Sleep disorders among frontline nurses after the COVID-19 outbreak: a large-scale cross-sectional study.

This large-scale cross-sectional multicenter study aims to investigate the prevalence of sleep disorders among frontline nurses in China after the COVID-19 pandemic and to identify potential influencing factors contributing to these sleep disturbances. A total of 2065 frontline nurses from 27 provinces in China participated in an online survey conducted through the Wenjuan Xing platform. Data on demographic characteristics, work-related factors, and mental health assessments, including the Pittsburgh Sleep Quality Index (PSQI), Zung Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS), were collected. Statistical analyses, including chi-square tests, t-tests, binary logistic regression, and ROC analysis, were conducted to explore the relationships between various factors and sleep disorders. Over half (52.7%) of the surveyed nurses exhibited sleep disorders, reflecting a considerable post-pandemic impact on sleep quality. Factors such as nursing titles, personality traits, COVID-19 infection status, and exercise frequency showed statistically significant associations with sleep disorders. Extraverted nurses and those who had recovered from COVID-19 displayed a lower risk of sleep disorders, while anxiety was identified as an independent risk factor. The study also identified a nuanced relationship between exercise frequency and sleep quality. The study highlights a high prevalence of sleep disorders among frontline nurses post-COVID-19, emphasizing the need for targeted interventions. Factors such as nursing titles, personality traits, COVID-19 infection status, exercise habits, and anxiety levels were found to influence sleep quality. Comprehensive support strategies addressing these factors are essential for improving the overall well-being of frontline nurses and, subsequently, sustaining a resilient healthcare workforce. Further research is recommended to explore additional influencing factors and consider diverse nurse populations.

Unraveling the pathogenic interplay between SARS-CoV-2 and polycystic ovary syndrome using bioinformatics and experimental validation.

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among polycystic ovary syndrome (PCOS) is significantly higher than in the general population. However, the mechanisms underlying this remain obscure. This study aimed to explore the mechanisms by identifying the genetic signature of SARS-CoV-2 infection in PCOS. In the present study, a total of 27 common differentially expressed genes (DEGs) were selected for subsequent analyses. Functional analyses showed that immunity and hormone-related pathways collectively participated in the development and progression of PCOS and SARS-CoV-2 infection. Under these, 7 significant hub genes were identified, including S100A9, MMP9, TLR2, THBD, ITGB2, ICAM1, and CD86 by using the algorithm in Cytoscape. Furthermore, hub gene expression was confirmed in the validation set, PCOS clinical samples, and mouse model. Immune microenvironment analysis with the CIBERSORTx database demonstrated that the hub genes were significantly correlated with T cells, dendritic cells, mast cells, B cells, NK cells, and eosinophils and positively correlated with immune scores. Among the hub genes, S100A9, MMP9, THBD, ITGB2, CD86, and ICAM1 demonstrated potential as possible diagnostic markers for COVID-19 and PCOS. In addition, we established the interaction networks of ovary-specific genes, transcription factors, miRNAs, drugs, and chemical compounds with hub genes with NetworkAnalyst. This work uncovered the common pathogenesis and genetic signature of PCOS and SARS-CoV-2 infection, which might provide a theoretical basis and innovative ideas for further mechanistic research and drug discovery of the comorbidity of the two diseases.

Circulating JKAP levels may correlate with postpartum anxiety and depression through its interaction with T helper 17 cells.

Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates CD4+ T-cell differentiation and immunity, which are linked to mental disorders. This study aimed to explore the relationships between JKAP and T helper 17 (Th17)/regulatory T (Treg) ratio, as well as their associations with anxiety and depression in postpartum women. Serum JKAP were measured by enzyme-linked immunosorbent assay and blood Th17 and Treg cells were measured by flow cytometry in 250 postpartum women. Anxiety and depression were evaluated by the 6-item State-Trait Anxiety Inventory (STAI6) and Edinburgh Postnatal Depression Scale (EPDS). Anxiety and depression rates were 22.0 and 28.4%, respectively, among postpartum women. Notably, JKAP was negatively associated with the STAI6 (P=0.002) and EPDS scores (P<0.001) in postpartum women and was lower in postpartum women with anxiety (P=0.023) or depression (P=0.002) than in those without. Moreover, JKAP was inversely related to Th17 cells and Th17/Treg ratio but positively correlated with Treg cells in postpartum women (all P<0.001). Interestingly, Th17 cells and Th17/Treg ratio were both positively associated with STAI6 and EPDS scores in postpartum women (all P<0.001). Furthermore, Th17 cells and Th17/Treg ratio were lower in postpartum women with anxiety or depression than in those without (all P<0.01). Nevertheless, Treg cells were not linked to anxiety or depression in postpartum women. JKAP was negatively associated with Th17 cells and Th17/Treg ratio; moreover, they all related to anxiety and depression in postpartum women, indicating that JKAP may be involved in postpartum anxiety and depression via interactions with Th17 cells.

