The causality between use of glucocorticoids and risk of pancreatitis: a Mendelian randomization study.

Background and aim: To date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship. Methods: We carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p < 5×10-8). Results: Our MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained. Conclusions: This MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.

Causal association between peripheral immune cells and IgA nephropathy: a Mendelian randomization study.

Background: The relationship between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is widely known; however, causal evidence of this link is lacking. Here, we aimed to determine the causal effect of peripheral immune cells, specifically total white blood cells, lymphocytes, monocytes, basophils, eosinophils, and neutrophils, as well as lymphocyte subset traits, on the IgAN risk using a Mendelian randomization (MR) analysis. Methods: The inverse-variance weighted (IVW) method was used for the primary analysis. We applied three complementary methods, including the weighted median, MR-Egger regression, and MR-PRESSO, to detect and correct for the effect of horizontal pleiotropy. Additionally, we performed a multivariable MR (MVMR) analysis, adjusting for the effects of C-reactive protein (CRP) levels. The roles of specific lymphocyte subtypes and their significance have garnered interest. Bidirectional two-sample MR analysis was performed to test the potential causal relationships between immune traits, including median fluorescence intensities (MFIs) and the relative cell count (AC), and IgAN. Results: The IVW-MR analysis suggested a potential causal relationship between lymphocyte counts and IgAN in Europe (OR per 1-SD increase: 1.43, 95% CI: 1.08-1.88, P = 0.0123). The risk effect of lymphocytes remained even after adjusting for CRP levels using the MVMR method (OR per 1-SD increase: 1.44, 95% CI: 1.05-1.96, P = 0.0210). The other sensitivity analyses showed a consistent trend. The largest GWAS published to date was used for peripheral blood immunophenotyping to explore the potential causal relationship between peripheral immune cell subsets and IgAN. Six AC-IgAN and 14 MFI-IgAN pairs that reached statistical significance (P < 0.05) were detected. Notably, CD3, expressed in eight subsets of T cells, consistently showed a positive correlation with IgAN. The bidirectional MR analysis did not reveal any evidence of reverse causality. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. Conclusions: Genetically determined high lymphocyte counts were associated with IgAN, supporting that high lymphocyte counts is causal risk factor for IgAN.

Bold rats (Niviventer confucianus) are more effective in seed dispersal: evidence both under enclosure conditions and in the field.

Rodents are important seed dispersers of plants because they move seeds far away from the parent trees and hoard seeds in the soil, benefiting seed dispersal and regeneration. Traits of plant seeds and animals are associated with rodent-mediated seed dispersal, but animal personality, the consistent individual behavioral differences in time and environments, has not been fully considered. Here, we first measured the personality of 26 Niviventer confucianus in the laboratory, and 10 individuals in the field of one population, and then tested their behavior of seed consumption and hoarding both in semi-natural enclosures and the field. We tested the hypothesis that individuals with different personalities have different preferences for seed consumption and hoarding, which has different implications for seed dispersal and regeneration. Under the enclosure conditions, all parameters of personality are repeatable; bold individuals harvested fewer seeds but scatter-hoarded more seeds and dispersed farther than timid ones, whereas active individuals consumed more seeds, but left fewer seeds on the ground surface than inactive ones. In the field, boldness, activity, and exploration of the animals are repeatable; bold individuals scatter-hoarded more seeds to farther distances than timid ones, whereas active individuals harvested and consumed more seeds than inactive ones. These results suggest that bold rats tended to scatter hoard seeds and disperse them to a longer distance, implying they are more effective in seed dispersal. In the future, animal personality (e.g. boldness and activity) should be considered in seed dispersal studies and ecological-based manipulation in seed dispersal and regeneration of forests.

Single­cell RNA sequencing analysis of human embryos from the late Carnegie to fetal development.

