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Zika virus (ZIKV) infection can cause severe neurological diseases including neonatal microcephaly and Guillain-Barre syndrome. Long noncoding RNAs (lncRNAs) are the by-products of the transcription process, which are considered to affect viral infection. However, it remains largely unexplored whether host lncRNAs play a role in ZIKV infection. Here, we identified a group of human lncRNAs that were up-regulated upon ZIKV infection and were dependent on the type I interferon (IFN) signaling. Overexpression of lncRNA ZAP-IT1 leads to an impairment of ZIKV infection. Correspondently, deficiency of ZAP-IT1 led to an enhancement of ZIKV infection. We further confirmed that ZAP-IT1, an intronic lncRNA with total 551 ​nt in length, is mainly located in the nuclear upon ZIKV infection. Knockout of ZAP-IT1 also led to the increase of dengue virus (DENV), Japanese encephalitis virus (JEV), or vesicular stomatitis virus (VSV) infection. Mechanically, we found that the antiviral effect of ZAP-IT1 was independent of the type I IFN signaling pathway. Therefore, our data unveiled that host lncRNA ZAP-IT1 induced by the type I IFN signaling, showed robust restriction on ZIKV infection, and even on DENV, JEV, and VSV infection, which may benefit the development of antiviral therapeutics.

Clinical internship is a focused and supervised practice where nursing students have opportunities to master clinical skills and better adapt to the real working environment, promoting the formation of professional practice quality. However, for African postgraduate nursing students who had an internship in China, the factors affecting their adaptation to the internship have not yet been sufficiently explored.To explore the facilitators and barriers of African postgraduate nursing students' adaptation to an internship.Qualitative descriptive study.A comprehensive university with three affiliated hospitals in southern China.Twelve African postgraduate nursing students who finished a three-month internship in the two-year postgraduate programme.Participants were recruited using purposive sampling. Semi-structured interviews were conducted between April and December 2021. Data were thematically analysed using the Colaizzi seven-step method.Three facilitators and four barriers to their adaptation to the internship emerged in the study. Facilitators included the teacher-student interactions, harmonious working atmosphere and positive inner incentives of the students. Barriers to adaptation were language barriers, unsuitable internship arrangements, lack of opportunities to practice clinical skills and disparities in hospital routine works.The present findings could contribute to the improvement of a more effective clinical training programme. Nursing colleges and teaching hospitals should make more efforts to enhance the current clinical internship programmes. Further support is necessary for international nursing students according to their culturally and linguistically diverse backgrounds.

The physicochemical and structural properties of waxy rice starch (WRS) and alcohol-alkali-treated waxy rice starch (AAT-WRS) were determined in the presence of different concentrations of NaCl (0, 2, 4, 6 and 8%). The results showed that NaCl decreased the transparency of WRS and AAT-WRS pastes, but enhanced both freeze-thaw stability and apparent viscosity (p 0.05). The rheological measurement results showed that the addition of NaCl could improve the modulus values of both WRS and AAT-WRS, and the effect on WRS was more significant than that on AAT-WRS. The textural parameters of WRS pastes were evidently enhanced by NaCl, but the presence of NaCl had no significant effect on the firmness of AAT-WRS pastes. The results of SEM and FT-IR revealed that NaCl could protect the granular morphology and increase the degree of short-range order of WRS and AAT-WRS.

Diquat is a widely used herbicide that is substituted for paraquat. With paraquat off the market, cases of diquat poisoning have been gradually increasing. The kidney is the most frequently impaired organ in diquat poisoning. Few cases of multiple organ failure caused by diquat have been reported. We herein describe a 30-year-old man who orally ingested about 160 mL of enriched diquat. Despite aggressive treatment, the patient’s condition progressed to multiple organ failure and death. The pulmonary lesions in this patient were different from those previously reported. This patient did not die of renal failure but of severe respiratory failure. He exhibited three different stages of pulmonary disease. The lung lesions in this case were unique. We hope that doctors will pay more attention to the lung lesions in patients with diquat poisoning in future and find new treatment methods to save the lives of such patients.

The evolution of emergency scenarios is usually hard to predict. To address this problem, a method for determining the severity of emergencies is proposed based on a decision paradigm obtained from the analysis of similar cases. First, the standardized indicators in the base case are used to input the target event so as to filter out some similar events as references. The severity of reference events is used to acquire the severity of the target event. When the target event evolves into an event whose average severity exceeds that of a major emergency, large group emergency decision making is initiated. Second, based on the fact that there is consistency interval existing in a hesitant fuzzy preference matrix, a method to measure the rationality of experts and determine their weights using an interval consistency composed of the average consistency and standard deviation indices is proposed in this paper. Finally, an example is given to illustrate the effectiveness of the proposed method.

