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Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.

Shigellosis is the major cause of dysentery globally. It is mainly attributed to two Shigella species, Shigella sonnei and Shigella flexneri, which leads to approximately 165 million infections and 1.1 million deaths each year. Rapid increase and widening of spectrum in antibiotics resistance make Shigella hard to be adequately controlled through existing prevention and treatment measures. It has also been observed that enhanced virulence and advent of antibiotic resistance (AR) could arise almost simultaneously. However, genetic linkages between the two factors are missing or largely ignored, which hinders experimental verification of the relationship. In this study, we sequenced 15 clinically isolated S. flexneri strains. Genome assembly, annotation and comparison were performed through routine pipelines. Differential resistant profiles of all 15 S. flexneri strains to nine antibiotics were experimentally verified. Virulence factors (VFs) belonging to 4 categories and 31 functional groups from the Virulence Factor Database (VFDB) were used to screen all Shigella translated CDSs. Distribution patterns of virulence factors were analysed by correlating with the profiles of bacterial antibiotics resistance. In addition, multi-resistant S. flexneri strains were compared with antibiotic-sensitive strains by focusing on the abundance or scarcity of specific groups of VFs. By doing these, a clear view of the relationships between virulence factors and antibiotics resistance in Shigella could be achieved, which not only provides a set of genetic evidence to support the interactions between VFs and AR but could also be used as a guidance for further verification of the relationships through manipulating specific groups of virulence factors.

Background Nowadays, lung cancer seriously affects human health in the world. Therefore, it is of great significance to develop effective anti-lung cancer drugs. Methods In this work, chalcone derivative HYQ97 was designed via a molecular hybridization strategy. It was synthesized by the cycloaddition in the presence of sodium ascorbate under mild conditions. Lung cancer cell lines were cultured to investigate its antitumor effects in vitro and in vivo. Results HYQ97 inhibited the proliferation of lung cancer cell lines. Specifically, its IC50 value against lung cancer A549 cells was 74.26 nM. It could inhibit heat shock protein 90 (Hsp90) and degrade its client proteins in a dose-dependent manner. Furthermore, HYQ97 suppressed the epithelial mesenchymal transition process and induced apoptosis of A549 cells. Importantly, HYQ97 also had significant inhibitory effects on tumor growth in vivo. Conclusions Chalcone derivative HYQ97 is a promising candidate for lung cancer treatment.

Glycogen is a highly branched polysaccharide that is widely present in all life domains. It has been identified in many bacterial species and functions as an important energy storage compound. In addition, it plays important roles in bacterial transmission, pathogenicity, and environmental viability. There are five essential enzymes (coding genes) directly involved in bacterial glycogen metabolism, which forms a single operon glgBXCAP with a suboperonic promoter in glgC gene in Escherichia coli. Currently, there is no comparative study of how the disruptions of the five glycogen metabolism genes influence bacterial phenotypes, such as growth rate, biofilm formation, and environmental survival, etc. In this study, we systematically and comparatively studied five E. coli single-gene mutants (ΔglgC, ΔglgA, ΔglgB, ΔglgP, ΔglgX) in terms of glycogen metabolism and explored their phenotype changes with a focus on environmental stress endurance, such as nutrient deprivation, low temperature, desiccation, and oxidation, etc. Biofilm formation in wild-type and mutant strains was also compared. E. coli wild-type stores the highest glycogen content after around 20-h culture while disruption of degradation genes (glgP, glgX) leads to continuous accumulation of glycogen. However, glycogen primary structure was abnormally changed in ΔglgP and ΔglgX. Meanwhile, increased accumulation of glycogen facilitates the growth of E. coli mutants but reduces glucose consumption in liquid culture and vice versa. Glycogen metabolism disruption also significantly and consistently increases biofilm formation in all the mutants. As for environmental stress endurance, glycogen over-accumulating mutants have enhanced starvation viability and reduced desiccation viability while all mutants showed decreased survival rate at low temperature. No consistent results were found for oxidative stress resistance in terms of glycogen metabolism disruptions, though ΔglgA shows highest resistance toward oxidation with unknown mechanisms. In sum, single gene disruptions in glgBXCAP operon significantly influence bacterial growth and glucose consumption during culture. Accumulation and structure of intracellular glycogen were also significantly altered. In addition, we observed significant changes in E. coli environmental viabilities due to the deletions of certain genes in the operon. Further investigations shall be focused on the molecular mechanisms behind these phenotype changes.

Shigellosis is a highly infectious disease that is mainly transmitted via fecal-oral contact of the bacteria Shigella. Four species have been identified in Shigella genus, among which Shigella flexneri is used to be the most prevalent species globally and commonly isolated from developing countries. However, it is being replaced by Shigella sonnei that is currently the main causative agent for dysentery pandemic in many emerging industrialized countries such as Asia and the Middle East. For a better understanding of S. sonnei virulence and antibiotic resistance, we sequenced 12 clinical S. sonnei strains with varied antibiotic-resistance profiles collected from four cities in Jiangsu Province, China. Phylogenomic analysis clustered antibiotic-sensitive and resistant S. sonnei into two distinct groups while pan-genome analysis reveals the presence and absence of unique genes in each group. Screening of 31 classes of virulence factors found out that type 2 secretion system is doubled in resistant strains. Further principle component analysis based on the interactions between virulence and resistance indicated that abundant virulence factors are associated with higher levels of antibiotic resistance. The result present here is based on statistical analysis of a small sample size and serves basically as a guidance for further experimental and theoretical studies.

