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Abstract Background Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. Methods Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. Results Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. Conclusion This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.

Abstract Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes.

Down syndrome (DS) is caused by the presence of an extra copy of the entire or a portion of human chromosome 21 (HSA21). This genomic alteration leads to elevated expression of numerous HSA21 genes, resulting in a variety of health issues in individuals with DS. Among the genes located in the DS “critical region” of HSA21, Down syndrome cell adhesion molecule (DSCAM) plays an important role in neuronal development. There is a growing body of evidence underscoring DSCAM’s involvement in various DS-related disorders. This review aims to provide a concise overview of the established functions of DSCAM, with a particular focus on its implications in DS. We delve into the roles that DSCAM plays in DS-associated diseases. In the concluding section of this review, we explore prospective avenues for future research to further unravel DSCAM’s role in DS and opportunities for therapeutic treatments.

ObjectiveTo investigate the content of copper in food in He’nan Province， and to evaluate the dietary intake of copper from food and its potential health risks in He’nan population.MethodsBased on the data of copper in foods in He’nan Province in 2014—2021 and the data of Chinese food consumption surveillance in 2012， the dietary intake of copper in He’nan population was evaluated by simple distribution model method.ResultsThe mean and high level （P97.5） daily intake of copper from food by the total survey population were 1.75 mg/d， and 3.51 mg/d， respectively. Of the total survey population， the percentage of people with a dietary intake of copper < estimated average requirement （EAR）， EAR - recommended nutrient intake （RNI）， RNI - tolerable upper intake level （UL）， ≥ UL were 0.21%， 1.16%， 98.10%， and 0.53%， respectively. Cereal （24.51%-40.50%）， vegetables （15.88%-30.98%）， fruits （4.14%-7.72%）， and drinking water （4.70%-6.91%） were the main sources of the dietary intake of copper.ConclusionThe copper intake from food in He’nan population was generally acceptable， and its health risk was small. The proportions of children in 2-3 years old group with an intake of copper less than EAR and exceeding UL were comparatively high， which need to be concerned.

Objective To investigate whether BZLF1 and BILF1 can inhibit the expression of major histocompatibility complex(MHC)molecules in Raji cells during Epstein-Barr virus (EBV) lytic cycle. Methods Reactivation was triggered by treating Raji cells with TPA and NaB. As the marker protein during EBV lytic state, the BZLF1 protein expression was detected by Western blot. The expression of BZLF1 and BILF1 at transcription level was analyzed by RT-qPCR in EBV reactivation. The expression of MHC class Ⅱ and MHC class Ⅰ molecules was analyzed by flow cytometry. After BZLF1 and BILF1 over-expression or gene silencing via siRNA in Raji cells by electroporation, the expression of MHC class Ⅱ and MHC class Ⅰ molecules was detected by flow cytometry and Western blot respectively. Results EBV reactivation can be triggered with TPA and NaB. The BZLF1 and BILF1 gene expression was observed by inducing EBV reactivation in Raji cells. The levels of MHC class Ⅱ and MHC class Ⅰ molecules were down regulated by inducing EBV reactivation or ectopic expression of BZLF1 and BILF1 (P＜0.05). Expression of MHC class Ⅱ and MHC class Ⅰ molecules was restored by specific siRNA. Conclusions BZLF1 and BILF1 down regulate the expression of MHC class Ⅱ and MHC class Ⅰ molecules in EBV reactivation respectively.

With the implementation of the C-strain vaccine, classical swine fever (CSF) has been under control in China, which is currently in a chronic atypical epidemic situation. African swine fever (ASF) emerged in China in 2018 and spread quickly across the country. It is presently occurring sporadically due to the lack of commercial vaccines and farmers’ increased awareness of biosafety. Atypical porcine pestivirus (APPV) was first detected in Guangdong Province, China, in 2016, which mainly harms piglets and has a local epidemic situation in southern China. These three diseases have similar clinical symptoms in pig herds, which cause considerable losses to the pig industry. They are difficult to be distinguished only by clinical diagnosis. Therefore, developing an early and accurate simultaneous detection and differential diagnosis of the diseases induced by these viruses is essential. In this study, three pairs of specific primers and Taq-man probes were designed from highly conserved genomic regions of CSFV (5′ UTR), African swine fever virus (ASFV) (B646L), and APPV (5′ UTR), followed by the optimization of reaction conditions to establish a multiplex real-time PCR detection assay. The results showed that the method did not cross-react with other swine pathogens (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), foot-and-mouth disease virus (FMDV), pseudorabies virus (PRV), porcine parvovirus (PPV), and bovine viral diarrhea virus BVDV). The sensitivity results showed that CSFV, ASFV, and APPV could be detected as low as 1 copy mL−1; the repeatability results showed that the intra-assay and inter-assay coefficient of variation of ASFV, CSFV, and APPV was less than 1%. Twenty-two virus samples were detected by the multiplex real-time PCR, compared with national standard diagnostic and patented method assay for CSF (GB/T 27540–2011), ASF (GB/T 18648–2020), and APPV (CN108611442A), respectively. The sensitivity of this triple real-time PCR for CSFV, ASFV, and APPV was almost the same, and the compliance results were the same (100%). A total of 451 clinical samples were detected, and the results showed that the positive rates of CSFV, ASFV, and APPV were 0.22% (1/451), 1.3% (6/451), and 0% (0/451), respectively. This assay provides a valuale tool for rapid detection and accurate diagnosis of CSFV, ASFV, and APPV.

Abstract Background Classical swine fever (CSF), African swine fever (ASF), and atypical porcine pestivirus (APPV) are acute, virulent, and contagious viral diseases currently hampering the pig industry in China, which result in mummification or stillbirths in piglets and mortality in pigs. Diagnostic assays for the differentiation of infection and vaccination of CSFV, in addition to the detection of ASFV and APPV, are urgently required for better prevention, control, and elimination of these viral diseases in China. Methods A quadruple PCR-based gene microarray assay was developed in this study to simultaneously detect wild-type and vaccine CSFV strains, ASFV and APPV according to their conserved regions. Forty-two laboratory-confirmed samples, including positive samples of 10 other swine viral diseases, were tested using this assay to confirm its high specificity. Results This assay's limit of detections (LODs) for the wild-type and vaccine CSFV were 6.98 and 6.92 copies/µL. LODs for ASFV and APPV were 2.56 × 10 and 1.80 × 10 copies/µL, respectively. When compared with standard RT-PCR or qPCR for CSFV (GB/T 26875–2018), ASFV (MARR issue No.172), or APPV (CN108611442A) using 219 clinical samples, the coincidence was 100%. The results showed that this assay with high sensitivity could specifically distinguish ASFV, APPV, and CSFV, including CSFV infection and immunization. Conclusion This assay provides a practical, simple, economic, and reliable test for the rapid detection and accurate diagnosis of the three viruses and may have good prospects for application in an epidemiological investigation, prevention, and control and elimination of these three diseases.

Neural networks are groups of interconnected neurons, which collectively give rise to emergent neural activities and functions that cannot be explained by the activity of single neurons. How neural networks are assembled is poorly understood. While all aspects of neuronal development are essential for the assembly of a functional neural network, we know little about high-level principles that govern neural network assembly beyond the basic steps of neuronal development. In this review, I use vertebrate spinal motor columns, Drosophila larval motor circuit, and the lamination in the vertebrate inner retina to highlight the spatial codes, temporal codes, and cell adhesion codes for neural network assembly. Nevertheless, these examples only show preliminary connections between neural network development and their functions. Much needs to be done to understand the molecular mechanisms that underlie the assembly of functional neural networks.