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Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and young children. Axl, a TAM family receptor tyrosine kinase, has been demonstrated to be a receptor mediating enveloped virus infection. Here we show that Axl functions as a suppressor of antiviral response during RSV infection. Knockdown of Axl expression in human cells resulted in cell resistance to RSV infection, although the treatment did not significantly affect RSV binding or cell entry. Mice deficient in

Long INterspersed Element 1 (LINE-1 or L1) acts as a major remodeling force in genome regulation and evolution. Accumulating evidence shows that virus infection impacts L1 expression, potentially impacting host antiviral response and diseases. The underlying regulation mechanism is unclear. Epstein–Barr virus (EBV), a double-stranded DNA virus linked to B-cell and epithelial malignancies, is known to have viral–host genome interaction, resulting in transcriptional rewiring in EBV-associated gastric cancer (EBVaGC). By analyzing publicly available datasets from the Gene Expression Omnibus (GEO), we found that EBVaGC has L1 transcriptional repression compared with EBV-negative gastric cancer (EBVnGC). More specifically, retrotransposition-associated young and full-length L1s (FL-L1s) were among the most repressed L1s. Epigenetic alterations, especially increased H3K9me3, were observed on FL-L1s. H3K9me3 deposition was potentially attributed to increased TASOR expression, a key component of the human silencing hub (HUSH) complex for H3K9 trimethylation. The 4C- and HiC-seq data indicated that the viral DNA interacted in the proximity of the TASOR enhancer, strengthening the loop formation between the TASOR enhancer and its promoter. These results indicated that EBV infection is associated with increased H3K9me3 deposition, leading to L1 repression. This study uncovers a regulation mechanism of L1 expression by chromatin topology remodeling associated with viral–host genome interaction in EBVaGC.

Respiratory syncytial virus (RSV) infection persists as a common pathogen of pulmonary infection in infants and in the elderly with high morbidity and mortality. However, no specific therapeutics are available.

Background The objective of this study was to assess human adenovirus (HAdV) infection in juvenile polyps (JPs) and to preliminarily establish a correlation to vitamin D receptor (VDR) expression. Methods The study includes 76 patients of 5.2 ± 2.8 years old. Seventy-eight JP specimens and 24 parapolyp tissues from polypectomy were used. PCR was used to detect HAdV DNA and quantitative reverse transcription-PCR for viral and host gene expression. The PCR products were sequenced for virus typing. The correlation between VDR expression and HAdV infection was established using nonparametric Spearman's analysis. Results Seventy-four children (97.4%) had a single polyp and two had two polyps. The histopathological characteristics of the polyps were in line with JP. Thirty-three samples had HAdV DNA (43.4%), including 32 subgroup C and 1 subgroup B HAdV; no enteric HAdV was detected. HAdV messenger RNA was detected in 5 of the 33 samples (15.2%). The samples had increased interleukin-1β (IL-1β), IL-6, and calprotectin expression, and reduced E-cadherin and VDR expression. JP samples with low VDR expression were more prevalent of HAdV DNA (r = 1.261, 95% confidence interval, 1.017-1.563), while VDR expression positively correlated with E-cadherin and negatively with inflammation gene expression. Conclusions HAdV latent infection was prevalent among JP tissues. The presence of HAdV correlated positively to low VDR expression. Impact The HAdVs infect the upper airways and gastrointestinal system and is found to persist in lymphoid tissues. The prevalence of HAdV and the status of the infection is unknown. The study investigated the prevalence of HAdV from polypectomy specimens of JP patients and found that HAdV was prevalent and was in a persistent state. HAdV infection was more prevalent in samples with low VDR expression. Whether HAdV infection and reactivation is a contributing factor to JPs is unknown. Factors such as proinflammation and bacterial metabolites that are known to promote HAdV reactivation warrant further investigation.

The nuclear factor-kappa B (NF-κB) signaling network constitutes a first line of defense against the invading viruses. However, viruses also adopted multiple strategies to interfere with NF-κB activation. Enterovirus 71 (EV71), in the family Picornaviridae, has become the main pathogen responsible for hand, foot, and mouth disease. Recent studies have reported that the nonstructural protein 2C of EV71 inhibits TNF-α induced NF-κB activation by suppressing IKKβ phosphorylation. In our study, we found that 2C can form inclusion bodies (IBs) in infected and transfected cells. Furthermore, 2C was able to sequester IKKβ into IBs through direct interaction with IKKβ. Although 2C did not directly interact with IKKα, viral protein 2C was able to sequester the IKKα into the IBs mediated by IKKβ. Our in vitro data further demonstrated that EV71 2C could suppress IKKα phosphorylation. These all together support a novel mechanism for EV71 to escape from NF-κB response, in which the phosphorylation of IKKα was suppressed by being recruited into viral IBs in the presence of 2C and IKKβ.

