Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Diabetic Foot Ulcer and Diabetic Microvascular Disease

Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes caused by multiple factors. Diabetic microvascular disease has a close linkage with DFU. However, the inter-relational mechanisms between them are still unclear. This article aimed to explore the shared gene signatures and potential molecular mechanisms in DFU and diabetic microvascular disease. Methods: In the GEO database, DFU microarray datasets (GSE80178, GSE68183) and diabetic microvascular disease microarray datasets (GSE43950) were downloaded. After data standardization processing, we used R software to analyze the transcriptome sequencing data of each data set to find the differentially expressed genes (DEGs) of DFU and diabetic microvascular disease. Then obtained the overlapped DEGs in DFU and diabetic microvascular disease database by Jvenn. Finally, the shared DEGs were enriched by pathway enrichment and protein-protein interaction (PPI) analysis, and the hub gene was found by node analysis. Results: Totally, 1007 DEGs were identified in the GSE80178 dataset, 338 DEGs were identified in the GSE68183 dataset, 1154 were identified in the GSE43950 dataset, Venn diagram analyses showed that there were 14 shared DEGs in these datasets. Enrichment analysis shows that the shared DEGs were mainly associated with chronic inflammatory response, leukocyte migration, cellular transition metal ion homeostasis, vascular wound healing, collagen-containing extracellular matrix and Toll-like receptor binding. Involved pathways were mainly enriched in IL-17 signaling, glycosaminoglycan degradation, and calcium signaling. PPI analysis of these shared DEGs shows that S100A9, S100A8, CSTA, ADAP2, CD34 and FGL2 were the hub gene whose plays a pivotal role in DFU.Conclusion: Our work has identified several new DFU candidate genes that can be used as biomarkers or potential therapeutic targets

Re-evaluation of single nucleotide variants and identification of structural variants in a cohort of 45 sudden unexplained death cases

Sudden unexplained death (SUD) takes up a considerable part in overall sudden death cases, especially in adolescents and young adults. During the past decade, many channelopathy- and cardiomyopathy-associated single nucleotide variants (SNVs) have been identified in SUD studies by means of postmortem molecular autopsy, yet the number of cases that remain inconclusive is still high. Recent studies had suggested that structural variants (SVs) might play an important role in SUD, but there is no consensus on the impact of SVs on inherited cardiac diseases. In this study, we searched for potentially pathogenic SVs in 244 genes associated with cardiac diseases. Whole-exome sequencing and appropriate data analysis were performed in 45 SUD cases. Re-analysis of the exome data according to the current ACMG guidelines identified 14 pathogenic or likely pathogenic variants in 10 (22.2%) out of the 45 SUD cases, whereof 2 (4.4%) individuals had variants with likely functional effects in the channelopathy-associated genes SCN5A and TRDN and 1 (2.2%) individual in the cardiomyopathy-associated gene DTNA. In addition, 18 structural variants (SVs) were identified in 15 out of the 45 individuals. Two SVs with likely functional impairment were found in the coding regions of PDSS2 and TRPM4 in 2 SUD cases (4.4%). Both were identified as heterozygous deletions, which were confirmed by multiplex ligation-dependent probe amplification. In conclusion, our findings support that SVs could contribute to the pathology of the sudden death event in some of the cases and therefore should be investigated on a routine basis in suspected SUD cases

Registration-Free Hybrid Learning Empowers Simple Multimodal Imaging System for High-quality Fusion Detection

Multimodal fusion detection always places high demands on the imaging system and image pre-processing, while either a high-quality pre-registration system or image registration processing is costly. Unfortunately, the existing fusion methods are designed for registered source images, and the fusion of inhomogeneous features, which denotes a pair of features at the same spatial location that expresses different semantic information, cannot achieve satisfactory performance via these methods. As a result, we propose IA-VFDnet, a CNN-Transformer hybrid learning framework with a unified high-quality multimodal feature matching module (AKM) and a fusion module (WDAF), in which AKM and DWDAF work in synergy to perform high-quality infrared-aware visible fusion detection, which can be applied to smoke and wildfire detection. Furthermore, experiments on the M3FD dataset validate the superiority of the proposed method, with IA-VFDnet achieving the best detection performance than other state-of-the-art methods under conventional registered conditions. In addition, the first unregistered multimodal smoke and wildfire detection benchmark is openly available in this letter

Lnc-BM Promotes Gastric Cancer Progression by Regulating Mitochondrial Respiratory Function Through FASTK/MT-ND6 Axis

Objective To explore the role and molecular mechanism of Lnc-BM in the occurrence and development of gastric cancer (GC). Methods GC tissues and paired adjacent normal tissues of 36 GC patients were collected, and the expression of Lnc-BM was detected by RT-qPCR. Colony formation and CCK-8 assays were used to investigate the proliferation of GC cells. The migration and invasion properties of GC cells were investigated via Transwell assay. RNA pull-down assay was applied to confirm the interaction between FASTK and Lnc-BM. Western blot assay was used to detect FASTK protein level in Lnc-BM overexpressing or knockdown cells. Mitochondrial respiratory capacity and the related proteins expression levels were detected by Seahorse and Western blot assays, respectively. Lnc-BM stably overexpressing GC cells were constructed and then injected subcutaneously into nude mice. The tumor growth was observed. Results Lnc-BM was highly expressed in GC tissues compared with their paired adjacent normal tissues. Lnc-BM overexpression significantly promoted GC cells proliferation migration and invasion, while Lnc-BM knockdown inhibited GC cells proliferation, migration and invasion (P < 0.05). RNA pull-down experiment demonstrated that Lnc-BM can directly bind to FASTK. Western blot results indicated that overexpression of Lnc-BM increased the protein levels of FASTK, while knockdown of Lnc-BM inhibited the expression of FASTK (P < 0.05). Compared to the control group, overexpression of Lnc-BM increased the levels of mitochondria associated proteins, such as MT-ND6 and TOM20 (P < 0.05). Seahorse results indicated that overexpression of Lnc-BM enhanced mitochondrial respiratory capacity (P < 0.05). Knocking down FASTK in Lnc-BM stably overexpressing cells can reverse the increase in mitochondrial respiratory capacity caused by Lnc-BM overexpression (P < 0.05). In vivo, the results of subcutaneously implanted tumor model in nude mouse showed that Lnc-BM overexpression promoted the tumor growth (P < 0.05). Conclusion Lnc-BM promotes GC progression by regulating mitochondrial respiratory function through the FASTK/MT-ND6 axis

First observation of the coexistence of multiple chiral doublet bands and pseudospin doublet bands in the A ≈ 80 mass region

Two nearly degenerate positive-parity bands with the π g2 9/2 ⊗ ν g−1 9/2 configuration and three nearly degenerate negative-parity bands with the π g9/2(p3/2, f5/2) ⊗ ν g−1 9/2 configuration have been identified in 81Kr. They are interpreted as chiral doublet bands and pseudospin-chiral triplet bands, which is supported by the constrained covariant density functional theory and the multiparticle plus rotor model calculations. The present work reports two new chiral configurations π g2 9/2 ⊗ ν g−1 9/2 and π g9/2(p3/2, f5/2) ⊗ ν g−1 9/2, and the first example of pseudospin-chiral triplet bands involving the π (p3/2, f5/2) pseudospin doublet