Control of dissolved H2 concentration enhances electron generation, transport and TCE reduction by indigenous microbial community.

Electrokinetic enhanced bioremediation (EK-Bio) is practical for trichloroethene (TCE) dechlorination because the cathode can produce a wide range of dissolved H2 (DH) concentrations of 1.3-0 mg/L from the electrode to the aquifer. In this study, TCE dechlorination was investigated under different DH concentrations. The mechanisms were discussed by analyzing the microbial community structure and abundance of organohalide-respiring bacteria (OHRB) using 16S rRNA, and the gene abundances of key enzymes in the TCE electron transport chain using metagenomic analysis. The results showed that the moderate DH concentration of 0.19-0.53 mg/L exhibited the most pronounced TCE dechlorination, even better than the higher DH concentrations, due to the optimal redox environment, the enrichments of OHRB, reductive dehalogenase (rdhA) genes and key enzyme genes in the electron generation and transport chain. More electrons were obtained from H2 metabolism by Dehalobacter by promoting the formation of [NiFe] hydrogenase (HupS/L/C) or from glycolysis by versatile OHRB by stimulating the formation of formate and enriching formate dehydrogenase (FDH) under moderate DH conditions. In addition, the enhanced amino acid metabolism improved the vitamin K cycle for electron transport and enriched the reductive dechlorinating enzyme (RDase) genes. This study identifies the optimal DH concentration that facilitates bioremediation efficiency, provides insights into microbial community shifts and key enzymatic pathways in EK-Bio remediation.

Diffusion behavior and environmental impact of odorants and TVOCs detected in a wastewater treatment plant for collaborative leachate treatment in Northwest China.

Wastewater treatment plants (WWTPs) are major sources of volatile gaseous compounds, especially in mixed-source systems such as domestic wastewater and landfill leachate. This study aimed to investigate the emission behavior and environmental impact of gaseous substances, such as hydrogen sulfide (H2S), ammonia (NH3), carbon sulfide (CS2), and phosphine (PH3), at a WWTP in Northwest China. Odorants were detected in the air surrounding the grid room (XGS), biochemical treatment tank (SHC), secondary sedimentation tank (ECC), and sludge dewatering room (NTS). For comparison, the upwind boundary (O-SF) and downwind boundaries (O-XF) monitoring points were used, with odor concentrations ranging from 3.95 to 725.27 odor units. The concentration ranges of the odorant substances were 5.27-88.69, 5.61-71.96, 5.70-32.63, and 0.12-5.87 mg/m3 for H2S, NH3, CS2, and PH3, respectively. Meteorological factors such as temperature, relative humidity, and wind speed and direction substantially influence odorant emissions. The concentrations of various odorants and volatile organic compounds (VOCs) detected at the O-XF monitoring point were higher than those detected at the O-SF monitoring point, indicating that the wind intensified their diffusion toward the downwind plant boundary. The average odor intensities of odorant substances emitted from wastewater or sludge treatment equipment were 3.37, 5.09, 4.42, 2.00, and 3.82 for total VOCs, H2S, NH3, CS2, and PH3, respectively. Among them four, with downwind diffusion, only H2S presented olfactory and chronic toxicity risks based on Gaussian plume model calculations. The hazard index ranking across monitoring sites was XGS > NTS > SHC > ECC > O-XF > O-SF. These findings emphasize the urgent need for effective measures to control and mitigate gaseous pollutants emitted by collaborative WWTPS, thereby protecting environmental quality and public health.

Transmission of carbapenem-resistant enterobacterales producing NDM-5 during the broiler breeding process in China.

