Surface Nanostructures Promote Droplet Splash on Hot Substrates.

Splash, one of the most visually apparent droplet dynamics, can manifest on any surface above a certain impact velocity, regardless of surface wettability. Previous studies demonstrate that elevating the substrate temperature can suppress droplet splash, which is unfavorable for many practical applications, such as spray cooling and combustion. Here, we report that the suppression effect of substrate temperature on splash is nullified by utilizing surfaces with nanostructures. By manipulating air evacuation time through surface nanostructures, we have identified a pathway for precise control over the splash threshold and the ability to tailor the dependence of the splash onset on surface temperature. We further propose a theoretical criterion to determine different splash regimes by considering the competition between air evacuation and the development of flow instabilities. Our findings underscore the crucial role of nanostructures in splash dynamics, offering valuable insights for the control of splash in various industrial scenarios.

Shaping membrane vesicles by adsorption of hinge-like nanoparticles.

The adsorption of particles onto fluid membranes can lead to membrane-mediated interactions between particles that promote their self-assembly and lead to changes in membrane morphology. However, in contrast with rigid particles, relatively little is known about deformable particles, which introduce additional complexities due to the mutual deformability of the particles and the membrane. Here, we use Monte Carlo simulations and umbrella sampling to investigate the equilibrium properties of hinge-like particles adsorbed on membrane vesicles by means of anisotropic, attractive interactions. We vary the hinge stiffness, adhesive area fraction, patterning of adhesive regions, and number of adsorbed particles. Depending on their properties, isolated particles can conform to the vesicle, induce invaginations of the membrane, or exhibit multistable behavior in which they sample distinct classes of configurations due to the interplay of particle and membrane deformations. With two adsorbed particles, the properties of the particles can be used to promote aggregation, bias the particles to different parts of the vesicle, or stabilize the coexistence of both cases. With multiple adsorbed particles, the number and type control their organization and collective impact on the vesicle, which can adopt shapes ranging from roughly spherical to dumbbell-like and multi-lobed. Our results highlight how modifying the mechanical properties and patterned adhesion of deformable particles, which is possible with DNA nanotechnology, influences their self-assembly and the resulting shapes of both the particles and vesicles.

Identification and characterization of the CRK gene family in the wheat genome and analysis of their expression profile in response to high temperature-induced male sterility.

Cysteine-rich receptor-like kinases (CRKs) play many important roles during plant development, including defense responses under both biotic and abiotic stress, reactive oxygen species (ROS) homeostasis, callose deposition and programmed cell death (PCD). However, there are few studies on the involvement of the CRK family in male sterility due to heat stress in wheat (Triticum aestivum L.). In this study, a genome-wide characterization of the CRK family was performed to investigate the structural and functional attributes of the wheat CRKs in anther sterility caused by heat stress. A total of 95 CRK genes were unevenly distributed on 18 chromosomes, with the most genes distributed on chromosome 2B. Paralogous homologous genes with Ka/Ks ratios less than 1 may have undergone strong purifying selection during evolution and are more functionally conserved. The collinearity analysis results of CRK genes showed that wheat and Arabidopsis (A. thaliana), foxtail millet, Brachypodium distachyon (B. distachyon), and rice have three, 12, 15, and 11 pairs of orthologous genes, respectively. In addition, the results of the network interactions of genes and miRNAs showed that five miRNAs were in the hub of the interactions map, namely tae-miR9657b-5p, tae-miR9780, tae-miR9676-5p, tae-miR164, and tae-miR531. Furthermore, qRT-PCR validation of the six TaCRK genes showed that they play key roles in the development of the mononuclear stage anthers, as all six genes were expressed at highly significant levels in heat-stressed male sterile mononuclear stage anthers compared to normal anthers. We hypothesized that the TaCRK gene is significant in the process of high-temperature-induced sterility in wheat based on the combination of anther phenotypes, paraffin sections, and qRT-PCR data. These results improve our understanding of their relationship.

Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions.

Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.

Constructing 3D Zincophilic Skeleton in Nitrogen-Doped Carbon Hybrid Fibers for Dendrite-Free Zn Anodes.

