scINRB: single-cell gene expression imputation with network regularization and bulk RNA-seq data.

Single-cell RNA sequencing (scRNA-seq) facilitates the study of cell type heterogeneity and the construction of cell atlas. However, due to its limitations, many genes may be detected to have zero expressions, i.e. dropout events, leading to bias in downstream analyses and hindering the identification and characterization of cell types and cell functions. Although many imputation methods have been developed, their performances are generally lower than expected across different kinds and dimensions of data and application scenarios. Therefore, developing an accurate and robust single-cell gene expression data imputation method is still essential. Considering to maintain the original cell-cell and gene-gene correlations and leverage bulk RNA sequencing (bulk RNA-seq) data information, we propose scINRB, a single-cell gene expression imputation method with network regularization and bulk RNA-seq data. scINRB adopts network-regularized non-negative matrix factorization to ensure that the imputed data maintains the cell-cell and gene-gene similarities and also approaches the gene average expression calculated from bulk RNA-seq data. To evaluate the performance, we test scINRB on simulated and experimental datasets and compare it with other commonly used imputation methods. The results show that scINRB recovers gene expression accurately even in the case of high dropout rates and dimensions, preserves cell-cell and gene-gene similarities and improves various downstream analyses including visualization, clustering and trajectory inference.

Glycomic Analysis Reveals That Sialyltransferase Inhibition Is Involved in the Antiviral Effects of Arbidol.

Due to the high mutation rate of influenza virus and the rapid increase of drug resistance, it is imperative to discover host-targeting antiviral agents with broad-spectrum antiviral activity. Considering the discrepancy between the urgent demand of antiviral drugs during an influenza pandemic and the long-term process of drug discovery and development, it is feasible to explore host-based antiviral agents and strategies from antiviral drugs on the market. In the current study, the antiviral mechanism of arbidol (ARB), a broad-spectrum antiviral drug with potent activity at early stages of viral replication, was investigated from the aspect of hemagglutinin (HA) receptors of host cells. N-glycans that act as the potential binding receptors of HA on 16-human bronchial epithelial (16-HBE) cells were comprehensively profiled for the first time by using an in-depth glycomic approach based on TiO2-PGC chip-Q-TOF MS. Their relative levels upon the treatment of ARB and virus were carefully examined by employing an ultra-high sensitive qualitative method based on Chip LC-QQQ MS, showing that ARB treatment led to significant and extensive decrease of sialic acid (SA)-linked N-glycans (SA receptors), and thereby impaired the virus utilization on SA receptors for rolling and entry. The SA-decreasing effect of ARB was demonstrated to result from its inhibitory effect on sialyltransferases (ST), ST3GAL4 and ST6GAL1 of 16-HBE cells. Silence of STs, natural ST inhibitors, as well as sialidase treatment of 16-HBE cells, resulted in similar potent antiviral activity, whereas ST-inducing agent led to the diminished antiviral effect of ARB. These observations collectively suggesting the involvement of ST inhibition in the antiviral effect of ARB. IMPORTANCE This study revealed, for the first time, that ST inhibition and the resulted destruction of SA receptors of host cells may be an underlying mechanism for the antiviral activity of ARB. ST inhibition has been proposed as a novel host-targeting antiviral approach recently and several compounds are currently under exploration. ARB is the first antiviral drug on the market that was found to possess ST inhibiting function. This will provide crucial evidence for the clinical usages of ARB, such as in combination with neuraminidase (NA) inhibitors to exert optimized antiviral effect, etc. More importantly, as an agent that can inhibit the expression of STs, ARB can serve as a novel lead compound for the discovery and development of host-targeting antiviral drugs.

Burden of Lung Cancer in China, 1990-2019: Findings from the Global Burden of Disease Study 2019.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.

Organobase-Catalyzed Umpolung of Amides: The Generation and Transfer of Carbamoyl Anion.

A novel organobase-catalyzed umpolung reaction of amides was disclosed. This method provides an efficient method to generate and transfer carbamoyl anions. In this transformation, some of the inherent disadvantages of carbamoyl metal were avoided. The mechanistic analysis revealed that the reaction proceeds through polarity inversion of amide, and various carbamoyl anions were applied in the reaction. Moreover, a wide range of substrates was achieved with moderate to excellent yield.

Associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer.

PURPOSE: Serum cortisol and inflammatory markers may play a role in depression and anxiety, but little is known about whether various features of serum cortisol and inflammatory markers have different associations with depression and anxiety. This study examines the associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. METHODS: Sixty-four young women with gynecologic cancer, aged 15-39 years, were recruited in a tertiary general hospital and a tertiary hospital specializing in oncology in China from May to December 2021. The Hospital Anxiety and Depression Scale was used to evaluate depression and anxiety. Blood samples were taken at 8 am, 4 pm, and 10 pm on the same day to examine the various features (average, variability, and diurnal patterns) of serum cortisol and inflammatory markers, namely C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RESULTS: Young women with gynecologic cancer who reported depression/anxiety had significantly higher average levels of serum cortisol, IL-6 and TNF-α than those who did not. The dysregulations in the diurnal patterns of serum cortisol and IL-6 were associated with depression and anxiety. Serum cortisol levels were significantly higher in the depression/anxiety group at 10 pm. Depression and anxiety were associated with elevated levels of IL-6 and TNF-α at each time point. CONCLUSION: This study revealed various associations of serum cortisol and inflammatory marker features with depression and anxiety in young women with gynecologic cancer. Further research is needed to understand the role of serum cortisol and inflammatory marker features in the progression of depression and anxiety.

Phage SPO1 Protein Gp49 Is a Novel RNA Binding Protein That Is Involved in Host Iron Metabolism.

Bacillus subtilis is a model organism for studying Gram-positive bacteria and serves as a cell factory in the industry for enzyme and chemical production. Additionally, it functions as a probiotic in the gastrointestinal tract, modulating the gut microbiota. Its lytic phage SPO1 is also the most studied phage among the genus Okubovrius, including Bacillus phage SPO1 and Camphawk. One of the notable features of SPO1 is the existence of a "host-takeover module", a cluster of 24 genes which occupies most of the terminal redundancy. Some of the gene products from the module have been characterized, revealing their ability to disrupt host metabolism by inhibiting DNA replication, RNA transcription, cell division, and glycolysis. However, many of the gene products which share limited similarity to known proteins remain under researched. In this study, we highlight the involvement of Gp49, a gene product from the module, in host RNA binding and heme metabolism-no observation has been reported in other phages. Gp49 folds into a structure that does not resemble any protein in the database and has a new putative RNA binding motif. The transcriptome study reveals that Gp49 primarily upregulates host heme synthesis which captures cytosolic iron to facilitate phage development.

Recent Progress in CDK4/6 Inhibitors and PROTACs.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.

Evolutionary and reverse engineering in Saccharomyces cerevisiae reveals a Pdr1p mutation-dependent mechanism for 2-phenylethanol tolerance.

BACKGROUND: 2-Phenylethanol (2-PE), a higher alcohol with a rose-like odor, inhibits growth of the producer strains. However, the limited knowledge regarding 2-PE tolerance mechanisms renders our current knowledge base insufficient to inform rational design. RESULTS: To improve the growth phenotype of Saccharomyces cerevisiae under a high 2-PE concentration, adaptive laboratory evolution (ALE) was used to generate an evolved 19-2 strain. Under 2-PE stress, its OD600 and growth rate increased by 86% and 22% than that of the parental strain, respectively. Through whole genome sequencing and reverse engineering, transcription factor Pdr1p mutation (C862R) was revealed as one of the main causes for increased 2-PE tolerance. Under 2-PE stress condition, Pdr1p mutation increased unsaturated fatty acid/saturated fatty acid ratio by 42%, and decreased cell membrane damage by 81%. Using STRING website, we identified Pdr1p interacted with some proteins, which were associated with intracellular ergosterol content, reactive oxygen species (ROS), and the ATP-binding cassette transporter. Also, the results of transcriptional analysis of genes encoded these proteins confirmed that Pdr1p mutation induced the expression of these genes. Compared with those of the reference strain, the ergosterol content of the PDR1_862 strain increased by 72%-101%, and the intracellular ROS concentration decreased by 38% under 2-PE stress. Furthermore, the Pdr1p mutation also increased the production of 2-PE (11% higher). CONCLUSIONS: In the present work, we have demonstrated the use of ALE as a powerful tool to improve yeast tolerance to 2-PE. Based on the reverse engineering, transcriptional and physiological analysis, we concluded that Pdr1p mutation significantly enhanced the 2-PE tolerance of yeast by regulating the fatty acid proportion, intracellular ergosterol and ROS. It provides new insights on Pdr1p mediated 2-PE tolerance, which could help in the design of more robust yeasts for natural 2-PE synthesis.

