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The global COVID-19 health pandemic caused major interruptions to educational assessment systems, partially due to shifts to remote learning environments, entering the post-COVID educational world into one that is more open to heterogeneity in instructional and assessment modes for secondary students. In addition, in 2020, educational inequities were brought to the forefront of social conscience. The purpose of this study is to empirically explore how contextual (i.e., school-level) race and economic factors may relate to and explain measurement challenges that can arise during shifts to remote learning. We fit a series of multilevel models to explore school-level factors in assessment data alongside psychometric problems of differential item functioning and person fit in classroom assessment measurement models. Our results demonstrate ways in which our project's classroom assessments were impacted by shifts to remote learning, emphasizing the importance of researchers and practitioners evaluating such concerns when seeking validity evidence for interpretation of classroom assessment data.

Although cyber victimization has been suggested as a significant risk factor for the development of adolescents' depression, the underlying psychopathological process that mediates this relationship needs further exploration. Based on the psychological inflexibility model, this study aimed to examine cognitive fusion and experiential avoidance as serial mediators in the relation between cyber victimization and depression. A total of 556 Chinese adolescents completed a set of online self-report questionnaires measuring cyber victimization, cognitive fusion, experiential avoidance, and depression. A bias-corrected bootstrap approach was used to test the serial mediation model. The results showed that cyber victimization predicted adolescents' depression not only directly but also indirectly through three paths: the mediating role of (1) cognitive fusion and (2) experiential avoidance, and (3) the serial mediating role of cognitive fusion and experiential avoidance. These findings provide insight into the interventions for depression in adolescent cyber victims.

Abstract This study investigated the association between serum albumin concentration and 12-weeks mortality of HIV/AIDS with late diagnosis in China. This retrospective cohort study included, 1079 inpatients diagnosis with late HIV/AIDS between January 2018 and December 2021. Disease progression was estimated based on the 12-weeks mortality rate. Cox proportional hazards regression models were used to evaluate the relationship between serum albumin levels and disease progression. The effects of serum albumin levels on mortality was estimated via Kaplan–Meier curves. The mortality risk decreased by 7% with every 1 g/L increase in serum albumin after adjustment ([HR] = 0.93, 95% CI: 0.88–0.97). Compared with that of the low (< 28 g/L) serum albumin group, the middle (28–34 g/L) group’s mortality risk decreased by 70% (HR = 0.30, 95% CI: 0.15–0.59), and that of the high (≥ 34 g/L) group decreased by 40% (HR = 0.6, 95% CI: 0.29–1.23) after adjustment. Our findings suggest a positive correlation between the increase in serum albumin levels upon admission and a decrease in mortality at 12 weeks post-discharge among patients with late AIDS/HIV diagnosis. Further research is needed to characterize the role of serum albumin in 12-weeks mortality prevention in patients with a late diagnosis.

Abstract With the rapid spread of the novel coronavirus (COVID-19), a sustained global pandemic has emerged. Globally, the cumulative death toll is in the millions. The rising number of COVID-19 infections and deaths has severely impacted the lives of people worldwide, healthcare systems, and economic development. We conducted a retrospective analysis of the characteristics of COVID-19 patients. This analysis includes clinical features upon initial hospital admission, relevant laboratory test results, and imaging findings. We aimed to identify risk factors for severe illness and to construct a predictive model for assessing the risk of severe COVID-19. We collected and analyzed electronic medical records of confirmed COVID-19 patients admitted to the Affiliated Hospital of Jiangsu University (Zhenjiang, China) between December 18, 2022, and February 28, 2023. According to the WHO diagnostic criteria for the novel coronavirus, we divided the patients into two groups: severe and non-severe, and compared their clinical, laboratory, and imaging data. Logistic regression analysis, the least absolute shrinkage and selection operator (LASSO) regression, and receiver operating characteristic (ROC) curve analysis were used to identify the relevant risk factors for severe COVID-19 patients. Patients were divided into a training cohort and a validation cohort. A nomogram model was constructed using the “rms” package in R software. Among the 346 patients, the severe group exhibited significantly higher respiratory rates, breathlessness, altered consciousness, neutrophil-to-lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) levels compared to the non-severe group. Imaging findings indicated that the severe group had a higher proportion of bilateral pulmonary inflammation and ground-glass opacities compared to the non-severe group. NLR and LDH were identified as independent risk factors for severe patients. The diagnostic performance was maximized when NLR, respiratory rate (RR), and LDH were combined. Based on the statistical analysis results, we developed a COVID-19 severity risk prediction model. The total score is calculated by adding up the scores for each of the twelve independent variables. By mapping the total score to the lowest scale, we can estimate the risk of COVID-19 severity. In addition, the calibration plots and DCA analysis showed that the nomogram had better discrimination power for predicting the severity of COVID-19. Our results showed that the development and validation of the predictive nomogram had good predictive value for severe COVID-19.

