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Abstract Background The fiber yield and quality of cotton are greatly and periodically affected by water deficit. However, the molecular mechanism of the water deficit response in cotton fiber cells has not been fully elucidated. Results In this study, water deficit caused a significant reduction in fiber length, strength, and elongation rate but a dramatic increase in micronaire value. To explore genome-wide transcriptional changes, fibers from cotton plants subjected to water deficit (WD) and normal irrigation (NI) during fiber development were analyzed by transcriptome sequencing. Analysis showed that 3427 mRNAs and 1021 long noncoding RNAs (lncRNAs) from fibers were differentially expressed between WD and NI plants. The maximum number of differentially expressed genes (DEGs) and lncRNAs (DERs) was identified in fibers at the secondary cell wall biosynthesis stage, suggesting that this is a critical period in response to water deficit. Twelve genes in cotton fiber were differentially and persistently expressed at ≥ five time points, suggesting that these genes are involved in both fiber development and the water-deficit response and could potentially be used in breeding to improve cotton resistance to drought stress. A total of 540 DEGs were predicted to be potentially regulated by DERs by analysis of coexpression and genomic colocation, accounting for approximately 15.76% of all DEGs. Four DERs, potentially acting as target mimics for microRNAs (miRNAs), indirectly regulated their corresponding DEGs in response to water deficit. Conclusions This work provides a comprehensive transcriptome analysis of fiber cells and a set of protein-coding genes and lncRNAs implicated in the cotton response to water deficit, significantly affecting fiber quality during the fiber development stage.

Abstract Background Risk scores are needed to predict the risk of death in severe coronavirus disease 2019 (COVID-19) patients in the context of rapid disease progression. Methods Using data from China (training dataset, n = 96), prediction models were developed by logistic regression and then risk scores were established. Leave-one-out cross validation was used for internal validation and data from Iran (test dataset, n = 43) was used for external validation. Results A NSL model (area under the curve (AUC) 0.932) and a NL model (AUC 0.903) were developed based on neutrophil percentage and lactate dehydrogenase with and without oxygen saturation (SaO2) using the training dataset. AUCs of the NSL and NL models in the test dataset were 0.910 and 0.871, respectively. The risk scoring systems corresponding to these two models were established. The AUCs of the NSL and NL scores in the training dataset were 0.928 and 0.901, respectively. At the optimal cut-off value of NSL score, the sensitivity and specificity were 94% and 82%, respectively. The sensitivity and specificity of NL score were 94% and 75%, respectively. Conclusions These scores may be used to predict the risk of death in severe COVID-19 patients and the NL score could be used in regions where patients' SaO2 cannot be tested.

Abstract Background Verticillium wilt is a widespread and destructive disease, which causes serious loss of cotton yield and quality. Long non-coding RNA (lncRNA) is involved in many biological processes, such as plant disease resistance response, through a variety of regulatory mechanisms, but their possible roles in cotton against Verticillium dahliae infection remain largely unclear. Results Here, we measured the transcriptome of resistant G. hirsutum following infection by V. dahliae and 4277 differentially expressed lncRNAs (delncRNAs) were identified. Localization and abundance analysis revealed that delncRNAs were biased distribution on chromosomes. We explored the dynamic characteristics of disease resistance related lncRNAs in chromosome distribution, induced expression profiles, biological function, and these lncRNAs were divided into three categories according to their induced expression profiles. For the delncRNAs, 687 cis-acting pairs and 14,600 trans-acting pairs of lncRNA-mRNA were identified, which indicated that trans-acting was the main way of Verticillium wilt resistance-associated lncRNAs regulating target mRNAs in cotton. Analyzing the regulation pattern of delncRNAs revealed that cis-acting and trans-acting lncRNAs had different ways to influence target genes. Gene Ontology (GO) enrichment analysis revealed that the regulatory function of delncRNAs participated significantly in stimulus response process, kinase activity and plasma membrane components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that delncRNAs participated in some important disease resistance pathways, such as plant-pathogen interaction, alpha-linolenic acid metabolism and plant hormone signal transduction. Additionally, 21 delncRNAs and 10 target genes were identified as being involved in alpha-linolenic acid metabolism associated with the biosynthesis of jasmonic acid (JA). Subsequently, we found that GhlncLOX3 might regulate resistance to V. dahliae through modulating the expression of GhLOX3 implicated in JA biosynthesis. Further functional analysis showed that GhlncLOX3-silenced seedlings displayed a reduced resistance to V. dahliae, with down-regulated expression of GhLOX3 and decreased content of JA. Conclusion This study shows the dynamic characteristics of delncRNAs in multiaspect, and suggests that GhlncLOX3-GhLOX3-JA network participates in response to V. dahliae invasion. Our results provide novel insights for genetic improvement of Verticillium wilt resistance in cotton using lncRNAs.