The efficacy of live music for adolescent and young adult patients during hematopoietic stem cell transplantation.

BACKGROUND: Music therapy can improve mood in patients undergoing hematopoietic stem cell transplantation (HSCT). However, live music (LM) delivered by professional music therapists is not common in developing countries owing to the shortage of professional music therapists. Thus, in this study, we explored the effects of a multidisciplinary collaborative intervention based on LM on physical and psychological well-being of adolescent and young adult (AYA) patients undergoing HSCT with a quasi-experimental design. METHODS: A total of 62 AYA patients agreed to participate and were randomly assigned to the intervention group receiving 4-week LM therapy (n = 31) or control group receiving usual care (n = 31). Depression, salivary cortisol, fatigue, and quality of life were the main outcome indicators measured at baseline, immediately after the intervention, 1 month, and 3 months follow-up. The intervention effects were analyzed by generalized estimating equations. RESULTS: Significant decrease in HADS-D scores occurred in the intervention group compared with wait-list controls at immediately after intervention (p < 0.05). Participants in the LM group had greater improvement in quality of life and lower salivary cortisol level than those in the wait-list control group at immediately, 1 month, and 3 months after intervention (p < 0.05). However, the interaction effects of the BFI scores were not significant. CONCLUSIONS: LM therapy significantly alleviated depression and salivary cortisol levels as well as improved quality of life of AYA patients undergoing HSCT.

Sexual Dysfunction After Traumatic Injury Can Be Corrected by Transcranial Magnetic Stimulation: A Case Report.

Neurogenic sexual dysfunction (NSD) is a common problem in patients after spinal and pelvic trauma. New treatment is needed beyond medicine or psychological therapies. A 24-year-old man who fell from a six-floor building suffered from subsequent NSD. Repetitive transcranial magnetic stimulation (rTMS) was the only method used to treat his NSD caused by multiple spinal and pelvic injuries. The therapy lasted for 3 courses. Motor and sensory conduction, as well as sexual function, were evaluated before and after the rTMS intervention. Improvements on patient's nerve conduction and sexual activity were confirmed at a 1-year follow-up. Our findings indicate that rTMS delivered a novel, positive and low-cost modality treatment to the patient with NSD. Clinical efficacy and potential mechanisms by which rTMS regulate NSD need to be investigated by further clinical trials.

Active video game on children and adolescents' physical activity and weight management: A network meta-analysis.

We synthesized evidence on the effectiveness of active video games (AVGs) versus no AVG-applied comparators on various physical activity (PA) levels and weight management outcomes in children and adolescents. We analyzed the comparative evidence on different sub-categories of AVGs and ranking the best option. An overview of systematic reviews (SRs) and network meta-analysis (NMA) (PROSPERO: CRD42021248499) was employed. A search for relevant literature published in English was conducted in six electronic databases from their inception until April 2021. SRs consisting of randomized control trials (RCTs) and satisfying our PICOS inclusion criteria were included. RCTs included were a comparison of groups among children and adolescents between 6 and 21, where groups with AVG interventions were compared with groups without them. Direct head-to-head pairwise meta-analyses were conducted using weighted mean difference between the two groups, and the comparative effectiveness of different sub-categories of AVGs was analyzed indirectly using NMA. Overall, 17 SRs were identified from the 6036 screened citations. Of these, 350 citations were retrieved, and 12 RCTs were finally included. Compared with no AVG group, AVG groups were shown to be more effective in achieving vigorous, moderate-to-vigorous, and moderate PA levels, and decreased BMI and body fat. NMA showed that rhythmic dance games had the highest probability of being the most effective sub-category for reducing BMI. AVGs are effective in attaining vigorous, moderate to vigorous, and moderate PA levels, and reducing BMI and body fat among children and adolescents. Dance appears to be the best option for reducing BMI among AVG subcategories.

