Comprehensive analysis of consensus molecular subtypes for ovarian cancer from bulk to single-cell perspectives.

Molecular subtypes play a pivotal role in guiding preclinical and clinical risk assessment and treatment strategies in cancer. In this study, we extracted whole-tissue transcriptomic data from 1,987 ovarian cancer patients spanning 26 independent GEO cohorts. A total of four consensus subtypes (C1-C4) were identified, notably, subtype C1 samples exhibited a poor prognosis and higher M2 macrophages infiltration, whereas subtype C2 samples demonstrated the best prognosis and higher CD4 resting T cells infiltration. Additionally, we characterized cancer- and stromal-specific gene expression profiles, and conducted an analysis of ligand-receptor interactions within these compartments. Based on cancer compartment, subtype-specific interactions as well as gene signatures for each molecular subtype were identified. Leveraging single-cell transcriptomic data, we delineated malignant epithelial cells with four molecular subtypes and observed an increase in C1 cell proportions from primary to relapse to metastasis stages, with a corresponding decrease in C2 cell proportions. Furthermore, we investigated subtype-specific interaction with T cells through integrated analysis of bulk and single-cell datasets. Finally, we developed a robust 10-gene risk model based on subtype gene signatures for prognostic evaluation in ovarian cancer, demonstrating its efficacy across independent datasets. In summary, this study systematically explored ovarian cancer molecular subtypes and provided a framework for other cancer types.

PARK2 suppresses the proliferation of high-grade serous ovarian carcinoma via inducing the proteasomal degradation of ZNF703.

High-grade serous ovarian cancer (HGSC) is an aggressive disease with poor prognosis. The oncoprotein ZNF703 is implicated in driving HGSC pathogenesis, but factors regulating its abundance remain unclear. In this study, we aim to investigate the potential connection between ZNF703 dysregulation and ubiquitin-mediated protein degradation in HGSC. Bioinformatics prediction was performed using BioGRID database. HGSC representative cell lines were utilized for in vitro and in vivo studies. Results showed that ZNF703 protein was stabilized upon proteasome inhibition, suggesting a regulation via ubiquitination. The ubiquitin E3 ligase PARK2 was found to interact with ZNF703 in a dose-dependent manner, promoting its polyubiquitination and subsequent proteasomal degradation. Re-expression of PARK2 in HGSC cells led to reduced ZNF703 levels together with decreased Cyclin D1/E1 abundance and G1 cell cycle arrest. ZNF703 overexpression alone increased S phase cells, Cyclin D1/E1 levels, and xenograft tumor growth, while co-expression with PARK2 mitigated these oncogenic effects. Collectively, our findings identify ZNF703 as a bona fide substrate of PARK2, reveal a tumor suppressive function for PARK2 in attenuating ZNF703-mediated G1/S transition and HGSC growth through instigating its degradation. This study elucidates a pivotal PARK2-ZNF703 axis with therapeutic implications for targeted intervention in HGSC.

Ribosomal DNA and Neurological Disorders.

Ribosomal DNA (rDNA) is important in the nucleolus and nuclear organization of human cells. Defective rDNA repeat maintenance has been reported to be closely associated with neurological disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, depression, suicide, etc. However, there has not been a comprehensive review on the role of rDNA in these disorders. In this review, we have summarized the role of rDNA in major neurological disorders to sort out the correlation between rDNA and neurological diseases and provided insights for therapy with rDNA as a target.

Research on the Shock Wave Overpressure Peak Measurement Method Based on Equilateral Ternary Array.

