Post-marketing safety concerns of sotorasib: A disproportionality analysis based on FDA adverse event reporting system.

Background: Sotorasib has been approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Due to the limitations of clinical trials, potential adverse events (AEs) and long-term safety issues cannot be detected. The presented study aimed to evaluate sotorasib-associated AEs using the FDA Adverse Event Reporting System (FAERS) database. Methods: Post-marketing AE reports of sotorasib in the database were collected for analysis. Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical bayes geometric mean (EBGM) algorithms, were performed to mine the signals of sotorasib-associated AEs. The median duration, quartiles and the Weibull shape parameter (WSP) test were used to assess the onset time data. Results: The database contained 1538 cases of sotorasib as primary suspect (PS), with 27 signals detected, scattering in 5 SOCs. The SOC of hepatobiliary disorders (182, ROR 4.48, PRR 4.07, IC 2.02, EBGM 4.07) met the four methodological thresholds. The median onset time of sotorasib-associated AEs was 42 days (interquartile range [IQR] 14-86.75 days). Different SOCs had different types of risk over time. Conclusion: After obtaining marketing authorization, the study identified all potentially relevant adverse event (AE) signals expected to have a reporting frequency higher than anticipated and characterized them during sotorasib treatment.

Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus.

Objective: In this study, we examined the therapeutic effects of Yinhuapinggan granules (YHPGs) in influenza-infected mice. We also examined how YHPGs affect the composition of the intestinal flora and associated metabolites. Methods: We used the nasal drip method to administer the influenza A virus (IAV) H1N1 to ICR mice. Following successful model construction, the mice were injected with 0.9% sterile saline and low (5.5 g/kg), medium (11 g/kg), and high (22 g/kg) doses of YHPGs. The pathological changes in the lungs and intestines were evaluated by gavage for 5 consecutive days. Detection of sIgA, IL-6, TNF-α, INF-γ, and TGF-ß cytokine levels in serum by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to measure the mRNA and protein expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) in the colon. To assess the influence of YHPGs on the intestinal microbiota, feces were obtained from the mice for 16s rRNA sequencing, and short-chain fatty acids (SCFAs) were measured in the feces. Results: By reducing the production of pro-inflammatory cytokines and increasing the relative expression of claudin-1, occludin, and ZO-1 in colon tissues, YHPGs had a protective effect in tissues from the lungs and colon. When YHPGs were administered to mice with IAV infection, the relative abundance of Lactobacillus, Coprobacillus, Akkermansia, Prevotella, Oscillospira, and Ruminococcus increased, whereas the relative abundance of Desulfovibrio decreased. Conclusion: The therapeutic mechanism of YHPGs against IAV infection in mice may be underpinned by modulation of the structural composition of colonic bacteria and regulation of SCFA production.

Use of CT-derived radiomic features to preoperatively identify invasive mucinous adenocarcinoma in solitary pulmonary nodules ≤3 cm.

Objective: In this study, we aimed to utilize computed tomography (CT)-derived radiomics and various machine learning approaches to differentiate between invasive mucinous adenocarcinoma (IMA) and invasive non-mucinous adenocarcinoma (INMA) preoperatively in solitary pulmonary nodules (SPN) ≤3 cm. Methods: A total of 538 patients with SPNs measuring ≤3 cm were enrolled, categorized into either the IMA group (n = 50) or INMA group (n = 488) based on postoperative pathology. Radiomic features were extracted from non-contrast-enhanced CT scans and identified using the least absolute shrinkage and selection operator (LASSO) algorithm. In constructing radiomics-based models, logistic regression, support vector machines, classification and regression trees, and k-nearest neighbors were employed. Additionally, a clinical model was developed, focusing on CT radiological features. Subsequently, this clinical model was integrated with the most effective radiomic model to create a combined model. Performance assessments of these models were conducted, utilizing metrics such as the area under the receiver operating characteristic curve (AUC), DeLong's test, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: The support vector machine approach showed superior predictive efficiency, with AUCs of 0.829 and 0.846 in the training and test cohorts, respectively. The clinical model had AUCs of 0.760 and 0.777 in the corresponding cohorts. The combined model had AUCs of 0.847 and 0.857 in the corresponding cohorts. Furthermore, compared to the radiomic model, the combined model significantly improved performance in both the training (DeLong test P = 0.045, NRI 0.206, IDI 0.024) and test cohorts (P = 0.029, NRI 0.125, IDI 0.032), as well as compared to the clinical model in both the training (P = 0.01, NRI 0.310, IDI 0.09) and test cohorts (P = 0.047, NRI 0.382, IDI 0.085). Conclusion: the combined model exhibited excellent performance in distinguishing between IMA and INMA in SPNs ≤3 cm.