The IS6family of bacterial and archaeal insertion sequences, first identified in the early 1980s, has proved to be instrumental in the rearrangement and spread of multiple antibiotic resistance. Two IS, IS26(found in many enterobacterial clinical isolates as components of both chromosome and plasmids) and IS257(identified in the plasmids and chromosomes of gram-positive bacteria), have received particular attention for their clinical impact. Although few biochemical data are available concerning the transposition mechanism of these elements, genetic studies have provided some interesting observations suggesting that members of the family might transpose using an unexpected mechanism. In this review, we present an overview of the family, the distribution and phylogenetic relationships of its members, their impact on their host genomes and analyse available data concerning the particular transposition pathways they may use. We also provide a mechanistic model that explains the recent observations on one of the IS6family transposition pathways: targeted cointegrate formation between replicons.

Highlights • The absolute values of CD3+, CD4+, and CD8 + T cells are lower in COVID-19 patients. • The levels of IL-6 and IL-10 are increased in COVID-19 patients. • The absolute values of CD4+ T cells are decreased in COVID-19 patients. • The severity of lung lesions predicts poor clinical outcomes. • CT signal may be a predictor of the transition from mild to severe., Objectives To study the and correlations of lymphocytes and cytokines between changes of lung lesion volumes in patients with COVID-19, and to predict their correlation. Methods 93 patients with COVID-19 were divided into mild and severe groups. The data of lymphocyte subgroups and cytokines were collected, the imaging characteristics were measured and correlation analysis was performed to analyze the differences. Results 60 mild and 33 severe patients were included, Lymphocyte subsets decreased in both groups. The percentages of reduction of absolute lymphocytes value in mild and severe groups were 32% and 64% respectively. The lung CT lesion volume of all patients was 241.45 ± 282.92 cm3, among which the mild group was 151.29 ± 226.04 cm3 and the severe group was 405.38 ± 304.90 cm3, respectively. In critically ill patients, the decrease of absolute value of CD4 + T cells and increase of IL-6 level are significantly correlated with the volume of lung lesions. Conclusions The absolute values of CD3+, CD4+, and CD8 + T cells are lower in patients with COVID-19, the levels of IL-6 and IL-10 are increased. The severity of lung lesions predicts poor clinical outcomes and may be a predictor of the transition from mild to severe.

Object. To investigate the clinicopathological features, imaging findings, treatment, and prognosis of primary pulmonary lymphoepitheliomatoid-like carcinoma. Methods. The clinical data of six patients with primary pulmonary lymphoepithelioma-like carcinoma treated in Zhejiang Taizhou Hospital of Taizhou Enze Medical Center (Group) from May 2014 to December 2018 were summarized and analyzed. Combined with the relevant literature, the primary pulmonary lymphoepithelioma-like carcinoma was analyzed retrospectively. Results. The main manifestations of six patients were respiratory symptoms, and cough was the most common. The imaging features of six patients were mainly round-like high-density mass shadow or nodule shadow. All patients were diagnosed by pathology. Microscopically, the cancer cells were nested, with large nuclei and vacuoles and abundant lymphocyte infiltration in the tumor stroma. The positive rates of EBER, p63, CK5/6, and Ki-67 were high, and TTF-1 was negative. Five patients received surgical treatment. One patient developed brain metastasis 12 months after operation and received craniocerebral radiotherapy. The other patients did not receive radiotherapy and chemotherapy, and one patient did not receive treatment. After follow-up, four patients survived so far, the longest survival time was 82 months, one patient lost follow-up, and one patient died of lung metastasis 24 months after operation. Conclusion. Primary pulmonary lymphoepitheliomatoid-like carcinoma is a rare lung malignant tumor, whose pathogenesis is related to Epstein-Barr virus infection. The clinical manifestations are nonspecific, but with unique pathological characteristics. Surgical resection is the proper treatment for early-stage patients, and comprehensive treatment with surgery as the main treatment is suitable for late-stage patients. The prognosis is good.

