LncRNA H19 promoted alcohol-associated liver disease through dysregulation of alternative splicing and methionine metabolism.

BACKGROUND AND AIMS: Long noncoding RNAs constitute a significant portion of the human genome. Among these, lncRNA H19, initially identified for its high expression during fetal development followed by a decline in the liver postnatally, re-emerges in various liver diseases. However, its specific role in alcohol-associated liver disease (ALD) remains unclear. APPROACH AND RESULTS: Elevated H19 levels were detected in peripheral blood and livers of patients with alcohol-associated cirrhosis and hepatitis, as well as in livers of ethanol-fed mice. Hepatic overexpression of H19 exacerbated ethanol-induced liver steatosis and injury. Metabolomics analysis revealed decreased methionine levels in H19-overexpressed mouse livers, attributable to H19-mediated inhibition of betaine homocysteine methyltransferase (BHMT), a crucial enzyme in methionine synthesis. H19 regulated BHMT alternative splicing through polypyrimidine tract-binding protein 1 (PTBP1), resulting in a reduced Bhmt protein-coding variant. The maternally specific knockout of H19 (H19Mat+/-) or liver-specific knockout of the H19 differentially methylated domain (H19DMDHep-/-) in ethanol-fed mice upregulated BHMT expression and ameliorated hepatic steatosis. Furthermore, BHMT restoration counteracted H19-induced ethanol-mediated hepatic steatosis. CONCLUSIONS: This study identifies a novel mechanism whereby H19, via PTBP1-mediated BHMT regulation, influences methionine metabolism in ALD. Targeting the H19-PTBP1-BHMT pathway may offer new therapeutic avenues for ALD.

Physician reported toxicities and patient reported quality of life of transperineal ultrasound-guided radiotherapy of prostate cancer.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8-169 ng/ml). At the median follow-up of 19 months (3-82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Early Rehabilitation Activity and Rehabilitation in ICU Wards in Central China: A Cross-Sectional Survey.

Background: Patients in Intensive Care Units (ICUs) face high risks of physical, functional, cognitive, and mental impairments. Early rehabilitation activities are crucial for reducing mortality and complication rates. This survey investigates the characteristics, current implementation, and detailed status of early rehabilitation activities in ICUs across Central China. Methods: A cross-sectional survey was conducted involving 158 hospitals, with 131 responding. Data on institutional characteristics and early rehabilitation activities were collected through questionnaires. Descriptive statistical analysis described the current status, and a univariate regression model identified factors associated with the implementation of early rehabilitation measures. Results: A total of 131 ICUs completed the survey, with a response rate of 82.91% (131/158). Results indicated that 82.44% (108/131) of ICUs implemented early rehabilitation activities, but only 65 (49.62%) had explicit early rehabilitation exercise protocols or standards/procedures. Before implementing early rehabilitation activities, approximately 89.97% (110/131) of ICUs conducted assessments, and 46.56% (61/131) regularly held structured interdisciplinary rounds to discuss early activity measures and goals. More than half of the participating adult ICUs reported screening patients for swallowing function (64.89%; 85/131), and 55.73% (73/131) of adult ICUs reported having a nutrition therapy specialist conduct regular consultations/visits. Only 26.72% (35/131) of adult ICUs reported having a speech therapist conduct consultations/visits. A total of 81.68% (107/131) of ICUs believed that the current implementation of early rehabilitation activities was insufficient. In the analysis of influencing factors, the presence of rehabilitation therapists in the ICU was a significant factor for the implementation of early rehabilitation activities (P<0.05). Conclusion: The majority of ICUs in hospitals in central China have implemented early rehabilitation activities; however, less than half have explicit early rehabilitation exercise protocols or standards/procedures. The presence of professional rehabilitation therapists in the ICU is a key factor in the implementation of early rehabilitation activities in ICUs in hospitals in Central China.

