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Abstract Background Gallstones are strongly associated with eating occasion (EO) and energy distribution, but few studies have addressed this aspect. Therefore, we utilize the data from 2017 to 2018 National Health and Nutrition Examination Survey (NHANES) to explore the association between temporal eating patterns and energy distribution patterns with the incidence of gallstones. Methods Our study comprised participants who completed the NHANES dietary intake interview and self-reported health questionnaire at age 20 or older. The self-report method for gallstones (have you ever been told by a doctor) was used. We use the latent class analysis (LCA) identified temporal eating patterns, and identified energy distribution patterns through latent profile analysis (LPA). The association between temporal eating patterns, energy distribution patterns, and gallstones was examined using logistic regression modeling. Results The study included a total of 4,692 participants. LCA identified four temporal eating patterns labeled as “Conventional,” “Early breakfast,” “Later breakfast,” and “Grazing.” Compared to the “Conventional” pattern, the “Early breakfast” pattern (OR 0.809, 95%CI 0.808–0.811) was associated with a reduced risk of gallstones, while the “Later breakfast” (OR 1.435, 95%CI 1.432–1.438) and “Grazing” (OR 1.147, 95%CI 1.145–1.148) patterns were associated with an increased risk of gallstones. LPA identified four energy distribution patterns labeled as “Guideline,” “High carbohydrates,” “Carbs-fat balance,” and “High fat.” The “High carbohydrates” pattern (OR 1.329, 95%CI 1.326–1.331) was associated with an increased risk of gallstones compared to the “Guideline” pattern. The “Carbs-fat balance” pattern (OR 0.877, 95%CI 0.876–0.879) and the “High fat” pattern (OR 0.848, 95%CI 0.846-0.850) were significantly and negatively associated with the risk of gallstones. Conclusions To summarize, inappropriate timing of eating and energy sources are associated with gallstones. As a dietary prevention measure for gallstones, we suggest adhering to a regular eating routine and avoiding overly casual and frequent food consumption. If the main EO routine occurs in the morning, this time should not exceed 9:00 a.m. Additionally, reducing carbohydrate intake and maintaining a moderate level of fat intake is believed to contribute to a lower risk of gallstones.

IntroductionMucosal deficiency is one of the most challenging conditions in patients with acute severe ulcerative colitis (ASUC). Intravenous corticosteroids (CS) are the first-line treatment, with infliximab (IFX) used as a rescue therapy. However, the efficacy remains unsatisfactory. We investigated whether CS combined with IFX as first-line therapy would improve outcomes in patients with ASUC with mucosal deficiency.MethodsA retrospective study was performed at a tertiary inflammatory bowel disease center. The primary outcomes included clinical remission, endoscopic improvement, and endoscopic remission at week 14. The secondary outcomes included the colectomy rate within 90 days and durable clinical remission.ResultsA total of 43 patients with ASUC with mucosal deficiency were included in the analysis (25 in the CS combined with the IFX group and 18 in the CS sequential IFX group). At week 14, endoscopic improvement was observed in 21 of 25 patients (84.0%) receiving the CS combined with the IFX regimen, compared to 9 of 18 (50.0%) patients receiving the CS sequential IFX regimen (p = 0.017). Durable clinical remission rates were significantly higher in the combined group than in the sequential group (85.7% vs. 35.7%, p = 0.004). There was no statistically significant difference between the two groups in terms of clinical and endoscopic remission at week 14 or colectomy rate within 90 days. Multivariate analysis confirmed that the CS combined with the IFX regimen was an independent predictive factor for a higher endoscopic improvement rate at week 14 (odds ratio (OR) 8.428, 95%confidence interval (CI) 1.539–46.153, p = 0.014) and a higher durable clinical remission rate (OR 10.800, 95%CI 2.095–55.666, p = 0.004).ConclusionCS combined with IFX as first-line therapy may be an effective induction strategy in patients with ASUC with mucosal deficiency. Further large-scale, multicenter prospective studies are needed.

IntroductionDeveloping antibiotic adjuvants is an effective strategy to combat antimicrobial resistance (AMR). The envelope of Gram-negative bacteria (GNB) is a barrier to prevent the entry of antibiotics, making it an attractive target for novel antibiotic and adjuvant development.Methods and ResultsIn this study, we identified Caspofungin acetate (CAS) as an antibiotic adjuvant against GNB in the repurposing screen of 3,158 FDA-approved drugs. Checkerboard assays suggested that CAS could enhance the antimicrobial activity of rifampin or colistin against various GNB strains in vitro, Moreover, Galleria mellonella larvae infection model also indicated that CAS significantly potentiated the efficacy of rifampin against multidrug-resistant Escherichia coli 72 strain in vivo. Most importantly, resistance development assay showed that CAS was less susceptible to accelerating the resistance development of drug-sensitive strain E. coli MG1655. Functional studies and RNA-seq analysis confirmed that the mechanisms by which CAS enhanced the antimicrobial activities of antibiotics were involved in permeabilizing the bacterial cell envelope, disrupting proton motive force and inhibiting bacterial biofilm formation. Additionally, it has been found that PgaC is the CAS target and enzymatic assay has confirmed the inhibition activity.DiscussionOur results illustrate the feasibility of CAS as an antibiotic adjuvant against GNB, which is an alternative strategy of anti-infection.

Background: Cuproptosis may represent a potential biomarker for predicting prognosis and immunotherapy response, but the available evidence is insufficient. Methods: The multiple single-cell RNA sequencing (scRNA-seq) datasets were analyzed to investigate the specific occurrence of cuproptosis in distinct cell populations. Utilizing 28 scRNA-seq datasets, TCGA pan-cancer cohort, and 10 immunotherapy cohorts, we developed a cuproptosis signature (Cup.Sig). This signature was used to construct prediction models for immunotherapy response and identify potential prognostic biomarkers for pan-cancer using 11 different machine learning algorithms. Results: Malignant cells demonstrate the higher cuproptosis scores in comparison to other cell types across diverse cancer types. The Cup.Sig exhibits significant associations with cancer hallmarks and immune cell response in multiple cancer types. Leveraging the Cup.Sig, the robust pan-cancer immunotherapy prediction model and prognostic biomarker have been established and validated using diverse datasets from various platforms. Conclusions: We developed a pan-cancer cuproptosis signature for predicting survival and immunotherapy response.

