Helicobacter pylori CagA Promotes the Formation of Gallstones by Increasing the Permeability of Gallbladder Epithelial Cells.

BACKGROUND: The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms. METHODS: scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation. RESULTS: Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation. CONCLUSIONS: Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.

Association between trans fatty acids and COVID-19: A multivariate Mendelian randomization study.

Traditional observational studies have suggested a potential association between trans fatty acids (TFAs), which are considered to be health-damaging fatty acids, and coronavirus disease 2019 (COVID-19). However, whether there is a causal relationship between them is currently unclear. We aimed to investigate the causal link between genetically determined TFAs and COVID-19. We performed univariate and multivariate Mendelian randomization (MR) studies using summary statistics from the European Pedigree TFAs (n = 8013), COVID-19 susceptibility (n = 159 840), COVID-19 hospitalization (n = 44 986), and COVID-19 severity (n = 18 152) genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary MR analysis, and several other methods were used as supplements. In univariate MR analysis, higher levels of circulating trans, cis-18:2 TFAs were positively associated with a higher COVID-19 hospitalization rate (p < 0.0033; odds ratio [OR] = 1.637; 95% confidence interval [CI]: 1.116-2.401) and COVID-19 severity (p < 0.0033; OR = 2.575; 95% CI: 1.412-4.698). Furthermore, in multivariate MR analysis, trans, cis-18:2 had an independent and significant causal association with a higher COVID-19 hospitalization rate (p = 0.00044; OR = 1.862; 95% CI = 1.316-2.636) and COVID-19 severity (p = 0.0016; OR = 2.268; 95% CI = 1.361-3.779) after the five TFAs were adjusted for each other. Together, our findings provide evidence that trans, cis-18:2 TFAs have an independent and robust causal effect on COVID-19 hospitalization and severity.

Association between the use of lipid-lowering drugs and the risk of inflammatory bowel disease.

BACKGROUND: Observational studies have suggested an association between lipid-lowering drugs and inflammatory bowel disease (IBD) risk. This study aimed to assess the causal influence of lipid-lowering agents on IBD risk using Mendelian randomization analysis. METHOD: In a population of 173,082 individuals of European ancestry, 55 single-nucleotide polymorphisms were identified as instrumental variables for 6 lipid-lowering drug targets (HMGCR, NPC1LC, PCSK9, LDLR, CETP and APOB). Summary statistics for the genome-wide association study of IBD, ulcerative colitis (UC) and Crohn's disease (CD) were obtained from the FinnGen consortium, Program in Complex Trait Genomics and UK Biobank. Inverse-variance weighted was employed as the primary MR method, and odds ratios (ORs) with 95% confidence intervals were reported as the results. Sensitivity analyses using conventional MR methods were conducted to assess result robustness. RESULTS: Gene-proxied inhibition of Niemann-Pick C1-like 1 (NPC1L1) was associated with an increased IBD risk (OR [95% CI]: 2.31 [1.38, 3.85]; p = .001), particularly in UC (OR [95% CI]: 2.40 [1.21, 4.74], p = .012), but not in CD. This finding was replicated in the validation cohort. Additionally, gene-proxied inhibition of low-density lipoprotein receptor was associated with reduced IBD (OR [95% CI]: .72 [.60, .87], p < .001) and UC risk (OR [95% CI]: .74 [.59, .92], p = .006), although this result was not replicated in the validation cohort. Other drug targets did not show significant associations with IBD, UC or CD risk. CONCLUSION: Inhibition of the lipid-lowering drug-target NPC1L1 leads to an increased IBD risk, mainly in the UC population.

Lifestyle factors and the risk of gallstones: results from the national health and nutrition examination survey 2018-2020 and mendelian randomization analysis.

OBJECTIVES: This study aimed to investigate the relationship between lifestyle and gallstones. MATERIALS AND METHODS: We performed an observational study using the 2018-2020 National Health and Nutrition Examination Survey (NHANES). Univariate and multivariate-adjusted logistic regression analyses were performed to assess the correlations between lifestyle factors and gallstone risk. Second, Mendelian randomization (MR) was applied to decrease the causal relationship between lifestyle factors and gallstones. RESULTS: This observational study enrolled 11,970 individuals. The risk of gallstones was found to increase with increased sitting time (odds ratio (OR) 1.03, 95% CI 1.00-1.05, p = 0.02). In contrast, the risk of gallstones was found to decrease with recreational activity (OR 0.50, 95% CI 0.29-0.87, p = 0.02). The results of the MR also showed that time spent watching television (OR 1.646; 95% CI 1.161-2.333, p = 0.005) and physical activity (OR 0.953, 95% CI 0.924-0.988, p = 0.003) remained independently causally associated with gallstones. CONCLUSIONS: Prolonged sitting increases the risk of gallstones, whereas recreational activity reduces the risk. These findings need to be verified in further prospective cohort studies with larger sample sizes and longer follow-up periods.

Will multi-industry supply chains' resilience under the impact of COVID-19 pandemic be different? A perspective from China's highway freight transport.

The pandemic caused by coronavirus disease 2019(COVID-19) continues to disrupt the global supply chain system, bringing new risks and challenges. The uncertainty created by COVID-19 makes it is difficult for various industries to deal with the pandemic. Since the pandemic, the supply chain's resilience has been discussed and examined in some studies. However, most existing works start from a single industry perspective or pay more attention to the disturbance caused by changes in the production side. Supply chain networks of different industries, mainly transport networks, are relatively limited under the epidemic's impact. In this paper, from the perspective of highway freight transport, a comprehensive competitiveness evaluation framework was proposed to reveal and the disruption and resilience of the supply chain under the outbreak based on nine indexes with five dimensions, including efficiency, capacity, activity, connectivity, and negotiability. Based on the availability of the data(Large-scale truck trajectory), we sorted out seven categories of Chinese industries(related to highway transport) and divided them into four categories respectively: (a) Slight disruption and worse resilience; (b) Slight disruption and remarkable resilience; (c) Serious disruption and worse resilience; (d) Serious disruption and remarkable resilience. The measurement results of supply chain network performance show that the industries (cold-chain, general products, and other industries) dominated by "Efficiency - Negotiability - Connectivity" are slightly disrupted (about 33%), forming a spatial diffusion with Wuhan(the city where the pandemic first broke out) as the disrupted center, spreading outward in a circle structure. Simultaneously, five urban agglomerations surrounding it have been impacted. By contrast, due to the strict isolation measures, the industries (building materials, construction, engineering, and high-value products industry) more vulnerable to be disrupted seriously (about 82%) tend to be the pattern of "Capacity - Activity". However, a large-scale centralized disruption was observed in the Triangle of Central China urban agglomeration was presented, resulting in almost stagnation of industry development. Meanwhile, as the future of the pandemic remains uncertain, the supply chain represented by the engineering industry, construction industry, etc are deserved to be paid more attention in line with they are prone to large-scale centralized damage due to the disruption of a single city node.

Concurrent OPA1 mutation and chromosome 3q deletion leading to Behr syndrome: a case report.

BACKGROUND: Optic atrophy 1 (OPA1) gene mutations are associated with dominantly inherited optic neuropathy resulting in a progressive loss of visual acuity. Compound heterozygous or homozygous variants that lead to severe phenotypes, including Behr syndrome, have been reported rarely. CASE PRESENTATION: Here, we present a 14-month-old boy with early onset optic atrophy, congenital cataracts, neuromuscular disorders, mental retardation, and developmental delay. Combined genetic testing, including whole exome sequencing (WES) and chromosomal microarray analysis, revealed a concurrent OPA1 variant (c.2189 T > C p.Leu730Ser) and de novo chromosome 3q deletion as pathogenic variants leading to the severe phenotype. CONCLUSIONS: Our case is the first reporting a novel missense OPA1 variant co-occurring with a chromosomal microdeletion leading to a severe phenotype reminiscent of Behr syndrome. This expands the mutation spectrum of OPA1 and inheritance patterns of this disease.

BMP-2-Loaded HAp:Ln3+ (Ln = Yb, Er, Gd) Nanorods with Dual-Mode Imaging for Efficient MC3t3-E1 Cell Differentiation Regulation.

Effective bone tissue reconstitution improves the treatment success rate of dental implantation and preserves natural teeth during periodontal tissue repair. Hydroxyapatite (HAp) has received much attention in bone remodeling field because its mineralized structure is similar to that of the natural bone tissue. For this reason, it has been used as a carrier for growth factors. Although HAp possesses outstanding biomedical properties, its capacity of loading and releasing bone growth factors and promoting osteogenesis is not well understood. In this study, Ln3+ (Ln = Yb3+, Er3+, Gd3+)-doped HAp (HAp:Ln3+) nanorods were synthesized by one-step hydrothermal method. To improve its biocompatibility and surface properties, bone morphogenetic protein-2 (BMP-2) was loaded onto the surface of HAp:Ln3+ nanorods. The results showed that BMP-2 incorporation promoted bone formation and enhanced the expression of early bone-related gene and protein (RunX2, SP7, OPN). In addition, Yb3+- and Er3+-doped HAp nanorods were examined by upconversion luminescence with 980 nm near-infrared laser irradiation to monitor the delivery position of BMP-2 protein. Furthermore, due to the positive magnetism correlated with the concentration of Gd3+, HAp:Ln3+ with enhanced contrast brightening can be deemed as T1 MIR contrast agents. These findings indicate that HAp doped with rare-earth ions and loaded with BMP-2 has the potential to promote bone tissue repair and execute dual-mode imaging.

IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study.

BACKGROUND: The interleukin (IL) plays a role in the development of acute pancreatitis (AP). However, the specific IL in AP has not been fully revealed. Therefore, the association between prospective IL and AP was studied via Mendelian randomization (MR). METHODS: The HUGO Gene nomenclature committee (HGNC) database provided 47 interleukin related genes (ILRGs). ILRGs and differentially expressed genes (DEGs) from GSE194331 were overlapped to create differently expressed ILRGs (DE-ILRGs). The integrative epidemiology unit (IEU) open genome-wide association study (GWAS) database provided exposure and outcome datasets. Univariate MR (UVMR) analysis using MR-Egger, IVW, simple mode, and weighted mode was done. UVMR results were verified using sensitivity analysis. Drug prediction, MVMR analysis, and PPI network development were also performed. RESULTS: Six DE-ILRGs were obtained. IL27 and IL1RN were substantially causally linked with AP by UVMR analysis (OR = 0.926, P < 0.001 and OR = 1.031, P = 0.023). Our sensitivity analysis showed the dependability of our results. Direct effect of IL27 was suggested by MVMR analysis. In the cytokine receptor binding pathway, IL27 and IL1RN interacted with IL36G and IL1R2. TAE-684, ARQ-680, and 12 other IL1RN and 14 IL27 medications were predicted. CONCLUSIONS: IL1RN was identified as a risk factor for acute pancreatitis (AP), but IL27 was found to be a protective factor for AP.

Gene Regulation of Neutrophils Mediated Liver and Lung Injury through NETosis in Acute Pancreatitis.

Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic tissue. When AP progresses to severe acute pancreatitis (SAP), it often causes multi-organ damage, leading to a high mortality rate. However, the molecular mechanisms underlying SAP-mediated organ damage remain unclear. This study aims to systematically mine SAP data from public databases and combine experimental validation to identify key molecules involved in multi-organ damage caused by SAP. Retrieve transcriptomic data of mice pancreatic tissue for AP, lung and liver tissue for SAP, and corresponding normal tissue from the Gene Expression Omnibus (GEO) database. Conduct gene differential analysis using Limma and DEseq2 methods. Perform enrichment analysis using the clusterProfiler package in R software. Score immune cells and immune status in various organs using single-sample gene set enrichment analysis (ssGSEA). Evaluate mRNA expression levels of core genes using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Validate serum amylase, TNF-α, IL-1ß, and IL-6 levels in peripheral blood using enzyme-linked immunosorbent assay (ELISA), and detect the formation of neutrophil extracellular traps (NETs) in mice pancreatic, liver, and lung tissues using immunofluorescence. Differential analysis reveals that 46 genes exhibit expression dysregulation in mice pancreatic tissue for AP, liver and lung tissue for SAP, as well as peripheral blood in humans. Functional enrichment analysis indicates that these genes are primarily associated with neutrophil-related biological processes. ROC curve analysis indicates that 12 neutrophil-related genes have diagnostic potential for SAP. Immune infiltration analysis reveals high neutrophil infiltration in various organs affected by SAP. Single-cell sequencing analysis shows that these genes are predominantly expressed in neutrophils and macrophages. FPR1, ITGAM, and C5AR1 are identified as key genes involved in the formation of NETs and activation of neutrophils. qPCR and IHC results demonstrate upregulation of FPR1, ITGAM, and C5AR1 expression in pancreatic, liver, and lung tissues of mice with SAP. Immunofluorescence staining shows increased levels of neutrophils and NETs in SAP mice. Inhibition of NETs formation can alleviate the severity of SAP as well as the levels of inflammation in the liver and lung tissues. This study identified key genes involved in the formation of NETs, namely FPR1, ITGAM, and C5AR1, which are upregulated during multi-organ damage in SAP. Inhibition of NETs release effectively reduces the systemic inflammatory response and liver-lung damage in SAP. This research provides new therapeutic targets for the multi-organ damage associated with SAP.

Total testosterone plays a crucial role in the pathway from hypothyroidism to broad depression in women.

BACKGROUND: Depression tends to develop in correlation with hypothyroidism, however it's unclear how testosterone traits contribute to this association. We examined the causal association between depression, testosterone traits, and hypothyroidism using Mendelian randomization (MR). METHOD: We conducted univariable and multivariable MR studies using summary-level statistics from genome-wide association studies (GWAS) of Hypothyroidism (n = 213,990), broad depression (n = 322,580), probable major depressive disorder (probable MDD) (n = 174,519), and International Classification of Diseases (ICD)-9 or ICD-10-coded MDD (n = 217,584) from European ancestry. The inverse variance weighted (IVW) method was used as the main MR analysis. RESULTS: In univariate MR analysis, there is a positive causal relationship between hypothyroidism and broad depression (P = 0.0074; OR = 1.0066; 95%CI: 1.0018-1.0114) and probable MDD (P = 0.0242; OR = 1.0056; 95%CI: 1.0007-1.0105). In females, there is a causal relationship between hypothyroidism and decreased total testosterone (P < 0.001; OR = 0.9747; 95%CI: 0.9612-0.9885) and sex hormone binding globulin (SHBG) levels (P = 0.0418; OR = 0.9858; 95%CI: 0.9723-0.9995). In females, there is an inverse causal relationship between total testosterone and broad depression (P = 0.0349; OR = 0.9898; 95%CI: 0.9804-0.9993). Furthermore, in multivariate MR analysis, after adjusting for total testosterone in females, hypothyroidism only has a positive causal relationship with probable MDD, and the relationship with broad depression is no longer significant. Most notably, after adjusting for hypothyroidism, the inverse causal effect of female total testosterone levels on broad depression becomes more significant (P = 0.0154; OR = 0.9878; 95%CI: 0.9780-0.9977). CONCLUSION: Hypothyroidism increases the risk of broad depression and probable MDD development. Total Testosterone appears to play an important role in the relationship between hypothyroidism and broad depression in female.

Characteristic Mapping for Ellipse Detection Acceleration.

It is challenging to characterize the intrinsic geometry of high-degree algebraic curves with lower-degree algebraic curves. The reduction in the curve's degree implies lower computation costs, which is crucial for various practical computer vision systems. In this paper, we develop a characteristic mapping (CM) to recursively degenerate 3n points on a planar curve of n th order to 3(n-1) points on a curve of (n-1) th order. The proposed characteristic mapping enables curve grouping on a line, a curve of the lowest order, that preserves the intrinsic geometric properties of a higher-order curve (ellipse). We prove a necessary condition and derive an efficient arc grouping module that finds valid elliptical arc segments by determining whether the mapped three points are colinear, invoking minimal computation. We embed the module into two latest arc-based ellipse detection methods, which reduces their running time by 25% and 50% on average over five widely used data sets. This yields faster detection than the state-of-the-art algorithms while keeping their precision comparable or even higher. Two CM embedded methods also significantly surpass a deep learning method on all evaluation metrics.

Fucosyltransferases Regulated by Fusobacterium Nucleatum and Act as Novel Biomarkers in Colon Adenocarcinoma.

Purpose: Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated mortality worldwide. Fucosyltransferases (FUTs) are associated with numerous cancers. We aimed to investigate the functions of FUTs in COAD. Patients and Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the expression and clinical relevance of FUTs in COAD. Real Time Quantitative PCR (RT-qPCR), Western blot, immunohistochemistry and ELISA were used to detect the relative RNA and protein expression levels. Colitis-associated cancer mice treated with Fusobacterium nucleatum were used to illustrate the effects of Fusobacterium nucleatum on FUTs and COAD. Luciferase reporting assay was used to investigate the binding of miRNA to mRNA. Results: TCGA and GEO datasets showed abnormal expression of FUTs in COAD at transcript level. RT-qPCR, Western blot and immunohistochemistry showed increased expression of FUT1, POFUT1 and POFUT2 in COAD. COAD patients with a high expression of FUT1, FUT11, FUT13 (POFUT2) had a worse prognosis, while patients with a high expression of FUT2, FUT3, FUT6 had a better prognosis. FUT1 and POFUT2 could independently predict the prognosis of COAD patients. Functional analysis by CancerSEA database showed that FUT3, FUT6, FUT8, FUT12 (POFUT1) and FUT13 are associated with differentiation, apoptosis, invasion, quiescence, and hypoxia. FUTs are associated with the tumor microenvironment of COAD. FUT1 regulated by miR-939-3p inhibit the expression of MUC2. Fusobacterium nucleatum may affect the expression of FUTs by affecting their transcription factors and miRNA levels. Moreover, Fusobacterium nucleatum promotes COAD progression through the miR-939-3p/FUT1/MUC2 axis. Conclusion: Fucosyltransferases play an important role and may be the mediator of Fusobacterium nucleatum promoting COAD progression.

The lncRNA TCONS_00021785/miR-21-5p/Trim33 axis regulates VMP1-mediated zymophagy, reduces the activation of trypsinogen, and promotes acinar cell recovery.

In the early stage of acute pancreatitis, trypsinogen in acinar cells is activated, and the cells clear trypsin through zymophagy to avoid damage. Studies have shown that the substrate of zymophagy is ubiquitinated pancreatin, but the mechanism of pancreatin ubiquitination and the regulatory mechanism of zymophagy are not fully understood. Our results show that Trim33 can enhance cell viability, reduce cell necrosis, and reduce trypsinogen activation. Trim33 is a key E3 ligase enzyme that mediates trypsin ubiquitination. The results showed that overexpression of Trim33 can significantly increase VMP1 mRNA and protein levels. However, knocking down Trim33 produced the opposite effect, which indicates that Trim33, as a transcriptional mediator, affects zymophagy by regulating the expression of VMP1. In addition, we explored the transcriptional regulation mechanism of the Trim33 molecule. Our research shows that lncRNA TCONS_00021785 can competitively bind miR-21-5p to upregulate Trim33, thereby initiating enzyme autophagy and reducing zymogen activation.

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma.

Ferroptosis is a recently discovered mode of cell death that inhibits tumor growth. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for analyzing tumor heterogeneity and the immune microenvironment at the single-cell level. We used CIBERSORT to identify cellular immune scores and found that monocytes had significantly infiltrated and were correlated with prognosis in cholangiocarcinoma. scRNA-seq data were extracted from the Gene Expression Omnibus database, and the FindCluster() package was used for cell cluster analysis, which obtained 21 cell clusters, and there was increased TNFSF13B-TFRC intercellular communication between monocytes and cholangiocytes. A weighted correlation network analysis was performed with the WGCNA package to obtain monocyte-related gene modules. Univariate and multivariate Cox analyses were then performed to further establish the signature, and the reliability of the signature was assessed by receiver operating characteristic curve and decision curve analysis. A nomogram signature based on the Kaplan-Meier survival analysis was established. We found that the communication between monocytes and malignant cells in cholangiocarcinoma may be a regulatory factor of ferroptosis in cancer cells. The prognostic stratification system of the three-gene signature related to monocytes and ferroptosis can accurately assess the prognostic risk for cholangiocarcinoma.

Genetic instability-related lncRNAs predict prognosis and influence the immune microenvironment in breast cancer.

Genome instability is a hallmark of cancer, and the function of lncRNAs in regulating genomic stability has been gradually characterized. However, the prognostic value of lncRNAs related to genetic instability has not been found in breast cancer. Here we constructed a genetic instability-related lncRNA model including U62317.4, SEMA3B-AS1, MAPT-AS1, AC115837.2, LINC01269, AL645608.7, and GACAT2. This model can evaluate the risk and predict the survival outcomes of patients. Further analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immunity and cornified envelope formation pathways. In addition, M2 macrophages infiltrated more obviously in the high-risk group. In summary, lncRNAs related to genetic instability may influence the development of breast cancer through immune infiltration and keratinization. This study provides a wider insight into breast cancer development and treatment.

ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes ANP32A, ANP32B, and ANP32E, are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that ANP32A, ANP32B, and ANP32E were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. ANP32A, ANP32B, and ANP32E had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that ANP32A, ANP32B, and ANP32E were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of ANP32B and ANP32E to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.

USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. According to reports, the mutation rate of COAD ranks third. However, whether these gene mutations are related to TMB and immune response is still unknown. Here, COAD somatic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics methods were used to study the relationships among gene mutations, COAD survival prognosis, and tumor immune response. A total of 22 of the top 40 mutations in TCGA and ICGC databases were the same. Among them, the USH2A mutation was associated with high TMB and poor clinical prognosis. According to Gene Set Enrichment Analysis (GSEA) and the CIBERSORT algorithm, we determined that the USH2A mutation upregulates signaling pathways involved in the immune system and the antitumor immune response. In cases with a USH2A mutation, the immune score and MSI score of TCGA samples increased, the expression of immune checkpoint genes decreased significantly, and the TIDE score decreased significantly. Dependent on the presence or absence of a USH2A mutation, TCGA COAD samples were analyzed for differentially expressed genes, 522 of which were identified. Using a univariate Cox analysis and LASSO COX analysis of these differential genes, a prediction model was established, which established significant differences in the infiltration of immune cells, immune checkpoint gene expression, immune score, MSI score, TMB, and TIDE in patients in high- and low-risk groups. In conclusion, mutation of USH2A is frequent in COAD and is related to an increase in TMB and the antitumor immunity. The differential genes screened by USH2A mutation allowed the construction of a risk model for predicting the survival and prognosis of cancer patients, in addition to providing new ideas for COAD immunotherapy.

Luminescent net-like inorganic scaffolds with europium-doped hydroxyapatite for enhanced bone reconstruction.

Bone reconstruction is an urgent problem during clinical treatment. In the past few decades, the construction of composite scaffolds has been a hot spot in the research field of bone tissue engineering (BTE). However, the disadvantages of composite materials raise our awareness to explore the potential application of hydroxyapatite (HAp) in bone substitutes due to the closest properties of HAp to natural bone tissue. In our study, we synthesized Eu3+-doped HAp (HAp:Eu3+) ultralong nanowires, which can be transformed to hydrophilic net-like scaffolds via a thiol-ene click reaction. The property of luminescence of HAp from Eu3+ is beneficial for identifying the relative position of materials and bone marrow mesenchymal stem cells (BMSCs). HAp:Eu3+ scaffolds with excellent cell biocompatibility could promote the expression of early bone formation markers (ALP and ARS) and enhance the expression of genes and proteins associated with osteogenesis (Runx 2, OCN, and OPN). In the end, the results of the in vivo osteogenesis experiment showed that pure HAp scaffolds presented different effects of bone tissue reconstruction compared with the composite scaffolds with HAp nanorods and polymer materials. The superior osteogenic effect could be observed in net-like pure HAp scaffold groups. Furthermore, the absorption of HAp:Eu3+ scaffolds could be monitored due to the luminescence property of Eu3+. This strategy based on ultralong HAp nanowires proved to be a new method for the construction of simple reticular scaffolds for potential osteogenic applications.

Amadis: A Comprehensive Database for Association Between Microbiota and Disease.

The human gastrointestinal tract represents a symbiotic bioreactor that can mediate the interaction of the human host. The deployment and integration of multi-omics technologies have depicted a more complete image of the functions performed by microbial organisms. In addition, a large amount of data has been generated in a short time. However, researchers struggling to keep track of these mountains of information need a way to conveniently gain a comprehensive understanding of the relationship between microbiota and human diseases. To tackle this issue, we developed Amadis (http://gift2disease.net/GIFTED), a manually curated database that provides experimentally supported microbiota-disease associations and a dynamic network construction method. The current version of the Amadis database documents 20167 associations between 221 human diseases and 774 gut microbes across 17 species, curated from more than 1000 articles. By using the curated data, users can freely select and combine modules to obtain a specific microbe-based human disease network. Additionally, Amadis provides a user-friendly interface for browsing, searching and downloading. We hope it can serve as a useful and valuable resource for researchers exploring the associations between gastrointestinal microbiota and human diseases.

The nomogram based on the 6-lncRNA model can promote the prognosis prediction of patients with breast invasive carcinoma.

Long non-coding RNA (lncRNA) is a prognostic biomarker for many types of cancer. Here, we aimed to study the prognostic value of lncRNA in Breast Invasive Carcinoma (BRCA). We downloaded expression profiles from The Cancer Genome Atlas (TCGA) datasets. Subsequently, we screened the differentially expressed genes between normal tissues and tumor tissues. Univariate Cox, LASSO regression, and multivariate Cox regression analysis were used to construct a lncRNA prognostic model. Finally, a nomogram based on the lncRNAs model was developed, and weighted gene co-expression network analysis (WGCNA) was used to predict mRNAs related to the model, and to perform function and pathway enrichment. We constructed a 6-lncRNA prognostic model. Univariate and multivariate Cox regression analysis showed that the 6-lncRNA model could be used as an independent prognostic factor for BRCA patients. We developed a nomogram based on the lncRNAs model and age, and showed good performance in predicting the survival rates of BRCA patients. Also, functional pathway enrichment analysis showed that genes related to the model were enriched in cell cycle-related pathways. Tumor immune infiltration analysis showed that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. In general, the 6-lncRNA prognostic model and nomogram could be used as a practical and reliable prognostic tool for invasive breast cancer.