Glucose Transporter-Targeting Chimeras Enabling Tumor-Selective Degradation of Secreted and Membrane Proteins.

Tumor-selective degradation of target proteins has the potential to offer superior therapeutic benefits with maximized therapeutic windows and minimized off-target effects. However, the development of effective lysosome-targeted degradation platforms for achieving selective protein degradation in tumors remains a substantial challenge. Cancer cells depend on certain solute carrier (SLC) transporters to acquire extracellular nutrients to sustain their metabolism and growth. This current study exploits facilitative glucose transporters (GLUTs), a group of SLC transporters widely overexpressed in numerous types of cancer, to drive the endocytosis and lysosomal degradation of target proteins in tumor cells. GLUT-targeting chimeras (GTACs) were generated by conjugating multiple glucose ligands to an antibody specific for the target protein. We demonstrate that the constructed GTACs can induce the internalization and lysosomal degradation of the extracellular and membrane proteins streptavidin, tumor necrosis factor-alpha (TNF-α), and human epidermal growth factor receptor 2 (HER2). Compared with the parent antibody, the GTAC exhibited higher potency in inhibiting the growth of tumor cells in vitro and enhanced tumor-targeting capacity in a tumor-bearing mouse model. Thus, the GTAC platform represents a novel degradation strategy that harnesses an SLC transporter for tumor-selective depletion of secreted and membrane proteins of interest.

Rhombohedral R3 Phase of Mn-Doped Hf0.5Zr0.5O2 Epitaxial Films with Robust Ferroelectricity.

HfO2-based ferroelectric materials are emerging as key components for next-generation nanoscale devices, owing to their exceptional nanoscale properties and compatibility with established silicon-based electronics infrastructure. Despite the considerable attention garnered by the ferroelectric orthorhombic phase, the polar rhombohedral phase has remained relatively unexplored due to the inherent challenges in its stabilization. In this study, the successful synthesis of a distinct ferroelectric rhombohedral phase is reported, i.e., the R3 phase, in Mn-doped Hf0.5Zr0.5O2 (HZM) epitaxial thin films, which stands different from the conventional Pca21 and R3m polar phases. These findings reveal that this R3 phase HZM film exhibits a remnant polarization of up to 47 µC cm- 2 at room temperature, along with an exceptional retention capability projected to exceed a decade and an endurance surpassing 109 cycles. Moreover, it is demonstrated that by modulating the concentration of Mn dopant and the film's thickness, it is possible to selectively control the phase transition between the R3, R3m, and Pca21 polar phases. This research not only sheds new light on the ferroelectricity of the HfO2 system but also paves the way for innovative strategies to manipulate ferroelectric properties for enhanced device performance.

[Prediction of hemorrhage rate after tonsil surgery in children based on random forest model].

Objective:Hemorrhage after tonsil surgery in children is a serious and potentially life-threatening complication. The purpose of this study was to establish a risk warning model for hemorrhage after tonsil surgery in children through a national multi-center retrospective study, providing a basis for hierarchical management after tonsil surgery in children. Methods:Stratified sampling was performed on 8 854 children who underwent tonsillectomy under general anesthesia from 15 research centers in different provinces from January 15, 2022 to May 15, 2023. The sample size of this study was 2 724 cases, including 1 096 males and 1 628 females. Children were divided into bleeding and non-bleeding groups according to whether or not they had bleeding after surgery. The random forest algorithm was used to build a risk warning model. By continuously exploring the optimized model, the accuracy of predicting the postoperative bleeding rate of tonsils in children was improved, and the prediction effectiveness of the model was verified by ten-fold cross-validation. Results:Among 2 724 children, 117 had postoperative bleeding after tonsillectomy, with a bleeding rate of 4.30%. The model constructed by the random forest algorithm for the training set was verified in the test set, and the obtained prediction accuracy was 98.72%, the recall rate was 78.95%, and the area under the ROC curve AUC was 0.96. Conclusion:Although the recall rate of the random forest model needs to be improved, the overall accuracy is quite excellent. It can effectively avoid misjudging positive cases as negative cases. It is a useful tool that can be used to predict the postoperative bleeding rate of tonsils and clinical medical decision-making, laying a good foundation for subsequent optimization and improvement.

PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right ventricular hypertrophy (RVH), associated with increased EndoMT markers and decreased EC markers. Interestingly, chronic hypoxia exacerbated right ventricular systolic pressure and RVH in Etv2 +/- mice. PPARγ transcriptionally activates the ETV2 promoter. Consistently, while mice overexpressing endothelial PPARγ increases the expression of ETV2 and endothelial markers with reduced EndoMT markers, endothelial PPARγ KO mice show decreased ETV2 expression and enhanced EndoMT markers. Inducible overexpression of ETV2 under induced-EndoMT cell model reduces number of cells with mesenchymal morphology and decreases expression of mesenchymal markers with increased EC makers, compared to control. Therefore, our study suggests that PPARγ-ETV2 signaling regulates PH pathogenesis through EndoMT.

Lysosome-targeting chimeras containing an endocytic signaling motif trigger endocytosis and lysosomal degradation of cell-surface proteins.

Lysosome-targeting degradation technologies have emerged as a promising therapeutic strategy for the selective depletion of target extracellular and cell-surface proteins by harnessing a cell-surface effector protein such as lysosome-targeting receptors (LTRs) or transmembrane E3 ligases that direct lysosomal degradation. We recently developed a lysosome-targeting degradation platform termed signal-mediated lysosome-targeting chimeras (SignalTACs) that functions independently of an LTR or E3 ligase; these are engineered fusion proteins comprising a target binder, a cell-penetrating peptide (CPP), and a lysosomal sorting signal motif (P1). Herein, we present the next-generation SignalTACs containing a single endocytic signal that bypasses the need for a CPP. We demonstrate that the fusion with a 10-amino acid endocytic signaling peptide (P3) derived from the cation-independent mannose-6-phosphate receptor (CI-M6PR) induces robust internalization and lysosomal degradation of the target protein. The P3-based SignalTAC exhibited enhanced antitumor efficacy compared to the parent antibody. We envision that the fusion of the endocytic signaling peptide P3 to a target binder may allow the construction of an effective degrader for membrane-associated targets. Furthermore, mechanistic studies identified different drivers for the activities of the P3- and P1-based SignalTACs, which is expected to provide crucial insights toward the harnessing of the intrinsic signaling pathways to direct protein trafficking and degradation.

Associations between parental rearing style and amygdala and hippocampal subfield abnormalities in drug-naive females with anorexia nervosa.

BACKGROUND: Altered volumes in the hippocampus and amygdala have been linked to anorexia nervosa (AN). This study aimed to investigate amygdala and hippocampal subfields volume abnormalities in AN patients, and their associations with parental rearing practices and clinical psychological characteristics. METHODS: This study included twenty-nine drug-naive females with AN from West China Hospital of Sichuan University, China, and fifty-nine age- and gender-matched healthy controls (HCs) recruited through advertisement. All participants underwent T1-weighted imaging. Amygdala and hippocampal subfields volume was calculated using FreeSurfer 7.0. The Core Self-Evaluation Scale (CSES) and Rosenberg Self-Esteem Scale (RSES) were used to assess the psychological characteristics of AN patients. The Egna Minnen av Barndoms Uppfostran (EMBU) was employed to evaluate parental rearing practices. Group differences in brain volumes were analyzed with covariates like age and total intracranial volume (TIV). Partial correlation analysis explored the correlations between brain region volumes and clinical psychological characteristics. RESULTS: AN patients exhibited lower RSES and CSES scores, and more adverse parental rearing style than healthy norms. After adjusting for covariates, AN patients showed decreased gray matter volume (GMV) in the left medial (Me) and cortical (Co) nucleus, as well as in the right hippocampal-amygdala transition area (HATA). GMV in the left Me was correlated with years of education among HCs but not among AN patients. GMV in the right HATA was positively correlated with paternal penalty and severity, as well as maternal overinterference. CONCLUSION: This study supports structure abnormalities in amygdala and hippocampus in AN patients and suggests that parental rearing practices may be associated with hippocampal abnormalities, potentially contributing to the pathophysiology of AN. Addressing appropriate parental rearing styles may offer a positive impact on AN.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment.

