Incorporation of small extracellular vesicles in PEG/HA-Bio-Oss hydrogel composite scaffold for bone regeneration.

Stem cell derived small extracellular vesicles (sEVs) have emerged as promising nanomaterials for the repair of bone defects. However, low retention of sEVs affects their therapeutic effects. Clinically used natural substitute Bio-Oss bone powder lack high compactibility and efficient osteo-inductivity that limit its clinical application in repairing large bone defects. In this study, a poly ethylene glycol/hyaluronic acid (PEG/HA) hydrogel was used to stabilize Bio-Oss and incorporate rat bone marrow stem cell-derived sEVs (rBMSCs-sEVs) to engineer a PEG/HA-Bio-Oss (PEG/HA-Bio) composite scaffold. Encapsulation and sustained release of sEVs in hydrogel scaffold can enhance the retention of sEVs in targeted area, achieving long-lasting repair effect. Meanwhile, synergistic administration of sEVs and Bio-Oss in cranial defect can improve therapeutic effects. The PEG/HA-Bio composite scaffold showed good mechanical properties and biocompatibility, supporting the growth of rBMSCs. Furthermore, sEVs enhanced in vitro cell proliferation and osteogenic differentiation of rBMSCs. Implantation of sEVs/PEG/HA-Bio in rat cranial defect model promoted in vivo bone regeneration, suggesting the great potential of sEVs/PEG/HA-Bio composite scaffold for bone repair and regeneration. This will hopefully provide a strategy for combining hydrogel composite scaffold systems and stem cell-derived sEVs in the field of applied tissue engineering repair. .

Maltol Improves Peripheral Nerve Function by Inhibiting Schwann Cell Apoptosis via the PERK/eIF2α/CHOP Pathway and MME Upregulation in Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is the most prevalent chronic complication among diabetic patients and a primary risk factor contributing to the deterioration of diabetic foot conditions. The pathogenesis of DPN remains complex and not fully understood, and there are hardly any effective treatment drugs. Maltol (3-hydroxy-2-methyl-4-pyranone) has demonstrated antioxidant and anti-inflammatory properties. However, the potential role of maltol in the treatment of DPN remains unclear. This study aimed to assess maltol's effects on DPN rats and high glucose (HG)/palmitic acid (PA)-induced rat Schwann cells (RSC96). The results indicated maltol's capacity to enhance peripheral nerve function in DPN rats. In RSC96 cells stimulated with high HG and PA, maltol treatment reduced DPN markers and apoptosis-related proteins. Functional enrichment analysis of differentially expressed genes revealed that endoplasmic reticulum (ER) stress pathways were involved in this process. Western blot results demonstrated the activation of ER stress pathway in HG/PA-induced RSC96 cells, with maltol attenuating ER stress-related protein expression. Furthermore, the knockdown of Membrane metallo-endopeptidase (MME) reversed maltol's effects on apoptosis-related protein expression, suggesting a potential therapeutic role for maltol via MME in treating DPN. These findings indicate that maltol may hold promise as a therapeutic agent for DPN treatment.

Hybrid Optimization Path Planning Method for AGV Based on KGWO.

To address the path planning problem for automated guided vehicles (AGVs) in challenging and complex industrial environments, a hybrid optimization approach is proposed, integrating a Kalman filter with grey wolf optimization (GWO), as well as incorporating partially matched crossover (PMX) mutation operations and roulette wheel selection. Paths are first optimized using GWO, then refined with Kalman filter corrections every ten iterations. Moreover, roulette wheel selection guides robust parent path selection, while an elite strategy and partially matched crossover (PMX) with mutation generate diverse offspring. Extensive simulations and experiments were carried out under a densely packed goods scenario and complex indoor layout scenario, within a fully automated warehouse environment. The results showed that this hybrid method not only enhanced the various optimization metrics but also ensured more predictable and collision-free navigation paths, particularly in environments with complex obstacles. These improvements lead to increased operational efficiency and safety, highlighting the method's potential in real-world applications.

Distribution and co-occurrence of microplastics and co-existing pollutants in bottom water and sediment of the East China Sea.