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation. Meanwhile, the abundant pores in the framework of the hybrid fibers provide a large space to relieve the structural stress and suppress the dendrite growth. Moreover, the good mechanical characteristics of the hybrid fiber ensure its high potential applications for flexible electronics. Theoretical analysis results disclose the strong interaction between Zn and Cu sites, and experimental results demonstrate the low voltage hysteresis, high reversibility, and dendrite-free behavior of the Cu@HLCF host for Zn plating/stripping. Moreover, the solid-state Zn-ion battery (ZIB) assembled with a Cu@HLCF/Zn anode shows the prominent flexibility, impressively reliability, and outstanding cycling capability. Therefore, this work not only provides a novel design for the efficient and stable Zn metal anode but also promotes the development of flexible power sources for flexible electronics.

Spatial distribution and assembly processes of bacterial communities in riverine and coastal ecosystems of a rapidly urbanizing megacity in China.

Rapid urbanization has precipitated significant anthropogenic pollution (nutrients and pathogens) in urban rivers and their receiving systems, which consequentially disrupted the compositions and assembly of bacterial community within these ecosystems. However, there remains scarce information regarding the composition and assembly of both planktonic and benthic bacterial communities as well as pathogen distribution in such environments. In this study, full-length 16S rRNA gene sequencing was conducted to investigate the bacterial community composition, interactions, and assembly processes as well as the distribution of potential pathogens along a riverine-coastal continuum in Shenzhen megacity, China. The results indicated that both riverine and coastal bacterial communities were predominantly composed of Gammaproteobacteria (24.8 ± 12.6 %), Alphaproteobacteria (16.1 ± 9.8 %), and Bacteroidota (14.3 ± 8.6 %), while sedimentary bacterial communities exhibited significantly higher diversity compared to their planktonic counterparts. Bacterial community patterns exhibited significant divergences across different habitats, and a significant distance-decay relationship of bacterial community similarity was particularly observed within the urban river ecosystem. Moreover, the urban river ecosystem displayed a more complex bacterial co-occurrence network than the coastal ecosystem, and a low ratio of negative:positive cohesion suggested the inherent instability of these networks. Homogeneous selection and dispersal limitation emerged as the predominant influences on planktonic and sedimentary bacterial communities, respectively. Pathogenic genera such as Vibrio, Bacteroides, and Acinetobacter, known for their roles in foodborne diseases or wound infection, were also identified. Collectively, these findings provided critical insights into bacterial community dynamics and their implications for ecosystem management and pathogen risk control in riverine and coastal environments impacted by rapid urbanization.

Factors influencing shoulder stiffness after open reduction and internal fixation of proximal humeral fractures.

OBJECTIVES: The study aimed to investigate the factors associated with shoulder stiffness following open reduction and internal fixation (ORIF) of proximal humeral fractures. PATIENTS AND METHODS: The retrospective study included a total of 151 patients who underwent ORIF of proximal humeral fractures between January 2016 and May 2021. Based on their shoulder joint motion at the latest follow-up, the patients were divided into two groups. The stiffness group (n=32; 8 males, 24 females; mean age: 62.4±9.3 years; range, 31 to 79 years), exhibited restricted shoulder forward flexion (<120°), limited arm lateral external rotation (<30°), and reduced back internal rotation below the L3 level. The remaining patients were included in the non-stiffness group (n=119; 52 males, 67 females; mean age: 56.4±13.4 years; range, 18 to 90 years). Various factors were examined to evaluate the association with shoulder stiffness following ORIF of proximal humeral fractures by multivariate unconditional logistic regression models. RESULTS: The mean follow-up duration was 31.8±12.6 (range, 12 to 68) months. Based on the results of the multivariate regression analysis, it was found that high-energy injuries [compared to low-energy injuries; adjusted odds ratio (aOR)=7.706, 95% confidence interval (CI): 3.564-15.579, p<0.001], a time from injury to surgery longer than one week (compared to a time from injury to surgery equal to or less than one week; aOR=5.275, 95% CI: 1.7321-9.472, p=0.031), and a body mass index (BMI) >24.0 kg/m2 (compared to a BMI between 18.5 and 24.0 kg/m2 ; aOR=4.427, 95% CI: 1.671-11.722, p=0.023) were identified as risk factors for shoulder stiffness following ORIF of proximal humeral fractures. CONCLUSION: High-energy injury, time from injury to surgery longer than one week, and BMI >24.0 kg/m2 were identified as independent risk factors for shoulder stiffness after proximal humeral fracture surgery, which should be treated with caution in clinical treatment.