This study conducted a four-month monitoring of carbapenem resistance in a broiler breeding farm in China. A total of 185 carbapenem-resistant bacterial isolates were obtained from 2298 cloacal swabs from broiler breeders and their offspring within a production cycle. The detection rate of carbapenem-resistant isolates was higher during the brooding period. Whole-genome sequencing (WGS) was performed on 133 isolates based on sampling stages, including 113 carbapenem-resistant Enterobacterales (CRE) isolates and 20 Stenotrophomonas pavanii isolates, which have intrinsic resistance to carbapenems. A total of 69 antibiotic resistance genes (ARGs), including blaNDM-1, mcr-1, and blaNDM-5, were identified among the sequenced CRE isolates. Notably, blaNDM-5 (92.0 %, 104/113) was the primary contributor to carbapenem resistance. CRE isolates from the same breeding stage exhibited close genomic relationships, and the blaNDM-5 genes were observed in similar genetic backgrounds, indicating the transmission of CRE strains and blaNDM-5 during the broiler breeding process. No CRE was isolated from 0 d broiler offspring, suggesting that broiler breeders were not the direct source of CRE in their offspring. Tracing the feeding process revealed that brooder and rearing houses were likely key factors in the cross-transmission of CRE between broiler breeders and their offspring. CRE pose a significant threat to public health and food safety. China is one of the world's leading poultry producing and consuming countries. This study provided insights into the epidemiological trends and key transmission nodes of carbapenem resistance and CRE within the broiler breeding process, which could help the control of antibiotic resistance and bacterial infections in the broiler industry.

Epidemiology of liver diseases: global disease burden and forecasted research trends.

We assessed the global incidence, mortality, and disability-adjusted life years (DALYs) associated with various liver diseases, including alcohol-related liver disease (ALD), hepatitis B/C virus infections (HBV or HCV), liver cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), and other chronic liver diseases, from the 2019 Global Burden of Disease study. Additionally, we analyzed the global trends in hepatology research and drug development. From 2000 to 2019, prevalence rates increased for ALD, MASLD and other liver diseases, while they decreased for HBV, HCV, and liver cancer. Countries with a high socio-demographic index (SDI) exhibited the lowest mortality rates and DALYs. The burden of liver diseases varied due to factors like sex and region. In nine representative countries, MASLD, along with hepatobiliary cancer, showed highest increase in funding in hepatology research. Globally, the major research categories in hepatology papers from 2000 to 2019 were cancer, pathobiology, and MASLD. The United States (U.S.) was at the forefront of hepatology research, with China gradually increasing its influence over time. Hepatologists worldwide are increasingly focusing on studying the communication between the liver and other organs, while underestimating the research on ALD. Cancer, HCV, and MASLD were the primary diseases targeted for therapeutic development in clinical trials. However, the proportion of new drugs approved for the treatment of liver diseases was relatively low among all newly approved drugs in the U.S., China, Japan, and the European Union. Notably, there were no approved drug for the treatment of ALD in the world.

Remarkable Enhancement of Bismuth Nanosphere Catalyst Activity for the Conversion of Electrocatalytic CO2 to Formate by Bromine Doping.

Driven by renewable energy, using electrocatalysis to reduce carbon dioxide (CO2) to chemicals is a key technology. It could dim global carbon emissions and promote the carbon cycle. Here, we reported an approach to prepare a Br-doped Bi nanosphere (Br-doped Bi NSP) catalyst for the preparation of formate by electrochemical conversion of CO2. The synthesized Br-doped Bi NSP catalyst manifests high selectivity toward HCOOH. At the applied potential of -0.9 V versus reversible hydrogen electrode, it could achieve a maximum FEHCOOH of 98%. It can remain constant, and the degradation is negligible in continuous electrolysis for 9 h. The excellent CO2 reduction performance is due to the electron richness at the surface of Br-doped Bi NSP induced by the electron transfer between Bi and Br. Density functional theory calculations and in situ attenuated total reflectance-Fourier transform infrared measurements were used to predict the underlying catalyst action's pathway. It can be concluded that the introduction of Br is advantageous to the *OCHO formation, which is conducive to the reduction of the determination step. This research could provide a meaningful view into anion-doping effects to enable effiective electrocatalytic material that selectively reduces carbon dioxide into valuable products.

Edible bird's nest improves hemorheology and immune function in mice with transplanted uterine leiomyomas.