Background Macular corneal dystrophy (MCD), a rare autosomal recessive disorder, is caused by pathogenic mutations in the carbohydrate sulfotransferase 6 gene (CHST6) and is characterized by bilateral progressive stromal clouding and vision loss. Corneal transplantation is often necessary. This study aimed to identify disease-causing mutations in a Han-Chinese MCD patient. Methods A 37-year-old female diagnosed with MCD was recruited. The clinical materials were observed and described, and peripheral blood sample was extracted. Whole exome sequencing (WES) and Sanger sequencing were used to reveal genetic defects. The pathogenicity of identified mutations was assessed using in silico analysis. Results The patient had typical features of MCD, including decreased vision, multiple irregular gray-white corneal opacities, and corneal thinning. A novel nonsense mutation c.544C>T (p.Gln182Ter) and a validated missense mutation c.631C>G (p.Arg211Gly) were identified in the CHST6 gene coding region, both classified as "pathogenic" following the American College of Medical Genetics and Genomics standards and guidelines. Conclusions This study reports a Han-Chinese MCD patient with a novel nonsense mutation c.544C>T (p.Gln182Ter) and a recurrent missense mutation c.631C>G (p.Arg211Gly), which expand the spectrum of genetic mutations. The results of this study extend genotype-phenotype correlations between the CHST6 gene mutations and MCD clinical findings, contributing to a more accurate diagnosis and the development of potential gene-targeted MCD therapies. Keywords Carbohydrate sulfotransferase 6 gene (CHST6); compound heterozygous mutations; Han Chinese family; macular corneal dystrophy (MCD).

Background Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. Method Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. Results In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as “suspected sHLH positive”. Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P 1922.58 ng/mL), low platelets (9/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. Conclusions HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.

Background: Studies have shown the failure of vancomycin treatment against vancomycin-sensitive gram-positive bacteria is common, possibly because the drug concentration did not reach the target serum concentration in time. In this study, we conducted a retrospective analysis to determine whether the target serum concentration could be reached earlier with the first loading dose of vancomycin.Methods: A retrospective single-center study was conducted in the Department of Critical Care Medicine, Ruijin Hospital North Affiliated to Shanghai Jiao Tong University School of Medicine between June 2018 and June 2020. The study enrolled patients who were suspected or confirmed with gram-positive bacterial infection and had been treated with vancomycin. According to whether the first loading dose of vancomycin was given, the patients were divided into the loading dose and the control groups. The serum concentration of vancomycin before the second dose and that before the fifth dose were compared to determine whether the target serum concentration was reached earlier with the first loading dose. And renal functions were monitored for a week to analyze whether the loading dose caused any acute kidney injury.Results: 55 patients were finally included in the study. Of these patients, 29 received first-loading dose of vancomycin, while the remaining 26 patients underwent the traditional dose regimen of vancomycin. The concentration of vancomycin before the second dose was 10.3±6.1 mg/L in the loading group, and 5.7±4.4 mg/L in the control group, significantly higher in the former group (P=0.002). The concentration of vancomycin before the fifth dose was 12.4±7.3 mg/L in the loading group, and 10.3±6.3 mg/L in the control group, where there was no inter-group difference (P=0.251). The 28-day motality of loading dose group is significantly lower (6.7% vs 34%, P=0.026) than the control group. There were no significant changes in serum creatinine levels in both groups, and there was no statistical difference in serum creatinine levels between the two groups.Conclusions: With the loading dose of vancomycin, the target serum concentration of vancomycin could be reached earlier without causing acute kidney injuries, also the mortality might be reduced.

Background. Recurrent spontaneous abortion (RSA) is intractable infertility and can be ameliorated with the use of traditional Chinese medicine preparation, the Wenjing decoction. This study aimed to identify the therapeutic mechanism of Wenjing decoction on specific target proteins involved in RSA. Methods. Wenjing decoction contains Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Ejiao, Mudanpi, Chishao, Dangshen, and Maidong. Using TCMSP and BATMAN databases, we queried for active ingredients and predicted their target proteins by BATMAN. Using the edgeR package, we analyzed the differentially expressed genes (DEGs) in the GSE121950 database between control samples and RSA (n = 3). The interaction between DEGs and the predicted target proteins was identified by the Venn diagram. Using the Cytoscape software and clusterProfiler package, enrichment analysis was conducted for the intersected target proteins. Additionally, the protein-protein interaction (PPI) network and pharmacological network were generated using the Cytoscape software. Results. In total, 31, 2, 7, 7, 5, 13, 93, 11, 29, and 21 active ingredients were identified from Wuzhuyu, Danggui, Chuanxiong, Guizhi, Shengjiang, Banxia, Gancao, Mudanpi, Chishao, and Dangshen, respectively. Additionally, 100 intersected target proteins were revealed by the Venn diagram. Moreover, 98 functional terms and 24 pathways (including C-type lectin receptor signaling pathway, chemokine signaling pathway, leukocyte transendothelial migration, fluid shear stress, and atherosclerosis, and AGE-RAGE signaling pathway in diabetic complications) were enriched. In the PPI network, 10 proteins involved in these five pathways were identified, namely, TNF-α (tumor necrosis factor-α), IL-10 (interleukin-10), TLR4 (Toll-like receptor 4), JUN (Jun proto-oncogene), IL-1B (interleukin-1-beta), CYBB (cytochrome b558 heavy chain gene), PTGS2 (prostaglandin-endoperoxide synthase 2), APOE (apolipoprotein E), SPI1 (salmonella pathogenicity island 1), and MPO (myeloperoxidase) which showed higher degrees. Conclusion. The abovementioned genes and pathways might be involved in the pharmacological activity of Wenjing decoction in RSA.