Abstract Purpose This research was conducted to investigate the potential of short-chain fatty acids (SCFAs) in protecting organs from heat stress-induced injuries and gut microbiota modulation. Methods Sprague–Dawley rats were randomly assigned to various groups including a control group, a room temperature training group, a hyperthermia training group, SCFAs pretreatment group, and recipients received feces from the HT group. After strenuous training at high temperatures, the levels of plasma enzymes AST, ALT, BUN, and Cr were evaluated. The changes in gut microbiota and fecal metabolites were detected using 16S rRNA sequencing and GC–MS methods. Pathological examination of colon and liver tissues was conducted, and immunohistochemical techniques were employed to assess intestinal barrier function. Results The findings indicate that SCFAs hold the potential for mitigating liver and colon damage caused by heat stress. With the intervention of SCFAs, there were observable changes in the structure and metabolites of the intestinal microbiota, as well as improvements in intestinal barrier function. Further support for the benefits of SCFAs was found through fecal microbiota transplantation, which demonstrated that modified gut microbiota can effectively reduce organ damage. Conclusions This study provides evidence that SCFAs, as metabolites of the gut microbiota, have a valuable role to play in regulating gut health and mitigating the harmful effects of heat stress.

Liposomes as drug carriers for the delivery of therapeutic agents have triggered extensive research but it remains a grand challenge to develop a novel technology for enabling rapid and mass fabrication of monodisperse liposomes. In this work, we constructed a novel ultrasonic microfluidic technology, namely ultrasonic microreactor (USMR) with two different conjunction structure (co-flow and impinge flow, corresponding to USMR-CF and USMR-IF, respectively), to prepare uniform liposomes by antisolvent precipitation method. In this process, the monodisperse liposomes with tunable droplet sizes (DS) in 60–100 nm and a polydispersity index (PDI) less than 0.1 can easily be achieved by tuning the total flow rate, flow rate ratio, ultrasonic power, and lipid concentration within the two USMRs. Impressively, the USMR-IF is superior for reducing the PDI and tuning DS of the liposomes over the USMR-CF. More importantly, the ultrasonic can effectively reduce DS and PDI at the low TFR and support the IF-micromixer in reducing the PDI even at a high TFR. These remarkable performances are mainly due to the rapid active mixing, fouling-free property and high operation stability for USMR-IF. In addition, diverse lipid formulations can also be uniformly assembled into small liposomes with narrow distribution, such as the prepared HSPC-based liposome with DS of 59.6 nm and PDI of 0.08. The liposomes show a high stability and the yield can reach a high throughput with 108 g/h by using the USMR-IF at an initial lipid concentration of 60 mM. The results in the present work highlight a novel ultrasonic microfluidic technology in the preparation of liposomes and may pave an avenue for the rapid, fouling-free, and high throughput fabrication of different and monodisperse nanomedicines with controllable sizes and narrow distribution.

IntroductionThis study explores the determinants of psychological well-being among 968 Chinese English as a Foreign Language (EFL) students by employing structural equation modeling (SEM). Focusing on academic self-efficacy, grit, and teacher support, this research aims to illuminate their roles in shaping the psychological well-being of EFL students within the Chinese educational context.MethodsData from a robust sample of Chinese EFL students were analyzed using SEM techniques to investigate the relationships between academic self-efficacy, grit, teacher support, and psychological well-being. Validated instruments were utilized to measure these constructs, ensuring accuracy and reliability. The study employed meticulous data collection procedures over a three-month period, maintaining strict ethical standards and anonymity for participants.ResultsThe SEM analysis revealed intricate connections among academic self-efficacy, grit, teacher support, and the psychological well-being of Chinese EFL students. Academic self-efficacy and grit emerged as direct predictors of psychological well-being, highlighting their significance in fostering students’ overall well-being. Additionally, teacher support was identified to play a mediating role in this relationship, emphasizing its critical influence on enhancing academic self-efficacy and grit, thereby contributing to students’ psychological well-being.DiscussionThese findings underscore the crucial importance of nurturing academic self-efficacy and grit to enhance the psychological well-being of Chinese EFL students. Furthermore, teacher support stands out as a pivotal factor in elevating students’ academic self-efficacy and grit, emphasizing the need for educational interventions centered on fostering these attributes among Chinese EFL learners. The implications of these results extend to educational practices, emphasizing the indispensable role of teacher support and interventions aimed at cultivating academic self-efficacy and grit to promote the psychological well-being of EFL students within the learning environment.

Lead (Pb) is a heavy metal that can have harmful effects on the environment, which has severe cytotoxicity in many animal tissues. N-acetylcysteine (NAC) has antioxidant activity, reducing lead-induced oxidative stress and apoptosis, but its role in chicken cells is unknown. The current study explored the antagonistic effect of NAC on lead-induced apoptosis and oxidative stress in chicken embryo fibroblast (CEF). In this study, CEF was used as a model to measure the cytotoxic effects of lead nitrate at different concentrations, demonstrating a dose-dependent effect on CEF activity. Employing inverted microscopy, the investigation of morphological alterations in CEF cells was conducted. Fluorescence staining methodology enabled the assessment of reactive oxygen species (ROS) levels within CEF cells. Moreover, an enzyme-linked immunosorbent assay was utilized to detect the presence of oxidative damage indicators encompassing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity, malondialdehyde (MDA) content, and total antioxidant capacity (T-AOC) within CEF cells. Furthermore, the determination of the apoptosis rate of CEF cells was accomplished through the utilization of the Hoechst 33258 staining method in combination with the Annexin V-FITC dual staining method. By using RT-qPCR for detection, lead treatment increased expression of pro-apoptotic genes, caspase-3, and caspase-9, and reduced expression of anti-apoptotic genes, Bcl-2, and BI-1. Reduced antioxidant capacity was shown by increased ROS and MDA levels in CEF cells after lead treatment. The results showed that NAC inhibited the expression of caspase-3 and caspase-9 in lead-treated CEF cells, while NAC had a certain inhibitory effect on the relative expression of Bcl-2 and BI-1 mRNA in lead-induced CEF cells. NAC significantly reduced lead-induced oxidative damage and apoptosis. Overall, our results demonstrate a novel protective effect of NAC against lead-induced injury in chicken cells, providing a theoretical basis for future investigations of drugs that are effective in preventing lead poisoning in animals.

