flying scenarios. These maps effectively test the algorithm's ability to handle various terrains, including extreme environments. The experimental results have verified the excellent performance of the BES algorithm, which can quickly, stably, and effectively solve complex three-dimensional path planning problems, making it highly competitive in this field.

Abstract Our previous study revealed that red kidney bean polysaccharides (RKB) exhibit a pronounced hypoglycemic effect on type 2 diabetic rats, while simultaneously exerting a significant ameliorative impact on hepatic damage in these animals. However, the precise mechanism underlying the effects of RKB on diabetes and liver metabolism remains unproven. In this study, we utilized a mouse model of type 2 diabetes induced by a high‐fat diet combined with streptozotocin to investigate the impact of RKB. We administered a combined intervention involving antibiotics, fexaramine, and RKB to elucidate the mechanism underlying RKB's effects. Our findings demonstrated that RKB significantly ameliorated liver function indices and histopathological injuries. Nevertheless, when antibiotics and fexaramine were introduced as interventions, they hindered the beneficial effects of RKB on liver function in type 2 diabetic mice. Furthermore, our nontargeted metabolomics analysis revealed that antibiotics and fexaramine exerted their inhibitory actions on RKB efficacy through modulation of distinct metabolites involved in glycerophospholipid and purine metabolic pathways.

Abstract Inulin, a recognized prebiotic with diverse biological activities, has not yet been reported for its potential in treating alcoholism. Therefore, this study investigated the antialcoholic effects of short, long, and phosphorylated long‐chain inulin and the possible mechanisms. An acute alcoholic intoxication mice model was established, with the water extract of Hovenia dulcis Thunb serving as a positive control. The different inulins were used for intervention, and the drunkenness of the mice was observed by an animal behavior experiment. The serum liver function indexes (TP, ALB, GLB, ALT, and ALP), as well as the activity of ethanol metabolizing enzymes (ADH and ALDH) in the liver were measured, and the changes in intestinal flora were analyzed. The results showed that short‐chain inulin could alleviate acute alcoholism by activating ethanol metabolizing enzyme activity and improving intestinal flora, and it had a potential protective effect on acute alcoholic liver injury in 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.

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.

In our previous study, red kidney bean polysaccharides (RKP) have been regarded as the functional polysaccharide with glucolipid metabolism regulation activity. The impact of different concentrations of RKP (2, 4, and 6 g/100 g of dough weight) on the water mobility, rheology, and microstructure of frozen dough was examined using low field nuclear magnetic resonance (LF-NMR) and scanning electron microscopy (SEM) in the present study. The findings demonstrated that RKP exerted a positive impact on the water absorption capacity, moisture distribution, and viscoelastic properties of frozen dough. The addition of RKP significantly improved the water absorption of the dough. Specifically, on day 0, adding 6% RKP increased the water absorption rate from 25% to 47% compared to the blank group. Notably, the hardness of steamed bread decreased significantly with the addition of RKP, in addition, its springiness and resilience dependently increased. This offered a theoretical foundation for the use of RKP in the industrial manufacture of wheat-based foods.

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.

Contamination with potentially toxic elements (PTEs) frequently occurs in surface water in coal mining areas. This study analyzed 34 surface water samples collected from the Yunnan–Guizhou Plateau for their hydrochemical characteristics, spatial distribution, source apportionment, and human health risks. Our statistical analysis showed that the average concentrations of PTEs in the surface water ranked as follows: Fe > Al > Zn > Mn > Ba > B> Ni > Li > Cd > Mo > Cu > Co > Hg > Se > As > Pb > Sb. The spatial analysis revealed that samples with high concentrations of Fe, Al, and Mn were predominantly distributed in the main stream, Xichong River, and Yangchang River. Positive matrix factorization (PMF) identified four sources of PTEs in the surface water. Hg, As, and Se originated from wastewater discharged by coal preparation plants and coal mines. Mo, Li, and B originated from the dissolution of clay minerals in coal seams. Elevated concentrations of Cu, Fe, Al, Mn, Co, and Ni were attributed to the dissolution of kaolinite, illite, chalcopyrite, pyrite, and minerals associated with Co and Ni in coal seams. Cd, Zn, and Pb were derived from coal melting and traffic release. The deterministic health risks assessment showed that 94.12% of the surface water samples presented non-carcinogenic risks below the health limit of 1. Meanwhile, 73.56% of the surface water samples with elevated As posed level III carcinogenic risk to the local populations. Special attention to drinking water safety for children is warranted due to their lower metabolic capacity for detoxifying PTEs. This study provides insight for PTE management in sustainable water environments.