Oolong tea was highly favored by consumers for its rich aroma. However, there was significant loss of fragrance in Oolong tea products during processing and storage, urgently necessitating the development of corresponding technologies to stabilize aroma molecules. Addressing this, this study investigated the stabilization of aroma compounds in Rougui Oolong tea. Employing spinning cone column distillation, volatile organic compounds (VOCs) were extracted from the tea. The effect of hydroxypropyl-β-cyclodextrin on inhibiting the aromatic loss of these extracted VOCs during storage was assessed using gas chromatography-ion mobility spectrometry. Results showed that after 7, 21, and 42 days of storage at room temperature (25 ℃), the samples treated with hydroxypropyl-β-cyclodextrin (experimental group) consistently contained significantly higher quantities of VOCs compared to the untreated controls (P

Abstract Background Severe COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial. Objective In this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients. Methods We conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal. Results Our analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages. Conclusion The TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease.

Abstract Purpose Sleep disorders are becoming more prevalent in hospitalized patients with acute myocardial infarction (AMI). We aimed to investigate the risk factors for sleep disorders in hospitalized patients with AMI, then develop and validate a prediction nomogram for the risk of sleep disorders. Methods Clinical data were collected from patients with AMI hospitalized in our hospital from January 2020 to June 2023. All patients were divided into the training group and the validation group with a ratio of 7:3 in sequential order. The LASSO regression analysis and multivariate logistic regression analysis were used to screen potential risk factors for sleep disorders. The concordance index (C-index), calibration curves, and decision curve analysis (DCA) were plotted. Results A total of 256 hospitalized patients with AMI were enrolled. Patients were divided into the training group (180) and the validation group (76) according to a scale of 7:3. Of the 256 patients, 90 patients (35.16%) suffered from sleep disorders, and 33 patients (12.89%) needed hypnotics. The variables screened by LASSO regression included age, smoking, NYHA class, anxiety status at admission, depression status at admission, and strangeness of environment. A nomogram model was established by incorporating the risk factors selected. The C-index, calibration curve, and DCA showed good predictive performance. Conclusions We identified six clinical characteristics as predictors of sleep disorders in hospitalized patients with AMI. It helps nurses make appropriate decisions in clinical practice.

The aim of this study was to develop a semantic search system for Khmer stone castles in the Greater Mekong Subregion (GMS), in alignment with UNESCO's cultural heritage preservation guidelines. The proposed database, curated with verified, high quality data, serves as a comprehensive knowledge base for educational and research purposes. The semantic search system demonstrated high effective-ness, showcasing its potential as a benchmark for cultural information retrieval. The study contributes to establishing similar systems in diverse domains, paving the way for ontology-driven approaches to support cultural heritage preservation and sus tainable web-based information search systems. The far-reaching implications offer valuable insights for the conservation and accessibility of cultural heritage.

Abstract Background This study aims to evaluate the effect of various background reference regions on spinal 18F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results. Results A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging. The stability of uptake across four regions, including the pons, C2, C2–C7, and T1–T3, was compared. The standardized uptake value ratio (SUVR) was then evaluated using various background regions, and their effectiveness in differentiating between spinal tumors and myelitis was compared. Additionally, we correlated the SUVR values derived from these regions with the Ki-67 proliferation index in tumor patients. The study found no significant difference in SUVmax (U = 110, p = 0.93) and SUVmean (U = 89, p = 0.35) values at lesion sites between myelitis and tumor patients. The pons had the highest average uptake (p

Abstract The formation of symbionts by using different combinations of endophytic bacteria, microalgae, and fungi to purify antibiotics-containing wastewater is an effective and promising biomaterial technology. As it enhances the mixed antibiotics removal performance of the bio-system, this technology is currently extensively studied. Using exogenous supplementation of various low concentrations of the phytohormone strigolactone analogue GR24, the removal of various antibiotics from simulated wastewater was examined. The performances of Chlorella vulgaris monoculture, activated sludge–C. vulgaris–Clonostachys rosea, Bacillus licheniformis–C. vulgaris–C. rosea, and endophytic bacteria (S395-2)–C. vulgaris–C. rosea co-culture systems were systematically compared. Their removal capacities for tetracycline, oxytetracycline, and chlortetracycline antibiotics from simulated wastewater were assessed. Chlorella vulgaris–endophytic bacteria–C. rosea co-cultures achieved the best performance under 0.25 mg L−1 antibiotics, which could be further enhanced by GR24 supplementation. This result demonstrates that the combination of endophytic bacteria with microalgae and fungi is superior to activated sludge–B. licheniformis–microalgae–fungi systems. Exogenous supplementation of GR24 is an effective strategy to improve the performance of antibiotics removal from wastewater.