IntroductionThe masked palm civet (Paguma larvata) serves as a reservoir in transmitting pathogens, such as Toxoplasma gondii, to humans. However, the pathogenesis of T. gondii infection in masked palm civets has not been explored. We studied the molecular changes in the brain tissue of masked palm civets chronically infected with T. gondii ME49.MethodsThe differentially expressed proteins in the brain tissue were investigated using iTRAQ and bioinformatics.ResultsA total of 268 differential proteins were identified, of which 111 were upregulated and 157 were downregulated. KEGG analysis identified pathways including PI3K-Akt signaling pathway, proteoglycans in cancer, carbon metabolism, T-cell receptor signaling pathway. Combing transcriptomic and proteomics data, we identified 24 genes that were differentially expressed on both mRNA and protein levels. The top four upregulated proteins were REEP3, REEP4, TEP1, and EEPD1, which was confirmed by western blot and immunohistochemistry. KEGG analysis of these 24 genes identified signaling cascades that were associated with small cell lung cancer, breast cancer, Toll-like receptor signaling pathway, Wnt signaling pathways among others. To understand the mechanism of the observed alteration, we conducted immune infiltration analysis using TIMER databases which identified immune cells that are associated with the upregulation of these proteins. Protein network analysis identified 44 proteins that were in close relation to all four proteins. These proteins were significantly enriched in immunoregulation and cancer pathways including PI3K-Akt signaling pathway, Notch signaling pathway, chemokine signaling pathway, cell cycle, breast cancer, and prostate cancer. Bioinformatics utilizing two cancer databases (TCGA and GEPIA) revealed that the four genes were upregulated in many cancer types including glioblastoma (GBM). In addition, higher expression of REEP3 and EEPD1 was associated with better prognosis, while higher expression of REEP4 and TEP1 was associated with poor prognosis in GBM patients.DiscussionWe identified the differentially expressed genes in the brain of T. gondii infected masked palm civets. These genes were associated with various cellular signaling pathways including those that are immune- and cancer-related.

Ultrasonically-induced nanoemulsions have been widely investigated for the development of functional food, cosmetics, and pharmaceuticals due to ideal droplet sizes (DS), low polydispersity index (PDI), and superior physical stability. However, a series of frequently-used ultrasonic set-ups mainly suffered from a low ultrasonic energy efficiency caused by the large acoustic impedance and energy consumption, subordinately confronted with a low throughput, complicated fabrication with complex structure and weak ultrasonic cavitation. Herein, we employed a typical ultrasonic microreactor (USMR) that ensured the high-efficient energy input and generated intense cavitation behavior for efficient breakage of droplets and continuous production of unified oil-in-water (O/W) nanoemulsions in a single cycle and without any pre-emulsification treatment. The emulsification was optimized by tuning the formula indexes, technological parameters, and numerical analysis using Response Surface Methodology (RSM), followed by a comparison with the emulsification by a traditional ultrasonic probe. The USMR exhibited superior emulsification efficiency and easy scale-up with remarkable uniformity by series mode. In addition, concurrent and uniform nanoemulsions with high throughput could also be achieved by a larger USMR with high ultrasonic power. Based on RSM analysis, uniform DS and PDI of 96.4 nm and 0.195 were observed under the optimal conditions, respectively, well consistent with the predicted values. Impressively, the optimal nanoemulsions have a uniform spherical morphology and exhibited superior stability, which held well in 45 days at 4℃ and 25℃. The results in the present work may provide a typical paradigm for the preparation of functional nanomaterials based on the novel and efficient emulsification tools.

In clinical neuroscience, epileptic seizures have been associated with the sudden emergence of coupled activity across the brain. The resulting functional networks-in which edges indicate strong enough coupling between brain regions-are consistent with the notion of percolation, which is a phenomenon in complex networks corresponding to the sudden emergence of a giant connected component. Traditionally, work has concentrated on noise-free percolation with a monotonic process of network growth, but real-world networks are more complex. We develop a class of random graph hidden Markov models (RG-HMMs) for characterizing percolation regimes in noisy, dynamically evolving networks in the presence of edge birth and edge death. This class is used to understand the type of phase transitions undergone in a seizure, and in particular, distinguishing between different percolation regimes in epileptic seizures. We develop a hypothesis testing framework for inferring putative percolation mechanisms. As a necessary precursor, we present an EM algorithm for estimating parameters from a sequence of noisy networks only observed at a longitudinal subsampling of time points. Our results suggest that different types of percolation can occur in human seizures. The type inferred may suggest tailored treatment strategies and provide new insights into the fundamental science of epilepsy.

ABSTRACT Marek’s disease virus (MDV) induces immunosuppression and neoplastic disease in chickens. The virus is controllable via an attenuated meq deletion mutant virus, which has the disadvantage of retaining the ability to induce lymphoid organ atrophy. To overcome this deficiency and produce more vaccine candidates, a recombinant MDV was generated from the highly virulent Md5BAC strain, in which both meq and a cytolytic replication-related gene, pp38, were deleted. Replication of the double deletion virus, Md5BAC ΔmeqΔpp38, was comparable with that of the parental virus in vitro. The double deletion virus was shown to be fully attenuated and to reduce lymphoid organ atrophy in vivo. Crucially, Md5BAC ΔmeqΔpp38 confers superior protection against highly virulent virus compared with a commercial vaccine strain, CVI988/Rispens. Transcriptomic profiling indicated that Md5BAC ΔmeqΔpp38 induced a different host immune response from CVI988/Rispens. In summary, a novel, effective, and safe vaccine candidate for prevention and control of MD caused by highly virulent MDV is reported. IMPORTANCE MDV is a highly contagious immunosuppressive and neoplastic pathogen. The virus can be controlled through vaccination via an attenuated meq deletion mutant virus that retains the ability to induce lymphoid organ atrophy. In this study, we overcame the deficiency by generating meq and pp38 double deletion mutant virus. Indeed, the successfully generated meq and pp38 double deletion mutant virus had significantly reduced replication capacity in vivo but not in vitro. It was fully attenuated and conferred superior protection efficacy against very virulent MDV challenge. In addition, the possible immunological protective mechanism of the double deletion mutant virus was shown to be different from that of the gold standard MDV vaccine, CVI988/Rispens. Overall, we successfully generated an attenuated meq deletion mutant virus and widened the range of potential vaccine candidates. Importantly, this study provides for the first time the theoretical basis of vaccination induced by fully attenuated gene-deletion mutant virus.

