METTL3 as a novel diagnosis and treatment biomarker and its association with glycolysis, cuproptosis and ceRNA in oesophageal carcinoma.

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.

DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma.

BACKGROUND: This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. METHODS: This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. RESULTS: DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. CONCLUSIONS: Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.

A stable Zr(IV)-MOF for efficient removal of trace SO2 from flue gas in dry and humid conditions.

Obtaining suitable adsorbents for selective separation of SO2 from flue gas still remains an important issue. A stable Zr(IV)-MOF (Zr-PTBA) can be conveniently synthesized through the self-assembly of a tetracarboxylic acid ligand (H4L = 4,4',4'',4'''-(1,4-phenylenebis(azanetriyl))tetrabenzoic acid) and ZrCl4 in the presence of trace water. It exhibits a three-dimensional porous structure. The BET surface area is 1112.72 m2/g and the average pore size distribution focus on 5.9, 8.0 and 9.3 Å. Interestingly, Zr-PTBA shows selective adsorption of SO2. The maximum uptake reaches 223.21 cm3/g at ambient condition. While it exhibits lower adsorption uptake of CO2 (30.50 cm3/g) and hardly adsorbs O2 (2.57 cm3/g) and N2 (1.31 cm3/g). Higher IAST selectivities of SO2/CO2 (21.9), SO2/N2 (912.7), SO2/O2 (2269.9) and SO2/CH4 (85.0) have been obtained, which reveal its' excellent gas separation performance. Breakthrough experiment further confirms its application for flue gas deep desulfurization both in dry and humid conditions. Furthermore, the gas adsorption results and mechanisms have also been studied by theoretical calculations.

Functional enrichment analysis reveals the involvement of DARS2 in multiple biological pathways and its potential as a therapeutic target in esophageal carcinoma.

OBJECTIVE: The enzyme Aspartyl tRNA synthetase 2 (DARS2) is a crucial enzyme in the mitochondrial tRNA synthesis pathway, playing a critical role in maintaining normal mitochondrial function and protein synthesis. However, the role of DARS2 in ESCA is unclear. MATERIALS AND METHODS: Transcriptional data of pan-cancer and ESCA were downloaded from UCSC XENA, TCGA, and GEO databases to analyze the differential expression of DARS2 between tumor samples and normal samples, and its correlation with clinicopathological features of ESCA patients. R was used for GO, KEGG, and GSEA functional enrichment analysis of DARS2 co-expression and to analyze the connection of DARS2 with glycolysis and m6A-related genes. In vitro experiments were performed to assess the effects of interfering with DARS2 expression on ESCA cells. TarBase v.8, mirDIP, miRTarBase, ENCORI, and miRNet databases were used to analyze and construct a ceRNA network containing DARS2. RESULTS: DARS2 was overexpressed in various types of tumors. In vitro experiments confirmed that interfering with DARS2 expression significantly affected the proliferation, migration, apoptosis, cell cycle, and glycolysis of ESCA cells. DARS2 may be involved in multiple biological pathways related to tumor development. Furthermore, correlation and differential analysis revealed that DARS2 may regulate ESCA m6A modification through its interaction with METTL3 and YTHDF1. A ceRNA network containing DARS2, DLEU2/has-miR-30a-5p/DARS2, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the upregulation of DARS2 in ESCA and its association with clinical features, glycolysis pathway, m6A modification, and ceRNA network. These discoveries provide valuable insights into the molecular mechanisms underlying ESCA.

FASTKD1 as a diagnostic and prognostic biomarker for STAD: Insights into m6A modification and immune infiltration.

Fas-activated serine/threonine kinase domain 1 (FASTKD1), a known modulator of mitochondrial-mediated cell death and survival processes, has garnered attention for its potential role in various biological contexts. However, its involvement in gastric cancer remains unclear. Thus, the present study aimed to investigate the relationship between FASTKD1 expression and key factors, including clinicopathological characteristics, immune infiltration and m6A modification in stomach adenocarcinoma (STAD). The expression of FASTKD1 was analyzed in STAD and normal adjacent tissues to assess its association with clinicopathological characteristics and survival prognosis. Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study. Additionally, the findings were validated through immunohistochemical staining. Co-expression analysis of FASTKD1 was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and LinkedOmics database analysis. An in-depth analysis was conducted using databases, such as Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GEO and TCGA to explore the potential correlation between FASTKD1 expression and immune infiltration and m6A modification in STAD. The results revealed that FASTKD1 was significantly upregulated across different tumor types, including STAD. Notably, FASTKD1 was able to distinguish between tumor and normal tissue samples with accuracy. Furthermore, the expression levels of FASTKD1 were significantly associated with clinical stage and survival. Through GO/KEGG enrichment analysis and GSEA, it was revealed that the genes co-expressed with FASTKD1 were active in a variety of biological processes. Within the TIMER, GEPIA and TCGA databases, a notable inverse correlation was observed between FASTKD1 expression and the abundance of immune cell subsets. Notably, significant correlations were established between FASTKD1 and m6A modification genes, YTHDF1 and LRPPRC, in both TCGA and GEO datasets. In conclusion, FASTKD1 may serve a significant role in m6A modification and immune infiltration processes, making it a potentially valuable diagnostic and prognostic biomarker in STAD.

