PGK1 inhibited AR ubiquitination levels and increased AR stability in an E3 ligase SKP2-dependent manner. Additionally, PGK1 promoted AR nuclear translocation, and RNA-seq data showed that critical ovulation-related genes were regulated by the PGK1-AR axis. PGK1 regulated GCs metabolism and interacted with AR to regulate the expression of key ovulation genes, and also mediated cell proliferation and apoptosis, which resulted in the etiology of PCOS. This work highlights the pathogenic mechanism and represents a novel therapeutic target for PCOS. National Key Research and Development Program of China; National Natural Science Foundation of China grant. National Key Research and Development Program of China; National Natural Science Foundation of China grant. Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. https://www.selleckchem.com/products/VX-770.html Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells impact on the diversification of aggressive lymphoma clones is still unknown. Combining in situ quantitative immunophenotypical analyses and RNA sequencing we investigated the intra-tumour heterogeneity and the specific mesenchymal modifications that are associated with A20 diffuse large B-cell lymphoma (DLBCL) cells seeding of different tissue microenvironments. Furthermore, we characterized features of lymphoma-associated stromatogenesis in human DLBCL samples using Digital Spatial Profiling, and established their relationship with prognostically relevant variables, such as MYC. We found that the tissue microenvironment casts a relevant influence over A20 transcriptioed by the Italian Foundation for Cancer Research (AIRC) (grants 15999 and 22145 to C. Tripodo) and by the University of Palermo. Although simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown. A retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients. Among the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour locati in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients. Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium (http//www.raids-fp7.eu/) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A "metagene" of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2]. To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA). Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pβ-Cat552), ranked highest for good prognosis, while pβ-Cat675 was associated with worse prognosis. These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pβ-Cat552 and pβ-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis. European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer. European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer. Slow neurotransmission including DARPP-32 signalling is implicated in substance use disorders (SUDs) by experimental systems but not yet in the human aetiology. PPP1R12B, encoding another protein in the DARPP-32 family, hasn't been studied in the brain. Brain-regional gene activity was assessed in three different animal models of SUDs for mRNA level alterations. Genetic associations were assessed by meta-analysis of pre-existing dbGaP GWAS datasets for main effects and epistasis with known genetic risks, followed by cell type-specific pathway delineation. Parkinson's disease (PD) was included as a dopamine-related disease control for SUDs. In animal models of SUDs, environmentally-altered PPP1R12B expression sex-dependently involves motivation-related brain regions. In humans with polysubstance abuse, meta-analysis of pre-existing datasets revealed that PPP1R12B and PPP1R1B, although expressed in dopamine vs. dopamine-recipient neurons, exerted similar interactions with known genetic risks such as ACTR1B and DRD2 in men but with ADH1B, HGFAC and DRD3 in women. These interactions reached genome-wide significances (P <10 ) for SUDs but not for PD (disease selectivity P=4.8×10 , OR=6.7 for PPP1R12B; P=8.0×10 , OR=2.1 for PPP1R1B). CADM2 was the common risk in the molecular signalling regardless of gender and cell type. Gender-dependant slow neurotransmission may convey both genetic and environmental vulnerabilities selectively to SUDs. Grants from National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) of U.S.A. and National Natural Science Foundation of China (NSFC). Grants from National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) of U.S.A. and National Natural Science Foundation of China (NSFC).