Search

ATM serine/threonine kinase (ATM; previously known as ataxia‐telangiectasia mutated) plays a critical role in maintaining genomic stability and regulates multiple downstream pathways, such as DNA repair, cell cycle arrest, and apoptosis. As a serine/threonine kinase, ATM has an array of downstream phosphorylation substrates, including checkpoint effector checkpoint kinase 2 (CHK2). ATM inhibits cell cycle progression by phosphorylating and activating CHK2, which plays an important role in the formation and development of tumors and participates in DNA repair responses after double‐stranded DNA breaks. In this study, we used a recently developed mammalian functional genetic screening system to explore a series of ATM substrates and their role in DNA damage to enhance our understanding of the DNA damage response. Ubiquilin 4 (UBQLN4), which belongs to the ubiquilin family characterized by its ubiquitin‐like (UBL) and ubiquitin‐associated (UBA) domains, was identified as a new substrate for ATM. UBQLN4 is involved in various intracellular processes, such as autophagosome maturation, p21 regulation, and motor axon morphogenesis. However, the biological function of UBQLN4 remains to be elucidated. In this study, we not only identified UBQLN4 as a substrate for ATM, but also found that UBQLN4 interacts with and stabilizes the anti‐apoptotic proteins Bcl‐2‐related protein A1 (BCL2A1) and Bcl‐2‐like protein 10 (BCL2L10) and prevents mesothelioma cell apoptosis in response to DNA damage. These findings expand our understanding of the role of UBQLN4 in mesothelioma and provide new insights into potential mesothelioma treatments targeting substrates for ATM., ATM phosphorylates an array of substrates that play essential roles in DNA damage response. In this study, we used a functional genetic screening system to explore ATM substrates and identified ubiquilin 4 (UBQLN4) as a new substrate for ATM. Phosphorylated UBQLN4 prevented cytochrome c release and inhibited apoptosis in mesothelioma during DNA damage by stabilizing BCL2A1 and BCL2L10. These findings expand our understanding of the role of UBQLN4 in mesothelioma and provide a new insight into mesothelioma treatment by targeting ATM substrates.

The subfamily Sarcophaginae is extremely diverse in morphology, habit and geographical distribution, and usually considered to be of significant ecological, medical, and forensic significance. In the present study, 18 mitochondrial genomes (mitogenomes) of sarcophagid flies were first obtained. The rearrangement and orientation of genes were identical with that of ancestral insects. The degrees of compositional heterogeneity in the datasets were extremely low. Furthermore, 13 protein-coding genes were evolving under purifying selection. The phylogenic relationship of the genus-group taxa Boettcheria + (Sarcophaga + (Peckia + (Ravinia + Oxysarcodexia))) was strongly supported. Four subgenera were recovered as monophyletic (Liopygia, Liosarcophaga, Pierretia, Heteronychia) in addition to Parasarcophaga as polyphyletic. The sister-relationships between S. dux and S. aegyptiaca, S. pingi and S. kawayuensis were recovered, respectively. Moreover, the molecular phylogenetic relationships among the subgenera Helicophagella, Kozlovea, Kramerea, Pandelleisca, Phallocheira, Pseudothyrsocnema, Sinonipponia and Seniorwhitea were rarely put forward prior to this study. This study provides insight into the population genetics, molecular biology, and phylogeny for the subfamily Sarcophaginae, especially for the subgeneric classification of Sarcophaga. However, compared with the enormous species diversity of flesh flies, the available mitogenomes are still limited for recovering the phylogeny of Sarcophaginae.