Both fine particulate matter (PM2.5) and ozone (O3) may have adverse effects on human health. However, previous studies on the effects of air pollutants mainly have focused on susceptible population, and evidence on healthy young adults is limited. We aimed to examine the associations of the two main air pollutants (PM2.5 and O3) with lung function, inflammation and oxidative stress in healthy young adults. We recruited 30 healthy young adults for a longitudinal panel study in Beijing and implemented health examination seven times, including lung function (FEV1 and PEF) and biomarkers of inflammation and oxidative stress (i.e. C-reactive protein, CRP; interleukin-6, IL-6; malondialdehyde, MDA) from December 2019 to May 2021. Hourly ambient air pollutants data were obtained from the closest air quality monitoring station. Linear mixed-effect model was applied to explore the associations between air pollutants and lung function, inflammation and oxidative stress. We observed higher PM2.5 exposure was associated with decrement in lung function and increment in CRP and MDA. Each 10 μg/m3 increase in PM2.5 (lag 2 day) is associated with a 17.06 ml (95% CI: −31.53, −2.58) decrease in FEV1, 46.34 ml/s (95% CI: −76.41, −16.27) decrease in PEF and increments of 2.86% (95% CI: 1.47%, 4.27%) in CRP, 1.63% (95% CI: 0.14%, 3.14%) in MDA respectively. However, there is no significant association between ozone exposure and health indicators. The study suggested that short-term exposure to PM2.5 may decrease lung function and induce inflammation and oxidative stress in healthy adults, but there is no association between O3 and each outcome.

Hydroxyapatite (HA) and tricalcium phosphate (TCP) constitute 60% of the content of the bone, and their combination has a better effect on bone tissue engineering than either single element. This study demonstrates a new degradable gelatin/carboxymethyl chitosan (CMC) bone scaffold loaded with both nano-HA and β-TCP (hereinafter referred to as HCP), and freeze drying combined with stir foaming was used to obtain highly connected macropores. Only a few studies have used these components to synthesize a four-component osteogenic scaffold. The aim of this study was to comprehensively assess the biocompatibility and osteoinductivity of the nanocomposites. Three HCP/CMC/gelatin scaffolds were made with different HCP contents: group A (10 wt% HCP), group B (30 wt% HCP), and group C (50 wt% HCP) (the ratio of nano-HA and β-TCP was fixed at 3:2). The scaffolds were macroporous with a high porosity and pore connectivity, as observed by morphological analysis by scanning electron microscopy. Additionally, the pore size of groups A and B was more homogeneous than that of group C. There were no significant differences in physicochemical characterization among the three groups. The Fourier-transform infrared (FTIR) spectroscopy test indicated that the scaffold contained active groups, such as hydroxyl, amino, or peptide bonds, corresponding to gelatin and CMC. The XRD results showed that the phase structures of HA and β-TCP did not change in the nanocomposite. The scaffolds had biodegradation potential and an appreciable swelling ratio, as demonstrated with the in vitro test. The scaffolds were cultured in vitro with MC3T3-E1 cells, showing that osteoinduction and osteoconduction increased with the HCP content. None of the scaffolds showed cytotoxicity. However, cell adhesion and growth in group B were better than those in group A and group C. Therefore, freeze drying combined with a stir foaming method may have a solid component limit. This study demonstrates a novel four-component scaffold via a simple manufacturing process. Group B (30% HCP) had the best characteristics for bone scaffold materials.

Abstract Background Lung adenocarcinoma (LUAD), as the most common subtype of lung cancer, is the leading cause of cancer deaths in the world. The accumulation of driver gene mutations enables cancer cells to gradually acquire growth advantage. Therefore, it is important to understand the functions and interactions of driver gene mutations in cancer progression. Methods We obtained gene mutation data and gene expression profile of 506 LUAD tumors from The Cancer Genome Atlas (TCGA). The subtypes of tumors with driver gene mutations were identified by consensus cluster analysis. Results We found 21 significantly mutually exclusive pairs consisting of 20 genes among 506 LUAD patients. Because of the increased transcriptomic heterogeneity of mutations, we identified subtypes among tumors with non‐silent mutations in driver genes. There were 494 mutually exclusive pairs found among driver gene mutations within different subtypes. Furthermore, we identified functions of mutually exclusive pairs based on the hypothesis of functional redundancy of mutual exclusivity. These mutually exclusive pairs were significantly enriched in nuclear division and humoral immune response, which played crucial roles in cancer initiation and progression. We also found 79 mutually exclusive triples among subtypes of tumors with driver gene mutations, which were key roles in cell motility and cellular chemical homeostasis. In addition, two mutually exclusive triples and one mutually exclusive triple were associated with the overall survival and disease‐specific survival of LUAD patients, respectively. Conclusions We revealed novel mutual exclusivity and generated a comprehensive functional landscape of driver gene mutations, which could offer a new perspective to understand the mechanisms of cancer development and identify potential biomarkers for LUAD therapy.

