Investigation into the role of H2-Ab1 in vascular remodeling in pulmonary arterial hypertension via Bioinformatics.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease of vascular remodeling characterized by persistent pulmonary arterial pressure elevation, which can lead to right heart failure and premature death. Given the complex pathogenesis and poor prognosis of PAH, the identification and investigation of biomarkers become increasingly critical for advancing further understanding of the disease. METHODS: PAH-related datasets, GSE49114, GSE180169 and GSE154959, were downloaded from the publicly available GEO database. By performing WGCNA on the GSE49114 dataset, a total of 906 PAH-related key module genes were screened out. By carrying out differential analysis on the GSE180169 dataset, a total of 576 differentially expressed genes were identified. Additionally, the GSE154959 single-cell sequencing dataset was also subjected to differential analysis, leading to the identification of 34 DEGs within endothelial cells. By taking intersection of the above three groups of DEGs, five PAH-related hub genes were screened out, namely Plvap, Cyp4b1, Foxf1, H2-Ab1, and H2-Eb1, among which H2-Ab1 was selected for subsequent experiments. RESULTS: A SuHx mouse model was prepared using the SU5416/hypoxia method, and the successful construction of the model was evaluated through Hematoxylin-Eosin staining, hemodynamic detection, fulton index, and Western Blot (WB). The results of WB and qRT-PCR demonstrated a significant upregulation of H2-Ab1 expression in SuHx mice. Consistent with the results of bioinformatics analysis, a time-dependent increase was observed in H2-Ab1 expression in hypoxia-treated mouse pulmonary artery endothelial cells (PAECs). To investigate whether H2-Ab1 affects the development and progression of PAH, we knocked down H2-Ab1 expression in PAECs, and found that its knockdown inhibited the viability, adhesion, migration, and angiogenesis, while concurrently promoted the apoptosis of PAECs. CONCLUSION: H2-Ab1 could regulate the proliferation, apoptosis, adhesion, migration, and angiogenesis of PAECs.

Unveiling the link between ACR TI-RADS grading and Bethesda score of thyroid nodules in diabetic patients: A comprehensive analysis.

This study aimed to explores the factors influencing thyroid nodules (TNs) in individuals with type 2 diabetes mellitus (T2DM) and evaluates the consistency between different American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) grades and Bethesda scores. Total of 642 T2DM patients were divided into TN group (245) and control group (397) based on the presence or absence of TNs. TN patients were further categorized into ACR TI-RADS classification (TR) 1 to 4 and TR5 subgroups. Diabetes-related clinical and biochemical parameters were collected, and differences were analyzed using univariate analysis. Logistic regression analysis was utilized to pinpoint independent influencing factors for TN occurrence and different TN classifications. Consequently, age, body mass index (BMI), fasting plasma glucose level (FBGL), low density lipoprotein cholesterol (LDL-C), diabetic progression, and family history of TNs emerged as independent risk factors for TN development in T2DM patients. Additionally, glycosylated hemoglobin (HbA1c), nodule diameter, and family history of TNs were identified as independent risk factors for TR5 TN development in T2DM patients. All TR1 to 2 nodules had a Bethesda score of 2 and all showed benign pathological findings. In 97.10% of cases (67/69), nodules classified as TR3 exhibited a Bethesda score of 2, with all pathological results indicating benign findings, aligning with the Bethesda score. In addition, the concordance between TR4 nodules and Bethesda score was only 78.57% (88/112). In conclusion, TNs and their malignancy in T2DM patients are significantly linked to blood glucose and lipid metabolism indexes. TR3 classification in T2DM patients poses a low malignancy risk, suggesting caution when conducting fine needle aspiration cytology (FNAC) testing.

Dense monocular depth estimation for stereoscopic vision based on pyramid transformer and multi-scale feature fusion.

Stereoscopic display technology plays a significant role in industries, such as film, television and autonomous driving. The accuracy of depth estimation is crucial for achieving high-quality and realistic stereoscopic display effects. In addressing the inherent challenges of applying Transformers to depth estimation, the Stereoscopic Pyramid Transformer-Depth (SPT-Depth) is introduced. This method utilizes stepwise downsampling to acquire both shallow and deep semantic information, which are subsequently fused. The training process is divided into fine and coarse convergence stages, employing distinct training strategies and hyperparameters, resulting in a substantial reduction in both training and validation losses. In the training strategy, a shift and scale-invariant mean square error function is employed to compensate for the lack of translational invariance in the Transformers. Additionally, an edge-smoothing function is applied to reduce noise in the depth map, enhancing the model's robustness. The SPT-Depth achieves a global receptive field while effectively reducing time complexity. In comparison with the baseline method, with the New York University Depth V2 (NYU Depth V2) dataset, there is a 10% reduction in Absolute Relative Error (Abs Rel) and a 36% decrease in Root Mean Square Error (RMSE). When compared with the state-of-the-art methods, there is a 17% reduction in RMSE.

Phosphine Catalysis of the Fluorination of Unactivated Tertiary Alkyl Chlorides under Mild and Convenient Conditions.