Abstract Background Postoperative pulmonary complications (PPCs) after one-lung ventilation (OLV) significantly impact patient prognosis and quality of life. Objective To study the impact of an optimal inspiratory flow rate on PPCs in thoracic surgery patients. Methods One hundred eight elective thoracic surgery patients were randomly assigned to 2 groups in this consort study (control group: n = 53 with a fixed inspiratory expiratory ratio of 1:2; and experimental group [flow rate optimization group]: n = 55). Measurements of Ppeak, Pplat, PETCO2, lung dynamic compliance (Cdyn), respiratory rate, and oxygen concentration were obtained at the following specific time points: immediately after intubation (T0); immediately after starting OLV (T1); 30 min after OLV (T2); and 10 min after 2-lung ventilation (T4). The PaO2:FiO2 ratio was measured using blood gas analysis 30 min after initiating one-lung breathing (T2) and immediately when OLV ended (T3). The lung ultrasound score (LUS) was assessed following anesthesia and resuscitation (T5). The occurrence of atelectasis was documented immediately after the surgery. PPCs occurrences were noted 3 days after surgery. Results The treatment group had a significantly lower total prevalence of PPCs compared to the control group (3.64% vs. 16.98%; P = 0.022). There were no notable variations in peak airway pressure, airway plateau pressure, dynamic lung compliance, PETCO2, respiratory rate, and oxygen concentration between the two groups during intubation (T0). Dynamic lung compliance and the oxygenation index were significantly increased at T1, T2, and T4 (P

Abstract Z-DNA binding protein 1 (ZBP1) is a crucial player in the intracellular recognition of Z-form nucleic acids (Z-NAs) through its Zαβ domain, initiating downstream interactions with RIPK1 and RIPK3 via RHIM domains. This engagement leads to the assembly of PANoptosomes, ultimately inducing programmed cell death to curb pathogen dissemination. How Zαβ and RHIM domain cooperate to trigger Z-NAs recognition and signal transduction remains unclear. Here, we show that ZBP1 condensate formation facilitates Z-NAs binding and antiviral signal transduction. The ZBP1 Zαβ dimerizes in a concentration-dependent manner, forming characteristic condensates in solutions evidenced by DLS and SAXS methods. ZBP1 exhibits a binding preference for 10-bp length CG (10CG) DNA and Z-RNA ligand, which in turn enhanced Zαβ dimerization, expediting the formation of droplet condensates in vitro and amyloid-like puncta in cells. Subsequent investigations reveal that Zαβ could form condensates with liquid-liquid phase separation property upon HSV and IAV infections, while full-length ZBP1 forms amyloid-like puncta with or without infections. Furthermore, ZBP1 RHIM domains show typical amyloidal fibril characterizations and cross-polymerize with RIPK1 depending on the core motif of 206IQIG209, while mutated ZBP1 could impede necroptosis and antiviral immunity in HT-29 cells. Thus, ZBP1 condensate formation facilitates the recognition of viral Z-NAs and activation of downstream signal transduction via synergic action of different domains, revealing its elaborated mechanism in innate immunity.

Abstract This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non‐dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24‐h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24‐h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone‐renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24‐h wSD of systolic BP (β = 0.383).The study also found significant correlations between the 24‐h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24‐h urinary microalbumin, underscoring the critical role of the 24‐h wSD of systolic BP (β = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Abstract Background and aims Electrophysiological characteristics and radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) originating from the superior septal left ventricle (SSLV) have not yet been fully characterized. Methods and results This study included 247 patients who underwent RFCA for PVCs arising from the ventricular outflow tract between February 2020 and August 2022. The successful ablation site was on the SSLV in 37 of the 247 patients. In 12 (32.4%) of those 37 patients, a low amplitude and high frequency spiky potential (SP) was recognized. Five patients showed a narrow QRS duration (86.8 ± 4.6 ms), with a discrete SP observed in PVCs and sinus rhythm, which showed an isoelectric line with the ventricular electrogram at the earliest activation site. Seven patients showed a wide QRS duration (131.6 ± 4.5 ms), with SP observed in PVCs without an isoelectric line with the ventricular electrogram. RFCA was successful at the site of the earliest SP in all 12 patients. The time from SP onset at the successful ablation site to the QRS onset (local activation time) was 30 ± 12 ms, which differed significantly from that for the remaining 25 patients withoutSP(22.1 ± 7.1 ms, P

