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The geological disasters caused by the ground deformation of the goaf have brought huge security risks to the ecological environment and society. Therefore, it is imminent to realize the effective monitoring and stability analysis of the ground deformation of the goaf. In this paper, taking the goaf of the gypsum mine in Diaodao District, Jingmen City as an example, through the investigation of the overall structure and distribution characteristics of the gypsum goaf, combined with the mechanical parameters of the rock mass selected from the site, the InSAR and GNSS technology are used to analyze the ground of the goaf of the gypsum mine. Deformation monitoring is carried out to give full play to the advantages of InSAR monitoring with high vertical accuracy and GNSS monitoring with high horizontal accuracy. Analyzed the thickness conditions of the mined-out area of pillar, roof and overlying rock, established the numerical model of the goaf, and used FLAC (3D) to carry out numerical simulation on this basis to evaluate the stability of the goaf. The research shows that two subsidence areas and three deformation areas were deciphered by DInSAR and time series InSAR, respectively, and the deep buried areas in the goaf were monitored by GNSS. The surface deformation is dominated by horizontal displacement, and the direction of horizontal displacement is the whole points to the goaf. Finally, based on the conclusion that the gob is in different degrees of deformation, the stability of the gob is analyzed, and the area of surface subsidence is obtained by FLAC (3D) simulation.

Acute myocardial infarction (MI) is one of the leading causes of death in humans. Our previous studies showed that gastrin alleviated acute myocardial ischaemia–reperfusion injury. We hypothesize that gastrin might protect against heart injury after MI by promoting angiogenesis. An MI model was simulated by ligating the anterior descending coronary artery in adult male C57BL/6J mice. Gastrin was administered twice daily by intraperitoneal injection for 2 weeks after MI. We found that gastrin reduced mortality, improved myocardial function with reduced infarct size and promoted angiogenesis. Gastrin increased HIF-1α and VEGF expression. Downregulation of HIF-1α expression by siRNA reduced the proliferation, migration and tube formation of human umbilical vein endothelial cells. These results indicate that gastrin restores cardiac function after MI by promoting angiogenesis via the HIF-1α/VEGF pathway.

Objectives Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC. Methods Paired liver metastatic tissue samples and peripheral blood from 32 liver oligometastatic NSCLC patients were concurrently collected for comprehensive genomic analysis using next-generation sequencing. Results A total of 206 mutated genes in 32 patients were detected, with a median of 4 mutations per sample. The most frequent alterations (> 10%) in liver oligometastasis were TP53 (72%), EGFR (50%), RB1 (19%) and SMARCA4 (12%). The co-occurrence rate of TP53 and RB1 in our cohort was significantly higher than that in the TCGA-LUAD cohort. Age, APOBEC, homologous recombination deficiency (HRD) and deficient mismatch repair (dMMR) established the mutational signature of liver oligometastatic NSCLC. The median tumor mutation burden (TMB) was 4.8 mutations/Mb. A total of 78.12% patients harbored at least one potentially actionable molecular alteration that may guide further targeted therapy according to the OncoKB evidence. Conclusions Our study comprehensively delineated the genomic characteristics of liver oligometastatic NSCLC - such findings were helpful to better understand the distinct clinic-biological features of oligometastasis and optimize personalized treatment of this population.

Background Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-tyrosine kinase inhibitors (TKIs) as first-line therapy and defer intracranial radiotherapy (RT). However, the effectiveness of upfront intracranial RT remains unclear. Methods This was a retrospective study including 217 patients from two institutions between January 2018 and December 2022. Clinical data of NSCLC patients with BMs who received EGFR-TKIs were collected. The patients were assigned to one of the three groups according to the therapeutic modality used: the upfront TKI + stereotactic radiosurgery (SRS) / fractionated stereotactic radiotherapy (fSRS) group (upfront TKI + SRS/fSRS ), the upfront TKI + whole-brain radiotherapy (WBRT) group (upfront TKI + WBRT) and the upfront TKI group. Results As of March 8, 2023, the median follow-up duration was 37.3 months (95% CI, 32.5–42.1). The median overall survival (OS) for the upfront TKI + SRS/fSRS, upfront TKI + WBRT, and upfront TKI groups were 37.8, 20.7, and 24.1 months, respectively ( p  = 0.015). In subgroup analysis, the upfront TKI + SRS/fSRS group demonstrated longer OS compared to the upfront TKI + WBRT and upfront TKI groups in patients treated with first or second-generation EGFR-TKIs ( p  = 0.021) and patients with L858R mutation ( p  = 0.017), whereas no survival benefit was observed in three-generation EGFR-TKIs or 19del subgroup. In the multivariable analysis, metachronous BMs, EGFR L858R mutation and nonclassic EGFR mutation were identified as independent risk factors for OS, while a DS-GPA score of 2.0–4.0 was the only independent protective factor. Conclusions This study demonstrated that upfront addition of SRS/fSRS to EGFR-TKIs was associated with longer OS compared to upfront WBRT or upfront TKI alone in EGFR-mutant NSCLC patients with BMs. This improvement was more significant in patients with L858R mutation and those treated with first or second-generation EGFR-TKIs. Further research with a larger sample size is warranted.

