Exploring the supersymmetric U(1)B−L×_{B-L} \times U(1)R_{R} model with dark matter, muon g−2g-2 and Z′Z^\prime mass limits

We study the low scale predictions of supersymmetric standard model extended by $U(1)_{B-L}\times U(1)_{R}$ symmetry, obtained from $SO(10)$ breaking via a left-right supersymmetric model, imposing universal boundary conditions. Two singlet Higgs fields are responsible for the radiative $U(1)_{B-L}\times U(1)_{R}$ symmetry breaking, and a singlet fermion $S$ is introduced to generate neutrino masses through inverse seesaw mechanism. The lightest neutralino or sneutrino emerge as dark matter candidates, with different low scale implications. We find that the composition of the neutralino LSP changes considerably depending on the neutralino LSP mass, from roughly half $U(1)_R$ bino, half MSSM bino, to singlet higgsino, or completely dominated by MSSM higgsino. The sneutrino LSP is statistically much less likely, and when it occurs it is a 50-50 mixture of right-handed sneutrino and the scalar $\tilde S$. Most of the solutions consistent with the relic density constraint survive the XENON 1T exclusion curve for both LSP cases. We compare the two scenarios and investigate parameter space points and find consistency with the muon anomalous magnetic moment only at the edge of $2\sigma$ deviation from the measured value. However, we find that the sneutrino LSP solutions could be ruled out completely by strict reinforcement of the recent $Z^\prime$ mass bounds. We finally discuss collider prospects for testing the model

Bi-directional Mendelian randomization analysis provides evidence for the causal involvement of dysregulation of CXCL9, CCL11 and CASP8 in the pathogenesis of ulcerative colitis

Background and Aims Systemic inflammation is well recognised to be associated with ulcerative colitis [UC], but whether these effects are causal or consequential remains unclear. We aimed to define potential causal relationship of cytokine dysregulation with different tiers of evidence. Methods We first synthesised serum proteomic profiling data from two multicentred observational studies, in which a panel of systemic inflammatory proteins was analysed to examine their associations with UC risk. To further dissect observed associations, we then performed a bidirectional two-sample Mendelian randomisation [TSMR] analysis from both forward and reverse directions using five genome-wide association study [GWAS] summary level data for serum proteomic profiles and the largest GWAS of 28 738 European-ancestry individuals for UC risk. Results Pooled analysis of serum proteomic data identified 14 proteins to be associated with the risk of UC. Forward MR analysis using only cis-acting protein quantitative trait loci [cis-pQTLs] or trans-pQTLs further validated causal associations of two chemokines and the increased risk of UC: C-X-C motif chemokine ligand 9 [CXCL9] [OR 1.45, 95% CI 1.08, 1.95, p = 0.012] and C-C motif chemokine ligand 11 [CCL11] [OR 1.14, 95% CI 1.09, 1.18, p = 3.89 x 10(-10)]. Using both cis- and trans-acting pQTLs, an association of caspase-8 [CASP8] [OR 1.04, 95% CI 1.03, 1.05, p = 7.63 x 10(-19)] was additionally identified. Reverse MR did not find any influence of genetic predisposition to UC on any of these three inflammation proteins. Conclusion Pre-existing elevated levels of CXCL9, CCL11 and CASP8 may play a role in the pathogenesis of UC

Cypermethrin Induces Macrophages Death through Cell Cycle Arrest and Oxidative Stress-Mediated JNK/ERK Signaling Regulated Apoptosis

Cypermethrin is one of the most highly effective synthetic pyrethroid insecticides. The toxicity of cypermethrin to the reproductive and nervous systems has been well studied. However, little is known about the toxic effect of cypermethrin on immune cells such as macrophages. Here, we investigated the cytotoxicity of cypermethrin on macrophages and the underlying molecular mechanisms. We found that cypermethrin reduced cell viability and induced apoptosis in RAW 264.7 cells. Cypermethrin also increased reactive oxygen species (ROS) production and DNA damage in a dose-dependent manner. Moreover, cypermethrin-induced G1 cell cycle arrest was associated with an enhanced expression of p21, wild-type p53, and down-regulation of cyclin D1, cyclin E and CDK4. In addition, cypermethrin treatment activated MAPK signal pathways by inducing c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 ERK1/2 phosphorylation, and increased the cleaved poly ADP-ribose polymerase (PARP). Further, pretreatment with antioxidant N-acetylcysteine (NAC) effectively abrogated cypermethrin-induced cell cytotoxicity, G1 cell cycle arrest, DNA damage, PARP activity, and JNK and ERK1/2 activation. The specific JNK inhibitor (SP600125) and ERK1/2 inhibitor (PD98059) effectively reversed the phosphorylation level of JNK and ERK1/2, and attenuated the apoptosis. Taken together, these data suggested that cypermethrin caused immune cell death via inducing cell cycle arrest and apoptosis regulated by ROS-mediated JNK/ERK pathway

