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Background The role of phytoestrogens in asthma/wheeze and lung function remains controversial. Thus, we aimed to examine whether phytoestrogens have beneficial effects on asthma/wheeze, lung function for subgroups and mortality.Methods Participants in this study were individuals aged 20 years or older from the National Health and Nutrition Examination Survey. Multivariate logistic regression models were fitted to examine the associations of urinary phytoestrogens with the risk of asthma/wheeze and lung function in individuals with and without asthma/wheeze. Cox proportional hazards regression was used to examine the relationship between urinary phytoestrogens and all-cause mortality. Stratified analyses were conducted based on gender and smoking status.Results We included 2465 individuals in this study. Enterolactone levels in the highest quartile were associated with a lower risk of asthma than those in the lowest quartile. As compared with the lowest quartile, the highest quartile of enterodiol and enterolactone was associated with a lower risk of wheeze. Significant associations were observed between subtypes of phytoestrogens (equol and enterolactone) and lung function (forced vital capacity (FVC) and forced expiratory volume in 1 s). Besides, FVC was higher in individuals with higher levels of enterodiol. The results were consistent in subpopulations without asthma/wheeze, while the significant difference was not observed in individuals with asthma/wheeze. The stratified analyses revealed that the associations between phytoestrogens and lung function differed by gender and smoking status among subgroups. No significant association was found between urinary phytoestrogens and all-cause mortality.Conclusion In summary, subtypes of phytoestrogens were associated with lower risk of asthma/wheeze and beneficial for lung function improvement in individuals without asthma/wheeze. Furthermore, gender and smoking may interact in the relationship between phytoestrogens and asthma/wheeze, and lung function. Further researches are needed to confirm these associations and explain the results of stratified analyses.

Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.

Introduction and Objectives: Blood glucose fluctuates severely in the diabetes (DM) and tumor microenvironment. Our previous works have found Hepatitis B virus X protein (HBx) differentially regulated metastasis and apoptosis of hepatoma cells depending on glucose concentration. We here aimed to explore whether HBx played dual roles in the angiogenesis of hepatocellular carcinoma varying on different glucose levels. Materials and Methods: We collected conditioned medium from HBx-overexpressing cells cultured with two solubilities of glucose, and then applied to EA.hy926 cells. Alternatively, a co-culture cell system was established with hepatoma cells and EA.hy926 cells. We analyzed the angiogenesis of EA.hy926 cells with CCK8, wound-healing, transwell-migartion and tube formation experiment. ELISA was conducted to detect the secretion levels of angiogenesis-related factors. siRNAs were used to detect the P53-VEGF axis. Results: HBx expressed in hepatoma cells suppressed VEGF secretion, and subsequently inhibited the proliferation, migration and tube formation of EA.hy926 cells in a high glucose condition, while attenuating these in the lower glucose condition. Furthermore, the p53-VEGF axis was required for the dual role of HBx in angiogenesis. Additionally, HBx mainly regulated the nuclear p53. Conclusions: These data suggest that the dual roles of HBx confer hepatoma cells to remain in a glucose-rich environment and escape from the glucose-low milieu through tumor vessels, promoting liver tumor progression overall. We exclusively revealed the dual role of HBx on the angiogenesis of liver tumors, which may shed new light on the mechanism and management strategy of HBV- and DM-related hepatocellular carcinoma.

Abstract Background Although sex bias has been reported in the development and progression of renal cell carcinoma (RCC), the underlying mechanisms remain enigmatic. Here, we investigated the sex differences in the tumor microenvironment (TME) of RCC and explored a promising combination drug regimen to enhance the efficacy of immunotherapy. Methods Single-cell RNA sequencing (scRNA-seq) data from four published datasets were analyzed to investigate the sex differences in RCC patients, and tumor tissues were collected to validate the sex differences using multiplex immunofluorescence (MxIF) and flow cytometry (FCM). The function of the androgen–androgen receptor axis in sex differences was explored in vivo and in vitro experiments. Results Our analysis of scRNA-seq data from 220,156 cells, as well as MxIF and FCM assays, revealed that CD8+ T-cells infiltrated highly in the TME of male RCC, but were mostly in an exhausted and dysfunctional state. In vitro and in vivo experiments indicated that the dysfunction and exhaustion of CD8+ T-cells in male TME were induced by androgen. Clinically, higher serum androgen was significantly associated with a worse prognosis in male RCC patients receiving immunotherapy. Androgen receptor inhibitors could activate tumor-infiltrating CD8+ T-cells and enhance the efficacy of immunotherapy of RCC in vivo. Conclusions Our study delineated the difference in TME between male and female patients with RCC, and demonstrated that the androgen–androgen receptor axis plays an important role in immunosuppression in male RCC. Our findings suggest that androgen receptor inhibitors in combination with immunotherapy may be a promising treatment option for male RCC patients.