Innate immunity and protective effects of orally administered betaine against viral and bacterial diseases in the olive flounder Paralichthys olivaceus (Temminck & Schlegel).

Sustainable methods that increase farmed fish yield while controlling infections are required to prevent economic losses in aquaculture farms. In this study, we evaluated the effects of betaine-supplemented (0%, 0.1%, 0.5%, and 1.0%) feed on the growth and immunity of the olive flounder Paralichthys olivaceus. Feed conversion ratios, post-infection cumulative mortality rates and innate immune responses were monitored. Weight gain was significantly higher with 0.5% and 1.0% than with 0% and 0.1% betaine-supplemented feed. Lysozyme activity was highest with 1.0% betaine. Respiratory burst activity was highest with 0.5% and 1.0% betaine. Serum bactericidal activity against Edwardsiella tarda was highest with 1.0% betaine (40% increase in survival rates compared with those in the control). Furthermore, serum virucidal activity against the viral haemorrhagic septicaemia virus (VHSV) was higher with 1.0% betaine than with other concentrations. With 0.5% and 1.0% betaine, the survival rates against VHSV were higher than those in the control until day 11, after which they declined. Our study suggests that betaine is a promising agent for promoting the growth of and enhancing immunity against E. tarda in olive flounders. Our findings may further contribute to developing necessary alternatives to conventional antibiotics in fish farming.

Nemonoxacin dosage adjustment in patients with severe renal impairment based on population pharmacokinetic and pharmacodynamic analysis.

AIMS: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic (PPK)/pharmacodynamic analysis. METHODS: The pharmacokinetics and safety of nemonoxacin was evaluated in a single-dose, open-label, nonrandomized, parallel-group study after single oral dose of a 0.5-g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 72 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment and the cumulative fraction of response against Streptococcus pneumoniae and Staphylococcus aureus was calculated by Monte Carlo simulation. RESULTS: The data best fitted a 2-compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L) and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4 ± 6.5% in severe renal impairment patients and 66.1 ± 16.8% in healthy controls. PPK/pharmacodynamic modelling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g every 48 hours (q48h) was the optimal dosing regimen in severe renal impairment patients, evidenced by higher probability of target attainment (92.7%) and cumulative fraction of response (>99%) at nemonoxacin minimum inhibitory concentration ≤ 1 mg/L against S. pneumoniae and S. aureus. The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if minimum inhibitory concentration = 1 mg/L. CONCLUSION: An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.

Association between small dense low-density lipoprotein cholesterol and neuroimaging markers of cerebral small vessel disease in middle-aged and elderly Chinese populations.

BACKGROUND: Cerebral small vascular disease (CSVD) is one of the leading causes of death in the aged population and is closely related to abnormalities in low-density lipoprotein cholesterol (LDL-C). Our study aims to clarify the relationship between small and dense low-density lipoprotein cholesterol (sdLDL-C) (a subcomponent of LDL-C) and neuroimaging markers of CSVD. METHODS: In total, 1211 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this retrospective study from January 2018 to May 2021. Serum lipids and other baseline characteristics were investigated in relation to the occurrence of CSVD. A logistic regression model was performed to analyze the relationships between LDL subtypes and CSVD risk, and the Pearson correlation coefficient was used to analyze the correlation between clinical characteristics and CSVD risk. ROC curves and AUCs were created and depicted to predict the best cutoff value of LDL-C subtypes for CSVD risk. Based on these data, we performed comprehensive analyses to investigate the risk factors for CSVD. RESULTS: Ultimately, 623 eligible patients were included in the present study. Of the 623 eligible patients, 487 were included in the CSVD group, and 136 were included in the group without CSVD (control group). We adjusted for confounders in the multivariate logistic regression model, and LDL-C3 was still higher in the CSVD patients than in the group of those without CSVD (OR (95% CI), 1.22(1.08-1.38), P < 0.05). Pearson correlation showed that there was a positive correlation between the levels of LDL-C3, LDL-C4, LDL-C5, glucose, age, hypertension, previous ischemic stroke and CSVD risk (r > 0.15, P < 0.01). Moreover, the best cutoff value of LDL-C3 to predict CSVD was 9.5 mg/dL with 68.4% sensitivity and 72.8% specificity, and the best cutoff value of LDL-C4 to predict CSVD was 5.5 mg/dL with 50.5% sensitivity and 90.4% specificity. CONCLUSION: The results indicate that LDL-C3 is an independent risk factor for CSVD. A new prediction model based on LDL-C3 and LDL-C4 can help clinicians identify high-risk CSVD, even in people with normal LDL-C levels. The levels of sdLDL-C should be considered in the assessment and management of CSVD.