Rationale: Epstein-Barr virus (EBV) is found in ~7% of gastric carcinoma cases worldwide, and all tumour cells harbour the clonal EBV genome. EBV can regulate pathways and protein expression to induce gastric carcinoma; however, the molecular mechanism underlying EBV-associated gastric carcinoma (EBVaGC) remains elusive. Methods: GEO microarray and molecular experiments were performed to compare CXCR4 expression between EBV-positive and EBV-negative gastric carcinoma (EBVnGC). Transfections with LMP2A plasmid or siRNA were carried out to assess the role of LMP2A in CXCR4 expression. The effects and mechanisms of CXCR4 on cell autophagy were analysed in vitro using molecular biological and cellular approaches. Additionally, we also determined the regulatory role of CXCR4 in latent EBV infection. Results: CXCR4 expression was significantly upregulated in EBVaGC tissues and cell lines. LMP2A could induce AKT phosphorylation to increase NRF1 expression, thereby binding to the CXCR4 promoter to increase its transcriptional level. Moreover, CXCR4 promoted ZEB1 expression to upregulate ATG7 synthesis, which could then activate autophagy. Moreover, CXCR4 increased the number of cells entering the G2/M phase and inhibited cell apoptosis via the autophagy pathway. Finally, CXCR4 knockdown was associated with elevated BZLF1 expression, but this effect was not influenced by autophagy. Conclusions: Our data suggested new roles for CXCR4 in autophagy and EBV replication in EBVaGC, which further promoted cell survival and persistent latent infection. These new findings can lead to further CXCR4-based anticancer therapy.

We reported 20 cases of discharged COVID‐19 patients whose RT‐PCR test results showed “re‐positive”. After finding “re‐positive ”, these patients were admitted to hospital for the second time and were followed up until the end of May 2020. Methods: Record detailed treatment and follow‐up process, and collect relevant data. The possible causes and potential clinical significance of this phenomenon are discussed. This article is protected by copyright. All rights reserved.

Background Although the fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer. Methods Paired prostate cancer samples were selected, and expressions of MCM3AP-AS1, miR-876-5p and WNT5A were examined by qRT-PCR. MCM3AP-AS1 shRNA was transfected into LNCaP and PC-3 cell lines, and then the proliferative activity and apoptosis of cancer cells were detected by CCK-8 assay, EdU assay and flow cytometry analysis, respectively. qRT-PCR and Western blot were used to analyze the changes of miR-876-5p and WNT5A. Luciferase reporter gene assay was employed to determine the regulatory relationship between miR-876-5p and MCM3AP-AS1, miR-876-5p and WNT5A. Results MCM3AP-AS1 was significantly up-regulated in cancerous tissues of prostate cancer samples, positively correlated with the expression of WNT5A, while negatively related with miR-876-5p. After transfection of MCM3AP-AS1 shRNA into prostate cancer cells, the proliferative ability of cancer cells was signally inhibited, but the apoptosis of cancer cells was increased. MCM3AP-AS1 shRNA could reduce the expression of WNT5A on both mRNA and protein levels. Besides, MCM3AP-AS1 was identified as a sponge of miR-876-5p. WNT5A was validated as a target gene of miR- 876-5p. Conclusion MCM3AP-AS1 is abnormally up-regulated in prostate cancer tissues and can modulate the proliferation and apoptosis of prostate cancer cells, which has the potential to be the “ceRNA” to regulate the expression of WNT5A by targeting miR-876-5p.

Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were mainly based on information from adult populations. Limited data are available for children with COVID-19, especially for infected infants. Methods We report a 55-day-old case with COVID-19 confirmed in China and describe the identification, diagnosis, clinical course, and treatment of the patient, including the disease progression from day 7 to day 11 of illness. Results This case highlights that children with COVID-19 can also present with multiple organ damage and rapid disease changes. Conclusions When managing such infant patients with COVID-19, frequent and careful clinical monitoring is essential., Data about infants infected with novel coronavirus disease (COVID-19) are scarce. Herein, we report a 55-day-old case who presented with COVID-19 pneumonia. The exposure, symptoms, laboratory indicators, and hospitalization are described in detail.

