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Membrane separation is a very promising and economical method for gravitational oil/water separation and the collection of oil spills. Both superhydrophilicity/underwater superhydrophobicity (SHL&UWSOB) and superhydrophobicity/superlipophilicity (SHB&SOL) are suitable materials for the solution. In this work, an ingenious design strategy of "two birds with one stone" to modify Ni foams (NFs) was developed, in which SHL&UWSOB was initially fabricated by the in situ growth of a bimetallic Fe/Ni-MOF on an NF surface by solvothermal synthesis. Further modification based on the resultant SHL&UWSOB-NF led to the construction of a SHB&SOL surface by simple immersion of stearic acid. The micro/nano structure beneficial to underwater superoleophobicity was tailored by optimizing the solvothermal reaction time in the range of 10–24 h. The results showed that SHL&UWSOB-NF was obtained with a high oil contact angle (OCA) of 165.9° under water when the time of the solvothermal reaction was kept at about 18 h. Likewise, the further modified NF exhibited an obvious SHB&SOL property with a water contact angle (WCA) of 156.3° and a water rolling angle (SCA) of 9°. The light oil (n-hexane) floating on the water's surface and heavy oil of carbon tetrachloride (CCl4) at the bottom of the water, as well as the mini-separation of oil/water, demonstrated its facile and versatile application as a separation medium. The strategy may offer new approaches for the fabrication of superwetting/superantiwetting separation materials for oil/water separation and oil collection. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC. [ABSTRACT FROM AUTHOR]

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) infection can cause severe reproductive failure in sows and respiratory distress in pigs of all ages, leading to major economic losses. To date, there are still no effective strategies to prevent and control PRRSV. Antibody-dependent enhancement (ADE), a phenomenon in which preexisting non-neutralizing antibodies or sub-neutralizing antibodies facilitate virus entry and replication, may be a significant obstacle in the development of effective vaccines for many viruses, including PRRSV. However, the contribution of ADE to PRRSV infection remains controversial, especially in vivo. Whether attenuated PRRSV vaccines prevent or worsen subsequent disease in pigs infected by novel PRRSV strains requires more research. In the present study, in vivo experiments were conducted to evaluate ADE under different immune statuses, which were produced by waiting different lengths of time after vaccination with a commercially available attenuated highly pathogenic PRRSV (HP-PRRSV) vaccine (JXA1-R) before challenging the pigs with a novel heterologous NADC30-like strain. Results: Piglets that were vaccinated before being challenged with PRRSV exhibited lower mortality rates, lower body temperatures, higher bodyweight gain, and lower viremia. These results demonstrate that vaccination with JXA1-R alleviated the clinical signs of PRRSV infection in all vaccinated groups. Conclusions: The obtained data indicate that the attenuated vaccine test here provided partial protection against the NADC30-like strain HNhx. No signs of enhanced PRRSV infection were observed under the applied experimental conditions. Our results provide some insight into the molecular mechanisms underlying vaccine-induced protection or enhancement in PRRSV. [ABSTRACT FROM AUTHOR]

[Display omitted] • Urolithin B effectively mitigates cerebral ischemia–reperfusion injury in rats. • Urolithin B attenuates oxidative stress via activation of the Nrf2 pathway. • We consider Urolithin B may also be beneficial in a clinical setting. Ischemia-reperfusion (IR) induces a wide range of irreversible injuries. Cerebral IR injury (IRI) refers to additional brain tissue damage that occurs after blood flow is restored following cerebral ischemia. Currently, no established methods exist for treating IRI. Oxidative stress is recognized as a primary mechanism initiating IRI and a crucial focal target for its treatment. Urolithin B, a metabolite derived from ellagitannins, antioxidant polyphenols, has demonstrated protective effects against oxidative stress in various disease conditions. However, the precise mechanism underlying UB's effect on IRI remains unclear. In our current investigation, we assessed UB's ability to mitigate neurological functional impairment induced by IR using a neurological deficit score. Additionally, we examined cerebral infarction following UB administration through TTC staining and neuron Nissl staining. UB's inhibition of neuronal apoptosis was demonstrated through the TUNEL assay and Caspase-3 measurement. Additionally, we examined UB's effect on oxidative stress levels by analyzing malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and immunohistochemistry analysis of inducible nitric oxide synthase (iNOS) and 8-hydroxyl-2′-deoxyguanosine (8-OHdG). Notably, UB demonstrated a reduction in oxidative stress levels. Mechanistically, UB was found to stimulate the Nrf2/HO-1 signaling pathway, as evidenced by the significant reduction in UB's neuroprotective effects upon administration of ATRA, an Nrf2 inhibitor. In summary, UB effectively inhibits oxidative stress induced by IR through the activation of the Nrf2/HO-1 signaling pathway. These findings suggest that UB holds promise as a therapeutic agent for the treatment of IRI. [ABSTRACT FROM AUTHOR]