BACKGROUND: The cell development atlas of transition stage from late Carnegie to fetal development (7-9 weeks) remain unclear. It can be seen that the early period of human embryos (7-9 weeks) is a critical research gap. Therefore, we employed single­cell RNA sequencing to identify cell types and elucidate differentiation relationships. RESULTS: The single­cell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7-9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. CONCLUSIONS: We provide the cell development atlas for human embryos (7-9 weeks). Two distinct cell development and differentiation pathways are revealed.

NEMF-mediated CAT-tailing defines distinct branches of translocation-associated quality control.

Ribosome stalling during co-translational translocation at the endoplasmic reticulum (ER) causes translocon clogging and impairs ER protein biogenesis. Mammalian cells resolve translocon clogging vial a poorly characterized translocation-associated quality control (TAQC) process. Here, we combine genome-wide CRISPR screen with live cell imaging to dissect the molecular linchpin of TAQC. We show that substrates translated from mRNAs bearing a ribosome stalling poly(A) sequence are degraded by lysosomes and the proteasome, while substrates encoded by non-stop mRNAs are degraded by an unconventional ER-associated degradation (ERAD) mechanism involving ER-to-Golgi trafficking and KDEL-dependent substrate retrieval. The triaging diversity appears to result from the heterogeneity of NEMF-mediated CATylation, because a systematic characterization of representative CAT-tail mimetics establishes an AT-rich tail as a "degron" for ERAD, whereas an AG-rich tail can direct a secretory protein to the lysosome. Our study reveals an unexpected protein sorting function for CAT-tailing that safeguards ER protein biogenesis.

CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patient. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.

Proximity labeling expansion microscopy (PL-ExM) evaluates interactome labeling techniques.

Understanding protein-protein interactions (PPIs) through proximity labeling has revolutionized our comprehension of cellular mechanisms and pathology. Various proximity labeling techniques, such as HRP, APEX, BioID, TurboID, and µMap, have been widely used to biotinylate PPIs or organelles for proteomic profiling. However, the variability in labeling precision and efficiency of these techniques often results in limited reproducibility in proteomic detection. We address this persistent challenge by introducing proximity labeling expansion microscopy (PL-ExM), a super-resolution imaging technique that combines expansion microscopy with proximity labeling techniques. PL-ExM enabled up to 17 nm resolution with microscopes widely available, providing visual comparison of the labeling precision, efficiency, and false positives of different proximity labeling methods. Our mass spectrometry proteomic results confirmed that PL-ExM imaging is reliable in guiding the selection of proximity labeling techniques and interpreting the proteomic results with new spatial information.

Combining transcriptomics and HPLC to uncover variations in quality formation between 'Benihoppe' and 'Fenyu No.1' strawberries.

'Benihoppe' and 'Fenyu No.1' are representative varieties of red and pink strawberries in China, possess distinct hue and flavor profiles. This study analyzed the underlying biochemical and molecular differences of two varieties utilizing transcriptomics and high-performance liquid chromatography (HPLC). Ripening 'Benihoppe' fruits accumulated more sucrose and pelargonin-3-glucoside (P3G) with a little cyanidin and higher firmness. Whereas ripening 'Fenyu No.1' fruits contained more fructose, glucose, malic acid and ascorbic acid (AsA), but less P3G and citric acid. Moreover, genotype significantly influenced phenolic compounds contents in strawberries. Transcriptome analysis revealed that pectin degradation (PL, PG, PE), sucrose synthesis (CWINV, SUS, TPS) and citric acid metabolism (α-OGDH, ICDH, GAD, GS, GDH, PEPCK, AST) were weakened in 'Benihoppe' fruit. In contrast, the synthesis of sucrose (CWINH, SPS), citric acid (CS, PEPC), anthocyanin (F3H, F3'H, F3'5'H, DFR, UFGT and ANS), and citric acid transport (V-ATPase) was enhanced. In 'Fenyu No.1' fruit, the degradation of sucrose, citric acid, and pectin was enhanced, along with the synthesis of malic acid (ME) and ascorbic acid (PMM, MDHAR and GaLUR). However, anthocyanins synthesis, glucose metabolism (HK, G6PI, PFK, G6PDH, PGK, PGM, ENO, PK), fructose metabolism (FK), citric acid synthesis and transport, and AsA degradation (AO, APX) were relatively weak. RT-qPCR results corroborated the transcriptome data. In conclusion, this study revealed the distinctions and characteristics of strawberries with different fruit colors regarding texture, flavor and color formation processes. These findings offer valuable insights for regulating metabolic pathways and identifying key candidate genes to improve strawberry quality.