Graphical Abstract Graphical Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. To investigate effect of silymarin on chronic obstructive pulmonary disease (COPD). The serum samples of 20 healthy controls, 20 patients with acute exacerbation of COPD and 20 patients with stable COPD were collected. LPS and smoking were used to induce COPD mouse model. Our results showed that in patients with acute exacerbation of COPD, O2-level release from peripheral blood neutrophils were negatively correlated with forced expiratory volume in the first second (FEV1), FEV1 in predicted value, FEV1/forced vital capacity (FVC), and arterial partial pressure (PaO2). (r=-0.898, -0.878, -874, -0.890, all P

Sarcophaga peregrina (Robineau-Desvoidy, 1830), a synanthropic flesh fly species found in different parts of the world, is of medical and forensic importance. Traditional methods of inferring developmental age rely on the life stage of insects and morphological changes. However, once the larvae reach the pupal and adult stage, morphological changes would become barely visible, so that the classic method would be invalid. Here, we studied the cuticular hydrocarbon profile of S. peregrina of the whole life cycle from larval stage to adult stage by GC–MS. Sixty-three compounds with carbon chain length ranging from 8 to 36 were detected, which could be categorized into four classes: n-alkanes, branched alkanes, alkenes, and unknowns. As developmental increased, branched alkanes dominant, and the content of high-molecular-weight hydrocarbons is variable, especially for 2-methyl C19, DiMethyl C21, docosane (C22), and tricosane (C23). This study shows that the composition of CHC could be used to determine the developmental age of S. peregrina and aid in postmortem interval estimations in forensic science.

Circular Ribonucleic Acid (CircRNA) plays regulatory roles in many biological processes, such as tumors and metabolic diseases. Due to the fact that circRNA is more stable and conservative than linear RNA, circRNA has become a potential biomarker in early clinical diagnosis and biomedical research. Therefore, the quantification of circRNA expression level is of importance for understanding their functions and their applications for disease diagnosis and treatment. Nevertheless, due to the low abundance of circRNA, it is still a challenge for the analysis of circRNA in cells. Herein, we proposed a sensitive detection method for circRNA based on the T7 exonuclease-assisted cycling enzymatic amplification. The fluorescent sensor was constructed by a hairpin molecular beacon and T7 exonuclease. With the cycling enzymatic amplification process, this sensor achieved the limit of detection of 1 pM with a good linear correlation in the range of 0 - 100 pM (R2 = 0.9891) using circBART2.2 as a model. Furthermore, we applied the proposed method in the determination of circBART2.2 in cell lysates. The results demonstrated that this method has promising applications in early diagnosis of Epstein-Barr virus (EBV) infection-related diseases using circRNA as the biomarker.

Epithelioid angiosarcoma arising in schwannoma is an extremely rare mesenchymal tumor that accounts for only 1 to 2% of all sarcomas. This type of tumor occurs in all parts of the body, most often in the skin and soft tissues and rarely in the mediastinum. The present study describes the case of an asymptomatic, 58-year-old male who presented with epithelioid angiosarcoma in the posterior mediastinum during a physical examination. Enhanced computed tomography of the chest revealed a 3.5 × 3.1-cm mass in the posterior mediastinum. Thoracoscopic mediastinal mass resection was performed under general anesthesia due to the possibility that the tumor was malignant. Pathological examination revealed the presence of angiosarcoma and schwannoma components. Immunohistochemical staining for cluster of differentiation (CD) 31, CD34, early growth response (EGR), vimentin, Sry-related HMG box (SOX)-10 and S-100 was strongly positive. The patient recovered and was discharged on postoperative day 5. Two months postsurgery, the patient returned for evaluation, and no evidence of tumor recurrence was observed.