The execution of saccadic eye movements suppresses visual processing of both color and luminance in the early visual cortex of humans.

Our eyes execute rapid, directional movements known as saccades, occurring several times per second, to focus on objects of interest in our environment. During these movements, visual sensitivity is temporarily reduced. Despite numerous studies on this topic, the underlying mechanism remains elusive, including a lingering debate on whether saccadic suppression affects the parvocellular visual pathway. To address this issue, we conducted a study employing steady-state visual evoked potentials (SSVEPs) elicited by chromatic and luminance stimuli, while observers performed saccadic eye movements. We also employed an innovative analysis pipeline to enhance the signal-to-noise ratio, yielding superior results compared to the previous method. Our findings revealed a clear suppression effect on SSVEP signals during saccades when compared to fixation periods. Notably, this suppression effect was comparable for both chromatic and luminance stimuli. We went further to measure the suppression effect across various contrast levels, which enabled us to model SSVEP responses using contrast response functions. The results suggest that saccades primarily reduce response gain without significantly affecting contrast gain, and that this reduction applies uniformly to both chromatic and luminance pathways. In summary, our study provides robust evidence that saccades similarly suppress visual processing in both the parvocellular and magnocellular pathways within the human early visual cortex, as indicated by SSVEP responses. The observation that saccadic eye movements impact response gain rather than contrast gain implies that they influence visual processing through a multiplicative mechanism.

Antimicrobial Properties of Carboxymethyl Cellulose/Starch/N'N Methylenebisacrylamide Membranes Endowed by Ultrasound and Their Potential Application in Antimicrobial Packaging.

Cellulose is used widely in antimicrobial packaging due to its abundance in nature, biodegradability, renewability, non-toxicity, and low cost. However, how efficiently and rapidly it imparts high antimicrobial activity to cellulose-based packaging materials remains a challenge. In this work, Ag NPs were deposited on the surface of carboxymethyl cellulose/starch/N'N Methylenebisacrylamide film using ultrasonic radiation. Morphology and structure analysis of as-prepared films were conducted, and the antibacterial effects under different ultrasonic times and reductant contents were investigated. These results showed that Ag NPs were distributed uniformly on the film surface under an ultrasonic time of 45 min. The size of Ag NPs changes as the reducing agent content decreases. The composite film demonstrated a slightly better antibacterial effect against E. coli than against S. aureus. Therefore, this work can provide valuable insights for the research on antimicrobial packaging.

Illness perceptions in relation to self-management behaviour among elderly patients with COPD: A cross-sectional study.

AIMS: The purpose of this study was to investigate the status of self-management behaviour and illness perceptions and to examine illness perceptions in relation to self-management behaviour in elderly patients with chronic obstructive pulmonary disease (COPD). METHODS: A cross-sectional study was conducted, and 152 elderly COPD patients were recruited via the convenience sampling method. The COPD Self-Management Scale and the Revised Illness Perception Questionnaire for COPD patients were used to examine self-management behaviour and illness perceptions. Pearson correlation analysis, univariate analysis and hierarchical linear regression analysis were used to explore illness perceptions in relation to self-management behaviour. RESULTS: The mean overall score for self-management behaviour was 2.90 ± 0.39. Among the subscales of self-management behaviour, information management had the lowest score of 2.20 ± 0.76. Patients' demographic and clinical characteristics, including educational level, smoking status, type of primary caregiver, home oxygen therapy and COPD duration, were found to be significant determinants of self-management behaviour. After controlling for these variables, several illness perception subscales, including treatment control, personal control, coherence, timeline cyclical and identity, were significantly correlated with self-management behaviour. CONCLUSIONS: This study confirmed that elderly COPD patients' self-management behaviour was unsatisfactory and that illness perceptions were significant determinants of self-management behaviour. The findings may contribute to the development of self-management interventions for elderly COPD patients.