Endotype-driven Co-module mechanisms of danhong injection in the Co-treatment of cardiovascular and cerebrovascular diseases: A modular-based drug and disease integrated analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. AIM OF THIS STUDY: To elucidate the underlying endotype mechanisms of DHI in the CTBH. MATERIALS AND METHODS: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. RESULTS: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments. CONCLUSIONS: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway.

Monocytes release cystatin F dimer to associate with Aß and aggravate amyloid pathology and cognitive deficits in Alzheimer's disease.

BACKGROUND: Understanding the molecular mechanisms of Alzheimer's disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aß) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aß clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aß by monocytes in AD remains unclear. METHODS: Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aß by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aß. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. RESULTS: Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aß deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aß by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aß to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aß. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. CONCLUSIONS: Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aß metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia.

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

Effects of the fermentation quality and microbial community of waxy maize mixed with fodder soybean silage.

Waxy maize (Zea mays L. sinensis Kulesh) is highly regarded for its high nutritional content and unique taste. Although the stalks and leaves contain high carbohydrate levels after ear harvesting, inadequate crude protein (CP) limits the utilization and promotion of waxy maize silage in animal husbandry. In this study, waxy maize and fodder soybeans were mixed for sowing in different proportions [1:0 (CK), 1:1 (A1), 1:2 (A2), 1:3 (A3), and 1:4 (A4)] to investigate the effects of different mixing ratios on the growth of the waxy maize, the chemical indices, fermentation quality, and the microbial community of the mixed silage after ear harvesting. The mixed planting of waxy maize and fodder soybeans in different proportions had no effect on the yield and quality of the waxy maize ears and increased the aboveground biomass after ear harvesting. After ear harvesting, the neutral detergent fiber (NDF) and acid detergent fiber (ADF) contents significantly decreased, and the CP content and relative feeding value (RFV) gradually increased in the mixed silage. The pH of the treatments was lower than 4.2 except for A4, and the lowest ammonia nitrogen (AN) concentration was observed in A3. With increasing proportions of fodder soybeans, the abundance of beneficial bacteria increased and that of harmful bacteria decreased; Firmicutes and Lactobacillus were the dominant phylum and genus, respectively, and both increased gradually. Redundancy analysis (RDA) revealed that the fermentation indices affecting the microbial community composition in the silage were inconsistent among the different mixed sowing combinations. The Mantel test showed that the composition of the microbial communities in the treatments was significantly correlated with the ADF, water-soluble carbohydrate (WSC), and propionic acid (PA) contents. Comprehensive analysis revealed that the optimal mixed sowing ratio of waxy maize to fodder soybeans was 1:3, and waxy maize and fodder soybeans silage can increase the utilization of aboveground biomass and improve the fermentation quality and feeding quality of silage by changing the microbial community. These findings lay a certain theoretical foundation for improving the utilization of waxy maize.

Strategies for multi-case physics-informed neural networks for tube flows: a study using 2D flow scenarios.