BACKGROUND: Prostate cancer (PCa) has high morbidity and mortality rates in elderly men. With a history of thousands of years, traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis, enhance therapeutic effects, and reduce the risk of recurrence and metastasis. Multiple studies have shown that Coridius chinensis (Cc) has anticancer effects. AIM: To elucidate the mechanism of action of Cc against PCa via network pharmacology and molecular docking. METHODS: Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software, the PharmMapper database and the GeneCards database. Then, the STRING database was used to construct the protein-protein interaction network. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and molecular docking analyses were subsequently conducted to identify the key targets, active ingredients and pathways involved. RESULTS: GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway (P value < 1.0 × 10-8). Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc. Seven active compounds (asponguanosines A, asponguanine B, asponguanine C, aspongpyrazine A, N-acetyldopamine, aspongadenine B and aspongpyrazine B) were selected for molecular docking with 9 potential targets, and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa (affinity<-5 kcal/mol, hydrogen bonding), but more studies are needed. CONCLUSION: We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa, supporting the development of Cc as a natural anticancer agent.

Hsa_circ_0043533 modulates apoptosis and viability of granulosa cells via miR-409-3p/BCL2 and EMT signalling in PCOS: Providing novel perspective of metformin.

Polycystic ovary syndrome (PCOS) represents a significant cause of infertility among women of reproductive age. Studies have established a close association between granulosa cells (GCs) and the abnormal follicle formation and ovulation processes characteristic of PCOS. The interactions among hsa_circ_0043533, miR-409-3p, and BCL2 were verified through luciferase activity assays. In PCOS patients, granulosa cells exhibit notably reduced apoptosis but enhanced growth, leading to their accumulation and the development of polycystic ovaries. The involvement of non-coding RNAs in PCOS has been documented, with elevated levels of hsa_circ_0043533 observed in this condition. A comprehensive series of experiments were conducted to explore the role of hsa_circ_0043533 in PCOS and elucidate its underlying mechanisms. Silencing hsa_circ_0043533 was found to promote apoptosis and hinder the migration, proliferation, and viability of KGN cells. Furthermore, we uncovered the regulatory effects of hsa_circ_0043533 on the miR-409-3p/BCL2 axis and key markers of Epithelial-Mesenchymal Transition (EMT). Additionally, it was observed that metformin modulates the hsa_circ_0043533/miR-409-3p/BCL2 axis. Overall, this study provides novel insights into the molecular mechanisms regulating granulosa cell proliferation and apoptosis in PCOS, further elucidating the molecular pathogenesis of this condition.

Heterogeneous Carbonylation of Alcohols on Charge-Density-Distinct Mo-Ni Dual Sites Localized at Edge Sulfur Vacancies.

Alcohols carbonylation is of great importance in industry but remains a challenge to abandon the usage of the halide additives and noble metals. Here we report the realization of direct alcohols heterogeneous carbonylation to carbonyl-containing chemicals, especially in methanol carbonylation, with a remarkable space-time-yield (STY) of 4.74 molacetyl/kgcat./h and a durable stability as long as 100 h on Ni@MoS2 catalyst. Mechanistic analysis reveals that the Mo-Ni dual sites localized at edge sulfur vacancies of Ni@MoS2 exhibit distinct charge density, which strongly activate CH3OH to break its C-O bond and non-dissociatively activate CO. Density functional theory calculations further suggest that the low charge density in Mo-Ni, the Ni site, could significantly lower the barrier for CO migration and nucleophilic attack of methoxy species, and finally leads to the rapid formation of acetyl products. Ni@MoS2 catalyst could also effectively realize the carbonylation of ethanol, n-propanol and n-butanol to their acyl products, which may demonstrate its universal application for alcohols carbonylation.

