Association between polypharmacy and 2-year outcomes among Chinese older inpatients: a multi-center cohort study.

BACKGROUND: The escalating global prevalence of polypharmacy presents a growing challenge to public health. In light of this issue, the primary objective of our study was to investigate the status of polypharmacy and its association with clinical outcomes in a large sample of hospitalized older patients aged 65 years and over. METHODS: A two-year prospective cohort study was carried out at six tertiary-level hospitals in China. Polypharmacy was defined as the prescription of 5 or more different medications daily, including over-the-counter and non-prescription medications. Baseline polypharmacy, multimorbidity, and other variables were collected when at admission, and 2-year outcomes were recorded by telephone follow-up. We used multivariate logistic regression analysis to examine the associations between polypharmacy and 2-year outcomes. RESULTS: The overall response rate was 87.2% and 8713 participants were included in the final analysis. The mean age was 72.40 years (SD = 5.72), and women accounted for 42.2%. The prevalence of polypharmacy among older Chinese inpatients is 23.6%. After adjusting for age, sex, education, marriage status, body mass index, baseline frailty, handgrip strength, cognitive impairment, and the Charlson comorbidity index, polypharmacy is significantly associated with frailty aggravation (OR 1.432, 95% CI 1.258-1.631) and mortality (OR 1.365, 95% CI 1.174-1.592), while inversely associated with readmission (OR 0.870, 95% CI 0.764-0.989). Polypharmacy was associated with a 35.6% increase in the risk of falls (1.356, 95%CI 1.064-1.716). This association weakened after adjustment for multimorbidity to 27.3% (OR 1.273, 95%CI 0.992-1.622). CONCLUSIONS: Polypharmacy was prevalent among older inpatients and was a risk factor for 2-year frailty aggravation and mortality. These results highlight the importance of optimizing medication use in older adults to minimize the risks associated with polypharmacy. Further research and implementing strategies are warranted to enhance the quality of care and safety for older individuals exposed to polypharmacy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017682, registered 09/08/2018.

An improved intelligent optimization algorithm for small-batch order production scheduling.

Although the critical path method (CPM) is effective for the integrated scheduling of small-batch orders, its overemphasis on vertical process relationships and neglect of horizontal parallel relationships have imposed limitations on scheduling, often leading to suboptimal outcomes in terms of the total product completion time. This study introduces an innovative algorithm designed to overcome these limitations and further optimize the total processing time of products. We propose a strategy of "exchanging adjacent processes on the same device", which operates based on the scheduling results of the CPM. By swapping adjacent and interchangeable processes within the constraints of the problem, this algorithm generates multiple new scheduling schemes, effectively expanding the solution space. This expansion enables the discovery of optimized solutions that leverage "horizontal parallel relationships", which is crucial for reducing the "total processing time of products". Finally, the effectiveness of the proposed algorithm is verified through experiments.

Causal relationship between circulating glutamine levels and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating respiratory disease with a median survival of less than 5 years. In recent years, glutamine has been reported to be involved in the regulation of collagen deposition and cell proliferation in fibroblasts, thereby influencing the progression of IPF. However, the relationships between glutamine and the incidence, progression, and treatment response of IPF remain unclear. Our study aimed to investigate the relationship between circulating glutamine levels and IPF, as well as its potential as a therapeutic target. METHODS: We performed a comprehensive Mendelian Randomization (MR) analysis using the most recent genome-wide association study summary-level data. A total of 32 single nucleotide polymorphisms significantly correlated to glutamine levels were identified as instrumental variables. Eight MR analysis methods, including inverse variance weighted, MR-Egger, weighted median, weighted mode, constrained maximum likelihood, contamination mixture, robust adjusted profile score, and debiased inverse-variance weighted method, were used to assess the relationship between glutamine levels with IPF. RESULTS: The inverse variance weighted analysis revealed a significant inverse correlation between glutamine levels and IPF risk (Odds Ratio = 0.750; 95% Confidence Interval : 0.592-0.951; P = 0.017). Sensitivity analyses, including MR-Egger regression and MR-PRESSO global test, confirmed the robustness of our findings, with no evidence of horizontal pleiotropy or heterogeneity. CONCLUSION: Our study provides novel evidence for a causal relationship between lower circulating glutamine levels and increased risk of IPF. This finding may contribute to the early identification of high-risk individuals for IPF, disease monitoring, and development of targeted therapeutic strategies.

TMEM100 acts as a TAK1 receptor that prevents pathological cardiac hypertrophy progression.