Cointegrate/hybrid plasmids combine the genetic elements of two or more plasmids and generally carry abundant antimicrobial resistance determinants. Hence, the spread of cointegrate plasmids will accelerate the transmission of AMR genes. To evaluate the transmission risk caused by cointegrate plasmids, we investigated the structural diversity, fitness cost, and stability of a cointegrate plasmid in Klebsiella pneumoniae YZ6 and Escherichia coli EC600. The cointegrate plasmid pSL131_IncA/C_IncX3 was from a clinical Salmonella Lomita strain. After transferring the plasmid into E. coli EC600 by conjugation, we observed plasmids with different structures, including a full-length original plasmid and two truncated versions. By contrast, DNA fragment deletion and blaCTX-M-14 gene insertion in the plasmid were detected in a transconjugant derived from K. pneumoniae YZ6. These results suggest that the structure of the plasmid was unstable during conjugation. Furthermore, both the full-length plasmid in EC600 and the structurally reorganized plasmid in YZ6 imposed a fitness cost on the bacterial host and enhanced biofilm formation ability. Serial passaging in antibiotic-free medium resulted in a rapid decline of the plasmid in YZ6. However, the stability of the structurally reorganized plasmid in YZ6 was improved via serial passaging in antibiotic-containing medium. SNP calling revealed that mutations of the outer membrane porin may play an essential role in this process. These findings indicate that structural versatility could contribute to the dissemination of cointegrate plasmids. Although the plasmid incurred a fitness cost in other Enterobacteriaceae species, positive selection could alleviate the adverse effects.

Background. Novel coronavirus disease 2019 (COVID-19) was discovered in December 2019 and has infected more than 80 million people worldwide, and more than 50 million people have achieved a clinical cure. In this study, the pulmonary function results of patients after clinical medicine for three months were reported. Objective. To investigate the effect of COVID-19 on lung function in patients. Methods. A retrospective analysis was performed on 56 COVID-19-infected patients who were cured after the clinical treatment at Taizhou Public Health Medical Center in Zhejiang Province from January 31, 2020, to March 10, 2020. At discharge and three months after discharge, lung function was measured, including inspiratory vital capacity (IVC), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), forced expiratory volume in first second to inspiratory vital capacity (FEV1/IVC), maximum mid-expiratory flow rate (MEF), peak expiratory flow rate (PEF), and carbon monoxide dispersion (DLCO). Results. At discharge, there were 37 patients (66.1%) with pulmonary dysfunction, 22 patients (39.3%) with ventilation dysfunction, 31 cases (55.4%) with small airway dysfunction, and 16 cases (28.6%) with restricted ventilation dysfunction combined with small airway dysfunction. At 3 months after discharge, 24 of the 56 patients still had pulmonary dysfunction and all of them had small airway dysfunction, of which 10 patients (17.9%) were restricted ventilation dysfunction combined with small airway dysfunction. DLCO was measured three months after discharge. Twenty-nine patients (51.8%) had mild to moderate diffuse dysfunction. All pulmonary function indexes of 56 patients recovered gradually after 3 months after release, except FEV1/IVC, and the difference was statistically significant ( P

EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Mefatinib is a novel, bioavailable, second-generation, irreversible pan-EGFR inhibitor. This phase Ib/II open-label, single-arm, multi-center study investigated the efficacy, safety, biomarker, and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC. This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg (n = 51) or 80 mg (n = 55). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The cohort achieved an ORR of 84.9% and DCR of 97.2%. The median PFS was 15.4 months and the median OS was 31.6 months. Brain metastasis was detected in 29% of patients (n = 31) at diagnosis and demonstrated an ORR of 87.1%, PFS of 12.8 months, and OS of 25.2 months. Adverse events primarily involved skin and gastrointestinal toxicities, which were well-tolerated and manageable. Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline, first follow-up 6 weeks from starting mefatinib therapy (F1), and at progression. Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53 (14.0 vs 15.4 months; p = 0.315). Furthermore, circulating tumor DNA clearance was associated with longer PFS (p = 0.040) and OS (p = 0.002). EGFR T790M was the predominant molecular mechanism of mefatinib resistance (42.1%, 16/38). First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC.

