Stigma and its associations with self-confidence and sexual relations in 4 types of premature ejaculation.

BACKGROUND: Although men with premature ejaculation (PE) always show more negative emotions, including embarrassment, guilt and worry, this may be related to the stigma of PE. To investigated stigma and its associations with self-confidence and sexual relations in 4 PE syndromes, a survey was conducted in our hospital from December 2018 to December 2019 among 350 men with self-reported PE and 252 men without self-reported PE. The stigma, self-confidence and sexual relations were assessed by the Social Impact Scale (SIS) and Self-Esteem and Relationship questionnaire (SEAR), respectively. Ejaculation control, sexual life satisfaction and distress caused by PE were evaluated by the Index of PE. RESULTS: Men with self-reported PE had higher internalized shame and social isolation scores and lower SEAR scores than control subjects. The highest score of internalized shame and social isolation and the lowest score of SEAR appeared in men with lifelong PE (LPE). After age adjustment, the positive relationships were stronger between distress about PE and internalized shame. Whereas, the stronger negative associations were found between social isolation and sexual satisfaction. The strongest association was observed between social isolation and sexual relationship. Therefore, the stigma associated with PE adversely affects the self-confidence, self-esteem, and sexual relationships of men with PE. CONCLUSION: Men with PE, especially LPE, have a high level of stigma and disharmonious sexual relations, and often lack self-confidence and self-esteem, which have a certain negative impact on their physical and mental health and life. These will be the key issues to be considered when we formulate a personalized treatment plan for PE.

RéSUMé: CONTEXTE: Bien que les hommes atteints d'éjaculation précoce (EP) montrent plus d'émotions négatives toujours, notamment de l'embarras, de la culpabilité et de l'inquiétude, cela peut être lié à la stigmatisation de l'EP. Afin d'étudier la stigmatisation et ses associations avec la confiance en soi et les relations sexuelles dans 4 syndromes d'EP, une enquête a été menée dans notre hôpital de décembre 2018 à décembre 2019 auprès de 350 hommes atteints d'EP autodéclarée et de 252 hommes sans EP autodéclarée. La stigmatisation, la confiance en soi et les relations sexuelles ont été évaluées respectivement à l'aide de l'échelle d'impact social (SIS) et du questionnaire sur l'estime de soi et les relations (SEAR). Le contrôle de l'éjaculation, la satisfaction de la vie sexuelle et la détresse causée par l'EP ont été évalués par l'indice d'EP. RéSULTATS: Les hommes ayant une EP autodéclarée avaient des scores de honte intériorisée et d'isolement social plus élevés, et des scores SEAR inférieurs, à ceux des sujets témoins. Le score le plus élevé de honte intériorisée et d'isolement social, et le score le plus bas de SEAR, sont apparus chez les hommes atteints d'EP à vie (EPL). Après ajustement sur l'âge, les relations positives étaient plus fortes entre la détresse due à l'EP et la honte intériorisée. Les associations négatives les plus fortes ont été trouvées entre l'isolement social et la satisfaction sexuelle. Par conséquent, la stigmatisation associée à l'EP affecte négativement la confiance en soi, l'estime de soi et les relations sexuelles des hommes atteints d'EP. CONCLUSION: Les hommes atteints d'EP, en particulier ceux atteints d'EPL, ont un niveau élevé de stigmatisation et de relations sexuelles disharmonieuses, et ils manquent souvent de confiance en soi et d'estime de soi; ce qui a un impact négatif certain sur leur santé physique et mentale, et sur leur vie. Ce seront les questions clés à prendre en compte lorsque nous formulerons un plan de traitement personnalisé pour l'EP.

The association between shift work, shift work sleep disorders and premature ejaculation in male workers.

