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Introduction: Calcium channel gene variations have been reported to be associated with hypertrophic cardiomyopathy (HCM) in family, but the relationship between calcium channel gene variations and HCM remains undefined in the population. Methods: A total of 719 HCM unrelated patients were initially enrolled. Finally, 371 patients were identified based on inclusion and exclusion criteria, including 145 patients with gene negative, 28 patients with a single rare calcium channel gene variation (calcium gene variation), 162 patients with a single pathogenic/likely pathogenic sarcomere gene variation (sarcomere gene variation) and 36 patients with a single pathogenic/likely pathogenic sarcomere gene variation and a single rare calcium channel gene variation (double gene variations). Then the demographic, electrocardiographic, echocardiographic, and follow-up data were collected. Results: Patients with double gene variations were at an earlier age and had more percent of family history of HCM, and had thicker walls, higher left ventricular outflow tract pressure gradient, more pathological Q waves, and more bundle branch blocks as compared with those with single sarcomere gene variation. During the follow-up period, patients with double gene variations had more primary endpoints than the other three groups (p = 0.0013). Multivariate analysis showed that double gene variations were the independent predictor of primary endpoint events in patients (HR: 4.82, 95% CI: 1.77–13.2; p = 0.002). Conclusion: We found that patients with double gene variations had more severe HCM phenotype and prognosis. The pathogenesis effects of sarcomere gene variation and calcium channel gene variation may be cumulative in HCM populations. [ABSTRACT FROM AUTHOR]

Background: A predictive model for acquired premature ejaculation (APE) in PE patients has not yet been established. Objectives: This study was aimed at determining which factors were independently associated with the possibility of predicting APE in PE patients, and whether an effective pre‐treatment nomogram for predicting their individual chances of being APE in PE patients can be developed. Materials and methods: We analyzed the medical histories of 915 PE patients diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) between May 2019 and May 2020. The diagnostic nomogram was developed using a multivariate logistic regression model by integrating selected significant variables determined through univariate analysis. Receiver operating characteristic curves were used to measure the predictive accuracy of the nomogram and its constituted variables, and calibrations were performed by making a comparison of nomogram‐predicted probability with actual rate of APE. Results: The independent predictors for APE that were identified include Age, Intra‐vaginal Ejaculation Latency Time (IELT), Frequency of sexual desire (FSD), and Eysenck Personality Questionnaire‐Revised Short Scale for Chinese (psychoticism) [EPQ‐RSC(P)] scores. The predictive accuracy of the nomogram was 0.782 (95% CI: 0.723–0.841). Also, excellent agreement was demonstrated between the nomogram‐predicted probability and the actual rate of APE. Discussion and conclusion: We identified 4 independent predictors for APE and demonstrated the potential significant differences in psychoticism between LPE and APE patients. This was the first internally validated predictive APE nomogram where good discrimination and calibration were applied, and it offers a promising role in clinical practice. More studies are necessary for verification of its universal applicability. [ABSTRACT FROM AUTHOR]

SUMMARY: Plants experiencing abiotic stress react by generating reactive oxygen species (ROS), compounds that, if allowed to accumulate to excess, repress plant growth and development. Anthocyanins induced by abiotic stress are strong antioxidants that neutralize ROS, whereas their over‐accumulation retards plant growth. Although the mechanism of anthocyanin synthesis has been revealed, how plants balance anthocyanin synthesis under abiotic stress to maintain ROS homeostasis is unknown. Here, ROS‐related proteins, SIMILAR TO RCD‐ONEs (SROs), were analysed in Zea mays (maize), and all six SRO1 genes were inducible by a variety of abiotic stress agents. The constitutive expression of one of these genes, ZmSRO1e, in maize as well as in Arabidopsis thaliana increased the sensitivity of the plant to abiotic stress, but repressed anthocyanin biosynthesis and ROS scavenging activity. Loss‐of‐function mutation of ZmSRO1e enhanced ROS tolerance and anthocyanin accumulation. We showed that ZmSRO1e competed with ZmR1 (a core basic helix‐loop‐helix subunit of the MYB–bHLH–WD40 transcriptional activation complex) for binding with ZmPL1 (a core MYB subunit of the complex). Thus, during the constitutive expression of ZmSRO1e, the formation of the complex was compromised, leading to the repression of genes, such as ZmA4 (encoding dihydroflavonol reductase), associated with anthocyanin synthesis. Overall, the results have revealed a mechanism that allows the products of maize SRO1e to participate in the abiotic stress response. Significance Statement: The SRO family is a plant‐specific group of proteins involved in the abiotic stress response, but the function and molecular mechanisms of maize SRO proteins in abiotic stress are unclear. In this study, we found that ZmSRO1e, the most stress responsive of all maize SROs, repressed anthocyanin synthesis and was involved in the maintenance of ROS homeostasis, which is important for balancing plant growth and abiotic stress tolerance. [ABSTRACT FROM AUTHOR]