The measurement process of ground shock wave overpressure is influenced by complex field conditions, leading to notable errors in peak measurements. This study introduces a novel pressure measurement model that utilizes the Rankine-Hugoniot relation and an equilateral ternary array. The research delves into examining the influence of three key parameters (array size, shock wave incidence angle, and velocity) on the precision of pressure measurement through detailed simulations. The accuracy is compared with that of a dual-sensor array under the same conditions. Static explosion tests were conducted using bare charges of 0.3 kg and 3 kg TNT to verify the numerical simulation results. The findings indicate that the equilateral ternary array shock wave pressure measurement method demonstrates a strong anti-interference capability. It effectively reduces the peak overpressure error measured directly by the shock wave pressure sensor from 17.73% to 1.25% in the test environment. Furthermore, this method allows for velocity-based measurement of shock wave overpressure peaks in all propagation direction, with a maximum measurement error of 3.59% for shock wave overpressure peaks ≤ 9.08 MPa.

Scenario analysis of energy consumption and related emissions in the transportation industry-a case study of Shaanxi Province.

In the context of pursuing carbon neutrality and balancing the use of fossil fuels with renewable energy, the transportation industry faces the challenge of accurately predicting energy demand, related emissions, and assessing the effectiveness of energy technologies and policies. This is crucial for formulating energy management plans and reducing carbon dioxide (CO2) and atmospheric pollutant emissions. Currently, research on energy consumption and emission forecasting primarily relies on energy consumption quantities and emission factors, which lack precision. This study employs the low emissions analysis platform (LEAP) model, utilizing a "bottom-up" modeling approach combined with scenario analysis to predict and analyze the energy demand and related emissions in the transportation industry. Compared to previous studies, the methodological framework proposed in this research offers higher precision and can explore energy-saving and emission-reduction pathways for different modes of transport, providing a valuable energy forecasting tool for transport policy formulation in other regions. The forecast results indicate that under the business-as-usual (BAU) scenario, by 2049, the energy consumption and related emissions in Shaanxi Province's transportation industry are expected to increase by 1.15 to 1.85 times compared to the baseline year. In the comprehensive (CP) scenario, the industry is projected to reach a carbon peak around 2033. The study also finds that energy consumption and emissions predominantly originate from private passenger vehicles, highway freight, and civil aviation passenger, which have the greatest potential for emission reduction under the transport structure optimized (TSO) scenario. Therefore, policymakers should consider regional development characteristics, combine different transportation modes, and specifically analyze the emission reduction potential of the transportation industry in various regions, formulating corresponding reduction policies accordingly.

Risk Prediction of Diabetes Progression Using Big Data Mining with Multifarious Physical Examination Indicators.

Purpose: The purpose of this study is to explore the independent-influencing factors from normal people to prediabetes and from prediabetes to diabetes and use different prediction models to build diabetes prediction models. Methods: The original data in this retrospective study are collected from the participants who took physical examinations in the Health Management Center of Peking University Shenzhen Hospital. Regression analysis is individually applied between the populations of normal and prediabetes, as well as the populations of prediabetes and diabetes, for feature selection. Afterward,the independent influencing factors mentioned above are used as predictive factors to construct a prediction model. Results: Selecting physical examination indicators for training different ML models through univariate and multivariate logistic regression, the study finds Age, PRO, TP, and ALT are four independent risk factors for normal people to develop prediabetes, and GLB and HDL.C are two independent protective factors, while logistic regression performs best on the testing set (Acc: 0.76, F-measure: 0.74, AUC: 0.78). We also find Age, Gender, BMI, SBP, U.GLU, PRO, ALT, and TG are independent risk factors for prediabetes people to diabetes, and AST is an independent protective factor, while logistic regression performs best on the testing set (Acc: 0.86, F-measure: 0.84, AUC: 0.74). Conclusion: The discussion of the clinical relationships between these indicators and diabetes supports the interpretability of our feature selection. Among four prediction models, the logistic regression model achieved the best performance on the testing set.

CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e+ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e- cells. CD66e+CD34+CD90+CD45RA- cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e-CD34+CD90+CD45RA-cells. CD66e expression also identified almost all repopulating HSCs within the CD34+CD90+CD45RA- population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

The clinical efficacy of Shenxiang Suhe Pill administration in posterior circulation ischemic vertigo: A randomized controlled trial.

