CISD2, a NEET protein that coordinates 2Fe-2S clusters through its CDGSH domain, is critical for normal development and iron homeostasis. CISD2 plays an important role in Fe-S cluster transfer and ...promotes cancer proliferation. However, its specific role in the development of non-small cell lung cancer (NSCLC) remains unclear. Bioinformatics of pan-cancer analysis from The Cancer Genome Atlas show that CISD2 has an aberrant expression in most types of human cancers. Moreover, CISD2 expression is associated with a higher hazard ratio and exhibits significantly poorer overall survival in lung adenocarcinoma (LUAD), uveal melanoma, head and neck squamous cell carcinoma, brain lower grade glioma, kidney chromophobe, and liver hepatocellular carcinoma. Further investigation revealed that CISD2 is highly expressed in LUAD and LUSC, which is associated with clinical pathological stages. In addition, survival data collected from GSE31210 and GSE13213, two datasets from the NCBI Gene Expression Omnibus, also confirmed that high CISD2 expression is associated with unfavorable survival in patients with LUAD. A cell-based assay indicated that the knockdown of CISD2 inhibited proliferation, invasion, and migration in A549 cells. Additionally, CISD2 knockdown accelerated the accumulation of cellular and mitochondrial reactive oxygen species, destroying the mitochondrial morphology and function. Moreover, CISD2 inhibition activated the iron starvation response, thus, accelerating iron accumulation in A549 cells. Pretreatment with DFO, the iron chelator, blocked mitochondrial dysfunction in CISD2-knockdown cells. Collectively, the present study provides novel insights into the regulatory role of CISD2 in NSCLC and presents a potential target to improve antitumor activity based on oxidative stress.
Understanding gene regulation is important but difficult. Elucidating tissue-specific gene regulation mechanism is even more challenging and requires gene co-expression network assembled from ...protein-protein interaction, transcription factor and gene binding, and post-transcriptional regulation (e.g., miRNA targeting) information. The miRNA binding affinity could therefore be changed by SNP(s) located at the 3' untranslated regions (3'UTR) of the target messenger RNA (mRNA) which miRNA(s) interacts with. Genome-wide association study (GWAS) has reported significant numbers of loci hosting SNPs associated with many traits. The goal of this study is to pinpoint GWAS functional variants located in 3'UTRs and elucidate if the genes harboring these variants along with their targeting miRNAs are associated with genetic traits relevant to certain tissues.
By applying MIGWAS, CoCoNet, ANNOVAR, and DAVID bioinformatics software and utilizing the gene expression database (e.g. GTEx data) to study GWAS summary statistics for 43 traits from 28 GWAS studies, we have identified a list of miRNAs and targeted genes harboring 3'UTR variants, which could contribute to trait-relevant tissue over miRNA-target gene network.
Our result demonstrated that strong association between traits and tissues exists, and in particular, the Primary Biliary Cirrhosis (PBC) trait has the most significant p-value for all 180 tissues among all 43 traits used for this study. We reported SNPs located in 3'UTR regions of genes (SFMBT2, ZC3HAV1, and UGT3A1) targeted by miRNAs for PBC trait and its tissue association network. After employing Gene Ontology (GO) analysis for PBC trait, we have also identified a very important miRNA targeted gene over miRNA-target gene network, PFKL, which encodes the liver subunit of an enzyme.
The non-coding variants identified from GWAS studies are casually assumed to be not critical to translated protein product. However, 3' untranslated regions (3'UTRs) of genes harbor variants can often change the binding affinity of targeting miRNAs playing important roles in protein translation degree. Our study has shown that GWAS variants could play important roles on miRNA-target gene networks by contributing the association between traits and tissues. Our analysis expands our knowledge on trait-relevant tissue network and paves way for future human disease studies.
Background
Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse ...causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR).
Methods
A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the “leave-one-out” approach and tests for potential pleiotropy.
Results
The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP).
Conclusion
The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D’s role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.
This research analyses straw degradation inside straw bale walls in the region and develops the prediction of degradation inside straw bale walls. The results show that the straw inside straw bale ...walls have no serious concerns of degradation in the high hygrothermal environment in the region with only moderate concerns of degradation in the area 2–3 cm deep behind the lime render. The onsite investigations indicate that the degradation isopleth model can only predict straw conditions behind the rendering layer, whereas the isothermal model fits the complete situation inside straw bale walls. This research develops the models for predicting straw degradation levels inside a straw bale building in a warm (humid) continental climate. The impact of this research will help the growth of low carbon energy efficient straw bale construction with confidence pertaining to its long-term durability characteristics both in the region and regions sharing similar climatic features globally.