Due to the significance of organofluorine compounds in disciplines ranging from medicine to agriculture to materials science, the invention of new methods for the creation of carbon-fluorine bonds is an important objective. Among the underdeveloped dimensions in this area are the fluorination of hindered alkyl halides (particularly chlorides) and the discovery of catalysts for such fluorination processes. Herein, we report a mild method for the fluorination of unactivated tertiary alkyl chlorides (and bromides), catalyzed by inexpensive PPh3. This straightforward process is compatible with a range of hindered electrophiles and a variety of functional groups.

Enantioselective Synthesis of cis-Decalins by Merging the Birch Reduction and Inverse-Electron-Demand Diels-Alder Reaction.

Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis-decalin scaffolds. Enabled by a well-modified chiral bis(oxazoline) ligand/CuII complex, a wide range of polysubstituted cis-decalin scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of the sesquiterpene (+)-occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the 1,3-cyclohexadienes formed in situ are the key intermediates, and efficient kinetic resolution occurs when C2- and/or C3-substituted 1,4-cyclohexadienes are utilized as substrates. DFT calculations elucidated that the Diels-Alder reaction proceeds in a stepwise fashion and revealed the origins of the stereoselectivities.

Evaluation of Pharmacokinetics and Safety With Bioequivalence of Voriconazole Injection of 2 Formulations in Chinese Healthy Volunteers: Bioequivalence Study.

Voriconazole is a first-line medicine for treating invasive aspergillosis. We aimed to evaluate the bioequivalence (BE) of voriconazole injection in Chinese healthy volunteers (HVs). In this single-center, randomized, single-dose, 2-cycle, fasting-dose BE study, HVs (n = 24) were 1:1 divided into 2 groups (test [T]-reference [R] and R-T) and received 6 mg/kg of voriconazole intravenously with a 7-day washout. The plasma was collected for up to 72 hours at the time point after dosing on day 1/day 8. The plasma concentration of voriconazole was measured by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were ascertained on the basis of a noncompartmental model. In the BE study, the geometric mean ratios of the maximum concentration, area under the concentration-time curve from time 0 to the last measurable plasma concentration, and area under the concentration-time curve from time 0 to infinity were 101.1%, 105.6%, and 105.5%, respectively, and the 90%CI fell within 80%-125%. Adverse events were observed in 26.1% of subjects in the T formulation stage and 17.4% in the R formulation stage. Under the BE study, voriconazole values from T and R formulations were bioequivalent.

Bioequivalence of Pomalidomide Capsules in Fasting and Fed States in Healthy Male Volunteers: A Randomized, Open, Single-Dose, Biperiodic, Double-Crossover Study.

This study evaluated the safety, pharmacokinetic parameters, and bioequivalence (BE) of pomalidomide (POM) capsules (specification: 4 mg) acquired from 2 sponsors (test [T] and reference [R]), under fasting and fed conditions. A single-center, randomized, open-label, 2-cycle, self-crossover, single-dose clinical trial was conducted. Subjects were divided into fasting (n = 28) and fed (n = 28) groups and assigned randomized treatment sequences (T-R or R-T). Blood samples for pharmacokinetic evaluation were collected within 48 hours of administration, and safety was assessed throughout. Exposure to POM was similar following single-oral-dose administrations of T or R between the fasting and fed states. T and R exhibited BE, as demonstrated by statistical analysis; the 90%CIs of the geometric mean ratios of maximum plasma concentration, area under the plasma concentration-time curve (AUC)from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the acceptable BE range (80%-125%). Administering POM capsules with high-fat meals resulted in a 2.5-hour delay in time to maximum concentration and an ≈20.4% reduction in maximum plasma concentration. However, AUCs were comparable after dose administrations with and without food. The fast and fed groups revealed that POM capsules were tolerated in healthy Chinese male subjects, and so were orally bioavailable in healthy subjects under fasting and fed states.

Association Between Statin Use and Prognosis of Breast Cancer: A Meta-Analysis of Cohort Studies.

Background: Statin, a lipid-lowering drug, has been suggested to confer anticancer efficacy. However, previous studies evaluating the association between statin use and prognosis in breast cancer showed inconsistent results. A meta-analysis was performed to evaluate the association between statin use and clinical outcome in women with breast cancer. Methods: Cohort studies comparing recurrence or disease-specific mortality in women with breast cancer with and without using of statins were identified by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, incorporating the inter-study heterogeneity, was used to combine the results. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcomes Results: Seventeen cohort studies with 168,700 women with breast cancer were included. Pooled results showed that statin use was significantly associated with a lower risk of breast cancer recurrence (adjusted hazard ratio [HR] = 0.72, p < 0.001) and breast cancer mortality (HR = 0.80, p < 0.001). Subgroup analysis showed that timing of statin use, statin type, study design, sample size, or quality score did not significantly affect the outcomes. However, statin use was associated with more remarkably reduced breast cancer recurrence in studies with mean follow-up duration ≤ 5 years (HR = 0.55, p < 0.001) than that in studies of >5 years (HR = 0.83, p = 0.01). Conclusions: Statin use is associated with reduced recurrence and disease-specific mortality in women with breast cancer. These results should be validated in randomized controlled trials.

