Constructing and Evaluating a Mitophagy-Related Gene Prognostic Model: Implications for Immune Landscape and Tumor Biology in Lung Adenocarcinoma.

Mitophagy, a conserved cellular mechanism, is crucial for cellular homeostasis through the selective clearance of impaired mitochondria. Its emerging role in cancer development has sparked interest, particularly in lung adenocarcinoma (LUAD). Our study aimed to construct a risk model based on mitophagy-related genes (MRGs) to predict survival outcomes, immune response, and chemotherapy sensitivity in LUAD patients. We mined the GeneCards database to identify MRGs and applied LASSO/Cox regression to formulate a prognostic model. Validation was performed using two independent Gene Expression Omnibus (GEO) cohorts. Patients were divided into high- and low-risk categories according to the median risk score. The high-risk group demonstrated significantly reduced survival. Multivariate Cox analysis confirmed the risk score as an independent predictor of prognosis, and a corresponding nomogram was developed to facilitate clinical assessments. Intriguingly, the risk score correlated with immune infiltration levels, oncogenic expression profiles, and sensitivity to anticancer agents. Enrichment analyses linked the risk score with key oncological pathways and biological processes. Within the model, MTERF3 emerged as a critical regulator of lung cancer progression. Functional studies indicated that the MTERF3 knockdown suppressed the lung cancer cell proliferation and migration, enhanced mitophagy, and increased the mitochondrial superoxide production. Our novel prognostic model, grounded in MRGs, promises to refine therapeutic strategies and prognostication in lung cancer management.

Outcomes of intermediate or high-risk CMML patients treated with hypomethylating agents combined with venetoclax: A single center experience.

Chronic myelomonocytic leukemia (CMML) treatment remains a pressing clinical challenge. We conducted a retrospective analysis on 52 CMML cases, exploring the effectiveness of combining venetoclax (Vene) with hypomethylating agents (HMAs). The study's findings show promise: the HMAs plus Vene group (n = 13, 53.8%) demonstrated superior overall response rates compared to the HMA monotherapy (mono) group (n = 19, 31.6%) and HMA plus arsenic trioxide group (n = 9, 22.2%) by the second cycle, and notably higher response rates (53.8% vs. 15.7%, p = 0.04) compared to the HMA mono group after four cycles. Over a median follow-up of 14.7 months, the HMAs plus Vene group exhibited significantly lower cumulative mortality (23.1%) compared to the other two groups (p = 0.003 and p = 0.008, respectively). Furthermore, this group displayed extended overall survival compared to the others. The study also delved into the molecular mechanisms, revealing significant BCL2 mRNA overexpression in patients with CMML. These findings suggest the potential for HMAs combined with Vene therapy in CMML but emphasize the necessity for further prospective studies to determine its precise role in managing CMML.

Diabetes Mellitus and Keratoconus: A Systematic Review and Meta-Analysis.

PURPOSE: Although previous studies have assessed the relationship between diabetes and keratoconus, the findings were controversial and warranted further clarifications. The objective of this study was to investigate the association between diabetes and keratoconus by conducting a systematic review and meta-analysis. METHODS: A comprehensive literature search was performed to identify eligible studies reporting the association of diabetes with keratoconus from their inception to April 2021 through PubMed, Embase, and Web of Science. The quality of included studies was assessed using the Newcastle-Ottawa scale. Combined odds ratios (ORs) and 95% confidence intervals were calculated using a random-effects model. RESULTS: In all, 8 case-control studies and 3 cohort studies reporting the association between diabetes and keratoconus were included in the meta-analysis. Diabetes was not associated with keratoconus in the overall analysis (combined OR = 0.85, 95% confidence interval: 0.66-1.10). The associations were found to be nonsignificant in subgroup analysis when stratified by study quality, design, source, types, and population. No publication bias was detected from either the Egger test (P = 0.46) or Begg test (P = 0.16). Sensitivity analysis revealed that differences between groups were not statistically significant. CONCLUSIONS: This meta-analysis indicates that current literature does not support a significant association between diabetes and keratoconus. Further studies with more definite control for confounders and well-designed cohorts or interventions are warranted.