ABSTRACTThe adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Abstract The profile of antibodies against antigenic epitopes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during neutralizing antibody (NAb) decay has not been clarified. Using a SARS‐CoV‐2 proteome microarray that contained viral antigenic peptides, we analyzed the characteristics of the humoral response in patients with coronavirus disease 19 (COVID‐19) in a longitudinal study. A total of 89 patients were recruited, and 226 plasma samples were serially collected in 2020. In the antigenic peptide microarray, the level of immunoglobulin G (IgG) antibodies against peptides within the S2 subunit (S‐82) and a conserved gene region in variants of interest, open reading frame protein 10 (ORF10‐3), were closely associated with the presence of SARS‐CoV‐2 NAbs. In an independent evaluation cohort of 232 plasma samples collected from 116 COVID‐19 cases in 2020, S82‐IgG titers were higher in NAbs‐positive samples (p = 0.002) than in NAbs‐negative samples using enzyme‐linked immunosorbent assay. We further collected 66 plasma samples from another cohort infected by Omicron BA.1 virus in 2022. Compared with the samples with lower S82‐IgG titers, NAb titers were significantly higher in the samples with higher S82‐IgG titers (p = 0.04). Our findings provide insights into the understanding of the decay‐associated signatures of SARS‐CoV‐2 NAbs.

Abstract Background Distant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine. Methods: Between 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared. Results A total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared. Conclusions Triweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.

Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.

The fault diagnosis of the inverter is fundamental to energy intelligence. Due to the complex characteristics of the inverter (e.g., high-dimensional decision and poor stability), it is challenging to solve the problem using traditional fault diagnosis methods. Recently, artificial intelligence (AI)-based approaches have emerged as the most promising methods. However, they often require to set hyperparameters manually, which hinders further AI-based applications in fault diagnosis of inverters. To fill the gap, we propose an inverter fault diagnosis method using fast Fourier Transform (FFT) and evolutionary neural network. This method combines the amplitude of low-frequency harmonic component of the three-phase inverter output current which is obtained by FFT and the average value in a period of three-phase inverter output current into the fault eigenvector. This method uses an evolutionary neural network trained by combining genetic algorithm (GA), ant colony optimization (ACO) algorithm and Back-propagation (BP) algorithm to realize fault diagnosis. This method can effectively resist noise interference and reduce the number of independent variables in the part of feature extraction, so that it can simplify the network model. In addition, this method can avoid the network training from trapping in local optima in the part of fault classification, with high accuracy and fast response speed. The experimental results show that the proposed algorithm and method of fault feature extraction can effectively detect and locate the insulated-gate bipolar transistor (IGBT) with open circuit (OC) fault in three-phase inverter, and can be applied to online monitoring.

Background: Chromobox family proteins (CBXs) are vital components of epigenetic regulation complexes and transcriptionally inhibit target genes by modifying the chromatin. Accumulating evidence indicates that CBXs are involved in the initiation and progression of multiple malignancies. However, the expression, function, and clinical relevance such as the prognostic and diagnostic values of different CBXs in esophageal carcinoma (ESCA) are still unclear.Methods: We applied Oncomine, TCGA, GEO, GEPIA, UALCAN, Kaplan–Meier plotter, cBioPortal, Metascape, and TIMER to investigate the roles of CBX family members in ESCA. Additionally, quantitative real-time PCR (RT-PCR), western blot, and immunofluorescence were used to verify the expression of CBX family members in ESCA clinical samples.Results: Compared with normal tissues, the mRNA expression levels of CBX1/3/8 were significantly increased in ESCA, whereas CBX7 mRNA expression was reduced in both the TCGA cohort and GEO cohort. In the TCGA cohort, ROC curves suggested that CBX1/2/3/4/8 had great diagnostic value in ESCA, and the AUCs were above 0.9. Furthermore, upregulation of CBX1/3/8 and downregulation of CBX7 were closely related to the clinicopathological parameters in ESCA patients, such as tumor grades, tumor nodal metastasis status, and TP53 mutation status. The survival analysis indicated that higher CBX1/3/8 mRNA expressions and lower CBX7 expression suggested an unfavorable prognosis in ESCA. High genetic change rate (52%) of CBXs was found in ESCA patients. Functions and pathways of mutations in CBXs and their 50 frequently altered neighbor genes in ESCA patients were investigated; the results showed that DNA repair and DNA replication were correlated to CBX alterations. Moreover, we found a significant correlation between the expression level of CBX family members and the infiltration of immune cells in ESCA. Finally, we verified the expression of CBX family members in clinical samples and found the results were consistent with the databases.Conclusion: Our study implied that CBX1/3/7/8 are potential targets of precision therapy for ESCA patients and new biomarkers for the prognosis.