Abstract Marek’s disease virus (MDV) induces severe immunosuppression and lymphomagenesis in the chicken, its natural host, and results in a condition that investigated the pathogenesis of MDV and have begun to focus on the expression profiling of circular RNAs (circRNAs). However, little is known about how the expression of circRNAs is referred to as Marek’s disease. Previous reports have is regulated during MDV replication. Here, we carried out a comprehensive profiling analysis of N6-methyladenosine (m6A) modification on the circRNA transcriptome in infected and uninfected chicken embryonic fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks and conserved motifs were not significantly different in cells that were infected with MDV, although reduced abundance of circRNA m6A modifications. However, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses revealed that the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. This is the first report to describe alterations in the transcriptome-wide profiling of m6A modified circRNAs in MDV-infected CEF cells.

In order to illustrate pollution characterization, source apportionment, and risk assessment of VOCs in Beijing, Baoding, and Shanghai, field observations of CO, NO, NO2, O3, and volatile organic compounds (VOCs) were conducted in 2019. Concentrations of VOCs were the highest in Beijing (105.4 ± 52.1 ppb), followed by Baoding (97.1 ± 47.5 ppb) and Shanghai (91.1 ± 41.3 ppb). Concentrations of VOCs were the highest in winter (120.3 ± 61.5 ppb) among the three seasons tested, followed by summer (98.1 + 50.8 ppb) and autumn (75.5 + 33.4 ppb). Alkenes were the most reactive VOC species in all cities, accounting for 56.0%, 53.7%, and 39.4% of ozone formation potential in Beijing, Baoding, and Shanghai, respectively. Alkenes and aromatics were the reactive species, particularly ethene, propene, 1,3,5-trimethylbenzene, and m/p-xylene. Vehicular exhaust was the principal source in all three cities, accounting for 27.0%, 30.4%, and 23.3% of VOCs in Beijing, Baoding, and Shanghai, respectively. Industrial manufacturing was the second largest source in Baoding (23.6%) and Shanghai (21.3%), and solvent utilization was the second largest source in Beijing (25.1%). The empirical kinetic modeling approach showed that O3 formation was limited by both VOCs and nitric oxides at Fangshan (the suburban site) and by VOCs at Xuhui (the urban site). Acrolein was the only substance with an average hazard quotient greater than 1, indicating significant non-carcinogenic risk. In Beijing, 1,2-dibromoethane had an R-value of 1.1 × 10−4 and posed a definite carcinogenic risk.

The African swine fever virus (ASFV) causes high mortality in domestic pigs. ASFV encodes an important protein target for subunit vaccine development, CD2v, but its most effective immunological regions are not known. Herein, we generated a monoclonal antibody (mAb) named IF3 by immunizing mice against the intracellular region of the CD2v protein (CD2v-IR). 1F3 specifically recognized CD2v, which is expressed transiently in transfected Sf9 cells and also in inactivated ASFV-infected porcine alveolar macrophage (PAM) cells. The epitope recognized by 1F3 is 264EPSPREP270, which is highly conserved in ASFV genotypes. Immunization of mice with this epitope elicited an increased IgG response, including IgG1 and IgG2a subtypes, and also increased CD8+ T cells and cytokine expression. Overall, these results indicate that this epitope induces both humoral and cellular immune responses that may be used for ASFV-related subunit vaccine design and development.

Abstract Background The newly discovered reversible N6-methyladenosine (m6A) modification plays an important regulatory role in gene expression. Long non-coding RNAs (lncRNAs) participate in Marek’s disease virus (MDV) replication but how m6A modifications in lncRNAs are affected during MDV infection is currently unknown. Herein, we profiled the transcriptome-wide m6A modification in lncRNAs in MDV-infected chicken embryo fibroblast (CEF) cells. Results Methylated RNA immunoprecipitation sequencing results revealed that the lncRNA m6A modification is highly conserved with MDV infection increasing the expression of lncRNA m6A modified sites compared to uninfected cell controls. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that lncRNA m6A modifications were highly associated with signaling pathways associated with MDV infection. Conclusions In this study, the alterations seen in transcriptome-wide m6A occurring in lncRNAs following MDV-infection suggest this process plays important regulatory roles during MDV replication. We report for the first time profiling of the alterations in transcriptome-wide m6A modification in lncRNAs of MDV-infected CEF cells.

Abstract Processing and packaging of herpesvirus genomic DNA is regulated by a packaging-associated terminase complex comprising of viral proteins pUL15, pUL28 and pUL33. Marek’s disease virus (MDV) homologs UL28 and UL33 showed conserved functional features with high sequence identity with the corresponding Herpes simplex virus 1 (HSV-1) homologs. As part of the investigations into the role of the UL28 and UL33 homologs of oncogenic MDV for DNA packaging and replication in cultured cells, we generated MDV mutant clones deficient in UL28 or UL33 of full-length MDV genomes. Transfection of UL28- or UL33-deleted BAC DNA into chicken embryo fibroblast (CEF) did not result either in the production of visible virus plaques, or detectable single cell infection after passaging onto fresh CEF cells. However, typical MDV plaques were detectable in CEF transfected with the DNA of revertant mutants where the deleted genes were precisely reinserted. Moreover, the replication defect of the UL28-deficient mutant was completely restored when fragment encoding the full UL28 gene was co-transfected into CEF cells. Viruses recovered from the revertant construct, as well as by the UL28 co-transfection, showed replication ability comparable with parental virus. Furthermore, the transmission electron microscopy study indicated that immature capsids were assembled without the UL28 expression, but with the loss of infectivity. Importantly, predicted three-dimensional structures of UL28 between MDV and HSV-1 suggests conserved function in virus replication. For the first time, these results revealed that both UL28 and UL33 are essential for MDV replication through regulating DNA cleavage and packaging.