Summary: Renal cell carcinoma (RCC) is one of the most common malignancies worldwide, and metabolic reprogramming has a profound effect on RCC tumorigenesis. mTORC1 inhibitors are widely used in RCC treatment, yet some types of RCC cells are resistant to these compounds. Thus, clarification of the metabolic mechanism of mTORC1 inhibitors and exploration of new therapeutic approaches are urgently needed. In this study, we found that the mTORC1 pathway was hyperactive in RCC. Immunohistochemistry and western blot analysis showed that phosphorylation of the mTORC1 substrate 4EBP1 at threonine 37/46 increased in RCC tissues compared with that in normal renal tissues. It was also found that mTORC1 inhibitor everolimus suppressed glucose consumption, lactate production, and multiple catalytic enzymes involved in glycolysis in 786-O and ACHN cells, but the accumulation of HIF1α induced by CoCl2 blocked the inhibitory effect of everolimus on aerobic glycolysis. Interestingly, western blot and metabolite analysis showed that the tumor suppressor NDRG2 (N-Myc downstream regulated gene 2) was able to inhibit mTORC1 activity and cooperate with an mTOR inhibitor to decrease aerobic glycolysis in 786-O and ACHN cells. These results demonstrate that NDRG2 may potentially synergize with mTORC1 inhibitors to suppress malignant phenotype of RCC. Taken together, these data provided preclinical evidence that the combination of NDRG2 and mTORC1 inhibitors might be a promising strategy for RCC therapy. [ABSTRACT FROM AUTHOR]

Summary: As one of the largest gene families in plants, the cytochrome P450 monooxygenase genes (CYPs) are involved in diverse biological processes including biotic and abiotic stress response. Moreover, P450 genes are prone to expanding due to gene tandem duplication during evolution, resulting in generations of novel alleles with the neo‐function or enhanced function. Here, the bread wheat (Triticum aestivum) gene TaCYP81D5 was found to lie within a cluster of five tandemly arranged CYP81D genes, although only a single such gene (BdCYP81D1) was present in the equivalent genomic region of the wheat relative Brachypodium distachyon. The imposition of salinity stress could up‐regulate TaCYP81D5, but the effect was abolished in plants treated with an inhibitor of reactive oxygen species synthesis. In SR3, a wheat cultivar with an elevated ROS content, the higher expression and the rapider response to salinity of TaCYP81D5 were related to the chromatin modification. Constitutively expressing TaCYP81D5 enhanced the salinity tolerance both at seedling and reproductive stages of wheat via accelerating ROS scavenging. Moreover, an important component of ROS signal transduction, Zat12, was proven crucial in this process. Though knockout of solely TaCYP81D5 showed no effect on salinity tolerance, knockdown of BdCYP81D1 or all TaCYP81D members in the cluster caused the sensitivity to salt stress. Our results provide the direct evidence that TaCYP81D5 confers salinity tolerance in bread wheat and this gene is prospective for crop improvement. [ABSTRACT FROM AUTHOR]

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)