Bragg Spot Finder (BSF): a new machine-learning-aided approach to deal with spot finding for rapidly filtering diffraction pattern images.

Macromolecular crystallography contributes significantly to understanding diseases and, more importantly, how to treat them by providing atomic resolution 3D structures of proteins. This is achieved by collecting X-ray diffraction images of protein crystals from important biological pathways. Spotfinders are used to detect the presence of crystals with usable data, and the spots from such crystals are the primary data used to solve the relevant structures. Having fast and accurate spot finding is essential, but recent advances in synchrotron beamlines used to generate X-ray diffraction images have brought us to the limits of what the best existing spotfinders can do. This bottleneck must be removed so spotfinder software can keep pace with the X-ray beamline hardware improvements and be able to see the weak or diffuse spots required to solve the most challenging problems encountered when working with diffraction images. In this paper, we first present Bragg Spot Detection (BSD), a large benchmark Bragg spot image dataset that contains 304 images with more than 66 000 spots. We then discuss the open source extensible U-Net-based spotfinder Bragg Spot Finder (BSF), with image pre-processing, a U-Net segmentation backbone, and post-processing that includes artifact removal and watershed segmentation. Finally, we perform experiments on the BSD benchmark and obtain results that are (in terms of accuracy) comparable to or better than those obtained with two popular spotfinder software packages (Dozor and DIALS), demonstrating that this is an appropriate framework to support future extensions and improvements.

Evaluation of factors associated the expression of anti-HBs in children in Hunan Province, China.

BACKGROUND AND OBJECTIVES: Vaccine is the most essential avenue to prevent hepatitis B virus (HBV) infection in infants and preschool children in China, with the largest populations carrying HBV in the world. This study aimed to evaluate the factors associating the response level of anti-HBs in children, providing instructions for HBV prevention clinically. METHODS: The children taking physical examinations in the Third Xiangya Hospital from January 2013 to April 2020 were recruited. Telephone follow-up were adopted to collect further information. Univariate logistic regression was used to analyse the relationship between age and anti-HBs expression. Grouping by age and anti-HBs expression, we used chi-square test and T test to compare qualitative and quantitative data between positive group and negative group in each age subgroup. The meaningful variables (P < 0.10) in chi-square test or T test were further assessed with collinearity and chosen for univariate and multivariate logistic regression analysis by the stepwise backward maximum likelihood method (αin = 0.05, αout = 0.10). RESULTS: A total of 5838 samples (3362 males, 57.6%) were enrolled. In total, the incidence of negative anti-HBs increased with age[OR = 1.037(1.022-1.051)]. Multivariate logistic regression analysis illustrated that anemia[OR = 0.392(0.185-0.835)], age[OR = 2.542(1.961-3.295)] and Vit D[OR = 0.977(0.969-0.984)] in 0.5-2.99 years subgroup, Zinc deficiency[OR = 0.713(0.551-0.923] and age[OR = 1.151(1.028-1.289)] in 3-5.99 years subgroup, Vit D[OR = 0.983(0.971-0.995)] in 12-18 years subgroup had significant association with anti-HBs. CONCLUSIONS: This retrospective study illustrated that age, anemia status, zinc deficiency and vitamin D were associated with anti-HBs expression in specific age groups of children, which could serve as a reference for the prevention of HBV.

Interaction between m6A and ncRNAs and Its Association with Diseases.

Noncoding RNAs (ncRNA) are a kind of endogenous RNA that regulate many vital bioprocesses with limited ability to encode polypeptides. Most of them are involved in transcriptional and posttranscriptional regulations, thus showing some biological effects. N6-methyladenosine (m6A) RNA modification is a reversible modification that adjusts RNA's functions and stability. The enzymes that regulate m6A can be divided into "writers," "readers," and "erasers." Mechanically, m6A modification of microRNA is mainly identified by DGVR8, participating in the processing of primary micro-RNAs, while m6A modification on long noncoding RNA (lnc-RNA) can change its spatial structure and stability to regulate its RNA- or protein-binding ability. The m6A-modified lnc-RNA and circular RNA can act as competing endogenous RNAs, sponge downstream miRNA. Moreover, ncRNA can also regulate m6A level of downstream molecules. Here, we elaborate on recent advances about pathways and underlying molecular mechanisms of how the interaction between m6A and ncRNA is involved in the occurrence and development of various diseases, especially cancer.

Identification and validation of four photodynamic therapy related genes inhibiting MAPK and inducing cell cycle alteration in squamous cell carcinoma.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and photodynamic therapy (PDT) is a promising modality against cSCC. This study investigated the impact of PDT on the MAPK pathway and cell cycle alternation of cSCC as well as the related molecular mechanisms. Method: Expressing mRNA profile data sets GSE98767, GSE45216, and GSE84758 were acquired from the GEO database. The functions of differently expressed genes (DEGs) were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Least absolute shrinkage and selection operator (Lasso) analysis were used to establish a diagnosis model based on GSE98767. A correlation analysis and a protein-protein interaction (PPI) network were used to evaluate the relationship between cSCC-PDT-related genes and the MAPK pathway. Single-sample gene set enrichment analysis (ssGSEA) was performed on GSE98767 to estimate MAPK activation and cell cycle activity. Finally, the effect of MAPK activation on the cell cycle was explored in vitro. Result: Four cSCC-PDT-related genes, DUSP6, EFNB2, DNAJB1, and CCNL1, were identified as diagnostic markers of cSCC, which were upregulated in cSCC or LC50 PDT-protocol treatment and negatively correlated with the MAPK promoter. Despite having a smaller MAPK activation score, cSCC showed higher cell cycle activity. The PDT treatment suppressed the G1 to G2/M phase in JNK overexpressed A431 cells. Conclusion: CCNL1, DNAJB1, DUSP6, and EFNB2 were identified as potential PDT target genes in cSCC treatment, whose potential therapeutic mechanism was inhibiting the MAPK pathway and inducing cell cycle alternation.