OBJECTIVE: To investigate the effect of edible bird's nest (EBN) on tumor growth, hemorheology and immune function of mice with transplanted uterine myomas. METHODS: A subcutaneous tumor model of human uterus myoma was established in mice, and the mice were randomly divided into a model group, EBN group, estradiol receptor (ER) group and ER+EBN group. Body weight and tumor volume were measured at 2 weeks, 4 weeks and 8 weeks after the uterus myoma transplantation. Eight weeks after transplantation, the tumor weight was assessed, the morphology of different organs was observed, and the pathological changes of the uterus myoma was observed. Besides, the levels of ER and progesterone receptor (PR), various hemorheological parameters (including hematocrit, plasma viscosity and whole blood viscosity under different shearing conditions), and immune functions (CD3 +, CD4 + and CD8 + cells) were also measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), nitricoxidesynthase (NOS) and vascular endothelial growth factor (VEGF) in each group. RESULTS: There were no statistical differences in body weight, tumor weight, tumor volume, uterus myoma pathology or the levels of ER and PR between the model group and EBN group, nor between the ER group and ER+EBN group (all P>0.05). Similarly, no notable morphological differences were observed in the heart, liver, spleen, lung, kidney, stomach, intestines and uterus among different groups (all P>0.05). However, in contrast to the model group, the EBN group exhibited significant reductions in hemorheology indicators, the proportion of CD8 + cells, as well as the levels of TNF-α, NOS and VEGF (all P<0.05). Conversely, the proportion of CD3 + and CD4 + cells, the CD4 +/CD8 + ratio and the level of IL-2 in the EBN group were obviously increased (all P<0.05). Compared with the ER group, the proportion of CD8 + cells, the levels of TNF-α, NOS and VEGF in the ER+EBN group were significantly decreased while the proportion of CD3 + and CD4 + cells, the CD4 +/CD8 + ratio and the level of IL-2 in the ER+EBN group were obviously increased. CONCLUSION: For mice with uterine myoma transplantation, EBN does not influence tumor growth but significantly regulates hemorheology and enhances immune function.

Revelation of comprehensive cell profiling of primary and metastatic tumour ecosystems in oral squamous cell carcinoma by single-cell transcriptomic analysis.

Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.

Stress Hormones: Unveiling the Role in Accelerated Cellular Senescence.

Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.

Licochalcone A Ameliorates Aspergillus fumigatus Keratitis by Reducing Fungal Load and Activating the Nrf2/HO-1 Signaling Pathway.

Fungal keratitis (FK) is a blinding corneal infectious disease. The prognosis is frequently unfavorable due to fungal invasion and an excessive host inflammatory response. Licochalcone A (Lico A) exhibits a broad spectrum of pharmacological activities, encompassing antifungal, anti-inflammatory, antioxidation, and antitumor properties. However, the role of Lico A has not yet been studied in FK. In this study, we discovered that Lico A could disrupt Aspergillus fumigatus (A. fumigatus) biofilms, inhibit fungal growth and adhesion to host cells, induce alterations of hyphal morphology, and impair the cell membrane and cell wall integrity and mitochondrial structure of A. fumigatus. Lico A can alleviate the severity of FK in mice, reduce neutrophil infiltration and fungal load, and significantly decrease the pro-inflammatory cytokines in mouse corneas infected with A. fumigatus. In vitro, we also demonstrated that Lico A increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) around the nucleus in human corneal epithelial cells (HCECs) stimulated with A. fumigatus. We verified that the anti-inflammatory effect of Lico A is associated with the activation of the Nrf2/HO-1 axis. These results indicated that Lico A could provide a protective role in A. fumigatus keratitis through its anti-inflammatory and antifungal activities.

High-Intensity Interval Training Mitigates Sarcopenia and Suppresses the Myoblast Senescence Regulator EEF1E1.

BACKGROUND: The optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high-intensity interval training (HIIT) over moderate-intensity continuous training (MICT) in ameliorating sarcopenia. METHODS: We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4-min high-intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT-specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case-control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC-II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D-galactose-induced myoblast senescence, measuring senescence-associated ß-galactosidase and markers like p21 and p53. RESULTS: The crossover trial, including 10 sedentary adults (32 years old, IQR 31-32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case-control study of 84 older adults (84 years old, IQR 69-81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02-27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index (R2 = 0.51, p < 0.001) and hand grip strength (R2 = 0.54, p < 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers and reduced muscle differentiation efficiency (all p < 0.05). HIIT reduced EEF1E1 expression and mitigated age-related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D-galactose-induced myoblast senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all p < 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process (p < 0.05). Further exploration indicated that the decrease in EEF1E1 was associated with increased SIRT1 level and enhanced autophagy. CONCLUSIONS: This study highlights the potential of HIIT as a promising approach to prevent and treat sarcopenia while also highlighting EEF1E1 as a potential intervention target.

The Regulatory Effect of Vitamin D on Pancreatic Beta Cell Secretion in Patients with Type 2 Diabetes.