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

[Urban and rural differences in aggregation risk of health risk behaviors among adolescents in Wuling Mountain Area].

OBJECTIVE: Understanding urban-rural differences in the risk of aggregation of adolescents' health-risk behaviors in the Wuling Mountain Area. METHODS: From March to May 2023, 7901 adolescents from junior to junior high school and senior high school grades in 32 middle schools in 8 counties(districts) in the Wuling Mountain Area were selected as survey respondents using the multi-stage stratified random cluster sampling method, with the age of the survey respondents being(14.82±1.50) years old. There were 4047 male students(51.22%) and 3854 female students(48.78%), 5126(64.88%) in junior high school and 2775(35.12%) in senior high school.2513(31.81%) in rural schools and 5388(68.19%) in urban schools. The Questionnaire on Health Risky Behaviors of Youth in Wuling Mountain Area was used to investigate 9 health risky behaviors of youth, such as partial feeding, smoking, and drinking alcohol. The χ~2 test was used to test the difference between urban and rural adolescents' risky health behaviors and their multivariate aggregation incidence rates, and to calculate the relative risk(RR) and the actual expected ratio(O/E). RESULTS: The incidence of bivariate to quintivariate cluster of adolescent health-risk behaviors was lower in all rural schools than in urban schools(χ~2 were 60.73, 34.97, 16.89, and 9.14, P<0.05). Rural school adolescents had the highest RR value for alcohol consumption behavior(18.02), while urban school adolescents had the highest RR value for insomnia behavior(15.05). In the bivariate cluster model, the O/E values for "smoking+alcohol consumption" were highest in both rural(8.18) and urban(6.14) school adolescents. In the trivariate cluster model, the O/E values for "smoking+alcohol consumption+fighting" were highest in both rural(28.41) and urban(18.15) school adolescents. In the quadrivariate cluster model, the O/E values for "smoking+alcohol consumption+insomnia+experiencing school bullying" were highest in rural school adolescents(95.10), while the O/E values for "smoking+alcohol consumption+fighting+experiencing school bullying" were highest in urban school adolescents(42.97). In the quintivariate cluster model, the O/E values for "smoking+alcohol consumption+fighting+insomnia+experiencing school bullying" were highest in both rural(309.57) and urban(129.28) school adolescents. CONCLUSION: Adolescents in urban schools in the Wuling Mountain Area are more prone to clustering harmful health behaviors compared to those in rural schools, and there are differences in the clustering risks of harmful health behaviors and their diverse clustering patterns between urban and rural areas.

Mn-Fe dual-metal Assemblages on Carbon-coated Al2O3 Spheres for Catalytic Ozonation Oxidation: Structure, Performance, and Reaction Mechanism.

Catalysts with high catalytic activity and low production cost are important for industrial application of heterogeneous catalytic ozonation (HCO). In this study, we designed a carbon-coated aluminum oxide carrier (C-Al2O3) and reinforced it with Mn-Fe bimetal assemblages to prepare a high-performance catalyst Mn-Fe/C-Al2O3. The results showed that the carbon embedding significantly improved the abundance of surface oxygen functional groups, conductivity, and adsorption capacity of γ-Al2O3, while preserving its exceptional mechanical strength as a carrier. The prepared Mn-Fe/C-Al2O3 catalyst exhibited satisfactory catalytic ozonation activity and stability in the degradation of p-nitrophenol (PNP). Electron paramagnetic resonance (EPR) and quenching experiments reveal that radical (•OH and •O2-) and nonradical oxidation (1O2) dominated the PNP degradation process. Theoretical calculations corroborated that the anchored atomic Fe and Mn sites regulated the local electronic structure of the catalyst. This modulation effectively promoted the activation of O3 molecules, resulting in the generation of atomic oxygen species (AOS) and reactive oxygen species (ROS). The economic analysis on Mn-Fe/C-Al2O3 revealed that it was a cost-competitive catalyst for HCO. This study not only deepens the understanding on the reaction mechanism of HCO with transition metal/carbon composite catalysts, also provides a high-performance and cost-competitive ozone catalyst for prospective application.

