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[Comparative analysis of comprehensive treatment outcomes in patients with chronic bacterial prostatitis with the addition of the multicomponent complex AndrOPREN].

INTRODUCTION: Type II chronic bacterial prostatitis is characterized by persistent infection, insufficient efficacy of standard therapy, and a high recurrence rate, which necessitates the search for additional treatment options. AIM: To evaluate the efficacy and safety of adding the multicomponent complex AndrOPREN to comprehensive therapy for type II chronic bacterial prostatitis. MATERIALS AND METHODS: This prospective, comparative, randomized study included 233 patients allocated to the main group (n=126) and the control group (n=107). In both groups, patients received standard therapy; men in the main group additionally received the multi-ingredient complex AndrOPREN at a dose of two capsules of No. 1 and two capsules of No. 2 daily for 1-2 months. The follow-up period was 60 days. Changes in symptoms according to the IPSS and QoL scores, urinalysis parameters, microscopy findings of expressed prostatic secretions, pathogen eradication, and biochemical safety parameters were assessed. RESULTS: Improvement was observed in both groups and was more pronounced in the main group. By day 14, the median IPSS score was 14.0 [12.0; 16.0] vs. 18.0 [15.0; 20.0] in the control group (p<0.001); by day 60, the corresponding values were 7.0 [5.0; 9.0] and 11.0 [9.0; 13.0] (p<0.001). At the end of follow-up, the QoL score was 2.0 [1.0; 2.0] and 3.0 [2.0; 3.0], respectively. No microbial growth was detected in 91.2% and 80.4% of patients, respectively (p=0.026); Escherichia coli eradication was achieved in 91.7% and 76.9%, respectively. No biochemical changes indicative of nephrotoxicity or hepatotoxicity were detected. DISCUSSION: The addition of the multicomponent complex AndrOPREN was associated with more rapid symptom resolution, a reduction in inflammatory changes, restoration of the secretory function of the prostate, and greater microbiological efficacy. CONCLUSION: The addition of the multicomponent complex AndrOPREN to comprehensive therapy for type II chronic bacterial prostatitis improves treatment efficacy while maintaining a favorable safety profile.

Humans

Mechanistic insights into flavor deterioration in bitter sturgeon caviar: Evidence from lipidomics and metagenomics.

This study systematically compared the flavor and multi-omics differences between normal caviar and bitter caviar based on quantitative descriptive analysis (QDA), volatile compounds (VOCs) analysis, untargeted lipidomics, and metagenomics. The results showed that bitter caviar was characterized not only by increased bitterness, but also by decreased positive sensory attributes, including buttery, nutty, and marine fresh. VOCs analysis indicated that the volatile profile of bitter caviar was reorganized. Compounds such as 3-hydroxy-2-butanone, 1-octen-3-ol, and (E, Z)-2,6-nonadienal showed higher relative odor activity values (rOAVs); however, these changes did not improve its overall sensory experience. Untargeted lipidomics identified 492 differential lipids. These changes were mainly characterized by decreased PC and increased DG and LPC in bitter caviar. KEGG pathways analysis showed that these differential lipids were mainly associated with glycerophospholipid metabolism, choline metabolism in cancer, and retrograde endocannabinoid signaling. Metagenomic analysis showed that bacteria dominated the microbial community of caviar. Among them, Bacillus and Micromonospora showed relatively high abundance in the caviar microbiota. They were also closely associated with lipid metabolic changes involving PC, DG, and LPC, suggesting their potential as candidate targets for future microbiota-directed regulation of caviar quality. These findings provide new insights into the mechanisms underlying sensory deterioration and flavor formation in bitter caviar, and offer a theoretical basis for improving caviar quality in industrial production.

Animals

Comprehensive identification of carboxylic acids by using bromine isotope-based chemical isotope labelling and structure-guided molecular network.