Deep learning-based inverse design of multi-functional metasurface absorbers.

A novel approach-integrating a simulated annealing (SA) algorithm with deep learning (DL) acceleration-is presented for the rapid and accurate development of terahertz perfect absorbers through forward prediction and backward design. The forward neural network (FNN) effectively deduces the absorption spectrum based on metasurface geometry, resulting in an 80,000-fold increase in computational speed compared to a full-wave solver. Furthermore, the absorber's structure can be precisely and promptly derived from the desired response. The incorporation of the SA algorithm significantly enhances design efficiency. We successfully designed low-frequency, high-frequency, and broadband absorbers spanning the 4 to 16 THz range with an error margin below 0.02 and a remarkably short design time of only 10 min. Additionally, the proposed model in this Letter introduces a novel, to our knowledge, method for metasurface design at terahertz frequencies such as the design of metamaterials across optical, thermal, and mechanical domains.

A spatial transcriptome map of the developing maize ear.

A comprehensive understanding of inflorescence development is crucial for crop genetic improvement, as inflorescence meristems give rise to reproductive organs and determine grain yield. However, dissecting inflorescence development at the cellular level has been challenging owing to a lack of specific marker genes to distinguish among cell types, particularly in different types of meristems that are vital for organ formation. In this study, we used spatial enhanced resolution omics-sequencing (Stereo-seq) to construct a precise spatial transcriptome map of the developing maize ear primordium, identifying 12 cell types, including 4 newly defined cell types found mainly in the inflorescence meristem. By extracting the meristem components for detailed clustering, we identified three subtypes of meristem and validated two MADS-box genes that were specifically expressed at the apex of determinate meristems and involved in stem cell determinacy. Furthermore, by integrating single-cell RNA transcriptomes, we identified a series of spatially specific networks and hub genes that may provide new insights into the formation of different tissues. In summary, this study provides a valuable resource for research on cereal inflorescence development, offering new clues for yield improvement.

Lead Isolation and Capture in Perovskite Photovoltaics toward Eco-Friendly Commercialization.

Perovskite solar cells (PSCs) are developed rapidly in efficiency and stability in recent years, which can compete with silicon solar cells. However, an important obstacle to the commercialization of PSCs is the toxicity of lead ions (Pb2+) from water-soluble perovskites. The entry of free Pb2+ into organisms can cause severe harm to humans, such as blood lead poisoning, organ failure, etc. Therefore, this work reports a "lead isolation-capture" dual detoxification strategy with calcium disodium edetate (EDTA Na-Ca), which can inhibit lead leakage from PSCs under extreme conditions. More importantly, leaked lead exists in a nontoxic aggregation state chelated by EDTA. For the first time, in vivo experiments are conducted in mice to systematically prove that this material has a significant inhibitory effect on the toxicity of perovskites. In addition, this strategy can further enhance device performance, enabling the optimized devices to achieve an impressive power conversion efficiency (PCE) of 25.19%. This innovative strategy is a major breakthrough in the research on the prevention of lead toxicity in PSCs.

Sphingolipids in prostate cancer prognosis: integrating single-cell and bulk sequencing.