Fluid dynamics computations for tube-like geometries are crucial in biomedical evaluations of vascular and airways fluid dynamics. Physics-Informed Neural Networks (PINNs) have emerged as a promising alternative to traditional computational fluid dynamics (CFD) methods. However, vanilla PINNs often demand longer training times than conventional CFD methods for each specific flow scenario, limiting their widespread use. To address this, multi-case PINN approach has been proposed, where varied geometry cases are parameterized and pre-trained on the PINN. This allows for quick generation of flow results in unseen geometries. In this study, we compare three network architectures to optimize the multi-case PINN through experiments on a series of idealized 2D stenotic tube flows. The evaluated architectures include the 'Mixed Network', treating case parameters as additional dimensions in the vanilla PINN architecture; the "Hypernetwork", incorporating case parameters into a side network that computes weights in the main PINN network; and the "Modes" network, where case parameters input into a side network contribute to the final output via an inner product, similar to DeepONet. Results confirm the viability of the multi-case parametric PINN approach, with the Modes network exhibiting superior performance in terms of accuracy, convergence efficiency, and computational speed. To further enhance the multi-case PINN, we explored two strategies. First, incorporating coordinate parameters relevant to tube geometry, such as distance to wall and centerline distance, as inputs to PINN, significantly enhanced accuracy and reduced computational burden. Second, the addition of extra loss terms, enforcing zero derivatives of existing physics constraints in the PINN (similar to gPINN), improved the performance of the Mixed Network and Hypernetwork, but not that of the Modes network. In conclusion, our work identified strategies crucial for future scaling up to 3D, wider geometry ranges, and additional flow conditions, ultimately aiming towards clinical utility.

Metabolic self-feeding in HBV-associated hepatocarcinoma centered on feedback between circulation lipids and the cellular MAPK/mTOR axis.

INTRODUCTION: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV- and HBV+ HCC have remained unchanged, limiting HCC treatment options. OBJECTIVES: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. METHODS: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. RESULTS: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. CONCLUSION: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids.

Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics.

BACKGROUND: Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. METHODS: We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. RESULTS: In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. CONCLUSIONS: We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.

Ultrasound treatment of crystalline oil-in-water emulsions stabilized by sodium caseinate: Impact on emulsion stability through altered crystallization behavior in the oil globules.

Partial coalescence is a key factor contributing to the instability of crystalline oil-in-water emulsions in products like dressings and sauces, reducing shelf life. The intrinsic characteristics of semi-crystalline droplets, including solid fat content, fat crystal arrangement, and polymorphism, play a pivotal role in influencing partial coalescence, challenging prevention efforts even with emulsifiers like amphiphilic proteins. High-intensity ultrasound (HIU) has emerged as an efficient and cost-effective technology for manipulating bulk fat crystallization, thereby enhancing physical properties. This study specifically investigates the impact of HIU treatment on fat crystallization on protein-stabilized crystalline emulsions, utilizing palm olein stearin (POSt) as the lipid phase and sodium caseinate (NaCas) as the surfactant under various HIU powers (100, 150, 200, 300, and 400 W). Results show that increasing HIU power maintained the interfacial potential (-20 mV) provided by NaCas in the emulsions without significant differences. Higher HIU power induced the most stable polymorphic form (ß) in the emulsions. Engagingly, the emulsions at 200 W exhibited better storage stability and slower partial coalescence kinetics. Semi-crystalline globules had more uniform and integral crystal clusters that were distributed tangentially near the droplet boundary, perhaps attributed to intermediate subcooling (40.4 °C) at 200 W. The acoustic energy of HIU significantly translates into thermal effects, influencing subcooling degrees as a dominant factor affecting crystallisation in the emulsions. This study establishes ultrasonic crystallization as a novel strategy for modifying the stability of emulsions containing fat crystals.

Omaveloxolone Prevents Polystyrene Microplastic-Induced Ovarian Granulosa Cell Apoptosis via the Keap1/Nrf2/HO-1 Pathway in Rats.