This paper studies the response of a parity-time-symmetric Laguerre-Gaussian-cavity optomechanical system to a weak probe field, where an active cavity is coupled to a Laguerre-Gaussian rovibrational-cavity system. It is shown that three-amplification-peak profile emerges for the probe transmission. The transmission rate can be adjusted by controlling the coupling coefficient, the pump amplitude and the topological charge. Besides, we find that the light transmission group delay can be altered between positive and negative value by adjusting the coupling coefficient and the topological charge. This study can be applied to light propagation manipulation and quantum precision measurement.

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus which has become a global epidemic threat due to its rapid spread and association with serious consequences of infection, including neonatal microcephaly. Inositol-requiring enzyme 1α (IRE1α) is an endoplasmic reticulum (ER)-related transmembrane protein that mediates unfolded protein response (UPR) pathway and has been indicated to play an important role in flavivirus replication. However, the mechanism of how IRE1α affects ZIKV replication remains unknown. In this study, we explored the role of IRE1α in ZIKV infection in vitro and in vivo by using CRISPR/Cas9-based gene knockout and RNA interference-based gene knockdown techniques. Both knockout and knockdown of IRE1α dramatically reduced ZIKV replication levels, including viral RNA levels, protein expression, and titers in different human cell lines. Trans-complementation with IRE1α restored viral replication levels decreased by IRE1α depletion. Furthermore, the proviral effect of IRE1α was dependent on its kinase and RNase activities. Importantly, we found that IRE1α promoted the replication of ZIKV through upregulating the accumulation of monounsaturated fatty acid (MUFA) rate-limiting enzyme stearoyl coenzyme A (stearoyl-CoA) desaturase 1 (SCD1), which further affected the production of oleic acid (OA) and lipid droplet. Finally, our data demonstrated that in the brain tissues of ZIKV-infected mice, the replication levels of ZIKV and virus-related lesions were significantly suppressed by both the kinase and RNase inhibitors of IRE1α. Taken together, our results identified IRE1α as a ZIKV dependency factor which promotes viral replication through affecting SCD1-mediated lipid metabolism, potentially providing a novel molecular target for the development of anti-ZIKV agents. IMPORTANCE Zika virus (ZIKV) has been linked to serious neurologic disorders and causes widespread concern in the field of global public health. Inositol requiring enzyme 1α (IRE1α) is an ER-related transmembrane protein that mediates unfolded protein response (UPR) pathway. Here, we revealed that IRE1α is a proviral factor for ZIKV replication both in culture cells and mice model, which relies on its kinase and RNase activities. Importantly, we further provided evidence that upon ZIKV infection, IRE1α is activated and splices XBP1 mRNA which enhances the expression of monounsaturated fatty acids rate-limiting enzyme stearoyl coenzyme A (stearoyl-CoA) desaturase 1 (SCD1) and subsequent lipid droplet production. Our data uncover a novel mechanism of IRE1α proviral effect by modulating lipid metabolism, providing the first evidence of a close relationship between IRE1α-mediated UPR, lipid metabolism, and ZIKV replication and indicating IRE1α inhibitors as potentially effective anti-ZIKV agents.

Cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, shows remarkable similarities to caspase-8, which plays a key role in the cleavage of gasdermin D (GSDMD). It has been reported that the oxygen-glucose deprivation/recovery (OGD/R) model and lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment could induce inflammation and pyroptosis. However, the regulatory role of c-FLIP in the pyroptotic death of retinal neurons is unclear. In this study, we hypothesized that c-FLIP might regulate retinal neuronal pyroptosis by GSDMD cleavage. To investigate this hypothesis, we induced retinal neuronal damage in vitro (OGD/R and LPS/ATP) and in vivo (acute high intraocular pressure [aHIOP]). Our results demonstrated that the three injuries triggered the up-regulation of pyroptosis-related proteins, and c-FLIP could cleave GSDMD to generate a functional N-terminal (NT) domain of GSDMD, causing retinal neuronal pyroptosis. In addition, c-FLIP knockdown in vivo ameliorated the already established visual impairment mediated by acute IOP elevation. Taken together, these findings revealed that decreased c-FLIP expression protected against pyroptotic death of retinal neurons possibly by inhibiting GSDMD-NT generation. Therefore, c-FLIP might provide new insights into the pathogenesis of pyroptosis-related diseases and help to elucidate new therapeutic targets and potential treatment strategies.

Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.

Background: With cerebral palsy children's psychological behavior problems loom large, it gradually be taken seriously. This research aimed to analyze the social emotional disorders of the Chinese children with cerebral palsy aged at 1~3 years, and further screen out the independent risk factors that affect their social emotional development.Methods: A total of 300 Chinese children with cerebral palsy aged 1~3 years-old(192 males, 108 females) and their parents took part in this cross-sectional survey, in which the Chinese Version of Infant Toddler Social-Emotional Assessment (CITSEA), the Bayley Scales of Infant Development (BSID) and the Gross Motor Function Measure (GMFM-88) were for children while the Coping Style Questionnaire, the Hospital Anxiety and Depression Scale ( HADS) were for parents. The independent risk factors related to social emotional disorders were screened out using a multivariate logistic or linear regression analysis.Results: The scores of the externalizing and competency domains for the children with cerebral palsy in different age groups were lower than those for healthy children of the same age and gender (pp=0.001). Conclusions: This study found that the parental emotional state, the education level, the parenting style and the perinatal factors are closely related to social emotional problems in the Chinese children with cerebral palsy.