Abstract Two potent greenhouse gases that are mostly found in agricultural soils are methane and nitrous oxide. Therefore, we investigated the effect of different moisture regimes on microbial stoichiometry, enzymatic activity, and greenhouse gas emissions in long-term paddy soils. The treatments included a control (CK; no addition), chemical fertilizer (NPK), and NPK + cattle manure (NPKM) and two moisture regimes such as 60% water-filled pore spaces (WFPS) and flooding. The results revealed that 60% water-filled pore spaces (WFPS) emit higher amounts of N2O than flooded soil, while in the case of CH4 the flooded soil emits more CH4 emission compared to 60% WFPS. At 60% WFPS higher N2O flux values were recorded for control, NPK, and NPKM which are 2.3, 3.1, and 3.5 µg kg−1, respectively. In flooded soil, the CH4 flux emission was higher, and the NPKM treatment recorded the maximum CH4 emissions (3.8 µg kg−1) followed by NPK (3.2 µg kg−1) and CK (1.7 µg kg−1). The dissolved organic carbon (DOC) was increased by 15–27% under all flooded treatments as compared to 60% WPFS treatments. The microbial biomass carbon, nitrogen, and phosphorus (MBC, MBN, and MBP) significantly increased in the flooded treatments by 8–12%, 14–21%, and 4–22%, respectively when compared to 60% WFPS. The urease enzyme was influenced by moisture conditions, and significantly increased by 42–54% in flooded soil compared with 60% WFPS while having little effect on the β-glucosidase (BG) and acid phosphatase (AcP) enzymes. Moreover DOC, MBC, and pH showed a significant positive relationship with cumulative CH4, while DOC showed a significant relationship with cumulative N2O. In the random forest model, soil moisture, MBC, DOC, pH, and enzymatic activities were the most important factors for GHG emissions. The PLS-PM analysis showed that soil properties and enzymes possessed significantly directly impacted on CH4 and N2O emissions, while SMB had indirect positive effect on CH4 and N2O emissions.

Abstract Background Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. Methods We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). Results The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004–2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004–2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. Conclusions In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Abstract Background To investigate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women after transcervical resection of endometrial polyps (TCRP). Methods This prospective study enrolled 507 women who underwent TCRP between January 1, 2022 and December 31, 2022. The patients were divided into a CE group (n = 133) and non-CE group (n = 374) based on the expression of CD138 in the endometrium. The EP recurrence rate at 1 year after TCRP was compared between the CE and non-CE groups and between groups with mild CE and severe CE. The impact of CD138 expression by resected EPs on EP recurrence also was investigated. Results The EP recurrence rate at 1 year post-TCRP was higher in the CE group than in the non-CE group (25.6% vs. 10.4%) and also higher in the severe CE group than in the mild CE group (34.5% vs. 18.7%). Additionally, the EP recurrence rate was higher among patients with CD138-expressing EPs than among those with EPs lacking CD138 expression (30.5% vs. 6.5%). The odds ratio (OR) for EP recurrence in the CE cohort compared with the non-CE cohort was 3.10 (95% confidence interval [CI] 1.84–5.23) after adjustment for EP number and precautions against EP recurrence. The ORs for EP recurrence in patients with mild CE and severe CE were 2.21 (95%CI 1.11–4.40) and 4.32 (95%CI 2.26–8.26), respectively. Similarly, the OR for EP recurrence in cases with CD138-expressing EPs relative to cases with EPs lacking CD138 expression was 6.22 (95%CI 3.59–10.80) after adjustment for EP number and precautions against EP recurrence. Conclusions CE multiplied the recurrence rate of EPs in premenopausal women after TCRP, and this effect positively correlated with CE severity. CD138 expression by EPs also was associated with a higher risk for EP recurrence.

Abstract The carbon capture‐transportation‐utilization (C‐CTU) chain strengthens the coupling between terminal energy consumption and renewable energy resources (RES), achieving carbon emission reduction in power generation sectors. However, the dynamic operation of the C‐CTU chain and the uncertainties induced by RES output pose new challenges for the low‐carbon operation. To address above challenges, the nonlinear dynamic operation model of C‐CTU chain is first proposed in this study. It is further incorporated into the day‐ahead operation scheme of the electricity‐carbon integrated system considering the stochastic nature of wind power. This scheme is treated as a two‐stage stochastic integer programming (TS‐SIP) problem with a mixed‐integer nonlinear recourse. By means of the polyhedral envelope‐based linearization method, this recourse is reformulated into its linear counterpart. To further improve the computational performance of classical decomposition algorithms, a novel Benders decomposition framework with hybrid cutting plane strategies is proposed to obtain better feasible solutions within a limited time. Simulations are conducted on two power system test cases with the C‐CTU chain. Numerical results indicate that the engagement of C‐CTU chain promotes the low‐carbon economic operation of the power system. Also, the proposed decomposition algorithm shows a superior solution capability to handle large‐scale TS‐SIP than state‐of‐the‐art commercial solvers.

A comparative study of high chromium (Super304H) and high manganese low chromium heat-resistant steel (HT630) was carried out at 650 °C in steam. Results indicate that the high manganese content in HT630 significantly improved its oxidation resistance. It is ascribed to the formation of a dense protective MnCr2O4 oxide layer during oxidation. MnCr2O4 layer effectively inhibits the diffusion of iron, suppresses the growth of iron-rich oxides, promotes the formation of an iron-rich protective interface with the matrix, and improves the overall oxidation resistance.