High expression of RIPK2 is associated with Taxol resistance in serous ovarian cancer

Abstract Background Taxol resistance in serous ovarian cancer is responsible for its poor prognosis, yet the underlying mechanism is still poorly understood. Thus, we probed the mechanism of Taxol resistance in serous ovarian cancer with multiple bioinformatic methods to provide novel insights into potential therapies. Methods The differentially expressed genes (DEGs) in Taxol-sensitive and Taxol-resistant cell lines and their relationship with the overall survival (OS) and progression-free interval (PFI) of ovarian cancer patients were analyzed using gene expression datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The role of receptor interacting serine/threonine kinase 2 (RIPK2) was validated via identification of its coexpressed genes, functional analysis and generation of a protein-protein interaction (PPI) network. The single sample gene set enrichment analysis (ssGSEA) was used to explore immune infiltration, and genomic alterations of RIPK2 were also analyzed via cBio Cancer Genomics Portal (cBioProtal). Results RIPK2 was highly expressed in Taxol resistant ovarian cancer cell lines, and its high expression was also linked with shorter OS and PFI in serous ovarian cancer patients. The PPI network analysis and pathway analysis demonstrated that RIPK2 might participate in the positive regulation of NF-κB transcription factor activity. RIPK2 expression was related to tumor microenvironment alterations, which might participate in the formation of Taxol resistance. Conclusions Our studies suggested that high expression of RIPK2 is related to Taxol resistance in serous ovarian cancer, and that RIPK2 induces Taxol resistance through NOD1/RIPK2/NF-κB inflammatory pathway activation and tumor microenvironment changes

Association between Different Types of Tea Consumption and Risk of Gynecologic Cancer: A Meta-Analysis of Cohort Studies

Plenty of studies have shown that tea has an effect of inhibiting gynecologic tumors. However, there still remained controversy of the association between tea and gynecologic tumors in epidemiological studies. In this study, PubMed, Embase, and Cochrane Database were used to search the literature from 1 January 1960 to 26 December 2022 to investigate the association between tea intake and gynecologic cancer risk. In total, 19 cohort studies with 2,020,980 subjects and 12,155 gynecological tumor cases were retrieved. The pooled relative risk (RR) of gynecologic tumor for tea intake was 1.00 (95% CI: 0.96–1.04). RRs were 0.94 (95% CI: 0.88–1.01) for ovarian cancer, 1.02 (95% CI: 0.97–1.07) for endometrial cancer, and 1.06 (95% CI: 0.91–1.23) for cervical cancer. Subgroup analyses were adopted based on the tea type and geographic location. Interestingly, significant preventive impact of non-herbal tea on ovarian cancer (pooled relative risk: 0.67; 95% CI: 0.55–0.81) was found, especially for black tea (pooled relative risk: 0.64; 95% CI: 0.51–0.80). Dose–response analysis indicated that although it is not statistically significant, a decreasing trend of ovarian cancer risk could be observed when the tea consumption was 1.40 to 3.12 cups/day. In conclusion, our findings suggested that ovarian cancer, but not other gynecologic cancers, could possibly be prevented by drinking non-herbal tea. In addition, the preventive impact of green tea on gynecologic cancer seemed to be relatively weak and needs further cohorts to validate it

High-Performance, Degradable, Self-Healing Bio-Based Nanocomposite Coatings with Antibacterial and Antioxidant Properties

The purpose of this study is to obtain a bio-based coating with good functional activity and self-healing ability, demonstrating its potential in food, materials, and other application fields. Plastic coatings can cause serious environmental pollution. It was a good solution to replace plastic coatings with degradable coatings. However, the development of degradable coatings in the fields of food and materials was limited due to their insufficient antibacterial ability and weak comprehensive properties. Therefore, chitosan nanoparticles (NPs) loaded with gallic acid (GA) were self-assembled with gelatin (GE) to prepare high-performance, degradable, self-healing bio-based nanocomposite coatings with antibacterial and antioxidant properties. The oxygen permeability of GE nanocomposite coatings decreased gradually with the addition of NPs, and the barrier properties increased significantly. At the same time, due to the excellent antioxidant and antibacterial ability of GA, the antioxidant effect of the nanocomposite coatings increased by 119%, and the antibacterial rate against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) increased by 32% and 58%, respectively, compared with the pure GE coatings. In addition, the nanocomposite coatings can be repaired within 24 h after being scratched at room temperature. Finally, GA coated with chitosan nanoparticles can significantly delay the escape of GA, and the retardation of gallic acid release exceeded 89% in simulated solutions after 24 h immersion, extending the service life of the nanocomposite coatings