Carboxylic acids (CAs) are important contributors to the flavor quality of sauce-flavor Chinese Baijiu, yet their comprehensive analysis remains challenging due to poor ionization efficiency, weak chromatographic retention, and limited annotation capability. Herein, we developed a workflow for the high-coverage discovery and annotation of CAs in Baijiu by coupling chemical isotope labeling-liquid chromatography-mass spectrometry with a structure-guided molecular network strategy (SGMNS). A bromine-containing derivatization reagent, 1-(3-aminopropyl)-3-bromoquinolin-1-ium bromide (APBQ), was designed and synthesized to exploit the natural isotope distribution of bromine and characteristic MS/MS fragmentation behavior. Following APBQ derivatization, the target CAs showed superior chromatographic retention and favorable analytical performance. Based on isotopic peak pairing in MS1 and diagnostic fragment validation in MS2, 372 potential CA derivatives were discovered from pooled Baijiu samples and 355 of them were validated by diagnostic fragments in MS2 spectra. To address the scarcity of derivatized spectral libraries, SGMNS was employed for annotation using a background network constructed from APBQ-labeled candidates derived from the Expanded Chinese Baijiu Compound Database. The developed method was further applied to profile Baijiu samples, revealing pronounced differences in CA composition across the seven fermentation rounds. Notably, rounds 3 to 5 exhibited the largest numbers of differential CAs. This study provided an effective analytical strategy for large-scale CA profiling, offering new insight into the chemical basis of flavor formation during multi-round fermentation of sauce-flavor Baijiu.

Isotope Labeling

The relationship between food intake and outdoor temperature in a longitudinal study: a public health perspective in the context of global warming.

BACKGROUND: Climate change affects human health and nutrition. Rising temperatures may significantly impact diets, but research on their influence on dietary habits in large populations remains limited. OBJECTIVES: We aimed to study the link between outdoor temperature and energy-adjusted food consumption across profiles in a longitudinal study. METHODS: This study included 100,851 participants from the NutriNet-Sant&#xe9; study (2009-2023) with 1,716,046 24-h dietary records linked to daily maximum outdoor temperature at the residence, from the nearest M&#xe9;t&#xe9;o-France station. Associations were analyzed using linear mixed models with interactions tested for sex and 6 socioeconomic profiles (employees, privileged, intermediate, young, disadvantaged, and retirees) derived from clustering. RESULTS: Across all subgroups, higher outdoor temperature was associated with higher consumption of fruits, vegetables, processed meats, sweet products, water, alcoholic beverages, and sugar-sweetened beverages, whereas consumption of red meat, pulses, and dairy products decreased. From 25&#xb0;C to 35&#xb0;C, the increase in alcohol consumption with temperature was more pronounced in males {150 g/d [95% confidence interval (CI): 147 g/d, 153 g/d] to 166 g/d [95% CI: 162 g/d, 171 g/d], +11%} than in females [101 g/d (95% CI: 98 g/d, 103 g/d) to 107 g/d (95% CI: 104 g/d, 109 g/d), +6%]. Across socioeconomic profiles, changes shared similar directions, but some trends were more marked, notably for alcoholic beverages among employees (95% CI: 114 g/d, 130 g/d; +14%) and sugar-sweetened beverages in young (95% CI: 56 g/d, 72 g/d; +29%). Consumption of fruits increased more modestly in the young (95% CI: 227 g/d, 248 g/d; +9%) than in employees (95% CI: 194 g/d, 227 g/d; +17%). These changes, although variable in magnitude, were not accompanied by substantial modifications in energy intake or overall diet quality scores. CONCLUSIONS: These results emphasize the importance of targeted prevention messages when temperatures exceed 25&#xb0;C, especially concerning alcoholic and sugar-sweetened beverages, and offer insight into potential long-term food consumption patterns (beyond seasonal changes) in the context of global warming.

Humans

Advances in cereal protein applications for infant and Young child nutrition.