Microplastics (MPs) contamination in marine environment has been an emerging issue worldwide, notably due to the potential ecological risks of MPs with co-existing environmental contaminants and released toxic plastic additives. To verify the co-occurrence characteristics of MPs and co-existing pollutants in the benthic boundary layer (BBL), the distribution characteristics of MPs, and selected heavy metals (HMs) and halogenated flame retardants (Polybrominated diphenyl ethers, PBDEs, and Dechlorane Plus) in the bottom water and sediment were comprehensively investigated in the East China Sea (ECS). The sampling sites were selected along the coast of ECS, where might be significantly affected by terrigenous inputs and anthropogenic sources. MPs were abundant in the bottom water (62.8-480.2 items/L) and sediment (80.1-1346.7 items/kg d.w.) with polyester, polyethylene, and polypropylene being as the most abundant types and characterized as fiber/line, particle size 200-500 µm, and transparent/white. The abundance and characteristics of MPs demonstrated strong correlations within the bottom water and sediment, which might be due to the frequent exchange of materials. In addition, the abundance of MPs was significantly positively correlated with HMs (Cd, Cr, Pb) in the bottom water and PBDEs in sediment, respectively. According to the scanning electron microscopy/energy dispersive X-ray spectrometry analysis, MPs might act as carriers to transport and co-sediment the co-existing pollutants in water, and physically adsorb or chemically bind with pollutants in sediment. These results could help to elucidate the sources, migration, and fate, and verify the occurrence and potential risks of MPs and their co-existing pollutants in BBL, thus realize the management and control of MPs contamination in marine.

Three-Dimensional Evaluation of Condylar Position and Joint Spaces Following Orthodontic Treatment With Quadruple Premolar Extractions.

This study aimed to assess the alterations in the temporomandibular joint among adult patients undergoing orthodontic treatment involving the extraction of four premolars. A cohort of 44 adults, with a mean age of 24.2 years, underwent orthodontic therapy that included quadruple premolar extractions. Cone-beam computed tomography scans were performed before and after the treatment to evaluate the temporomandibular joints. The three-dimensional assessment focused on the condylar position relative to the cranial base and the articular fossa, the axial condylar rotation, and the joint spaces. Notably, a significant posterior shift of the condyle was detected (P≤0.01), averaging a 0.41mm retraction. The posterior joint space narrowed by 0.32mm post-treatment. Additionally, a medial tilt of 0.62° in the condyle's long axis was observed in the frontal plane. No significant changes were recorded for the other condylar positions, rotations, or joint space dimensions. The findings suggest that orthodontic treatment with four premolar extractions may instigate condylar repositioning and rotation. These insights can inform refinements in treatment protocols.

Genetic evidence for the causal association of neuroticism with intracranial aneurysms: A Mendelian randomization study.

OBJECTIVE: The aim of this study was to assess the potential causal relationship between neuroticism and 12 neuroticism items with intracranial aneurysms (IAs) and aneurysmal subarachnoid hemorrhage (aSAH) using a two-sample Mendelian randomization (MR) approach. METHODS: Study data were obtained from the Genome-Wide Association Study (GWAS) pooled dataset, and we extracted summary statistics for neuroticism, 12 neuroticism items, and IAs, which were categorized into ruptured and unruptured aneurysms (IA), aSAH, and unruptured IAs (uIA). Single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs) to explore the causal relationship between exposure and outcome using five Mendelian randomization methods, with Inverse variance weighted (IVW) as the primary study method. Horizontal multiple validity tests, sensitivity analyses, and inverse MR ensured the stability of the results. RESULTS: The two-sample MR showed a genetically predictive association between neuroticism and IA [odds ratio (OR) = 1.16; 95 % confidence interval (95 % CI): 1.04-1.30; p = 0.009], aSAH (OR = 1.17; 95 % CI: 1.03-1.33; p = 0.013) and uIA (OR = 1.30; 95 % CI: 1.07-1.59; p = 0.009) were all genetically predictive of association. Ivw showed a positive association between 5 neuroticism items and IA risk, 5 neuroticism items and aSAH risk as well as no genetically predictive association between neuroticism items and uIA. Sensitivity analysis and inverse MR confirmed the robustness of the results. CONCLUSION: Our Mendelian randomization analysis demonstrated genetic causality between neuroticism and neuroticism items with intracranial aneurysms, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysms, and further studies are needed to confirm these results and explore potential mechanisms of action.

Customized Corneal Cross-Linking with Microneedle-Mediated Riboflavin Delivery for Keratoconus Treatment.

In this study, a novel customized corneal cross-linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional "one-size-fits-all" approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi-circular, annular and butterfly shaped, are crafted for loading an optimized RF-hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross-linking effects that are comparable to the conventional epi-off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods.