Genome-wide association studies (GWAS) have identified many genetic variants in genes related to lipid metabolism. However, how these variations affect lipid levels remains elusive. Long non-coding RNAs (lncRNAs) have been implicated in a variety of biological processes. We hypothesize lncRNAs are likely to be located within disease or trait-associated DNA regions to regulate lipid metabolism. The aim of this study was to investigate whether and how lncRNAs in lipid- associated DNA regions regulate cholesterol homeostasis in hepatocytes. In this study, we identified a novel long non-coding RNA in Lipid Associated Single nucleotide polymorphism gEne Region (LASER) by bioinformatic analysis. We report that LASER is highly expressed in both hepatocytes and peripheral mononuclear cells (PBMCs). Clinical studies showed that LASER expression is positively related with that of cholesterol containing apolipoprotein levels. In particular, we found that LASER is positively correlated with plasma PCSK9 levels in statin free patients. siRNAs mediated knock down of LASER dramatically reduces intracellular cholesterol levels and affects the expression of genes involved in cholesterol metabolism. Transcriptome analyses show that knockdown of LASER affects the expression of genes involved in metabolism pathways. We found that HNF-1α and PCSK9 were reduced after LASER knock-down. Interestingly, the reduction of PCSK9 can be blocked by the treatment of berberine, a natural cholesterol-lowering compound which functions as a HNF-1α antagonist. Mechanistically, we found that LASER binds to LSD1 (lysine-specific demethylase 1), a member of CoREST/REST complex, in nucleus. LASER knock-down enhance LSD1 targeting to genomic loci, resulting in decreased histone H3 lysine 4 mono-methylation at the promoter regions of HNF-1α gene. Conversely, LSD1 knock-down abolished the effect of LASER on HNF-1α and PCSK9 expressions. Finally, we found that statin treatment increased LASER expression, accompanied with increased PCSK9 expression, suggesting a feedback regulation of cholesterol on LASER expression. This observation may partly explain the statin escape during anti-cholesterol treatment. These findings identified a novel lncRNA in cholesterol homeostasis. Therapeutic targeting LASER might be an effective approach to augment the effect of statins on cholesterol levels in clinics.

Objectives Emerging evidence have demonstrated that oligometastatic non-small cell lung cancer (NSCLC) can achieve clinical benefit from local consolidative therapy. Bone oligometastasis is common in advanced lung cancer, but little is known about its molecular features. The purpose of our study aimed to investigate the genomic landscape bone oligometastatic NSCLC. Methods We collected paired blood and tissue samples from 31 bone oligometastatic NSCLC patients to make a comprehensive analysis of mutations by performing next-generation sequencing. Results A total of 186 genomic mutations were detected from 105 distinct cancer-relevant genes, with a median number of 6 alterations per tumor. The most frequently mutated genes were EGFR (58%) and TP53 (55%), followed by KRAS (16%), CDKN2A (13%) and MET (13%). The signatures related to smoking, aging, homologous recombination deficiency and APOBEC were identified as the most important mutational processes in bone oligometastasis. The median tumor mutation burden was 4.4 mutations/Mb. Altogether, genetic alterations of bone oligometastasis are highly targetable that 74.19% of patients had at least one actionable alteration that was recommended for targeted therapy based on the OncoKB evidence. Of these patients, 16.13% had two actionable alterations that could potentially benefit from a different combination of targeted drugs to achieve better outcomes. Conclusion Our research comprehensively elucidates the genomic features of bone oligometastatic NSCLC patients, which may optimize individualized cancer treatment in the era of precision medicine.

Amidst the increasing urgency of global climate change, achieving carbon neutrality has become a critical objective for rapidly developing economies like China. This study presents an innovative carbon emission forecasting framework for the Yangtze River Middle Reaches—comprising Hubei, Hunan, and Jiangxi provinces—by integrating an extended STIRPAT model with partial least squares (PLS) regression. Distinct from existing provincial-level research, our approach incorporates a broader set of socio-economic and environmental drivers, utilizes variable importance analysis, and employs scenario-based projections to systematically compare emission trajectories and driving mechanisms across multiple provinces. By simulating carbon emission pathways from 2001 to 2021 and projecting future trends to 2080 under three differentiated scenarios, the study reveals pronounced regional heterogeneity in emission peaks, neutrality timelines, and driver effects. Results indicate that while all three provinces are likely to achieve peak emissions around 2030, the path to carbon neutrality by 2060 remains highly challenging due to persistent technological and structural constraints, particularly in provinces with slower industrial transformation. The findings underscore the necessity of region-specific, adaptive mitigation strategies—balancing economic growth, industrial upgrading, and energy structure optimization—to ensure practical progress toward China’s dual-carbon goals. This work not only advances carbon forecasting methodology by quantifying the interactive effects of multiple drivers at a subnational scale, but also offers empirical evidence to inform targeted, differentiated policy interventions.