Analyzing Risk Factors for Delayed Extubation Following Posterior Approach Surgery for Congenital Scoliosis: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Investigate the risk factors for delayed extubation after posterior approach orthopedic surgery in patients with congenital scoliosis. METHODS: The clinical data of patients who received surgery for congenital scoliosis at the First Affiliated Hospital of Xinjiang Medical University between January 2021 and July 2023 have been gathered. Patients are categorized into the usual and the delayed extubation groups, depending on the duration of tracheal intubation after surgery. The study employs univariate and multivariate logistic regression models to examine the clinical characteristics of the two cohorts and discover potential risk factors linked to delayed extubation. In addition, a prediction model is created to visually depict the significance of each risk factor in terms of weight according to the nomogram. RESULTS: A total of 119 patients (74.8% females), with a median age of 15 years, are included. A total of 32 patients, accounting for 26.9% of the sample, encountered delayed extubation. Additionally, 13 patients (10.9%) suffered perioperative complications, with pneumonia being the most prevalent. The multivariate regression analysis revealed that the number of osteotomy segments, postoperative hematocrit, postoperative Interleukin-6 levels, and weight are predictive risk factors for delayed extubation. CONCLUSIONS: Postoperative hematocrit and Interleukin-6 level, weight, and number of osteotomy segments can serve as independent risk factors for predicting delayed extubation, with combined value to assist clinicians in evaluating the risk of delayed extubation of postoperative congenital scoliosis patients, improving the success rate of extubation, and reducing postoperative treatment time in the intensive care unit.

HPV 16/18 E7 oncoprotein detection as a promising triage strategy for HPV 16/18-positive patients: A prospective multicenter study with a 2-year follow up.

OBJECTIVE: To explore the effectiveness of HPV 16/18 E7 oncoprotein in detecting high-grade cervical intraepithelial neoplasia (CIN) and predicting disease outcomes in HPV 16/18-positive patients. METHODS: The present study was a cross-sectional study with a 2-year follow up. We collected 915 cervical exfoliated cell samples from patients who tested positive for HPV 16/18 in gynecologic clinics of three tertiary hospitals in Beijing from March 2021 to October 2022 for HPV 16/18 E7 oncoprotein testing. Subsequently, 2-year follow up of 408 patients with baseline histologic CIN1 or below were used to investigate the predictive role of HPV 16/18 E7 oncoprotein in determining HPV persistent infection and disease progression. RESULTS: The positivity rate of the HPV 16/18 E7 oncoprotein assay was 42.06% (249/592) in the inflammation/CIN 1 group and 85.45% (277/324) in the CIN2+ group. For CIN2+ detection, using the HPV 16/18 E7 oncoprotein assay combined with HPV 16/18 testing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.45%, 57.94%, 52.57%, and 87.95%, respectively. During the 2-year follow up, the sensitivity, specificity, PPV, and NPV for predicting persistent HPV infection were 48.44%, 58.21%, 34.64%, and 71.18% in the baseline inflammation and CIN1 group. CONCLUSIONS: As a triage method for high-grade CIN screening in HPV 16/18-positive patients, HPV 16/18 E7 oncoprotein demonstrated a relatively high NPV, making it suitable for clinical use in triaging HPV 16/18-positive cases and potentially reducing the colposcopic referral rate. HPV 16/18 E7 oncoprotein exhibited a preferably predictive value in determining HPV infection outcomes and disease progression.

Kinase CPK10 regulates low light-induced tomato flower drop downstream of IDL6 in a calcium-dependent manner.

Flower drop is a major cause for yield loss in many crops. Previously, we found that tomato (Solanum lycopersicum) INFLORESCENCE DEFICIENT IN ABSCISSION-Like (SlIDL6) contributes to flower drop induced by low light. However, the molecular mechanisms by which SlIDL6 acts as a signal to regulate low light-induced abscission remain unclear. In this study, SlIDL6 was found to elevate cytosolic Ca2+ concentrations ([Ca2+]cyt) in the abscission zone (AZ), which was required for SlIDL6-induced flower drop under low light. We further identified that one calcium-dependent protein kinase gene (SlCPK10) was highly expressed in the AZ and up-regulated by SlIDL6-triggered [Ca2+]cyt. Over-expression and knockout of SlCPK10 in tomato resulted in accelerated and delayed abscission, respectively. Genetic evidence further indicated that knockout of SlCPK10 significantly impaired the function of SlIDL6 in accelerating abscission. Furthermore, Ser-371 phosphorylation in SlCPK10 dependent on SlIDL6 was necessary and sufficient for its function in regulating flower drop, probably by stabilizing the SlCPK10 proteins. Taken together, our findings reveal that SlCPK10, as a downstream component of the IDL6 signaling pathway, regulates flower drop in tomato under low light stress.

