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Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects. This study investigates the role of UGT2B15, an essential enzyme for androgen metabolism, in PCOS pathogenesis and its potential as a therapeutic target. Methods: We used RNA sequencing to examine the effects of UGT2B15 knockdown in KGN cells. To modulate UGT2B15 expression, we employed siRNA and (R)/(S)-NAF (naftopidil), a chemical inducer of UGT2B15 identified in our previous studies on a prostate hyperplasia model. The effects of siRNA and (R)/(S)-NAF on dihydrotestosterone (DHT) levels, cell apoptosis, and the expression of apoptosis-related proteins in KGN cells were evaluated. In a PCOS mouse model, we assessed the effects of (R)-NAF and (S)-NAF on serum androgen levels, menstrual cycles, ovarian morphology, and UGT2Bs expression. Additionally, luciferase reporter and ChIP assays were utilized to study UGT2B15 regulation by NR1H4. Results: Elevated androgens were found to suppress UGT2B15 expression in ovarian granulosa cells, leading to DHT accumulation and apoptosis. (R)-NAF and (S)-NAF treatments reversed these effects, alleviating PCOS symptoms in mice such as hyperandrogenism, irregular menstrual cycles, and the presence of ovarian cysts. NR1H4 negatively regulated the transcription of UGT2B15 in KGN cells. (R)-NAF and (S)-NAF disrupted NR1H4 binding to the UGT2B15 promoter without affecting its protein levels, indicating direct interference with its regulation. Conclusions: UGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment. [ABSTRACT FROM AUTHOR]

An ultra-thin spiral diffractive lens (SDL) was fabricated by using focused ion beam milling on a fiber end-facet coated with a 100 nm thick Au film. Focusing vortex beams (FVBs) were successfully excited by the SDLs due to the coherent superposition of diffracted waves and their azimuth dependence of the phase accumulated from the spiral aperture to the beam axis. The polarization and phase characteristics of the FVBs were experimentally investigated. Results show that the input beams with various polarization states were converted to FVBs, whose polarization states were the same as those of the input beams. Furthermore, the focal length of the SDL and the in-tensity and phase distribution at the focus spot of the FVBs were numerically simulated by the FDTD method in the ultra-wide near-infrared waveband from 1300 nm to 1800 nm. The focal length was tuned from 21.8 μm to 14.7 μm, the intensity profiles exhibited a doughnut-like shape, and the vortex phase was converted throughout the broadband range. The devices are expected to be candidates for widespread applications including optical communications, optical imaging, and optical tweezers. [ABSTRACT FROM AUTHOR]

In order to study the influence of diameter on the performance of basalt fiber-asphalt mixture, AC-13 asphalt mixtures mixed with basalt fibers with diameters of 7, 16 and 25 μm were designed and prepared. Rutting test, uniaxial penetration test, low temperature trabecular test, immersion Marshall test and freeze-thaw splitting test were used to study its road performance. Ideal cracking test and dynamic modulus test were used to test its mechanical properties. The results show that the diameter of basalt fiber has a great effect on the improvement of various performance indexes of asphalt mixture. The optimum oil-stone ratio of asphalt mixture increases slightly with the decrease of basalt fiber diameter. Under the same fiber content and fiber length, the smaller the fiber diameter, the larger amount of fibers, and the richer the reinforcement network. Therefore, the 7 μm diameter basalt fiber has the most significant improvement effect on the high and low frequency dynamic modulus, medium and low temperature crack resistance and high temperature deformation resistance of asphalt mixture. The findings of the present work provides reference for the further design of basalt fiber asphalt mixture. [ABSTRACT FROM AUTHOR]

Mastitis, the inflammation of the mammary gland caused by both gram-positive and gram-negative bacteria, causes the global dairy industry over $20 billion annually in losses due to changes in milk yield and quality. The goal of this study was to identify genetic variants, genes, and biological pathways that are associated with mastitis. We performed genome-wide association studies (GWAS) on 1,858 cows from two lactations with both medium (n = 87,493) and high density (n = 624,300) single nucleotide polymorphisms (SNP) using a single SNP mixed linear model implemented in GCTA software. A total of 288 SNPs across all evaluated models passed the 5% genome-wise false discovery rate threshold across all autosomes with emphasis on chromosomes 3, 14, 16, 12, 6, and 2. These SNPs were mapped to their corresponding genes using the bovine genome. Gene enrichment analysis was then performed to identify significant biological pathways associated with mastitis. The current study identified potential genes that are involved in the MAPK, C5a, and ion binding pathways, which have been previously associated with immune function and inflammation. Further validation and investigation are required to confirm the identified genes and pathways before implementation in breeding programs. [ABSTRACT FROM AUTHOR]

Background: Although glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the most common inherited disorder in the Chinese population, there is scarce evidence regarding the epidemiology, evolutionary origin, and malaria‐induced positive selection effects of G6PD‐deficient alleles in various Chinese ethnic populations. Methods: We performed a large population‐based screening (n = 15,690) to examine the impact of selection on human nucleotide diversity and to infer the evolutionary history of the most common deficiency alleles in Chinese populations. Results: The frequencies of G6PD deficiency ranged from 0% to 11.6% in 12 Chinese ethnic populations. A frequency map based on geographic information showed that G6PD deficiency was highly correlated with historical malaria prevalence in China and was affected by altitude and latitude. The five most frequently occurring G6PD gene variants were NM_001042351.3:c.1376G>T, NM_001042351.3:c.1388G>A, NM_001042351.3:c.95A>G, NM_001042351.3:c.1311T>C, and NM_001042351.3:c.1024C>T, which were distributed with ethnic features. A pathogenic but rarely reported variant site (NM_001042351.3:c.448G>A) was identified in this study. Bioinformatic analysis revealed a strong and recent positive selection targeting the NM_001042351.3:c.1376G>T allele that originated in the past 3125 to 3750 years and another selection targeting the NM_001042351.3:c.1388G>A allele that originated in the past 5000 to 6000 years. Additionally, both alleles originated from a single ancestor. Conclusion: These results indicate that malaria has had a major impact on the Chinese genome since the introduction of rice agriculture. [ABSTRACT FROM AUTHOR]