Glycyrrhizic acid (GA), also known as glycyrrhizin, is a triterpene glycoside isolated from plants of Glycyrrhiza species (licorice). GA possesses a wide range of pharmacological and antiviral activities against enveloped viruses including severe acute respiratory syndrome (SARS) virus. Since the S protein (S) mediates SARS coronavirus 2 (SARS-CoV-2) cell attachment and cell entry, we assayed the GA effect on SARS-CoV-2 infection using an S protein-pseudotyped lentivirus (Lenti-S). GA treatment dose-dependently blocked Lenti-S infection. We showed that incubation of Lenti-S virus, but not the host cells with GA prior to the infection, reduced Lenti-S infection, indicating that GA targeted the virus for infection. Surface plasmon resonance measurement showed that GA interacted with a recombinant S protein and blocked S protein binding to host cells. Autodocking analysis revealed that the S protein has several GA-binding pockets including one at the interaction interface to the receptor angiotensin-converting enzyme 2 (ACE2) and another at the inner side of the receptor-binding domain (RBD) which might impact the close-to-open conformation change of the S protein required for ACE2 interaction. In addition to identifying GA antiviral activity against SARS-CoV-2, the study linked GA antiviral activity to its effect on virus cell binding.

The adenoviral DNA is prevalent in adenotonsillectomy specimens from pediatric patients, though the virus seems to be in latent state. The tonsils are at the forefront of airway entry point and are the first line of defense against airway viral and bacterial infections. We hypothesized that tonsil microbiota plays a role in human adenovirus (HAdV) latency and reactivation. In this study, we surveyed the presence of HAdV in tonsillectomy samples from 81 patients and found that HAdV DNA was in 85.2% of the tonsil samples. We then determined the microbiota of the samples. Taxonomic profiling showed that Proteobacteria, Firmicutes, Fusobacteriota, and Bacteroidota accounted for approximately 70% of the total phyla in tonsil samples. A correlation analysis showed that the HAdV-positive samples had significantly higher abundance of Neisseria and Bifidobacterium and lower abundance of Streptococcus, Ochrobactrum, and Lactobacillus than that of the HAdV-negative samples. Culture-based isolation followed by 16S rRNA sequencing identified Staphylococcus aureus, Streptococcus pneumoniae, Veillonella, Prevotella, Capnocytophaga sputigena, Pseudomonas aeruginosa, Neisseria, and Moraxella catarrhalis from the samples. Gas chromatography-mass spectrometry (GC-MS) profiling of short-chain fatty acids in bacterial cultures of minced tonsillectomy tissues or representative isolates showed the cultures contained various amounts of short-chain fatty acids (SCFAs). Treatment of isolated tonsil lymphocytes with bacterial lipopolysaccharide (LPS) or with SCFAs promoted HAdV reactivation. The compounds also promoted HAdV reactivation in a xenograft model with implanted tonsil fragments. This study shows a potential interplay between tonsil microbiota and HAdV reactivation that may lead to recurrent virus infection of respiratory tract disease. IMPORTANCE Human adenovirus infection is common among pediatric patients and can be life-threatening among organ transplant recipients. Adenovirus is transmitted by close contact, but it is believed that a majority of invasive events appear to arise from viral reactivation. The human tonsil is a reservoir for virus latency and has a high prevalence of latently infected adenovirus. Also, tonsils are located at the gateway of the respiratory tracts and are commonly exposed to bacterial pathogens. Here, we uncovered adenoviral DNA-positive and -negative samples that appeared to harbor distinct distribution patterns of microorganisms. SCFAs, primary metabolites of microbiota on tonsils, could induce the adenovirus reactivation in tonsil lymphocytes, resulting in adenovirus replication and production of infectious virions. The study suggests that viral-bacterial interaction plays a role in virus reactivation from latency and could be a contributing factor for recurrent viral infection in pediatric patients.

A case report of coinfection with Talaromyces marneffei (T. marneffei) and Cryptococcus neoformans (C. neoformans) is presented in a 57-year-old woman with hemolytic anemia who received dexamethasone for 8 years. To the best of our knowledge, this patient was successfully treated with voriconazole. This is the first case of T. marneffei and C. neoformans coinfection in a HIV-negative host. Clinicians should be aware of concomitant infection with T. marneffei and other pathogens in immunocompromised hosts. The current case report highlights the importance of clinician awareness of concurrent infections with T. marneffei and other pathogens in immunosuppressed patients.

MgZrNb2−x(Sn1/2W1/2)xO8 (0 ≤ x ≤ 0.15) dielectric ceramics were synthesized through solid state reaction route. SnO2, WO3 and Nb2O5 were pre-calcined to promote the substitution element to fully enter the Nb-site when reacting with MgO and ZrO2. The formation of solid solutions with monoclinic wolframite structure were confirmed. Rietveld refinement and P–V–L theory were used as intrinsic factors of analyzing the changes in microwave dielectric properties. With the increase of (Sn1/2W1/2)5+ substitution amount, er of highly densified MgZrNb2−x(Sn1/2W1/2)xO8 ceramic decreased slowly, which was mainly ascribed to low bond iconicity. The optimal substitution of isovalent composite ions enhances the total lattice energy, leading to an increase in Q × f value. The increase of τf was closely correlated with the decrease of the total bond energy. When x = 0.06, the optimal dielectric properties, er= 24.61, Q × f = 93346.3 GHz, τf= − 48.46 ppm/°C, were successfully obtained for the MgZrNb2−x(Sn1/2W1/2)xO8 specimens sintered at 1300 °C.