Pan-cancer analysis reveals correlation between RAB3B expression and tumor heterogeneity, immune microenvironment, and prognosis in multiple cancers.

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (ß=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). CONCLUSIONS: Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

SFXN1 as a potential diagnostic and prognostic biomarker of LUAD is associated with 18F-FDG metabolic parameters.

BACKGROUND: Sideroflexin 1 (SFXN1) has been discovered as a novel tumor marker for lung adenocarcinoma, but data on its importance in the development of lung adenocarcinoma is still limited. This study evaluated the correlation between SFXN1 and parameters related to 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and further explored the role of SFXN1 in the value-added and glycolytic processes of LUAD. METHOD: The expression and prognostic value of SFXN1 mRNA in LUAD were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data base. Retrospective analysis of 18F-FDG PET imaging and metabolic parameters in 42 patients to explore the relationship between the expression of SFXN1 and glucose metabolism levels in lung adenocarcinoma and its clinical significance. H1975 cells were selected as the in vitro research object, and the biological effects of SFXN1 on LUAD were further elucidated through Edu proliferation assay, CCK8 activity assay, wound healing experiment, and cell flow cytometry. RESULT: SFXN1 is highly expressed in various tumors, including LUAD, and its high expression can serve as an independent predictor of overall survival in lung adenocarcinoma. In addition, the expression of SFXN1 in LUAD was significantly correlated with 18F-FDG PET/CT parameters: maximum and average standardized uptake values (SUVmax and SUVmean), as well as total lesion glycolysis (TLG) (rho = 0.574, 0.589, and 0.338, p < 0.05), which can predict the expression of SFXN1 with an accuracy of 0.934. In vitro functional experiments have shown that knocking down SFXN1 inhibits the proliferation and migration of LUAD cells, promotes cell apoptosis, and may inhibit tumor activity by regulating the expression of glycolytic related genes SLC2A1, HK2, GPI, ALDOA, GAPDH, ENO1, PKM, and LDHA. CONCLUSION: The overexpression of SFXN1 is closely related to FDG uptake, and SFXN1, as a promising prognostic biomarker, may mediate the development of LUAD through the glycolytic pathway.

Pattern of Brain Parenchymal Damage Related to Cerebral Small Vessel Disease in Carriers of Rare NOTCH3 Variants.

BACKGROUND AND OBJECTIVES: Previous studies reported that carriers of rare NOTCH3 variants comprised more than 10% of the general population and are susceptible to a heavy overall burden of cerebral small vessel disease while the injury patterns remain uncovered. This study aimed to investigate the imaging features in relation to rare NOTCH3 variants and the interaction between cortical atrophy and white matter lesions from a longitudinal view, with respect to spatial and dynamic patterns. METHODS: As part of a community-based cohort, we included participants with complete whole-exome sequencing and brain MRI in the baseline analysis. All participants were invited for a 5-year follow-up MRI, and those who did not complete the follow-up were excluded from the longitudinal analysis. NOTCH3 variants with minor allele frequency <1% in all 4 public population databases were defined as rare variants. We used general linear models to compare the volume of white matter hyperintensity (WMH) volume and brain parenchymal fraction between rare NOTCH3 variant carriers and noncarriers. In addition, we compared the WMH probability map and vertex-wise cortex maps at a voxel/vertex-wise level. RESULTS: A total of 1,054 participants were included in baseline analysis (13.56% carried rare NOTCH3 variants), among whom 661 had a follow-up brain MRI (13.76% carried rare NOTCH3 variants). Rare NOTCH3 variant carriers had a heavier white matter hyperintensity burden (1.65 vs 0.85 mL, p = 0.025) and had more extensive WMH distributed in the periventricular areas. We also found that rare NOTCH3 variant carriers were susceptible to worse cortical atrophy (ß = -0.004, SE = 0.002, p = 0.057, adjusted for age and sex). Cortical atrophy of multiple regions in the frontal and parietal lobes was related to white matter hyperintensity progression. DISCUSSION: Individuals with rare NOTCH3 variants have a distinct pattern of brain parenchymal damage related to CSVD. Our findings uncover the important genetic predisposition in age-related cerebral small vessel disease in the general population.

Comparing characteristics and outcomes of in-hospital stroke and community-onset stroke.

BACKGROUND: In-hospital strokes account for 4-17% of all strokes and usually lead to urgent and severe conditions. However, features of in-hospital strokes have been scarcely reported in China, and the management systems of in-hospital strokes are unestablished. The study aims to analyze the characteristics of in-hospital strokes in comparison to community-onset strokes and provides evidence for the development of national in-patient stroke care systems. METHODS: We retrospectively analyzed consecutive patients with in-hospital strokes (IHS group) and community-onset strokes (COS group) hospitalized in our hospital between June 2012, and January 2022. Clinical characteristics, care measures, and outcomes were compared between the two groups. RESULTS: A total of 1162 patients (age 61 ± 16 and 65% male) were included, of whom 193 (16.6%) had an in-hospital stroke and 969 (83.4%) had community-onset stroke. Compared with COS group, patients in IHS group had higher NIHSS at onset (7.25 vs 5.96, P = 0.054), higher use of endovascular therapy (10.4% vs 2.0%, P < 0.001), and lower use of intravascular thrombolysis (1.6% vs 7.2%, P = 0.003). Also, in-hospital strokes were associated with lower rate of mRS0-2 at discharge (OR[95%CI] = 0.674[0.49, 0.926], P = 0.015) and increased in-hospital mobility (OR[95%CI] = 3.621[1.640, 7.996], P = 0.001), after adjusting for age, sex, and cardiovascular risk factors. CONCLUSION: Compared with community-onset strokes, the patients with in-hospital stroke had insufficient urgent treatment and poorer outcomes, reflecting the need for increased awareness of in-patient stroke, and strategies to streamline in-hospital acute stroke care.

Deep medullary veins are associated with widespread brain structural abnormalities.

Our aim is to investigate the association of cerebral deep medullary veins (DMVs) with white matter microstructural integrity and regional brain atrophy in MRI. In a community-based cohort of 979 participants (mean age 55.4 years), DMVs were identified on susceptibility-weighted imaging. Brain structural measurements including gray matter and hippocampus volumes, as well as diffusion tensor metrics, were evaluated. The mean (SD)number of DMVs was 19.0 (1.7). A fewer number of DMVs was related to lower fractional anisotropy and higher mean diffusivity in multiple voxels on the white matter skeleton (threshold-free cluster enhancement corrected p < 0.05, adjusted for age and sex). Also, fewer DMVs were significantly related to a lower gray matter fraction and a hippocampal fraction (0.10 and 0.11 per DMV, respectively; SE, 0.03 for both; p < 0.001 for both). A significant correlation between DMVs' reduction and cortical atrophy was observed in the bilateral occipital lobes, temporal lobes, hippocampus, and frontal lobes (p < 0.001, adjusted for age, sex, and total intracranial volume). Our results provided evidence that cerebral small venules disease play a role in brain parenchymal lesions and neurodegenerative processes.

Regional Disruption of White Matter Integrity and Network Connectivity Are Related to Cognition.

BACKGROUND: Cognitive impairment is common in the elderly population. Exploring patterns of white matter damage at the microstructural level would give important indications for the underlying mechanisms. OBJECTIVE: To investigate the spatial patterns of white matter microstructure and structural network alternations in relation to different cognition domainsMethods:Participants from the community-based Shunyi Study were included to investigate the association between white matter measurements and cognition cross-sectionally, via both global and local analysis. Cognitive functions were assessed using digit span, trail making test (TMT)-A/B, Fuld object Memory, and 12-Word Philadelphia Verbal Learning Test (PVLT). White matter measurements including fractional anisotropy (FA), mean diffusivity (MD), and structural network parameters were calculated based on diffusion tensor imaging. RESULTS: Of the 943 participants included, the mean (SD) age was 55.8 (9.1) years, and the mean (SD) education level was 6.7 (3.2) years. We found the whole set of cognitive measurements was related to diffused white matter microstructural integrity damage and lower global efficiency. Poor executive functions (TMTA/B complete time) were related to lower FA and higher MD predominantly on the anterior white matter skeleton, while verbal memory loss (PVLT test scores) was related to sub-network dysconnectivity in the midline and the right temporal lobe. CONCLUSION: The anterior brain is dominantly involved in executive dysfunction, while midline and right temporal brain disconnection are more prominent in verbal memory loss. Global and regional disruption of white matter integrity and network connectivity is the anatomical basis of the cognitive impairment in the aging population.

Dryopteriswulingshanensis (Dryopteridaceae), a new species from Hunan, China.

Dryopteriswulingshanensis, a new species growing on limestone in the Wulingshan Mountains, Hunan, China, is described and illustrated. This species is most similar to D.jishouensis and D.gymnophylla on general morphological traits, such as the form of scales, rhizome and sori, but differs by the number of vascular bundles at the base of the petiole, length to width ratio of lamina, stalk length of basal pinnae, division of the lamina, apex form of the pinnule and habitat. Moreover, molecular phylogenetic analysis using the chloroplast rbcL gene suggested that D.wulingshanensis, as the sister group of D.jishouensis, is a monophyletic clade. According to its restricted geographic range, small populations and few individuals, D.wulingshanensis should be considered endangered, according to the IUCN Red List criteria.