BACKGROUND: Shenxiang Suhe Pill (SXSHP) is a traditional Chinese medicine (TCM) widely used to treat coronary heart disease. The present study aims to investigate the effect of SXSHP on posterior circulation ischemic (PCI) vertigo. METHODS: One hundred and twenty patients with PCI vertigo were randomly divided into the control, low-dose, and high-dose groups with 40 patients in each group. The control group was treated with basic Western medicine. The low-dose and high-dose groups were treated with 0.7 g SXSHP once a day in the morning and twice a day in the morning and evening, respectively. The assessments were performed on days 14 and 28. The traditional Chinese medicine symptom score, average blood flow velocity of vertebral artery and basilar artery, blood viscosity, blood lipids, serum C-reactive protein level (CRP), blood routine test, and liver and kidney function were compared before and after treatment among the 3 groups. RESULTS: In the evaluation of the traditional Chinese medicine symptom score, both low-dose and high-dose SXSHP treatments showed higher efficacy than the control group (P = .013). The average blood flow velocity of vertebral artery and basilar artery in the 3 groups showed an upward trend from baseline (P < .05). The blood viscosity and levels of fibrinogen, hematocrit, and CRP in the 3 groups showed a downward trend from baseline level (P < .05). The levels of total cholesterol, triglycerides, low-density lipoprotein, and CRP in the low-dose group and high-dose group were lower than those in the control group on day 28 (P < .05). There were no significant differences in the routine blood test and liver and kidney function between the low-dose and high-dose groups compared with the baseline values (P > .05). CONCLUSION: SXSHP effectively improved PCI vertigo by inhibiting blood viscosity, regulating blood lipid levels, anti-inflammation, and improving cerebrovascular blood flow without affecting liver and kidney functions.

From normal population to prediabetes and diabetes: study of influencing factors and prediction models.

Objective: The purpose of this study is to investigate the independent influencing factors of the transition from normal population to prediabetes, and from prediabetes to diabetes, and to further construct clinical prediction models to provide a basis for the prevention and management of prediabetes and diabetes. Materials and methods: The data for this study were based on clinical information of participants from the Health Management Center of Peking University Shenzhen Hospital. Participants were classified into normal group, prediabetes group, and diabetes group according to their functional status of glucose metabolism. Spearman's correlation coefficients were calculated for the variables, and a matrix diagram was plotted. Further, univariate and multivariate logistic regression analysis were conducted to explore the independent influencing factors. The independent influencing factors were used as predictors to construct the full-variable prediction model (Full.model) and simplified prediction model (Simplified.model). Results: This study included a total of 5310 subjects and 22 variables, among which there were 1593(30%) in the normal group, 3150(59.3%) in the prediabetes group, and 567(10.7%) in the diabetes group. The results of the multivariable logistic regression analysis showed that there were significant differences in 9 variables between the normal group and the prediabetes group, including age(Age), body mass index(BMI), systolic blood pressure(SBP), urinary glucose(U.GLU), urinary protein(PRO), total protein(TP), globulin(GLB), alanine aminotransferase(ALT), and high-density lipoprotein cholesterol(HDL-C). There were significant differences in 7 variables between the prediabetes group and the diabetes group, including Age, BMI, SBP, U.GLU, PRO, triglycerides(TG), and HDL.C. The Full.model and Simplified.model constructed based on the above influencing factors had moderate discriminative power in both the training set and the test set. Conclusion: Age, BMI, SBP, U.GLU, PRO, TP, and ALT are independent risk factors, while GLB and HDL.C are independent protective factors for the development of prediabetes in the normal population. Age, BMI, SBP, U.GLU, PRO, and TG are independent risk factors, while HDL.C is an independent protective factor for the progression from prediabetes to diabetes. The Full.model and Simplified.model developed based on these influencing factors have moderate discriminative power.

