FOXA1 regulates ribosomal RNA transcription in prostate cancer.

BACKGROUND: Ribosome biogenesis is excessively activated in tumor cells, yet it is little known whether oncogenic transcription factors (TFs) are involved in the ribosomal RNA (rRNA) transactivation. METHODS: Nucleolar proteomics data and large-scale immunofluorescence were re-analyzed to jointly identify the proteins localized at nucleolus. RNA-Seq data of five prostate cancer (PCa) cohorts were combined and integrated with multi-dimensional data to define the upregulated nucleolar TFs in PCa tissues. Then, ChIP-Seq data of PCa cell lines and two PCa clinical cohorts were re-analyzed to reveal the TF binding patterns at ribosomal DNA (rDNA) repeats. The TF binding at rDNA was validated by ChIP-qPCR. The effect of the TF on rRNA transcription was determined by rDNA luciferase reporter, nascent RNA synthesis, and global protein translation assays. RESULTS: In this study, we reveal the role of oncogenic TF FOXA1 in regulating rRNA transcription within nucleolar organization regions. By analyzing human TFs in prostate cancer clinical datasets and nucleolar proteomics data, we identified that FOXA1 is partially localized in the nucleolus and correlated with global protein translation. Our extensive FOXA1 ChIP-Seq analysis provides robust evidence of FOXA1 binding across rDNA repeats in prostate cancer cell lines, primary tumors, and castration-resistant variants. Notably, FOXA1 occupancy at rDNA repeats correlates with histone modifications associated with active transcription, namely H3K27ac and H3K4me3. Reducing FOXA1 expression results in decreased transactivation at rDNA, subsequently diminishing global protein synthesis. CONCLUSIONS: Our results suggest FOXA1 regulates aberrant ribosome biogenesis downstream of oncogenic signaling in prostate cancer.

Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

The genome of Eleocharis vivipara elucidates the genetics of C3-C4 photosynthetic plasticity and karyotype evolution in the Cyperaceae.

Eleocharis vivipara, an amphibious sedge in the Cyperaceae family, has several remarkable properties, most notably its alternate use of C3 photosynthesis underwater and C4 photosynthesis on land. However, the absence of genomic data has hindered its utility for evolutionary and genetic research. Here, we present a high-quality genome for E. vivipara, representing the first chromosome-level genome for the Eleocharis genus, with an approximate size of 965.22 Mb mainly distributed across 10 chromosomes. Its Hi-C pattern, chromosome clustering results, and one-to-one genome synteny across two subgroups indicates a tetraploid structure with chromosome count 2n = 4x = 20. Phylogenetic analysis suggests that E. vivipara diverged from Cyperus esculentus approximately 32.96 million years ago (Mya), and underwent a whole-genome duplication (WGD) about 3.5 Mya. Numerous fusion and fission events were identified between the chromosomes of E. vivipara and its close relatives. We demonstrate that E. vivipara has holocentromeres, a chromosomal feature which can maintain the stability of such chromosomal rearrangements. Experimental transplantation and cross-section studies showed its terrestrial culms developed C4 Kranz anatomy with increased number of chloroplasts in the bundle sheath (BS) cells. Gene expression and weighted gene co-expression network analysis (WGCNA) showed overall elevated expression of core genes associated with the C4 pathway, and significant enrichment of genes related to modified culm anatomy and photosynthesis efficiency. We found evidence of mixed nicotinamide adenine dinucleotide - malic enzyme and phosphoenolpyruvate carboxykinase type C4 photosynthesis in E. vivipara, and hypothesize that the evolution of C4 photosynthesis predates the WGD event. The mixed type is dominated by subgenome A and supplemented by subgenome B. Collectively, our findings not only shed light on the evolution of E. vivipara and karyotype within the Cyperaceae family, but also provide valuable insights into the transition between C3 and C4 photosynthesis, offering promising avenues for crop improvement and breeding.