Background Coronavirus disease 2019 (COVID-19) was first detected in patients with pneumonia in December 2019 in China and it spread rapidly to the rest of the world becoming a global pandemic. Several observational studies have reported that cancer is a risk factor for COVID-19. On the other hand, ACE2, a receptor for the SARS-CoV-2 virus, was found to be aberrantly expressed in many tumors. However, the characterization of aberrant ACE2 expression in malignant tumors has not been elucidated. Here, we conducted a systematic analysis of the ACE2 expression profile across 31 types of tumors. Methods Distribution of ACE2 expression was analyzed using the GTEx, CCLE, TCGA pan-cancer databases. We evaluated the effect of ACE2 on clinical prognosis using the Kaplan-Meier survival plot and COX regression analysis. Correlation between ACE2 and immune infiltration levels was investigated in various cancer types. Additionally, the correlation between ACE2 and immune neoantigen, TMB, microsatellite instability, Mismatch Repair Genes (MMRs), HLA gene members, and DNA Methyltransferase (DNMT) was investigated. The frequency of ACE2 gene mutation in various tumors was analyzed. Functional enrichment analysis was conducted in various cancer types using the GSEA method. Results In normal tissues, ACE2 was highly expressed in almost all 31 organs tested. In cancer cell lines, the expression level of ACE2 was low to medium. Although aberrant expression was observed in most cancer types, high expression of ACE2 was not linked to OS, DFS, RFS, and DFI in most tumors in TCGA pan-cancer data. We found that ACE2 expression was significantly correlated with the infiltrating levels of macrophages and dendritic cells, CD4+ T cells, CD8+ T cells, and B cells in multiple tumors. A positive correlation between ACE2 expression and immune neoantigen, TMB, and microsatellite instability was found in multiple cancers. GSEA analysis which was carried out to determine the effect of ACE2 on tumors indicated that several cancer-associated pathways and immune-related pathways were hyperactivated in the high ACE2 expression group of most tumors. Conclusion These findings suggest that ACE2 is not correlated with prognosis in most cancer types. However, elevated ACE2 is significantly correlated with immune infiltrating levels, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in lung and breast cancer patients. These findings suggest that ACE2 may affect the tumor environment in cancer patients with COVID-19.

Outer membrane protein A (OmpA) of Acinetobacter baumannii (A. baumannii) is associated with autophagy, which plays an important role in its pathogenicity. However, its exact pathophysiological role in the process of lung tissue cell autophagy remains unclear. In this study, animal and cell infection models were established by wild A. baumannii strain and An OmpA knockout mutant (OmpA-/- A. baumannii) strain. The expression levels of markers autophagy, histological change, cell viability and protein expression levels of inflammatory cytokines were examined. OmpA-/- A. baumannii was successfully constructed. The capacities of bacterial adhesion and invasion to host cells increased more obviously in the AB group and the AB + Rapa group than in the OmpA-/- AB group and AB + CQ group. The AB group and AB + Rapa group could produce double membrane vacuoles, endoplasmic reticulum dilation, mitochondrial ridge rupture, and mitochondrial vacuoles. OmpA could lead to increased LC3, AMPK, and PAMPK protein release, and decreased levels of P62, mTOR and pmTOR proteins in vivo and in vitro. OmpA caused lung pathology and the release of inflammatory cytokines. A. baumannii OmpA promotes autophagy in lung cells through the mTOR signalling pathway, which increases the bacterial colonization ability in the double-layer membrane autophagosome formed by the autophagy reaction to escape the clearance of bacteria by the host, promote the release of inflammatory mediators and aggravate the damage to the host.

Bladder cancer (BCa) is the most common cancer of the human urinary system, and is associated with poor patient prognosis and a high recurrence rate. Cancer stem cells (CSCs) are the primary cause of tumor recurrence and metastasis, possessing self‑renewal properties and resistance to radiation therapy. Our previous studies indicated that phosphorylated signal transduction and transcription activator 3 (STAT3) may be a potential biomarker to predict radiation tolerance and tumor recurrence in patients with BCa, following conventional radiotherapy. The aim of the present study was to investigate the underlying mechanism of STAT3 in the radio‑resistance of BCa cells. It was found that fractionated irradiation promoted the activation of two STAT3‑associated CSCs signaling pathways in BCa cells, namely suppressor of variegation 3‑9 homolog 1/GATA binding protein 3/STAT3 and Janus kinase 2/STAT3. Surviving cells exhibited elevated migratory and invasive abilities, enhanced CSC‑like characteristics and radio‑resistance. Furthermore, knockdown of STAT3 expression or inhibition of STAT3 activation markedly decreased the self‑renewal ability and tumorigenicity of radiation‑resistant BCa cells. Kaplan‑Meier analysis revealed that decreased STAT3 mRNA levels were associated with increased overall survival times in patients with BCa. Taken together, these data indicated that STAT3 may be an effective therapeutic target for inhibiting the progression, metastasis and recurrence of BCa in patients receiving radiotherapy.