SARS­CoV­2 infection exacerbates diaphragmatic eventration: A case report.

Adult congenital localized diaphragmatic eventration (DE) is an uncommon condition that, due to the absence of notable symptoms, is often ignored and is consequently not frequently treated following diagnosis. Furthermore, the progression of localized DE into complete DE is rare. The recent coronavirus disease 2019 pandemic has placed a strain on global health care systems, including those in China, and exacerbated several underlying medical complications and diseases. This has resulted in a rapid progression of underlying diseases and even death in cases of diabetes or pre-existing respiratory diseases and other chronic conditions. The present study describes the case of a patient with congenital localized DE that progressed to complete DE following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient had a medical history of localized DE with persistent cough, chest tightness and abdominal distension following infection with SARS-CoV-2. Chest X-ray and computed tomography examinations confirmed the diagnosis of complete DE on the left side. Therefore, the patient underwent thoracic surgery for left-sided diaphragmatic plication. At the 6-month follow-up visit, the patient had recovered well and did not show any complications. Overall, the present study demonstrated that SARS-CoV-2 infection exacerbated the progression of left-sided congenital localized DE, which had no obvious symptoms, to complete DE accompanied by severe symptoms.

Emerging role of liver-bone axis in osteoporosis.

Background: Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone. Methods: Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research). Results: Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis. Conclusion: During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.The translational potential of this article is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.

Developing a Novel Prognostic Model Based on Muscle-Invasive Bladder Cancer Types: A Multicenter Retrospective Cohort Study of Patients Who Received Radical Cystectomy and Chemotherapy.

BACKGROUND: To develop a prognostic model to manage patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) and chemotherapy. PATIENTS AND METHODS: Clinicopathologic characteristics and survival data were collated from a North American database to develop a model. Genomic and clinicopathologic data were also obtained from European and Asian databases to externally validate the model. Patients were classified as either "primary" or "progressive" MIBC according to non-muscle invasive stage history. Optimized cancer-specific survival (CSS) models, based on MIBC types, were constructed using Cox's proportional hazard regression. Differences of biological function and tumor immunity, between two risk-based groups stratified according to the prognostic model, were estimated. RESULTS: There were 2631 participants in the American cohort, 291 in the European cohort and 142 in the Asian cohort. Under Cox's regression analysis, tumor stage, lymph node stage, age, ethnicity, and MIBC types were independent CSS predictors (all p < 0.05). The constructed nomogram, which integrated these variables, improved the predictive power. This model had good discrimination and calibration. Patients were categorized into high- or low-risk groups according to the total points calculated. Kaplan-Meier curves revealed that patients in the high-risk group had poorer survival (p < 0.001). This was confirmed with two external validation cohorts (both with p < 0.001). Higher stromal scores and increased M0 and M2 macrophage numbers were observed in samples from the high-risk group, whereas regulatory T cells had lower infiltration in these populations (all with p < 0.05). CONCLUSIONS: This MIBC type-based nomogram provides accurate CSS predictions, which could help improve patient management and clinical decision-making.

Association between breastfeeding duration and neurodevelopment in Chinese children aged 2 to 3 years.

OBJECTIVE: The aim of this study was to explore the relationship between breastfeeding duration and neurodevelopment in children aged 2 to 3 years in a Chinese population. METHODS: This study was based on a cross-sectional survey. The data were from the National Nutrition and Health Systematic Survey for children in China which was conducted from 2019 to 2020. Characteristics of parents and children and the breastfeeding duration were obtained using interview-administered questionnaires. Children's neuropsychological development was assessed by a trained child health care physician using the Child Psychological Development Scale. A multivariable linear regression model was used to analyze the association between breastfeeding duration and neuropsychological development. RESULTS: A total 1290 children aged 2-3 years were included in the present analysis. In multivariable linear regression models, after adjustment for potential confounders, children who were breastfed for 7-12 months had a 3.59-point increase in gross motor development (ß = 3.59; 95 % confidence interval [CI]: 1.23 to 6.34), a 3.73-point increase in fine motor development (ß = 3.73; 95 % CI: 1.09 to 6.47), and a 2.87-point in language development (ß = 2.87; 95 % CI: 1.12 to 5.31) compared with those who were never breastfed. Children who were breastfed for > 12 months had a 3.77-point increase in fine motor development (ß = 3.77; 95 % CI: 0.98 to 6.86) compared with those who were never breastfed. CONCLUSIONS: Longer breastfeeding duration was associated with increased gross motor, fine motor, and language scores in our study population. Mothers in China should be encouraged to initiate and continue breastfeeding.

Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms, Clinical Management and Innovative Treatment.

With the continuous refinement of therapeutic measures, the survival rate of tumor patients has been improving year by year, while cardiovascular complications related to cancer therapy have become increasingly prominent. Exploring the mechanism and prevention strategy of cancer therapy-related cardiovascular toxicity (CTR-CVT) remains one of the research hotspots in the field of Cardio-Oncology in recent years. Cardiotoxicity of anticancer drugs involves heart failure, myocarditis, hypertension, arrhythmias and vascular toxicity, mechanistically related to vascular endothelial dysfunction, ferroptosis, mitochondrial dysfunction and oxidative stress. To address the cardiotoxicity induced by different anticancer drugs, various therapeutic measures have been put in place, such as reducing the accumulation of anticancer drugs, shifting to drugs with less cardiotoxicity, using cardioprotective drugs, and early detection. Due to the very limited treatments available to ameliorate anticancer drugs-induced cardiotoxicity, a few innovations are being shifted from animal studies to human studies. Examples include mitochondrial transplantation. Mitochondrial transplantation has been proven to be effective in in vivo and in vitro experiments. Several recent studies have demonstrated that intercellular mitochondrial transfer can ameliorate doxorubicin(DOX)-induced cardiotoxicity, laying the foundation for innovative therapies in anticancer drugs-induced cardiotoxicity. In this review, we will discuss the current status of anticancer drugs-induced cardiotoxicity in terms of the pathogenesis and treatment, with a focus on mitochondrial transplantation, and we hope that this review will bring some inspiration to you.

Bioprinted mesenchymal stem cell microfiber-derived extracellular vesicles alleviate unilateral renal ischemia-reperfusion injury and fibrosis by inhibiting tubular epithelial cells ferroptosis.

Renal unilateral ischemia-reperfusion injury (UIRI) constitutes a significant global health challenge, with poor recovery leading to chronic kidney disease and subsequent renal fibrosis. Extracellular vesicles (EVs) present substantial potential benefits for renal diseases. However, the limited yield and efficacy of EVs produced through traditional methodologies (2D-EVs) severely restrict their widespread application. Moreover, the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored. In this study, we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology (3D-EVs) with a tail vein injection method, introducing a novel treatment strategy for UIRI. Our comparison of the biological functions of 2D-EVs and 3D-EVs, both in vitro and in vivo, reveals that 3D-EVs significantly outperform 2D-EVs. Specifically, in vitro, 3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation (H/R)-induced injuries by reducing epithelial-mesenchymal transformation, extracellular matrix deposition, and ferroptosis. In vivo, 3D-EVs exhibit enhanced therapeutic effects, as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys. We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells (TECs) ferroptosis through the modulation of SLC7A11 and GPX4 expression. Our findings suggest that bioprinted mesenchymal stem cells microfiber-derived EVs significantly ameliorate renal UIRI, opening new avenues for effective and efficient EV-based therapies in UIRI treatment.

Electrical Kinetic Model of a Hydroxylated Graphene FET Gas Sensor.

Graphene transistor sensors, with advantages such as facile surface functionalization and high sensitivity, have gained extensive research interest in gas detection applications. This study fabricated back-gated graphene transistors and employed a hydroxylation scheme for the surface functionalization of graphene. On the basis of the interaction mechanisms between gas molecules and graphene's electrical properties, a compact electrical kinetics model considering the gas-solid surface reaction of graphene transistors is proposed. The model can accurately predict the electrical kinetic performance and can be used to optimize sensor characteristics. The bias condition of a higher response can be rapidly determined. In addition, the density of hydroxyl groups on graphene is revealed to be the direction of improvement and a key factor of response. Hence, the gas detection capacity of sensors with varying densities of hydroxyl groups was assessed concerning ammonia gas, and design technology co-optimization (DTCO) is realized. Measurement results show that the sensor with 70 s of hydroxylation time has a 7.7% response under 22 ppm ammonia gas.