Bile acids (BAs) play essential roles in facilitating lipid digestion and absorption in the intestine. Gastric BAs were attributed to abnormal refluxing from duodenal compartments and correlated with the occurrence of gastric inflammation and carcinogenesis. However, the differences in gastric BAs between physiologically compromised and healthy individuals have not been fully investigated. In this study, gastric juice was collected from patients clinically diagnosed as gastritis with/without bile reflux and healthy subjects for BA profiles measurements. As a result, we found that the conjugated BAs became prominent components in bile reflux juice, whereas almost equal amounts of conjugated and unconjugated BAs existed in non-bile reflux and healthy juice. To investigate whether gastric BA changes were regulated by hepatic BA synthesis, C57BL/6J mice were intervened with GW4064/resin to decrease/increase hepatic BA synthesis. The results revealed that changes of gastric BAs were coordinated with hepatic BA changes. Additionally, gastric BAs were detected in several healthy mammals, in which there were no obvious differences between the conjugated and unconjugated BAs. Pigs were an exception. Thus, increased levels of conjugated BAs are associated with human bile reflux gastritis. Gastric conjugated BAs could become a panel of biomarkers to facilitate diagnosis of pathological bile reflux.

Background Stroke outpatients have a high risk of falling. However, fall prevention measures in the community are insufficient to effectively reduce the fall rate among outpatients with stroke. We aimed to determine the correlation between fall prevention knowledge and behavior among outpatients with stroke and provide new strategies for community fall prevention. Methods We recruited 124 patients with stroke who were followed up in the outpatient department of a tertiary hospital in Zhuhai, China. Patients were assessed using a general information questionnaire, a fall prevention knowledge questionnaire for patients with stroke, and the Stroke Fall Prevention Behavior Scale. IBM SPSS 22.0 software was used for statistical analysis. Results The median fall prevention knowledge was 82.76 (68.97, 93.10) points, out of 100. The mean (SD) score for fall prevention behavior was 2.90 (0.52; range, 1-4) points. Fall prevention knowledge scores were positively related to those fall prevention behavior (Spearman r = 0.454, P Conclusion Levels of fall prevention knowledge among outpatients with stroke were adequate, and this population had medium to high levels of fall prevention behavior. Better knowledge was accompanied with better prevention of falls. However, whether enriching the knowledge could lead to improvement of fall prevention is still undetermined.

This paper proposed a method for predicting failure loads of masonry wall panels subject to uniformly distributed lateral loading based on a concept of structural stress state. Firstly, the characteristics of the structural stress state of masonry wall panels subjected to uniform distributed lateral loading were investigated through experimental results. Then, a new parameter was proposed to characterize the structural stress state. Next, the relation of the failure loads between a specified base wall panels and other wall panel was established using the proposed parameter. In this way, a method (called a ST method) based on a structural stress state parameter to predict the failure load of masonry wall panel from the base wall panel was established. The following case studies validated the ST method by comparing the predicted failure load with the experimental results, as well as those predicted from the existing yield line theory (YLT), the FEA method and the GSED-based cellular automata (CA) method. The ST method provided an innovative way of structural analysis on the basis of structural stress state.

Metal complexes that contain carbohydrate-substituent (Carb-) N-heterocyclic carbenes (NHCs) ligand have demonstrated great success as catalysts for organic synthesis reactions. In this study, four new Carb-NHC-Pd complexes 2a-d were prepared and their catalytic activities for Suzuki-Miyaura reaction were evaluated. The Carb-NHC-Pd complex behaved as a general surfactant which leads to the formation of a temporary oil-in-water contact interface, thereby promoting the Suzuki-Miyaura reaction. A long hydrophobic alkyl chain (

High porosity nitrogen and phosphorous co-doped carbon nanosheets with high surface area (1057.9 m2 g−1) are fabricated by using polyacrylonitrile and red phosphorous as the precursors. The catalyst exhibits outstanding catalytic performance towards oxygen reduction reaction (ORR), with its half-wave potential 35 mV more superior to that of Pt/C. In addition to high ORR performance, our catalyst also exhibits remarkable methanol tolerance, outstanding stability, as well as high catalytic efficiency (almost 100% selectivity towards four-electron path). Based on the characterization results, we find that moderate P introduction can significantly modify catalysts N compositions, as well as porous structures, which, we suggest, should be the proper origins to our catalyst's outstanding performance.

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region. There is the likely risk for ZIKV to spread to more countries. There is also the potential for the re-emergence of ZIKV in all places with prior reports of the virus transmission. The current status of ZIKV transmission and spread is, however, a global health threat, and from the aforementioned, has the potential to re-emerge as an epidemic. This review summarizes the past and present spread of ZIKV outbreak-2007-2019, the genome, transmission cycle, clinical manifestations, vaccine and antiviral drug advancement.