The connections between urinary organophosphate ester (OPE) metabolites and child growth have been identified in prior research, but there is currently a dearth of epidemiological evidence regarding the sex-specific impact of OPEs on child growth trajectories. This study enrolled 804 maternal–child pairs, and five OPE congeners were quantified in maternal serum during pregnancy. In this study, the impact of prenatal OPE exposure on child growth trajectories was assessed using linear mixed-effect models and a group-based trajectory model (GBTM), with consideration given to sex-specific effects. Fetuses were frequently exposed to OPEs in utero, and tris(2-butoxyethel) phosphate (TBEP) exhibited the highest concentration levels in maternal serum. Among male children, an increase of 2.72 ng/g lipid in TBEP concentration was associated with a 0.11-unit increase in head circumference-for-age z-score (HCAZ), and the effect was mainly concentrated at 1 and 2 months of age. Among female children, an increase of 2.72 ng/g lipid in tris(2-chloro-1-(chloromethyl) ethyl) phosphate (TDCPP) concentration was associated with a 0.15-unit increase in length-for-age z-score (LAZ) and a 0.14-unit increase in weight-for-age z-score (WAZ), and the effects were mainly concentrated at 9 months of age. For HCAZ trajectories, higher prenatal TBEP exposure was associated with higher odds for the fast growth group in male children. For the LAZ and WAZ trajectories, higher prenatal TDCPP exposure was associated with higher odds for the fast growth group in female children. The trajectory analysis approach provided insight into the complex associations between OPE exposure and child growth.

Abstract Background High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear. Objective Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon. Results High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group. Conclusions For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract

Abstract Coxsackievirus A16 (CV-A16) is still an important pathogen that causes hand, foot and mouth disease (HFMD) in young children and infants worldwide. Previous studies indicated that CV-A16 infection is usually mild or self-limiting, but it was also found that CV-A16 infection can trigger severe neurological complications and even death. However, there are currently no vaccines or antiviral compounds available to either prevent or treat CV-A16 infection. Therefore, investigation of the virus‒host interaction and identification of host proteins that play a crucial regulatory role in the pathogenesis of CV-A16 infection may provide a novel strategy to develop antiviral drugs. Here, to increase our understanding of the interaction of CV-A16 with the host cell, we analyzed changes in the proteome of 16HBE cells in response to CV-A16 using tandem mass tag (TMT) in combination with LC‒MS/MS. There were 6615 proteins quantified, and 172 proteins showed a significant alteration during CV-A16 infection. These differentially regulated proteins were involved in fundamental biological processes and signaling pathways, including metabolic processes, cytokine‒cytokine receptor interactions, B-cell receptor signaling pathways, and neuroactive ligand‒receptor interactions. Further bioinformatics analysis revealed the characteristics of the protein domains and subcellular localization of these differentially expressed proteins. Then, to validate the proteomics data, 3 randomly selected proteins exhibited consistent changes in protein expression with the TMT results using Western blotting and immunofluorescence methods. Finally, among these differentially regulated proteins, we primarily focused on HMGB1 based on its potential effects on viral replication and virus infection-induced inflammatory responses. It was demonstrated that overexpression of HMGB1 could decrease viral replication and upregulate the release of inflammatory cytokines, but deletion of HMGB1 increased viral replication and downregulated the release of inflammatory cytokines. In conclusion, the results from this study have helped further elucidate the potential molecular pathogenesis of CV-A16 based on numerous protein changes and the functions of HMGB1 Found to be involved in the processes of viral replication and inflammatory response, which may facilitate the development of new antiviral therapies as well as innovative diagnostic methods.