Bio-based flame retardant coatings for polyester/cotton fabrics with high physical properties using ammonium vinyl phosphonate-grafted chitosan complexes.

Polyester/cotton (T/C) blended fabrics are widely utilized in textile due to the dimensional stability and high elasticity provided by polyester, combined with the comfort and moisture absorption offered by cotton. However, simultaneously enhancing the flame retardancy and maintaining the physical properties of T/C blended fabrics for clothing and furniture applications remains a big challenge. This study introduces a bio-based flame-retardant coating using polyelectrolyte complexes (PEC) composed of ammonium vinyl phosphonate-grafted chitosan (AMVP-g-CS). The protonation degree of the PEC coating is controlled by adjusting the pH to solidify and stabilize the complex structure, preparing bio-based PEC flame retardant T/C blended fabric. Flame retardant analysis reveals that the coated fabrics achieved a limiting oxygen index of 30.5 % and a char length of 11 mm, indicating significantly improved flame retardancy. The combustible volatile substances are significantly reduced for the coated fabrics, achieving a gas-phase flame retardant effect, and forming an expansive char layer with thermal insulation and oxygen blocking properties. Importantly, physical analysis proves that the PEC deposition improved mechanical properties, satisfactory whiteness index and hand feeling of the fabrics. This work opens up a pragmatic and industrially feasible strategy for the development of CSs in the field of flame retardant coating.

Microbacterium rhizophilus sp. nov., an indole acetic acid-producing actinobacterium isolated from rhizosphere soil.

A novel gram-stain-positive, short rod, aerobic, non-motile and non-spore-forming actinobacterial strain, designated GXG1230T was isolated from the rhizosphere soil of a coastal mangrove forest in Beihai city, Guangxi Zhuang Autonomous Region, PR China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GXG1230T was affiliated with the genus Microbacterium. Additionally, it demonstrated a high degree of similarity to Microbacterium paludicola US15T (97.9%) and Microbacterium marinilacus YM11-607T (97.3%). Chemotaxonomic characteristics showed that the whole-cell sugars were glucose, xylose, rhamnose and galactose. Menaquinones MK-11 and MK-12 were detected as respiratory quinones. Lysine was found in the peptidoglycan hydrolysate and the polar lipids were diphosphatidylglycerol, one phospholipid and two unidentified glycolipid. The major fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The strain GXG1230T exhibited a genomic DNA G + C content of 71.7%. Furthermore, the average nucleotide identity values of GXG1230T with the reference strains were 75.4% and 81.9%, respectively, while the digital DNA-DNA hybridization values were 20.1% and 25.0%. Based on physiological, chemotaxonomic and phylogenetic information, strain GXG1230T is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium rhizophilus sp.nov is proposed, with GXG1230T (= MCCC 1K09302T = KCTC 59252T) as the type strain.

A low-voltage-driven MEMS ultrasonic phased-array transducer for fast 3D volumetric imaging.

Wearable ultrasound imaging technology has become an emerging modality for the continuous monitoring of deep-tissue physiology, providing crucial health and disease information. Fast volumetric imaging that can provide a full spatiotemporal view of intrinsic 3D targets is desirable for interpreting internal organ dynamics. However, existing 1D ultrasound transducer arrays provide 2D images, making it challenging to overcome the trade-off between the temporal resolution and volumetric coverage. In addition, the high driving voltage limits their implementation in wearable settings. With the use of microelectromechanical system (MEMS) technology, we report an ultrasonic phased-array transducer, i.e., a 2D piezoelectric micromachined ultrasound transducer (pMUT) array, which is driven by a low voltage and is chip-compatible for fast 3D volumetric imaging. By grouping multiple pMUT cells into one single drive channel/element, we propose an innovative cell-element-array design and operation of a pMUT array that can be used to quantitatively characterize the key coupling effects between each pMUT cell, allowing 3D imaging with 5-V actuation. The pMUT array demonstrates fast volumetric imaging covering a range of 40 mm × 40 mm × 70 mm in wire phantom and vascular phantom experiments, achieving a high temporal frame rate of 11 kHz. The proposed solution offers a full volumetric view of deep-tissue disorders in a fast manner, paving the way for long-term wearable imaging technology for various organs in deep tissues.

Development of a prognostic model for NSCLC based on differential genes in tumour stem cells.