Zika virus (ZIKV) is an emerging arthropod-borne virus and belongs to the Flaviviridae family. The infection of ZIKV has become the global health crisis because of its rapid spread and association with severe neurological disorders, including congenital microcephaly and Guillain-Barre Syndrome. To identify host factors contributing to ZIKV pathogenesis, transcriptomic landscape in ZIKV-infected cells was examined with mRNA microarray analysis and we observed that the expression of hydroxycarboxylic acid receptor 2 (HCAR2) could be significantly induced by ZIKV infection. By utilizing two IRE1 inhibitors and XBP1-specific shRNAs, we revealed that the up-regulation of HCAR2 expression induced by ZIKV was dependent on the IRE1-XBP1 pathway. Through the CRISPR/Cas9 system, we generated HCAR2-deficient cell clones in two cell types (human lung carcinoma epithelial A549 cell and human hepatoma Huh7.5 cell). We found that the depletion of HCAR2 significantly increased the replication level of ZIKV, including RNA levels, protein expression levels, and viral titers. In addition, our data demonstrated that the antiviral effect of HCAR2 was not involved in viral entry process and was not dependent on its antilipolytic effect on nicotinic acid/HCAR2-mediated signaling pathway. Taken together, our results indicated that HCAR2 could function as a restriction factor in control of ZIKV replication, potentially providing a novel molecular target for anti-ZIKV therapeutics.

This paper conducts the experimental and simulative analysis of stressing state characteristics for parabolic concretefilled steel tubular (CFST) arches undergoing vertical loads. The measured stain data is firstly modeled as the generalized strain energy density (GSED) to describe structural stressing state mode. Then, the normalized GSED sum Ej,norm at each load Fj derives the Ej,norm-Fj curve reflecting the stressing state characteristics of CFST arches. Furthermore, the Mann-Kendall criterion is adopted to detect the stressing state change of the CFST arch during its load-bearing process, leading to the revelation of a vital stressing state leap characteristic according to the natural law from quantitative change to qualitative change of a system. The revealed qualitative leap characteristic updates the existing definition of the CFST arch’s failure load. Finally, the accurate formula is derived to predict the failure/ultimate loads of CFST arches. Besides, a method of numerical shape function is proposed to expand the limited strain data for further analysis of the stressing state submodes. The GSED-based analysis of structural stressing state opens a new way to recognize the unseen working behavior characteristics of arch structures and the updated failure load could contribute to the improvement on the structural design codes.

This study aimed to explore potential new drugs in the treatment of ischemic stroke by Connectivity Map (CMap) and to determine the role of luteolin on ischemic stroke according to its effects on matrix metalloproteinase-9 (MMP9) and PI3K/Akt signaling pathway. Based on published gene expression data, differentially expressed genes were obtained by microarray analysis. Potential compounds for ischemic stroke therapy were obtained by CMap analysis. Cytoscape and gene set enrichment analysis (GSEA) were used to discover signaling pathways connected to ischemic stroke. Cell apoptosis and viability were, respectively, evaluated by flow cytometry and an MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were used to test the expression of MMP9 and the PI3K/Akt signaling pathway-related proteins in human brain microvascular endothelial cells (HBMECs) and tissues. Additionally, the infarct volume after middle cerebral artery occlusion (MCAO) was determined by a TTC (2,3,5-triphenyltetrazolium chloride) assay. The microarray and CMap analyses identified luteolin as a promising compound for future therapies for ischemic stroke. Cytoscape and GSEA showed that the PI3K/Akt signaling pathway was crucial in ischemic stroke. Cell experiments revealed that luteolin enhanced cell viability and downregulated apoptosis via inhibiting MMP9 and activating the PI3K/Akt signaling pathway. Experiments performed in vivo also demonstrated that luteolin reduced the infarct volume. These results suggest that luteolin has potential in the treatment of ischemic stroke through inhibiting MMP9 and activating PI3K/Akt signaling pathway., Ischemic stroke: Compound in fruit and vegetables may offer benefit A metabolite commonly found in fruit and vegetables may provide protection against brain damage after a stroke, according to researchers in China. Lei Zhang and co-workers at Sun Yat-sen University in Guangdong employed the Connectivity Map (CMap), a tool for analyzing genome-wide data and identifying connections between diseases, genes, and potential treatments. They confirmed that the metabolite luteolin may benefit patients who have suffered ischemic stroke, which is caused by a blocked artery to the brain. Using an existing database comprising genetic details of stroke patients and controls, the team found that a major signaling pathway is inactivated and an enzyme called MMP9 is increased in stroke victims. Studies in cultured human brain cells and rats showed that luteolin can inhibit MMP9 and reactivate the signaling pathway.

This paper proposes a scheme for wide-range precision measurement of the environmental temperature in a double-cavity optomechanical system. This system consists of an optomechanical cavity coupling to the other cavity via photon tunneling interaction. Bycontrolling the tunnelling strength between the two cavities, double optomechanically induced transparency (double OMIT) effect is observed in the homodyne spetra of the outfield. It is shown that the central peak value depends linearly on the environmental temperature. Based on this linear relationship, the environmental temperature can be inferred from the central peak value of the output homodyne spectrum. This scheme is robust against mechanical decay and it shows high sensivity over a wide temperature range.