Opencast iron mine and mine solid waste (OIM-MSW) are closely associated with a wide range of environmental issues, such as destroying soil structure, affecting air quality, and damaging ...biodiversity. Therefore, accurately grasping the distribution of OIM-MSW is of great significance to monitoring and managing environmental conditions. In order to reduce the impact of background features on the identification of OIM-MSW, we constructed an index based on medium spatial resolution satellite data, and proposed a semiautomatic method to determine the threshold value of the index. Experimental results indicated that: 1) The proposed index (OIM-MSWI) can effectively identify the OIM-MSW of which the OA (overall accuracy) and K (kappa coefficient) value are 0.98 and 0.75, respectively. 2) The index owns satisfying performance in identifying OIM-MSW in different months, and its recognition ability in plant growing season is better than that in the nonplant growing season. 3) Both Landsat 8 images and Sentinel 2 images have the potential to identify OIM-MSW via the proposed index, but the recognition accuracy of Landsat 8 images (OA = 0.98, K = 0.75) is slightly better than Sentinel 2 images (OA = 0.96, K = 0.64). (4) OIM-MSWI is effective in different climatic conditions, with OA and K of 0.98, 0.75 and 0.97, 0.63 in the cases of semiarid and humid zones, respectively. In conclusion, OIM-MSWI is a simple and effective index for identifying OIM-MSW, and can provide support for OIM-MSW monitoring and management.
•Two frailty trajectory classes were identified.•Subjective support delays frailty progression through preventing depression.•Objective support delays frailty progression through promoting physical ...activity.•Support utilization delays frailty progression through promoting physical activity.•Social support should be considered in the management of frailty.
To investigate whether and how social support influenced frailty progression through depressive symptoms and physical activity.
Of 1235 community-dwelling older adults enrolled at baseline, 778 (63.0%) undergoing at least one yearly follow-up were included in the final analysis. Data were collected on frailty, social support, depressive symptoms, physical activity and covariates.
Two frailty trajectory classes were identified and labeled as alleviated frailty and deteriorated frailty. Subjective support prevented the deterioration of frailty through decreased depressive symptoms, while objective support and support utilization prevented the deterioration of frailty through increased physical activity.
The pathways through which social support ameliorates frailty vary by support types. Subjective support interventions should be included in the multifactorial interdisciplinary management of frailty to address social and psychological vulnerabilities, along with objective support and support utilization interventions addressing physical inactivity.
•Nicotine deteriorates blood lipid and glucose in high-fat diet (HFD)-fed mice than in normal chow-fed ones.•Nicotine exposure significantly altered the gut microbiota.•Nicotine’s impact on the gut ...microbiota is secondary to diet.
As the primary active component in tobacco, nicotine affects many aspects of human metabolism. Diet and gut microbiota are key factors that profoundly influence human lipid and glucose metabolism. However, the diet-based differential impacts of nicotine on blood lipid and glucose levels as well as on the gut microbiota are still largely unknown. Here we show that 4-week oral administration of nicotine (2 mg/kg) resulted in bodyweight and fat decrease in both normal-chow (NCD)- and high-fat diet (HFD)-fed mice. But nicotine showed little influence on the plasma levels of lipids, glucose and inflammatory cytokines in NCD-fed mice but moderately deteriorated these parameters in HFD-fed ones. 16S sequencing showed that nicotine perturbed bacterial diversity and community composition of gut microbiota more pronouncedly in HFD mice. At genus level, nicotine dramatically increased Ruminococcaceae UCG-009 in HFD condition but not in NCD feeding. Interestingly, co-treatment with antibiotics (ampicillin + norfloxacin) substantially abolished the lipid-enhancing effect of nicotine in HFD-fed mice, suggesting an important role of gut microbes in the lipid-modulatory effect of nicotine. Together, our results indicate that the harmful effects of nicotine on metabolism and systemic inflammation are diet-dependent. Chronic exposure to nicotine may alter the gut microbiota especially in HFD-fed animals.
Obesity is a worldwide epidemic. Promoting browning of white adipose tissue (WAT) contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin (Cpn), a ...natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1 (UCP1) and other thermogenic genes in WAT and 3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase (AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.
Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self‐assembled three‐dimensional cell clusters which are of great ...significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high‐throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient‐derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling.
The recent advancements in artificial intelligence have brought about significant changes in education. In the context of intelligent campus development, target detection technology plays a pivotal ...role in applications such as campus environment monitoring and the facilitation of classroom behavior surveillance. However, traditional object detection methods face challenges in open and dynamic campus scenarios where unexpected objects and behaviors arise. Open-World Object Detection (OWOD) addresses this issue by enabling detectors to gradually learn and recognize unknown objects. Nevertheless, existing OWOD methods introduce two major uncertainties that limit the detection performance: the unknown discovery uncertainty from the manual generation of pseudo-labels for unknown objects and the known discrimination uncertainty from perturbations that unknown training introduces to the known class features. In this paper, we introduce a Parallel OWOD Framework with Uncertainty Mitigation to alleviate the unknown discovery uncertainty and the known discrimination uncertainty within the OWOD task. To address the unknown discovery uncertainty, we propose an objectness-driven discovery module to focus on capturing the generalized objectness shared among various known classes, driving the framework to discover more potential objects that are distinct from the background, including unknown objects. To mitigate the discrimination uncertainty, we decouple the learning processes for known and unknown classes through a parallel structure to reduce the mutual influence at the feature level and design a collaborative open-world classifier to achieve high-performance collaborative detection of both known and unknown classes. Our framework provides educators with a powerful tool for effective campus monitoring and classroom management. Experimental results on standard benchmarks demonstrate the framework’s superior performance compared to state-of-the-art methods, showcasing its transformative potential in intelligent educational environments.
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