A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs

BackgroundPolycystic ovary syndrome (PCOS), a common endocrine and reproductive disorder, lacks precise diagnostic strategies. Necroptosis was found to be crucial in reproductive and endocrine disorders, but its function in PCOS remains unclear. We aimed to identify differentially diagnostic genes for necroptosis (NDDGs), construct a diagnostic model to assess the progression of PCOS and explore the potential therapeutic drugs.MethodsGene expression datasets were combined with weighted gene co-expression network analysis (WGCNA) and necroptosis gene sets to screen the differentially expressed genes for PCOS. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a necroptosis-related gene signatures. Independent risk analyses were performed using nomograms. Pathway enrichment of NDDGs was conducted with the GeneMANIA database and gene set enrichment analysis (GSEA). Immune microenvironment analysis was estimated based on ssGSEA algorithm analysis. The Comparative Toxicogenomics Database (CTD) was used to explore potential therapeutic drugs for NDDGs. The expression of NDDGs was validated in GSE84958, mouse model and clinical samples.ResultsFour necroptosis-related signature genes, IL33, TNFSF10, BCL2 and PYGM, were identified to define necroptosis for PCOS. The areas under curve (AUC) of receiver operating characteristic curve (ROC) for training set and validation in diagnostic risk model were 0.940 and 0.788, respectively. Enrichment analysis showed that NDDGs were enriched in immune-related signaling pathways such as B cells, T cells, and natural killer cells. Immune microenvironment analysis revealed that NDDGs were significantly correlated with 13 markedly different immune cells. A nomogram was constructed based on features that would benefit patients clinically. Several compounds, such as resveratrol, tretinoin, quercetin, curcumin, etc., were mined as therapeutic drugs for PCOS. The expression of the NDDGs in the validated set, animal model and clinical samples was consistent with the results of the training sets.ConclusionIn this study, 4 NDDGs were identified to be highly effective in assessing the progression and prognosis of PCOS and exploring potential targets for PCOS treatment

Variations in methylmercury contamination levels and associated health risks in different fish species across three coastal bays in China

The growing atmospheric mercury (Hg) emissions in China have raised ongoing concerns regarding contamination in marine fish. To better understand the pollution patterns and associated risks, we examined methylmercury (MeHg) content in demersal and pelagic fish from four commonly found families in three geographically distinct bays along the Chinese coast. We identified significant spatial variations in MeHg levels within the same fish family across regions. Specifically, fish collected from the Beibu Gulf in the South China Sea consistently exhibited significantly higher MeHg levels compared to those from the Laizhou Bay in the Northeast and/or Haizhou Bay in the East of China. In contrast, MeHg levels in fish collected from Haizhou Bay consistently remained the lowest. Within each region, we observed significantly higher MeHg concentrations in demersal species compared to pelagic species. This trend was particularly evident in fish species including bartail flathead (Platycephalus indicus), small-scale tongue sole (Cynoglossus microlepis) and greater lizardfish (Saurida tumbil) from the Beibu Gulf (0.50, 0.21, and 0.18 mg/kg dw, respectively), as well as bartail flathead and slender lizardfish (Saurida elongata) from Laizhou Bay (0.09 and 0.12 mg/kg dw, respectively). By comparison, MeHg content in silver pomfret (Pampus argenteus) from all three regions consistently remained relatively lower than in other species. Using target hazardous quotient (THQ) calculations, we estimated potential health risks in local populations associated with the consumption of the studied fish species. Our results showed a lack of apparent health risks to local residents, as all THQ values obtained from the three regions fell within the safe limits (0.02–0.94). However, it remains important to conduct additional assessments and spatiotemporal monitoring that encompass a broader range of species and regions

Optimum design and research on novel vehicle hybrid excitation synchronous generator

Hybrid excitation is an organic combination of permanent magnet excitation and electric excitation. Hybrid excitation synchronous generator (HESG) both has the advantages of light quality, less losses and high efficiency like permanent magnet generator and the advantages of good magnetic field adjusting performance like electric excitation generator, so it is very suitable for the vehicle application. This paper presented a novel vehicle HESG which has skew stator core, permanent magnet rotor and both armature winding and field winding in the stator. Using ANSYS software, simulating the electric excitation field and the magnetic field, and finally the main parameters of HESG were designed. The simulation and the test results both show that the novel vehicle PMSG has the advantages of small cogging torque, high efficiency, small harmonic component output voltage and low waveform aberration, so as to meet the design requirements fully

Searches for heavy Higgs bosons in two-Higgs-doublet models and for t → c h decay using multilepton and diphoton final states in p p collisions at 8 TeV

Searches are presented for heavy scalar (H) and pseudoscalar (A) Higgs bosons posited in the two doublet model (2HDM) extensions of the standard model (SM). These searches are based on a data sample of pp collisions collected with the CMS experiment at the LHC at a center-of-mass energy of root s = 8 TeV and corresponding to an integrated luminosity of 19.5 fb(-1). The decays H - GT hh and A - GT Zh, where h denotes an SM-like Higgs boson, lead to events with three or more isolated charged leptons or with a photon pair accompanied by one or more isolated leptons. The search results are presented in terms of the H and A production cross sections times branching fractions and are further interpreted in terms of 2HDM parameters. We place 95% C.L. cross section upper limits of approximately 7 pb on sigma B for H - GT hh and 2 pb for A - GT Zh. Also presented are the results of a search for the rare decay of the top quark that results in a charm quark and an SM Higgs boson, t - GT ch, the existence of which would indicate a nonzero flavor-changing Yukawa coupling of the top quark to the Higgs boson. We place a 95% C.L. upper limit of 0.56% on B(t - GT ch)