Dengue virus (DENV) utilizes host factors throughout its life cycle. In this study, we identified RNA helicase A (RHA), a member of the DEAD/H helicase family, as an important host factor of DENV. In response to DENV2 infection, nuclear RHA protein was partially redistributed into the cytoplasm. The short interfering RNA-mediated knockdown of RHA significantly reduced the amounts of infectious viral particles in various cells. The RHA knockdown reduced the multistep viral growth of DENV2 and Japanese encephalitis virus but not Zika virus. Further study showed that the absence of RHA resulted in a reduction of both viral RNA and protein levels, and the data obtained from the reporter replicon assay indicated that RHA does not directly promote viral protein synthesis. RHA bound to the DENV RNA and associated with three nonstructural proteins, including NS1, NS2B3, and NS4B. Further study showed that different domains of RHA mediated its interaction with these viral proteins. The expression of RHA or RHA-K417R mutant protein lacking ATPase/helicase activity in RHA-knockdown cells successfully restored DENV2 replication levels, suggesting that the helicase activity of RHA is dispensable for its proviral effect. Overall, our work reveals that RHA is an important factor of DENV and might serve as a target for antiviral agents. IMPORTANCE Dengue, caused by dengue virus, is a rapidly spreading disease, and currently there are no treatments available. Host factors involved in the viral replication of dengue virus are potential antiviral therapeutic targets. Although RHA has been shown to promote the multiplication of several viruses, such as HIV and adenovirus, its role in the flavivirus family, including dengue virus, Japanese encephalitis virus, and emerging Zika virus, remains elusive. The current study revealed that RHA relocalized into the cytoplasm upon DENV infection and associated with viral RNA and nonstructural proteins, implying that RHA was actively engaged in the viral life cycle. We further provide evidence that RHA promoted the viral yields of DENV2 independent of its helicase activity. These findings demonstrated that RHA is a new host factor required for DENV replication and might serve as a target for antiviral drugs.

Purpose Retinoblastoma (RB) is the most common intraocular malignancy in children. Deregulation of several microRNAs (miRNAs) has been identified in RB. However, the specific effect of let-7a on RB remains unclear. The present study aims to explore the effect of let-7a on malignant biological behaviors of RB cells and angiogenesis in RB. Methods The expressions of let-7a and mammalian sterile-20 like kinase 4 (MST4) in RB were determined with the use of real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Next, in order to explore effects of let-7a and MST4 on RB cellular functions, RB cells were transfected with let-7a-mimic, let-7a inhibitor, si-MST4, or co-transfected with let-7a-mimic and oe-MST4 plasmids. Subsequently, the interaction among let-7a, MST4, and the MAPK signaling pathway was evaluated by RT-qPCR, dual-luciferase reporter gene assay, and Western blot analysis. Finally, the effects of let-7a and MST4 were further confirmed in vivo by injecting nude mice with RB cells stably expressing let-7a agomir or sh-MST4. Results Rb tissues and cells presented with downregulated Let-7a and upregulated MST4. Let-7a negatively targeted MST4 to block the activation of the MAPK signaling pathway. Upregulation of let-7a promoted apoptosis, and facilitated proliferation, angiogenesis, migration, and invasion of RB cells by decreasing MST4. Elevation of let-7a or silencing MST4 restricted angiogenesis and tumorigenesis in RB mice. Conclusions Taken together, let-7a inhibits angiogenesis in RB by silencing MST4 and inhibiting the MAPK signaling pathway.

In our previous study, we reported that peptidyl-prolyl isomerase 1 (Pin1)-modulated regulated necrosis (RN) occurred in cultured retinal neurons after glutamate injury. In the current study, we investigated the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in Pin1-modulated RN in cultured rat retinal neurons, and in an animal in vivo model. We first demonstrated that glutamate might lead to calcium overloading mainly through ionotropic glutamate receptors activation. Furthermore, CaMKII activation induced by overloaded calcium leads to Pin1 activation and subsequent RN. Inactivation of CaMKII by KN-93 (KN, i.e., a specific CaMKII inhibitor) application can decrease the glutamate-induced retinal neuronal RN. Finally, by using an animal in vivo model, we also demonstrated the important role of CaMKII in glutamate-induced RN in rat retina. In addition, flash electroretinogram results provided evidence that the impaired visual function induced by glutamate can recover after CaMKII inhibition. In conclusion, CaMKII is an up-regulator of Pin1 and responsible for the RN induced by glutamate. This study provides further understanding of the regulatory pathway of RN and is a complementary mechanism for Pin1 activation mediated necrosis. This finding will provide a potential target to protect neurons from necrosis in neurodegenerative diseases, such as glaucoma, diabetic retinopathy, and even central nervous system diseases.

Oxymatrine (OMT) as a type of alkaloids collected from Sophora flavescens Ait exerts some biological functions including anticancer properties. Here, we investigated the therapeutic effects of OMT in gastric cancer cells (HGC 27 and AGS). As a result, the exposure of gastric cancer (GC) cells to OMT contributed to the suppression of cell proliferation and invasion. Interleukin 21 receptor (IL-21R) was identified to be differentially expressed between OMT treatment group (4 mg/mL) and control group (0 mg/mL), and knockdown of IL-21R repressed cell proliferation and invasion via inactivation of the JAK2/STAT3 pathway. The rescue experiment showed that IL-21R overexpression attenuated the anti-tumor effects of OMT through activation of the JAK2/STAT3 pathway. Moreover, the expression of IL-21R was significantly upregulated in GC samples compared with the adjacent normal tissues and associated with overall survival (OS) and tumor recurrence of GC patients. Taken together, in this study, we evaluated the anti-tumor effects of OMT on GC by investigating proliferation and invasion ability changes, and our findings show that OMT exhibits effects via regulation of JAK/STAT signaling pathway. Through the mechanism study, we may enlighten the potential therapeutic target for treatment of GC.