OBJECTIVE: Shift work and Shift Work Sleep Disorder (SWSD) are known to affect the secretion of several neurotransmitters and hormones associated with premature ejaculation (PE). However, their specific influence on the regulation of male ejaculation remains unclear. This study explores the relationship between shift work, SWSD, and PE. METHODS: From April to October 2023, a cross-sectional survey was conducted across five regions of China to explore the work schedules, sleep quality, and sexual function of male workers. Participants' sleep quality was evaluated using a validated SWSD questionnaire, and their erectile function and ejaculatory control were assessed with the International Inventory of Erectile Function (IIEF-5) scores and Premature Ejaculation Diagnostic Tool (PEDT) scores, respectively. Univariate and multivariate linear regression analyses were employed to identify risk factors associated with PE. Confounders were controlled using multiple regression models, and clinical prediction models were developed to predict PE onset and assess the contribution of risk factors. RESULTS: The study included 1239 eligible participants, comprising 840 non-shift workers and 399 shift workers (148 with SWSD and 251 without SWSD). Compared to non-shift working males, those involved in shift work (ß 1.58, 95% CI 0.75 - 2.42, p < 0.001) and those suffering from SWSD (ß 2.86, 95% CI 1.86 - 3.85, p < 0.001) they had significantly higher PEDT scores. Additionally, we identified daily sleep of less than six hours, depression, anxiety, diabetes, hyperlipidemia, frequent alcohol consumption (more than twice a week), and erectile dysfunction as risk factors for PE. The predictive model for PE demonstrated commendable efficacy. CONCLUSION: Both shift work and SWSD significantly increase the risk of premature ejaculation, with the risk magnifying in tandem with the duration of shift work. This study reveals the potential impact of shift work and SWSD on PE and provides new theoretical foundations for the risk assessment and prevention of this condition.

Cell Membrane Engineered Polypeptide Nanonets Mimicking Macrophage Aggregates for Enhanced Antibacterial Treatment.

Drug-resistant bacterial infections and their lipopolysaccharide-related inflammatory complications continue to pose significant challenges in traditional treatments. Inspired by the rapid initiation of resident macrophages to form aggregates for efficient antibacterial action, this study proposes a multifunctional and enhanced antibacterial strategy through the construction of novel biomimetic cell membrane polypeptide nanonets (R-DPB-TA-Ce). The design involves the fusion of end-terminal lipidated polypeptides containing side-chain cationic boronic acid groups (DNPLBA) with cell membrane intercalation engineering (R-DPB), followed by coordination with the tannic acid-cerium complex (TA-Ce) to assemble into a biomimetic nanonet through boronic acid-polyphenol-metal ion interactions. In addition to the ability of RAW 264.7 macrophages cell membrane components' (R) ability to neutralize lipopolysaccharide (LPS), R-DPB-TA-Ce demonstrated enhanced capture of bacteria and its LPS, leveraging nanoconfinement-enhanced multiple interactions based on the boronic acid-polyphenol nanonets skeleton combined with polysaccharide. Utilizing these advantages, indocyanine green (ICG) is further employed as a model drug for delivery, showcasing the exceptional treatment effect of R-DPB-TA-Ce as a new biomimetic assembled drug delivery system in antibacterial, anti-inflammatory, and wound healing promotion. Thus, this strategy of mimicking macrophage aggregates is anticipated to be further applicable to various types of cell membrane engineering for enhanced antibacterial treatment.

Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic: A Cross-sectional Study.

OBJECTIVE: The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement. The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019 (COVID-19) pandemic and analyzed the influence of psychological state on medication safety. METHODS: Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits. Depression was evaluated by the Self-Rating Depression Scale (SDS). Anxiety was evaluated by the Self-Rating Anxiety Scale (SAS). Medication adherence was evaluated by the Morisky scale. RESULTS: A total of 309 patients (aged 52.2±11.4 years) were included in the present study. The SDS score of all included patients was 36.9±9.4 points, of which 11 (3.6%) patients were diagnosed as having depression. The SAS score of all included patients was 43.1±9.3 points, of which 71 (23%) patients were diagnosed as having anxiety. Seven patients (2.3%) had both anxiety and depression. Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression. Regarding anxiety, patients who underwent repeated operations had a 2.264-fold greater risk, and patients who received combination medication had a 2.140-fold greater risk. More bleeding events and coagulation disorders could be observed in patients with anxiety, depression or both. When anxiety occurred, patients showed worse medication adherence. However, depression had no significant effect on medication adherence. CONCLUSION: During the COVID-19 pandemic, the detection rate of mental illnesses such as anxiety and depression was high, which seriously affected the medication safety of warfarin. Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

Differential interplay between multimorbidity patterns and frailty and their mutual mediation effect on mortality in old age.