Non-small cell lung cancer (NSCLC) constitutes a significant portion of lung cancers and cytotoxic drugs (e.g. cisplatin) are currently the first-line treatment. However, NSCLC has developed resistance to this drug, which limits the therapeutic effect and thus affects prognosis. NSCLC sc-RNA-seq data were downloaded from the GEO database and Ku Leuven Laboratory for Functional Epigenetics, and bulk RNA-seq data were obtained from the TCGA database. The "Seurat" package was employed for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were applied for downscaling and cluster identification. Use the FindAllMarkers function to find differential genes (DEGs) for tumor stem cells. Then, we performed univariate regression analyses on the DEGs to identify potential prognostic genes. We created a machine learning framework based on potential prognostic genes, which combines 10 machine learning methods and their 101 combinations to get the optimal prognostic risk model. The model was evaluated in the training set and validation set. A nomogram was developed to provide physicians with a quantitative tool for prognosis prediction. Finally, we evaluated the expression and functionality of SLC2A1. We discovered 22 cell clusters containing 218379 cells by examining single-cell RNA sequencing datasets (GSE148071, KU_lom, GSE131907, GSE136246, GSE127465). Tumour cells were isolated for subpopulation analysis and 162 differential genes from SOX2_cancer were obtained. After univariate Cox analysis, we found 23 genes with prognostic potential prognostic value and utilized them to develop 101­combination machine learning computational framework. We eventually picked the best performing 'StepCox[both] + RSF', which includes 8 genes. The model has a relatively high prediction accuracy in both TCGA and GEO datasets. In in vitro investigations, targeted suppression of the SLC2A1 gene resulted in significant reductions in proliferation, invasion and migration in A549 cells. In addition, a significant reduction in cisplatin resistance was seen in A549/DDP cells. The outcomes demonstrated the precision and credibility of the prognostic model for NSCLC, highlighting its potential significance in the treatment and prognosis of individuals affected by this disease. SLC2A1 may become a promising prognostic marker and a potential therapeutic target, offering valuable insights to inform clinical treatment decisions.

Machine-learning-derived online prediction models of outcomes for patients with cholelithiasis-induced acute cholangitis: development and validation in two retrospective cohorts.

Background: Cholelithiasis-induced acute cholangitis (CIAC) is an acute inflammatory disease with poor prognosis. This study aimed to create machine-learning (ML) models to predict the outcomes of patients with CIAC. Methods: In this retrospective cohort and ML study, patients who met the both diagnosis of 'cholangitis' and 'calculus of gallbladder or bile duct' according to the International Classification of Disease (ICD) 9th revision, or met the diagnosis of 'calculus of bile duct with acute cholangitis with or without obstruction' according to the ICD 10th revision during a single hospitalization were included from the Medical Information Mart for Intensive Care database, which records patient admissions to Beth Israel Deaconess Medical Center, MA, USA, spanning June 1, 2001 to November 16, 2022. Patients who were neither admitted in an emergency department nor underwent biliary drainage within 24 h after admission, had an age of less than 18, or lost over 20% of the information were excluded. Nine ML methods, including the Logistic Regression, eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine, Adaptive Boosting, Decision Tree, Gradient Boosting Decision Tree, Gaussian Naive Bayes, Multi-Layer Perceptron, and Support Vector Machine were applied for prediction of in-hospital mortality, re-admission within 30 days after discharge, and mortality within 180 days after discharge. Patients from Zhongda Hospital affiliated to Southeast University in China between January 1, 2019 and July 30, 2023 were enrolled as an external validation set. The area under the receiver operating characteristic curve (AUROC) was the main index for model performance assessment. Findings: A total of 1156 patients were included to construct models. We performed stratified analyses on all patients, patients admitted to the intensive care unit (ICU) and those who underwent biliary drainage during ICU treatment. 13-16 features were selected from 186 variables for model training. The XGBoost method demonstrated the most optimal predictive efficacy, as evidenced by training set AUROC of 0.996 (95% CI NaN-NaN) for in-hospital mortality, 0.886 (0.862-0.910) for re-admission within 30 days after discharge, and 0.988 (0.982-0.995) for mortality within 180 days after discharge in all patients, 0.998 (NaN-NaN), 0.933 (0.909-0.957), and 0.988 (0.983-0.993) in patients admitted to the ICU, 0.987 (0.970-0.999), 0.908 (0.873-0.942), and 0.982 (0.971-0.993) in patients underwent biliary drainage during ICU treatment, respectively. Meanwhile, in the internal validation set, the AUROC reached 0.967 (0.933-0.998) for in-hospital mortality, 0.589 (0.502-0.677) for re-admission within 30 days after discharge, and 0.857 (0.782-0.933) for mortality within 180 days after discharge in all patients, 0.963 (NaN-NaN), 0.668 (0.486-0.851), and 0.864 (0.757-0.970) in patients admitted to the ICU, 0.961 (0.922-0.997), 0.669 (0.540-0.799), and 0.828 (0.730-0.925) in patients underwent biliary drainage during ICU treatment, respectively. The AUROC values of external validation set consisting of 61 patients were 0.741 (0.725-0.763), 0.812 (0.798-0.824), and 0.848 (0.841-0.859), respectively. Interpretation: The XGBoost models could be promising tools to predict outcomes in patients with CIAC, and had good clinical applicability. Multi-center validation with a larger sample size is warranted. Funding: The Technological Development Program of Nanjing Healthy Commission, and Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds.