Microplastics (MPs) are persistent environmental pollutants that enter the circulatory system and subsequently reduce sperm quantity and quality. However, the influence of polystyrene MPs (PS-MPs) on the ovary and relevant mechanisms remain elusive. Herein, we aimed to examine the impact of PS-MPs on oxidative disorders in ovarian tissues and elucidate the underlying mechanisms. Healthy female rats were treated with different concentrations of 0.5 µm PS-MPs (diluted in deionized H2O) for 90 days. Upon examination of hematoxylin-eosin-stained ovarian tissue sections, the number of growing follicles was reduced in PS-MP-treated rats when compared with that in control rats. Enzyme-linked immunosorbent assays revealed that PS-MP exposure markedly reduced anti-Müllerian hormone (AMH) levels. Treatment with PS-MPs downregulated superoxide dismutase, glutathione, and catalase activities in ovarian tissues while upregulating malondialdehyde levels. Furthermore, exposure to PS-MP blocked the Keap1/Nrf2/HO-1 signal transduction pathway. PS-MPs also triggered apoptosis in the ovarian tissue, as evidenced by increased TUNEL staining and expression levels of cleaved caspase-9, Bax, and Bcl-2. To reactivate the Keap1/Nrf2/HO-1 pathway, rats were co-administered PS-MPs and omaveloxolone (Oma), an Nrf2 activator, for 1 week. We found that Oma could counteract the PS-MP-mediated effects on oxidative disorder, apoptosis, AMH production, and follicle number in rat ovarian tissues. To develop an in vitro model, granulosa cells (GCs) were treated with 10 µM H2O2 for 12 h to induce oxidative stress. H2O2-stimulated GCs exhibited attenuated cell growth and upregulated apoptosis and oxidative stress. Oma administration could ameliorate the H2O2-induced effects in terms of regulating cell viability, apoptosis, and oxidative stress in GCs. In summary, PS-MPs could induce apoptosis and oxidative stress via the Keap1/Nrf2/HO-1 signaling pathway in both rats and GCs.

Adverse Events of Oral GLP-1 Receptor Agonist (Semaglutide Tablets): A Real-World Study Based on FAERS from 2019 to 2023.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous preparations can only be subcutaneously injected. Oral administration of GLP-1RAs semaglutide helps to broaden treatment options, but its safety in the real world still needs to be observed. This study is based on FDA adverse event reporting system (FAERS) database to mine adverse drug events (ADE) of oral semaglutide, and provide references for the clinical safe use of this drug. METHODS: To analyze the signal quality of oral semaglutide, which is a drug used in the FAERS database from the third quarter of 2019 to the third quarter of 2023, we collected ADE data and performed data mining by using disproportionate analysis. Then, we standardized the data and used a variety of signal-quantification techniques, including reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian belief propagation neural network (BCPNN), and multiple empirical Bayesian gamma Poisson contractions (MGPS), for further analysis. RESULTS: We screened 2398 reports on the use of semaglutide tablets, involving a total of 5653 ADE. These reports were mainly submitted by consumers, and the reporting country was mainly the United States. A total of 23 system organ classes (SOC) and 93 preferred terms (PT) were mined for the signals of semaglutide tablets. The three most common SOC were gastrointestinal disorders, general disorders and administration site conditions, and investigations. At the PT level, metabolism and nutrition disorders exhibit the highest number of signals, with the top three being thyroid cyst, acute cholecystitis, and ketosis. Gastrointestinal disorders rank second, primarily involving eructation, pancreatitis, impaired gastric emptying, and regurgitation. In addition, vith nerve paralysis occurs and the signal intensity is high. CONCLUSIONS: Our study provides a deeper and broader understanding of the safety of oral semaglutide. The results of the ROR, PRR, BCPNN, and MGPS algorithms exhibit high consistency, with metabolism and nutrition-related disorders having the highest number of signals. The conclusions align with the technical specifications of the product. Notably, other unexpected effects are reported, including acute cholecystitis, paralysis of the abducens nerve, and positional vertigo.

CT data analysis of catheter morphology and displacement in peritoneal dialysis: an exploratory study.