Lnc557 promotes Bombyx mori nucleopolyhedrovirus replication by interacting with BmELAVL1 to enhance its stability and expression.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen that threatens the growth and sustainability of the sericultural industry. Currently, accumulated studies showed that long non-coding RNAs (lncRNAs) play important roles in the genesis and progression of various viruses and host-pathogens interactions. However, the functions and regulatory mechanisms of lncRNAs in insect-virus interaction are still limited. In this study, transcriptome sequencing and ribosome profiling sequencing (Ribo-seq) were performed in the BmNPV-infected midgut and control tissue, and a total of 9 differentially expressed (DE) lncRNAs and 27 small ORFs (sORFs) with micropeptide coding potential were identified. Among them, lncRNA XR_001139971.3 (lnc557) is verified to be significantly up-regulated upon BmNPV infection and may have the potential to encode a small peptide (ORF-674). The subcellular localization experiment showed that lnc557 was expressed in the cytoplasm. Overexpression of lnc557 promotes BmNPV replication and vice versa. By combining RNA pull-down, mass spectrometry, protein truncation and RNA immunoprecipitation (RIP) assays, we confirmed that lnc557 can bind to the RRM-5 domain of BmELAVL1 protein. Subsequently, we found that lnc557 could promote the expression of BmELAVL1 by enhancing the stability of BmELAVL1. Further, enhancing the expression of BmELAVL1 can promote the proliferation of BmNPV, while knockdown shows the opposite effect. Our data suggest that lnc557-mediated BmELAVL1 expression enhancement could play a positive role in BmNPV replication, which will provide a new insight into the molecular mechanism of interaction between Bombyx mori and virus.

Comparison of eliminating artificial hydronephrosis and creating artificial hydronephrosis in percutaneous nephrolithotomy in oblique supine position.

INTRODUCTION: The safety and effectiveness of percutaneous nephroscopic surgery without artificial hydronephrosis remain controversial, and there are few relevant studies. This retrospective study aimed to compare the efficacy of two different methods of eliminating and creating artificial hydronephrosis in percutaneous nephrolithotomy(PCNL) in the oblique supine position. METHODS: This is a retrospective study. A total of 162 patients who underwent PCNL in an oblique supine position at our hospital were divided into two groups according to the surgical method: the free artificial hydronephrosis group (Group A) and the artificial hydronephrosis group (Group B). Group A was directly treated with PCNL under ultrasound guidance and group B was treated with artificial hydronephrosis before PCNL. Several outcomes were measured, including operation time, stone clearance rate, and incidence of complications. RESULTS: The operation time in Group A lower than that in Group B, and the incidence of sepsis was significantly lower in group A than in Group B (P<0.05). There was no statistical difference in stone clearance rate, success rate of primary establishment of puncture channel, unilateral change in perioperative red blood cell count, change in perioperative renal function, and perioperative complications (except sepsis) between the two groups (P>0.05). CONCLUSION: For experienced physicians, percutaneous nephrolithotomy without artificial hydronephrosis in an oblique supine position can be attempted to reduce the number of surgical steps without affecting the stone clearance rate and increasing the occurrence of complications.

HBsAg and TLR7/8 dual-targeting antibody-drug conjugates induce sustained anti-HBV activity in AAV/HBV mice: a preliminary study.

Hepatitis B virus (HBV) infection is a significant global health concern due to elevated immunosuppressive viral antigen levels, the host immune system's inability to manage HBV, and the liver's immunosuppressive conditions. While immunotherapies utilizing broadly reactive HBV neutralizing antibodies present potential due to their antiviral capabilities and Fc-dependent vaccinal effects, they necessitate prolonged and frequent dosing to achieve optimal therapeutic outcomes. Toll-like receptor 7/8 (TLR7/8) agonists have been demonstrated promise for the cure of chronic hepatitis B, but their systemic use often leads to intense side effects. In this study, we introduced immune-stimulating antibody conjugates which consist of TLR7/8 agonists 1-[[4-(aminomethyl)phenyl]methyl]-2-butyl-imidazo[4,5-c]quinolin-4-amine (IMDQ) linked to an anti-hepatitis B surface antigen (HBsAg) antibody 129G1, and designated as 129G1-IMDQ. Our preliminary study highlights that 129G1-IMDQ can prompt robust and sustained anti-HBsAg specific reactions with short-term administration. This underscores the conjugate's potential as an effective strategy for HBsAg clearance and seroconversion, offering a fresh perspective for a practical therapeutic approach in the functional cure of CHB. Highlights: HBV-neutralizing antibody 129G1 was linked with a TLR7/8 agonist small molecule compound IMDQ.Treatment with 129G1-IMDQ has shown significant promise in lowering HBsAg levels in AAV/HBV mice.129G1-IMDQ were eliciting a strong and lasting anti-HBsAg immune response after short-term treatment in AAV/HBV mice.