Abstract Background Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such associations remains unclear. Methods Cigarette exposure, trouble sleeping, and depression were assessed by standard questionnaires, and the levels of cotinine and sex steroid hormones were determined among 9900 adults from the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression, logistic regression, and mediation models were conducted to evaluate the associations between smoking, sex steroid hormones, trouble sleeping, and depression. Results With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293) as well as testosterone level (β = 0.083, 95% CI: 0.028, 0.140). Pack-years of smoking and cigarettes per day were positively associated with the prevalence of trouble sleeping and depression as well as testosterone level (P trend 0.05). Conclusion Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms, and ceasing smoking may reduce the risk of such complications.

Abstract Backgrounds Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. Methods We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/ ) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman’s correlation analysis. Results We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. Conclusion MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. Methods: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150–200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1–14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9–18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5–21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3–23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2–57.2; P = 0.004) were associated with a significantly shorter PFS. Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Abstract The development of artificial intelligence-enabled medical health care has created both opportunities and challenges for next-generation biosensor technology. Proteins are extensively used as biological macromolecular markers in disease diagnosis and the analysis of therapeutic effects. Electrochemical protein biosensors have achieved desirable specificity by using the specific antibody–antigen binding principle in immunology. However, the active centers of protein biomarkers are surrounded by a peptide matrix, which hinders charge transfer and results in insufficient sensor sensitivity. Therefore, electrode-modified materials and transducer devices have been designed to increase the sensitivity and improve the practical application prospects of electrochemical protein sensors. In this review, we summarize recent reports of electrochemical biosensors for protein biomarker detection. We highlight the latest research on electrochemical protein biosensors for the detection of cancer, viral infectious diseases, inflammation, and other diseases. The corresponding sensitive materials, transducer structures, and detection principles associated with such biosensors are also addressed generally. Finally, we present an outlook on the use of electrochemical protein biosensors for disease marker detection for the next few years.

Abstract Background Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. Methods A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). Results Patients with BD showed significant cognitive impairment (p

Abstract Background Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear. Objective This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans. Materials and methods Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann–Whitney test, p

In order to clarify the succession pattern and potential functions of the microbial communities in fermented grains for Nongxiangxing baijiu, high-throughput sequencing was used to investigate the dynamic change of microbial community structure, and the correlations between microbial community structure and physicochemical indicators were analyzed at different fermentation stages. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict the potential functions of microbial communities in fermented grains. The results showed that Firmicutes, Proteobacteria, Actinobacteriota, Ascomycota, and Basidiomycota were the dominant phyla in fermented grains. The dominant genera were Lactobacillus, Bacillus, Staphylococcus, Thermoactinomyces, Kazachstania, Wickerhamomyces, Penicillium, Candida, Aspergillus, Meyerozyma, Debaryomyces, with Lactobacillus, Kazachstania and Wickerhamomyces being the absolutely dominant ones. The contents of reducing sugar and starch showed a significantly positive correlation with 8 bacterial genera (P < 0.05). Acidity and moisture content showed a significantly negative correlation with 10 bacterial genera. Some fungi were significantly correlated with physicochemical indicators. PICRUSt analysis showed that the relative abundance of functional enzymes was significantly different at different fermentation stages, and the dominant microorganisms in fermented grains participated in glycolysis, acid metabolism and ethanol synthesis to form a complete metabolic chain, indicating that the microbial community succession of fermented grains could be the major reason for the differences in metabolism at different fermentation stages. The findings of this study would provide a theoretical basis for the study of the metabolic mechanisms of microorganisms used for baijiu brewing.

Let GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon}) $ be a $ k $-dimensional generalized Reed-Solomon (GRS) code over $ \mathbb{F}_q $ associated with $ \boldsymbol{\alpha} = (\alpha_1, \ldots, \alpha_n) $ and $ \boldsymbol{\upsilon} = (\upsilon_1, \ldots, \upsilon_n) $. In this paper, we determined the dimension of the Euclidean hull GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon})\; \cap $ GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon})^\bot $, which addresses an open problem posed in [Chen et al., IEEE-TIT, 2023]. We also presentd a new approach to generating all self-dual RS codes.

Abstract Background The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. Methods The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. Results A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. The PI3K/AKT signaling pathway plays a key role in the development of ESCC. CircRNAs have been reported to be involved in the regulation of the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC. Methods Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC–MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A. Results We found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S–S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo. Conclusion The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents. Graphical Abstract The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of esophageal squamous cell carcinoma.