Aortic Root Reinforcement Combined with Vascular Grafts Eversion and Built-in Procedure (XJ-Procedure) for Acute Type A Aortic Dissection Surgery.

INTRODUCTION: Current root reinforcement methods for acute type A aortic dissection (ATAAD) risk the tearing of endothelial tissue by sutures. This study proposed a novel technique for aortic root reinforcement and evaluated its effectiveness. METHODS: Patients who diagnosed with ATAAD and had mild to moderate aortic root involvement, combined with aortic arch involvement undergoing Sun's procedure in the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to December 2021, were retrospectively enrolled. They were divided into two groups according to their surgical procedures of aortic root: continuous aortic root suture group (CARS group) and aortic root reinforcement combined with vascular grafts eversion and built-in procedure (XJ-procedure) group. The 30-day mortality rates and incidence of operation-related complications were evaluated. RESULTS: The study cohort comprised 183 patients, including 114 in the XJ-procedure group. The 30-day mortality rates were 7.2% in the CARS group and 6.9% in the XJ-procedure group (P = 1.000). The incidence of residual aortic root dissection in the XJ-procedure group was lower than that in the CARS group before discharge (1.8% vs. 10.1%, P = 0.028), at 3-month (0% vs. 8.7%, P = 0.002) and 6-month (0% vs. 7.2%, P = 0.007) follow-up. In the CARS group, the incidence of anastomotic pseudoaneurysm was 2.9%, 2.9%, and 2.9% compared with none in the XJ-procedure group before discharge, at 3 and 6 months. The XJ-procedure group also showed less chest tube drainage in the first 24-h after the surgery, with lower incidence of hemodialysis and sepsis during hospitalization. No differences were observed in the incidence of bleeding necessitating reoperation and severe aortic regurgitation between the two groups. CONCLUSIONS: The XJ-procedure did not increase 30-day mortality and effectively reduced the incidence of residual aortic root dissection during the 6-month follow-up. Subsequent studies with larger samples and prolonged follow-up are needed to evaluate it. TRIAL REGISTRATION: NCT05751200. The video showed the partial process of the XJ-procedure in managing the aortic root in the ATAAD surgery. The vascular graft was folded outward about 15 mm, and the eversion was intermittently sutured to the full layers aortic wall using 2-0 pad polyester sutures. Then, the eversion of the graft and aortic wall were continuously sutured in one more turn using 3-0 polypropylene sutures. (XJ-procedure, aortic root reinforcement combined with vascular grafts eversion and built-in procedure; ATAAD, acute type A aortic dissection.). (MP4 297097 kb).

Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice.

BACKGROUND: The endogenous adenosine deaminases acting on RNA (ADAR) have been harnessed to facilitate precise adenosine-to-inosine editing on RNAs. However, the practicability of this approach for therapeutic purposes is still ambiguous due to the variable expression of intrinsic ADAR across various tissues and species, as well as the absence of all-encompassing confirmation for delivery methods. RESULTS: In this study, we demonstrate that AAV-mediated delivery of circular ADAR-recruiting RNAs (arRNAs) achieves effective RNA editing in non-human primates at dosages suitable for therapy. Within a time frame of 4 to 13 weeks following infection, the editing efficiency in AAV-infected cells can reach approximately 80%, with no discernible toxicity, even at elevated dosages. In addition, when AAV-delivered circular arRNAs are systematically administered to a humanized mouse model of Hurler syndrome, it rectifies the premature stop codon precisely and restores the functionality of IDUA enzyme encoded by the Hurler causative gene in multiple organs. CONCLUSIONS: These discoveries considerably bolster the prospects of employing AAV-borne circular arRNAs for therapeutic applications and exploratory translational research.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

Elevated Serum Total Bilirubin Might Indicate Poor Coronary Conditions for Unstable Angina Pectoris Patients beyond as a Cardiovascular Protector.