BACKGROUND: The increasing use of plant-derived proteins in infant and young child nutrition necessitates tailored amino acid profiles, high digestibility and strict safety controls. Cereal proteins, such as rice, oat, maize, millet, barley, and wheat, are widely used in complementary foods but face intrinsic limitations, notably lysine and tryptophan deficits, antinutritional factors that reduce bioavailability, gluten immunogenicity in wheat/barley, and inorganic arsenic risks in rice. SCOPE AND APPROACH: This review synthesizes recent advances in processing and formulation strategies, including enzymatic hydrolysis, fermentation, germination, extrusion, cereal-legume complementation, and micronutrient fortification. Their impacts on digestibility, techno-functionality, iron and zinc bioavailability, and protein quality, including Protein Digestibility-Corrected Amino Acid Score (PDCAAS) and Digestible Indispensable Amino Acid Score (DIAAS) are critically reviewed using data from in vitro assays, product development, and clinical trials. KEY FINDINGS AND CONCLUSIONS: Processing and blending approaches can substantially improve protein digestibility, amino acid balance and micronutrient availability, and hydrolyzed rice protein holds clinical promise for cow's milk protein allergy (CMPA). However, most evidence is preclinical, reporting of protein quality is inconsistent, and industrial translation is constrained by sensory, shelf-life, contaminant and cost issues. We recommend standardized DIAAS-based reporting, large-scale feeding trials, sensory /stability optimization, and targeted exploration of underutilized grains (e.g., oat, millet) with active allergen monitoring. Prioritizing amino acid-focused formulation coupled with strategies to enhance micronutrient bioavailability will accelerate safe adoption of cereal proteins in early-life nutrition.

Humans

Hope is linked with more favorable tumor molecular signatures in serous ovarian cancer.

INTRODUCTION: Hope has been associated with improved quality of life and lower mortality in cancer, but the underlying biological mechanisms are poorly characterized. We previously reported that hope was associated with less inflammation and more normalized diurnal cortisol pre-treatment among women with ovarian cancer. We also reported associations of socio-environmental factors with pro-metastatic processes. Here, we used genome-wide transcriptional profiling to quantify associations between hope and tumor molecular signatures reflecting invasiveness, inflammation, and cellular immunity. METHOD: Participants were 74 women with serous ovarian cancer who provided demographic information and completed surveys pre-surgery. Hope was assessed using a face-valid item from the Center for Epidemiological Studies Depression Scale (CES-D). Depression was assessed using the full CES-D without the hope item. Illumina HT12 microarrays were used to assay tumor RNA, and associations between hope and tumor gene expression were quantified, adjusting for depression, age, BMI, grade, and stage. RESULTS: Adjusting for covariates, hope was associated with multiple favorable differences in RNA expression, including lower levels of mesenchymal differentiation (p&#x202f;=&#x202f;0.008) and pro-inflammatory gene regulation (NF-&#x3ba;B: p&#x202f;<&#x202f;0.001; IRF1: p&#x202f;=&#x202f;0.024; STAT: p&#x202f;=&#x202f;0.018), elevated epithelial differentiation (p&#x202f;=&#x202f;0.011), and elevated activity of the IRF7 transcription factor which promotes cellular immunity (p&#x202f;=&#x202f;0.016). CONCLUSIONS: These data suggest that hope is associated with an ovarian tumor gene expression profile characterized by reduced epithelial-mesenchymal transition (EMT) and inflammatory activity, and increased activity of a transcription factor promoting cellular immunity. These findings highlight potential biological implications of a resilience factor such as hope, but need replication with more robust assessments of hope.

Epithelial mesenchymal transition

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

Humans

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1&#x3b1; axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n&#x2009;=&#x2009;146) or osimertinib monotherapy (n&#x2009;=&#x2009;148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P&#x2009;<&#x2009;.001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult

Integrated electronic nose, GC-MS, and metagenomic analyses reveal volatile flavor and microbial community differences in heap-fermented grains of Jiangxiangxing Baijiu across different fermentation degrees.