High-Entropy Oxide Derived from Metal-Organic Framework as a Bifunctional Electrocatalyst for Efficient Urea Oxidation and Oxygen Evolution Reactions.

High-entropy oxides (HEOs) offer unique features through a combination of incompatible metal cations to a single crystalline lattice. Owing to their special characteristics such as abundant cation compositions, high entropy stabilization, chemical and thermal stability, and lattice distortion effect, they have drawn ever-increasing attention for various applications. However, very few studies have been reported for catalytic application, and developing HEOs with large surface areas for efficient catalytic application is still in infancy. Herein, we design nanostructured HEO of (FeNiCoCrCu)3O4 using metal-organic frameworks (MOFs) as sacrificial templates to achieve a large surface area, high density of exposed active sites, and more oxygen vacancies. Single-crystalline phase HEOs with surface area as large as 206 m2 g-1 are produced and further applied as bifunctional electrocatalysts for the urea oxidation reaction (UOR) and oxygen evolution reaction (OER). Benefiting from enhanced oxygen vacancies and a large surface area with abundant exposed active sites, the optimized HEO exhibited excellent electrocatalytic activity toward UOR with a very low potential of 1.35 V at the current density of 10 mA cm-2 and showed long-term stability for 36 h operation, making a significant catalytic performance over previously reported HEOs. Moreover, the HEO demonstrated an efficient catalytic performance toward OER with a low overpotential of 270 mV at 10 mA cm-2 and low Tafel slope of 49 mV dec-1. The excellent catalytic activity is ascribed to the starting MOF precursor and favorable high-entropy effect.

Silver-enhanced fluorescence of bimetallic Au/Ag nanoclusters as ultrasensitive sensing probe for the detection of folic acid.

Folic acid (FA) is the natural form of water-soluble vitamins widely found in most plants and animal products and its deficiency leads to several human body abnormalities. The advancements of metal nanoclusters are highly increasing due to their molecule-like optical properties and attractive applications. Because of increasingly demand of noble metal nanoclusters as sensing templates, different synthesis methods have been developed for facile synthesis of noble metal nanoclusters. Herein, red-emitting fluorescent bovine serum albumin (BSA)-capped Au-Ag bimetallic NCs are facilely synthesized through green one-pot synthetic approach. The effect of silver on the fluorescence properties of Au NCs was investigated and it was found that introduction of silver can enhance the fluorescence intensity. The fluorescence intensity of the as-prepared Au-Ag nanoclusters gets quenched in the presence of folic acid in an aqueous medium and it was used as ultrasensitive sensing probe for FA detection. The developed Au-Ag NCs-based sensing probe shows linear response in the wide range of 0-100 µM and the detection limit is as low as 0.47 nM. Its applicability has also been confirmed successfully in real human serum, urine and FA tablet samples. Due to the high stability, sensitivity and selectivity, the developed bimetallic cluster sensing system is highly promising to be applied in the pharmaceutical and clinical laboratories.

Association of semenogelin (SEMG) gene variants in idiopathic male infertility in Chinese-Han population.