Abstract Background Dirigent (DIR) proteins mediate regioselectivity and stereoselectivity during lignan biosynthesis and are also involved in lignin, gossypol and pterocarpan biosynthesis. This gene family plays a vital role in enhancing stress resistance and in secondary cell-wall development, but systematical understanding is lacking in cotton. Results In this study, 107 GbDIRs and 107 GhDIRs were identified in Gossypium barbadense and Gossypium hirsutum, respectively. Most of these genes have a classical gene structure without intron and encode proteins containing a signal peptide. Phylogenetic analysis showed that cotton DIR genes were classified into four distinct subfamilies (a, b/d, e, and f). Of these groups, DIR-a and DIR-e were evolutionarily conserved, and segmental and tandem duplications contributed equally to their formation. In contrast, DIR-b/d mainly expanded by recent tandem duplications, accompanying with a number of gene clusters. With the rapid evolution, DIR-b/d-III was a Gossypium-specific clade involved in atropselective synthesis of gossypol. RNA-seq data highlighted GhDIRs in response to Verticillium dahliae infection and suggested that DIR gene family could confer Verticillium wilt resistance. We also identified candidate DIR genes related to fiber development in G. barbadense and G. hirsutum and revealed their differential expression. To further determine the involvement of DIR genes in fiber development, we overexpressed a fiber length-related gene GbDIR78 in Arabidopsis and validated its function in trichomes and hypocotyls. Conclusions These findings contribute novel insights towards the evolution of DIR gene family and provide valuable information for further understanding the roles of DIR genes in cotton fiber development as well as in stress responses.

Abstract Objectives A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. Results 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

Abstract Background NEK2 has an established involvement in hepatocellular carcinoma (HCC) but the roles of NEK2 and its interacting proteins in HCC have not been systematically explored. Methods This study examined NEK2 and its interacting proteins in HCC based on multiple databases. Results NEK2 mRNA was highly expressed in HCC tissues compared with normal liver tissues. The survival of HCC patients with high NEK2 mRNA expression was shorter than those with low expression. MAD1L1, CEP250, MAPK1, NDC80, PPP1CA, PPP1R2 and NEK11 were the interacting proteins of NEK2. Among them, NDC80 and CEP250 were the key interacting proteins of NEK2. Mitotic prometaphase may be the key pathway that NEK2 and its interacting proteins contributed to HCC pathogenesis. NEK2, NDC80 and CEP250 mRNAs were highly expressed in HCC tissues compared with normal liver tissues. The mRNA levels of NEK2 were positively correlated with those of NDC80 or CEP250. Univariate regression showed that NEK2, NDC80 and CEP250 mRNA expressions were significantly associated with HCC patients’ survival. Multivariate regression showed that NDC80 mRNA expression was an independent predictor for HCC patients’ survival. Methylations and genetic alterations of NEK2, NDC80 and CEP250 were observed in HCC samples. The alterations of NEK2, NDC80 and CEP250 genes were co-occurrence. Patients with high mRNA expression and genetic alterations of NEK2, NDC80 and CEP250 had poor prognosis. Conclusions NEK2 and its interacting proteins NDC80 and CEP250 play important roles in HCC development and progression and thus may be potentially used as biomarkers and therapeutic targets of HCC.

Abstract Background LIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown. Methods This study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated. Results LIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491–0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561–0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439–0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503–0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445–0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019). Conclusions These results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.

Abstract Background Evaluating phenotypic traits is very important for the selection of elite lines in Gossypium hirsutum L. Cotton breeders are interested in using diverse genotypes in hybridization that can segregate for traits of interested with the possibility of selection and genetic gain. Information on phenotypic and molecular diversity helps the breeders for parental selection. Methods In this study, 719 global collections of G. hirsutum L. were evaluated for five fibre-related traits during two consecutive years in eight different environments. A series of phenotypic data for fibre quality traits were obtained and the elite accessions were further screened using principal component analysis and phylogenetic tree construction based on single nucleotide polymorphism markers. Results We found that fibre quality traits showed a wide range of variation among the G. hirsutum accessions over 2 years. In general, accessions from outside China tended to have higher fibre length (FL) and fibre strength (FS) than did Chinese accessions. Among different regional accessions in China, North/Northwest accessions tended to have the highest FL, FS and best fibre macronaire. By assessing five fibre quality traits over 2 years with genotypic data, 31 elite germplasms reaching double-thirty quality values (FL ≥ 30 mm and FS ≥ 30 cN·tex− 1) were selected. Conclusions This study provided a detailed phenotypic diversity description of a population representing a wide range of upland cotton germplasm. Our findings provide useful information about possible elite fibre quality parents for cotton breeding programs.