Foliar application of sodium selenite affects the growth, antioxidant system, and fruit quality of strawberry.

Introduction: Selenium (Se) plays a vital role in various physiological processes in plants and is regarded as an essential micronutrient for human health as well. Methods: In this study, sodium selenite solution at 10, 40, 70, and 100 mg·L-1 concentrations was foliar sprayed, and the strawberry plant growth, antioxidant system, and fruit quality with an emphasis on sugar and acid content were assessed. Results: The results showed that 10 mg·L-1 of sodium selenite treatment promoted plant growth, while all the treated concentrations could enhance photosynthesis, the antioxidant system in leaves, the content of Se, and ascorbic acid in fruits. More importantly, 40 mg·L-1 sodium selenite treatment significantly increased fruit weight, total soluble solid, total phenolic content, and anthocyanins, as well as improved the shape index. Furthermore, it decreased the total flavonoid and proanthocyanidin content. Particularly, sodium selenite treatment at 40 and 70 mg·L-1 largely increased the ratio of soluble sugars to titratable acid. The changes of predominant sugars and organic acids during fruit development were further investigated. The sucrose, fructose, and glucose content was upregulated by sodium selenite treatment through upregulating the activities of sucrose phosphate synthase (SPS) and acid invertase, as well as the FaSPS expression. In addition, sodium selenite treatment inhibited the activity of citrate synthase and phosphoenolpyruvate carboxylase, rather than modulating their transcript levels to reduce the citric acid content. Conclusions: This work presented a potentially efficient approach to enhance plant growth and fruit quality and supplement Se in strawberry, providing insights into the mechanism of regulating sugar and acid metabolism by Se.

Trioxane-based MS-cleavable Cross-linking Mass Spectrometry for Profiling Multimeric Interactions of Cellular Networks.

Cross-linking mass spectrometry (XL-MS) is a powerful technology for mapping protein-protein interactions (PPIs) at the systems-level. By covalently connecting pairs of proximal residues, cross-linking reagents provide distance restraints to infer protein conformations and interaction interfaces. While binary cross-links have been remarkably informative, multimeric cross-links can offer enhanced spatial resolution to facilitate the characterization of dynamic and heterogeneous protein complexes. However, the identification of multimeric cross-links remains extremely challenging due to fragmentation complexity and the vast expansion of database search space. Here, we present a novel trioxane-based MS-cleavable homotrifunctional cross-linker TSTO, which can target three proximal lysine residues simultaneously. Owing to its unique structure and MS-cleavability, TSTO enables fast and unambiguous identification of cross-linked peptides using LC-MS n analysis. Importantly, we have demonstrated that the TSTO-based XL-MS platform is effective for mapping PPIs of protein complexes and cellular networks. The trimeric interactions captured by TSTO have uncovered new structural details that cannot be easily revealed by existing reagents, allowing in-depth description of PPIs to facilitate structural modeling. This development not only advances XL-MS technologies for global PPI profiling from living cells, but also offers a new direction for creating multifunctional MS-cleavable cross-linkers to further push structural systems biology forward in the future.

Identifying potential anthocyanin biosynthesis regulator in Chinese cherry by comprehensive genome-wide characterization of the R2R3-MYB transcription factor gene family.