Abstract Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, in the 3C-like protease (3CLpro) that confer resistance to a novel non-covalent inhibitor, WU-04, which is currently in phase III clinical trials (NCT06197217). Crystallographic analysis indicates that the M49K mutation destabilizes the WU-04-binding pocket, impacting the binding of WU-04 more significantly than the binding of 3CLpro substrates. The M165V mutation directly interferes with WU-04 binding. The S301P mutation, which is far from the WU-04-binding pocket, indirectly affects WU-04 binding by restricting the rotation of 3CLpro’s C-terminal tail and impeding 3CLpro dimerization. We further explored 3CLpro mutations that confer resistance to two clinically used inhibitors: ensitrelvir and nirmatrelvir, and revealed a trade-off between the catalytic activity, thermostability, and drug resistance of 3CLpro. We found that mutations at the same residue (M49) can have distinct effects on the 3CLpro inhibitors, highlighting the importance of developing multiple antiviral agents with different skeletons for fighting SARS-CoV-2. These findings enhance our understanding of SARS-CoV-2 resistance mechanisms and inform the development of effective therapeutics.

Abstract Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut–liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite–host–microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut–liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis. Graphical Abstract

Abstract Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Abstract Background Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women’s physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited. Results This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering. Conclusion The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women’s health.

Abstract Background Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. Methods In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. Results Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. Conclusion Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

Abstract Background The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression. Methods In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups. Results The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to that in plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer. Conclusions Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.

In this study, the mesoporous material NCNT was prepared by treating carbon nanotubes (CNT) with hydrazine and subsequently loaded with Cu-Fe layered double hydroxide (CuFeLDH) to create a multiphase catalyst (CuFeLDH-NCNT). Its application as a multiphase catalyst was investigated in an ultrasound-assisted Fenton process for ciprofloxacin (CIP) degradation in aqueous solution. In addition, the impacts of catalyst dosage, ultrasonic power, H2O2 dosage, and beginning pH on CIP removal efficiency were carefully evaluated to maximize the removal efficiency of CIP. The findings indicated that the elimination rate of the initial CIP concentration of 20 mg/L surpassed 94.66% after a mere 100 min, while the TOC degradation rate was 70.4%. The high removal rate was due to the synergistic action between the nanoparticles, H2O2, and ultrasonography. The degradation intermediates of CIP were examined, and putative degradation pathways and mechanisms were postulated. HIGHLIGHTS Preparation of CuFeLDH–NCNT material as an efficient catalyst for ultrasound-assisted Fenton-like reaction.; Enhanced catalytic performance of H2O2 by the synergistic effect of CuFeLDH–NCNT.; Effective degradation of CIP by CuFeLDH–NCNT/US/H2O2.; Good stability and reusability of CuFeLDH–NCNT, with a low metal leaching rate.;

Abstract Thyroid carcinoma (THCA) is the most common endocrine cancer. Phosphodiesterase (PDE) 4 enzyme family, as specific regulator of cyclic adenosine monophosphate, may play a important role in THCA. However, few studies on PDE4 enzyme family in THCA have been reported yet. Therefore, this study aimed to systematically analyze the changes of PDE4 enzyme family in THCA, and look for potential target for THCA therapy. We systematically analyzed the expression differences, prognostic value, genetic alteration, methylation modification, and the correlation with tumor immune microenvironment of PDE4 family in THCA using several public databases, including TCGA, GEO, GSCA, TNMplot, cBioPortal, DiseaseMeth and TIMER. Besides, functional enrichment analysis and protein–protein interaction (PPI) network of PDE4 family was investigated using Metascape and STRING databases. The expression levels of PDE4A, PDE4B and PDE4D were down-regulated in THCA patients at different cancer stages, while the expression level of PDE4C was significantly up-regulated. Moreover, THCA patients with higher PDE4C expression had shorter progress free survival compared with those with lower PDE4C expression. The low genomic alteration frequencies and mildly increased methylation levels of PDE4 family were found in THCA patients. Except for PDE4A, the expression levels of PDE4B, PDE4C and PDE4D could affect many immune cells infiltration during THCA progression. Four PDE4 subtypes were all enriched in cAMP catabolic process. Nevertheless, PDE4C was not enriched in the cAMP binding signal pathway, and PDE4B was not enriched in the G alphas signaling events. Notably, PDE4C participated in cAMP metabolic process by regulating adenylate cyclases (ADCYs), which involved ADCY1, ADCY5, ADCY6, ADCY8 and ADCY9. The findings of this study provide a partial basis for the role of PDE4 family in the occurrence and development of THCA. In addition, this study also suggested that PDE4C might be a potential prognostic marker of THCA, which could serve as a reference for future basic and clinical research.