The purpose of this study is to investigate whether calpastatin (CAST) plays an important role in the regulated necrosis (RN) in rat retinal neurons under an excessive glutamate condition and furthermore to investigate whether this process is regulated by calapin1 and calpain2. In the present study, glutamate triggered CAST inhibition, calpain2 activation and retinal neuronal RN after injury. The application of CAST active peptide could provide protective effects against activated calpain2 mediated RN. However, the calpain1 activity was not changed in these processes. Finally, in vivo studies further confirmed the role of the CAST-calpain2 pathway in cellular RN in the rat retinal ganglion cell layer and inner nuclear layer after glutamate excitation. In addition, flash electroretinogram results provided evidence that the impaired visual function induced by glutamate could recover after CAST peptide treatment. This research indicated that excessive glutamate may lead to CAST inhibition and activated calpain2, but not calpain1 activation, resulting in RN.

Background and objectives Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. Materials and methods 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Results Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Conclusion Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment.

The purpose of the current study was to investigate whether peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) can interact with calpastatin (CAST) and regulate CAST/calpain2, under excessive glutamate conditions, and subsequently regulate necrosis in rat retinal neurons. Glutamate triggered CAST/calpain2-mediated necrosis regulation in primary cultured retinal neurons, as demonstrated by propidium iodide-staining and lactate dehydrogenase assay. Co-IP results and a computer simulation suggested that Pin1 could bind to CAST. Western blot, real-time quantitative polymerase chain reaction, immunofluorescence, and phosphorylation analysis results demonstrated that CAST was regulated by Pin1, as proven by the application of juglone (i.e., a Pin1 specific inhibitor). The retinal ganglion cell 5 cell line, combined with siRNA approach and flow cytometry, was then used to verify the regulatory pathway of Pin1 in CAST/calpain2-modulated neuronal necrosis that was induced by glutamate. Finally, in vivo studies further confirmed the role of Pin1 in CAST/calpain2-modulated necrosis following glutamate excitation, in the rat retinal ganglion cell and inner nuclear layers. In addition, a flash electroretinogram study provided evidence for the recovery of impaired visual function, which was induced by glutamate, with juglone treatment. Our work aims to investigate the involvement of the Pin1-CAST/calpain2 pathway in glutamate-mediated excitotoxicity.

Figure S3. Cell cycle analysis. a, Cell cycle assays of AGS transfected with circYAP1 or circYAP1 + miR-367-5p mimics. b Cell cycle assays of MKN-45 transfected with circYAP1 or circYAP1 + miR-367-5p mimics. c Cell cycle assays of HGC-27 cells transfected with si-circYAP1 or si-circYAP1 + miR-367-5p inhibitor. *P

Figure S2. a, CircYAP1 expression in GES-1 and GC cell lines. b-c, AGS and MKN-45 GC cells transfected with the circYAP1 overexpression lentivirus. d-e, miR-367-5p mimics were transfected into AGS and MKN-45 GC cells. f, qPCR analysis of the transfection efficiency of si-circYAP1 vectors after transfection for 48 h in HGC-27 cells. *P

This paper proposed a method for predicting failure loads of masonry wall panels subject to uniformly distributed lateral loading based on a concept of structural stress state. Firstly, the characteristics of the structural stress state of masonry wall panels subjected to uniform distributed lateral loading were investigated through experimental results. Then, a new parameter was proposed to characterize the structural stress state. Next, the relation of the failure loads between a specified base wall panels and other wall panel was established using the proposed parameter. In this way, a method (called a ST method) based on a structural stress state parameter to predict the failure load of masonry wall panel from the base wall panel was established. The following case studies validated the ST method by comparing the predicted failure load with the experimental results, as well as those predicted from the existing yield line theory (YLT), the FEA method and the GSED-based cellular automata (CA) method. The ST method provided an innovative way of structural analysis on the basis of structural stress state.

Tables S1. Sequences of primers in the study. Table S2. Clinic-pathological data of GC patients from Tissue Microarray. Table S3. Correlation of circYAP1 expression with clinic-pathologic characteristics of GC patients. Table S4. Summary of univariate and multivariate Cox regression analysis of overall survival duration (DOCX 20 kb)

Figure S1. a, The expression levels of circYAP1 in GC patients with TS â Ľ5Â cm or