Licoricesaponin G2 ameliorates bleomycin-induced pulmonary fibrosis via targeting TNF-α signaling pathway and inhibiting the epithelial-mesenchymal transition.

Background: Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored. Methods: Network analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-ß1 (TGF-ß1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2's effects against PF. Results: Network analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway. Conclusion: LG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

Individual and combinatorial application of nanosilica and carbon nanoparticles alleviate nickel stress in barley (Hordeum vulgare L.): Impacts on gene expression, AsA - GSH cycle, cellular fractionation, and proline metabolism.

Nanotechnology is grabbing great attention all over the world because of its stimulating use in numerous fields, and the nanosilica (nSi) and carbon nanoparticles (CNPs) application has been examined in various studies. Conversely, the nSi and CNPs combinatorial use is a new method and researched in limited literature. For this purpose, a pot experiment was conducted to examine various growth and biochemical parameters in barley (Hordeum vulgare L.) under the toxic concentration of nickel (Ni) i.e., 200 mg kg-1 which were primed with combined application of two NPs of nSi at 3 mM and CNPs i.e., 200 µM respectively. The results showed that the Ni toxicity in the soil showed a significantly (P < 0.05) declined in the growth, gas exchange attributes, sugars, AsA-GSH cycle, cellular fractionation, proline metabolism in H. vulgare. However, Ni toxicity significantly (P < 0.05) increased oxidative stress biomarkers, enzymatic and nonenzymatic antioxidants including their gene expression in H. vulgare. Although, the application of nSi and CNPs showed a significant (P < 0.05) increase in the plant growth and biomass, gas exchange characteristics, enzymatic and non-enzymatic compounds and their gene expression and also decreased the oxidative stress, and Ni uptake. In addition, individual or combined application of nSi and CNPs enhanced the cellular fractionation and decreases the proline metabolism and AsA-GSH cycle in H. vulgare. These results open new insights for sustainable agriculture practices and hold immense promise in addressing the pressing challenges of heavy metal contamination in agricultural soils.

Short- and long-term effects of concurrent aerobic and resistance training on circulating irisin levels in overweight or obese individuals: a systematic review and meta-analysis of randomized controlled trials.