Abstract Background Patients with hepatitis C virus (HCV) genotype 3 infection remain a difficult-to-cure population. This study evaluated the efficacy and safety of sofosbuvir-based regimen in genotype 3 patients in a real-world setting. Methods HCV genotype 3a-infected adults with compensated liver disease were treated with sofosbuvir (SOF)/velpatasvir (VEL) or SOF/daclatasvir (DCV) with or without ribavirin (RBV) for 12 or 24 weeks, respectively. Efficacy was measured by sustained virologic response at post-treatment week 12 (SVR12). Adverse events were evaluated throughout the treatment and follow-up course. Results A total of 41 genotype 3a-infected patients were included. Of them, 10 patients (24%) had cirrhosis, 3 (7%) had renal impairment, and 2 (5%) failed previous treatment. Nine patients (22%) were treated with SOF/VEL and 32 (78%) with SOF/DCV with or without RBV. SVR 12 was achieved in 100% (9/9) of patients treated with SOF/VEL for 12 weeks and in 97% (31/32) of those treated with SOF/DCV for 12 or 24 weeks. RBV addition and extension of treatment duration did not improve the SVR of SOF/DCV (RR: 1.04; P = 0.99 and RR: 1.09; P = 0.375, respectively). Ten patients with cirrhosis, 1 on hemodialysis and 2 with treatment-experience achieved SVR12. One treatment-naïve non-cirrhotic patient on hemodialysis treated with SOF/DCV for 24 weeks relapsed at week 8 post-treatment. No serious adverse events and relevant laboratory abnormalities were observed. Conclusion SOF/VEL and SOF/DCV are highly efficacious and well tolerated in genotype 3a-infected patients with or without cirrhosis. RBV coadministration and extension of SOF/DCV treatment appear to add no improvement for efficacy.

Abstract Background Signal transducer and activator of transcription 3 (STAT3) is involved in hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC). The association between polymorphism rs1053005 and haplotypes formed by rs1053004 and rs1053005 in the 3′UTR of STAT3 and chronic HBV infection has yet to be investigated. Methods This study included 567 patients with chronic HBV infection (239 chronic hepatitis, 141 liver cirrhosis and 187 HCC), 98 HBV infection resolvers, and 169 healthy controls. STAT3 rs1053004 and rs1053005 polymorphisms were genotyped by TaqMan SNP Genotyping Assays. Results The rs1053004 genotype CC [P value by Bonferroni correction (P c ) = 0.002] and allele C (P c = 0.019) were more frequent in patients with chronic HBV infection than in healthy controls. The rs1053005 genotype GG was also more frequent in patients with chronic HBV infection than in healthy controls (P c = 0.046). The rs1053004-rs1053005 haplotype T-G was less frequent in patients with chronic HBV infection than in healthy controls (P c

Abstract Background Chronic hepatitis B virus (HBV) infection remains an important public health issue. A20, a ubiquitin-editing protein encoded by tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene, is complicated in HBV infection and liver injury. The tandem polymorphisms (rs148314165, rs200820567), deletion T followed by a T to A transversion and collectively referred to as TT > A in TNFAIP3, may attenuate A20 expression. Methods The rs148314165 and rs200820567 polymorphisms were examined using PCR amplification followed by direct sequencing in 419 patients with chronic HBV infection, 77 HBV infection resolvers and 175 healthy controls of Chinese Han ethnicity. Results The genotypes and alleles of rs148314165 and rs200820567 polymorphisms determined and the haplotypes constructed were consistently identical, confirming the reliable determination of the TT > A variant. The genotypes of rs148314165 and rs200820567 in HBV patients, HBV infection resolvers and healthy controls are in Hardy-Weinberg equilibrium (P > 0. 05). The patients with chronic HBV infection had higher frequency of TT > A variant than healthy controls (6.6% vs. 3.4%; OR, 1.979; 95% CI, 1.046–3.742; P = 0.033). The frequency of TT > A variant between patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma had no significant differences. Conclusions The TT > A variant of TNFAIP3 may be associated with the susceptibility of chronic HBV infection but not the clinical diseases. Studies in large sample size of HBV patient and control populations are required to further clarify the role of this important variant in chronic HBV infection and the disease progression related to the infection.