Dual-site molecular glues for enhancing protein-protein interactions of the CDK12-DDB1 complex.

Protein-protein interactions (PPIs) stabilization with molecular glues plays a crucial role in drug discovery, albeit with significant challenges. In this study, we propose a dual-site approach, targeting the PPI region and its dynamic surroundings. We conduct molecular dynamics simulations to identify critical sites on the PPI that stabilize the cyclin-dependent kinase 12 - DNA damage-binding protein 1 (CDK12-DDB1) complex, resulting in further cyclin K degradation. This exploration leads to the creation of LL-K12-18, a dual-site molecular glue, which enhances the glue properties to augment degradation kinetics and efficiency. Notably, LL-K12-18 demonstrates strong inhibition of gene transcription and anti-proliferative effects in tumor cells, showing significant potency improvements in MDA-MB-231 (88-fold) and MDA-MB-468 cells (307-fold) when compared to its precursor compound SR-4835. These findings underscore the potential of dual-site approaches in disrupting CDK12 function and offer a structural insight-based framework for the design of cyclin K molecular glues.

Myocardial hypertrophy: the differentiation of uremic, hypertensive, and hypertrophic cardiomyopathies by cardiac MRI.

OBJECTIVES: To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC's etiology and further support the development of therapeutic strategies. METHODS: A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. RESULTS: UC patients demonstrated significantly higher native T1 (p < 0.001 for all) and T2 (p < 0.002 for all) values compared with the other three groups. UC patients revealed higher left atrial reservoir strain rate (p < 0.001 for all) and left atrial conduit strain rate (p < 0.001 for all) absolute values as compared with HTN and HCM patients. A significant correlation between T1 and T2 values in UC patients (r = 0.511, p < 0.001) was found. The combination of T1 values and strain parameters was the best discriminator between UC and HTN patients (AUC = 0.872, 95% CI: 0.801-0.943) and between UC and HCM patients (AUC = 0.840, 95% CI: 0.746-0.934). CONCLUSION: UC reveals distinguishing tissue characteristics as evidenced by T1 and T2 mapping, as well as distinguishing functional strain parameters as compared with other hypertrophic phenotypes such as HTN and HCM. CRITICAL RELEVANCE STATEMENT: The use of CMR imaging in UC patients offers incremental information to elucidate its complex etiology, contributing to ongoing discourse on effective treatment pathways. KEY POINTS: This study investigated uremic, hypertensive, and hypertrophic cardiomyopathies using cardiac MRI. UC patients have higher T1 and T2 values and better preserved cardiac function. Combined strain and T1 values distinguish UC from other cardiomyopathies.

Risk factors for postoperative ileus in hysterectomy: A systematic review and meta-analysis.

OBJECTIVE: The study intended to evaluate the risk factors of postoperative ileus in hysterectomy patients. STUDY DESIGN: Systematic review and meta-analysis. METHODS: This study conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Program for Systematic Review and Meta-analysis statement. PubMed, Web of Science, Embase, the Cochrane Library and China National Knowledge Internet were searched. The search period was restricted from the earliest records to March 2024. Key words used were: (hysterectomy) AND (postoperative ileus OR postoperative intestinal obstruction OR ileus OR intestinal obstruction). Two researchers screened literatures and extracted data, and used Newcastle-Ottawa scale and Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies to evaluate their quality. Then, Stata17 software was used for statistical analysis. RESULT: A total of 11 literatures were included. Personal factors and previous history of disease factors of postoperative ileus in hysterectomy patients included use opioids (OR = 3.91, 95%CI: 1.08-14.24), dysmenorrhea (OR = 2.51, 95%: 1.25-5.05), smoking (OR = 1.55, 95%: 1.18-2.02), prior abdominal or pelvic surgery (OR = 1.46, 95%CI: 1.16-1.83) and age (OR = 1.03, 95%: 1.02-1.04). Surgery-related factors included perioperative transfusion (OR = 4.50, 95%CI: 3.29-6.16), concomitant bowel surgery (OR = 3.79, 95%CI: 1.86-7.71), anesthesia technique (general anesthesia) (OR = 2.73, 95%CI: 1.60, 4.66), adhesiolysis (OR = 1.97, 95%CI: 1.52-2.56), duration of operation (OR = 1.78, 95%CI: 1.32-2.40), operation approach (laparoscopic hysterectomy) (OR = 0.43, 95%CI: 0.29-0.64) and operation approach (vaginal hysterectomy) (OR = 0.35, 95%CI: 0.18-0.69). CONCLUSIONS: The results of this study were personal factors and previous history of disease factors, surgery-related factors, which may increase the risk of postoperative ileus in hysterectomy patients. After the conclusion of risk factors, more accurate screening and identification of high-risk groups can be conducted and timely preventive measures can be taken to reduce the incidence of postoperative ileus. TRIAL REGISTRATION: The study protocol for this meta-analysis was registered (CRD42023407167) with the PROSPERO database (www.crd.york.ac.uk/prospero).