Abstract Parent–child and teacher–child relationship closeness have been shown to be crucial for children’s development of socioemotional competencies from preschool to school-age stages. However, less is known about the importance of developing close relationships with young infants and toddlers attending childcare group settings for their early socioemotional development. The current study aimed to address this gap and to explore how child gender may influence the associations. Participants included 378 Hong Kong Chinese children (196 girls; M age = 22.05 months, SD = 9.81 months) enrolled in childcare centres, along with their parents and teachers. Parents reported on children’s socioemotional competencies as well as their relationship closeness with children; teachers reported on their relationship closeness with children. Multiple group structural equation modelling was used to analyse the results. The findings showed that both parent–child and teacher–child closeness were positively associated with children’s social competence, while teacher–child closeness was negatively associated with children’s anxiety behaviour. Parents of girls reported greater parent–child closeness, higher levels of social competence, and higher levels of anxiety behaviours compared to parents of boys. Furthermore, teacher–child closeness was significantly associated with social competence exclusively among girls, while parent–child closeness was significantly associated with anxiety behaviours solely among boys. Findings are discussed in terms of the role of child gender in influencing the associations between parent–child closeness, teacher–child closeness, and children’s socioemotional competencies in the earliest years.

Abstract Background Acute kidney injury (AKI) is a common clinical disorder with complex etiology and poor prognosis, and currently lacks specific and effective treatment options. Mitochondrial dynamics dysfunction is a prominent feature in AKI, and modulation of mitochondrial morphology may serve as a potential therapeutic approach for AKI. Methods We induced ischemia–reperfusion injury (IRI) in mice (bilateral) and Bama pigs (unilateral) by occluding the renal arteries. ATP depletion and recovery (ATP-DR) was performed on proximal renal tubular cells to simulate in vitro IRI. Renal function was evaluated using creatinine and urea nitrogen levels, while renal structural damage was assessed through histopathological staining. The role of Drp1 was investigated using immunoblotting, immunohistochemistry, immunofluorescence, and immunoprecipitation techniques. Mitochondrial morphology was evaluated using confocal microscopy. Results Renal IRI induced significant mitochondrial fragmentation, accompanied by Dynamin-related protein 1 (Drp1) translocation to the mitochondria and Drp1 phosphorylation at Ser616 in the early stages (30 min after reperfusion), when there was no apparent structural damage to the kidney. The use of the Drp1 inhibitor P110 significantly improved kidney function and structural damage. P110 reduced Drp1 mitochondrial translocation, disrupted the interaction between Drp1 and Fis1, without affecting the binding of Drp1 to other mitochondrial receptors such as MFF and Mid51. High-dose administration had no apparent toxic side effects. Furthermore, ATP-DR induced mitochondrial fission in renal tubular cells, accompanied by a decrease in mitochondrial membrane potential and an increase in the translocation of the pro-apoptotic protein Bax. This process facilitated the release of dsDNA, triggering the activation of the cGAS-STING pathway and promoting inflammation. P110 attenuated mitochondrial fission, suppressed Bax mitochondrial translocation, prevented dsDNA release, and reduced the activation of the cGAS-STING pathway. Furthermore, these protective effects of P110 were also observed renal IRI model in the Bama pig and folic acid-induced nephropathy in mice. Conclusions Dysfunction of mitochondrial dynamics mediated by Drp1 contributes to renal IRI. The specific inhibitor of Drp1, P110, demonstrated protective effects in both in vivo and in vitro models of AKI.

Motivated by the excellent detonation performance of octanitrocubane, prismane is another potential backbone with high strain energy in energetic molecule design. In this work, we aim to screen out candidates of highly energetic molecules from the space of prismane derivatives. The high-throughput computation (HTC) is performed based on 200 molecules derived from the molecule space of 1503 prismane derivatives with four substituents. Based on the calculated results, the machine learning (ML) models of density, detonation velocity, detonation pressure, heat of formation and detonation heat are established, and thereby the performances of the remaining 1303 samples are predicted. It is found that the –NHNO2 group increases density, while both –NO2 and –C(NO2)3 groups promote detonation performances. Based on the detonation velocity and bond dissociation energy as criteria representing energy and molecular stability, four molecules were screened out with good detonation performance and acceptable thermal stability. This work demonstrates the efficiency of HTC and ML combined strategy for screening high-quality energetic molecules.

CDT1, a gene that shows excessive expression in various malignancies, functions as a pivotal regulator of replication licensing. In this study, we observed a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD). Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1, as confirmed by ChIP-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Furthermore, we identified an upregulation of CDT1 mRNA level in Chinese LUAD samples. Notably, in the loss-of-function assays, depletion of CDT1 in LUAD cell lines inhibited cell proliferation, migration, and invasion. Concurrently, it promoted cell apoptosis and induced G0/G1 phase arrest using MTT, flow cytometry, and Transwell assays, reinforcing its role as an oncogene.Furthermore, enhanced tumor ablation was determined in a CDT1-downregulated LUAD tumor-bearing nude mouse model. Collectively, our results strongly suggest that E2F2 positively regulates CDT1 expression and actively participates in the progression of lung adenocarcinoma, thereby providing valuable insights into identifying novel therapeutic targets for LUAD treatment.