PURPOSE: Catheter displacement is a common complication of peritoneal dialysis. The aim of this study was to explore the correlation between catheter morphology and displacement by analyzing CT data, providing a scientific basis for optimizing catheter morphology within abdominal wall layers. METHODS: We retrospectively analyzed the clinical data of 94 patients. The parameters for analyzing catheter morphology were defined based on six key points identified from CT images. The covariates considered in the analysis included demographics, primary disease, body size, peritoneal dialysis method, and total weekly urea clearance index. RESULTS: During a mean follow-up period of 1056 ± 480 days, only the angle of the intramuscular part (IM angle) of the catheter significantly correlated with the time to first catheter displacement according to the multivariate analysis (hazard ratio [HR]: 1.039, 95% confidence interval [CI] 1.02-1.058, p < 0.01). When the cut-off value of IM angle was 39.4 ∘ , the area under receiver-operating characteristic (ROC) curve for predicting catheter displacement was 0.791 (95% CI 0.701-0.881, p < 0.01), with a sensitivity and specificity of 82.9% and 66.0%, respectively. Kaplan-Meier survival curves showed that the catheter survival rate was significantly higher in the group with an IM angle < 39.4 ∘ than in the group with an IM angle > 39.4 ∘ (log-rank χ 2 =19.479, p < 0.01). None of the catheter morphology parameters were significantly correlated with technique survival in the multivariate analysis. CONCLUSION: There is a correlation between catheter morphology and catheter displacement. An IM angle > 39.4 ∘ is an independent risk factor for catheter displacement, while the position and angle of the subcutaneous part are not correlated with catheter displacement.

From scraps to purification: innovative use of food waste-derived hydrochar in eradicating pharmaceutical pollutants.

Chemical products (CPs) such as carbamazepine and naproxen, present in aquatic environments, pose significant risks to both aquatic life and human health. This study investigated the use of hydrothermally carbonized food waste-derived hydrochar (AC-HTC) at three distinct temperatures (200, 250, and 300 °C) as an adsorbent to remove these CPs from water. Our research focused on the impact of hydrothermal carbonization temperature on hydrochar properties and the effects of chemical activation with phosphoric acid on adsorption capacity. Hydrothermal carbonization increased the hydrochar's surface area from 1.47 to 7.52 m2/g, which was further enhanced to 32.81 m2/g after activation with phosphoric acid. Batch adsorption experiments revealed that hydrochar produced at 250 °C (AC-HTC-250) demonstrated high adsorption capacities of 49.10 mg/g for carbamazepine and 14.35 mg/g for naproxen, outperforming several conventional adsorbents. Optimal adsorption occurred at pH 4, aligning well with the Langmuir and pseudo-first-order models. The hydrochar showed potential for regeneration and multiple uses, suggesting its applicability in sustainable wastewater treatment. Future research will explore scalability and effectiveness against a broader range of pollutants.

Optimizing patient outcomes: the impact of multimodal preemptive analgesia in video-assisted thoracoscopic lobectomy.

OBJECTIVES: To evaluate the efficacy of a multimodal preemptive analgesia management approach, specifically incorporating ultrasound-guided thoracic paravertebral block (UG-TPVB) in conjunction with intravenous analgesia, after video-assisted thoracoscopic (VATS) lobectomy under the guidance of Enhanced Recovery After Surgery (ERAS). METHODS: A total of 690 patients who underwent VATS lobectomy between October 2021 and March 2022 were divided into the UG-TPVB group (group T, n = 345) and control group (group C, n = 345). Patients in group T received UG-TPVB prior to the induction of general anaesthesia, while group C did not undergo nerve block. A comparison was conducted between the two groups regarding various indicators, including postoperative sedation, static/dynamic numeric rating scale (NRS) scores, intraoperative fentanyl consumption, duration of mechanical ventilation/anaesthesia recovery/hospitalization, postoperative complications, and other relevant factors. RESULTS: The static/dynamic NRS scores of group T were lower than those of group C after surgery. Intraoperative fentanyl consumption in group T (0.384 ± 0.095 mg) was lower than that in group C (0.465 ± 0.053 mg). The duration of mechanical ventilation, anaesthesia recovery, and hospitalization were significantly shorter in group T compared to group C. Patient satisfaction rate in group T (70.1%) was higher than that in group C (53.6%). All differences were statistically significant (P < 0.05). CONCLUSIONS: The multimodal preemptive analgesia management strategy effectively reduces postoperative pain, decreases opioid consumption, and promotes faster recovery in patients undergoing VATS lobectomy.