The fermentation degree of heap-fermented grains in Jiangxiangxing Baijiu production is a critical factor influencing base Baijiu quality. However, conventional assessment methods largely rely on empirical experience and therefore suffer from limited objectivity and accuracy. In this study, integrated volatile profiling and metagenomic approaches were employed to investigate volatile characteristics and microbial functional potential differentiation in fermented grains with different fermentation degrees (under-fermented, normally fermented, and over-fermented). Significant differences in physicochemical properties were observed among fermentation degrees, particularly in acidity and reducing sugar content. Electronic nose analysis revealed distinct sensor response patterns among different fermentation degrees, indicating differences in overall volatile odor fingerprint patterns. A total of 81 volatile compounds were identified by HS-SPME-GC-MS, with aldehydes, ketones, and pyrazines showing pronounced variations among fermentation degrees, and acetaldehyde exhibiting strong discriminatory potential. LEfSe analysis identified 18 microbial taxa as potential biomarkers associated with different fermentation degrees, including Pichia kudriavzevii, Lentibacillus daiqui, and Acetobacter pasteurianus. Correlation analysis revealed significant positive associations between acetaldehyde levels and Acetobacter abundance. Furthermore, KEGG, CAZy, and eggNOG analyses revealed differentiated functional potentials among fermentation degrees, providing insights into the potential metabolic basis associated with flavor differentiation. Overall, these findings highlight that fermentation degree differentiation is closely associated with coordinated changes in physicochemical conditions, microbial communities, and functional potentials, providing ecological insights into flavor differentiation and theoretical support for objective fermentation degree evaluation and quality control of Jiangxiangxing Baijiu production.

Fermentation

Genome-wide identification of CXE gene family in soybean and functional characterization of GmCXE31 in lipid biosynthesis and salt tolerance.

GmCXE31 negatively regulates salt tolerance and lipid synthesis in soybean, and the cxe31-edited lines improve soybean yield and seed quality. Carboxylesterases (CXEs), as essential lipid hydrolases of the &#x3b1;/&#x3b2;-hydrolase fold superfamily, are critical for plant stress responses, hormone signaling and secondary metabolism. The key candidate gene GmCXE31 was previously identified in our laboratory through a genome&#x2011;wide association study (GWAS) of soybean lipid&#x2011;related traits. In the present study, we further identified 60 GmCXE family genes in soybean. Phylogenetic analysis clustered them into 11 conserved subfamilies. Cis-acting element analysis showed their promoters are enriched with elements related to abiotic stress, growth and hormone signaling, suggesting potential roles in soybean development and stress adaptation. GmCXE31 is highly expressed in seedling roots and responsive to strigolactones (SLs) and salt stress. Functional assays revealed that GmCXE31 negatively regulates soybean salt tolerance: its overexpression reduced salt tolerance in Arabidopsis and soybean under 150&#x202f;mM NaCl stress, while its knockout enhanced this trait. Lipid profiling revealed GmCXE31-edited lines had higher seed oil content, elevated oleic/linoleic acid ratio and lower saturated fatty acid proportion, which was achieved by regulating lipid synthesis-related genes like GmNFYA. Agronomic trait analysis showed GmCXE31-edited lines had increased nodule number, plant height and single-plant yield at maturity, with opposite phenotypes in overexpression lines. In conclusion, this study elucidates the multifaceted roles of GmCXE31 in coordinating soybean salt tolerance, lipid metabolism and agronomic traits, providing theoretical and genetic resources for salt-tolerant and high-quality soybean molecular breeding.

Glycine max

Latent profile analysis of pregnant exercise adherence and the relationship with demographic and socio-psychological factors: a multicentre cross-sectional study.