Risk assessment is the key process for environmental management and remediation of soil contamination. Metals, such as beryllium (Be), cadmium (Cd), nickel (Ni), and cobalt (Co) are considered important soil contaminants and environmental challenges, which cause a potential risk of harm to human health through inhalation exposure routes but show limitations regarding cross-discussion and in-depth analysis of previous works. We introduce a systematic and multidimensional perspective to assess the human health risk caused by four metals soil contamination via the 338 regional PM10 levels on a city scale from 2015 to 2021. As the significant characteristics, total carcinogenic risk (TCR), hazard index (HIn), and risk control level (RCL) are calculated for the detailed analysis of annual and seasonal performance. The inhalation is the main risk exposure pathway of Be, Ni, and Cd soil contamination. TCR and HIn show the lowest levels in 2021 among other years with all regions below the risk thresholds, and the RCLs are yearly increasing according to the different calculated methods by the annual average PM10. This refined study can provide a detailed strategy for the environmental risk assessment of metals soil contamination on a regional scale and promise desirable support for the protection of human health.

BackgroundCough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. ObjectiveThe aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. MethodsIn this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. ResultsThere were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). ConclusionsCough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Summary: Hypoxia-induced pulmonary hypertension (HPH) is a fatal cardiovascular disease characterized by an elevation in pulmonary artery pressure, resulting in right ventricular dysfunction and eventual heart failure. Exploring the pathogenesis of HPH is crucial, and small noncoding RNAs (sncRNAs) are gaining recognition as potential regulators of cellular responses to hypoxia. In this study, we conducted a comprehensive analysis of sncRNA profiles in eight tissues of male HPH rats using high-throughput sequencing. Our study unveiled several sncRNAs, with the brain, kidney, and spleen exhibiting the highest abundance of microRNA (miRNA), tRNA-derived small RNA (tDR), and small nucleolar RNA (snoRNA), respectively. Moreover, we identified numerous tissue-specific and hypoxia-responsive sncRNAs, particularly miRNAs and tDRs. Interestingly, we observed arm switching in miRNAs under hypoxic conditions and a significant increase in the abundance of 5′ tRNA-halves among the total tDRs during hypoxia. Overall, our study provides a comprehensive characterization of the sncRNA profiles in HPH rats.

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 (R2 = 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.

Abstract Ankylosing spondylitis (AS) is a common rheumatic disorder distinguished by chronic inflammation and heterotopic ossification at local entheses sites. Currently available medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) and TNF inhibitors, are limited by side effects, high costs and unclear inhibitory effects on heterotopic ossification. Herein, we developed manganese ferrite nanoparticles modified by the aptamer CH6 (CH6-MF NPs) that can efficiently scavenge ROS and actively deliver siRNA into hMSCs and osteoblasts in vivo for effective AS treatment. CH6-MF NPs loaded with BMP2 siRNA (CH6-MF-Si NPs) effectively suppressed abnormal osteogenic differentiation under inflammatory conditions in vitro. During their circulation and passive accumulation in inflamed joints in the Zap70 mut mouse model, CH6-MF-Si NPs attenuated local inflammation and rescued heterotopic ossification in the entheses. Thus, CH6-MF NPs may be an effective inflammation reliever and osteoblast-specific delivery system, and CH6-MF-Si NPs have potential for the dual treatment of chronic inflammation and heterotopic ossification in AS.

Abstract Background Seagull as a migratory wild bird has become most popular species in southwest China since 1980s. Previously, we analyzed the gut microbiota and intestinal pathogenic bacteria configuration for this species by using 16S rRNA sequencing and culture methods. To continue in-depth research on the gut microbiome of migratory seagulls, the metagenomics, DNA virome and RNA virome were both investigated for their gut microbial communities of abundance and diversity in this study. Results The metagenomics results showed 99.72% of total species was bacteria, followed by viruses, fungi, archaea and eukaryota. In particular, Shigella sonnei, Escherichia albertii, Klebsiella pneumonia, Salmonella enterica and Shigella flexneri were the top distributed taxa at species level. PCoA, NMDS, and statistics indicated some drug resistant genes, such as adeL, evgS, tetA, PmrF, and evgA accumulated as time went by from November to January of the next year, and most of these genes were antibiotic efflux. DNA virome composition demonstrated that Caudovirales was the most abundance virus, followed by Cirlivirales, Geplafuvirales, Petitvirales and Piccovirales. Most of these phages corresponded to Enterobacteriaceae and Campylobacteriaceae bacterial hosts respectively. Caliciviridae, Coronaviridae and Picornaviridae were the top distributed RNA virome at family level of this migratory animal. Phylogenetic analysis indicated the sequences of contigs of Gammacoronavirus and Deltacoronavirus had highly similarity with some coronavirus references. Conclusions In general, the characteristics of gut microbiome of migratory seagulls were closely related to human activities, and multiomics still revealed the potential public risk to human health.