BACKGROUND: Chinese cherry [Cerasus pseudocerasus (Lindl.) G.Don] (syn. Prunus pseudocerasus Lindl.) is an economically important fruiting cherry species with a diverse range of attractive colors, spanning from the lightest yellow to the darkest black purple. However, the MYB transcription factors involved in anthocyanin biosynthesis underlying fruit color variation in Chinese cherry remain unknown. RESULTS: In this study, we characterized the R2R3-MYB gene family of Chinese cherry by genome-wide identification and compared it with those of 10 Rosaceae relatives and Arabidopsis thaliana. A total of 1490 R2R3-MYBs were classified into 43 subfamilies, which included 29 subfamilies containing both Rosaceae MYBs and AtMYBs. One subfamily (S45) contained only Rosaceae MYBs, while three subfamilies (S12, S75, and S77) contained only AtMYBs. The variation in gene numbers within identical subfamilies among different species and the absence of certain subfamilies in some species indicated the species-specific expansion within MYB gene family in Chinese cherry and its relatives. Segmental and tandem duplication events primarily contributed to the expansion of Chinese cherry R2R3-CpMYBs. The duplicated gene pairs underwent purifying selection during evolution after duplication events. Phylogenetic relationships and transcript profiling revealed that CpMYB10 and CpMYB4 are involved in the regulation of anthocyanin biosynthesis in Chinese cherry fruits. Expression patterns, transient overexpression and VIGS results confirmed that CpMYB10 promotes anthocyanin accumulation in the fruit skin, while CpMYB4 acts as a repressor, inhibiting anthocyanin biosynthesis of Chinese cherry. CONCLUSIONS: This study provides a comprehensive and systematic analysis of R2R3-MYB gene family in Chinese cherry and Rosaceae relatives, and identifies two regulators, CpMYB10 and CpMYB4, involved in anthocyanin biosynthesis in Chinese cherry. These results help to develop and utilize the potential functions of anthocyanins in Chinese cherry.

Genome-Wide Analysis of Polygalacturonase Gene Family Reveals Its Role in Strawberry Softening.

Fruit softening is a prominent attribute governing both longevity on shelves and commercial worth. Polygalacturonase (PG) plays a major role in strawberry fruit softening. However, the PG gene family in strawberry has not been comprehensively analyzed. In this study, 75 FaPG genes were identified in the octoploid strawberry genome, which were classified into three groups according to phylogenetic analysis. Subcellular localization prediction indicated that FaPGs are mostly localized to the plasma membrane, cytoplasm, and chloroplasts. Moreover, the expression of FaPGs during strawberry development and ripening of 'Benihoppe' and its softer mutant was estimated. The results showed that among all 75 FaPGs, most genes exhibited low expression across developmental stages, while two group c members (FxaC_21g15770 and FxaC_20g05360) and one group b member, FxaC_19g05040, displayed relatively higher and gradual increases in their expression trends during strawberry ripening and softening. FxaC_21g15770 was selected for subsequent silencing to validate its role in strawberry softening due to the fact that it exhibited the highest and most changed expression level across different developmental stages in 'Benihoppe' and its mutant. Silencing FxaC_21g15770 could significantly improve strawberry fruit firmness without affecting fruit color, soluble solids, cellulose, and hemicellulose. Conversely, silencing FxaC_21g15770 could significantly suppress the expression of other genes related to pectin degradation such as FaPG-like, FaPL, FaPME, FaCX, FaCel, FaGlu, FaXET, and FaEG. These findings provide basic information on the FaPG gene family for further functional research and indicate that FxaC_21g15770 plays a vital role in strawberry fruit softening.

[Mechanism of Dabugan Decoction in treatment of generalized anxiety disorder based on network pharmacology and experimental verification].

This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1ß, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1ß in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.

Exposure to a mixture of metal(loid)s and sleep quality in pregnant women during early pregnancy: A cross-sectional study.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

Multiparameter MRI-based radiomics analysis for preoperative prediction of type II endometrial cancer.

