Cross-species modeling of plant genomes at single nucleotide resolution using a pre-trained DNA language model.

Understanding the function and fitness effects of diverse plant genomes requires transferable models. Language models (LMs) pre-trained on large-scale biological sequences can learn evolutionary conservation, thus expected to offer better cross-species prediction through fine-tuning on limited labeled data compared to supervised deep learning models. We introduce PlantCaduceus, a plant DNA LM based on the Caduceus and Mamba architectures, pre-trained on a carefully curated dataset consisting of 16 diverse Angiosperm genomes. Fine-tuning PlantCaduceus on limited labeled Arabidopsis data for four tasks involving transcription and translation modeling demonstrated high transferability to maize that diverged 160 million years ago, outperforming the best baseline model by 1.45-fold to 7.23-fold. PlantCaduceus also enables genome-wide deleterious mutation identification without multiple sequence alignment (MSA). PlantCaduceus demonstrated a threefold enrichment of rare alleles in prioritized deleterious mutations compared to MSA-based methods and matched state-of-the-art protein LMs. PlantCaduceus is a versatile pre-trained DNA LM expected to accelerate plant genomics and crop breeding applications.

Association between Waist-Hip Ratio and Female Infertility in the United States: Data from National Health and Nutrition Examination Survey 2017-2020.

INTRODUCTION: Obesity has previously been correlated with an elevated risk of reproductive system diseases in women. The waist-hip ratio (WHR) has been shown to be correlated with visceral fat, making it one of the most commonly used indicators of abdominal obesity. However, little is known about the relationship between WHR and infertility. Therefore, the aim of this study was to evaluate the effect of the WHR on infertility in women of childbearing age. METHODS: The study used cross-sectional data from women aged 20-45 who participated in the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2017 and 2020. We collected details of their waist circumference, hip circumference, fertility status, and several other essential variables. We used multivariate logistic regression analysis and subgroup analyses to assess the association between WHR and infertility. RESULTS: There were 976 participants, with 12.0% (117/976) who experienced infertility. After adjusting for potential confounding factors, our multivariate logistic regression analysis revealed that every 0.1 unit increase in WHR resulted in a more than 35% higher risk of infertility (odds ratio [OR; 95% confidence interval [CI]: 1.35 [1.01∼1.81], p = 0.043). Compared to the group with WHR <0.85, the risk of infertility increased in the group with WHR ≥0.85, with an adjusted OR of 1.74 (95% CI: 1.06∼2.85). When WHR was treated as a continuous variable, it was observed that each 0.1 unit increase in WHR was associated with a relatively high risk in the secondary infertility population after adjusting all covariates, with an OR of 1.66 (95% CI: 1.14∼2.40, p = 0.01). When WHR was analyzed as a categorical variable, the group with WHR ≥0.85 exhibited a significantly higher risk of secondary infertility than the group with WHR <0.85, with the OR of 2.75 (95% CI: 1.35-5.59, p = 0.01) after adjusting for all covariates. Furthermore, the interaction analysis indicated that there was a significant interaction between age status on WHR and the risk of infertility. CONCLUSION: WHR showed a positive correlation with the risk of infertility. This study highlights the importance of effectively managing abdominal fat and promoting the maintenance of optimal WHR levels to mitigate the progression of infertility, particularly for younger women.

Integrating single-cell RNA-sequencing and bulk RNA-sequencing data to explore the role of mitophagy-related genes in prostate cancer.