BACKGROUND: Stratifying patient risk and exploring the tumor microenvironment are critical endeavors in prostate cancer research, essential for advancing our understanding and management of this disease. METHODS: Single-cell sequencing data for prostate cancer were sourced from the pradcellatlas website, while bulk transcriptome data were obtained from the TCGA database. Dimensionality reduction cluster analysis was employed to investigate heterogeneity in single-cell sequencing data. Gene set enrichment analysis, utilizing GO and KEGG pathways, was conducted to explore functional aspects. Weighted gene coexpression network analysis (WGCNA) identified key gene modules. Prognostic models were developed using Cox regression and LASSO regression techniques, implemented in R software. Validation of key gene expression levels was performed via PCR assays. RESULTS: Through integrative analysis of single-cell and bulk transcriptome data, key genes implicated in prostate cancer pathogenesis were identified. A prognostic model focused on sphingolipid metabolism (SRSR) was constructed, comprising five genes: "FUS," "MARK3," "CHTOP," "ILF3," and "ARIH2." This model effectively stratified patients into high-risk and low-risk groups, with the high-risk cohort exhibiting significantly poorer prognoses. Furthermore, distinct differences in the immune microenvironment were observed between these groups. Validation of key gene expression, exemplified by ILF3, was confirmed through PCR analysis. CONCLUSION: This study contributes to our understanding of the role of sphingolipid metabolism in prostate cancer diagnosis and treatment. The identified prognostic model holds promise for improving risk stratification and patient outcomes in clinical settings.

Prevalence and plasma exosome-derive microRNA diagnostic biomarker screening of adolescent idiopathic scoliosis in Yunnan Province, China.

Background: Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study. Methods: From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs. Results: The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value. Conclusions: We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study.

BACKGROUND: Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end-stage kidney disease (ESKD), and death in patients with chronic kidney disease. METHODS AND RESULTS: Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score. Multivariable-adjusted Cox proportional hazards regression was used to investigate the associations of cumulative CVH with risks of adjudicated CVD (myocardial infarction, stroke, and heart failure), ESKD, and all-cause mortality. A total of 3939 participants (mean age, 57.7 years; 54.9% men) were included. The mean (SD) cumulative CVH score attained during 5 years was 55.5% (12.3%). Over a subsequent median 10.2-year follow-up, 597 participants developed CVD, 656 had ESKD, and 1324 died. A higher cumulative CVH score was significantly associated with lower risks of CVD, ESKD, and mortality, independent of the CVH score at year 5. Multivariable-adjusted hazard ratios and 95% CIs per 10% higher cumulative CVH score during 5 years were 0.81 (0.69-0.95) for CVD, 0.82 (0.70-0.97) for ESKD, and 0.80 (0.72-0.89) for mortality. CONCLUSIONS: Among patients with chronic kidney disease stages 2 to 4, a better CVH status maintained throughout 5 years is associated with lower risks of CVD, ESKD, and all-cause mortality. The findings support the need for interventions to maintain ideal CVH status for prevention of adverse outcomes in the population with chronic kidney disease.

On the mechanism of wogonin against acute monocytic leukemia using network pharmacology and experimental validation.

Wogonin is a natural flavone compound from the plant Scutellaria baicalensis, which has a variety of pharmacological activities such as anti-cancer, anti-virus, anti-inflammatory, and immune regulation. However, the potential mechanism of wogonin remains unknown. This study was to confirm the molecular mechanism of wogonin for acute monocytic leukemia treatment, known as AML-M5. The potential action targets between wogonin and acute monocytic leukemia were predicted from databases. The compound-target-pathway network and protein-protein interaction network (PPI) were constructed. The enrichment analysis of related targets and molecular docking were performed. The network pharmacological results of wogonin for AML-M5 treatment were verified using the THP-1 cell line. 71 target genes of wogonin associated with AML-M5 were found. The key genes TP53, SRC, AKT1, RELA, HSP90AA1, JUN, PIK3R1, and CCND1 were preliminarily found to be the potential central targets of wogonin for AML-M5 treatment. The PPI network analysis, GO analysis and KEGG pathway enrichment analysis demonstrated that the PI3K/AKT signaling pathway was the significant pathway in the wogonin for AML-M5 treatment. The antiproliferative effects of wogonin on THP-1 cells of AML-M5 presented a dose-dependent and time-dependent manner, inducing apoptosis, blocking the cell cycle at the G2/M phase, decreasing the expressions of CCND1, CDK2, and CyclinA2 mRNA, as well as AKT and p-AKT proteins. The mechanisms of wogonin on AML-M5 treatment may be associated with inhibiting cell proliferation and regulating the cell cycle via the PI3K/AKT signaling pathway.