This study assessed second-line therapy options for metastatic non-clear cell renal cell carcinoma (nccRCC) patients following first-line tyrosine kinase inhibitor (TKI) treatment. Among 65 patients, combination therapy (TKI plus anti-PD1) showed improved response rates (ORR 50.0%, DCR 70.5%) compared to TKI monotherapy (ORR 14.3%, DCR 28.6%). Median progression-free survival (PFS) for combination therapy was 9.2 months vs. 5.4 months for TKI monotherapy, with similar adverse event rates. Anti-PD-1 plus TKI therapy appears effective and safe for nccRCC patients who progressed after initial TKI treatment. Objectives: Guidelines recommend clinical trials or tyrosine kinase inhibitor (TKI) as the first-line option for systemic therapy for non-clear cell renal cell carcinoma (nccRCC) with limited efficacy. However, the preferred subsequent options remain unclear when patients progress after first-line treatment. This study aimed to evaluate the efficacy and safety of anti-PD-1 plus TKI therapy as the second-line regimen in nccRCC. Patients and Methods: We conducted a retrospective analysis of patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020. The baseline characteristics of the patients and adverse events (AEs) were collected. Efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: The current study enrolled 65 patients, with a median age of 48 (interquartile 37-60) years. Among all patients, 21 received TKI monotherapy while 44 patients received combination therapy (TKI plus anti-PD1). The ORR and DCR for the whole cohort were 38.5% and 56.9%, respectively. ORR (50.0% vs. 14.3%, P = .006) and DCR (70.5% vs. 28.6%, P = .001) were improved in the combination group compared with the TKI group. The overall second-line PFS was 7.7 (95% CI: 6.1-9.3) months and OS was 25.2 (19.5-30.8) months. Patients receiving combination therapy had a longer PFS compared with those receiving TKI monotherapy [median PFS (95% CI): 9.2 (5.9-12.4) vs. 5.4 (2.6-8.2) m, Log-rank P = .002]. The incidence of treatment-related AEs of grade 3 or higher was comparable between the 2 groups (56.8% vs. 52.4%). Conclusion: Anti-PD-1 plus TKI therapy appeared effective and safe in the treatment of patients with metastatic nccRCC who progressed after first-line TKIs. [ABSTRACT FROM AUTHOR]

Aerosol is important to climate and air pollution, and different aerosol types have a non-negligible impact on the environment and climate system. Based on long-term satellite lidar profiles from 2006 to 2020, the four-dimensional (x-y-z-t) spatiotemporal characteristics of different aerosol types, including clean marine (CM), dust (DU), polluted continental/smoke (PC), clean continental (CC), polluted dust (PD), elevated smoke (ES), and dusty marine (DM), over the coastal waters of the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) were revealed for the first time and compared to the surrounding northern South China Sea (NSCS). (1) The dominant aerosol types in both study areas were found to be CM, ES, and DM, whose proportions summed up to more than 85%. In spring, ES was the dominant aerosol type (>40%); in other seasons, CM dominated (>34%). The proportions of anthropogenic aerosols (PC, PD, and ES) and dust-related aerosols (DU, PD, and DM) were higher in spring and winter than in summer and autumn. (2) Vertically, the number of all aerosol types declined with increasing altitude, with the exception of abnormal increase at the heights of approximately 1.5–2.8 km in spring, which was probably attributed to the effect of local and regional anthropogenic pollutants. Below the height of 2 km, the main aerosol types were CM and DM, whereas ES, PD, and DU aerosols were dominant above 2 km. (3) Horizontally, the dominant aerosol types were spatially uniform in the lower atmosphere ( 4 km) showed significant horizontal heterogeneity in space. The proportion of anthropogenic aerosols over the coastal waters of the GBA was higher than that over the NSCS, due to terrestrial pollution transportation. (4) In terms of the long-term trend, the proportion of CM aerosols was found to be steadily increasing, with the anthropogenic aerosols and dust-related aerosols showing a fluctuating and decreasing trend, which resulted from the enforcement of effective air pollution control policies. Overall, the terrestrial aerosol influence tended to decrease in the study areas. The insight into aerosol types and its variation will facilitate the understanding of the aerosol climate effects and pollutant control in the coastal waters of the GBA and the NSCS.