MsABCG1, ATP-Binding Cassette G transporter from Medicago Sativa, improves drought tolerance in transgenic Nicotiana Tabacum.

Drought has a devastating impact, presenting a formidable challenge to agricultural productivity and global food security. Among the numerous ABC transporter proteins found in plants, the ABCG transporters play a crucial role in plant responses to abiotic stress. In Medicago sativa, the function of ABCG transporters remains elusive. Here, we report that MsABCG1, a WBC-type transporter highly conserved in legumes, is critical for the response to drought in alfalfa. MsABCG1 is localized on the plasma membrane, with the highest expression observed in roots under normal conditions, and its expression is induced by drought, NaCl and ABA signalling. In transgenic tobacco, overexpression of MsABCG1 enhanced drought tolerance, evidenced by increased osmotic regulatory substances and reduced lipid peroxidation. Additionally, drought stress resulted in reduced ABA accumulation in tobacco overexpressing MsABCG1, demonstrating that overexpression of MsABCG1 enhanced drought tolerance was not via an ABA-dependent pathway. Furthermore, transgenic tobacco exhibited increased stomatal density and reduced stomatal aperture under drought stress, indicating that MsABCG1 has the potential to participate in stomatal regulation during drought stress. In summary, these findings suggest that MsABCG1 significantly enhances drought tolerance in plants and provides a foundation for developing efficient drought-resistance strategies in crops.

Sustained-release mechanism of ß-Cyclodextrin/cationic cellulose-stabilized Pickering emulsions loaded with citrus essential oil.

Citrus oil (CO) is a commonly used natural flavor with high volatility, which is not conducive to sustained release under food environmental stress. This study constructed novel ß-cyclodextrin/cationic cellulose nanocrystal (ß-CD/C-CNC) complexes via noncovalent interaction, which were used to stabilize CO-loaded Pickering emulsions (PEß-CD/C-CNC). The C-CNC greatly improved the physical stability, droplet dispersion and viscoelasticity of PEß-CD/C-CNC by forming a tight network structure, as verified by rheological behavior. Moreover, C-CNC improved the wettability of ß-CD/C-CNC complexes and enhanced the interaction between adjacent ß-CD/C-CNC complexes. C-CNC also contributed to the interfacial viscoelasticity, hydrated mass, and layer thickness via the interfacial dilational modulus and QCM-D. ß-CD/C-CNC complexes adsorbed on the oil-water interface gave rise to a dense filling layer as a physical barrier, enhancing the sustained-release performance of PEß-CD/C-CNC by limiting diffusion of citrus essential oil into the headspace. This study provides new technical approaches for aroma retention in the food industry.

FOXC1 and FOXC2 Ablation Causes Abnormal Valvular Endothelial Cell Junctions and Lymphatic Vessel Formation in Myxomatous Mitral Valve Degeneration.