The dense MgZr(Nb1−xSbx)2O8 ceramics were synthesized through standard solid state reaction route. All samples were identified as the pure phase with monoclinic wolframite structure and P2/c space group. SEM was carried out to study the effect of surface morphology on dielectric properties. Rietveld refinement was utilized to observe the impact of equivalent substitution (Sb5+) at the Nb-site on the microstructure of crystals. The phenomenon of non-monotonic changing in quality factor (Q × f) and monotonic increase in dielectric constant (er) was explained by bond ionicity and lattice energy based on the P-V-L theory. In addition, the deterioration of temperature coefficient of resonant frequency (τf) was closely related to the reduction of bond energy. Finally, the optimum dielectric properties of MgZr(Nb0.92Sb0.08)2O8 sample sintered at 1320 °C for 6 h were obtained: er = 25.69, Q × f = 83505.2 GHz, τf = −58.74 ppm/°C.

Background: In December 2019, the discovery of the novel coronavirus was first reported in Wuhan, China, which subsequently and rapidly spread throughout the country and worldwide, resulting in a pandemic.After a year of intense research, our knowledge of the new coronaviruses has gradually improved; however, knowledge regarding the time of their complete clearance from the body and the factors influencing clearance are currently inadequate. Results: We conducted a retrospective observational study comprising 135 patients above the age of 18 years with a confirmed diagnosis of COVID-19 pneumonia, who were admitted to the Public Health Center of Taizhou Hospital of Zhejiang Province, Zhejiang University from January 23, 2020, to March 11, 2020. The findings regarding the duration of the infection from the time of onset to the time of being asymptomatic (whichever was observed first) indicated that novel coronaviruses were cleared from the respiratory tract in a maximum of 84 days and a minimum of 1 day with a median clearance time (quartile) of 20 (13, 30) days. Moreover, viruses were cleared from the digestive tract in a maximum of 72 days and a minimum of 5 days with a median clearance time (quartile) of 25 (20.75, 31) days. The viral shedding time of SARS in the digestive tract was found to be longer than that in the respiratory tract (p = 0.03). Severe disease (P < 0.001), advanced age (P < 0.001), lymphopenia (P = 0.01) and elevated CRP (P = 0.036) were significantly associated with longer clearance time in the respiratory tract. Gender (P = 0.754), novel coronavirus antibodies (P = 0.75), and antibiotic use (P = 0.093) were not associated with the time span required for the novel coronavirus to be cleared from the respiratory tract. Conclusions: Independent risk factors for the longer clearance time of novel coronaviruses in the digestive tract versus that in the respiratory tract were compared. Severe disease, advanced age, lymphopenia, and elevated CRP were determined to be factors prolonging the clearance of novel coronaviruses.

LINC01089, a newly discovered long non-coding RNA (lncRNA), has been reported to inhibit the progression of various types of cancers. This study aimed to characterize LINC01089 in the pathogenesis of lung adenocarcinoma (LUAD). LINC01089 expression in LUAD tissues or/and cells and its association with the overall survival of LUAD patients was analyzed in The Cancer Genome Atlas (TCGA)-LUAD database, by qRT-PCR or by Kaplan-Meier's curve. Databases of StarBase, LncBase, and DEmiRNA were used to predict and confirm the interaction between LINC01089 and potential LINC01089-targeted microRNAs (miRNAs). The expressions of these miRNAs in LUAD tissues or/and cells were determined by qRT-PCR, and dual-luciferase reporter assay was performed to validate lncRNA-miRNA interaction. The expressions of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cleaved caspase-3 in LUAD cells were analyzed by Western blot. LINC01089 improved overall survival of LUAD patients and was low-expressed in LUAD. Upregulating LINC01089 expression reduced LUAD cell viability, inhibited colony formation, enhanced apoptosis, accompanied by downregulated Bcl-2 and miR-543 and upregulated Bax and Cleaved caspase-3. MiR-543 was determined as a target gene of LINC01089, and was high-expressed in LUAD tissues. Upregulating miR-543 expression induced the opposite effects to LINC01089 upregulation on these cellular biological behaviors and the expressions of Bcl-2, Bax and Cleaved caspase-3. Moreover, the effects of miR-543 upregulation and LINC01089 upregulation were mutually counteracted by each other. LINC01089 inhibited lung adenocarcinoma cell proliferation and promoted apoptosis via sponging miR-543.