Targeting Tumor Heterogeneity by Breaking a Stem Cell and Epithelial Niche Interaction Loop.

Tumor heterogeneity, the presence of multiple distinct subpopulations of cancer cells between patients or among the same tumors, poses a major challenge to current targeted therapies. The way these different subpopulations interact among themselves and the stromal niche environment, and how such interactions affect cancer stem cell behavior has remained largely unknown. Here, it is shown that an FGF-BMP7-INHBA signaling positive feedback loop integrates interactions among different cell populations, including mammary gland stem cells, luminal epithelial and stromal fibroblast niche components not only in organ regeneration but also, with certain modifications, in cancer progression. The reciprocal dependence of basal stem cells and luminal epithelium is based on basal-derived BMP7 and luminal-derived INHBA, which promote their respective expansion, and is regulated by stromal-epithelial FGF signaling. Targeting this interaction loop, for example, by reducing the function of one or more of its components, inhibits organ regeneration and breast cancer progression. The results have profound implications for overcoming drug resistance because of tumor heterogeneity in future targeted therapies.

Effect of Electroacupuncture Combined with Pelvic Floor Muscle Exercise on Urinary Symptoms, Sexual Dysfunction and Pelvic Floor Muscle Strength in Female Patients with Overactive Bladder: A Retrospective Study.

OBJECTIVE: This study aimed to investigate the effect of electroacupuncture combined with pelvic floor muscle exercise in the treatment of female overactive bladder (OAB). METHODS: The clinical data of 134 female patients with OAB admitted to our hospital from April 2022 to June 2023 were retrospectively analysed. The patients were divided into the combination group (n = 74) and the single group (n = 60). The general demographic data, total effective rate, pad weight, female sexual function index (FSFI) score, oxford muscle grading scale and incontinence impact questionnaire short form (IIQ-7) were collected. Propensity score matching (PSM) was used to match the baseline data of the two groups at 1:1 ratio, and t test, chi-square test and analysis of variance were used for calculation. RESULTS: A total of 90 patients were selected after PSM. No significant difference in baseline data was found between the two groups (p > 0.05). Before treatment, no significant difference in FSFI score, oxford muscle grading scale and IIQ-7 score was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the single group (p < 0.05). After 3 weeks and 1 month of treatment, in addition to orgasm and sexual desire, the scores of sexual excitement and sexual satisfaction in the combination group were higher than those in the single group (p < 0.05). The combination group displayed higher oxford muscle grading scale and lower IIQ-7 and pad weight than the single group, and the differences were statistically significant (p < 0.05). CONCLUSIONS: The effect of electroacupuncture stimulation combined with pelvic floor muscle exercise is more significant, which can alleviate urinary symptoms, reduce urine leakage, enhance pelvic floor muscle strength and alleviate sexual dysfunction.

Evolutionary game analysis of multiple subjects in the management of major public health emergencies.

The frequent occurrence of major public health emergencies (MPHEs) significantly challenges national security, economic stability, social operation and the safety of people's lives and property worldwide. Consequently, enhancing the emergency management of MPHEs is critically urgent. This paper constructs a game model involving local government, social organisations, and the public for MPHE management, exploring strategy combinations and influencing factors across various scenarios. Several results were obtained. (1) Local government, social organisations, and the public each have positive and negative strategy choices based on cost-benefit analysis, leading to eight different strategy combinations. Furthermore, all three take positive strategies as the optimal way to achieve the game equilibrium. (2) The transformation of strategy combinations is primarily influenced by the cost-benefit gap and the strategic decisions of local government. (3) Altering a subject's initial strategy value doesn't change its final choice but impacts the time to achieve a stable strategy equilibrium. The severity of local government punishments on social organisations influences their strategic choices and the time to optimal strategy, whereas rewards to the public or social organisations only affect the time to achieve this strategy. The findings of this study can not only help improve the collaborative governance system of MPHEs but also provide scientific guidance on how governments can manage MPHEs.