Candidiasis causes high morbidity and mortality among immunocompromised patients. Antifungal drug resistance and cytotoxicity highlight the need of effective antifungal therapeutics. In this study, we found that kalopanaxsaponin A (KPA), a triterpenoid saponin natural product, could inhibit the proliferation of various Candida species, and exerted a fungicidal effect against C. albicans. To further explore its antifungal action mode, spectrofluorophotometer, fluorescence microscopy and transmission electron microscopy were performed, showing that KPA treatment induced the accumulation of intracellular reactive oxygen species (ROS), resulting in mitochondrial dysfunction. Meanwhile, KPA treatment also broke down the membrane barrier of C. albicans causing the leakage of intracellular trehalose, the entrance of extracellular impermeable substance and the decrease of ergosterol content. Both ROS accumulation and membrane destruction contributed to the death of C. albicans cells. Our work preliminarily elucidated the potential mechanisms of KPA against C. albicans on a cellular level, and might provide a potential option for the treatment of clinical candidiasis.

Lung cancer is the leading cause of cancer deaths in both men and women in the US. While most sporadic lung cancer cases are related to environmental factors such as smoking, genetic susceptibility may also play an important role and a number of lung cancer associated single-nucleotide polymorphisms (SNPs) have been identified although many remain to be found. The collective effects of genome-wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have been linked with quantitative variations of complex traits and diseases. Here we studied MAC in lung cancer using previously published SNPs data sets (US and Finland samples) and found higher MAC in cases relative to matched controls. A set of 5400 SNPs with MA (MAF

Kallmann syndrome (KS) is a congenital hypogonadotropic hypogonadism that coincides with anosmia or hyposmia. Although this rare genetic disease has a very low incidence, it harbors a complicated genetic heterogeneity, which indicates X-linked, autosomal, and oligogenic inheritance of puberty, sexuality, reproductivity, and olfactory defects. There has been limited elucidation of molecular etiologies completed to date. Here, a chromosome reciprocal translocation (46, XX, t (3; 13) (p13; q22)) was identified in a 27-year-old Chinese female diagnosed with KS. Genome sequencing found an intronic breakpoint of SCEL in chromosome 13 and an intergenic breakpoint between ROBO1 and ROBO2 in chromosome 3. This translocation resulted in the reduced expression levels of these genes. An array-CGH test captured no abnormal genomic copy numbers of clinical significance. The basic features of all known KS-related genes were also reviewed and analyzed for their roles in KS onset with bioinformatic methods. Signal pathway and gene enrichment analysis of KS-related genes suggested that these genes have integrated functions in neuronal migration and differentiation. An interesting chromosome locational pattern of KS-related genes was also discovered. This study provided constructive clues for further investigations into the molecular etiology of KS.

Shigellosis is a highly infectious disease that are mainly transmitted via faecal-oral contact of the bacteria Shigella. Four species have been identified in Shigella genus, among which S. flexneri is used to be the most prevalent species globally and commonly isolated from developing countries. However, it is being replaced by S. sonnei that is currently the main causative agent for dysentery pandemic in many emerging industrialized countries such as Asia and the Middle East with unclear reasons. For a better understanding of S. sonnei virulence and antibiotic resistance, we sequenced 12 clinical S. sonnei strains with varied antibiotic-resistance profiles collected from four cities in Jiangsu Province, China. Phylogenomic analysis clustered antibiotic sensitive and resistant S. sonnei into two distinct groups while pangenome analysis reveals the presence and absence of featured genes in each group. Screening of 31 classes of virulence factors found out that type 2 secretion system is doubled in resistant strains. Further principle component analysis based on the interactions between virulence and resistance indicated that abundant virulence factors are associated with higher resistant phenotypes. The result present here is based on statistical analysis of a small sample size and serves basically as a guidance for further experimental and theoretical studies.

Objective The aim of this study was to investigate the shared molecular pathways of obesity and cancer by exploring the role of RIZ1 in obesity and the phospatidylinositol 3-kinase (PI3K)/V-Akt murine thymoma viral oncogene homolog (PKB) (AKT)/mechanistic target of rapamycin (mTOR) pathway. Methods Male wild type (WT) and Riz1(-/-) mice (KO) were fed a standard diet (STD) or a high-fat (HF) diet for up to 8 months. These mice were studied for phenotypic and molecular changes. Results Riz1(-/-) mice gained more weight on a HF diet compared to WT mice, with higher free fatty acid and increased visceral fat. Metabolic cage analysis of Riz1(-/-) mice showed lower oxygen consumption but no changes in food intake and ambulatory activity. Riz1(-/-) mice showed impaired glucose regulation but no change in insulin sensitivity. RNA-seq and quantitative RT-PCR analysis found altered expression in certain glycolysis and ATP production genes such as Ubiad1, Atp5g2, and Cyp4a12. The PI3K/AKT/mTOR pathway was activated in the Riz1(-/-) mice fed a HF diet with higher Akt3 mRNA levels and increased phosphorylation of AKT (Ser473), mTOR, and S6. Conclusions The results identify RIZ1 as an important regulator of both Akt3 transcription and AKT phosphorylation and suggest a role for RIZ1 in HF-induced obesity and the AKT pathway.