Increasing evidence suggests that vitamin D is one of the causes of accelerated development of Insulin Resistance (IR) and islet cell secret dysfunction. Numerous studies have shown that vitamin D can reduce inflammation, activate the transcription of the insulin receptors and related genes, and increase insulin-mediated glucose transport, thereby reducing IR. This article reviews the molecular mechanisms related to vitamin D deficiency and pancreatic ß-cell dysfunction in patients with Type 2 Diabetes (T2D).

Migration of depleted uranium from a corroded penetrator in soil vadose zone in Bosnia and Herzegovina.

Depleted uranium (DU) from corroded armor penetrators can migrate through the soil vadose zone and cause environmental problems, yet studies on such migration at former theatres of war are scarce. Here, we investigated vertical DU migration in a soil profile due to a penetrator (3-8 cm beneath the soil surface) corroded over 7 years in Bosnia and Herzegovina. The highest concentration of DU was ∼45,300 mg/kg at 6-10 cm, with the concentration decreasing markedly with increasing depth. The majority of the DU accumulated within the top 20 cm and the DU front reached ∼42 cm beneath the penetrator. In addition, particles with varying U concentrations (3-65 wt%) were observed at 0-15 cm, with U primarily co-located with O, Si, Al, maghemite, and hematite. Particularly, metaschoepite was identified at 6-10 cm. Finally, X-ray absorption spectroscopy analysis found U was hexavalent in the soil profile. These findings suggest that the downward migration of DU was likely present as a soluble form adsorbed on clay minerals and Fe oxides. Overall, we show that the rate of DU migration within the vadose zone is comparatively slow, although if the penetrator is left in the soil for decades, it could pose a serious long-term risk. ENVIRONMENTAL IMPLICATIONS: Over 90 % of the depleted uranium (DU) penetrators fired in previous conflicts missed their armored targets and were left in the soil to corrode. The corroded penetrators can not only contaminate soil but also pose a risk to groundwater. The present study examined the migration of DU in a soil profile that included a DU penetrator that had been corroding for over 7 years. Studying the dynamics of DU migration is essential to develop effective remediation strategies to mitigate long-term environmental risks and safeguard ecosystems and human health from DU contamination.

Predicting Pathological Characteristics of HER2-Positive Breast Cancer from Ultrasound Images: a Deep Ensemble Approach.

The objective is to evaluate the feasibility of utilizing ultrasound images in identifying critical prognostic biomarkers for HER2-positive breast cancer (HER2 + BC). This study enrolled 512 female patients diagnosed with HER2-positive breast cancer through pathological validation at our institution from January 2016 to December 2021. Five distinct deep convolutional neural networks (DCNNs) and a deep ensemble (DE) approach were trained to classify axillary lymph node involvement (ALNM), lymphovascular invasion (LVI), and histological grade (HG). The efficacy of the models was evaluated based on accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curves, areas under the ROC curve (AUCs), and heat maps. DeLong test was applied to compare differences in AUC among different models. The deep ensemble approach, as the most effective model, demonstrated AUCs and accuracy of 0.869 (95% CI: 0.802-0.936) and 69.7% in LVI, 0.973 (95% CI: 0.949-0.998) and 73.8% in HG, thus providing superior classification performance in the context of imbalanced data (p < 0.05 by the DeLong test). On ALNM, AUC and accuracy were 0.780 (95% CI: 0.688-0.873) and 77.5%, which were comparable to other single models. The pretreatment US-based DE model could hold promise as a clinical guidance for predicting pathological characteristics of patients with HER2-positive breast cancer, thereby providing benefit of facilitating timely adjustments in treatment strategies.

JC virus spread is potentiated by glial replication and demyelination-linked glial proliferation.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating infection of the immunosuppressed brain, mediated by the gliotropic polyomavirus JCV. JCV replicates in human glial progenitor cells and astrocytes, which undergo viral T antigen-triggered mitosis, enabling viral replication. We asked if JCV spread might therefore be accelerated by glial proliferation. Using both in vitro analysis and a human glial chimeric mouse model of JCV infection, we found that dividing human astrocytes supported JCV propagation to a substantially greater degree than did mitotically quiescent cells. Accordingly, bulk and single cell RNA-sequence analysis revealed that JCV-infected glia differentially manifested cell cycle-linked disruption of both DNA damage response and transcriptional regulatory pathways. In vivo, JCV infection of humanized glial chimeras was greatly accentuated by cuprizone-induced demyelination and its associated mobilization of GPCs. Importantly, in vivo infection triggered the death of uninfected as well as infected glia, reflecting significant bystander death. Together, these data suggest that JCV propagation in PML may be accelerated by glial cell division. As such, the accentuated glial proliferation attending disease-associated demyelination may provide an especially favorable environment for JCV propagation, thus potentiating oligodendrocytic bystander death and further accelerating demyelination in susceptible hosts.