Comparing GDF9 in mature follicles and clinical outcomes across different PCOS phenotype.

Background: Polycystic ovary syndrome (PCOS) is main cause of anovulatory infertility in women with gestational age. There are currently four distinct phenotypes associated with individualized endocrinology and metabolism. Growth differentiation factor 9 (GDF9) is a candidate as potential biomarker for the assessment of oocyte competence. The effect on oocyte capacity has not been evaluated and analyzed in PCOS phenotypes. Objective: We aimed to screen the expression levels of GDF9 in mature follicles of women with controlled ovarian hyperstimulation (COS) with different PCOS phenotypes. To determine the correlation between the expression level of GDF9 and oocyte development ability. Methods: In Part 1, we conducted a retrospective study comparing the clinical outcomes and endocrine characteristics of patients with PCOS according to different subgroups (depending on the presence or absence of the main features of polycystic ovarian morphology (PCOM), hyperandrogenism (HA), and oligo-anovulation (OA)) and non-PCOS control group. We stratified PCOS as phenotype A (n = 29), phenotype B (n = 18) and phenotype D (n = 24). In Part 2, the expression of GDF9 in follicular fluid (FF) and cumulus cells (CCs) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Results: In Part 1, the baseline clinical, hormonal, and ultrasonographic characteristics of the study population were matched with the presence or absence of the cardinal features of each PCOS phenotypes showed a clear difference. Phenotypes A and D had statistically significant associations with blastocyst formation and clinical pregnancy compared with phenotypes B (p < 0.001). In Part 2, the levels of GDF9 in FF and CCs for phenotype A and B were significantly were higher than those of phenotype D (P = 0.019, P = 0.0015, respectively). Multivariate logistic regression analysis showed that GDF9 was an important independent predictor of blastocyst formation (P＜0.001). The blastocyst formation rate of phenotype A was higher than that of phenotype B and D (P＜0.001). Combining the results of the two parts, GDF9 appears to play a powerful role in the development of embryos into blastocysts. Conclusions: GDF9 expression varies with different PCOS phenotypes. Phenotype A had higher GDF9 levels and blastocyst formation ability.

Identification of S100A8/A9 involved in thromboangiitis obliterans development using tandem mass tags-labeled quantitative proteomics analysis.

Thromboangiitis obliterans (TAO) is characterized by inflammation and obstruction of small-and medium-sized distal arteries, with limited pharmacotherapies and surgical interventions. The precise pathogenesis of TAO remains elusive. By utilizing the technology of tandem mass tags (TMT) for quantitative proteomics and leveraging bioinformatics tools, a comparative analysis of protein profiles was conducted between normal and TAO rats to identify key proteins driving TAO development. The results unveiled 1385 differentially expressed proteins (DEPs) in the TAO compared with the normal group-comprising 365 proteins with upregulated expression and 1020 proteins with downregulated expression. Function annotation through gene ontology indicated these DEPs mainly involved in cell adhesion, positive regulation of cell migration, and cytosol. The principal signaling pathways involved regulation of the actin cytoskeleton, vascular smooth contraction, and focal adhesion. The roles of these DEPs and associated signaling pathways serve as a fundamental framework for comprehending the mechanisms underpinning the onset and progression of TAO. Furthermore, we conducted a comprehensive evaluation of the effects of S100A8/A9 and its inhibitor, paquinimod, on smooth muscle cells (SMCs) and in TAO rats. We observed that paquinimod reduces SMCs proliferation and migration, promotes phenotype switching and alleviates vascular stenosis in TAO rats. In conclusion, our study revealed that the early activation of S100A8/A9 in the femoral artery is implicated in TAO development, targeting S100A8/A9 signaling may provide a novel approach for TAO prevention and treatment.