Highlights • PRRSV infection induces IL-1β mRNA and protein expression in microglia. • Myeloid differentiation primary response gene 88 (MyD88), extracellular signal-regulated kinase1/2 (ERK) and AP-1 signaling pathways are involved in PRRSV induced IL-1β production in microglia. • In microglia, PRRSV infection actually increased the phosphorylation of ERK1/2 and c-Jun. • NLRP3 inflammasome was proved to be activated by PRRSV and required for IL-1β secretion in microglia. Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) infection which caused severe reproductive failure and respiratory disorders in swine is accompanied with severe nervous symptoms. Our previous studies demonstrated that microglia, the resident innate immune cells in central nervous system (CNS), could support PRRSV infection and replication in vitro. And PRRSV infection led to the increased expressions of large amounts of proinflammatory cytokines and chemokines which contributed to neuropathogenesis of PRRSV. Interleukin-1β (IL-1β) is one of the increased proinflammatory cytokines, which possesses diverse functions in immune response upon virus infection, including activation of innate immune and modulation of adaptive immune responses. Importantly, considerable evidences indicated that 1L-1β is involved in neuronal injury. Here, we demonstrated that PRRSV infection up-regulated IL-1β expression at both the mRNA and protein levels in microglia in a dose-dependent manner. Myeloid differentiation primary response gene 88 (MyD88), extracellular signal-regulated kinase1/2 (ERK) and activator protein 1 (AP-1) were involved in PRRSV induced IL-1β production in microglia. Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome is activated by PRRSV in microglia, which is required for IL-1β secretion. Taken together, our data indicated that PRRSV infection could induce IL-1β up-regulation, which was likely mediated by MyD88/ERK/AP-1 and NLRP3 inflammasome. These findings will provide new insights into the molecular mechanisms of IL-1β production and some implications for neuropathogenesis of PRRSV. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the potential of the monocyte to red blood cell count ratio (MRR), the neutrophil to red blood cell count ratio (NRR), the lymphocyte to red blood cell count ratio (LRR) and the product of lymphocyte count and albumin concentration (LA) for the diagnosis of lung cancer. The cases of 216 patients with newly diagnosed lung cancer and 184 healthy volunteers were retrospectively analysed. The MRR and NRR were found to be higher in patients with lung cancer compared with those in healthy controls, while the LRR and LA were lower. The receiver operating characteristic curve analysis revealed that of the four markers, the MRR and LA yielded a higher area under the curve (AUC) (MRR: AUC, 0.810; 95% CI, 0.768-0.847; and LA: AUC, 0.721; 95% CI, 0.674-0.764). The combination of MRR, LA, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) achieved the highest diagnostic value when compared with other single or combined markers (AUC, 0.882; 95% CI, 0.846-0.912; sensitivity, 81.9%; specificity, 81.0%). As the disease progressed, the MRR tended to increase, while LA exhibited a decreasing trend. Binary logistic regression analysis revealed an increase in the MRR, as well as in CEA and CYFRA21-1 concentrations, and a decrease in the LA, which could all be possible risk factors for lung cancer. Differences in the MRR and LA between patients with early stage (IA-IIIA) lung cancer and healthy controls were observed. Further analysis revealed that the MRR also exhibited the potential to detect early stage (IA-IIIA) lung cancer in the model. The present findings demonstrated that the MRR and LA may be used as auxiliary biomarkers for the diagnosis of lung cancer and could partly indicate disease progression. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) has been epidemic more than 30 years in America and 20 years in China. It is still one of the most important causative agents to the worldwide swine industry. Here, we systematically analyzed the prevalence status of PRRSV in China by a molecular epidemiological perspective. Now both PRRSV-1 and PRRSV-2 are circulating and approximately more than 80% of pig farms are seropositive for PRRSV. For PRRSV-2, there are four lineages (lineage 1, lineage 3, lineage 5, lineage 8) circulating in the fields. Lineage 8 (CH-1a-like) and lineage 5 (BJ-4-like) appeared almost at the same time during 1995-1996. Notably, BJ-4 shares 99.6% and 99.8% identity with VR2332 and RespPRRS MLV, respectively. It means that lineage 5 is likely to be imported from America. Now highly pathogenic PRRSV (HP-PRRSV) which was considered to be evolved from local diversity of lineage 8 strains is predominant with different variants. Lineage 3 appeared in 2010 which is mainly sporadic in south of China. Lineage 1, also known as NADC30-like strains in China, has been prevalent since 2013 and leads to PRRS pandemic again. For PRRSV-1, although sporadic at present, more than 9 provinces/regions have been reported. All the circulating strains belong to subtype I. It should be paid more attention since there are no vaccines available. Our analysis would help to deeply understand the prevalent status of PRRSV in China and provide useful information for prevention and control of porcine reproductive and respiratory syndrome (PRRS). [ABSTRACT FROM AUTHOR]

On one hand, advances in neonatal care and rescue technology allow for the healthy survival or prolonged survival time of critically ill newborns who, in the past, would have been non-viable. On the other hand, many of the surviving critically ill infants have serious long-term disabilities. If an infant eventually cannot survive or is likely to suffer severe disability after surviving, ethical issues in the treatment process are inevitable, and this problem arises not only in developed countries but is also becoming increasingly prominent in developing countries. In addition, ethical concerns cannot be avoided in medical research. This review article introduces basic ethical guidelines that should be followed in clinical practice, including respecting the autonomy of the parents, giving priority to the best interests of the infant, the principle of doing no harm, and consent and the right to be informed. Furthermore, the major ethical concerns in neonatal intensive care units (NICUs) in China are briefly introduced. [ABSTRACT FROM AUTHOR]