Additional file 2: Figure S2. Alignment of a representative sample of the transposases of IS6 family members including members of each major clade. Alignment was by Clustal [129] and the graphic output from SnapGene. The figure shows the probable zinc finger N-terminal extension (consecutive CxxC motifs), the helix-turn-helix domain (HTH) and the catalytic domain (DDE K/R).

Additional file 1: Figure S1a-g. Left (IRL) and right IRR and a combined IRL + IRR inverted terminal repeats for each clade are shown in WebLogo format [25]. Figure S1h. The last section shows an alignment of the ends of clade Aiv adjusted by hand.

PD-L1 is one of the current biomarkers for immune checkpoint inhibitor (ICI) therapy in patients with non-small-cell lung cancer. However, the expression of PD-L1 in the real world and its related influencing factors remain unclear. We want to observe the expression of PD-L1 in the real world and study the related influencing factors through the collection and analysis of clinical data. R software (version 4.0) was used to perform data analysis and the “corplot” package for correlation analysis. A total of 296 individuals (mean [SD] age, 67 [9] years; 23%female) were assessed. According to the expression amount of PD-L1, the cohort was divided into low nonexpression group ( PD ‐ L 1 < 1 % , 26.7%), low-expression group ( 1 % ≤ PD ‐ L 1 < 50 % , 49.3%), and high-expression group ( PD ‐ L 1 ≥ 50 % , 23.5%). Age, gender, underlying diseases, smoking status, and PD-L1 expression level were not statistically significant. We found that the expression of PD-L1 was correlated with serum albumin ( P < 0.05 ) and pathological type ( P < 0.05 ) and had a negative correlation with EGFR mutation but did not correlate with gender, age, smoking status, combined with underlying diseases, tumor stage, whether it was initially treated or not, sampling site, specimen type, specimen storage time, R-IFN, CD4, CD8, NLR, CRP, and LDH. The present findings indicated that serum albumin, pathological type, and EGFR mutations are associated with PD-L1 expression in patients with NSCLC, which may provide a new basis for individualized immunotherapy and need further study to confirm. The results of this study help to further reveal the actual expression of PD-L1 in non-small-cell lung cancer patients with real events.

The nuclear factor-kappa B (NF

Background: The outbreak of COVID-19 has a significant impact on the health of people around the world. In the clinical condition of COVID-19, the condition of critical cases changes rapidly with a high mortality rate. Therefore, early prediction of disease severity and active intervention play an important role in the prognosis of severe patients.Methods: All the patients with COVID-19 in Taizhou city were retrospectively included and segregated into the non-severe and severe group according to the severity of the disease. The clinical manifestations, laboratory examination results, and imaging findings of the 2 groups were analysed for comparing the differences between the 2 groups. Univariate and multivariate logistic regression were used for screening the factors that could predict the disease, and the nomogram was constructed.Results: A total of 143 laboratory-confirmed cases were included in the study, including 110 non-severe patients and 33 severe patients. The median age of patients was 47 years (range, 4–86 years). Fever (73.4%) and cough (63.6%) were the most common initial clinical symptoms. By using the method of multivariate logistic regression, the variables to construct nomogram include age (OR: 1.052, 95% CI: 1.020–1.086, P = 0.001), body temperature (OR: 2.252, 95% CI: 1.139–4.450, P = 0.020), lymphocyte count (OR: 1.128, 95% CI: 1.000–1.272, P = 0.049), ADA (OR: 1.163, 95% CI: 1.023–1.323, P = 0.021), PaO2 (OR: 0.972, 95% CI: 0.953–0.992, P = 0.007), IL-10 (OR: 1.184, 95% CI: 1.037–1.351, P = 0.012), and bronchiectasis (OR: 3.818, 95% CI: 1.694–8.605, P = 0.001). The AUC of the established nomogram was 0.877.Conclusions: This study established a stable nomogram for predicting the severity of COVID-19, and the clinicians can use the established nomogram for predicting the severity of newly diagnosed COVID-19 patients and to conduct active intervention for minimising the mortality rate and improving the prognosis of severe patients.