Abstract Backgrounds The respiratory microbiota and radiomics correlate with the disease severity and prognosis of chronic obstructive pulmonary disease (COPD). We aim to characterize the respiratory microbiota and radiomics features of COPD patients and explore the relationship between them. Methods Sputa from stable COPD patients were collected for bacterial 16 S rRNA gene sequencing and fungal Internal Transcribed Spacer (ITS) sequencing. Chest computed tomography (CT) and 3D-CT analysis were conducted for radiomics information, including the percentages of low attenuation area below − 950 Hounsfield Units (LAA%), wall thickness (WT), and intraluminal area (Ai). WT and Ai were adjusted by body surface area (BSA) to WT/ $$\sqrt{\text{B}\text{S}\text{A}}$$ and Ai/BSA, respectively. Some key pulmonary function indicators were collected, which included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion lung carbon monoxide (DLco). Differences and correlations of microbiomics with radiomics and clinical indicators between different patient subgroups were assessed. Results Two bacterial clusters dominated by Streptococcus and Rothia were identified. Chao and Shannon indices were higher in the Streptococcus cluster than that in the Rothia cluster. Principal Co-ordinates Analysis (PCoA) indicated significant differences between their community structures. Higher relative abundance of Actinobacteria was detected in the Rothia cluster. Some genera were more common in the Streptococcus cluster, mainly including Leptotrichia, Oribacterium, Peptostreptococcus. Peptostreptococcus was positively correlated with DLco per unit of alveolar volume as a percentage of predicted value (DLco/VA%pred). The patients with past-year exacerbations were more in the Streptococcus cluster. Fungal analysis revealed two clusters dominated by Aspergillus and Candida. Chao and Shannon indices of the Aspergillus cluster were higher than that in the Candida cluster. PCoA showed distinct community compositions between the two clusters. Greater abundance of Cladosporium and Penicillium was found in the Aspergillus cluster. The patients of the Candida cluster had upper FEV1 and FEV1/FVC levels. In radiomics, the patients of the Rothia cluster had higher LAA% and WT/ $$\sqrt{\text{B}\text{S}\text{A}}$$ than those of the Streptococcus cluster. Haemophilus, Neisseria and Cutaneotrichosporon positively correlated with Ai/BSA, but Cladosporium negatively correlated with Ai/BSA. Conclusions Among respiratory microbiota in stable COPD patients, Streptococcus dominance was associated with an increased risk of exacerbation, and Rothia dominance was relevant to worse emphysema and airway lesions. Peptostreptococcus, Haemophilus, Neisseria and Cutaneotrichosporon probably affected COPD progression and potentially could be disease prediction biomarkers.

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.