Prostate cancer (PCa) is the most common malignancy of the male urinary system. Mitophagy, as a type of autophagy, can remove damaged mitochondria in cells. Mitophagy-related genes (MRGs) have been shown to play critical roles in the development of PCa. To this end, based on the comprehensive analysis of RNA-seq and scRNA-seq data of PCa samples and their controls, this paper identified PCa subtypes and constructed a prognostic model. In this paper, we downloaded scRNA-seq and RNA-seq data from Gene Expression Omnibus (GEO) and TCGA database. Based on the R package "Seurat" to process the scRNA-seq data, a total of five cell types were identified. Each cell population was scored based on the R package "AUCell" and using the intersection genes between MRGs and each cell population. The B cell population was then identified as a high-scoring cell population. Differentially expressed genes in RNA-seq data were identified based on the R package "limma" and intersected with previously intersected genes. Then, based on univariate Cox regression analysis and Lasso-Cox regression analysis, the prognostic genes were screened, and the risk model was constructed (composed of ADH5, CAT, BCAT2, DCXR, OGT, and FUS). The model is validated on internal and external test sets. Independent prognostic analysis identified age, N stage, and risk score as independent prognostic factors. This paper's risk models and prognostic genes can provide a reference for developing novel therapeutic targets for PCa.

HIV-related stress predicts depression over five years among people living with HIV.

Introduction: Extant literature has demonstrated significant associations between HIV-related stress, social support, and depression among PLWH. However, little research has been conducted on the changes in such associations over time. Our study aims to explore the longitudinal relationship between HIV-related stress, social support, and depression among PLWH over five years. Methods: 320 PLWH were recruited from Changsha Center for Disease Control and Prevention (CDC), Hunan Province, China. They were assessed for depressive symptoms, HIV-related stress, and social support within 1 month of HIV diagnosis, 1 year after diagnosis, and five years after diagnosis, respectively. Relationships between these variables were examined using a fixed effect model. Result: The prevalence of depressive symptoms within the first month, first year, and fifth years of HIV diagnosis was 35, 12.2, and 14.7%, respectively. Emotional stress (ß: 0.730, 95% CI: 0.648, 0.811), social stress (ß: 0.066, 95% CI: 0.010, 0.123), instrumental stress (ß: 0.133, 95% CI:0.046, 0.221) positively predicted depression, while social support utilization (ß: -0.176, 95% CI: -0.303, -0.049) negatively predicted depression. Conclusion: Our study suggests that HIV-related stress and social support predict depressive symptoms over time among PLWH and that reducing HIV-related stress and improving social support in the early stages of diagnosis is extremely important in preventing depressive symptoms among PLWH.

TRIPBASE: a database for identifying the human genomic DNA and lncRNA triplexes.

Long-non-coding RNAs (lncRNAs) are defined as RNA sequences which are >200 nt with no coding capacity. These lncRNAs participate in various biological mechanisms, and are widely abundant in a diversity of species. There is well-documented evidence that lncRNAs can interact with genomic DNAs by forming triple helices (triplexes). Previously, several computational methods have been designed based on the Hoogsteen base-pair rule to find theoretical RNA-DNA:DNA triplexes. While powerful, these methods suffer from a high false-positive rate between the predicted triplexes and the biological experiments. To address this issue, we first collected the experimental data of genomic RNA-DNA triplexes from antisense oligonucleotide (ASO)-mediated capture assays and used Triplexator, the most widely used tool for lncRNA-DNA interaction, to reveal the intrinsic information on true triplex binding potential. Based on the analysis, we proposed six computational attributes as filters to improve the in-silico triplex prediction by removing most false positives. Further, we have built a new database, TRIPBASE, as the first comprehensive collection of genome-wide triplex predictions of human lncRNAs. In TRIPBASE, the user interface allows scientists to apply customized filtering criteria to access the potential triplexes of human lncRNAs in the cis-regulatory regions of the human genome. TRIPBASE can be accessed at https://tripbase.iis.sinica.edu.tw/.

Association of short sleep with risk of periodontal disease: A meta-analysis and Mendelian randomization study.