Pathological Characteristics and Classification of Unstable Coronary Atherosclerotic Plaques.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

A Review of Chronic Lateral Ankle Instability and Emerging Alternative Outcome Monitoring Tools in Patients following Ankle Ligament Reconstruction Surgery.

Ankle sprains are exceedingly common injuries in both athletes and the general population. They account for 10 to 30% of all sports injuries. Although the vast majority of lateral ankle ligament injuries respond successfully to conservative management, the absolute number of those that progress to chronic lateral ankle instability (CLAI) remains considerably important. This condition is characterized by persistent symptoms and may be associated with short-term and long-term complications and functional deficits. There is still a lack of ideal postoperative management of CLAI patients. Furthermore, an evidence-based rehabilitation phasing does not exist and most of the published studies regarding this subject suggest some protocols based on a wide variety of functional assessment scores and other modalities that are not accurate enough. Moreover, the literature that assesses the ability to return to work (RTW) and return to sport (RTS) in the general population and athletes operated for CLAI most commonly shows aggregated results with global rates of RTW or RTS without describing a detailed timeline based on the readiness of patients to return to each level of activity. Although stress radiographs and MRI have been assessed as potential tools to improve postoperative management of CLAI patients, the first modality is limited by its low sensitivity to detect laxity and the second one by its static character and its inability to predict neither the healing process phase nor the mechanical properties of the repaired/reconstructed ligaments. Bioelectrical impedance, mechanical impedance and near-infrared spectroscopy are non-invasive methods of measurement that could be potential assessment tools to help surgeons improve the postoperative management of patients after CLAI surgery.

[Effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery for early-stage breast cancer in different quadrants].

Objective: To compare the effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery (SMPSL-BCS) in treating early-stage breast cancer patients with tumors in different quadrants. Methods: A retrospective analysis was conducted on 200 early-stage breast cancer female patients admitted between January 2023 and December 2023. According to the quadrant where the tumor was located, the patients were allocated into the upper outer quadrant group (UO group), lower outer quadrant group (LO group), upper inner quadrant group (UI group), and lower inner quadrant group (LI group), with 50 cases in each group. There was no significant difference ( P>0.05) in the baseline data, including age, body mass index, smoking history, marital status, comorbidities, affected breast side, maximum tumor diameter on ultrasound, maximum pathological tumor diameter, clinical tumor stage, molecular subtype, and disease duration. The operation time, intraoperative blood loss, postoperative drainage volume, and extubation time were recorded and compared between groups. Additionally, the occurrence of early-stage complications (1-3 months after operation; including subcutaneous fluid accumulation, incision infection, superficial skin burns) and late-stage complications (>3 months after operation; including pectoralis major muscle adhesion, changes in breast appearance and shape, sensory discomfort) were assessed. At 6 months after operation, the cosmetic outcome of breast-conserving surgery was rated for all groups. Results: The UO group had the shortest operation time, followed by the UI group, LO group, and LI group, showing significant differences between groups ( P<0.05). The UO group had the least intraoperative blood loss, followed by the LO group, UI group, and LI group; except for the difference between UO group and LO group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The UO group had the least postoperative drainage volume, followed by the LO group, UI group, and LI group; except for the difference between LO group and UI group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The extubation time of the LI group was significantly longer than that of the other groups ( P<0.05). All patients were followed up 4-12 months, with an average of 8 months. And 193 patients were followed up more than 6 months, including 48 patients in UO group, 47 in LO group, 49 in UI group, and 49 in LI group. In the early-stage period, the LI group had a higher incidence of subcutaneous fluid accumulation after tube removal compared to the UO group and LO group ( P<0.05), while there was no significant difference in the incidences of other early complications between groups ( P>0.05). In the late-stage period, the LI group had significantly higher incidences of pectoralis major muscle adhesion and changes in breast appearance and shape than UO group and LO group ( P<0.05), and a significantly higher incidence of sensory discomfort than UO group ( P<0.05). There was no significant difference in the incidences of other late-stage complications between groups ( P>0.05). At 6 months after operation, the cosmetic outcomes of breast-conserving surgery were significantly better in UO group, LO group, and UI group than in LI group ( P<0.05); there was no significant difference between the other groups ( P>0.05). Conclusion: In the treatment of early-stage breast cancer using SMPSL-BCS, patients with tumors located in the upper outer quadrant show the best effectiveness. The effectivenesses are similar for patients with tumors in the lower outer and upper inner quadrants. However, patients with tumors in the lower inner quadrant do not experience significant advantages. Therefore, it is recommended that SMPSL-BCS should not be the first-choice surgical method for patients with tumors in the lower inner quadrant.