Sarcophaga dux (Diptera: Sarcophagidae) is a necrophagous flesh fly species with potential forensic value for estimating minimum postmortem interval (PMImin). The basic developmental data and precise age estimates of the pupae are significant for PMImin estimation in forensic investigations. In the present study, we investigated the development data of that species at seven constant temperatures varying from 16 °C to 34 °C, including body length changes of the larve, developmental duration and accumulated degree hours of the preadults. Several reference genes for relative quantification of the differentially expressed genes (DEGs) were firstly selected and evaluated in the pupae of different ages under different temperatures. The DEGs of the insects during the pupal period at different constant temperatures (34, 25 and 16 °C) were further analyzed for more precise age estimation. The results showed that the developmental durations of the preadults at 16, 19, 22, 25, 28, 31 and 34 °C were 1478.6 ± 18.3 h, 726.1 ± 15.8 h, 538.5 ± 0.9 h, 394.1 ± 9.5 h, 375.6 ± 10.8 h, 284.1 ± 7.3 h, and 252.5 ± 6.1 h, respectively. The developmental threshold temperature the flies was 12.27 ± 0.35 °C, and the thermal summation constant was 5341.71 ± 249.29° hours. The most reliable reference genes during the pupal period at different temperatures were found: GST1 and 18S rRNA for the 34 °C group, GST1 and RPL49 for 25 °C, and 18S rRNA and 28S rRNA for 16 °C. The four differential expression genes (Hsp60, A-alpha, ARP, and RPL8) have the potential to be used for more precise age estimation of pupal S. dux. This work provides important basic developmental data and a more precise age estimation method for pupal S. dux, and improves the value of this species for PMImin estimation in forensic investigations.

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by excessive collagen in the extracellular matrix (ECM) of the lungs. Collagen is the primary protein component of the ECM. However, the exact mechanisms underlying the formation and deposition of collagen in the ECM under normal and pathological conditions remain unclear. Previous studies showed that lysyl hydroxylase (LH) plays a crucial role in the formation of collagen. Minoxidil is an FDA-approved anti-hypertensive agent that inhibits LH that reduces fibrosis. In this study, we investigated the functional roles of LHs (LH1, LH2, and LH3) in pulmonary fibrosis and the anti-fibrotic effects of minoxidil. MATERIAL AND METHODS Patient serum samples were examined for their expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLOD) 1-3, the genes encoding LH 1-3. Mice with bleomycin (BLM 2.5 mg/kg)-induced pulmonary fibrosis were administered a minoxidil solution (30 mg/kg) by oral gavage. RESULTS The PLOD mRNA levels were significantly higher in the IPF patients than in the healthy control subjects. Minoxidil suppressed the BLM-induced pulmonary fibrosis in vivo. These effects were associated with blocking TGF-β₁/Smad3 signal transduction and attenuating the expression and activity of LHs, resulting in decreased collagen formation, thus reducing the pulmonary fibrosis. The anti-fibrotic effects of minoxidil may be mediated through competitive inhibition of LHs activity, resulting in decreased pyridine cross-link formation and collagen production and deposition. CONCLUSIONS The results of this study suggest that LH represents a target to prevent or treat pulmonary fibrosis, and minoxidil may provide an effective agent to inhibit LHs.