Background Gracilaria lemaneiformis is a common red alga used as a raw material source for the agar industry. Its extract is rich in natural volatile constituents (VCs) having antioxidant activities. Herein, a sustainable method was used to recover VCs from the alga. The chemical composition of VCs present in the n-hexane fraction was analyzed by gas chromatography–mass spectroscopy (GC–MS) and the antioxidant potential was measured using a series of in vitro biochemical assays, including DPPH, hydroxyl, and superoxide radical scavenging assays. Results The recovery yield of the VCs was 0.823 wt% of the dry mass of G. lemaneiformis. A total of 25 VCs were successfully identified, comprising approximately 99.94% of the total volume. The major component was n-hexadecanoic acid (38.57%), followed by oleic acid (25.48%), arachidonic acid (12.84%), and tetradecanoic acid (2.52%). In addition, The VCs displayed strong free radical scavenging activity in the DPPH (IC50 = 21.56 mg/L), hydroxyl (IC50 = 18.34 mg/L), and superoxide (IC50 = 391.12 mg/L) radical scavenging assays. The antioxidant activities of the VCs exhibited a dose-dependence at concentrations ranging from 5 to 200 mg/L. Conclusion The results indicated that the sustainable process improved the agar quality and that the extract contained many natural VCs with antioxidant activities, which have the potential to be used in functional food and cosmetics instead of as a discarded byproduct of the agar industry.

To investigate clinical outcomes of neuromyelitis optica (NMO) patients with brain magnetic resonance imaging (MRI) abnormalities.

Tripartite and bipartite quantum correlations in the three-qubit XXZ Heisenberg spin chain with two types of three-site interactions and an external magnetic field are investigated. We show that the increase in XZY − YZX interaction can enhance the robustness of both tripartite and bipartite correlations, whereas the increase in XZX $$+$$ YZY interaction could improve the robustness of tripartite quantum correlations, but diminish the robustness of bipartite quantum correlations. Tripartite measurement-induced disturbance is the most robust against temperature, and bipartite entanglement is the most fragile. Tripartite entanglement is even more robust than bipartite quantum discord when XZX $$+$$ YZY or XZY − YZX interaction is relatively large. The cooperative effect of XZX $$+$$ YZY and XZY − YZX interaction could induce bipartite entanglement even at high temperature. The cooperative effect of XZX $$+$$ YZY and XZY − YZX interaction is the most optimal to improve the robustness of all quantum correlations when the magnetic field is negative. When the magnetic field is positive, the effective of XZY − YZX interaction alone is more ideal to preserve different quantum correlations.

Receptor-interacting protein 3 (RIP3) is an essential component of the necroptosis signaling pathway. Phosphorylation of its downstream target, mixed lineage kinase domain-like protein (MLKL), has been proposed to induce necroptosis by initiating Ca2+ influx. Our previous studies have shown that RGC-5 retinal ganglion cells undergo RIP3-mediated necroptosis following elevated hydrostatic pressure (EHP). However, the molecular mechanism underlying necroptosis induction downstream of RIP3 is still not well understood. Here, we investigated the effects of MLKL during EHP-induced necroptosis, and primarily explored the relationship between MLKL and Ca2+ influx. Immunofluorescence staining showed that the expression of MLKL was increased 12 h after EHP. Western blot analysis demonstrated that the phosphorylated and unphosphorylated forms of both RIP3 and MLKL were up-regulated 12 h after EHP, while inhibition of RIP3 by GSK'872 decreased the expression of phosphorylated MLKL at the same stage. Propidium iodide staining, lactate dehydrogenase release assays, flow cytometry, and electron microscopy revealed the increased necrosis of RGC-5 cells 12 h after EHP, which coincided with elevated cytosolic Ca2+ concentrations. Depletion of extracellular Ca2+ and siRNA-mediated silencing of MLKL significantly reduced EHP-induced necrosis. Both MLKL-specific siRNA and GSK'872 treatment diminished Ca2+ influx. Thus, our findings suggest that MLKL may be the key mediator of necroptosis downstream of RIP3 phosphorylation and may be involved in increasing intracellular Ca2+ concentrations in EHP-induced RGC-5 necroptosis.

The binding sites of circLARP4 with miRNAs. a Schematic representation of potential binding sites of miRNAs with circLARP4. b The effects of miR-424 mimic or inhibitor on the expression level of circLARP4 in HCG-27 or MKN-28 cell line indicated by qRT-PCR. c The binding sites of wild type or mutant circLARP4 3’UTR with miR-424.-5p. d qRT-PCR analysis of the expression levels of LATS1 and YAP after transfection with circLARP4 + miR-424 in HGC-27 cells or si-circLARP4 + miR-424 inhibitor in MKN-28 cells. e the luciferase activity of wild type LATS1 3’UTR was examined by co-transfection with miR-424 mimic + circLARP4 in HGC-27 cells. f the luciferase activity of wild type LATS1 3’UTR was detected by co-transfection with miR-424 inhibitor + si-circLARP4 in MKN-28 cells. *P

The effects of circLARP4 on GC cell proliferation. a The expression level of LATS1 was examined after transfection with miR-424 mimic and (or) LATS1 in HGC-27 cells, and miR-424 inhibitor and (or) sh-LATS1 in MKN-28 cells indicated by qRT-PCR. b The expression level of circLARP4 was detected in GC cell lines and GES-1 cells by qRT-PCR and spearman correlation analysis of the correlation of circLARP4 with miR-424 and LATS1 expression in GC cells. c Detection of cell proliferation of HGC-27 or MKN-28 cells transfected with circLARP4 overexpression or si-circLARP4 vectors by MTT assay. d Assessment of cell colony formation of HGC-27 or MKN-28 cells transfected with circLARP4 overexpression or si-circLARP4 vectors. *P