Backgrounds: Serum total bilirubin (STB) is recently more regarded as an antioxidant with vascular protective effects. However, we noticed that elevated STB appeared in unstable angina pectoris (UAP) patients with diffused coronary lesions. We aimed to explore STB's roles in UAP patients, which have not been reported by articles. Methods and Results: 1120 UAP patients were retrospectively screened, and 296 patients were finally enrolled. They were grouped by Canadian Cardiovascular Society (CCS) angina grades. The synergy between PCI with TAXUS stent and cardiac surgery score (SYNTAX score) and corrected thrombolysis in myocardial infarction flow count (CTFC) were adopted to profile coronary features. The results showed that STB, mean platelet volume (MPV), hs-CRP, fasting blood glucose (FBG), red blood cell width (RDW), and CTFC elevated significantly in the CCS high-risk group. STB (B = 0.59, 95% CI: 0.39-0.74, P < 0.01) and MPV (B = 0.86, 95% CI: 0.42-1.31, P < 0.01) could indicate SYNTAX score changes for these patients. STB (≥21.7 µmol/L) could even indicate a coronary slow flow condition (AUC: 0.88, 95% CI: 0.84-0.93, P < 0.01). Moreover, UAP patients with elevated STB had a lower event-free survival rate by the Kaplan-Meier curve. STB ≥21.7 µmol/L could reflect a poor coronary flow status and indicate 1-year poor outcomes for these patients (HR: 2.01, 95% CI: 1.06-3.84, P < 0.01). Conclusion: Elevated STB in UAP patients has a close relationship with changes in SYNTAX score. STB (over 21.7 µmol/L) could even indicate a coronary slow flow condition and poor outcomes for the UAP patients.

E2F8 knockdown suppresses cell proliferation and induces cell cycle arrest via Wnt/ß-Catenin pathway in ovarian cancer.

Ovarian cancer is one of the leading causes of death in female reproductive system cancers. However, the pathogenesis of ovarian cancer remains elusive. Our aim is to investigate the potential targets for ovarian cancer. Two microarray datasets were obtained from the Gene Expression Omnibus public database. Using R package limma, the differentially expressed genes (DEGs) were identified from the datasets. There were 95 overlapping DEGs in two microarray datasets. GO, KEGG pathway analysis, and protein-protein interaction (PPI) network analysis were carried out based on the DEGs. Wnt signaling pathway and cell cycle were enriched in the KEGG pathway analysis. Moreover, the top 10 hub genes with the most nodes were determined by PPI network analysis. E2F8, one of hub genes was positively linked to a bad outcome in ovarian cancer patients. Furthermore, E2F8 knockdown suppressed cell proliferation and induced cell cycle arrest in ovarian cancer. In addition, we found that silencing E2F8 inhibited the Wnt/ß-catenin signaling pathway. In ovarian cancer cells with E2F8 knockdown, overexpressing ß-catenin restored both the suppressed capacity of cell proliferation and cell cycle progression. Therefore, our results revealed that E2F8 had an involvement in the development of ovarian cancer which might act as a therapeutic target.

Flower-like WSe2 used as bio-matrix in ultrasensitive label-free electrochemical immunosensor for human immunoglobulin G determination.