ABSTRACT The Sansha Yongle Blue Hole (SYBH), the deepest blue hole in the world, is an excellent habitat for revealing biogeochemical cycles in the anaerobic environment. However, how sulfur cycling is mediated by microorganisms in the SYBH hasn’t been fully understood. In this study, the water layers of the SYBH were divided into oxic zone, hypoxic zone, anoxic zone I and II, and microbial-mediated sulfur cycling in the SYBH was comprehensively interpreted. The 16S rRNA genes/transcripts analyses showed that the microbial community structures associated with the sulfur cycling in each zone had distinctive features. Sulfur-oxidizing bacteria were mostly constituted by Gammaproteobacteria, Alphaproteobacteria, Campylobacterota, and Chlorobia above the anoxic zone I and sulfate-reducing bacteria were dominated by Desulfobacterota in anoxic zones. Metagenomic analyses showed that the sulfide-oxidation-related gene sqr and genes encoding the Sox system were mainly distributed in the anoxic zone I, while genes related to dissimilatory sulfate reduction and sulfur intermediate metabolite reduction were mainly distributed in the anoxic zone II, indicating different sulfur metabolic processes between these two zones. Moreover, sulfur-metabolism-related genes were identified in 81 metagenome-assembled genomes (MAGs), indicating a high diversity of microbial communities involved in sulfur cycling. Among them, three MAGs from the candidate phyla JdFR-76 and AABM5-125-24 with genes related to dissimilatory sulfate reduction exhibited distinctive metabolic features. Our results showed unique and novel microbial populations in the SYBH sulfur cycle correlated to the sharp redox gradients, revealing complex biogeochemical processes in this extreme environment. IMPORTANCE Oxygen-deficient regions in the global ocean are expanding rapidly and affect the growth, reproduction and ecological processes of marine organisms. The anaerobic water body of about 150 m in the Sansha Yongle Blue Hole (SYBH) provided a suitable environment to study the specific microbial metabolism in anaerobic seawater. Here, we found that the vertical distributions of the total and active communities of sulfur-oxidizing bacteria (SOB) and sulfate-reducing bacteria (SRB) were different in each water layer of the SYBH according to the dissolved oxygen content. Genes related to sulfur metabolism also showed distinct stratification characteristics. Furthermore, we have obtained diverse metagenome-assembled genomes, some of which exhibit special sulfur metabolic characteristics, especially candidate phyla JdFR-76 and AABM5-125-24 were identified as potential novel SRB. The results of this study will promote further understanding of the sulfur cycle in extreme environments, as well as the environmental adaptability of microorganisms in blue holes.

Neuropathological damage has been considered to be the main cause of death from EV-A71 infection, but the underlying mechanism has not been elucidated. Pyroptosis, a new form of inflammatory programmed cell death, has been verified to be involved in the pathogenesis of various viruses. circRNAs are a novel type of endogenous noncoding RNA gaining research interest in recent years, especially their special roles in the process of virus infection. Thus, in this study, we combined EV-A71, pyroptosis and circRNA to find a breakthrough in the pathogenesis of EV-A71 infection. Firstly, whether EV-A71 infection leaded to pyroptosis formation was examined by a series detection of cell death, cell viability, LDH release, caspase 1 activity, the expression levels of pyroptosis-related molecules and the concentrations of IL-1β and IL-18. Secondly, high-throughput sequencing of circRNAs was carried out to excavate the circRNA-miRNA-mRNA regulatory axis which might be associated with pyroptosis formation. Finally, the gain- and loss-of-functional experiments were further conducted to identify their functions. Our results showed that EV-A71 infection caused pyroptosis formation in SH-SY5Y cells. The circRNA sequencing analyzed the differentially expressed circRNAs and their possible functions. It was found that the hsa_circ_0045431/hsa_miR_584/NLRP3 regulatory axis might be involved in pyroptosis formation during EV-A71 infection. Then, hsa_circ_0045431 sponged hsa_miR_584 and hsa_miR_584 directly targeted NLRP3 were validated by IF, dual-luciferase, qRT-PCR and WB assays. Functional experiments were performed to further uncover that the up-regulation of hsa_circ_0045431 and NLRP3 promoted the inflammatory pyroptosis and viral replication, while the up-regulation of hsa_miR_584 suppressed the inflammatory pyroptosis and viral replication, and vice versa. Collectively, our study demystified that EV-A71 infection induced pyroptosis formation by activating hsa_circ_0045431/hsa_miR_584/NLRP3 regulatory axis, which could further effect viral replication. These findings provided novel insights into the pathogenesis of EV-A71 infection, and meanwhile revealed that the hsa_circ_0045431/ hsa_miR_584/NLRP3 regulatory axis can serve as a potential biological therapeutic target for EV-A71 infection.