Infertility is known to occur frequently worldwide, and the incidence is continuing to rise in China. It is known that semenogelin (SEMG) protein secreted by human seminal vesicles plays an important role in male reproductive system function. However, an association between alterations in SEMG gene functions and idiopathic male infertility occurrence in Chinese-Han population has not been examined. The aim of this study was thus to investigate the inherent relationship between SEMG gene alterations and idiopathic male infertility using a method of variant genotyping selection and semen quality analysis. A population of 484 males with clinically diagnosed idiopathic male infertility and 246 fertile controls were selected after signing consent forms. Results demonstrated a significantly increased frequency of idiopathic infertility with abnormal semen parameters such as semen volume, sperm concentration, sperm number per ejaculate, and sperm motility in variants carrying the rs2301366 TA genotype. Combined association analysis from target single-nucleotide polymorphisms (SNPs) was selected from the genotype database of unrelated Chinese-Han in Beijing individuals from the Hap Map. SNP array analysis in blood samples in each group was carried out by TaqMan Universal PCR Master Mix and TaqMan SNP Genotyping Assays. In addition, the interaction between SEMG SNPs and binding protein epididymal protease inhibitor (EPPIN) SNPs was determined. Our findings demonstrated that the presence of SEMG SNPs and EPPIN SNPs increased the frequency of idiopathic male infertility in Chinese-Han population. It is proposed that measurement of SEMG SNPs and EPPIN SNPs in carriers may thus be utilized to identify idiopathic male infertility.

Utility of GDF-15 as a diagnostic biomarker in gastric cancer: an investigation combining GEO, TCGA and meta-analysis.

It was recently suggested that growth differentiation factor-15 (GDF-15) is associated with gastric cancer (GC) carcinogenesis. However, the diagnostic potential of GDF-15 for GC remains unclear. To address this issue, we obtained RNA sequencing and microarray data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and searched PubMed, Google Scholar and Web of Science for relevant literature. We then used STATA to perform a meta-analysis. In total, reports of 253 GC patients and 112 healthy controls who contributed peripheral blood samples were taken from the four literature sources, while information on 754 GC tumor and 263 gastric normal tissues was drawn from TCGA and seven GEO datasets. The expression level of GDF-15 mRNA was significantly higher in tumor tissues than in normal tissues, with a standard mean difference (SMD) of 0.79% and a 95% confidence interval (95% CI) of 0.63-0.95. Consistently, the GDF-15 protein in blood was significantly increased in GC patients as compared to controls (SMD  = 3.74, 95% CI = 1.81-5.68). In addition, based on information from TCGA and GEO datasets, the expression level of GDF-15 mRNA may be of use for the diagnosis of GC, with a combined sensitivity, specificity and odds ratio of 0.69 (95% CI = 0.58-0.79), 0.90 (95% CI = 0.84-0.93) and 6.32 (95% CI = 4.22-9.49), respectively. The summary receiver operating characteristic curve demonstrated that the area under the curve was 0.90 (95% CI = 0.87-0.93). The results suggest higher levels of GDF-15 may be associated with GC tumorigenesis and may have the potential to be a diagnostic biomarker of GC.

Sensitive colorimetric assay for uric acid and glucose detection based on multilayer-modified paper with smartphone as signal readout.

In this work, a multilayer-modified paper-based colorimetric sensing platform with improved color uniformity and intensity was developed for the sensitive and selective determination of uric acid and glucose with smartphone as signal readout. In detail, chitosan, different kinds of chromogenic reagents, and horseradish peroxidase (HRP) combined with a specific oxidase, e.g., uricase or glucose oxidase (GOD), were immoblized onto the paper substrate to form a multilayer-modified test paper. Hydrogen peroxide produced by the oxidases (uricase or GOD) reacts with the substrates (uric acid or glucose), and could oxidize the co-immoblized chromogenic reagents to form colored products with HRP as catalyst. A simple strategy by placing the test paper on top of a light-emitting diode lamp was adopted to efficiently prevent influence from the external light. The color images were recorded by the smartphone camera, and then the gray values of the color images were calculated for quantitative analysis. The developed method provided a wide linear response from 0.01 to 1.0 mM for uric acid detection and from 0.02 to 4.0 mM for glucose detection, with a limit of detection (LOD) as low as 0.003 and 0.014 mM, respectively, which was much lower than for previously reported paper-based colorimetric assays. The proposed assays were successfully applied to uric acid and glucose detection in real serum samples. Furthermore, the enhanced analytical performance of the proposed method allowed the non-invasive detection of glucose levels in tear samples, which holds great potential for point-of-care analysis. Graphical abstract ᅟ.