BACKGROUND: Mitral valve (MV) disease including myxomatous degeneration is the most common form of valvular heart disease with an age-dependent frequency. Genetic evidence indicates that mutations of the transcription factor FOXC1 are associated with MV defects, including MV regurgitation. In this study, we sought to determine whether murine Foxc1 and its closely related factor, Foxc2, are required in valvular endothelial cells (VECs) for the maintenance of MV leaflets, including VEC junctions and the stratified trilaminar ECM (extracellular matrix). METHODS: Adult mice carrying tamoxifen-inducible, vascular endothelial cell (EC), and lymphatic EC-specific, compound Foxc1;Foxc2 mutations (ie, EC-Foxc-DKO and lymphatic EC-Foxc-DKO mice, respectively) were used to study the function of Foxc1 and Foxc2 in the maintenance of MVs. The EC and lymphatic EC mutations of Foxc1/c2 were induced at 7 to 8 weeks of age by tamoxifen treatment, and abnormalities in the MVs of these mutant mice were assessed via whole-mount immunostaining, immunohistochemistry/RNAscope, Movat pentachrome/Masson Trichrome staining, and Evans blue injection. RESULTS: EC deletions of Foxc1 and Foxc2 in mice resulted in abnormally extended and thicker MVs by causing defects in the regulation of ECM organization with increased proteoglycan and decreased collagen. Notably, reticular adherens junctions were found in VECs of control MV leaflets, and these reticular structures were severely disrupted in EC-Foxc-DKO mice. PROX1 (prospero homeobox protein 1), a key regulator in a subset of VECs on the fibrosa side of MVs, was downregulated in EC-Foxc1/c2 mutant VECs. Furthermore, we determined the precise location of lymphatic vessels in murine MVs, and these lymphatic vessels were aberrantly expanded and dysfunctional in EC-Foxc1/c2 mutant MVs. Lymphatic EC deletion of Foxc1/c2 also resulted in similar structural/ECM abnormalities as seen in EC-Foxc1/c2 mutant MVs. CONCLUSIONS: Our results indicate that Foxc1 and Foxc2 are required for maintaining the integrity of the MV, including VEC junctions, ECM organization, and lymphatic vessel formation/function to prevent myxomatous MV degeneration.

Virus-Mimetic Extracellular-Vesicle Vaccine Boosts Systemic and Mucosal Immunity via Immune Recruitment.

Mucosal vaccines can prevent viruses from infecting the respiratory mucosa, rather than only curtailing infection and protecting against the development of disease symptoms. The SARS-CoV-2 spike receptor-binding domain (RBD) is a compelling vaccine target but is undermined by suboptimal mucosal immunogenicity. Here, we report a SARS-CoV-2-mimetic extracellular-vesicle vaccine developed using genetic engineering and dendritic cell membrane budding. After mucosal immunization, the vaccine recruits antigen-presenting cells rapidly initiating a strong innate immune response. Notably, it obviates the need for adjuvants and can induce germinal center formation through both intramuscular and intratracheal vaccination. It not only elicits high levels of RBD-specific antibodies but also stimulates extensive cellular immunity in the respiratory mucosa. A sequential immunization strategy, starting with an intramuscular injection followed by an intratracheal booster, significantly bolsters mucosal immunity with high levels of IgA and tissue-resident memory T cell responses, thereby establishing a formidable defense against pseudovirus infection.

Mitochondrial control of proteasomal Psmb5 drives the differentiation of tissue-resident memory T cells in patients with rheumatoid arthritis.

OBJECTIVE: To explore T-cell-intrinsic mechanisms underpinning the mal-differentiation of tissue-resident memory T (Trm) cells in patients with rheumatoid arthritis (RA). METHODS: Circulating T cells from RA patients and healthy individuals were used for Trm cell differentiation. The role of Hobit in Trm differentiation was investigated through targeted silencing experiments. Psmb5 expression regulation was explored by identifying BRD2 as a key transcription factor, with the interaction validated through ChIP-qPCR. The impact of BRD2 succinylation on Trm differentiation was examined by manipulating succinyl-CoA levels in T cells. Humanized NSG chimeras representing synovitis provided insights into Trm infiltration in RA synovitis and were utilized for translational experiments. RESULTS: In RA patients, a notable predisposition of CD4+ T cells towards differentiation into Trm cells was observed, demonstrating a positive correlation with the Disease Activity Score 28. Remarkably, Hobit was a pivotal facilitator in the formation of RA CD4+ Trm cells. Mechanistic studies unveiled the dysregulation of proteasomal Psmb5 in T cells of RA patients as the key factor contributing to elevated Hobit protein levels. The deficiency of proteasomal Psmb5 was intricately linked to BRD2, with succinylation exerting a significant impact on Psmb5 transcription and Trm cell differentiation. This heightened BRD2 succinylation was attributed to elevated levels of mitochondrial succinyl-CoA in RA T cells. Consequently, targeting succinyl-CoA within CD4+ T cells controlled the inflammation of synovial tissues in humanized chimeras. CONCLUSION: Mitochondrial succinyl-CoA fosters the succinylation of BRD2, resulting in compromised transcription of proteasomal Psmb5 and the differentiation of Trm cells in RA.