Over the recent years, potential associations between Toxoplasma gondii (T. gondii) infection and cancer risk have attracted a lot of attention. Nevertheless, the association between T. gondii infection and oral cancer remains relatively unexplored. We performed a case–control study of 861 oral cancer patients and 861 control subjects from eastern China with the aim to detect antibodies to T. gondii by enzyme-linked immunosorbent assay (ELISA) in these patients. The results showed that oral cancer patients (21.72%, 187/861) had a significantly higher seroprevalence than control subjects (8.25%, 71/861) (P < 0.001). Among them, 144 (16.72%) oral cancer patients and 71 (8.25%) control subjects were positive for IgG antibodies to T. gondii, while 54 (6.27%) oral cancer patients and 9 (1.05%) controls were positive for IgM antibodies to T. gondii. In addition, multiple logistic analysis showed that T. gondii infection in oral cancer patients was associated with blood transfusion history, keeping cats at home, and oyster consumption. To our knowledge, this is the first study that provided a serological evidence of an association between T. gondii infection and oral cancer patients. However, further studies are necessary to elucidate the role of T. gondii in oral cancer patients.

Sarcophila mongolica Chao & Zhang, 1988 (Diptera: Sarcophagidae) is considered to be of ecological and medical significance. In this study, we report the mitochondrial genome (mitogenome) of S. mon...

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a unique type of gastric carcinomas that promoter hypermethylation of tumor-related genes is extremely frequent to be found. Aquaporin 3 (AQP3) is a small membrane transport protein that plays a crucial role in cancer progression and metastasis. However, there is no experimental study on the expression of AQP3 in EBVaGC and the regulation mechanism of EBV on AQP3. In this study, the loss of AQP3 was contributed by the hypermethylation status of AQP3 promoter in EBVaGC which was caused by elevated expression of DNMT3a. In addition, stable and transient transfection system in SGC7901 showed that viral latent membrane protein 2A (LMP2A) activated phosphorylated ERK and up-regulated DNMT3a. Taken together, LMP2A induced the phosphorylation of ERK, which activated DNMT3a transcription and caused AQP3 expression loss through CpG island methylation of AQP3 promoter in EBVaGC.

Epidemiological data for Toxoplasma gondii regarding malignancy have gained increasing attention; however, the information about T. gondii infection among children with malignant lymphoma (ML) in China is unclear. Therefore, 314 children with lymphoma and 314 healthy children, age- and gender-matched, were recruited to estimate the seroprevalence of T. gondii in the participants and identify the risk factors of infection. Blood samples from all participants were collected and examined for T. gondii IgG and IgM antibodies using ELISA. The results showed that the overall seroprevalence of T. gondii antibodies (including IgG and/or IgM) in ML patients and healthy controls was 19.8% and 9.9%, respectively. Contact with the cats, consumption of oysters and history of chemotherapy were estimated to be the risk factors for T. gondii infection in children with lymphoma by multivariable logistic regression analysis, whereas in healthy children, contact with cats and consumption of oysters were the risk factors. Moreover, among various histological types of lymphoma, individuals with NK/T-cell lymphoma, B-small lymphocytic lymphoma, marginal zone B-lymphoma and Hodgkin's lymphoma had a higher seroprevalence than healthy controls (P < 0.05). These findings indicated the high prevalence of T. gondii infection in children with lymphoma, and hence, efforts should be performed to evaluate the effect of the infection further in lymphoma patients.

Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of caspase-1 degradation by proteasome inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections.

Aims: The aim of this project was to explore the different CTX-M expression levels occurring from a single conserved promoter with different spacer sequences, the variation of which is hypothesized to be a key factor in fluctuating levels of CTX-M. Methods: The blaCTX-M promoter fragments with five different spacer sequences were amplified, sequenced and cloned into the pUA66 expression vector carrying the green fluorescent protein (GFP) gene. The expression of blaCTX-M in the transconjugants was analyzed using fluorescence microscopy, flow cytometry and qRT-PCR. Results: The promoters of all the blaCTX-M genes were provided by ISEcp1 and were extremely conserved. The promoter-associated spacer sequences varied from 42 to 127 bp and variations in GFP expression in the five transconjugants were observed. A nucleic acid deletion and point mutation were detected in the spacer sequences by variations in which the expression of blaCTX-M was influenced. Conclusion: The different spacer sequences have a significant impact on the activity of the conserved promoter. The shorter spacer sequence between the conserved promoter and the blaCTX-M gene does not specifically enhance the expression of blaCTX-M, contrary to previous reports. The expression of blaCTX-M may be regulated by changes in promoter activity caused by diverse spacer sequences.