The abnormal concentrations of human immunoglobulin G (hIgG) refers to many kinds of diseases. Analytical methods with the characteristics of rapid response, easy operation and high sensitivity should be designed to accurately determinate the hIgG levels in human serum. In this work, a label-free electrochemical immunosensor based on WSe2/rGO was developed to sensitively detect human immunoglobulin G. First, the flower-like transition metal dichalcogenides (TMDCs) Tungsten Diselenide (WSe2) with large effective specific surface area and porous structure was synthesized by hydrothermal synthesis. As a bio-matrix, the flower-like WSe2 efficiently increased the active sites for loading antibodies. Meanwhile, reduced graphene oxide (rGO) obtained by tannic acid reduction was used to improve the current response of the sensing interface. WSe2 was combined with rGO and the electrochemical active surface area (ECSA) of the sensing interface was enlarged to 2.1 times that of GCE. Finally, the combination of flower-like WSe2 and rGO broadened the detection range and reduced the detection limit of the sensing platform. The immunosensor exhibited a high sensitivity with a wide linear range of 0.01-1000 ng/mL and low detection limit of 4.72 pg/mL. The real sample analysis of hIgG were conducted under optimal conditions, and the spiked recovery rates were between 95.5 and 104.1%. Moreover, satisfactory results were obtained by testing the stability, specificity and reproducibility of the immunosensor. Therefore, it can be concluded that the as-proposed immunosensor has the application potential of clinical analyze of hIgG in human serum.

The relationship between pre-operative right ventricular longitudinal strain and low-cardiac-output syndrome after surgical aortic valve replacement.

Objectives: This study was performed to investigate the relationship between right ventricular free wall longitudinal strain (RVFWSL) and low cardiac output syndrome (LCOS) after surgical aortic valve replacement (SAVR) and to further explore its association with readmission within 2 years in patients who developed LCOS after SAVR. Methods: This single-center retrospective observational study involved consecutive patients who underwent SAVR at our hospital from May 2018 to June 2020. Preoperative echocardiography was obtained within 3 days before SAVR. The longitudinal strain of the right ventricle was analyzed using the right ventricle as the main section, and the RVFWSL and right ventricular four-chamber longitudinal strain (RV4CSL) were obtained. The primary observation was the occurrence of LCOS. The secondary prognostic indicators were mainly the readmission rates within 2 years. Results: In total, 146 patients were finally included in this study. The RVFWSL was significantly lower in the LCOS group than in the No-LCOS group (16.63 ± 2.10) vs. (23.95 ± 6.33), respectively; P < 0.001). The multivariate regression analysis showed that the RVFWSL was associated with LCOS (odds ratio, 1.676; 95% confidence interval, 1.258-2.232; P < 0.001). The receiver operating characteristic curve showed that the cut-off value for RVFWSL to predict LCOS was less than -18.3, with an area under the curve of 0.879, sensitivity of 100%, and specificity of 80.47%. The multivariate regression analysis showed that LCOS was an independent risk factor for readmission within 2 years in patients undergoing SAVR. Conclusion: Patients with RVFWSL (<-18.3%) may be an increased risker for LCOS after SAVR. The occurrence of LCOS after SAVR is Yong-jian Zhang a risk factor for readmission within 2 years. Right ventricular function monitoring may have some predictive value for the postoperative prognosis in patients undergoing SAVR.

YAP-galectin-3 signaling mediates endothelial dysfunction in angiotensin II-induced hypertension in mice.

BACKGROUND: Vascular endothelial dysfunction is regarded as an early event of hypertension. Galectin-3 (Gal-3) is known to participate in various pathological processes. Whilst previous studies showed that inhibition of Gal-3 effectively ameliorates angiotensin II (Ang II)-induced atherosclerosis or hypertension, it remains unclear whether Ang II regulates Gal-3 expression and actions in vascular endothelium. METHODS: Using techniques of molecular biology and myograph, we investigated Ang II-mediated changes in Gal-3 expression and activity in thoracic aortas and mesenteric arteries from wild-type and Gal-3 gene deleted (Gal-3-/-) mice and cultured endothelial cells. RESULTS: The serum level of Gal-3 was significantly higher in hypertensive patients or in mice with chronic Ang II-infusion. Ang II infusion to wild-type mice enhanced Gal-3 expression in the aortic and mesenteric arteries, elevated systolic blood pressure and impaired endothelium-dependent relaxation of the thoracic aortas and mesenteric arteries, changes that were abolished in Gal-3-/- mice. In human umbilical vein endothelial cells, Ang II significantly upregulated Gal-3 expression by promoting nuclear localization of Yes-associated protein (YAP) and its interaction with transcription factor Tead1 with enhanced YAP/Tead1 binding to Gal-3 gene promoter region. Furthermore, Gal-3 deletion augmented the bioavailability of nitric oxide, suppressed oxidative stress, and alleviated inflammation in the thoracic aorta of Ang II-infused mice or endothelial cells exposed to Ang II. CONCLUSIONS: Our results demonstrate for the first time that Ang II upregulates Gal-3 expression via increment in YAP nuclear localization in vascular endothelium, and that Gal-3 mediates endothelial dysfunction contributing to the development of hypertension.