BackgroundDexmedetomidine (DEX) is a commonly used sedative in the intensive care unit and has demonstrated cardioprotective properties against ischemia-reperfusion injury in preclinical studies. However, the protective effects of early treatment of DEX in patients with acute myocardial infarction (AMI) and its underlying mechanism are still not fully understood. This study aims to investigate the association between early DEX treatment and in-hospital mortality in patients with AMI, and to explore the potential mediating role of white blood cell (WBC) reduction in this relationship.MethodsA retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with AMI were divided into the DEX and non-DEX group, based on whether they received DEX treatment in the early stage of hospitalization. The primary outcome measured was in-hospital mortality. The study evaluated the association between DEX use and in-hospital mortality using the Kaplan-Meier (KM) method and Cox proportional hazards model. Additionally, 1:1 propensity score matching (PSM) was conducted to validate the results. Furthermore, causal mediation analysis (CMA) was utilized to explore potential causal pathways mediated by WBC reduction between early DEX use and the primary outcome.ResultsThis study analyzed data from 2,781 patients, with 355 in the DEX group and 2,426 in the non-DEX group. KM survival analysis revealed a significantly lower in-hospital mortality rate in the DEX group compared to the non-DEX group. After adjusting for multiple confounding factors, the Cox regression model demonstrated a significant positive impact of DEX on the risk of in-hospital mortality in patients with AMI, with hazard ratios (HR) of 0.50 (95% confidence interval (CI): 0.35–0.71, p < 0.0001). PSM analysis confirmed these results, showing HR of 0.49 (95% CI: 0.31–0.77, p = 0.0022). Additionally, CMA indicated that 13.7% (95% CI: 1.8%–46.9%, p = 0.022) of the beneficial effect of DEX on reducing in-hospital mortality in patients with AMI was mediated by the reduction in WBC.ConclusionThe treatment of DEX was associated with a lower risk of in-hospital mortality in patients with AMI, potentially due to its anti-inflammatory properties.

ObjectiveAuditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia.MethodsWe performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included “auditory hallucinations”, “continuous theta burst stimulation” and “transcranial magnetic stimulation”. Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data.ResultsA total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented “low risk” in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group.ConclusionsAlthough preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Guanine deaminase (GD)plays important roles in the diagnosis of liver function. However, there is no totally rapid and simple for the eatimation of GD activity in clinical application. Herein, we have constructed an enzymatic assay system with highly sensitive and strong stability for quantification of GD activity by highly double enzyme-coupling (xanthine oxidase and uric acid oxidase) and adding compound stabilizer in GD kit. In this study, we validated parameters, including reagent blank, sensitivity, accuracy, inter-batch difference, intra-batch difference, linear range. Furthermore, composite stabilizers, containing gentamicin sulfate, bovine serum albumin, and mannitol, were selected to improve stability of GD kit during long-term storage. The experimental results showed that the absorbance of the reagent blank was 0.99). All indicators met the kit requirements for clinical applications. When gentamicin sulfate, bovine serum albumin, and mannitol were used as a stabilizer, the kit remained stable for 12 months without significant loss of enzymatic activity. These results indicated that GD kit possesses high sensitivity and strong stability, which can be used for routine biochemical applications and is of great significance for the diagnosis and differential diagnosis of liver diseases.

BackgroundThe majority of patients with lung cancer exhibit drug resistance after anti-PD-1 immunotherapy, leading to shortened patient survival time. Previous studies have suggested an association between epigenetic abnormalities such as methylation and clinical response to anti-PD-1 immunotherapy, while the role of SUMOylation in resistance to anti-PD-1 antibody immunotherapy is still unclear.MethodsHere, the mRNA expression of 15 SUMO machinery components in PBMC from lung cancer patients receiving anti-PD-1 immunotherapy were analyzed using real-time PCR. Base on the percentage change in mRNA levels, the relationship between the expression of SUMO machinery components and outcomes of anti-PD-1 immunotherapy, and the influencing factors of SUMOylation were evaluated. PBMC was treated with different concentrations of 2-D08 (a specific inhibitor of SUMOylation) in vitro, and analyzed the activation and the death rates of lymphocyte subsets by flow cytometry analysis.ResultsA predictive method, base on the gene expression of three SUMO machinery components (SUMO1, SUMO3 and UBE2I), were developed to distinguish non-responders to PD-1 inhibitors. Furthermore, the number of lymphocytes in peripheral blood significantly reduced in the dysregulated SUMOylation groups (the percentage change >100 or -50 ~ -100 groups). In vitro studies confirmed that lightly low SUMOylation level improved the activation status of T and NK lymphocytes, but extremely low SUMOylation level lead to the increased death rates of lymphocytes.ConclusionOur findings implied that dysregulated gene expression of SUMO machinery components could induce the resistance of anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes. These data might provide effective circulating biomarkers for predicting the efficacy of anti-PD-1 immunotherapy, and uncovered a novel regulatory mechanism of resistance to anti-PD-1 immunotherapy.