Parental betaine supplementation promotes gosling growth with epigenetic modulation of IGF gene family in the liver.

Betaine is widely used as a feed additive in the chicken industry to promote laying performance and growth performance, yet it is unknown whether betaine can be used in geese to improve the laying performance of goose breeders and the growth traits of offspring goslings. In this study, laying goose breeders at 39 wk of age were fed basal (Control, CON) or betaine-supplemented diets at low (2.5 g/kg, LBT) or high (5 g/kg, HBT) levels for 7 wk, and the breeder eggs laid in the last week were collected for incubation. Offspring goslings were examined at 35 and 63 d of age. The laying rate tended to be increased (P = 0.065), and the feed efficiency of the breeders was improved by betaine supplementation, while the average daily gain of the offspring goslings was significantly increased (P < 0.05). Concentrations of insulin-like growth factor 2 (IGF-2) in serum and liver were significantly increased in the HBT group (P < 0.05), with age-dependent alterations of serum T3 levels. Concurrently, hepatic mRNA expression of the IGF gene family was significantly increased in goslings derived from betaine-treated breeders (P < 0.05). A higher ratio of proliferating cell nuclear antigen (PCNA)-immunopositive nuclei was found in the liver sections of the HBT group, which was confirmed by significantly upregulated hepatic expression of PCNA mRNA and protein (P < 0.05). Moreover, hepatic expression of thyroxine deiodinase type 1 (Dio1) and thyroid hormone receptor ß (TRß) was also significantly upregulated in goslings of the HBT group (P < 0.05). These changes were associated with significantly higher levels of global DNA 5-mC methylation, together with increased expression of methyl transfer genes (P < 0.05), including betaine-homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT), and DNA (cytosine-5-)-methyltransferase 1 (DNMT1). The promoter regions of IGF-2 genes, as well as the predicted TRß binding site on the IGF-2 gene, were significantly hypomethylated (P < 0.05). These results indicate that gosling growth can be improved by dietary betaine supplementation in goose breeders via epigenetic modulation of the IGF gene family, especially IGF-2, in the liver.

The goose industry plays important roles in economics, cultures, and ecosystems, yet the low laying and growth rates of many indigenous breeds hinders the development of the goose farming. Betaine, an important methyl donor, is commonly used as a feed additive in livestock and poultry to enhance animal growth. Dietary supplementation of betaine in laying hens or gestational sows has been reported to promote the growth of their offspring. Here, we sought to investigate whether and how dietary betaine supplementation affects the growth and development of offspring goslings. In this study, goose breeders, both male and female, were fed a basal diet supplemented respectively with 0, 2.5, or 5 g/kg betaine for 7 wk. Goslings hatched from the breeder eggs of different groups were raised under the same standard condition for assessing the growth performance. Parental betaine increases the growth rate of offspring goslings with decreased DNA methylation on the IGF-2 gene promoter and increased expression of the IGF-2 gene in the liver. These results provide scientific evidence for the inter-generational effect of betaine on gosling growth.

Magnetic Seizure Therapy vs Modified Electroconvulsive Therapy in Patients With Bipolar Mania: A Randomized Clinical Trial.