Owing to the abuse of antibiotics, drug resistance of pathogenic bacteria becomes more and more serious. Therefore, it is interesting to develop a more reasonable way to solve this issue. Because they can destroy the bacterial cell structure and then kill the infectious bacterium, the bacterial cell wall lyases are suitable candidates of antibacteria sources. Thus, it is urgent to develop an accurate and efficient computational method to predict the lyases. Based on the consideration, in this paper, a set of objective and rigorous data was collected by searching through the Universal Protein Resource (the UniProt database), whereafter a feature selection technique based on the analysis of variance (ANOVA) was used to acquire optimal feature subset. Finally, the support vector machine (SVM) was used to perform prediction. The jackknife cross-validated results showed that the optimal average accuracy of 84.82% was achieved with the sensitivity of 76.47% and the specificity of 93.16%. For the convenience of other scholars, we built a free online server called Lypred. We believe that Lypred will become a practical tool for the research of cell wall lyases and development of antimicrobial agents. [ABSTRACT FROM AUTHOR]

Abstract: Atypical porcine reproductive and respiratory syndrome (PRRS) caused by a highly pathogenic PRRS virus (HP-PRRSV) is characterized by high fever, high morbidity, high mortality, and associated with severe neurological symptoms. Microglia are the resident innate immune cells in central nervous system (CNS), and their activation has been implicated as an important contributor to the pathogenesis of CNS diseases. In the present study, we successfully cultured porcine microglia and demonstrated that microglia could support PRRSV infection and replication in vitro. We further showed that HP-PRRSV infection significantly up-regulated the key inflammatory factors including IL-1β, TNF-α, IL-6, IL-12, IL-8, CXCL10, MCP-1, CCL3, CCL4, and CCL5 in cultured microglia as well as in the CNS of HP-PRRSV-infected pigs. The transcription factors NF-κB and AP-1, which are widely reported to regulate cytokine and chemokine productions, were activated by HP-PRRSV infection in microglia. Meanwhile, we found that HP-PRRSV induced cellular ROS formation in microglia and ROS scavenger was proved to significantly abolish the activation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8), suggesting that ROS are crucial for pro-inflammatory gene production. Importantly, incubation with supernatants from HP-PRRSV-infected microglia cell culture remarkably induced SH-SY5Y neuroblastoma cell death. Collectively, these results showed that PRRSV infection induced cytokine and ROS up-regulation in microglia, which might contribute to neurotoxicity. These data have implications for us to understand the neuropathogenesis of HP-PRRSV in pigs. [Copyright &y& Elsevier]

In a previous study, a metatranscriptomics survey of RNA viruses in several important lower vertebrate host groups revealed huge viral diversity, transforming the understanding of the evolution of vertebrate-associated RNA virus groups. However, the diversity of the DNA and retro-transcribing viruses in these host groups was left uncharacterized. Given that RNA sequencing is capable of revealing viruses undergoing active transcription and replication, we collected previously generated datasets associated with lower vertebrate hosts, and searched them for DNA and retro-transcribing viruses. Our results revealed the complete genome, or "core gene sets", of 18 vertebrate-associated DNA and retro-transcribing viruses in cartilaginous fishes, ray-finned fishes, and amphibians, many of which had high abundance levels, and some of which showed systemic infections in multiple organs, suggesting active transcription or acute infection within the host. Furthermore, these new findings recharacterized the evolutionary history in the families Hepadnaviridae, Papillomaviridae, and Alloherpesviridae, confirming long-term virus–host codivergence relationships for these virus groups. Collectively, our results revealed reliable and sufficient information within metatranscriptomics sequencing to characterize not only RNA viruses, but also DNA and retro-transcribing viruses, and therefore established a key methodology that will help us to understand the composition and evolution of the total "infectome" within a diverse range of vertebrate hosts. [ABSTRACT FROM AUTHOR]

• PRRSV infection induces SOCS3 upregulation. • AP-1 signaling pathways are indispensable for PRRSV-induced SOCS3 expression. • SOCS3 facilitates PRRSV replication. SOCS3 belongs to the suppressor of cytokine signaling (SOCS) family, which function as negative factors in host immune responses. Prior studies have noted the importance of SOCS family proteins in immunosuppression induced by some viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine-borne viruses and has threatened the global swine industry with huge economic losses since it was first described in the 1980s. PRRSV is the etiological agent of PRRS, which causes reproductive failure and respiratory disorders. PRRSV causes immunosuppression thus establishing persistent infection. In this study, it was observed that SOCS3 was upregulated in PRRSV-infected primary porcine alveolar macrophages (PAMs) and Marc-145 cells with dose-dependent effects, which depends on virus replication. Deletion of AP-1 binding motif located in SOCS3 promoter inhibited promoter activities, which indicates that AP-1 is essential for PRRSV-induced SOCS3. This result was confirmed by experiments using AP-1 inhibitor, whose pretreatment suppressed SOCS3 mRNA and protein expression. Further research showed that p38 was crucial for PRRSV-induced SOCS3 production. Importantly, SOCS3 enhanced PRRSV replication during infection. Taken together, this study indicates that PRRSV infection induced SOCS3 expression through p38/AP-1 signaling pathway. These results revealed the molecular basis of SOCS3 upregulation and would advance further understanding of the strategy for viral immune evasion. [ABSTRACT FROM AUTHOR]