Abstract Background Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists are novel agents for asthma but with controversial efficacies in clinical trials. Therefore, we conducted a meta-analysis to determine the roles of CRTH2 antagonists in asthma. Methods We searched in major databases for RCTs comparing CRTH2 antagonists with placebo in asthma. Fixed- or random-effects model was performed to calculate mean differences (MD), risk ratio (RR) or risk difference (RD) and 95% confidence interval (CI). Results A total of 14 trails with 4671 participants were included in our final analysis. Instead of add-on treatment of CRTH2 antagonists to corticosteroids, CRTH2 antagonist monotherapy significantly improved pre-bronchodilator FEV1 (MD = 0.09, 95% CI 0.04 to 0.15, P = 0.0005), FEV1% predicted (MD = 3.65, 95% CI 1.15 to 6.14, P = 0.004), and AQLQ (MD = 0.25, 95% CI 0.09 to 0.41, P = 0.002), and reduced asthma exacerbations (RR = 0.45, 95% CI 0.23 to 0.85, P = 0.01). Rescue use of SABA was significantly decreased in both CRTH2 antagonist monotherapy (MD = − 0.04, 95% CI -0.05 to − 0.03, P

The lung is constantly exposed to environmental particulates such as aeroallergens, pollutants, or microorganisms and is protected by a poised immune response. Innate lymphoid cells (ILCs) are a population of immune cells found in a variety of tissue sites, particularly barrier surfaces such as the lung and the intestine. ILCs play a crucial role in the innate immune system, and they are involved in the maintenance of mucosal homeostasis, inflammation regulation, tissue remodeling, and pathogen clearance. In recent years, group 3 innate lymphoid cells (ILC3s) have emerged as key mediators of mucosal protection and repair during infection, mainly through IL-17 and IL-22 production. Although research on ILC3s has become focused on the intestinal immunity, the biology and function of pulmonary ILC3s in the pathogenesis of respiratory infections and in the development of chronic pulmonary inflammatory diseases remain elusive. In this review, we will mainly discuss how pulmonary ILC3s act on protection against pathogen challenge and pulmonary inflammation, as well as the underlying mechanisms.

The transforming growth factor-β (TGF-β) signaling pathway exhibits an important role in cancer invasion and metastasis. Excessive expression of TGF-β activates Smad4, leading to the upregulation of downstream metastasis-associated genes. Thus, the inhibition of the TGF-β/Smad4 signaling pathway may be a novel strategy for treatment of cancer metastasis. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to exert strong anti-tumor activity towards various types of cancer. In the present study the effect of baicalein on migration and invasion of cancer cells was evaluated using wound-healing and Transwell assays. In order to investigate the possible molecular mechanisms of the anti-metastatic effects of baicalein, quantitative polymerase chain reaction (qPCR) and western blot analyses were performed to examine the effect on the expression of TGF-β, Smad4, N-cadherin, vimentin, ZEB1 and ZEB2. It was determined that baicalein inhibited the migration and invasion of AGS cells by suppressing the TGF-β/Smad4 signaling pathway. In addition, baicalein treatment reduced the expression of the metastasis-associated N-cadherin, vimentin, ZEB1 and ZEB2, downstream target genes of the TGF-β/Smad4 signaling pathway. Collectively, these results suggest that inhibition of the metastasis of cancer cells via inactivation of TGF-β/Smad4 signaling is one of the mechanisms by which baicalein may treat cancer. [ABSTRACT FROM AUTHOR]