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Abstract Background Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infections. Some of these infections are linked to specific clinical and immunological subgroups of GBS, suggesting a potential correlation between viral infections and the development of GBS. However, observational studies have several limitations, including the presence of confounding factors. Method We explored the potential correlation between HIV, SARS-CoV-2, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, hepatitis B virus, and influenza virus with GBS using a two-sample Mendelian randomization approach. The data was derived from published summary statistics from genome-wide association studies (GWAS). After removing linkage disequilibrium, selecting strong instrumental variables and addressing confounding factors, we would conduct a two-sample Mendelian randomization analysis along with sensitivity testing and the MR-Steiger directional test. Result HIV may have a causal association with GBS (IVW: p = 0.010, OR [95% CI] 1.240 [1.052–1.463]), while no such relationship exists with COVID-19 (IVW: p = 0.275, OR [95% CI] 0.831[0.596–1.159]), varicella (IVW: p = 0.543, OR [95% CI] 0.919 [0.701–1.206]), herpes zoster (IVW: p = 0.563, OR [95% CI] 0.941 [0.766–1.156]), HSV (IVW: p = 0.280, OR [95% CI] 1.244 [0.837–1.851]), EBV (IVW: p = 0.218, OR [95% CI] 0.883 [0.724–1.076]), HBV (IVW: p = 0.179, OR [95% CI] 1.072 [0.969–1.187]), or influenza virus (IVW: p = 0.917, OR [95% CI] 0.971 [0.553–1.703]). We did not find any abnormal SNPs, pleiotropy, or heterogeneity, nor is there any reverse causation. Conclusion Our study results indicate a causal relationship between HIV and GBS, providing new research directions for the etiology of GBS.

Abstract To clarify the survival benefit of sequential curative treatment post transcatheter arterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), we retrospectively analyzed HCC patients at a hospital. From July 2017 to July 2020, 787 treatment-naïve HCC patients underwent initial treatment; 77 (9.8%) meeting inclusion criteria were enrolled. Their initial treatments were TACE only (n = 68, 88.3%) or TACE with other treatments (n = 9, 11.7%). Median survival of the TACE-only group was 30 months. Treatment response was evaluated after 2 or 3 consecutive TACEs for patients (54/68, 79.4%) with available pre-/post-TACE computerized tomography (CT) or magnetic resonance imaging (MRI). Treatment responses was divided into 4 groups: complete (n = 14, 26%, group (Gr) 1), incomplete without new tumor growth (n = 28, 52.0%, Gr2), incomplete with new growth (n = 6, 11%, Gr3), and progression (n = 6, 11%, Gr4). Of Gr2, further treatment after TACE were had radiofrequency ablation (n = 13, Gr2a), TACE (n = 9, Gr2b), other modalities (n = 6, Gr2c. Gr2a’s median survival was longer than Gr2b’s (> 60 vs. 20 months, p = 0.007). Nine patients in Gr2a (69%, 9/13) achieved a complete response, but none in Gr2b (p = 0.001). Conclusively, in TACE-suitable BCLC stage B HCC patients, a partial response without new tumor growth can serve as an indicator of treatment effectiveness following initial TACE treatment. This can facilitate the selection of appropriate candidates to receive RFA, potentially resulting in improved patient survival.

Abstract As one of the two main histologic subtypes of gastric cancer (GC), diffuse-type gastric cancer (DGC) containing poorly cohesive gastric carcinoma (PCC) components has a worse prognosis and does not respond well to typical therapies. Despite the large number of studies revealing the complex pathogenic network of DGC, the molecular heterogeneity of DGC is still not fully understood. We obtained single-cell RNA-seq data and bulk data from the tumor immune single cell hub, the public gene expression omnibus, and the cancer genome atlas databases. A series of bioinformatics analyses were performed using R software. Immunofluorescence staining, hematoxylin and eosin staining, western blot, and functional experiments were used for experimental validation. Caudin-3, -4 and -7 were lowly expressed in DGC and their expression levels were further reduced in PCC. The PCC components were mainly located in the deeper layers of the DGC and had a high level of hypoxic Wnt/β-catenin signaling and stemness. We further identified Insulin Like Growth Factor Binding Protein 7 (IGFBP7) as a marker for PCC components in the deep layer. IGFBP7 is stimulated by hypoxia and promotes cancer cell invasiveness and reduced claudin expression. In addition, programmed death-1 ligand (PD-L1) was specifically expressed in the deep layer, reflecting deep layer-specific immunosuppression. The PCC components are predominantly situated in the deeper layers of DGC. Initial molecular characterization of these PCC components revealed distinct features, including low expression of claudin-3, -4, and -7, high expression of IGFBP7, and the presence of PD-L1. These molecular traits may partially account for the pronounced tumor heterogeneity observed in GC.