BACKGROUND: Multimorbidity and frailty often concurrently occur among older adults. OBJECTIVES: To assess the reciprocal association between multimorbidity (condition count and patterns) and frailty and examine the mutual mediation effect of multimorbidity and frailty in their associations with mortality among Chinese older adults. METHODS: This nationwide population-based longitudinal study included 16,563 participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey who were surveyed in 2008 and followed up in 2011, 2014, and 2018. Frailty phenotype was assessed by the modified Fried criteria and vital status was ascertained from family members. Cross-lagged panel model (CLPM) was used to test bidirectional associations between multimorbidity and frailty. The direct and indirect effects of multimorbidity and frailty on mortality were evaluated using the combined CLPM with survival analysis. RESULTS: Three multimorbidity patterns were identified: cardiometabolic diseases, cognitive-sensory disorder, and arthritis-digestive-respiratory diseases. The number of chronic conditions and cognitive-sensory disease pattern showed bidirectional associations with frailty across waves (range for ß: 0.046-0.109; all P < 0.001), while cardiometabolic and arthritis-digestive-respiratory patterns unidirectionally predicted frailty change. Furthermore, frailty mediated 23%-27% of the association between multimorbidity and mortality. Only the number of conditions and cognitive-sensory disease pattern were significant mediators in the association between frailty and mortality, with the proportion of mediation ranging 4%-12%. CONCLUSIONS: Multimorbidity measures including condition count and cognitive-sensory disease pattern are bi-directionally associated with frailty in older adults. These multimorbidity measures and frailty partially mediated each other's association with mortality, with frailty acting as a more prominent pathway in the association between multimorbidity and mortality.

Impact of antiphospholipid antibodies on cardiac valve lesions in systemic lupus erythematosus: a systematic review and meta-analysis.

This meta-analysis assesses antiphospholipid antibodies' (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58-3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26-10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47-4.93, p = 0.001), and anti-ß2 glycoprotein I (aß2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17-2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05-6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.

Identification and validation of potential common biomarkers for papillary thyroid carcinoma and Hashimoto's thyroiditis through bioinformatics analysis and machine learning.

There is a growing body of evidence suggesting that Hashimoto's thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein-protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.

Wireless Powered Microwave-Light Conversion Platform with Dual-Stimulus Nanoresponder Coating for Deep-Seated Photodynamic Therapy.

Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively and minimally damage eliminate deep-seated infection, owing to the poor penetrability of light and low reactive oxygen species (ROS) stimulation capability of MW. Herein, an implantable and wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which external MW can be converted into internal light via MW wireless-powered light-emitting chips, is designed to eradicate deep-seated tissue infections by MW-induced deep-seated photodynamic therapy. In application, CNT-FeTHQ-TS is implanted at internal lesions, and the chip emits light under external MW irradiation. Subsequently, CNT-FeTHQ coating in the platform can respond to both MW and light simultaneously to generate ROS and MW-hyperthermia for rapid and precise sterilization at focus. Importantly, MW also improves the photodynamic performance of CNT-FeTHQ by introducing vacancies in FeTHQ to facilitate the photoexcitation process and changing the spin state of electrons to inhibit the complexation of photogenerated electron-hole pairs, which were confirmed by simulation calculations and in situ MW-irradiated photoluminescence experiments. In vivo, CNT-FeTHQ-TS can effectively cure mice with Staphylococcus aureus infection in dorsal subcutaneous tissue. This work overcomes the key clinical limitations of safe energy transmission and conversion for treating deep-seated infections.

Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Prediction of developmental toxic effects of fine particulate matter (PM2.5) water-soluble components via machine learning through observation of PM2.5 from diverse urban areas.

The global health implications of fine particulate matter (PM2.5) underscore the imperative need for research into its toxicity and chemical composition. In this study, zebrafish embryos exposed to the water-soluble components of PM2.5 from two cities (Harbin and Hangzhou) with differences in air quality, underwent microscopic examination to identify primary target organs. The Harbin PM2.5 induced dose-dependent organ malformation in zebrafish, indicating a higher level of toxicity than that of the Hangzhou sample. Harbin PM2.5 led to severe deformities such as pericardial edema and a high mortality rate, while the Hangzhou sample exhibited hepatotoxicity, causing delayed yolk sac absorption. The experimental determination of PM2.5 constituents was followed by the application of four algorithms for predictive toxicological assessment. The random forest algorithm correctly predicted each of the effect classes and showed the best performance, suggesting that zebrafish malformation rates were strongly correlated with water-soluble components of PM2.5. Feature selection identified the water-soluble ions F- and Cl- and metallic elements Al, K, Mn, and Be as potential key components affecting zebrafish development. This study provides new insights into the developmental toxicity of PM2.5 and offers a new approach for predicting and exploring the health effects of PM2.5.

Integrated 68 Ga-FAPI-04 PET/MR in Pancreatic Cancer : Prediction of Tumor Response and Tumor Resectability After Neoadjuvant Therapy.

PURPOSE: This study aimed to investigate the value of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. PATIENTS AND METHODS: This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68 Ga-FAPI PET/MRI from June 2020 to June 2022. The SUV max , SUV mean , SUV peak , uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBR muscle ) and blood (TBR blood ) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3-4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. RESULTS: A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders ( P < 0.05). The SUV max , SUV mean , and TBR muscle were significantly higher in unresectable patients than in resectable ones ( P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUV max (AUC = 0.838, P = 0.016), SUV mean (AUC = 0.812, P = 0.026), and TBR muscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response ( P = 0.032) and was an independent predictor of tumor response ( P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability ( P = 0.043). CONCLUSIONS: This pilot study demonstrates the value of 68 Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.

Berberine ameliorates chronic intermittent hypoxia-induced cardiac remodelling by preserving mitochondrial function, role of SIRT6 signalling.

Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.

Maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion for pesticide delivery.

The salt-responsiveness of Pickering emulsions has significantly influenced their applications due to the large amount of salt on the surface of plant leaves. The present study provided a maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion (MACNCs-HIPPEs) that was stable to high-concentration salt and used for pesticide delivery. The stability of MACNCs-HIPPEs was investigated by adjusting the oil-phase volume fraction (φ), the MACNCs concentration, NaCl dosages, and the rheological properties. The high internal phase Pickering emulsion was obtained at φ of 0.8 and MACNCs concentration of 2wt% and showed excellent salt stability (NaCl, 1200 mM) and significant storage stability (60 days). The sustained release of imidacloprid (IMI) from imidacloprid-loaded MACNCs-HIPPEs (IMI@MACNCs-HIPPEs) showed a positive correlation to the temperature (15°C, 25°C, 35°C), indicating clear thermo-responsiveness of the prepared pesticide formulation. The test of spread and retention of IMI@MACNCs-HIPPEs on the leaf surface showed a significant advantage compared with the commercial IMI water dispersible granules (CG). All the advantages mentioned above showed the excellent potential of the MACNCs-HIPPEs in delivering lipophilic pesticides.

A novel mechanism behind irreversible development of cartilage degradation driven articular cartilage defects revealed by rat model: The chain reaction initiated by extracellular vesicles delivered LOC102546541.