NADC30-like strains of porcine reproductive and respiratory syndrome virus (PRRSV) were firstly reported in China in 2013. Since then, these strains have been epidemic in more than 13 provinces/regions. During 2016–2017, a total of 18 PRRSV isolates were obtained from 52 clinical samples in Henan province. Based on comparative and phylogenetic analyses of ORF5 and partial Nsp2 genes, 83.3% (15/18) isolates belonged to NADC30-like strains, and the ORF5 shared 87.4%–95.5% nucleotide identity with NADC30/JL580 and 84.2%–89.9% with JXA1/CH-1a, respectively. The genetic variation analysis showed that extensive amino acid substitutions happened in the significant regions of ORF5 including major linear antigenic epitopes (27-30aa, 37-45aa, 52-61aa) and the potential N-glycosylation sites (32-35aa). 16.7% (3/18) isolates were very close to HP-PRRSV derived attenuated strains. Moreover, these three isolates shared common residues at the positions 33D, 59 N, 164R, 196R in ORF5 and 303D, 399T, 575V, 598R, 604G in Nsp2, which were thought to be unique to modified live vaccines (MLVs) or their derivatives. Therefore, they were probably the revertants from MLVs. Our studies showed that the HP-PRRSV strains seemed to be gradually disappearing and NADC30-like strains had become the main causative agents of PRRS in central China. Comparing with HP-PRRSVs, the ORF5 of NADC30-like PRRSV strains displayed extensive amino acid mutations which may be related with immune evasion. Furthermore, the circulation of MLV derivatives in the fields made the diagnosis and control of PRRSV more complicated. • The clinical PRRS cases were mainly caused by NADC30-like PRRSVstrains in central China. • The ORF5 genes had extensive amino acid substitutions in signal peptide, major linear epitopes and N-glycosylation sites. • The circulation of MLV derivatives made the diagnosis and control of PRRSV more complicated in China. [ABSTRACT FROM AUTHOR]

Background: Porcine epidemic diarrhea (PED), caused by PED virus (PEDV), is a severe enteric disease burdening the global swine industry in recent years. Especially, the mortality of PED in neonatal piglets approaches 100%. Maternal antibodies in milk, particularly immunoglobulin A (IgA) antibodies, are of great importance for protection neonatal suckling piglets against PEDV infection as passive lactogenic immunity. Therefore, appropriate detection methods are required for detecting PEDV IgA antibodies in milk. In the current study, we prepared monoclonal antibodies (mAbs) against PEDV spike (S) glycoprotein. An enzyme-linked immunosorbent assay (ELISA) was subsequently developed based on PEDV antigen capture by a specific anti-S mAb. Results: The developed ELISA showed high sensitivity (the maximum dilution of milk samples up to 1:1280) and repeatability (coefficient of variation values < 10%) in detecting PEDV IgA antibody positive and negative milk samples. More importantly, the developed ELISA showed a high coincidence rate with a commercial ELISA kit for PEDV IgA antibody detection in clinical milk samples. Conclusions: The developed ELISA in the current study is applicable for PEDV IgA antibody detection in milk samples, which is beneficial for evaluating vaccination efficacies and neonate immune status against the virus. [ABSTRACT FROM AUTHOR]

Although membrane separation technology has been widely used in the treatment of oily wastewater, the complexity and high cost of the membrane preparation, as well as its poor stability, limit its further development. In this study, via the vacuum-assisted suction filtration method, polydopamine (PDA)-coated TiO2 nanoparticles were tightly attached and embedded on both sides of laboratory filter paper (FP). The resultant FP possessed the typical wettability of high hydrophilicity in the air with the water contact angle (WCA) of 28°, superoleophilicity with the oil contact angle (OCA) close to 0°, underwater superoleophobicity with the underwater OCA greater than 150°, and superhydrophobicity under the water with the underoil WCA over 150° for five kinds of organic solvents (carbon tetrachloride, toluene, n-hexane, n-octane, and iso-octane). The separation efficiency of immiscible oil/water, oil-in-water, and water-in-oil emulsions using the modified FP is higher than 99%. After 17 cycles of emulsion separation, a high separation efficiency of 99% was still maintained for the FP, along with good chemical and mechanical stability. In addition, successful separation and purification were also realized for the oil-in-water emulsion that contained the methylene blue (MB) dye, along with the complete degradation of MB in an aqueous solution under UV irradiation. [ABSTRACT FROM AUTHOR]

Vesicular stomatitis (VS), characterized by vesicular lesions, produces significant economic losses in livestock industry. Infection by its causative agent, VS virus (VSV), has been previously shown to be mediated by the glycoprotein (G) during attachment, endocytosis and membrane fusion. In the current study, we revealed a novel role of VSV G protein in negative regulation of host cell pro-inflammatory responses. We determined that VSV G protein inhibited lipopolysaccharide (LPS)-induced pro-inflammatory responses as naïve VSV virions in murine peritoneal macrophage-like cell line RAW 264.7. Furthermore, we identified that VSV G protein suppressed nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK)-mediated pro-inflammatory pathways in a dose-dependent manner. Moreover, we demonstrated that α2-3-linked sialic acids on VSV G protein were involved in antagonizing NF-κB- and MAPK-mediated pro-inflammatory responses. All these results expand the knowledge of VSV pathogenesis and strengthen the importance of VSV G protein in host innate immunity, which support implications for the development of VSV-based vaccination and oncolysis. [ABSTRACT FROM AUTHOR]