Determinants for the development of creative tourism: A stakeholder perspective.

This study aims to investigate the determinants that contribute to the sustainable development of creative tourism, a transformative shift from traditional cultural tourism which possess high economic potential. Grounded in stakeholder theory, a qualitative approach was employed to explore the perspectives of 23 existing suppliers of creative tourism in the Greater Bay Area, China, through semi-structured, in-depth interviews with key management in exiting business, this study uncovers determinants for the development of creative tourism. The findings shed light on the significance of fostering creative synergies and their implications for sustainable growth in the industry. While a positive attitude from suppliers is crucial, this study emphasizes the importance of mutual understanding of creativity to generate momentum, integration of local culture and regional knowledge, and the development of creative products. Moreover, removing barriers faced by suppliers such as a lack of financial support, insufficient government policies and regulations, and inadequate infrastructure is imperative for sustainable development. This research significantly contributes to the existing body of knowledge by providing an overview of the current research status on suppliers' perspectives towards creative tourism. It offers valuable directions for future scholarly inquiry in this field. Moreover, the research offers valuable insights that can assist policymakers and destination planners in developing efficient policies and sustainable planning approaches.

[Mechanism of protective effect of n-butanol extract of Pulsatilla Decoction on vaginal epithelial cells under Candida albicans stimulation through EGFR/MAPK pathway based on transcriptomics].

This study aimed to investigate the protective effect and its underlying mechanism of n-butanol extract of Pulsatilla Decoction(BEPD) containing medicinal serum on vaginal epithelial cells under Candida glabrata stimulation via the epidermal growth factor receptor/mitogen activated protein kinase( EGFR/MAPK) pathway based on transcriptomics. A vulvovaginal candidiasis(VVC) mouse model was established first and transcriptome sequencing was performed for the vaginal mucosa tissues to analyze the gene expression differences among the control, VVC model, and BEPD intervention groups. Simultaneously, BEPD-containing serum and fluconazole-containing serum were prepared. A431 cells were divided into the control, model, blank serum, fluconazole-containing serum, BEPD-containing serum, EGFR agonist and EGFR inhibitor groups. Additionally, in vitro experiments were conducted using BEPD-containing serum, fluconazole-containing serum, and an EGFR agonist and inhibitor to investigate the intervention mechanisms of BEPD on C. glabrata-induced vaginal epithelial cell damage. Cell counting kit-8(CCK-8) assay was utilized to determine the safe concentrations of C. glabrata, drug-containing serum, and compounds on A431 cells. Enzyme-linked immunosorbent assay(ELISA)was employed to measure the expression levels of interleukin(IL)-1ß, IL-6, granulocyte-macrophage colony-stimulating factor(GMCSF), granulocyte CSF(G-CSF), chemokine(C-X-C motif) ligand 20(CCL20), and lactate dehydrogenase(LDH). Gram staining was used to evaluate the adhesion of C. glabrata to vaginal epithelial cells. Flow cytometry was utilized to assess the effect of C.glabrata on A431 cell apoptosis. Based on the transcriptomics results, immunofluorescence was performed to measure the expressions of p-EGFR and p-ERK1/2 proteins, while Western blot validated the expressions of p-EGFR, p-ERK1/2, p-C-Fos, p-P38, Bax and Bcl-2 proteins. Sequencing results showed that compared with the VVC model, BEPD treatment up-regulated 1 075 genes and downregulated 927 genes, mainly enriched in immune-inflammatory pathways, including MAPK. Mechanistically, BEPD significantly reduced the expression of p-EGFR, p-ERK1/2, p-C-Fos and p-P38, as well as the secretion of IL-1ß, IL-6, GM-CSF, G-CSF and CCL20, LDH release induced by C. glabrata, and the adhesion of C. glabrata to A431 cells, suggesting that BEPD exerts a protective effect on vaginal epithelial cells damaged by C. glabrata infection by modulating the EGFR/MAPK axis. In addition, BEPD downregulated the pro-apoptotic protein Bax expression and up-regulated the anti-apoptotic protein Bcl-2 expression, leading to a reduction in C. glabrata-induced cell apoptosis. In conclusion, this study reveals that the intervention of BEPD in C. glabrata-induced VVC may be attributed to its regulation of the EGFR/MAPK pathway, which protects vaginal epithelial cells.