Vitamin D content and prevalence of vitamin D deficiency in patients with epilepsy: a systematic review and meta-analysis.

Introduction: The prevalence of vitamin D deficiency and vitamin D levels in patients with epilepsy (PWE) were systematically evaluated, and the differences between subgroups were analyzed. Method: We identified all articles investigating the prevalence of vitamin D deficiency in patients with epilepsy from the database established in March 2024 from PubMed, Web of Science, and Embase. We divided them into anti-seizure medication (ASM) interventions and non-ASM interventions according to whether or not someone used ASM. Results: A total of 68 articles were included. The prevalence of newly diagnosed epilepsy was 50.2% (95% CI: 38.7-61.7%), and the prevalence after ASM intervention was 47.9% (95% CI: 40-55.9%), including 7,070 patients with epilepsy. Subgroup and meta-regression analyses were performed according to the diagnostic criteria, economic development level, region, age, ASM treatment, and other factors. The results showed that the differences were not significant. In addition, the vitamin D content of epilepsy patients (18.719 ng/mL) was lower than that of healthy people (20.295 ng/mL). Conclusion: The prevalence of vitamin D deficiency in patients with epilepsy is very high. Still, the related factors have little effect on the high prevalence of vitamin D in epilepsy, and ASM intervention can reduce the vitamin D content in patients with epilepsy. Therefore, it is emphasized that monitoring vitamin D levels is part of the routine management of patients with epilepsy. Systematic review registration: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). (registration number CRD42023493896). https://www.crd.york.ac.uk/PROSPERO/ # myprospero.

Comprehensive analysis to identify IL7R as a immunotherapy biomarker from pan-cancer analysis to in vitro validation.

BACKGROUND: Immunotherapy faces a major challenge in treatment resistance, highlighting the need for efficacy biomarkers identification. The tumor microenvironment (TME) significantly influences treatment outcomes, necessitating molecular TME exploration to address immunotherapy resistance. METHODS: The study initially pinpointed IL7R as a pivotal TME gene and then examined its impact on TME's CD8 + T cells at the single-cell level. Bulk-RNA analysis investigated IL7R function, immune cell infiltration related to IL7R in TCGA pan-cancer samples with its expression verified in clinical samples through immunohistochemistry. Genome instability and immune-related molecular expression associated with IL7R were also assessed. Furthermore, the clinical efficacy of IL7R was evaluated in various immunotherapy treatment cohorts. RESULTS: Our single-cell analyses and cell-cased experiment revealed that T cells with high IL7R expression tended to be non-terminal and correlated with favorable immunotherapy responses. High IL7R expression corresponded to increased immune and stromal cell signiture, immune pathway enrichment, and an immune-inflamed environment in Bulk-RNA analysis and immunohistochemistry verification. These patients exhibited higher proportions of memory T cells and M1 cells within the TME, along with frequent genome instability and immune molecular upregulation. While IL7R had varied prognostic impact across the TCGA dataset, patients with high IL7R expression showed extended survival under immunotherapy. CONCLUSION: IL7R plays a critical role in shaping TME diversity across cancer types and holds promise as a relevant biomarker for predicting immunotherapy benefits.

A gene regulatory network-aware graph learning method for cell identity annotation in single-cell RNA-seq data.