Abstract The aim of this pilot study was to predict the risk of gestational diabetes mellitus (GDM) by the elemental content in fingernails and urine with machine learning analysis. Sixty seven pregnant women (34 control and 33 GDM patient) were included. Fingernails and urine were collected in the first and second trimesters, respectively. The concentrations of elements were determined by inductively coupled plasma-mass spectrometry. Logistic regression model was applied to estimate the adjusted odd ratios and 95% confidence intervals. The predictive performances of multiple machine learning algorithms were evaluated, and an ensemble model was built to predict the risk for GDM based on the elemental contents in the fingernails. Beryllium, selenium, tin and copper were positively associated with the risk of GDM while nickel and mercury showed opposite result. The trained ensemble model showed larger area under curve (AUC) of receiver operating characteristic curve (0.81) using fingernail Ni, Cu and Se concentrations. The model was validated by external data set with AUC = 0.71. In summary, the results of the present study highlight the potential of fingernails, as an alternative sample, together with machine learning in human biomonitoring studies.

Using HYSPLIT and GDAS, it will be analyzed what is the water vapor contribution of the 16 rainstorms, and what includes backward water vapor trajectory tracking, main channels and different sources in the warm season of 1981-2020 in western southern Xinjiang (April-September). the result shows: Water vapor mainly originates from Southwest Asia, Central Asia, the Mediterranean Sea and the Black Sea and their vicinity, the Atlantic Ocean and its coasts, at 850 hPa in the plain area, there is water vapor originating from southern and northern Xinjiang. At 500 hPa, water vapor mainly enters the rainstorm area from the west channel, the contribution of water vapor to the heavy rain is greater and the loss is also greater, that comes from Southwest Asia and Central Asia. In the lower troposphere, there are two main channels for water vapor to enter the rainstorm area from the west and east. At 700 hPa, the contribution of each channel and each water vapor source to the rainstorm is different in different regions. In the plain area of 850 hPa, the eastward channel of the heavy rain contributed the most to the heavy rain, and the water vapor loss along the source area was small, and the largest contribution to the heavy rain was in the source area of northern Xinjiang. In the plain area, water vapor originates from Southwest Asia, Central Asia, Southern Xinjiang and Northern Xinjiang. It is mainly transported to 700 hPa and below. It originates from the water vapor near the Mediterranean Sea and the Black Sea, the Atlantic Ocean and its coast, it is mainly transported to a height above 700 hPa. At 500 hPa in the plain area, the water vapor transport of heavy rain is dominant from more than 2000 m, while the mountainous area is the opposite. In the western part of southern Xinjiang, there are sources of water vapor from southern and northern Xinjiang during heavy rains, and under certain conditions, there are sources of water vapor from North America and North Africa, which are different from previous research results.

Water inrush is one of the most serious phenomena threatening the safety of tunnel construction. The West Qinling 1# tunnel, as the major section of the Bailong River diversion project, traverses a complicated karst area and would be faced with a water inrush disaster. Based on geological and hydrogeological conditions, the Finite element subsurface flow system software is used to simulate and predict the development of the natural seepage field and dredging construction conditions of the seepage field on the West Qinling 1# tunnel area. The prediction results show that the groundwater level will drop up to 113.9 m under dredging construction conditions, with an impact radius of up to 11.5 km. Seepage field evolution and water influx were simulated under two conditions of construction plugging construction, respectively. The prediction results show that the groundwater level in the middle part of tunnel 1# is 112.68 m depth without blocking condition with an influence range of 10.5 km. The maximum water volume per unit length of the karst cave increases to 4.32 m3/d·m. In the plugging condition, the influencing scope does not significantly reduce, but the extent of the impact is greatly weakened. The groundwater level generally dropped at 10–25 m depth and the karst cave section unit length of the maximum water volume of 0.83 m3/d·m in the rainy season. The achievements of this study would provide a vital reference for the prevention of water inrush in karst tunnel construction.