BACKGROUND: Articular cartilage defects (ACD) are injuries with a diameter greater than 3 mm, resulting from wear and tear on joints. When the diameter of the defect exceeds 6 mm, it can further damage the surrounding joint cartilage, causing osteoarthritis (OA). Try to explain why OA is an irreversible disease, we hypothesize that damaged articular chondrocytes (DAC) may have reduced capacities to repair cartilage because its extracellular vesicle (EVs) that might directly contribute to OA formation. METHODS: In this study, DAC-EVs and AC-EVs were isolated using ultracentrifugation. Next-generation sequencing was employed to screen for a pathogenic long non-coding RNA (lncRNA). After verifying its function in vitro, the corresponding small interfering RNA (siRNA) was constructed and loaded into extracellular vesicles, which were then injected into the knee joint cavities of rats. RESULTS: The results revealed that DAC-EVs packaged lncRNA LOC102546541 acts as a competitive endogenous RNA (ceRNA) of MMP13, down-regulating miR-632. Consequently, the function of MMP13 in degrading the extracellular matrix is enhanced, promoting the development of osteoarthritis. CONCLUSIONS: This study uncovered a novel mode of OA pathogenesis using rat models, which DAC deliver pathogenic LOC102546541 packaged EVs to normal articular chondrocytes, amplifying the degradation of the extracellular matrix. Nonetheless, the functions of highly homologous human gene of LOC102546541 need to be verified in the future.

Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients.

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

Preparation and Performance Study of Boron Adsorbent from Plasma-Grafted Polypropylene Melt-Blown Fibers.

In this study, the plasma graft polymerization technique was used to graft glycidyl methacrylate (GMA) onto polypropylene (PP) melt-blown fibers, which were subsequently aminated with N-methyl-D-glucamine (NMDG) by a ring-opening reaction, resulting in the formation of a boron adsorbent denoted as PP-g-GMA-NMDG. The optimal conditions for GMA concentration, grafting time, grafting temperature, and the quantity of NMDG were determined using both single factor testing and orthogonal testing. These experiments determined the optimal process conditions to achieve a high boron adsorption capacity of PP-g-GMA-NMDG. Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersion spectrum analysis (EDS), and water contact angle measurements were performed to characterize the prepared adsorbent. Boron adsorption experiments were carried out to investigate the effects of pH, time, temperature, and boron concentration on the boron adsorption capacity of PP-g-GMA-NMDG. The adsorption isotherms and kinetics of PP-g-GMA-NMDG for boron were also studied. The results demonstrated that the adsorption process followed a pseudo-second-order kinetic model and a Langmuir isothermal model. At a pH of 6, the maximum saturation adsorption capacity of PP-g-GMA-NMDG for boron was 18.03 ± 1 mg/g. In addition, PP-g-GMA-NMDG also showed excellent selectivity for the adsorption of boron in the presence of other cations, such as Na+, Mg2+, and Ca2+, PP-g-GMA-NMDG, and exhibited excellent selectivity towards boron adsorption. These results indicated that the technique of preparing PP-g-GMA-NMDG is both viable and environmentally benign. The PP-g-GMA-NMDG that was made has better qualities than other similar adsorbents. It has a high adsorption capacity, great selectivity, reliable repeatability, and easy recovery. These advantages indicated that the adsorbents have significant potential for widespread application in the separation of boron in water.

Poloxamer 407 modified collagen/ß-tricalcium phosphate scaffold for localized delivery of alendronate.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/ß-tricalcium phosphate (ß-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit.