Metabolic syndrome and the incidence of lung cancer: a meta-analysis of cohort studies.

BACKGROUND: Metabolic syndrome (MetS) has been related to the pathogenesis of variety categories of cancers. This meta-analysis aimed to determine the association between MetS and the incidence of lung cancer. METHODS: Relevant cohort studies were identified by search of PubMed, Embase, and Cochrane's Library databases. Cochrane's Q test and I2 statistic were used to analyze the heterogeneity. Random-effect model which incorporates the potential heterogeneity was used for the meta-analysis. RESULTS: Five cohort studies with 188,970 participants were included. A total of 1,295 lung cancer cases occurred during follow-up. Meta-analyses showed that neither MetS defined by the revised NCEP-ATP III criteria (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.84 to 1.05, p = 0.25; I2 = 0) nor the IDF criteria (HR: 0.82, 95% CI: 0.61 to 1.11, p = 0.20; I2 = 0) was associated with an affected risk of lung cancer. Subgroup analyses showed consistent results in women and in men, in studies performed in Asian and non-Asian countries, and in prospective and retrospective cohorts (p all > 0.05). Meta-analysis limited to studies with the adjustment of smoking status also showed similar results (HR: 0.91, 95% CI: 0.80 to 1.05, p = 0.21; I2 = 0). No publication bias was detected based on the Egger regression test (p = 0.32). CONCLUSIONS: Current evidence from cohort studies does not support that MetS is an independent risk factor for the incidence of lung cancer.

Hepatitis E virus seroprevalence and molecular study among blood donors in China.

BACKGROUND: The risk of hepatitis E virus (HEV) infection from blood transfusion has aroused increasing concern in many countries. The aim of this study was to analyze the potential risk of HEV infection through blood transfusion in China. STUDY DESIGN AND METHODS: Qualified blood donations and donations with isolated alanine aminotransferase (ALT) elevations from five geographically diverse Chinese regions were tested for anti-HEV immunoglobulin (Ig)M and IgG and HEV antigen. The positive samples for anti-HEV IgM and HEV antigen were tested for HEV RNA. HEV open reading frame (ORF)2 partial sequences were analyzed from HEV RNA-positive samples. RESULTS: The seroprevalence rates of HEV antigen and anti-HEV IgM and IgG among qualified donations were 0.06% (6/10,741), 1.02% (109/10,741), and 27.42% (2945/10,741), respectively. Samples with isolated ALT elevations had higher prevalence of HEV markers, namely, HEV antigen of 0.25% (2/797), anti-HEV IgM of 2.76% (22/797), and anti-HEV IgG of 40.02% (319/797). The HEV antibody prevalence varied significantly by age, sex, and geographic region. All 131 samples that were anti-HEV IgM positive were negative for HEV RNA, whereas four of eight (50%) samples positive for HEV antigen were HEV RNA positive. HEV ORF2 sequences from three of four HEV RNA-positive samples were determined and grouped with Genotype 4. CONCLUSION: Qualified donations after routine blood donor screening still carry potential risk for transmitting HEV. HEV antigen screening could be one measure to reduce the risk of HEV transmission by blood transfusion.

[Application of microfluidic chip analytical systems in ABO genotyping].

Limitations of polyacrylamide gel or agarose gel electrophoretic methods in genotyping research affect the interpreting of detection results. In order to develop a simple and reliable method for appraising results of ABO genotyping detection, the microfluidic chip analysis system was established by using microfluidic chip to replace the gel electrophoresis and combining with multiplex-PCR-RFLP technique. 150 blood samples were tested by this microfluidic chip analysis system with multiplex-PCR-RFLP technique to evaluate its stability and accuracy. The results showed that all the testing results were consistent with serologic ABO genotyping results and 1 blood sample with decrease of B antigen caused by CML was identified. In conclusion, the established microfluidic chip analysis system is stable and reliable technique. Application of this technique enables the ABO genotyping results to be more objective and accurate.

[ABO genotyping of Han population in Beijing].

The aim of this study was to establish a diagnostic method for ABO genotyping and to investigate the distribution of ABO genotype in Beijing Han population so as to understand the distribution characteristics and regularity of ABO genotype. An ABO genotyping method was established by using multiplex-PCR-RFLP and PCR-SSP techniques, and the ABO allele frequency in Beijing Han population was investigated. The results showed that A102, O1 and B allele were more common genes in Beijing Han individuals. And A102 allele was predominant in the phenotype A group in this population. Three O2 alleles were found and no A201 allele was found while gene frequency investigation was performed. No A101A101, A101O2, A102O2, BO2 and O2O2 in this population were discovered. It is concluded that the primary regularity of ABO allele distribution in Beijing Han population is found through this study. It provides basic reference for further study of ABO types.