Current Status of MicroRNAs that Target the Wnt Signaling Pathway in Regulation of Osteogenesis and Bone Metabolism: A Review.

The directional differentiation of bone mesenchymal stem cells (BMSCs) is regulated by a variety of transcription factors and intracellular signaling pathways. In the past, it was thought that the directional differentiation of BMSCs was related to transforming growth factors, such as bone morphogenetic protein (BMP) and MAPK pathway. However, in recent years, some scholars have pointed out that the Wnt signaling pathway, which is a necessary complex network of protein interactions for biological growth and development, takes a significant role in this process and plays a major part in regulating the development of osteoblasts by exerting signal transduction into cells. Also, they have proved the Wnt protein therapeutic truly have positive effects on the viability and osteogenic capacity of bone graft. Recent studies have shown that microRNAs (miRNAs) play an important regulatory role in this process. MiRNAs such as miRNA-218, miRNA-335, miRNA-29, microRNA-30 and other miRNAs exert negative or positive effects on some crucial molecules in the Wnt/ß-catenin pathway, which in turn affect bone metabolism and osteopathy. Thus, miRNAs have been suggested as therapeutic targets for some metabolic bone diseases. This article aims to provide an update on the current status of microRNAs that target the Wnt signaling pathway in the regulation of osteogenesis and bone metabolism and includes a discussion of future areas of research, which can be a theoretical basis for bone metabolism-related diseases.

Comprehensive Glycomic Profiling of Respiratory Tract Tissues of Tree Shrews by TiO2-PGC Chip Mass Spectrometry.

Due to its relatively small size, homology to humans, and susceptibility to human viruses, the tree shrew becomes an ideal alternative animal model for the study of human viral infectious diseases. However, there is still no report for the comprehensive glycan profile of the respiratory tract tissues in tree shrews. In this study, we characterized the structural diversity of N-glycans in the respiratory tract of tree shrews using our well-established TiO2-PGC chip-Q-TOF-MS method. As a result, a total of 219 N-glycans were identified. Moreover, each identified N-glycan was quantitated by a high sensitivity and accurate MRM method, in which 13C-labeled internal standards were used to correct the inherent run-to-run variation in MS detection. Our results showed that the N-glycan composition in the turbinate and lung was significantly different from the soft palate, trachea, and bronchus. Meanwhile, 28 high-level N-glycans in turbinate were speculated to be correlated with the infection of H1N1 virus A/California/04/2009. This study is the first to reveal the comprehensive glycomic profile of the respiratory tract of tree shrews. Our results also help to better understand the role of glycan receptors in human influenza infection and pathogenesis.

Adipose-derived stem cell-conditioned medium protects fibroblasts at different senescent degrees from UVB irradiation damages.