Here we report a case of a laboratory-confirmed 2019 novel coronavirus (2019-nCoV)-infected patient with COVID-19 (coronavirus disease 2019) who developed respiratory failure and shock accompanied by persistent diarrhoea despite conventional therapeutic interventions. The patient avoided mechanical ventilation and showed an immediate clinical and radiological improvement following treatment with intensive plasma exchange (PE) followed by intravenous immunoglobulin (IVIG). Successful therapeutic strategies in this case suggest that timely initiation of PE treatment followed by IVIG in critically ill patients with COVID-19 may prevent the disease from worsening and help to reduce the requirement for mechanical ventilation and intensive supportive care. Moreover, it may improve poor clinical outcomes of these patients.

Introduction Lysyl hydroxylase 3 (LH3) is a collagen post-translational modifying enzyme; it is abnormally activated during the formation of collagen cross-links. iCRT3 is an inhibitor of both Wnt and β-catenin responsive transcription. We hypothesized that LH3 is regulated by TGFβ1/Smad3 signaling and Wnt/β-catenin signaling pathways. Some evidence suggested that there is complicated cross-talk between the two signal pathways in the genesis of pulmonary fibrosis. Material and methods The normal culturing human lung cancer cell line A549 was derived from pulmonary epithelial cells. Transforming growth factor-β1 (TGF-β1) was induced A549 cells of pulmonary fibrosis. MTT assays detected cell growth stimulation by TGF-β1; collagen pyridine-crosslinking contents were detected by ELISA kits. Immunofluorescence were used to evaluate expression of key molecules in PLOD3 (LH3), Wnt/β-catenin and TGFβ1/Smad3 pathways. Results Our findings suggested that iCRT3 could decrease LH3 protein expression (p < 0.01), Wnt1, β-catenin and p-Smad3 protein expression (p < 0.05). Knock-down PLOD3 could decrease LH3, collagen I gene and protein expression (p < 0.05). These effects were associated with decreasing collagen pyridine-crosslinking production (p < 0.05). However, ovexpression PLOD3 could increase LH3, collagen I gene and protein expression (p < 0.05). The result showed that LH3 plays an important role in collagen post-translational modifications, and it is regulated by Wnt/β-catenin and TGFβ1/Smad3 pathways. Conclusions This study suggests that PLOD3 (LH3) represents a target to prevent pulmonary fibrosis.

Interleukin (IL)-33 treatment has been reported to reduce mortality in a rat model of sepsis, and the present study aimed to determine whether this effect of IL-33 is achieved through a reduction in the systemic inflammatory response in Acinetobacter baumannii pneumonia. After induction of pneumonia, rats were treated with normal saline or IL-33, and mortality over 5 days was recorded. Inflammation within lung tissues was evaluated by hematoxylin and eosin staining as well as measurement of the concentrations of IL-8 and tumor necrosis factor alpha (TNF-α) in the bronchoalveolar lavage fluid (BALF) and plasma by enzyme-linked immunosorbent assay. In addition, the expression of Toll-like receptor 4 (TLR4), ST2, and nuclear factor kappa B (NF-κB) in rat lung tissues was assessed by western blotting. The result showed that the mortality rate and systemic inflammation were significantly increased in rats upon infection with A. baumannii, as evidenced by significant increases in the IL-8 and TNF-α levels in BALF and plasma as well as increased NF-κB activity and TLR4 expression in rat lung tissues. Importantly, IL-33 (1 μg/kg) treatment significantly decreased mortality and pulmonary inflammation in A. baumannii-infected rats. Moreover, IL-33 treatment suppressed the elevation of IL-8 and TNF-α levels and inhibited TLR4 expression and NF-κB activation. Overall, these results suggest that IL-33 may decrease the mortality and inhibit the systematic inflammatory response associated with A. baumannii pneumonia by suppressing TLR4/NF-κB signaling.