Background: Porcine epidemic diarrhea (PED), caused by PED virus (PEDV), is a severe enteric disease burdening the global swine industry in recent years. Especially, the mortality of PED in neonatal piglets approaches 100%. Maternal antibodies in milk, particularly immunoglobulin A (IgA) antibodies, are of great importance for protection neonatal suckling piglets against PEDV infection as passive lactogenic immunity. Therefore, appropriate detection methods are required for detecting PEDV IgA antibodies in milk. In the current study, we prepared monoclonal antibodies (mAbs) against PEDV spike (S) glycoprotein. An enzyme-linked immunosorbent assay (ELISA) was subsequently developed based on PEDV antigen capture by a specific anti-S mAb. Results: The developed ELISA showed high sensitivity (the maximum dilution of milk samples up to 1:1280) and repeatability (coefficient of variation values < 10%) in detecting PEDV IgA antibody positive and negative milk samples. More importantly, the developed ELISA showed a high coincidence rate with a commercial ELISA kit for PEDV IgA antibody detection in clinical milk samples. Conclusions: The developed ELISA in the current study is applicable for PEDV IgA antibody detection in milk samples, which is beneficial for evaluating vaccination efficacies and neonate immune status against the virus. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS), characterized by respiratory disorders in piglets and reproductive failure in sows, is still the great threat of swine industry. Recently, Emergence of the novel NADC30-like PRRS viruses (PRRSVs) has caused widespread outbreaks of PRRS. To investigate the epidemic characteristics of PRRSVs in Central China since 2014, 6372 clinical serum samples were tested by ELISA, 250 tissue samples were tested by RT-PCR, and among these, 30 ORF5 and 17 Nsp2 genes sequences were analyzed. Phylogenetic tree based on ORF5 revealed that, 17 isolates were clustered into subgroup 1, represented by the NADC30. And for the Nsp2, The strains which had a discontinuous 131-amino-acid deletion in Nsp2, called NADC30-like strains, were clustered into subgroup 2. Our data suggested that the NADC30-like PRRSV strains spread quickly and are now circulating and prevalent in Central China as well as the classical HP-PRRSV strains. In addition, amino acid variation analysis of GP5 revealed that the amino acid sequences of NADC30-like PRRSV strains underwent rapid evolution and contained extensive amino acid substitutions in important motifs, such as potential neutralization epitope and the N-glycosylation sites. In summary, our data would provide a large amount of detailed information on molecular variation and genetic diversity of PRRSV in central China. [ABSTRACT FROM AUTHOR]

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome‐wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein–protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF‐specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1‐20 and 37.0% including Chr21/22. In chromosomes 1‐20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF‐specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF. [ABSTRACT FROM AUTHOR]

Tuberculosis is killing millions of lives every year and on the blacklist of the most appalling public health problems. Recent findings suggest that secretory protein of Mycobacterium tuberculosis may serve the purpose of developing specific vaccines and drugs due to their antigenicity. Responding to global infectious disease, we focused on the identification of secretory proteins in Mycobacterium tuberculosis. A novel method called MycoSec was designed by incorporating g-gap dipeptide compositions into pseudo amino acid composition. Analysis of variance-based technique was applied in the process of feature selection and a total of 374 optimal features were obtained and used for constructing the final predicting model. In the jackknife test, MycoSec yielded a good performance with the area under the receiver operating characteristic curve of 0.93, demonstrating that the proposed system is powerful and robust. For user’s convenience, the web server MycoSec was established and an obliging manual on how to use it was provided for getting around any trouble unnecessary. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the specially designed medical dressing screen during wound dressing changes of children who suffered burns to their hand or foot.Design: Randomized controlled trial.Setting: Burns and Plastic Reconstruction Unit.Participants: Children (N=120) with burns on up to 1-5% of the total body surface area.Interventions: The patients were selected and randomly allocated to 3 equal-sized groups as follows: control group (N=40): the children received only regular dressing changes; computer group (N=40): a touch-screen computer was used for children during dressing changes; medical screen group (N=40): a medical screen combined with the touch-screen computer were used for children during dressing changes. All patients underwent a dressing change once per day for four days. Data were distributed four times: immediately after the initial dressing change (T1); and immediately after each times at next three consecutive days (T2-T4).Main Outcome Measures: The Pain level of the children evaluated by medical staffs was the primary outcome, the Pain level of the children evaluated by children's parents and the satisfaction of wound therapist were used as second outcomes.Results: The mean scores related to pain level at the medical screen group displayed significantly better results than those of control group and those of the computer group. Additionally, the results of the pain evaluated by parents and satisfaction score of the wound therapist at the medical screen group was also better than other groups.Conclusions: This study demonstrated "that the" application of the medical screen for burns can relieve the pain of 1-3 years old children suffering from a burns during dressing changes. Additionally, the application of the medical screen also increased the satisfaction of the parents and the wound therapist performing the dressing changes. [ABSTRACT FROM AUTHOR]