ABSTRACT Nuclear factor of activated T‐cells, cytoplasmic 4 (NFATc4), a transcription factor of the NFAT family, has been reported to participate in the tumorigenesis and progression of several cancers. However, the function and regulation of NFATc4 in lung adenocarcinoma (LUAD) remain poorly understood. Here, we report for the first time that NFATc4 is significantly overexpressed in LUAD tissues, and high NFATc4 expression correlates with lymphatic metastasis, advanced tumor stage, and poor prognosis in patients. Subsequent functional studies revealed that NFATc4 depletion inhibits LUAD cell viability, proliferation, and tumor growth by inducing cell cycle arrest in the G2/M phase and apoptosis. A mechanistic study shows that NFATc4 knockdown leads to significant enrichment of cellular process‐related pathways and differentially expressed genes, especially downregulated genes Cyclin B1 (CCNB1) and cyclin‐dependent kinase 1 (CDK1). NFATc4 directly binds to the CCNB1 promoter to regulate the CCNB1/CDK1 pathway, resulting in cell cycle arrest and inhibition of cell proliferation. This study identifies NFATc4/CCNB1/CDK1 as a novel regulatory pathway involved in LUAD development and provides a potential prognostic biomarker and molecular therapeutic target for LUAD. NFATc4 is upregulated in LUAD, and its high expression correlates with the malignant progression of patients. NFATc4 enhances LUAD cell viability and proliferation by regulating the G2/M phase transition and apoptosis. Functionally, NFATc4 directly binds to the CCNB1 promoter, modulating the CCNB1/CDK1 pathway, which results in cell cycle arrest and inhibition of cell proliferation.

Circular RNAs (circRNAs) have been recently recognized as playing a role in the pathogenesis of vascular remodeling-related diseases by modulating the functions of miRNAs. However, the interplay between circRNAs and proteins during vascular remodeling remains poorly understood. Here, we investigated a previously identified circRNA, circEsyt2, whose expression is known to be upregulated during vascular remodeling. Loss- and gain-of‑function mutation analyses in vascular smooth muscle cells (VSMCs) revealed that circEsyt2 enhanced cell proliferation and migration and inhibited apoptosis and differentiation. Furthermore, the silencing of circEsyt2 in vivo reduced neointima formation, while circEsyt2 overexpression enhanced neointimal hyperplasia in the injured carotid artery, confirming its role in vascular remodeling. Using unbiased protein-RNA screening and molecular validation, circEsyt2 was found to directly interact with polyC-binding protein 1 (PCBP1), an RNA splicing factor, and regulate PCBP1 intracellular localization. Additionally, circEsyt2 silencing substantially enhanced p53β splicing via the PCBP1-U2AF65 interaction, leading to the altered expression of p53 target genes (cyclin D1, p21, PUMA, and NOXA) and the decreased proliferation of VSMCs. Thus, we identified a potentially novel circRNA that regulated vascular remodeling, via altered RNA splicing, in atherosclerotic mouse models.

Goaf restoration is an important part of urban space management. With mining of coal resources, appearance of goaf and subsidence areas causes serious geological disasters and environmental and ecological problems, which significantly affect urban safety, development, and construction. Therefore, repair of goafs is crucial. In this study, the goaf of Jingmen Garden Expo Park was taken as an example. Through acquisition of engineering geological condition parameters and data on the goaf combined with the mechanical parameters selected for the site, the deformation mechanism of the overlying strata of the goaf was analyzed, and a numerical model of the goaf was established. On this basis, FLAC(3D) was used for numerical simulation to evaluate the stability of the goaf; the suitability of the site was evaluated and divided, and the ecological restoration model of the goaf in Jingmen Garden Expo Park was studied. The results showed that different degrees of ecological restoration and construction of various facilities and buildings could be carried out in the goaf. Based on the varying degrees of stability in the goaf, an appropriate restoration path is suggested according to the suitability of these different degrees. The green, innovative, and sustainable restoration design of the goaf can be carried out according to these restoration paths in order to establish a green ecological system in Jingmen Garden Expo Park.