Background: Concurrent training (CT) is emerging as a practical and effective approach to enhance body composition, cardiovascular function, and muscle mass, thereby elevating overall individual health. This study aims to systematically investigate the effects of short- and long-term concurrent aerobic and resistance training on circulating irisin levels in overweight or obese individuals. Methodology: The electronic databases, including China National Knowledge Infrastructure, PubMed, Embase, Wan Fang Database, and Web of Science, were systematically searched for articles on "concurrent training" and "irisin" published from their inception to 30 November 2023. The pooled effect size was determined using standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs). The study protocol received registration with the International Prospective Register of Systematic Reviews (CRD42023494163). Results: All nine studies, encompassing a total of 264 participants, were randomized controlled trials and met the eligibility criteria. Results indicate that short- and long-term concurrent training moderately increased circulating irisin levels compared to the control group (SMD = 0.56, 95% CI [0.33-0.80], p = 0.00; I 2 = 36.6%, heterogeneity p = 0.106). Subgroup analyses revealed that both equal to or less than 10 weeks (SMD = 0.78, 95% CI [0.18-1.37], p = 0.01; I 2 = 62.3%, heterogeneity p = 0.03) and more than 10 weeks (SMD = 0.45, 95% CI [0.14-0.76], p = 0.00; I 2 = 0%, heterogeneity p = 0.54) of concurrent training significantly increased circulating irisin levels in overweight or obese individuals. There were no significant between-group differences (I 2 = 0%, p = 0.34). Additionally, concurrent training significantly increased irisin levels in overweight or obese participants (SMD = 1.06, 95% CI [0.34-1.78], p = 0.00; I 2 = 50.6%, heterogeneity p = 0.13) and in type 2 diabetes patients (SMD = 0.70, 95% CI [0.30-1.10], p = 0.00; I 2 = 0%, heterogeneity p = 0.99). However, no significant effect was observed in patients with metabolic syndrome (SMD = 0.21, 95% CI [-0.25-0.68], p = 0.37; I 2 = 38.7%, heterogeneity p = 0.18). There were significant between-group differences (I 2 = 53.9%, p = 0.11). Lastly, concurrent training significantly increased circulating irisin levels in overweight or obese individuals aged 45-60 years (SMD = 0.56, 95% CI [0.25-0.86], p = 0.00; I 2 = 6.5%, heterogeneity p = 0.38), and a significant increase in irisin levels was observed 12 h post-intervention (SMD = 0.70, 95% CI [0.35-1.05], p = 0.00; I 2 = 0%, heterogeneity p = 0.74). However, none of the above categorical variables showed significant between-group differences. Conclusions: Short- and long-term concurrent training can effectively improve circulating irisin levels in overweight or obese individuals. However, the effects of short- and long-term concurrent training should consider the participants' health status, age, and the timing of post-exercise measurements to maximize health benefits.

NUCB2 promotes hepatocellular carcinoma cell growth and metastasis by activating the E2F4/PTGR1 axis.

Background: The important role of nucleobindin 2 (NUCB2) in various cancers has been recently recognized. However, its biological functions and regulatory mechanisms in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression level of NUCB2 in HCC was assessed using public databases, immunohistochemistry, and Western blotting. The effects of NUCB2 on cell proliferation and metastasis were investigated using colony formation, EdU, Transwell assays, and an in vivo mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and in vivo ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays. Results: This study found that NUCB2 expression was significantly higher in HCC tissues than in normal liver tissues, and patients with high expression displayed shorter survival rates. Inhibition of NUCB2 reduced the proliferation and metastatic potential of HCC cells in vitro and in vivo. NUCB2 depletion reduced PTGR1 expression, which reduced cell proliferation and migration. Our findings suggested that NUCB2 suppressed E2F4 degradation by interacting with E2F4. Additionally, increased E2F4 levels facilitated PTGR1 transcription by directly binding to the PTGR1 promoter. Conclusion: This study demonstrated the oncogenic properties of NUCB2 in HCC and suggested that NUCB2 facilitates hepatocellular carcinoma progression by activating the E2F4/PTGR1 axis.

Standardization and application of ARMS TaqMan real-time PCR for screening of folate metabolism genes in Han Chinese.

Folate has antioxidant properties, and low concentration in seminal plasma may be associated with increased DNA damage in sperm. Mutations of the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes, including MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), and MTRR A66G (rs1801394), can lead to decreased activity of the encoded folate metabolic enzymes, thereby affecting male reproduction. The current SNP detection methods commonly used in clinical practice have some shortcomings, such as long time-consuming, complex detection steps, or high cost. The purpose of this study was to establish a simple, time-saving, sensitive, accurate, and easy to clinical popularization method for folate metabolism gene detection. We combined ARMS-PCR with TaqMan fluorescent probe to establish an ARMS TaqMan real-time PCR detection method. According to the variation of rs1801131, rs1801133, and rs1801394, two specific primers (one wild type and one mutant) were designed. Mismatched nucleotides were introduced at the penultimate or third position to improve the specificity of the primer. Specific TaqMan probe was introduced to detect PCR products to improve the sensitivity of the method. The results showed that the sensitivity of ARMS TaqMan real-time PCR in SNP genotyping was 1 ng, and the accuracy was 100%. A total of 249 clinical samples were detected by the established method, and the correlation between three SNPs and semen quality was analyzed. We found that individuals carrying the AG + GG genotype of rs1801394 had a lower risk of abnormal semen quality. In conclusion, we developed a highly sensitive, accurate, rapid, and easy to be popularized method for detecting SNPs of rs1801394, rs1801131, and rs1801133. ARMS TaqMan real-time PCR is a reliable SNP genotyping method in folate metabolism genes.