The abnormal disposal process of electronic waste (e-waste) always emits a variety of toxic substances that enter the human body through various environmental media and can have many adverse health effects. Metals are thought to be inextricably linked to neurodegeneration. In the present study, we tried to explore the neurodegenerative status of subjects exposed to e-waste and the association between metal intake and neurodegeneration. We recruited the residents near the e-waste recycling area (the exposed group) and the residents without any e-waste contact history (the reference group) for a comparative study with detection and analysis of metals, biomarkers associated with neurodegeneration or oxidative stress (OS). The results showed that the metals between the reference and exposed group were significantly different. The concentrations of Brain-derived neurotrophic factor (BDNF) and β-amyloid protein 42 (Aβ42) in the exposed groups were significantly lower, while the levels of Euchromatic Histone lysine Methyltransferase 1 (EHMT1), Bromodomain Adjacent to Zinc finger domain 2B (BAZ2B) and Malondialdehyde (MDA) were significantly higher than in the reference groups. Although the ratio of Aβ42/Aβ40 had no statistical significance in the two groups, the medians of the ratio in the exposed group was lower than in the reference group. The linear regression and mediating effect analysis showed that MDA (OS) might mediate the effects of metals on EHMT1(pAg-MDA

The pathogenesis of chronic refractory immune thrombocytopenia (C/RITP) is mechanistically complex and considerably varies across patients. Few studies have focused on the genetic characteristics of C/RITP in children. The aim of this study was to analyze and summarize the clinical manifestations and genetic characteristics of C/RITP children with mutations in immune-related genes. In the study, 51 children with variants in immune-related genes (mutation group) and 103 children with no abnormal mutations (control group) were enrolled. Children in the mutation group showed severity of hemorrhage, a higher incidence of abnormal immunological indices, and an increased expression of SLE biomarkers. The number of peripheral T and B lymphocytes in the mutation group significantly increased. Nine patients (17.6%) had probable pathogenic variant genes associated with primary immunodeficiencies ( TNFRSF13B , CARD11 , CBL , and RAG2 ), and 42 patients (82.4%) had variants of uncertain significance in 23 genes. C/RITP patients with variants in immune-related genes had more severe bleeding, abnormal immunological indices, and an increased expression of SLE biomarker. Next-generation sequenciong (NGS) might be a useful way to differentiate those patients from C/RITP.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

The heavy metals pollution and related health issues were widely reported in e-waste sites, while the impacts of e-waste exposure on the essential trace elements have been neglected. The aim of this study was focused on the internal Cu, Fe, Mn and Zn levels in the residents from an e-waste site and the potential endocrine disrupting effects of these essential trace elements on the hypothalamic-pituitary-thyroid (HPT) axis. This was a cross-sectional study that 87 subjects were recruited from the e-waste site and 81 from the reference site. The results indicated that the e-waste exposed group had significantly lower Fe, Mn level when compared with the reference group (p

Background Glioblastoma multiforme (GBM) is a highly, malignant tumor of the primary central nervous system. Patients diagnosed with this type of tumor have a poor prognosis. Lymphocyte activation plays important roles in the development of cancers and its therapeutic treatments. Objective We sought to identify an efficient lymphocyte activation-associated gene signature that could predict the progression and prognosis of GBM. Methods We used univariate Cox proportional hazards regression and stepwise regression algorithm to develop a lymphocyte activation-associated gene signature in the training dataset (TCGA, n = 525). Then, the signature was validated in two datasets, including GSE16011 (n = 150) and GSE13041 (n = 191) using the Kaplan Meier method. Univariate and multivariate Cox proportional hazards regression models were used to adjust for clinicopathological factors. Results We identified a lymphocyte activation-associated gene signature (TCF3, IGFBP2, TYRO3 and NOD2) in the training dataset and classified the patients into high-risk and low-risk groups with significant differences in overall survival (median survival 15.33 months vs 12.57 months, HR = 1.55, 95% CI [1.28–1.87], log-rank test P

Layouts of bus networks in cities are always irrational currently, transport service frequencies also need to be optimized according to the real network layouts, operation conditions and travel experience of passengers, so it is essential to optimize bus transit network layouts and transport service frequencies systematically. Different stakeholders are involved in the optimization of urban bus transit network layouts like the government, operators and passengers, whose interests are always contradictory. In order to optimize transit network layout and service frequencies from the view point of operators and utilizers, this research constructs a multi-objective model and proposes a solution algorithm. The proposed multi-objective model is established from the perspective of operators with the goal of minimizing total operating costs for one day, and from the perspective of the utilizers to minimize the total travel time, respectively. Also with the application of electric bus in cities, buses in this research are electric buses all for green travel. Moreover, a solution algorithm is proposed in this research to solve the proposed multi-objective model with simulated annealing algorithm and genetic algorithm. Simulated annealing algorithm is used as the main framework of the solution algorithm from the perspective of operators to minimize operating costs, while genetic algorithm is used as the subroutine of simulated annealing algorithm to optimize total travel time. Verification of the proposed model and the solution algorithm is based on an intuitive network. The application results of a numerical experiment verified that the proposed optimization model and the solution algorithm are able to optimize the network layout and service frequencies at the same time.

The conventional fracture in shale hydraulic fracturing belongs to the type-I fracture, and the size of the fracture process zone (FPZ) is an important index to measure the fracability of rock mass. This index is also one of the feasible entry points to study the complexity of the fracture network. In order to visually observe the type-I FPZ at the tip of shale fractures, and to study the relationship between the mechanical properties, the shape and size of the FPZ, and the bedding structure, Notched Semi-Circular Bend (NSCB) tests were conducted with three typical fracture direction-bedding orientations (splitter, arrester, divider). The digital image correlation (DIC) method was used to realize the intuitive observation of the real fracture process and the FPZ near the fracture tip. The test found that the FPZ of shale is narrow and long as a whole and is “flame-like”. The height-to-length ratio of the FPZ at the fracture tip determines whether bending and deflection happen between the new fracture and the prefabricated cracks when the fracture occurs. Most of the specimens often appear in the FPZ with a beaded high shear strain zone before the fracture, which is caused by the oblique communication of micro-cracks in the FPZ before the fracture. The appearance of a beaded zone of high shear strain indicates that macroscopic fracture is imminent. The research results can be used for the design of disaster early warning and prevention programs.