Flexible supercapacitors are an important portable energy storage but suffer from low capacitance, inability to stretch, etc. Therefore, flexible supercapacitors must achieve higher capacitance, energy density, and mechanical robustness to expand the applications. Herein, a hydrogel electrode with excellent mechanical strength was created by simulating the collagen fiber network and proteoglycan in cartilage using silk nanofiber (SNF) network and polyvinyl alcohol (PVA). The Young's modulus and breaking strength of the hydrogel electrode increased by 205 % and 91 % compared with PVA hydrogel owing to the enhanced effect of the bionic structure, respectively, which are 1.22 MPa and 1.3 MPa. The fracture energy and fatigue threshold reached 1813.5 J/m2 and 1585.2 J/m2, respectively. The SNF network effectively connected carbon nanotubes (CNTs) and polypyrrole (PPy) in series, affording a capacitance of 13.62 F/cm2 and energy density of 1.2098 mWh/cm2. This capacitance is the highest among currently reported PVA hydrogel capacitors, which can maintain >95.2 % after 3000 charge–discharge cycles. This capacitance Notably, the cartilage-like structure endowed the supercapacitor with high resilience; thus, the capacitance remained >92.1 % under 150 % deformation and >93.35 % after repeated stretching (3000 times), which was far superior to that of other PVA-based supercapacitors. Overall, this effective bionic strategy can endow supercapacitors with ultrahigh capacitance and effectively ensure the mechanical reliability of flexible supercapacitors, which will help expand the applications of supercapacitors. • This bionic supercapacitor was prepared by imitating the cartilage structure. • Mechanical properties are enhanced owing to the enhancement of bionic structure. • The bionic supercapacitor exhibited an ultrahigh areal capacitance. • Supercapacitor retains almost all capacitance after high and repeated stretching. [ABSTRACT FROM AUTHOR]

• 14 PEDV COE-specific mAbs were prepared. • A novel linear B-cell epitope 592TSLLASACTIDLFGYP607 was identified. • The 606Y, 605G and 604F were core residues for recognition. • The epitope and core residues are conserved among PEDV strains. • The difference of mAb reactivity suggested antigenic changes in the S protein. The porcine epidemic diarrhea virus (PEDV) collagenase equivalent domain (COE, residues 499–638), a crucial antigenic region within the viral spike (S) glycoprotein, has been widely utilized for the development of subunit vaccines to prevent viral infection. In the current study, we immunized BALB/c mice with recombinant truncated PEDV COE protein and obtained 14 COE-specific monoclonal antibodies (mAbs). Based on the reactivity analysis of the mAbs with two prevalent PEDV strains in G2 type and the attenuated CV777 strain in G1 type, 6 mAbs were selected for subsequent identification of COE mAb-binding epitopes. Dot-blot hybridization and enzyme-linked immunosorbent assays (ELISAs) identified the peptide 592TSLLASACTIDLFGYP607 as a novel linear B-cell epitope involved in binding of mAbs 4D8F10 and 6F3E3. Subsequently, alanine (A)-scanning mutagenesis demonstrated that residues 606Y, 605G and 604F were core residues involved in recognition. Importantly, this novel COE epitope, including core residues, is conserved among G1 and G2 type PEDV strains. Further experiment indicates that the mAbs 4D8F10 and 6F3E3 were suitable for PEDV detection via mAb binding to the conserved epitope. The current work actually provides potential uses for the development of diagnostic methods to detect PEDV. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the value of hematocrit (HCT) level in predicting the outcomes of critically ill patients with acute kidney injury (AKI). A retrospective study of a total of 14,350 intensive care unit (ICU) patients, who were selected from Beth Israel Deaconess Medical Center (Boston, MA, USA) and met the inclusion criteria, was carried out. And the patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.3 (MIMIC-III v1.3). In our study, HCT quintiles were used to categorize the subjects into groups. The clinical outcomes were 30- and 90-day mortality in the ICU. Cox proportional-hazards models were used to evaluate the association between the HCT and survival. A total of 2827 30-day deaths and 3828 90-day deaths occurred. In univariate analysis, low HCT was significantly associated with increased 30- and 90-day mortality among females, which, however, was not observed in multivariate analysis adjusted for age, ethnicity, dialysate, continuous renal replacement therapy (CRRT), use of insulin, use of ventilator, AKI stages, and report of obesity. In subgroup analysis, an inverse association between HCT levels and risk of mortality for 90-day outcome was observed for female patients by exclusion of dialysate use, receiving CRRT, and obesity reports. Therefore, these findings suggest that lower HCT was associated with an increased risk of mortality in critically ill patients with AKI, and the effect appears to be stronger among women than men. The prognostic value of HCT seems dependent on other factors, for example, dialysate use, CRRT, and obesity. Further multicenter study is in demand to confirm the validity of the results presented in this article. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea (PED) has caused huge economic losses to the global pork industry. Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). Interestingly, some recent studies have indicated that pAPN is not a functional receptor for PEDV. To date, there is a lack of a direct evidence for the interaction between pAPN and PEDV S protein in vitro . Here, we prepared pAPN ectodomain and the truncated variants of PEDV S protein in Drosophila S2 cells. These recombinant proteins were homogeneous after purification by metal-affinity and size-exclusion chromatography. We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Finally, we characterized their interactions by gel filtration chromatography, native-polyacrylamide gel electrophoresis (PAGE) and surface plasmon resonance (SPR) analyses. The results showed that their affinities were too low to form complexes, which suggest that pAPN may be controversial as the genuine receptor for PEDV. Therefore, further research needs to be carried out to elucidate the interaction between PEDV and its genuine receptor. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11, a member of the transforming growth factor‑β superfamily, has been reported to be involved in colorectal cancer. However, the roles of GDF11 in Chinese patients with liver cancer and the underlying mechanisms have remained elusive. The present study assessed the expression of GDF11 in 10 paired samples of cancerous and normal tissues from Chinese liver cancer patients. The results indicated that the expression of GDF11 was significantly lower in cancerous tissues than in normal tissues. In vitro, the expression of GDF11 was reduced in a panel of liver cancer cell lines compared with that in a normal liver cell line at the mRNA and protein level. Treatment with GDF11 reduced the viability of HepG2 for up to 72 h and GDF11 treatment reduced the viability of SMMC‑7721 after 48 and 72 h. Furthermore, GDF11 activated Smad2/3 signaling in HepG2 cells. In conclusion, GDF11 has a tumor suppressor role in liver cancer, exerts its effects through Smad2/3 signaling and may serve as a novel tumor marker in liver cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: This study explored the sensitivity and specificity of ultrasound for diagnosing transient tachypnea of the newborn (TTN).Methods: Ultrasound was performed by one export. Patients were placed in a supine, lateral recumbent, or prone position. The probe was placed perpendicular or parallel to the ribs, and each region of the lung was scanned. The scan results were compared with conventional chest radiographic results.Results: A total of 1,358 infants were included in this study. We identified 412 cases without pulmonary diseases, 228 TTN cases, 358 respiratory distress syndrome (RDS) cases, 85 meconium aspiration syndrome (MAS) cases, 215 infectious pneumonia cases, and 60 other cases. The primary ultrasonic characteristic of TTN was pulmonary edema. "White lung" or a "compact B-line" were only observed in severe cases, whereas TTN primarily presented as pulmonary interstitial syndrome or "double lung point." Furthermore, double lung point could appear during the recovery period of severe TTN or RDS, MAS, and pneumonia. Lung consolidation with air bronchograms was not observed in TTN patients. The results showed that white lung or a compact B-line exhibited a sensitivity of 33.8% and a specificity of 91.3% in diagnosing TTN, whereas double lung point exhibited a sensitivity of 45.6% and a specificity of 94.8% in diagnosing severe TTN.Conclusions: Pulmonary edema, alveolar-interstitial syndrome, double lung point, white lung, and compact B-line are the primary ultrasound characteristics of TTN. Ultrasonic diagnosis of TTN based on these findings is accurate and reliable. TTN can be ruled out in the presence of lung consolidation with air bronchograms. [ABSTRACT FROM AUTHOR]