Objectives: This study aimed to develop and validate a radiomics nomogram based on multiparameter MRI for preoperative differentiation of type II and type I endometrial carcinoma (EC). Methods: A total of 403 EC patients from two centers were retrospectively recruited (training cohort, 70 %; validation cohort, 30 %). Radiomics features were extracted from T2-weighted imaging, dynamic contrast-enhanced T1-weighted imaging at delayed phase(DCE4), and apparent diffusion coefficient (ADC) maps. Following dimensionality reduction, radiomics models were developed by logistic regression (LR), random forest (RF), bootstrap aggregating (Bagging), support vector machine (SVM), artificial neural network (ANN), and naive bayes (NB) algorithms. The diagnostic performance of each radiomics model was evaluated using the ROC curve. A nomogram was constructed by incorporating the optimal radiomics signatures with significant clinical-radiological features and immunohistochemistry (IHC) markers obtained from preoperative curettage specimens. The diagnostic performance and clinical value of the nomogram were evaluated using ROC curves, calibration curves, and decision curve analysis (DCA). Results: Among the radiomics models, the NB model, developed from 12 radiomics features derived from ADC and DCE4 sequences, exhibited strong performance in both training and validation sets, with the AUC values of 0.927 and 0.869, respectively. The nomogram, incorporating the radiomics model with significant clinical-radiological features and IHC markers, demonstrated superior performance in both the training (AUC = 0.951) and the validation sets (AUC = 0.915). Additionally, it exhibited excellent calibration and clinical utility. Conclusions: The radiomics nomogram has great potential to differentiate type II from type I EC, which may be an effective tool to guide clinical decision-making for EC patients.

Ursolic acid attenuates oligospermia in busulfan-induced mice by promoting motor proteins.

Background: Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid's effect on busulfan-induced oligospermia in mouse models. Methods: A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results: The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.

Total sputum nitrate/nitrite is associated with exacerbations and Pseudomonas aeruginosa colonisation in bronchiectasis.

Background: Sputum nitrate/nitrite, which is the main component of reactive nitrogen species, is a potential biomarker of disease severity and progression in bronchiectasis. This study aimed to determine the association between nitrate/nitrite and exacerbations and airway microbiota in bronchiectasis. Methods: We measured total nitrate/nitrite concentration in sputum samples collected from 85 patients with stable bronchiectasis, performed 16S ribosomal RNA sequencing of sputum samples and predicted the denitrification ability of airway microbiota using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Relationships between sputum total nitrate/nitrite and disease severity, exacerbations and airway microbiota were examined. Results: Higher total sputum nitrate/nitrite was associated with more severe bronchiectasis defined by E-FACED (exacerbation, forced expiratory volume in 1 s, age, chronic colonisation by Pseudomonas aeruginosa, radiological extension and dyspnoea) (p=0.003) or Bronchiectasis Severity Index (p=0.006) and more exacerbations in the prior 12 months (p=0.005). Moreover, total sputum nitrate/nitrite was significantly higher in patients with worse cough score (p=0.03), worse sputum purulence score (p=0.01) and worse Medical Research Council dyspnoea score (p=0.02). In addition, the total sputum nitrate/nitrite of the P. aeruginosa colonised (PA) group was higher than that of the non-P. aeruginosa colonised (NPA) group (p=0.04), and the relative abundance of P. aeruginosa was positively correlated with total nitrate/nitrite (r=0.337, p=0.002). Denitrification module (M00529) was also significantly enriched in the PA group compared to the NPA group through PICRUSt analyses. Using receiver-operating characteristic analysis, total nitrate/nitrite was associated with exacerbations during 1-year follow-up (area under the curve 0.741, p=0.014). Conclusions: Sputum nitrate/nitrite is a biomarker of disease severity and associated with P. aeruginosa colonisation in bronchiectasis.

Exposure to Titanium Dioxide Nanoparticles Leads to Specific Disorders of Spermatid Elongation via Multiple Metabolic Pathways in Drosophila Testes.