Some representatives of flesh flies visiting/colonizing the decomposed remains demonstrated their values in estimating the minimal postmortem interval (PMImin) since death. However, the utility of sarcophagid flies has been seriously hampered by limited ecological, biological and taxonomic knowledge of them. Although mitochondrial genes have been proposed as a potential DNA barcode for the species-level identification of sarcophagids, some defects still remain such as the substantial memory and processing time taken for homologous comparisons online. Moreover, species identification is mainly achieved by Sanger sequencing based on PCR with genus-specific primers. In the present study we characterized 24 single nucleotide polymorphisms (SNPs) as robust markers of genetic variation for identifying different sarcophagids based on available cytochrome c oxidase I (COI) data and verified them through pyrosequencing (PSQ) technology to establish a SNP-based genotyping system. The system provides a preliminary foundation for developing a rapid, reliable, and high-throughput assay so as to efficiently and accurately identify the sarcophgid flies. Furthermore, the PSQ approach is proved to be faster, more cost-effective as well as more sensitive and specific than custom Sanger sequencing.

Hydrotaea dentipes (Diptera: Muscidae) is one of the forensically important fly species and distributed worldwide. We describe the complete mitochondrial genome of the H. dentipes for the first tim...

Graphomya rufitibia (Diptera: Muscidae) was distributed worldwide. In this study, the complete mitogenome of G. rufitibia was sequenced and annotated, and the full-length was a 15,374 bp fragment, consisting of A (40.64%), G (8.96%), T (36.80%), and C (13.59%). The mitogenome is composed of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a non-coding AT-rich region. Most PCGs used the canonical putative codon to start and stop, 21 tRNAs are folded into the classic clover-leaf structure, with the one exception of tRNA-Ser (AGN). A total length of 11,182 bp encoding 3727 amino acids, and account for 72.7% of the whole mitogenome. Phylogenetic analyses showed that G. rufitibia belongs to family Mydaeinae.

Limited information is available concerning the epidemiology of Toxoplasma gondii infection in children with leukemia in Eastern China. Therefore, a case-control study was conducted to estimate the seroprevalence of toxoplasmosis in this patient group and to identify risk factors and possible routes of infection. Serum samples were collected from 339 children with leukemia and 339 age matched health control subjects in Qingdao from September 2014 to March 2018. Enzyme linked immunoassays were used to screen anti- T. gondii IgG and anti- T. gondii IgM antibodies. Forty-eight (14.2%) children with leukemia and 31 (9.1%) control subjects were positive for anti-T. gondii IgG antibodies (P T. gondii IgM antibodies (P = 0.84). Multivariate analysis showed exposure to soil and a history of blood transfusion were risk factors for T. gondii infection. Compared with IgG, patients with a history of blood transfusion were more likely to present anti- T. gondii IgM (P = 0.003). Moreover, patients with chronic lymphocytic leukemia and acute lymphocytic leukemia had higher T. gondii seroprevalence in comparison to control subjects (P = 0.002 and P = 0.016, respectively). The results indicated that the seroprevalence of T. gondii infection in children with leukemia is higher than that of healthy children in Eastern China. This information may be used to guide future research and clinical management, and further studies are necessary to elucidate the role of T. gondii in children with leukemia.

A secondary bacterial infection of the influenza virus in the lungs is a key cause of exacerbation and death. The pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the destruction of the physical barrier of the airways and the dysregulation of the immune response. This article will review the progress of the mechanism of secondary bacterial infection of influenza virus and provide strategies for preventing the co-infection of influenza virus and bacteria.