• PRRSV infection induces vimentin rearrangement during post-entry stage. • Vimentin enwraps PRRSV replication complex at the perinuclear site. • Vimentin rearrangement is beneficial for PRRSV replication. • Vimentin (Ser38) phosphorylation by CaMKIIγ is responsible for rearrangement. Vimentin, a member of intermediate filaments, has been documented to be involved in viral infections. Despite several studies focusing on its involvement in porcine reproductive and respiratory syndrome virus (PRRSV) infection, the detailed mechanisms by which vimentin takes effect remain to be fully elucidated. In the present study, we identified a previously unrecognized role of vimentin rearrangement in PRRSV replication. We monitored that PRRSV infection induced vimentin reorganization during post-entry stage, which was beneficial for viral replication. In detail, the serine residue of vimentin was phosphorylated at position 38 (Ser38) by calcium calmodulin-dependent protein kinase II gamma (CaMKIIγ), and vimentin filaments reorganized into cage-like structures enwrapping PRRSV replication complex (RC) at the perinuclear location. Taken together, these results expand the knowledge of PRRSV replication, and provide novel targets for prevention and control of PRRSV. [ABSTRACT FROM AUTHOR]

Background: African swine fever (ASF) is the most important disease to the pigs and cause serious economic losses to the countries with large-scale swine production. Vaccines are recognized as the most useful tool to prevent and control ASF virus (ASFV) infection. Currently, the MGF505 and MGF360 gene-deleted ASFVs or combined with CD2v deletion were confirmed to be the most promising vaccine candidates. Thus, it is essential to develop a diagnosis method to discriminate wide-type strain from the vaccines used. Results: In this study, we established a duplex TaqMan real-time PCR based on the B646L gene and MGF505-2R gene. The sequence alignment showed that the targeted regions of primers and probes are highly conserved in the genotype II ASFVs. The duplex real-time assay can specifically detect B646L and MGF505-2R gene single or simultaneously without cross-reaction with other porcine viruses tested. The limit of detection was 5.8 copies and 3.0 copies for the standard plasmids containing B646L and MGF505-2R genes, respectively. Clinical samples were tested in parallel by duplex real-time PCR and a commercial ASFV detection kit. The detection results of these two assays against B646L gene were well consistent. Conclusion: We successfully developed and evaluated a duplex TaqMan real-time PCR method which can effectively distinguish the wide type and MGF505 gene-deleted ASFVs. It would be a useful tool for the clinical diagnosis and control of ASF. [ABSTRACT FROM AUTHOR]