Importance: Bipolar mania is a common disabling illness. Electroconvulsive therapy (ECT) is an effective treatment for patients with severe mania, though it is limited by the risk of cognitive adverse effects. Magnetic seizure therapy (MST) as an alternative treatment to ECT for bipolar mania has not yet been reported. Objective: To compare the effectiveness and cognitive adverse effects of MST and ECT in bipolar mania. Design, Setting, and Participants: This randomized clinical trial was conducted at the Shanghai Mental Health Center from July 1, 2017, through April 26, 2021. Forty-eight patients with bipolar mania were recruited and randomly allocated to receive MST or ECT. The data analysis was performed from June 5, 2021, through August 30, 2023. Interventions: Patients completed 2 or 3 sessions of MST or ECT per week for a total of 8 to 10 sessions. The MST was delivered at 100% device output with a frequency of 75 Hz over the vertex. Main Outcomes and Measures: The primary outcomes were reduction of total Young Manic Rating Scale (YMRS) score and response rate (more than 50% reduction of the total YMRS score compared with baseline). An intention-to-treat (ITT) analysis and repeated-measures analyses of variance were conducted for the primary outcomes. Results: Twenty patients in the ECT group (mean [SD] age, 31.6 [8.6] years; 12 male [60.0%]) and 22 patients in the MST group (mean [SD] age, 34.8 [9.8] years; 15 male [68.2%]) were included in the ITT analysis. The response rates were 95.0% (95% CI, 85.4%-100%) in the ECT group and 86.4% (95% CI, 72.1%-100%) in the MST group. The YMRS reduction rate (z = -0.82; 95% CI, -0.05 to 0.10; P = .41) and response rate (χ2 = 0.18; 95% CI, -0.13 to 0.31; P = .67) were not significantly different between the groups. The time-by-group interaction was significant for the language domain (F1,24 = 7.17; P = .01), which was well preserved in patients receiving MST but worsened in patients receiving ECT. No serious adverse effects were reported in either group. Conclusions and Relevance: These findings suggest that MST is associated with a high response rate and fewer cognitive impairments in bipolar mania and that it might be an alternative therapy for the treatment of bipolar mania. Trial Registration: ClinicalTrials.gov Identifier: NCT03160664.

Childhood maltreatment and personality disorders in adolescents and adults with psychotic or non-psychotic disorders.

Introduction: While the attention to personality disorders (PD) and childhood maltreatment (CM) has grown in recent years, there remains limited understanding of the prevalence and distinctions of PD and CM in clinical populations of Chinese adolescents in comparison to adults. Methods: A total of 1,417 participants were consecutively sampled from patients diagnosed with either psychotic or non-psychotic disorders in the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. The participants were categorized into two groups based on their age: adolescents (aged 15-21 years) and adults (aged 22-35 years). PDs were evaluated using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were assessed using the Chinese version of the Child Trauma Questionnaire Short Form. Results: When comparing self-reported PD traits and CM between adolescents and adults, differences emerge. Adolescents, particularly in the psychotic disorder group, exhibit more pronounced schizotypal PD traits (p=0.029), and this pattern extends to non-psychotic disorders (p<0.001). Adolescents in the non-psychotic disorder group also report higher levels of emotional abuse (p=0.014), with a notable trend in physical abuse experiences compared to adults (p=0.057). Furthermore, the most prevalent PDs in the clinical sample are avoidant, borderline, and obsessive-compulsive PDs. Among patients with psychotic disorders, adolescents exhibit higher rates of schizoid, schizotypal, and obsessive-compulsive PDs compared to adults. Logistic regression analyses highlight distinct predictors for psychotic and non-psychotic disorders in adolescents and adults. Discussion: The findings emphasize distinct differences in PDs and CMs between adolescent and adult groups, shedding light on their potential roles in psychotic and non-psychotic disorders.