Search

Colorectal cancer (COCA) has a poor prognosis, with growing evidence implicating basement membranes (BMs) in cancer progression. Our goal was to investigate the role and predictive significance of BMs in COCA patients. We obtained BMs‐related genes from cutting‐edge research and used TCGA and GTEx databases for mRNA expression and patient information. Cox regression and LASSO regression were used for prognostic gene selection and risk model construction. We compared prognosis using Kaplan–Meier analysis and examined drug sensitivity differences. The CMAP dataset identified potential small molecule drugs. In vitro tests involved suppressing a crucial gene to observe its impact on tumour metastasis. We developed a 12 BMs‐based approach, finding it to be an independent prognostic factor. Functional analysis showed BMs concentrated in cancer‐associated pathways, correlating with immune cell infiltration and immune checkpoint activation. High‐risk individuals exhibited increased drug sensitivity. AGRN levels were linked to decreased progression‐free survival (p < 0.001). AGRN knockdown suppressed tumour growth and metastasis. Our study offers new perspectives on BMs in COCA, concluding that AGRN is a dependable biomarker for patient survival and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis. Patients and Methods: Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues. Results: Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues. Conclusion: We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Germanium diselenide (GeSe2) has recently emerged as a new member of in‐plane anisotropic 2D materials, notable for its wide bandgap of 2.74 eV, excellent air stability, and high performance in polarization‐sensitive photodetection. However, the interlayer interaction in GeSe2 has never been reported, which usually plays an important role in layer‐number‐dependent physical properties. Here, the interlayer coupling in GeSe2 is systematically investigated from theory to experiment. Unexpectedly, all of density functional theory (DFT) calculations about layer‐dependent band structures, cleavage energy, binding energy, translation energy, and interlayer differential charge density demonstrate the much weaker interlayer interaction in GeSe2 when compared with black phosphorus (BP). Furthermore, both thickness‐dependent and temperature‐dependent Raman spectra of GeSe2 flakes, which exhibit no detectable changes of Raman peaks with the increase in thickness and a small first‐order temperature coefficient of −0.0095 cm−1 K−1, respectively, experimentally confirm the weakly coupled layers in GeSe2. The results establish GeSe2 as an unusual member of in‐plane anisotropic 2D materials with weak interlayer interaction. The ultraweak interlayer interaction in anisotropic GeSe2 is reported here. Azimuth‐dependent reflectance difference microscopy (ADRDM) verifies in‐plane anisotropy of GeSe2. DFT calculations including layer‐dependent band structures, cleavage energy, binding energy, translation energy, and interlayer differential charge density confirm weak interlayer interaction in GeSe2, which is further demonstrated by experimental studies, such as thickness‐dependent and temperature‐dependent Raman spectra. [ABSTRACT FROM AUTHOR]

Germanium diselenide (GeSe2) has recently emerged as a new member of in‐plane anisotropic 2D materials, notable for its wide bandgap of 2.74 eV, excellent air stability, and high performance in polarization‐sensitive photodetection. However, the interlayer interaction in GeSe2 has never been reported, which usually plays an important role in layer‐number‐dependent physical properties. Here, the interlayer coupling in GeSe2 is systematically investigated from theory to experiment. Unexpectedly, all of density functional theory (DFT) calculations about layer‐dependent band structures, cleavage energy, binding energy, translation energy, and interlayer differential charge density demonstrate the much weaker interlayer interaction in GeSe2 when compared with black phosphorus (BP). Furthermore, both thickness‐dependent and temperature‐dependent Raman spectra of GeSe2 flakes, which exhibit no detectable changes of Raman peaks with the increase in thickness and a small first‐order temperature coefficient of −0.0095 cm−1 K−1, respectively, experimentally confirm the weakly coupled layers in GeSe2. The results establish GeSe2 as an unusual member of in‐plane anisotropic 2D materials with weak interlayer interaction. The ultraweak interlayer interaction in anisotropic GeSe2 is reported here. Azimuth‐dependent reflectance difference microscopy (ADRDM) verifies in‐plane anisotropy of GeSe2. DFT calculations including layer‐dependent band structures, cleavage energy, binding energy, translation energy, and interlayer differential charge density confirm weak interlayer interaction in GeSe2, which is further demonstrated by experimental studies, such as thickness‐dependent and temperature‐dependent Raman spectra. [ABSTRACT FROM AUTHOR]

Introduction: Eplerenone is approved for the treatment of hypertension as well as symptomatic heart failure with reduced ejection fraction (HFrEF) following an acute myocardial infarction. However, the adverse events (AEs) have not been systematically analyzed. The aim of this study was to identify adverse drug reactions (ADRs) related to eplerenone using the FDA Adverse Event Reporting System (FAERS) database. By identifying previously unreported AEs, the study could potentially contribute to updating the drug's label. Methods: In order to find significant AEs, four algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM), were used to analyze the signal strength of the ADRs connected to eplerenone that were gathered from the FAERS database over the previous 20 years. Results: From 2004Q1 to 2023Q4, a total of 20, 629, 811 reported cases were gathered from the FAERS database for this study. After processing the data and filtering, 1,874 case reports were analyzed. Of these cases, 1,070 AEs were identified, 128 of which were eplerenone-related ADRs. We investigated the occurrence of ADRs induced by eplerenone in 27 organ systems. Our study showed that the AEs listed in the medication's package insert correspond with those listed in the literature, including hyperkalemia and increased creatinine. Additionally, the prescription label for eplerenone does not include all system organ class (SOC) terms, like Vascular disorders, hepatobiliary Disorders, etc. Discussion: The study used multiple algorithms to quantify the signal strength and then identified any previously unrecognized ADRs, further studies are needed to confirm the association of ADRs with eplerenone. The findings of this study may provide important insights into the safety profile of eplerenone, ensure that healthcare providers have up-to-date information about their potential risks and help guide them in the correct use of the drug., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guan, Yang, Li, Feng, Li and Li.)

The IASLC/ATS/ERS classification system was proposed in 2011 to improve the histological subtypes of lung adenocarcinoma, while the prognostic value of the combination of histological predominant subtypes is not consistent. IMP3 is an oncofetal protein which has been proved associated with aggressive tumor behavior in malignancies, but few reports were investigated in lung adenocarcinoma. The aim of this study is to explore the prognostic value of the IASLC/ATS/ERS classification and IMP3 expression in lung adenocarcinoma of Chinese cases. A total of 196 cases were classified according to the IASLC/ATS/ERS classification system and immunohistochemically analyzed by using a monoclonal antibody against IMP3. Univariate survival analysis indicated patients with solid-predominant subtype had shorter disease-free survival (P = 0.003) and overall survival (P = 0.014) compared to those with non-solid predominant subtype. Multivariate survival analysis revealed that solid-predominant subtype could be an independent prognostic factor for disease-free survival (HR: 1.22, 95% CI: 1.05-1.41; P = 0.008). Analysis of IMP3 expression showed that IMP3 was more frequently overexpressed in tumors with advanced pTNM stage (P < 0.001), larger tumor size (P = 0.036), poorer histological differentiation (P < 0.001), lymph node metastasis (P < 0.001), and solid-predominant subtype (P < 0.001). Survival analysis also confirmed that patients in IMP3 high-expression group had both worse disease-free survival (P = 0.039) and overall survival (P = 0.029) than those in IMP3 low-expression group. Our results illustrated that solid-predominant subtype according to the IASLC/ATS/ERS classification is an independent prognostic factor, and IMP3 overexpression is associated with aggressive tumor behavior and poor clinical outcome in lung adenocarcinoma.