Titanium dioxide nanoparticles (TiO2 NPs) have been extensively utilized in various applications. However, the regulatory mechanism behind the reproductive toxicity induced by TiO2 NP exposure remains largely elusive. In this study, we employed a Drosophila model to assess potential testicular injuries during spermatogenesis and conducted bulk RNA-Seq analysis to elucidate the underlying mechanisms. Our results reveal that while prolonged exposure to lower concentrations of TiO2 NPs (0.45 mg/mL) for 30 days did not manifest reproductive toxicity, exposure at concentrations of 0.9 and 1.8 mg/mL significantly impaired spermatid elongation in Drosophila testes. Notably, bulk RNA-seq analysis revealed that TiO2 NP exposure affected multiple metabolic pathways including carbohydrate metabolism and cytochrome P450. Importantly, the intervention of glutathione (GSH) significantly protected against reproductive toxicity induced by TiO2 NP exposure, as it restored the number of Orb-positive spermatid clusters in Drosophila testes. Our study provides novel insights into the specific detrimental effects of TiO2 NP exposure on spermatid elongation through multiple metabolic alterations in Drosophila testes and highlights the protective role of GSH in countering this toxicity.

Protein profile of circulating extracellular vesicles reveals biomarker candidates for diagnosis of post-traumatic deep vein thrombosis.

BACKGROUND AND OBJECTIVE: Deep vein thrombosis (DVT) is a common complication after trauma and mostly without specific symptoms. Timely diagnosis and early appropriate treatment measures can prevent further development of thrombosis for patients with traumatic lower extremity fractures. Although extracellular vesicles (EVs) are confirmed as promising disease biomarkers, little is known about the role of altered levels and composition in the diagnosis of post-traumatic DVT. METHOD: The levels of circulating EVs subgroups were measured using flow cytometry. Isolated EVs were characterized and subjected to proteomics analysis to screen for differentially expressed proteins (DEPs) between DVT and non-DVT patients. Regularized logistic regression analysis based on L2 penalty terms using R's caret package was applied to build a model for DVT diagnosis. RESULTS: Compared to non-DVT patients, DVT patients had higher circulating hepatocyte-derived EVs (hEVs) with good predictive value for post-traumatic DVT diagnosis. The results of the proteomic analysis showed that differentially expressed proteins (DEPs) of circulating EVs between the DVT group and non-DVT group were enriched in the complement and coagulation cascade. Finally, an integrated model of five biomarkers including SERPING1, C8G, CFH, FIX, and hEVs level was established for post-traumatic DVT diagnosis with robust identification of the traumatic patients with and without DVT (AUC 0.972). CONCLUSION: Post-traumatic DVT patients had changed levels and composition of circulating EVs compared to non-DVT patients and healthy controls. Circulating EVs may acquire pathological protein signatures and become potential biomarkers for identifying subjects' post-traumatic DVT.

Clinical Application of Artificial Intelligence in the Ultrasound Classification of Hepatic Cystic Echinococcosis.

Hepatic cystic echinococcosis (HCE) is a zoonotic disease that occurs when the larvae of Echinococcus granulosus parasitize the livers of humans and mammals. HCE has five subtypes, and accurate subtype classification is critical for choosing a treatment strategy. To evaluate the clinical utility of artificial intelligence (AI) based on convolutional neural networks (CNNs) in the classification of HCE subtypes via ultrasound imaging, we collected ultrasound images from 4,012 HCE patients at the First Affiliated Hospital of Xinjiang Medical University between 2008 and 2020. Specifically, 1,820 HCE images from 967 patients were used as the training and validation sets for the construction of the AI model, and the remaining 6,808 images from 3,045 patients were used as the test set to evaluate the performance of the AI models. The 6,808 images were randomly divided into six groups, and each group contained equal proportions of the five subtypes. The data of each group were analyzed by a resident physician. The accuracy of HCE subtype classification by the AI model and by manual inspection was compared. The AI HCE classification model showed good performance in the diagnosis of subtypes CE1, CE2, CE4, and CE5. The overall accuracy of the AI classification (90.4%) was significantly greater than that of manual classification by physicians (86.1%; P <0.05). The CNN can better identify the five subtypes of HCE on ultrasound images and should help doctors with little experience in more accurately diagnosing HCE.