• Elastase is highly expressed in HP-PRRSV-infected lung tissues. • Elastase facilitates HP-PRRSV entry independent of low pH and CME. • Elastase mediates HP-PRRSV entry via membrane fusion at the cell surface. • HP-PRRSV GP5 is cleaved by elastase. Infection by enveloped viruses includes endocytosis and/or membrane fusion at the plasma membrane, where host cell proteases play an essential role. Among them, elastase-mediated infection has been documented for several enveloped viruses. Porcine reproductive and respiratory syndrome virus (PRRSV), an economically critical factor in global swine industry, is previously reported to infect host cells via low pH-dependent clathrin-mediated endocytosis (CME) and undergo membrane fusion in recycling endosomes. In the current study, we identified that elastase was significantly elevated in the lung tissues of highly pathogenic PRRSV (HP-PRRSV)-infected pigs compared to the mock-infected ones. We subsequently demonstrated that elastase contributed to HP-PRRSV infection in both MARC-145 cells and porcine alveolar macrophages (PAMs). Mechanistically, HP-PRRSV entered host cells at the cell surface via elastase-mediated membrane fusion, independent of low pH and CME, and its glycoprotein 5 (GP5) was cleaved by the protease during this process. All these findings deepen our understanding of HP-PRRSV infection, and are beneficial for prevention and control of the disease. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS) has caused huge economic losses to global swine industry. Porcine sialoadhesin (poSn) was previously reported to be a putative receptor for the causative agent, PRRS virus (PRRSV). In the current study, we first observed that PRRSV infection up-regulated expression of poSn in a dose- and time-dependent manner. Subsequently, we found that PRRSV-triggered transcription of type I interferons (IFNs) was involved in poSn up-regulation through the IFN-signal transducer and activator of transcription (STAT) signaling cascade. Interestingly, poSn up-regulation was shown to promote PRRSV infection during post-entry process. Taken together, this work deepens our understanding of PRRSV pathogenesis and provides a novel idea on its establishment of persistent infection, which will be interesting to unravel the detailed mechanisms in the future. • PRRSV infection up-regulated poSn expression. • poSn up-regulation was induced by PRRSV-triggered type I IFNs. • IFN-STAT signaling cascade was involved in poSn induction. • poSn up-regulation contributed to PRRSV infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the value of hematocrit (HCT) level in predicting the outcomes of critically ill patients with acute kidney injury (AKI). A retrospective study of a total of 14,350 intensive care unit (ICU) patients, who were selected from Beth Israel Deaconess Medical Center (Boston, MA, USA) and met the inclusion criteria, was carried out. And the patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.3 (MIMIC-III v1.3). In our study, HCT quintiles were used to categorize the subjects into groups. The clinical outcomes were 30- and 90-day mortality in the ICU. Cox proportional-hazards models were used to evaluate the association between the HCT and survival. A total of 2827 30-day deaths and 3828 90-day deaths occurred. In univariate analysis, low HCT was significantly associated with increased 30- and 90-day mortality among females, which, however, was not observed in multivariate analysis adjusted for age, ethnicity, dialysate, continuous renal replacement therapy (CRRT), use of insulin, use of ventilator, AKI stages, and report of obesity. In subgroup analysis, an inverse association between HCT levels and risk of mortality for 90-day outcome was observed for female patients by exclusion of dialysate use, receiving CRRT, and obesity reports. Therefore, these findings suggest that lower HCT was associated with an increased risk of mortality in critically ill patients with AKI, and the effect appears to be stronger among women than men. The prognostic value of HCT seems dependent on other factors, for example, dialysate use, CRRT, and obesity. Further multicenter study is in demand to confirm the validity of the results presented in this article. [ABSTRACT FROM AUTHOR]

Background: Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined. Methods: Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression. Loss- and gain-of function assays were performed to investigate the role of Chibby in NPC cells. Western blot, cell proliferation, Glucose uptake, Lactate release, ATP level, and O2 consumption assays were used to determine the mechanism of Chibby regulation of underlying targets. Finally, immunohistochemistry assay of fresh NPC and nasopharyngeal normal tissue sample were used to detect the expression of Chibby, β-Catenin, and PDK1 by immunostaining. Results: We observed that Chibby, a β-catenin-associated antagonist, is down-regulated in nasopharyngeal carcinoma cell lines and inhibits Wnt/β-Catenin signaling induced Warburg effect. Mechanism study revealed that Chibby regulates aerobic glycolysis in NPC cells through pyruvate dehydrogenase kinase 1(PDK1), an important enzyme involved in glucose metabolism. Moreover, Chibby suppresses aerobic glycolysis of NPC via Wnt/β-Catenin-Lin28/let7-PDK1 cascade. Chibby and PDK1 are critical for Wnt/β-Catenin signaling induced NPC cell proliferation both in vitro and in vivo. Finally, immunostaining assay of tissue samples provides an important clinical relevance among Chibby, Wnt/β-Catenin signaling and PDK1. Conclusions: Our study reveals an association between Chibby expression and cancer aerobic glycolysis, which highlights the importance of Wnt/β-catenin pathway in regulation of energy metabolism of NPC. These results indicate that Chibby and PDK1 are the potential target for NPC treatment. [ABSTRACT FROM AUTHOR]