Multifaceted roles of IKZF1 gene, perspectives from bench to bedside.

The IKZF1 gene encodes a transcription factor that belongs to the family of zinc-finger DNA-binding proteins associated with chromatin remodeling. The protein product, IKAROS, had been proved to regulate lymphopoiesis. Subsequent mouse model studies have further confirmed its regulating role in lymphopoiesis as well as in hematopoiesis; besides, it associates with immune function, certain immune disorders like common variable immunodeficiency and dysgammaglobulinemia have been proved to be associated with germline IKZF1 mutations. Dysfunction of IKAROS also bears paramount significance in leukemic transformation and alterations of IKZF1 gene predicts a poor prognosis in hematological malignancies. As an independent prognostic marker, IKZF1 has been incorporated in the risk stratification of BCP-ALL and stratification-guided therapy has also been generated. In this review, we provide a concise and comprehensive overview on the multifaceted roles of IKZF1 gene.

Ethnic-specific genetic susceptibility loci for endometriosis in Taiwanese-Han population: a genome-wide association study.

Endometriosis is a common gynecological disorder affecting around 10% of reproductive-age women. Although many hypotheses were proposed, genetic alteration has been considered as one of the key factors promoting pathogenesis. Due to racial/ethnic disparities in the process of hormone regulation and nutrition metabolism, a genome-wide association study (GWAS) with 2794 cases and 27,940 controls was conducted in a Taiwanese-Han population. Our study identified five significant susceptibility loci for endometriosis, and three of them, WNT4 (on the 1p36.12), RMND1 (6q25.1), and CCDC170 (6q25.1), have been previously associated with endometriosis across different populations, including European and Japanese descent cohorts. Other two including C5orf66/C5orf66-AS2 (5q31.1) and STN1 (10q24.33) are newly identified ones. Functional network analysis of potent risk genes revealed the involvement of cancer susceptibility and neurodevelopmental disorders in endometriosis development. In addition, long non-coding RNAs (lncRNAs) C5orf66 and C5orf66-AS2 can interact with many RNA-binding proteins (RBPs) which can influence RNA metabolic process, mRNA stabilization, and mRNA splicing, leading to dysregulation in tumor-promoting gene expression. Those findings support clinical observations of differences in the presentation of endometriosis in Taiwanese-Han population with higher risks of developing deeply infiltrating/invasive lesions and the associated malignancies.

CBIL-VHPLI: a model for predicting viral-host protein-lncRNA interactions based on machine learning and transfer learning.