HPV-ferroptosis related genes as biomarkers to predict the prognosis of cervical cancer.

BACKGROUND: Ferroptosis can be used as a powerful predictor of cancer prognosis. HPV persistent infection is the main cause of cervical cancer, so it is very important to improve the prognosis of patients. Therefore, it is necessary to explore the value of HPV-ferroptosis related genes as prognostic biomarkers of cervical cancer patients. METHODS: In this study, differentially expressed HPV-ferroptosis related genes were obtained from GSE7410, HPV gene set crossed with iron death genes. Five HPV-ferroptosis related genes with prognostic features were finally identified: CYBB, VEGFA, CKB, EFNA1 and HELLS. Multifactorial Cox regression was applied to establish and validate the prognostic model, and drug susceptibility and immune infiltration analyses were also performed. RESULTS: The prognostic model was validated in the training set (TCGA) and validation set (GSE44001). Kaplan-Meier curves reveal significant differences in overall survival (OS) between high-risk and low-risk groups. Receiver operating characteristic (ROC) curve reflects the stability and accuracy of the prognostic model established in this study. In terms of immune function, T cell costimulation was better in the low-risk group than in the high-risk group (P < 0.01). The therapeutic effects of cisplatin, paclitaxel, docetaxel and cyclophosphamide, commonly used chemotherapy drugs for cervical cancer, are better in the high-risk group than in the low-risk group (P < 0.001). CONCLUSION: HPV-ferroptosis related gene prognostic model not only has good stability and accuracy in predicting the prognosis of cervical cancer patients, but also has certain guiding value for clinicians in terms of drug sensitivity and immune microenvironment.

Meticulous nursing care for coronary CT angiography: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to investigate the effects of meticulous nursing care (MNC) for patients with coronary heart disease undergoing coronary CT angiography (CCTA). METHODS: We conducted a comprehensive search of the Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure, and Wangfang databases from inception to January 1, 2024. Randomized clinical trials (RCTs) evaluating the effects of MNC for CCTA were included. Outcomes assessed included self-rating anxiety scale (SAS), self-rating depression scale (SDS), overall satisfaction of nursing care (OSNC), examination time (ET, min), radiation dose received (RDR, mSv), breathing control time (BCT), and heart rate control time (HRCT).The methodological quality of all included RCTs was evaluated using the Cochrane risk-of-bias tool, while statistical analysis was conducted using RevMan 5.4 software. RESULTS: Six eligible trials involving 1064 patients were included. The results of the meta-analysis showed significant differences in SAS (MD = -2.84, 95% CI [-3.31, -2.37], I2 = 0%, P < .001), SDS (MD = -2.55, 95% CI [-3.51, -1.58], I2 = 0%, P < .001), OSNC (OR = 3.13, 95% CI [1.59, 6.17], I2 = 23%, P = .001), BCT (MD = -23.43, 95% CI [-25.07, -21.80], I2 = 45%, P < .001), HRCT (MD = -20.08, 95% CI [-21.70, -18.46], I2 = 29%, P < .001), ET (MD = -2.31, 95% CI [-2.56, -2.06], I2 = 5%, P < .001), and RDR (MD = -2.11, 95% CI [-2.45, -1.77], I2 = 0%, P < .001). CONCLUSION: MNC may benefit for patients with coronary heart disease undergoing CCTA. Future studies are still needed to warrant the current findings.