Coxsackievirus A10 (CV-A10) has been one of the main etiologies of hand, foot, and mouth disease (HFMD) epidemics in recent years and can cause mild to severe illness and even death. Most of these severe and fatal cases were closely associated with neurological impairments, but the potential mechanism of neuropathological injury triggered by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a post-transcriptional manner, play a vital role in the pathogenesis of various central nervous system (CNS) diseases; therefore, they serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights into the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected human umbilical vein endothelial cells (HUVECs) and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could induce 189 and 302 significantly differentially expressed miRNAs in HUVECs at 24 and 72 hpi, respectively, compared with the uninfected control. Moreover, the expression of four selected miRNAs and their relevant mRNAs was determined to verify the sequencing data by quantitative reverse transcription–polymerase chain reaction (RT–qPCR) methods. After that, gene target prediction and functional annotation revealed that the targets of these dysregulated miRNAs were mostly enriched in cell proliferation, signal transduction, cAMP signalling pathway, cellular response to interleukin-6, ventral spinal cord interneuron differentiation, negative regulation of glial cell differentiation, neuron migration, positive regulation of neuron projection development, etc., which were primarily involved in the processes of basic physiology, host immunity, and neurological impairments and further reflected vital regulatory roles of miRNA in viral pathogenicity. Finally, the construction of a miRNA-regulated network also suggested that the complex regulatory mechanisms mediated by miRNAs might be involved in viral pathogenesis and virus–host interactions during CV-A10 infection. Furthermore, among these dysregulated miRNAs, miR-143-3p was demonstrated to be involved in the maintenance of blood–brain barrier (BBB) integrity.

Wx is the key gene that controls amylose content (AC), and various alleles have been found in rice populations. Wxb is the major allele in japonica and produces moderate AC (15~18%). It was recently found that editing the promoter of Wx could produce a series of alleles that have different Wx activities. Although some studies have edited the promoter, few studies have focused on the natural variations in Wx. Here, we used the Rice3K database to investigate variations in the Wx promoter and found that the allele Wx1764178 (A/G) has a higher LD (linkage disequilibrium) with the two key SNPs (1765751, T/G; 1768006, A/C), which could produce different Wx alleles and influence AC, as reported previously. Further study showed that the Wx1764178 allele (A/G) is functional and influences the expression of Wx positively. Editing the A allele using CRISPR‒Cas9 produced 36 and 3 bp deletions and caused a decrease in the expression of Wx. The apparent amylose content (AAC) in the edited lines was decreased by 7.09% and 11.50% compared with that of the wild type, which was the japonica variety Nipponbare with Wxb and the A allele at 1764178, while a complementary line with the G allele showed a lower AAC than the A allele with no effect on other agronomic traits. The AAC of the edited lines showed a higher increase than that of the wild type (Nipponbare, Wxb) in low-nitrogen conditions relative to high-nitrogen conditions. We also developed a dCAPS marker to identify the allele and found that the G allele has widely been used (82.95%) in japonica-bred varieties from Jiangsu Province, China. Overall, we found a functional allele (Wx1764178, A/G) in the Wx promoter that could affect AAC in japonica cultivars and be developed as markers for quality improvement in rice breeding programs.

Abstract Background Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits. Methods In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared. Results CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p

Abstract Background Breeding of conventional and hybrid rice (Oryza sativa L.) have solved hunger problems and increased farmers' income in the world. Molecular markers have been widely used in marker-assisted breeding and identification of larger numbers of different bred varieties in the past decades. The recently developed SNP markers are applied for more stable and detectable compared with other markers. But the cost of genotyping lots SNPs is high. So, it is essential to select less representative SNPs and inexpensive detecting methods to lower the cost and accelerate variety identification and breeding process. KASP (Kompetitive Allele-Specific PCR) is a flexible method to detect the SNPs, and large number of KASP markers have been widely used in variety identification and breeding. However, the ability of less KASP markers on massive variety identification and breeding remains unknown. Results Here, 48 KASP markers were selected from 378 markers to classify and analyze 518 varieties including conventional and hybrid rice. Through analyzing the population structure, the 48 markers could almost represent the 378 markers. In terms of variety identification, the 48 KASP markers had a 100% discrimination rate in 53 conventional indica varieties and 193 hybrid varieties, while they could distinguish 89.1% conventional japonica rice from different breeding institutes. Two more markers added would increase the ratio from 68.38 to 77.94%. Additionally, the 48 markers could be used for classification of subpopulations in the bred variety. Also, 8 markers had almost completely different genotypes between japonica and indica, and 3 markers were found to be very important for japonica hybrid rice. In hybrid varieties, the heterozygosity of chromosomes 3, 6 and 11 was relatively higher than others. Conclusions Our results showed that 48 KASP markers could be used to identify rice varieties, and the panel we tested could provide a database for breeders to identify new breeding lines. Also, the specific markers we found were useful for marker-assisted breeding in rice, including conventional and hybrid.