Virus‒host protein‒lncRNA interaction (VHPLI) predictions are critical for decoding the molecular mechanisms of viral pathogens and host immune processes. Although VHPLI interactions have been predicted in both plants and animals, they have not been extensively studied in viruses. For the first time, we propose a new deep learning-based approach that consists mainly of a convolutional neural network and bidirectional long and short-term memory network modules in combination with transfer learning named CBIL‒VHPLI to predict viral-host protein‒lncRNA interactions. The models were first trained on large and diverse datasets (including plants, animals, etc.). Protein sequence features were extracted using a k-mer method combined with the one-hot encoding and composition-transition-distribution (CTD) methods, and lncRNA sequence features were extracted using a k-mer method combined with the one-hot encoding and Z curve methods. The results obtained on three independent external validation datasets showed that the pre-trained CBIL‒VHPLI model performed the best with an accuracy of approximately 0.9. Pretraining was followed by conducting transfer learning on a viral protein-human lncRNA dataset, and the fine-tuning results showed that the accuracy of CBIL‒VHPLI was 0.946, which was significantly greater than that of the previous models. The final case study results showed that CBIL‒VHPLI achieved a prediction reproducibility rate of 91.6% for the RIP-Seq experimental screening results. This model was then used to predict the interactions between human lncRNA PIK3CD-AS2 and the nonstructural protein 1 (NS1) of the H5N1 virus, and RNA pull-down experiments were used to prove the prediction readiness of the model in terms of prediction. The source code of CBIL‒VHPLI and the datasets used in this work are available at https://github.com/Liu-Lab-Lnu/CBIL-VHPLI for academic usage.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

[Whole Process Analysis and Fate Behavior of Microplastics in Urban Wastewater Treatment Plants, Including their Occurrence Forms, Components, and Removal Efficiency].

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that： fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance； the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances （PET, PBT）, cellulose, and polypropylene （PP） were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was （73 ±5） n·L-1, the effluent abundance was （14 ±2） n·L-1, and the overall removal rate was （80.8 ±12.1）%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids （49.2 ±7.4）% and secondary sedimentation tanks （92.4 ±13.9）%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.

Effects of seaweed fertilizer application on crops' yield and quality in field conditions in China-A meta-analysis.

Seaweed fertilizer, formulated primarily with seaweed extract as its main ingredient, has been extensively studied and found to significantly improve nutrient use efficiency, increase crop yield and quality, and enhance soil properties under field conditions. This growing body of evidence shows that seaweed fertilizer is a suitable option for sustainable agriculture in China. However, a comprehensive and quantitative analysis of the overall effects of seaweed fertilizer application in China is lacking. To address this gap, we conducted a meta-analysis of relevant studies on the effects of seaweed fertilizers under field conditions in China with MetaWin and SPSS software. Our analysis examined the effects of seaweed fertilizers on crop yield, quality, and growth under different preparation methods, application techniques, and regions. Our results showed that the application of seaweed fertilizer led to a significant average increase in crop yield of 15.17% compared with the control treatments. Root & tuber crops exhibited the most pronounced response, with a yield boost of 21.19%. Moreover, seaweed fertilizer application significantly improved crop quality, with elevations in the sugar-acid ratio (38.32%) vitamin C (18.07%), starch (19.65%), and protein (11.45%). In addition, plant growth parameters such as height, stem thickness, root weight, and leaf area showed significant enhancement with seaweed fertilizer use. The yield-increasing effect of seaweed fertilizers varied depending on their preparation and use method, climate, and soil of application location. Our study provides fundamental reference data for the efficient and scientific application of seaweed fertilizers in agricultural practices.

Effectiveness of molnupiravir for treating COVID-19 in patients with psychiatric disorders.

Objectives: This study investigated the clinical effectiveness of molnupiravir for treating non-hospitalized COVID-19 patients with pre-existing psychiatric disorder. Methods: This retrospective cohort study used the TriNetX research network to identify patients with psychiatric disorder who experienced non-hospitalized COVID-19 between 1 January 2022, and 1 May 2023. The propensity score matching (PSM) method was used to match patients receiving molnupiravir (treated group) with those who did not (untreated group). The outcome included short-term outcomes - the composite of all-cause hospitalization or death within 30 days and the risk of post-COVID-19 conditions up to a year after COVID-19 diagnosis. Results: Two groups of 9,421 patients, each with balanced baseline characteristics, were identified using the PSM method. During the 30-day follow-up, treated group was associated with a reduced risk of hospitalization or mortality compared to untreated group (HR, 0.760; 95% CI, 0.665-0.869). Compared to untreated group, treated group also exhibited a decreased risk of experiencing post-COVID-19 conditions, including chest/throat pain (HR, 0.615; 95% CI, 0.543-0.696), abnormal breathing (HR, 0.761; 95% CI, 0.687-0.884), abdominal symptoms (HR, 0.748; 95% CI, 0.674-0.831), fatigue (HR, 0.718; 95% CI, 0.638-0.808), headache (HR, 0.753; 95% CI, 0.665-0.852), cognitive symptoms (HR, 0.769; 95% CI, 0.630-0.940), myalgia (HR, 0.647; 95% CI, 0.530-0.789), cough (HR, 0.867; 95% CI, 0.770-0.978), and palpitation (HR, 0.641; 95% CI, 0.534-0.770) during the 1-year follow-up. Conclusion: Molnupiravir could be associated with lower rates of all-cause hospitalization or death and also lower risk of post-COVID-19 condition among non-hospitalized COVID-19 patients with pre-existing psychiatric disorder.