BACKGROUND: Pregnancy physical activity (PA) and exercise benefits both mothers and babies, but requires sustained adherence. Many pregnant women fail to meet recommended levels. The reasons for low adherence comprised fluctuating physiological and environmental factors. This study aims to identify discrete profiles of pregnant women based on exercise adherence and to examine differences in demographic and socio-psychological factors across these profiles. METHODS: A survey was conducted among 1,255 pregnant women in three hospitals in Shenzhen, Dongguan, and Shunde, China, using the Exercise Adherence Rating Scale (EARS), the Pregnancy Exercise Self-Efficacy Scale (P-ESES), and the Pregnancy Physical Activity Social Support Scale (P-PASSS). In the analysis, EARS items were scored higher, indicating a healthier state (e.g., sufficient time and energy). Latent profile analysis (LPA) was employed to classify adherence profiles, and multinomial logistic regression was used to examine differences in demographic, self-efficacy, and social support across four groups. RESULTS: Four profiles of exercise adherence were identified: (1) Profile 1 (16.97%), characterized by deficits in time and energy, (2) Profile 2 (15.22%), a group with sufficient time resources but the lowest self-efficacy, (3) Profile 3 (43.98%), characterized by high adherence despite moderate barriers, and (4) Profile 4 (23.83%), a group with optimal exercise adherence, confidence, and resources. Women with higher P-ESES (OR: 1.14-1.38) and P-PASSS (OR: 1.04-1.06) scores were more likely to be in Profiles 3 and 4. Additionally, women's partners who never or occasionally exercise were significantly more likely to be categorized into Profile 1 (OR = 0.18 for Profile 4 vs. Profile 1). Furthermore, the first trimester emerged as a significant risk period for lower exercise adherence, whereas overweight/obesity was independently associated with higher odds of membership in Profile 4. CONCLUSION: The study identified four distinct profiles of exercise adherence among pregnant women. 32.19% of participants were in the two lower exercise-adherence groups. Pregnant women in Profile 1 were characterized by challenges related to a lack of time and knowledge. Participants in Profile 2 showed the lowest exercise self-efficacy and social support among the four profiles. Furthermore, women in early pregnancy were more likely to have lower adherence profiles. Hence, targeted interventions addressing these specific groups are warranted to improve exercise adherence during pregnancy.

Humans

Flavoromics-based profiling reveals taste and aroma differences between infant formula and breast milk.

Flavor differences between infant formula (IF) and breast milk (BM) are considered a potential factor affecting infants' acceptance of IF. This experiment employs flavoromics combined with multivariate statistical analysis to systematically compare the flavor profiles of IF and BM. Electronic tongue analysis and amino acid correlation revealed that IF was characterised by pronounced saltiness and umami richness, whereas BM exhibited greater bitterness and astringency. Volatile compound profiling identified five key flavor constituents in IF, predominantly aldehydes such as hexanal and pentanal. In contrast, BM contained a broader array of compounds-including acids, aldehydes, and esters-resulting in a more complex flavor profile. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based metabolic pathway annotation, together with fatty acid profiling, suggested that some volatiles may be associated with lipid oxidation, Maillard reaction and sulfur-containing amino acid degradation pathways, offering a theoretical basis for the targeted optimisation of IF flavor.

Humans

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-&#x3ba;B, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans

Meningioma methylation profiling as a complement to WHO grading: a single-center experience.

OBJECTIVE: The methylation profile of meningiomas is a promising predictive tool that may improve risk stratification beyond WHO grading. This study aimed to evaluate the clinical relevance and real-world applicability of routine epigenetic testing in meningioma management. METHODS: The authors retrospectively analyzed patients who underwent meningioma resection between January 2021 and December 2023. Histopathological grading (WHO 2021) and methylation profiling (methylation class [MC]) with the MethylationEPIC v1.0 (850k) chip were performed by an independent neuropathologist. RESULTS: A total of 106 patients were included; 81 tumors (76%) were classified as WHO grade 1, 20 (19%) as grade 2, and 5 (5%) as grade 3. Epigenetically, 55 tumors (52%) were classified as benign, 18 (17%) as intermediate, and 2 (2%) as malignant; 31 (29%) could not be classified. Discordances between WHO grading and methylation profiling were observed in 18 of 74 cases. Tumor board decisions were made after a median of 8 days postoperatively, guided by WHO grading; however, the epigenetic report was only available after a median of 23 days. During follow-up, 20 patients experienced tumor progression. Progression was significantly associated with the MC (r = -0.4, p < 0.001) and tumor volume (r = 0.4, p = 0.0005), but not with WHO grading (r = 0.17, p = 0.084). However, the relatively high rate of unclassified tumors and delayed result availability limited the direct impact of MC profiling on immediate clinical decision-making. Interestingly, progression-free survival in MC-unclassified tumors mirrored that of the intermediate group. CONCLUSIONS: Methylation profiling demonstrates superior predictive accuracy for meningioma progression and complements WHO grading, especially in identifying malignant meningiomas. However, its current clinical utility is constrained by technical and logistical limitations. In real-world practice, epigenetic classification should therefore be considered a complementary tool rather than a replacement for established histopathological assessment.