Objective To construct a FLO8 gene knockout strain of Candida glabrata and analyze the effect of FLO8 knockout on the expression of EPA family in Candida glabrata. Methods By fusion PCR technology, the knockout components were constructed with the genomic DNA of Candida glabrata ATCC2001 strain and the plasmid DNA with screening marker NAT as templates. The knockout components were transfected into Candida glabrataATCC2001 by lithium acetate transfection method to obtainflo8△strain. The expression of EPA1, EPA6 and EPA7 genes were detected by real-time quantitative PCR. Results The FLO8 gene knockout strain of Candida glabrata was efficiently constructed. The expression levels of EPA1, EPA6 and EPA7genes in flo8△strain were significantly lower than those in ATCC2001 strain (all P

Abstract The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Graphical Abstract

As artificial intelligence-based automatic generation technology advances, the emergence of misinformation in more sophisticated guises has become a significant threat to the economy and social order. Among its forms, out-of-context misinformation stands out as particularly deceptive and readily executable. This type of misinformation involves malicious actors enhancing the credibility of false narratives by misrepresenting contextual details such as individuals, events, and locations within real images. To address the shortcomings of current detection algorithms, which heavily depend on knowledge bases and often overlook the stance relationship between the information under scrutiny and online evidence, a stance analysis-based out-of-context misinformation detection method was developed. This method involved several steps for the detection of an image-caption pair along with the corresponding textual and visual evidence retrieved from the Internet. Initially, a stance gain score for each piece of textual evidence was calculated based on the co-occurrence of named entities. Subsequently, independent stance analysis networks were utilized to perform hierarchical clustering on both the image and visual evidence, as well as on the caption and textual evidence. This process involved the extraction of semantic stance representations, facilitated by multiple attention mechanisms and a stance analysis module. The authenticity of the image-caption pair was subsequently predicted based on the outcomes of semantic comparison and stance analysis. Experimental results indicate that the incorporation of stance analysis significantly enhances the method's detection capabilities. Specifically, the accuracy of this method outperforms the state-of-the-art algorithm that employs Internet evidence for detection by 2.3%.

Autonomous underwater helicopters (AUHs) are complex electromechanical systems consisting of multiple interconnected sub-disciplines, posing a significant challenge for traditional sequential design strategies in managing their interactions. To address this challenge, a multidisciplinary collaborative optimization (MCO) strategy is proposed, integrating structural, hydrodynamic, and energy disciplines to enhance AUH cruising range. Additionally, a novel approximation model is introduced, combining the Logistic-Tent chaos sparrow search algorithm (LTC-SSA) with the backpropagation neural network (BPNN) algorithm. This method aims to replace costly computational fluid dynamics (CFD) and structural mechanics calculations, thus reducing AUH optimization costs. The laminate design of the composite pressure hull follows classic lamination theory (CLT) and the Tsai-Wu failure criterion. Results demonstrate that the multidisciplinary co-design strategy significantly reduces optimization time costs of AUH, from several months to several days. Furthermore, the proposed LTC-SSA-BPNN algorithm accurately evaluates sailing resistance and Tsai-Wu failure index, with maximum errors of 1.64% and 9.32% respectively. Additionally, the composite pressure shell achieves a 30.4% weight reduction and a 4.1% reduction in sailing resistance while maintaining structural stability. Moreover, the maximum cruising range increases by 34.4%. This strategy offers theoretical support for AUH conceptual design and promises performance enhancement in practical engineering applications.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. Methods: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. Results: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). Conclusion: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Objective To explore the efficacy and safety of single-incision laparoscopic (SIL) technique compared with the traditional three-port total extraperitoneal (TEP) technique for inguinal hernia repair. Methods This prospective, randomised study involved patients who underwent surgery for inguinal hernia at our hospital from December 2021 to July 2023. Patients were randomly assigned to SIL-TEP or TEP groups based on a computer-generated random number table. Perioperative clinical indicators for the surgical approaches were evaluated. Results Of the 127 patients eligible for study, 66 were randomised to the SIL-TEP group and 61 to the TEP group. The operation time for SIL-TEP was significantly longer than for TEP but the time to return to normal activities was significantly shorter and short-term pain score was significantly lower. There were no differences between groups in intraoperative blood loss, postoperative hospital stays, pain relief time, hospitalization costs or cosmetic satisfaction scores. Conclusion While SIL-TEP is more challenging than TEP for hernia repair, we found that at our centre it is comparable with regard to overall safety and feasibility. Further studies are needed to validate our findings.