Background: In December 2019, the first case of pneumonia associated with the SARS-CoV-2 was found in Wuhan and rapidly spread throughout China, so data are needed on the affected patients. The purpose of our study was to find the clinical manifestations and CT features of COVID-19.Methods: All patients with COVID-19 in Taizhou city were retrospectively included and divided into non-severe group and severe group according to the severity of the disease. The clinical manifestations, laboratory examinations and imaging features of COVID-19 patients were analyzed, and the differences between the two groups were compared.Results: A total of 143 laboratory-confirmed cases were included in the study, including 110 non-severe patients and 33 severe patients. The median age of patients was 47 (range 4–86 years). Fever (73.4%) and cough (63.6%) were the most common initial clinical symptoms. Between two groups of cases, the results of aspartate transaminase, creatine kinase and lactate dehydrogenase, serum albumin, CR, glomerular filtration rate, amyloid protein A, fibrinogen, calcitonin level and oxygen partial pressure, IL – 10, absolute value of CD3, CD4, CD8 were different, and the difference was statistically significant (P Conclusions: Most of the cases of COVID-19 in Taizhou have mild symptoms and no death. In addition to clinical symptoms, some laboratory tests (such as absolute values of CD4 and CD8) and CT findings can be used to assess the severity of the disease.

Adenovirus (HAdV) infection is a common cause of illness among young children, immunocompromised patients, and transplant recipients. The majority of HAdV infections are self-limited, but recurring infection is frequently encountered in young children and may require hospitalization. In this study, we surveyed the presence of HAdV in tonsillectomy samples and investigated epigenetic conditions that contributed to HAdV reactivation. HAdV DNA was detected from 86.7% donors. The lymphocytes isolated from the samples failed to produce infectious HAdV after incubation, suggesting the viruses remained in a latent status. To determine whether epigenetic factors played a role in HAdV reactivation, isolated lymphocytes were treated with a small compound library. Viral DNA replication and infectious HAdV production were assayed by PCR and by a secondary infection assay. We identified several compounds, mainly pan- and selective histone deacetylase (HDAC) inhibitors, which showed activity to reactivate HAdV from latency. The viruses were isolated and were determined as species C HAdV. Using a model of HAdV lytic infection, we showed that the compounds promoted histone-3 acetylation and association with viral early gene promoters. In addition to demonstrate the palatine tonsils as a reservoir of latent HAdV, this study uncovers a critical role of histone acetylation in HAdV reactivation, linking HAdV latency to recurrent HAdV infection. IMPORTANCE Respiratory tract infection by adenoviruses is among the most common diseases in children, attributing to approximately 20% of hospitalizations of children with acute respiratory infection (ARI). Adenovirus transmits by direct contact, but recurrent infection is common. Ever since its isolation, adenovirus has been known to have the ability to establish persistent or latent infection. We found 87.7% tonsillectomy specimens contained detectable amounts of adenoviral DNA. Isolated lymphocytes did not produce infectious adenoviruses without stimulation. By screening an epigenetic informer compound library, we identified several histone deacetylase inhibitors that promoted adenovirus reactivation that was evidenced by increased viral DNA replication and production of infectious viruses. The human tonsils are covered with bacterial pathogens that may utilize pathogen-associated pattern molecules or metabolites to cause epigenetic activation and proinflammatory gene transcription, which may lead to viral reactivation from latency. The study shows that recurrent adenovirus infection could arise from reactivation of residing virus from previous infections.

Copy‐out/paste‐in transposition is a major bacterial DNA mobility pathway. It contributes significantly to the emergence of antibiotic resistance, often by upregulating expression of downstream genes upon integration. Unlike other transposition pathways, it requires both asymmetric and symmetric strand transfer steps. Here, we report the first structural study of a copy‐out/paste‐in transposase and demonstrate its ability to catalyze all pathway steps in vitro. X‐ray structures of ISC th4 transposase, a member of the IS 256 family of insertion sequences, bound to DNA substrates corresponding to three sequential steps in the reaction reveal an unusual asymmetric dimeric transpososome. During transposition, an array of N‐terminal domains binds a single transposon end while the catalytic domain moves to accommodate the varying substrates. These conformational changes control the path of DNA flanking the transposon end and the generation of DNA‐binding sites. Our results explain the asymmetric outcome of the initial strand transfer and show how DNA binding is modulated by the asymmetric transposase to allow the capture of a second transposon end and to integrate a circular intermediate., Structures of ISC th4 transposase/DNA complexes at different stages of the transposition pathway provide first insight into transpososome architecture and reaction mechanism of this major bacterial DNA mobility pathway.