Humans

Evolutionary characterization and expression profiling of ACC and FASN genes in Chinese mitten crab Eriocheir sinensis.

Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) are rate-limiting enzymes in the fatty acid biosynthetic pathway, yet their evolutionary relationships, sequence features, and expression profiles remain poorly understood in crustaceans, particularly in the economically important Chinese mitten crab (Eriocheir sinensis). Here, we identified and systematically analyzed ACC and FASN genes in E. sinensis using comparative genomic analyses across 43 species. ACC was highly conserved as a single-copy gene in invertebrates, in contrast to the multiple paralogs observed in vertebrates. Similarly, FASN was generally maintained as a single-copy gene across most taxa but exhibited lineage-specific expansion in certain insect groups. Phylogenetic and structural analysis revealed strong conservation of both genes within crustaceans, supported by multiple conserved motifs and canonical functional domains. Expression profiling showed predominant expression in the hepatopancreas and midgut, suggesting their potential involvement in crustacean lipid metabolism. During the molting cycle, ACC and FASN exhibited higher expression levels during stages C and D, suggesting an increased capacity for fatty acid biosynthesis before molting. In addition, dietary lipid levels experiment revealed that ACC and FASN expression responded dynamically to dietary lipid availability, with increased expression at moderate lipid levels but reduced expression under excessive lipid supplementation, indicating a possible adaptive transcriptional response to lipid status. Collectively, this study provides insights into the evolutionary conservation and expression dynamics of ACC and FASN and improves our understanding of lipid metabolic adaptation in crustaceans.

Animals

Safety profiles of CAR-T cell therapy in systematic autoimmune diseases: a systematic review and analysis.

BACKGROUND: Chimeric antigen receptors (CARs)-T cell therapy is emerging as a potent approach for autoimmune diseases. However, its application in autoimmune conditions remains limited, and safety outcomes observed in malignancies can't reliably serve as a reference. Therefore, it's necessary to summarize the safety profiles in autoimmune diseases to provide evidence for future expanding trials. METHODS: A systematic review was conducted to analyze the CAR-T therapy safety in rheumatic diseases via database searches up to December 2025. Studies reporting safety data were included, while abstracts, reviews, and cases with malignancies were excluded. Factors associated with cytokine release syndrome (CRS) were analyzed using Firth's penalized logistic regression. RESULTS: This study included 38 studies, involving a total of 115 patients with autoimmune disease. Severe adverse events were rare. CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 70.4% and 4.3% of patients, respectively. Most CRS were low-grade. Multivariate analysis identified BCMA-targeted therapy and allogeneic CAR-T products may as independent factors associated with a reduced risk of CRS. Transient hematologic toxicity and hypogammaglobulinemia were frequently reported, with infections occurring in nearly half of the patients. However, prolonged cytopenia and severe infection were infrequent. CONCLUSION: Based on the current available evidence, CAR-T therapy appears to have a generally manageable safety profile in autoimmune diseases, supporting its potential as a promising treatment option for patients with relapsed or refractory autoimmune diseases. However, these findings remain preliminary, and further expanded studies are warranted in the future to provide higher-level evidence.

Humans

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3&#x3b2;-Hydroxysteroid dehydrogenase/&#x394;5-&#x394;4 isomerase (3&#x3b2;-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals