Novel insights into biomarkers of progression in Desmoid tumor

Desmoid tumor (DT) is a rare neoplasm characterized by the proliferation of myofibroblastic cells that infiltrates and invades adjacent tissues. Due to its locally aggressive and recurrent nature, DT often causes local symptoms and can be challenging to manage clinically. Therefore, identifying biomarkers that can predict the progression of DT and guide treatment decisions is critical. This review summarizes several biomarkers that have been implicated in active surveillance (AS) and the prediction of postoperative recurrence and attempts to elucidate their underlying mechanisms. Some of these novel markers could provide prognostic value for clinicians, and ultimately help facilitate optimal and accurate therapeutic decisions for DT

Escherichia coli infection indicates favorable outcomes in patients with infected pancreatic necrosis

IntroductionInfected pancreatic necrosis (IPN) is a severe complication of acute necrotizing pancreatitis with increasing morbidity. Escherichia coli is the most frequently cultured microorganism in IPN. However, the implications of Escherichia coli infection on the outcomes of patients with IPN remain unclear. Therefore, this study aimed to evaluate the clinical impacts of Escherichia coli infection on IPN.MethodsA prospective database with consecutive patients with IPN between January 2010 and April 2022 at a tertiary hospital was post-hoc analyzed. The clinical and microbiological characteristics, surgical management, and follow-up data of patients with and without Escherichia coli infection were compared.ResultsA total of 294 IPN patients were enrolled in this cohort. Compared with non-Escherichia coli infection cases (n=80, 27.2%), patients with Escherichia coli infection (n=214, 72.8%) were characterized by more frequent polymicrobial infections (77.5% vs. 65.0%, P=0.04) but a lower occurrence of severe acute pancreatitis (SAP) (42.5% vs. 61.7%, P=0.003). In addition, significantly lower mortality (12.5% vs. 30.4%, p=0.002), fewer step-up surgical interventions (73.8% vs. 85.1%, P=0.025), and a lower rate of multiple organ failure (MOF) (25.0% vs. 40.2%, P=0.016) were also observed in patients with Escherichia coli infection. Multivariate analysis of mortality predictors indicated that MOF (odds ratio [OR], 6.197; 95% confidence interval [CI], 2.373–16.187; P<0.001) and hemorrhage (OR, 3.485; 95% CI, 1.623–7.487; P=0.001) were independent predictors associated with higher mortality in patients with IPN. Escherichia coli infection was significantly associated with a lower mortality (OR, 0.302; 95% CI, 0.121–0.751; P= 0.01).ConclusionEscherichia coli infection indicates a favorable prognosis in patients with IPN, although the mechanism needs further investigation

Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk

Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted the largest genome-wide association study in East Asians with 14,963 CRC cases and 31,945 controls and identified six new loci associated with CRC risk (P = 3.42 × 10−8 to 9.22 × 10−21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcription regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9) and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC loci. Our study provides insights into the genetic basis of CRC and suggests new biological pathways

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

A Differentially Private Big Data Nonparametric Bayesian Clustering Algorithm in Smart Grid

Smart systems, including smart grid (SG) and Internet of Things (IoT), have been playing a critical role in addressing contemporary issues. Taking full advantage of the big data generated by the smart grid can enhance the system stability and reliability, increase asset utilization, and offer better customer experience. To better support the data-driven smart grid, the machine learning technologies such as cluster analysis can be applied to process the massive data generated in smart grid. However, the process of cluster analysis may cause the disclosure of personal private information. In this paper, to achieve privacy-preserving cluster analysis in smart grid, we propose IDPC, a Differentially Private Clustering algorithm based on the Infinite Gaussian mixture model (IGMM). IDPC uses a combination of nonparametric Bayesian method and differential privacy. The nonparametric Bayesian method allows certain parameters to change along with the data and it is usually adopted in a clustering algorithm without a fixed number of clusters. The Laplace mechanism is used in data releasing process to make IDPC differentially private. We present how to make the nonparametric Bayesian clustering algorithm differentially private by adding Laplace noise. By security analysis and performance evaluation, IDPC is proved to be privacy-preserving as well as efficient.The work was supported in part by Beijing Natural Science Foundation under Grant 4182060 and in part by the National Natural Science Foundation of China under Grant 61972148

Combined Transcriptomic and Proteomic of <i>Corynebacterium pseudotuberculosis</i> Infection in the Spleen of Dairy Goats

Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a zoonotic chronic infectious disease. It mainly occurs in dairy goats reared in herds, and once it invades the dairy goats, it is difficult to completely remove it, causing great harm to the development of the sheep industry. This study mainly was based on TMT-based quantitative proteomics and RNA-seq methods to measure the spleen samples of infected dairy goats at different time periods. Nine four-month-old dairy goats were divided into three groups, with three goats in each group. The dairy goats in the first group (NC group) were inoculated with 1.0 mL of sterilized normal saline subcutaneously, and the second (72 h group) and third groups (144 h group) were inoculated with 1.0 mL of 1 × 107 cfu/mL bacterial solution subcutaneously in the neck. Significant changes in the protein and mRNA expression were observed in different infection and control groups. In the 72 h group, 85 genes with differential genes and proteins were up-regulated and 91 genes were down-regulated in this study. In the 144 h group, 38 genes with differential genes and proteins were up-regulated and 51 genes were down-regulated. It was found that 21 differentially expressed genes and proteins were co-up-regulated in the two groups. There were 20 differentially expressed genes and proteins which were co-down-regulated in both groups. The 72 h group were mainly enriched in protein processing in the endoplasmic reticulum, lysosome, amino sugar and nucleotide sugar metabolism and the estrogen signaling pathway. In the 144 h group, they were protein processing in the endoplasmic reticulum pathway which was enriched by mRNA–proteins pairs co-upregulated by the five pairs. The combined transcriptomic and proteomic analyses were performed to provide insights into the effects of C. pseudotuberculosis through several regulatory features and pathways. We found that in the early stage of infection (72 h), the co-upregulated gene–protein pairs were enriched in multiple pathways, which jointly defended against a bacterial invasion. However, in the later stages of infection (144 h), when the disease stabilizes, a few co-upregulated gene–protein pairs played a role in protein processing in the endoplasmic reticulum pathway. In addition, the mRNA and protein expressions of dairy goats infected with the bacteria at different periods of time indicated the adaptability of dairy goats to the bacteria. At the same time, it guides us to carry out a corresponding treatment and feeding management for dairy goats according to different periods of time

Analysis and Evaluation of the Flagellin Activity of <i>Bacillus amyloliquefaciens</i> Ba168 Antimicrobial Proteins against <i>Penicillium expansum</i>

Blue mold caused by Penicillium expansum is one of the most common apple diseases, and it is becoming a serious threat in apple production. The strain Bacillus amyloliquefaciens Ba168 showed high levels of antimicrobial activity in our previous study. To analyze the antimicrobial protein of Ba168, a high-resolution LC-MS/MS proteomic analysis was performed. A total of 1155 proteins were identified from 5233 unique peptides. A total of 16 potential antimicrobial-activity-related proteins were identified; 10 of these proteins have direct antimicrobial effects, while 6 of these proteins are associated with the formation of antimicrobial substances. Then, an antifungal protein of Ba168 was isolated and purified by the sequential chromatography of DEAE Bio-sep FF anion exchange and Sephadex G-75. The single protein, named BP8-2, showed antifungal activity towards Penicillium expansum. The peptide mass fingerprinting of the protein band of BP8-2 had a high similarity with the amino acid sequences of flagellin protein. The results showed that BP8-2 significantly inhibited the growth of P. expansum and slowed the spread of apple blue mold. The results indicated that flagellin is one of the important antimicrobial substances from Ba168

Observation of enhanced spin-spin correlations at triple point in 2D ferromagnetic Cr2X2Te6 (X=Si, Ge)

The domain dynamics and spin-spin correlation of 2D ferromagnets Cr2X2Te6 (X=Si, Ge) are investigated by a composite magnetoelectric method. The magnetic field-temperature phase diagrams for both in-plane and out-of-plane magnetic fields disclose a triple point around TC and 1 kOe, where ferromagnetic, paramagnetic, and spin-polarized phases coexist. The magnetoelectric signal shows peak features at the phase boundaries and reaches the maximum at the triple point, suggesting significant enhancement of spin-spin correlations at this point. A comparison between two systems reveals that the spin-spin correlations in Cr2Si2Te6 are stronger than that in Cr2Ge2Te6.Comment: 17 pages, 6 figures, submitted to PR

Association of fat-soluble vitamins (A, D, and E) status with humoral immune response to COVID-19 inactivated vaccination

BackgroundFat-soluble vitamins (A, D, and E) are essential for the proper functioning of the immune system and are of central importance for infection risk in humans. Vitamins A, D, and E have been reported to be associated with the immune response following vaccination; however, their effects on the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination remain unknown.MethodsWe measured the neutralizing antibody titers against wild type and omicron within 98 days after the third homologous boosting shot of inactivated SARS-CoV-2 vaccine (BBIBP-CorV or CoronaVac) in 141 healthy adults in a prospective, open-label study. High-performance liquid chromatography-tandem mass spectroscopy was used to determine the concentrations of plasma vitamins A, D, and E.ResultsWe found that the anti-wide-type virus and anti-omicron variant antibody levels significantly increased compared with baseline antibody levels (P &lt; 0.001) after the third vaccination. 25(OH)D3 was significantly negatively associated with the baseline anti-wide-type virus antibody concentrations [beta (95% CI) = −0.331 (−0.659 ~ −0.003)] after adjusting for covariates. A potentially similar association was also observed on day 98 after the third vaccination [beta (95% CI) = −0.317 (−0.641 ~ 0.007)]. After adjusting for covariates, we also found that 25(OH)D3 was significantly negatively associated with the seropositivity of the anti-omicron variant antibody at day 98 after the third vaccination [OR (95% CI) = 0.940 (0.883 ~ 0.996)]. The association between plasma 25(OH)D3 with anti-wild-type virus antibody levels and seropositivity of anti-omicron variant antibodies were persistent in subgroup analyses. We observed no association between retinol/α-tocopherol and anti-wide-type virus antibody levels or anti-omicron variant antibody seropositive in our study.ConclusionThe third inactivated SARS-CoV-2 vaccination significantly improved the ability of anti-SARS-CoV-2 infection in the human body. Higher vitamin D concentrations could significantly decrease the anti-wide-type virus-neutralizing antibody titers and anti-omicron variant antibody seropositive rate after the inactivated SARS-CoV-2 vaccination in people with adequate levels of vitamin D, better immune status, and stronger immune response; further studies comprising large cohorts of patients with different nutritional status are warranted to verify our results