Cell identity annotation for single-cell transcriptome data is a crucial process for constructing cell atlases, unraveling pathogenesis, and inspiring therapeutic approaches. Currently, the efficacy of existing methodologies is contingent upon specific data sets. Nevertheless, such data are often sourced from various batches, sequencing technologies, tissues, and even species. Notably, the gene regulatory relationship remains unaffected by the aforementioned factors, highlighting the extensive gene interactions within organisms. Therefore, we propose scHGR, an automated annotation tool designed to leverage gene regulatory relationships in constructing gene-mediated cell communication graphs for single-cell transcriptome data. This strategy helps reduce noise from diverse data sources while establishing distant cellular connections, yielding valuable biological insights. Experiments involving 22 scenarios demonstrate that scHGR precisely and consistently annotates cell identities, benchmarked against state-of-the-art methods. Crucially, scHGR uncovers novel subtypes within peripheral blood mononuclear cells, specifically from CD4+ T cells and cytotoxic T cells. Furthermore, by characterizing a cell atlas comprising 56 cell types for COVID-19 patients, scHGR identifies vital factors like IL1 and calcium ions, offering insights for targeted therapeutic interventions.

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

The pineapple reference genome: Telomere-to-telomere assembly, manually curated annotation, and comparative analysis.

Pineapple is the third most crucial tropical fruit worldwide and available in five varieties. Genomes of different pineapple varieties have been released to date; however, none of them are complete, with all exhibiting substantial gaps and representing only two of the five pineapple varieties. This significantly hinders the advancement of pineapple breeding efforts. In this study, we sequenced the genomes of three varieties: a wild pineapple variety, a fiber pineapple variety, and a globally cultivated edible pineapple variety. We constructed the first gap-free reference genome (Ref) for pineapple. By consolidating multiple sources of evidence and manually revising each gene structure annotation, we identified 26,656 protein-coding genes. The BUSCO evaluation indicated a completeness of 99.2%, demonstrating the high quality of the gene structure annotations in this genome. Utilizing these resources, we identified 7,209 structural variations across the three varieties. Approximately 30.8% of pineapple genes were located within ±5 kb of structural variations, including 30 genes associated with anthocyanin synthesis. Further analysis and functional experiments demonstrated that the high expression of AcMYB528 aligns with the accumulation of anthocyanins in the leaves, both of which may be affected by a 1.9-kb insertion fragment. In addition, we developed the Ananas Genome Database, which offers data browsing, retrieval, analysis, and download functions. The construction of this database addresses the lack of pineapple genome resource databases. In summary, we acquired a seamless pineapple reference genome with high-quality gene structure annotations, providing a solid foundation for pineapple genomics and a valuable reference for pineapple breeding.

Effect of supplementation with Glycyrrhiza uralensis extract and Lactobacillus acidophilus on growth performance and intestinal health in broiler chickens.

Intestinal microbiota community is an important factor affecting the nutritional and health status of poultry, and its balance is crucial for improving the overall health of poultry. The study aimed to investigate the effect of dietary supplementation with Glycyrrhiza uralensis extract (GUE), Lactobacillus acidophilus (Lac) and their combination (GL) on growth performance and intestinal health in broilers in an 84-day feeding experiment. Supplementary 0.1% GUE and 4.5×107 CFU/g Lac significantly increased average daily gain (ADG), and GL (0.1% GUE and 4.5×107 CFU/g Lac) increased ADG and average daily feed intake (ADFI), and decreased feed conversion rate (FCR) in broilers aged 29 to 84 d and 1 to 84 d. Dietary GUE, Lac and GL increased the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and decreased Malondialdehyde (MDA) content in the jejunum mucosa of broilers, and increased secretory IgA (sIgA) content in broilers at 84 d. Moreover, GUE, Lac and GL increased cecal microbial richness and diversity, and modulated microbial community composition. Both GUE and Lac reduced the harmful bacteria Epsilonbacteraeota, Helicobacter, and H. pullorum at 28 d and Proteobacteria, Escherichia, and E. coli at 84 d, while Lac and GL increased beneficial bacteria Lactobacillus and L. gallinarum at 28 d. Compared with individual supplementation, GL markedly increased the SOD activity and the sIgA content, and reduced Helicobacter and Helicobacter pullorum. In conclusion, GUE and Lactobacillus acidophilus as feed additives benefit growth performance and intestinal health, and their combined use shows an even more positive effect in broilers.

Safety and Risk Assessment of No-Prescription Online Semaglutide Purchases.

This qualitative study assesses the quality, amount of active ingredient, and characteristics associated with counterfeiting of semaglutide purchased from illegal online pharmacies without a prescription.