Maximizing interface stability in all-solid-state lithium batteries through entropy stabilization and fast kinetics.

The positive electrode|electrolyte interface plays an important role in all-solid-state Li batteries (ASSLBs) based on garnet-type solid-state electrolytes (SSEs) like Li6.4La3Zr1.4Ta0.6O12 (LLZTO). However, the trade-off between solid-solid contact and chemical stability leads to a poor positive electrode|electrolyte interface and cycle performance. In this study, we achieve thermodynamic compatibility and adequate physical contact between high-entropy cationic disordered rock salt positive electrodes (HE-DRXs) and LLZTO through ultrafast high-temperature sintering (UHS). This approach constructs a highly stable positive electrode|electrolyte interface, reducing the interface resistance to 31.6 Ω·cm2 at 25 °C, making a 700 times reduction compared to the LiCoO2 | LLZTO interface. Moreover, the conformal and tight HE-DRX | LLZTO solid-state interface avoids the transition metal migration issue observed with HE-DRX in liquid electrolytes. At 150 °C, HE-DRXs in ASSLBs (Li|LLZTO | HE-DRXs) exhibit an average specific capacity of 239.7 ± 2 mAh/g at 25 mA/g, with a capacity retention of 95% after 100 cycles relative to the initial cycle-a stark contrast to the 76% retention after 20 cycles at 25 °C in conventional liquid batteries. Our strategy, which considers the principles of thermodynamics and kinetics, may open avenues for tackling the positive electrode|electrolyte interface issue in ASSLBs based on garnet-type SSEs.

Bacterial membrane vesicles from swine farm microbial communities harboring and safeguarding diverse functional genes promoting horizontal gene transfer.

Antibiotic resistance (AMR) poses a significant global health challenge, with swine farms recognized as major reservoirs of antibiotic resistance genes (ARGs). Recently, bacterial membrane vesicles (BMVs) have emerged as novel carriers mediating horizontal gene transfer. However, little is known about the ARGs carried by BMVs in swine farm environments and their transfer potential. This study investigated the distribution, sources, and microbiological origins of BMVs in three key microbial habitats of swine farms (feces, soil, and fecal wastewater), along with the ARGs and mobile genetic elements (MGEs) they harbor. Characterization of BMVs revealed particle sizes ranging from 20 to 500 nm and concentrations from 108 to 1012 particles/g, containing DNA and proteins. Metagenomic sequencing identified BMVs predominantly composed of members of the Proteobacteria phyla, including Pseudomonadaceae, Moraxellaceae, and Enterobacteriaceae, carrying diverse functional genes encompassing resistance to 14 common antibiotics and 74,340 virulence genes. Notably, multidrug resistance, tetracycline, and chloramphenicol resistance genes were particularly abundant. Furthermore, BMVs harbored various MGEs, primarily plasmids, and demonstrated the ability to protect their DNA cargo from degradation and facilitate horizontal gene transfer, including the transmission of resistance genes. In conclusion, this study reveals widespread presence of BMVs carrying ARGs and potential virulence genes in swine farm feces, soil, and fecal wastewater. These findings not only provide new insights into the role of extracellular DNA in the environment but also highlight concerns regarding the gene transfer potential mediated by BMVs and associated health risks.

Linking industrial emissions and dietary exposure to human burdens of polychlorinated naphthalenes.

Relationships between toxic pollutant emissions during industrial processes and toxic pollutant dietary intakes and adverse health burdens have not yet been quantitatively clarified. Polychlorinated naphthalenes (PCNs) are typical industrial pollutants that are carcinogenic and of increasing concern. In this study, we established an interpretable machine learning model for quantifying the contributions of industrial emissions and dietary intakes of PCNs to health effects. We used the SHapley Additive exPlanations model to achieve individualized interpretability, enabling us to evaluate the specific contributions of individual feature values towards PCNs concentration levels. A strong relationship between PCN dietary intake and body burden was found using a robust large-scale PCN diet survey database for China containing the results of the analyses of 17,280 dietary samples and 4480 breast milk samples. Industrial emissions and dietary intake contributed 12 % and 52 %, respectively, of the PCN burden in breast milk. The model quantified the contributions of food consumption and industrial emissions to PCN exposure, which will be useful for performing accurate health risk assessments and developing reduction strategies of PCNs.