Background: An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19), has spread throughout China and received worldwide attention. After nearly 2 months efforts by the Chinese government and people from all walks of life, the epidemic in China has gradually been controlled. The awareness of the disease has gradually increased. We have detected the SARS-CoV-2 gene in the patient's sputum, throat swabs and feces, blood and even urine samples, but whether the SARS-CoV-2 RNA is detected in the upper and lower respiratory tracts and the extrapulmonary age is unknown.Methods: We collected data from 146 patients admitted to the Public Health Center of Taizhou Hospital, Zhejiang University, China from January 23, 2020 to March 11, 2020, and confirmed the diagnosis of new-type coronavirus pneumonia by RT-PCR. The final selection was made after screening. For a total of 134 confirmed patients, we collected their clinical data and sputum, nasopharyngeal swabs or throat swabs, fecal nucleic acid test results, and calculated the age of each specimen.Results: A total of 134 confirmed patients were included in the study; of them, 93 were of the common type, and 41 were critically ill. There were no significant differences between males and females, P = 0.853) and their epidemiological history (P = 0.441). The average age of severe patients was 55.85 ± 13.28 years, which was higher than that of common patients at 44.06 ± 12.86 years (P = 0.00). The results showed that the time of SARS-CoV-2 RNA in the upper respiratory tract was 15.1 ± 7.23 days for common patients and 20.56 ± 6.59 days for severe patients, which was longer than that of common patients (P = 0.00). The time of SARS-CoV-2 RNA in the lower respiratory tract was 27.45 ± 10.06 days for common patients and 29.78 ± 10.11 days for severe patients. There was no statistical difference (P = 0.328); SARS-CoV-2 RNA existed in the digestive tract. The time was 22.6 ± 7.69 days for common patients and 27.24 ± 7.86 days for severe patients, which was longer than that of common patients (P = 0.01). SARS-CoV-2 existed for a shorter time in the upper respiratory and digestive tracts than in the lower respiratory tract.CONCLUSION: SARS-CoV-2 is present in the lower respiratory tract for longer than the upper respiratory and digestive tracts, and there were no statistical differences in the lower respiratory tract between common and severe patients.

Background The number of patients with pneumonia stemming from the 2019 novel coronavirus (COVID-19) infection has increased rapidly. However, the clinical characteristics of discharged patients remain little known. Here, we attempt to describe the clinical characteristics and treatment experiences of discharged cases from Taizhou, China. Methods A total of 60 patients with COVID-19-infected pneumonia who were discharged from Taizhou Enze Medical Center (Group), from January 31, 2020, to February 16, 2020, were included in the analysis. The discharge criteria were based on the New Coronavirus Pneumonia Prevention and Control Program (Fifth Edition, China). Results Of the 60 patients, the median age was 41 years, and 58.3% were male. Only 13.3% of patients were identified as having severe novel coronavirus pneumonia. All patients received combined antiviral treatment on admission, including β-interferon, lopinavir/tonavir, Abidol and oseltamivir. All patients with severe conditions received gamma globulin and hormone therapy. No patients had endotracheal intubation or died. The median duration from symptom onset to hospitalization was 3 (range, 0-15) days. The median duration of COVID-19 shedding was 14 (range, 5-26) days, and the median duration of hospital stay was 15 (range, 7-23) days. Conclusions Early therapy and comprehensive therapy are key to the outcome for patients with COVID-19-infected pneumonia, especially for those with severe pneumonia. Trial registration number ChiCTR2000029866.

Background: In December 2019, the first case of pneumonia associated with the 2019 novel coronavirus was found in Wuhan and rapidly spread throughout China, so

Dense Mg(Zr1-xGex)Nb2O8 (x = 0, 0.1, 0.2, 0.3, 0.4) ceramics were successfully synthesized through traditional solid state reaction route. The relations between microstructure and microwave dielectric properties were studied. The formation of single MgZrNb2O8 phase with the monoclinic wolframite structure was verified by XRD patterns. Experimental dielectric constant was found to be closely related to bond polarizability, and theoretical dielectric constant calculated based on P-V-L theory shows the same tendency with the experimental dielectric constant when the substitution amount of Ge4+ changes. The increase in Q×f and |τf| were mainly attributed to the increase in packing fraction and the Nb-site bond valence, respectively. Excellent dielectric properties were obtained for Mg(Zr1-xGex)Nb2O8 (x = 0.2) ceramic sintered at 1300 °C for 4 h: er= 24.26, Q×f= 80,492.8 GHz, τf= -51.95 ppm/°C.