Schizophrenia is a common neuropsychiatric disorder with a lifetime risk of 1%. Accumulation of common polygenic variations has been found to be an important risk factor. Recent studies showed a role for the enrichment of minor alleles (MAs) of SNPs in complex diseases such as Parkinson’s disease. Here we similarly studied the role of genome wide MAs in schizophrenia using public datasets. Relative to matched controls, schizophrenia cases showed higher average values in minor allele content (MAC) or the average amount of MAs per subject. By risk prediction analysis based on weighted genetic risk score (wGRS) of MAs, we identified an optimal MA set consisting of 23 238 variants that could be used to predict 3.14% of schizophrenia cases, which is comparable to using 22q11 deletion to detect schizophrenia cases. Pathway enrichment analysis of these SNPs identified 30 pathways with false discovery rate (FDR)

Lung cancer is the leading cause of cancer deaths in both men and women in the US. While most sporadic lung cancer cases are related to environmental factors such as smoking, genetic susceptibility may also play an important role and a number of lung cancer associated single nucleotide polymorphisms (SNPs) have been identified although many remain to be found. The collective effects of genome wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have been linked with quantitative variations of complex traits and diseases. Here we studied MAC in lung cancer using previously published SNP datasets and found higher MAC in cases relative to matched controls. A set of 25883 SNPs with MA (MAF < 0.5) more common in cases (P < 0.1) was found to have the best predictive accuracy. A weighted risk score calculated by using this set can predict 2.6% of lung cancer cases (100% specificity). These results identify a novel genetic risk element or higher MAC in lung cancer susceptibility and provide a useful genetic method to identify a small fraction of lung cancer cases.

Recent studies found three Neolithic super-grandfather Y haplotypes among Han Chinese, consistent with the legend of Yan and Huang Emperors. Individuals of royal and noble ancestry or high social economic status (SES) are known to practice assortative mating and consanguineous marriages, which can produce offspring of both higher and lower than average fitness. However, the roles of the super-grandfather Y haplotypes and their descendant lines in history, fitness, and the male biased autism spectrum disorder (ASD) remain unknown. Here we show a link between the super-grandfathers and the legend ofYan-HuangEmperors and between their descendant haplotypes and ASD. We found that subjects carrying the O3a1c and O3a2c1a super-grandfather haplotypes were enriched withYanandHuangrelated surnames, respectively, in two independent datasets of 1564 and 772 male Han subjects. We identified high and low SES descendant haplotypes of the super-grandfathers using the Han dataset of the 1000 genomes project based on two criteria: more descendant branches and fewer mutations before star-like expansions. By genotyping 505 fathers of ASD affected male children from the Autism Clinical and Genetic Resources in China with surnames either closely related to Huang (Ying group) or less related (Ji group), we found the high SES haplotypes within the O3a2c1a clade at ∼2 fold lower (odds ratio 2.05, 95% CI 1.28-3.26, P=0.0026) while the low SES haplotypes at ∼2 fold higher frequency (odds ratio 1.92, 95% CI 1.01-3.64, P = 0.046) in the fathers relative to 505 normal subjects. The fraction of low SES haplotypes was greater than that of high SES in ASD fathers of the Ying group, in contrast to Ying controls or the Ji fathers and Ji controls. Consistently, analysis of 2366 ASD affected children showed higher male to female ratio for Ying versus Ji group (6.52 +/-1.11 v 4.59 +/-0.41, P = 0.028, one tailed). These results provide evidence for the Yan-Huang legend and suggest a role for Y in ASD.

Parents of children affected with autism spectrum disorders (ASD) often have mild forms of autistic-like characteristics. Past studies have focused on searching for individual genetic risk loci of ASD. Here we studied the overall properties of the genomes of ASD trios by using previously published genome-wide data for common SNPs. The pairwise genetic distance (PGD) between a spousal pair with ASD-affected children was found smaller than that of a random pair selected among the spouses in the ASD trios, and spousal relatedness correlated with severe forms of ASD. Furthermore, for a set of 970 ASD associated SNPs, cases showed higher homozygous minor allele content than parents. These results indicate new genetic elements in the broad phenotypes of parents with ASD-affected offspring and in ASD pathogenesis.HighlightsThe overall properties of the genomes of ASD trios show ASD specific features.A spousal pair with ASD-affected children showed smaller genetic distance than that of a randomly selected pair among the spouses in the ASD trios.Minor allele contents in ASD-associated SNPs in ASD cases were greater than those in the parents of cases.