LncRNA AFAP1-AS1 Induces Gefitinib Resistance of Lung Adenocarcinoma Through the miR-653-5p/AGR2 Axis.

Purpose: Gefitinib resistance limits the therapeutic efficacy of gefitinib to lung adenocarcinoma (LUAD). The goal of this research is to learn more about the lncRNA AFAP1-AS1 and how it functions in gefitinib-resistant LUAD cells. Methods: RT-qPCR was performed to test the expression of AFAP1-AS1, miR-653-5p and AGR2 in LUAD tissues with acquired resistance to gefitinib or not as well as in gefitinib-resistant LUAD cells. Cell proliferation, invasion and apoptosis were measured by CCK8 assays, transwell invasion assays and flow cytometry, respectively. Luciferase reporter assay showed that miR-653-5p and AFAP1-AS1 or AGR2 interactions. Results: In gefitinib-resistant LUAD cells and tissues, AFAP1-AS1 was overexpressed. Meanwhile, silencing AFAP1-AS1 reduced proliferation and migration while increasing apoptosis and gefitinib sensitivity. Mechanically, AFAP1-AS1 sequestered the miR-653-5p and blocked the inhibition of miR-653-5p to AGR2 and stepwise upregulated AGR2 overexpression in LUAD gefitinib resistant cells, resulting gefitinib resistance in LUAD. Conclusion: AFAP1-AS1 promotes gefitinib-resistance LUAD cells through a previously unrecognized miR-653-5p/AGR2 axis, suggesting targeting AFAP1-AS1/miR-653-5p/AGR2 axis might be a promising way for LUAD intervention.

Behavior and physiology in female Cricetulus barabensis are associated with the expression of circadian genes.

The circadian clock regulates the behavior, physiology, and metabolism of mammals, and these characteristics, such as sleep-wake cycles, exercise capacity, and hormone levels, exhibit circadian rhythms. Light signaling is the main stimulator of the mammalian circadian system. The photoperiod regulates the reproductive cycle of seasonal breeding animals, and the circadian clock plays a pivotal role in this process. However, the role of the clock in coordinating animal behavior and physiology in response to photoperiodic changes needs further investigation. The present study investigated the changes and correlation of behavioral activities, physiological indicators, and gene expression in female striped hamsters (Cricetulus barabensis) within 24 h under a 12L:12D photoperiod. We found that the daily rhythms of sleep-wake and open field were significant in hamsters. The expression of clock genes, melatonin receptor genes, and genes involved in general metabolism oscillated significantly in central and peripheral tissues (brain, hypothalamus, liver, ovary, and thymus) and was significantly associated with behavior and physiology. Our results revealed that the neuroendocrine system regulated the rhythmicity of behavior and physiology, and central and peripheral clock genes (Bmal1, Clock, Per1, Per2, Cry1, and Cry2), melatonin receptor genes (MT1, MT2, and GPR50), and metabolizing genes (SIRT1, FGF21, and PPARα) played important roles. Our results suggest that central and peripheral circadian clocks, melatonin receptors, and genes involved in general metabolism may play key roles in maintaining circadian behavior and metabolic homeostasis in striped hamsters. Our results may have important implication for rodent pest control.