Public health education using social learning theory: a systematic scoping review.

BACKGROUND: Public health education (PHE) in social environments plays a crucial role in mitigating the impact of public health events, especially with the recent surge in global incidents. Social learning theory (SLT) provides a strong theoretical foundation for implementing PHE. The objective of this study is to conduct a systematic scoping review of PHE using SLT, synthesizing the target populations, types of research, main findings, and future directions. METHODS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR) guidelines. We conducted a comprehensive search of five electronic databases (Web of Science, Scopus, PubMed, ProQuest, and APA PsycInfo) for English articles related to PHE using SLT. Two reviewers independently screened the titles and abstracts. Descriptive statistics were utilized to analyze the characteristics of the articles included in the study, followed by a comprehensive narrative analysis of the results. RESULTS: Research on PHE using SLT mainly focuses on adolescents, students, special patients, and vulnerable populations. The study sample includes seven research types and nine commonly used experimental methods. Four modes of PHE using SLT are identified, along with four types of summarized research results. CONCLUSION: PHE research based on SLT can be prioritized for preventing widespread infectious diseases, spreading fundamental public health information, and assisting patients with particular illnesses. To enhance the implementation of PHE, researchers and policymakers should integrate online and offline health education resources, ensure the accessibility of up-to-date information, and leverage digital technologies in PHE. More highly interactive and participatory health education courses will be established in social learning environments to encourage public participation in PHE.

Quantification of subclinical plaque characteristics and perivascular fat using coronary computed tomography angiography (CCTA) among individuals with human immunodeficiency virus (HIV).

Background: People infected with human immunodeficiency virus (PIWH) have a higher risk of cardiovascular events. This study was designed to compare the differences in plaque characteristics and perivascular fat between subclinical coronary atherosclerosis in PIWH and healthy controls (HC) by coronary computed tomography angiography (CCTA). We also assessed the associations between human immunodeficiency virus (HIV) infection, antiretroviral therapy (ART), and coronary artery disease (CAD). Methods: This cross-sectional study included a total of 158 PIWH and 79 controls. CCTA was used to evaluate coronary artery plaque prevalence, coronary stenosis severity, plaque composition, plaque volume, and perivascular fat attenuation index (FAI). Logistic regression analyses were used to assess the associations between the prevalence of coronary artery plaque and HIV-related clinical indicators. Results: There was no difference in total coronary artery plaque prevalence between PIWH and controls (44.3% vs. 32.9%; P=0.09), but the prevalence of noncalcified plaque was significantly higher in PIWH compared with the controls (33.5% vs. 16.5%; P=0.006). After adjustment for age, sex, statin use, and family history of cardiovascular disease (CVD), the prevalence of noncalcified plaque remained 2 times higher in PIWH [odds ratio (OR), 2.082; 95% confidence interval (CI): 1.007-4.304; P=0.048]. The perivascular FAI measured around the left anterior descending artery (LAD) was higher in PIWH (-71.4±5.7 vs. -73.5±7.0; P=0.03) compared with that of the controls. The intra-group analyses of PIWH suggested that the decrease in nadir CD4+ T-cell count was associated with the increased prevalence of noncalcified plaque (OR, 4.139; 95% CI: 1.312-13.060; P=0.02). Conclusions: PIWH have a higher risk of developing noncalcified plaque and greater perivascular fat. In addition, the increased noncalcified plaque prevalence in PIWH may be associated with the immunodeficiency caused by HIV.