Adipose-derived stem cells (ADSCs) and their derivatives have aroused intense interest in fields of dermatological and aesthetic medicine. As a major component detected in ADSCs secretome, platelet-derived growth factor AA (PDGF-AA) has been reported mediating extracellular matrix deposition and remodeling, thus might contribute to its anti-aging effect. On the basis of establishing an experimental model that simulate actual skin aging by exposing HDFs to both intrinsic and extrinsic aging factors, we pretreated human dermal fibroblasts (HDFs) with ADSC-conditioned medium (ADSC-CM) before being irradiated, aiming at exploring preventive effects of ADSCs secretome against aging damages. 48 h after irradiation, we detected cellular proliferation; ß-galactosidase stain; mRNA expressions of MMP-1, MMP-9, and TIMP-1; and protein expressions of collagen I, collagen III, and elastin. Moreover, we detected related protein expression of PI3K/Akt signal pathway, which can be activated by PDGF-AA and was newly found to promote extracellular matrix protein synthesis. Concentration of PDGF-AA in the prepared ADSC-CM decreased over time and maintained excellent bioactivity at low temperature until the 11th week. ADSC-CM pretreatment can slightly or significantly improve cellular proliferative activity and reduce cellular senescence in irradiated HDFs. Besides, ADSC-CM pretreatment increased collagen I, collagen III, elastin, and TIMP-1 expressions but decreased MMP-1 and MMP-9 expressions both in irradiated and nonirradiated HDFs. ADSC-CM pretreatment significantly increased pAkt protein expression, and ECM protein expression greatly decreased in case of LY294002 application. The results were similar in three generations of HDFs, yet varied with different degrees. Generally, ADSC-CM we prepared demonstrates a certain degree of positive role in preventing HDFs from intrinsic and extrinsic aging damages and that PDGF-AA may contribute to making it become effective with some other components in ADSC-CM.

Comprehensive overview of COVID-19 based on current evidence.

In December 2019, twenty-seven pneumonia patients with unknown causes originated in South China seafood market in Wuhan. The virus infection spread rapidly and swept through China in less than a month. Subsequently, the virus was proven a novel coronavirus and named SARS-CoV-2. The outbreak of novel coronavirus has been determined as a Public Health Emergency of International Concern (PHEIC) by WHO on January 31, 2020. Similar to other coronaviruses like the Middle East Respiratory Syndrome (MERS) CoV and Severe Acute Respiratory Syndrome (SARS) CoV, the novel coronavirus was reported to spread via respiratory droplets and close contact from human to human, which means the virus is highly infectious and dangerous. Unfortunately, till now the virus has spread to over 200 countries/territories/areas around the world and the Coronavirus Disease 2019 (COVID-19) outbreak is continuing to grow. Currently, information sharing and transparency are essential for risk assessment and epidemic control in all endemic areas. In this article, we compared SARS-CoV-2 with SARS-CoV and influenza virus, discussed current researching progress of COVID-19, including clinical characteristics, pathological changes, treatment measures, and so on.

Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer.

BACKGROUND: Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co-receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro. METHODS: A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC-1 and PANC-1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assay, respectively. CCK-8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability. RESULTS: Results of qRT-PCR and Western blot showed successfully established, stably transfected shRNA-NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01). CONCLUSIONS: NRP1-shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing.

Posttranslational histone modifications play important roles in regulating chromatin-based nuclear processes. Histone H2AK119 ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing. However, the underlying mechanism remains largely obscure. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF complex, as a H2Aub binding protein, which mediates the gene-silencing function of this histone modification. RSF1 associates specifically with H2Aub, but not H2Bub nucleosomes, through a previously uncharacterized and obligatory region designated as ubiquitinated H2A binding domain. In human and mouse cells, genes regulated by RSF1 overlap significantly with those controlled by RNF2/Ring1B, the subunit of Polycomb repressive complex 1 (PRC1) which catalyzes the ubiquitination of H2AK119. About 82% of H2Aub-enriched genes, including the classic PRC1 target Hox genes, are bound by RSF1 around their transcription start sites. Depletion of H2Aub levels by Ring1B knockout results in a significant reduction of RSF1 binding. In contrast, RSF1 knockout does not affect RNF2/Ring1B or H2Aub levels but leads to derepression of H2Aub target genes, accompanied by changes in H2Aub chromatin organization and release of linker histone H1. The action of RSF1 in H2Aub-mediated gene silencing is further demonstrated by chromatin-based in vitro transcription. Finally, RSF1 and Ring1 act cooperatively to regulate mesodermal cell specification and gastrulation during Xenopus early embryonic development. Taken together, these data identify RSF1 as a H2Aub reader that contributes to H2Aub-mediated gene silencing by maintaining a stable nucleosome pattern at promoter regions.