AIM: The aim of this meta-analysis and Mendelian randomization (MR) study was to assess the association between short sleep and periodontal disease, including tooth loss and periodontitis. MATERIALS AND METHODS: The meta-analysis of relevant studies was conducted to assess the association between short sleep and periodontal disease. MR analyses were conducted with the inverse-variance-weighted (IVW) method, weighted median method, MR-Egger method, and MR-Robust Adjusted Profile Score (RAPS) method to assess the causal effect of short sleep on tooth loss and periodontitis. RESULTS: Seven cross-sectional studies involving 40,196 individuals were included in the meta-analysis. The association between short sleep and periodontal disease was not statistically significant (odds ratios (OR) =1.13, 95% confidence interval (CI): 0.99, 1.28; p = 0.076). In the MR analysis, we did not observe statistically significant causal associations of genetically determined short sleep with tooth loss (ß: -0.056; 95% CI: -0.181 to 0.068; p = 0.376) and periodontitis (ß: -0.112; 95% CI: -0.340 to 0.117; p = 0.339). CONCLUSIONS: Short sleep is not associated with the risk of periodontal disease according to current evidence. Future studies need to pay attention to the measurement of sleep duration, the choice of statistical models, and other domains of sleep health.

[Anti-oxidation and anti-apoptosis mechanism of Xinshao formula on cerebral ischemia reperfusion injury].

The cerebral ischemia-reperfusion model was established to investigate the anti-oxidation and anti-apoptosis mechanism of Xinshao formula on the cerebral ischemia reperfusion injury in rats. SD rats were randomly divided into five groups: sham operation group, model group, and low, middle and high-dose Xinshao formula groups (0.31, 0.62, 1.25 g·kg⁻¹). After administration with Xinshao formula for 7 days, the rats were used to establish the cerebral ischemia-reperfusion model. The neurological behavior was evaluated. TTC staining was implemented to determine the volume of cerebral infarction. The levels of ROS, SOD, GSH-PX, NO and iNOS in serum were examined, and the mRNA and protein levels of Bcl-2, Bax and caspase 3 in hippocampal CA1 were detected by qRT-PCR, immunohistochemical assay and Western blot. It is found that Xinshao formula could significantly reduce the symptoms of nervous function and the volume of cerebral infarction in MACO rats. Compared with model group, the rats in Xinshao formula group showed increases in the activities of SOD and GSH-PX (P<0.01), and decreases in the activities of iNOS and the contents of NO, ROS and MDA (P<0.01). In addition, Xinshao formula could down-regulate the mRNA and protein levels of Bax and caspase 3 (P<0.01), and up-regulated those of Bcl-2 (P<0.01) in MACO rats. In conclusion, Xinshao formula showed aprotective effect on cerebral ischemia reperfusion injuryin rats, which may be associated with the promotion of anti-oxidation and anti-apoptosis.

[EFFECTIVENESS OF MODIFIED Park METHOD OF BLEPHAROPLASTY FOR CORRECTION OF MILD BLEPHAROPTOSIS].

OBJECTIVE: To explore the effectiveness of the modified Park method of blepharoplasty for correction of mild blepharoptosis. METHODS: Between October 2012 and January 2015, a new modified Park method of blepharoplasty was performed on 23 patients with foldless eyelid combined mild blepharoptosis. There were 14 males and 9 females, aged 16 to 35 years (mean, 25 years). Unilateral eyelid was involved in 16 cases, bilateral eyelids in 7 cases. The upper eyelid was located at the edge of the pupil, and the drop was 1-2 mm (mean, 1.5 mm). RESULTS: All incisions healed at the first stage; no obvious blood stasis and swelling occurred. The patients were followed up 4 to 26 months, with an average of 15 months. The double eyelid fold was natural and smooth, and ptosis was completely corrected; the eyelid shape and position were symmetry when in situ fixation and movement. According to "double eyelid operation effect evaluation standard discussion" method by Chinese Medical Cosmetology Association, the results were excellent in all patients. CONCLUSION: The modified Park method of blepharoplasty can achieve blepharoplasty and correcting blepharoptosis at the same time for correction of foldless eyelid combined mild blepharoptosis during operation without separated and amputated levator aponeurosis, with small surgical trauma, good controllability, and maneuverability in correction amplitude.