BACKGROUND: Cirrhotic patients with acute-on-chronic liver failure (ACLF) in the intensive care unit (ICU) have a poor but variable prognoses. Accurate prognosis evaluation can guide the rational management of patients with ACLF. However, existing prognostic scores for ACLF in the ICU environment lack sufficient accuracy. AIM: To develop a new prognostic model for patients with ACLF in ICU. METHODS: Data from 938 ACLF patients in the Medical Information Mart for Intensive Care (MIMIC) database were used to develop a new prognostic model (MIMIC ACLF) for ACLF. Discrimination, calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve (AUROC), calibration curve and decision curve analysis (DCA), respectively. MIMIC ACLF was then externally validated in a multiple-center cohort, the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in China. RESULTS: The MIMIC ACLF score was determined using nine variables: ln (age) × 2.2 + ln (white blood cell count) × 0.22 - ln (mean arterial pressure) × 2.7 + respiratory failure × 0.6 + renal failure × 0.51 + cerebral failure × 0.31 + ln (total bilirubin) × 0.44 + ln (internationalized normal ratio) × 0.59 + ln (serum potassium) × 0.59. In MIMIC cohort, the AUROC (0.81/0.79) for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF (0.76/0.74), Model for End-stage Liver Disease (MELD; 0.73/0.71) and MELD-Na (0.72/0.70) (all P < 0.001). The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing scores. The net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50% threshold probability. The superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external cohorts. CONCLUSION: We developed and validated a new prognostic model with satisfactory accuracy for cirrhotic patients with ACLF hospitalized in the ICU. The model-based risk stratification and online calculator might facilitate the rational management of patients with ACLF.

Amino acid metabolomics and machine learning for assessment of post-hepatectomy liver regeneration.

Objective: Amino acid (AA) metabolism plays a vital role in liver regeneration. However, its measuring utility for post-hepatectomy liver regeneration under different conditions remains unclear. We aimed to combine machine learning (ML) models with AA metabolomics to assess liver regeneration in health and non-alcoholic steatohepatitis (NASH). Methods: The liver index (liver weight/body weight) was calculated following 70% hepatectomy in healthy and NASH mice. The serum levels of 39 amino acids were measured using ultra-high performance liquid chromatography-tandem mass spectrometry analysis. We used orthogonal partial least squares discriminant analysis to determine differential AAs and disturbed metabolic pathways during liver regeneration. The SHapley Additive exPlanations algorithm was performed to identify potential AA signatures, and five ML models including least absolute shrinkage and selection operator, random forest, K-nearest neighbor (KNN), support vector regression, and extreme gradient boosting were utilized to assess the liver index. Results: Eleven and twenty-two differential AAs were identified in the healthy and NASH groups, respectively. Among these metabolites, arginine and proline metabolism were commonly disturbed metabolic pathways related to liver regeneration in both groups. Five AA signatures were identified, including hydroxylysine, L-serine, 3-methylhistidine, L-tyrosine, and homocitrulline in healthy group, and L-arginine, 2-aminobutyric acid, sarcosine, beta-alanine, and L-cysteine in NASH group. The KNN model demonstrated the best evaluation performance with mean absolute error, root mean square error, and coefficient of determination values of 0.0037, 0.0047, 0.79 and 0.0028, 0.0034, 0.71 for the healthy and NASH groups, respectively. Conclusion: The KNN model based on five AA signatures performed best, which suggests that it may be a valuable tool for assessing post-hepatectomy liver regeneration in health and NASH.

Differences in proteomic profiles and immunomodulatory activity of goat and cow milk fat globule membrane.

This study aimed to clarify the composition and bioactivity differences between goat and cow milk fat globule membrane (MFGM) protein by proteomic, and the immunomodulatory activity of MFGM proteins was further evaluated by using mouse splenic lymphocytes in vitro. A total of 257 MFGM proteins showed significant differences between goat and cow milk. The upregulated and unique MFGM proteins in goat milk were significantly enriched in the positive regulation of immune response, negative regulation of Interleukin-5 (IL-5) secretion, and involved in nucleotide-binding oligomerization domain (NOD)-like receptor signaling. The contents of IL-2 and Interferon-γ in the supernatant of spleen lymphocytes treated with goat MFGM proteins were much higher than those of IL-4 and IL-5, suggesting a Th1-skewed immune response. These results revealed that goat MFGM proteins could possess better immunomodulatory effects as compared to cow milk. Our findings may provide new insights to elucidate the physiological functions and nutritional of goat milk.