Abstract Coxsackievirus A10 (CV-A10), the causative agent of hand, foot, and mouth disease (HFMD), caused a series of outbreaks in recent years and often leads to neurological impairment, but a clear understanding of the disease pathogenesis and host response remains elusive. Cellular microRNAs (miRNAs), a large family of non-coding RNA molecules, have been reported to be key regulators in viral pathogenesis and virus-host interactions. However, the role of host cellular miRNAs defensing against CV-A10 infection is still obscure. To address this issue, we systematically analyzed miRNA expression profiles in CV-A10-infected 16HBE cells by high-throughput sequencing methods in this study. It allowed us to successfully identify 312 and 278 miRNAs with differential expression at 12 h and 24 h post-CV-A10 infection, respectively. Among these, 4 miRNAs and their target genes were analyzed by RT-qPCR, which confirmed the sequencing data. Gene target prediction and enrichment analysis revealed that the predicted targets of these miRNAs were significantly enriched in numerous cellular processes, especially in regulation of basic physical process, host immune response and neurological impairment. And the integrated network was built to further indicate the regulatory roles of miRNAs in host-CV-A10 interactions. Consequently, our findings could provide a beneficial basis for further studies on the regulatory roles of miRNAs relevant to the host immune responses and neuropathogenesis caused by CV-A10 infection.

Introduction: Carboxylesterases (CXEs) and glutathione S-transferases (GSTs) can terminate olfactory signals during chemosensation by rapid degradation of odorants in the vicinity of receptors. The tea grey geometrid, Ectropis grisescens (Lepidoptera, Geometridae), one of the most devastating insect herbivores of tea plants in China, relies heavily on plant volatiles to locate the host plants as well as the oviposition sites. However, CXEs and GSTs involved in signal termination and odorant clearance in E. grisescens remains unknown.Methods: In this study, identification and spatial expression profiles of CXEs and GSTs in this major tea pest were investigated by transcriptomics and qRT-PCR, respectively.Results: As a result, we identified 28 CXEs and 16 GSTs from female and male antennal transcriptomes. Phylogenetic analyses clustered these candidates into several clades, among which antennal CXEs, mitochondrial and cytosolic CXEs, and delta group GSTs contained genes commonly associated with odorants degradation. Spatial expression profiles showed that most CXEs (26) were expressed in antennae. In comparison, putative GSTs exhibited a diverse expression pattern across different tissues, with one GST expressed specifically in the male antennae.Disscussion: These combined results suggest that 12 CXEs (EgriCXE1, 2, 4, 6, 8, 18, 20-22, 24, 26, and 29) and 5 GSTs (EgriGST1 and EgriGST delta group) provide a major source of candidate genes for odorants degradation in E. grisescens.

Abstract In this paper, a curve approximation approach using bio-inspired polar coordinate bald eagle search algorithm (PBES) is proposed. PBES algorithm is inspired by the spiral mechanism of bald eagle during predation. By introducing polar coordinate, the spiral predation process of the bald eagle will become more intuitive, which is more conducive for the algorithm to polar coordinate optimization problems. The initialization stage of PBES algorithm is modified to make the distribution of initialized individuals more uniform and some parameters are introduced to strengthen the exploration and exploitation capabilities of algorithm. The performance of the PBES algorithm is tested in three aspects: polar coordinate transcendental equation, curve approximation and robotic manipulator. The experimental results show that the PBES algorithm is superior to the well-known metaheuristic algorithms as it is effectively applicable for curve approximation problem.