Aim: This study aimed to identify common variable immunodeficiency (CVID) by high-throughput next-generation sequencing (NGS) in children with refractory immune thrombocytopenia (RITP) to facilitate early diagnosis.Methods: CVID-related genetic mutations were explored in patients with RITP during 2016–2019. They were tested consecutively through NGS by the ITP team of the tertiary children hospital in China. An evaluation system was devised based on the phenotype, genetic rule, and serum immunoglobulins (Igs) of all patients with RITP. The patients were divided into highly suspicious, suspicious, and negative groups using the evaluation system.Results: Among 176 patients with RITP, 16 (9.1%) harbored CVID-related genetic mutations: 8 (4.5%) were highly suspicious of CVIDs. Five had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), one in lipopolysaccharide responsive beige-like anchor protein (LRBA), one in nuclear factor kappa-B2 (NF-κB2), and one in caspase recruitment domain11 (CARD11). Others were classified into the suspicious group because the clinical phenotype and pedigree were suggestive, yet insufficient, for diagnosis. Repeated infection existed in all patients. Two had an allergic disease. Positive autoimmune serologies were noted in 62.5%. Five had a definite positive family history. The median serum immunoglobulin (Ig)A, IgG, and IgM levels were 0.3875, 6.14, and 0.522 g/L, respectively. Nearly 85.7% of patients had insufficient serum IgA levels, while 37.5% had low IgG and IgM levels.Conclusions: High-throughput NGS and a thorough review of the medical history are beneficial for the early diagnosis of patients without any significant clinical characteristics, distinguishing them from those with primary pediatric ITP. The cases suspicious of CVID need further investigation and follow-up to avoid deterioration.

Breast cancer (BRCA) is the most common cancer and a major cause of death in women. Long non-coding RNAs (lncRNAs) are emerging as key regulators and have been implicated in carcinogenesis and prognosis. In this study, we aimed to develop a lncRNA signature of BRCA patients to improve risk stratification. In the training cohort (GSE21653, n = 232), 17 lncRNAs were identified by univariate Cox proportional hazards regression, which were significantly associated with patients’ survival. The least absolute shrinkage and selection operator-penalized Cox proportional hazards regression analysis was used to identify a six-lncRNA signature. According to the median of the signature risk score, patients were divided into a high-risk group and a low-risk group with significant disease-free survival differences in the training cohort. A similar phenomenon was observed in validation cohorts (GSE42568, n = 101; GSE20711, n = 87). The six-lncRNA signature remained as independent prognostic factors after adjusting for clinical factors in these two cohorts. Furthermore, this signature significantly predicted the survival of grade III patients and estrogen receptor-positive patients. Furthermore, in another cohort (GSE19615, n = 115), the low-risk patients that were treated with tamoxifen therapy had longer disease-free survival than those who underwent no therapy. Overall, the six-lncRNA signature can be a potential prognostic tool used to predict disease-free survival of patients and to predict the benefits of tamoxifen treatment in BRCA, which will be helpful in guiding individualized treatments for BRCA patients.

This study aimed to examine the role of perceptual interference, semantic interference, and relational integration (RI) in the development of analogical reasoning, and to compare the interactive pattern of interference and RI in children and adults. In Experiment 1, we tested 31 3- and 4-year-olds, 27 5- and 6-year-olds, and 40 adults for perceptual interference and RI in analogical reasoning. Perceptual interference emerged when proper mapping between analogically matching objects was incoherent with their perceptual features. RI was evaluated via manipulation of the number of objects in an analogical scene. Significant main effects of perceptual interference and RI were found in children and adults. In Experiment 2, we tested 30 3- and 4-year-olds, 27 5- and 6-year-olds, and 40 adults for semantic interference and RI in analogical reasoning. Semantic interference emerged when proper mapping between analogically matching objects was incoherent with their categorical features. Results showed significant main effects of semantic interference and RI in children and adults. The results of both experiments suggested different mechanisms of interference and RI in children and adults. For children, interference and RI depended on shared cognitive sources. If one factor (i.e., interference resolution) needed more cognitive demand, there would be limited resources available for another factor (i.e., RI). Furthermore, for adults, the increased load of RI and interference on adults’ analogical reasoning exceeded the sum of their respective singular effects. For 3- and 4-year-olds, the degree of perceptual interference was larger than the degree of semantic interference in the Binary Relation condition, whereas there was no significant difference between the degree of two types of interference in the Quaternary Relation condition. Moreover, for 5- and 6-year-olds, the degree of semantic interference was larger than the degree of perceptual interference in both relation conditions. For adults, there was no difference between the degree of two types of interference in both relation conditions. The article also discusses the theoretical and practical implications of this research.

Background/Aims: Schizophrenia is a severe psychiatric disorder, and complement 3 (C3) is closely related to schizophrenia. We investigated the association between C3 polymorphisms and schizophrenia in a Northeast Han Chinese population. Methods: A total of 2240 Chinese people, consisting of 1086 patients with schizophrenia and 1154 healthy controls, were recruited for this study. Ten single nucleotide polymorphisms (SNPs; rs11569562, rs344555, rs2241393, rs2241392, rs11569514, rs445750, rs451760, rs11672613, rs2230205, and rs2250656) in C3 were selected and genotyped. Results: Genotype distribution analysis indicated that rs11569514 was significantly associated with schizophrenia. In the dominant model (AA vs. GG+GA genotypes), we found a significant protective effect for rs344555 against schizophrenia (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.53–0.99, P = 0.04). In the codominant model (TT vs. AA), we found a significant risk effect for rs11569514 on schizophrenia (OR: 4.39, 95% CI: 2.06–9.37, P < 0.001). Haplotypes, including TG (rs11569562 and rs344555), TGG (rs11569562-rs344555-rs2241393), AG (rs344555-rs2241393), CGGGT (rs11569562-rs344555-rs2241393-rs2241392-rs11569514), and ACGTG (rs11569514-rs445750-rs451760-rs11672613-rs2230205), showed either a risk or protective role for schizophrenia. Conclusions: SNP rs11569514 in C3 and haplotypes of C3 variants were associated with schizophrenia in a Han Chinese population.

Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) of African swine fever virus (ASFV) is an essential enzyme required for efficient virus replication. Previous crystallography data have indicated that dUTPase (E165R) may serve as a therapeutic target for inhibiting ASFV replication; however, the specificity of the targeting site(s) in ASFV dUTPase remains unclear. In this study, 19 mouse monoclonal antibodies (mAbs) were produced, in which four mAbs showed inhibitory reactivity against E165R recombinant protein. Epitope mapping studies indicated that E165R has three major antigenic regions: 100–120 aa, 120–140 aa, and 140–165 aa. Three mAbs inhibited the dUTPase activity of E165R by binding to the highly conserved 149–RGEGRFGSTG–158 amino acid sequence. Interestingly, 8F6 mAb specifically recognized ASFV dUTPase but not Sus scrofa dUTPase, which may be due to structural differences in the amino acids of F151, R153, and F154 in the motif V region. In summary, we developed anti-E165R-specific mAbs, and identified an important antibody-binding antigenic epitope in the motif V of ASFV dUTPase. Our study provides a comprehensive analysis of mAbs that target the antigenic epitope of ASFV dUTPase, which may contribute to the development of novel antibody-based ASFV therapeutics.

Background Schizophrenia (SCZ) is a complex and severe mental illness. There is a lack of effective biomarkers for SCZ diagnosis. The aim of this study was to explore the possibility of using serum peptides for the diagnosis of SCZ as well as analyze the association of variants in genes coding for these peptides and SCZ. Methods After bead-based fractionation, the matrix-assisted laser desorption ionization/time-of-flight mass spectrometry technique was used to identify peptides that showed different expressions between 166 SCZ patients and 201 healthy controls. Differentially expressed peptides were verified in a second set of samples (81 SCZ patients and 103 healthy controls). The association of SCZ and three tagSNPs selected in genes coding for differentially expressed peptides was performed in 1,126 SCZ patients and 1,168 controls. Results The expression level of peptides with m/z 1,945.07 was significant lower in SCZ patients than in healthy controls (P < 0.000001). The peptide with m/z 1,945.07 was confirmed to be a fragment of Kininogen-1. In the verification tests, Kininogen-1 had a sensitivity of 95.1% and a specificity of 97.1% in SCZ prediction. Among the three tagSNPs (rs13037490, rs2983639, rs2983640) selected in the Cystatin 9 gene (CST9) which encodes peptides including Kininogen-1, tagSNP rs2983640 had its genotype distributions significantly different between SCZ patients and controls under different genetic models (P < 0.05). Haplotypes CG (rs2983639–rs2983640) and TCG (rs13037490–rs2983639–rs2983640) were significantly associated with SCZ (CG: OR = 1.21, 95% CI [1.02–1.44], P = 0.032; TCG: OR = 24.85, 95% CI [5.98–103.17], P < 0.0001). Conclusions The present study demonstrated that SCZ patients had decreased expression of Kininogen-1 and genetic variants in Kininogen-1 coding gene CST9 were significantly associated with SCZ. The findings from both protein and genetic association studies suggest that Kininogen-1 could be a biomarker of SCZ.

The effects of Spartina alterniflora invasion on macrobenthos have long been of concern; however, there is currently no unified conclusion regarding these effects. Most studies on crabs focus on one species or limited habitat types, and assessments of the community-level effects of S. alterniflora invasion considering multiple species and habitat types have rarely been conducted. In this study, we sampled crabs along a habitat gradient from the shoreline to inland areas on the Yellow Sea coast, including the mudflat, S. alterniflora marsh, Suaeda salsa marsh and Phragmites australis marsh. A total of 10 crab species were found among all habitats, with five species in the mudflat, six species in S. alterniflora marsh, seven species in S. salsa marsh and four species in P. australis marsh. The Shannon index values for the crab communities were similar between S. alterniflora marsh and S. salsa marsh, and these values were significantly higher than those for the mudflat and P. australis marsh. However, the total biomass of crabs was highest in the mudflat, and Metaplax longipes, Philyra pisum and Macrophthalmus dilatatus exclusively preferred the mudflat. The analysis of principal components and similarities showed that the crab community structure in S. alterniflora marsh was most similar to that in S. salsa marsh, while the crab community structure in the mudflat was most different from that in the other habitat types. Our results demonstrate that the distribution of crabs varies across a habitat gradient after S. alterniflora invasion and that the crab community in S. alterniflora marsh is slightly different from that associated with the local vegetation but shows a large difference from that in the mudflat. This study indicates that some crab species may have adapted to habitat containing alien S. alterniflora, while other crab species reject this new marsh type. The effects of the distribution of crabs after S. alterniflora invasion on the regional ecosystem need further study in the future.

The effects of gravity on the heat transfer performance of supercritical CO2 flowing within a vertical tube with a diameter of 4.75 mm are numerically studied in this paper. The main objectives are to comprehensively investigate the action of gravity and buoyancy on the supercritical heat transfer. An effective numerical method, which employs a modified Shear Stress Transfer k-ω model (SST k-ω), is applied at various gravity conditions. It is found that, for both upward and downward flows, the heat transfer of supercritical CO2 is improved with increased gravity magnitude. The effect of gravity on heat transfer are more pronounced under a low mass flux condition than that under a high mass flux condition and it is closely related to the variations of thermal properties. For the upward flow, the increased gravity magnitude accelerates the near wall fluid and creates a classic “M-shaped” radial velocity distribution. For the downward flow, the increased gravity magnitude decelerates the near wall fluid and creates a parabola-like radial velocity distribution. On one hand, the turbulent kinetic energies of both the upward and downward flows are enhanced as the gravity magnitude increases, which benefits heat transfer dominated by turbulent eddy diffusion. On the other hand, high-density fluid with high thermal conductivity occupies the near wall region as the gravity magnitude increases, which benefits heat transfer dominated by molecular diffusion. The results might provide some instructive advice to improve the design and operation safety of heat exchanger at various gravity conditions.

Four new indolyl diketopiperazines, aspamides A–E (1–4) and two new diketopiperazines, aspamides F–G (5–6), along with 11 known diketopiperazines and intermediates were isolated from the solid culture of Aspergillus versicolor, which is an endophyte with the sea crab (Chiromantes haematocheir). Further chiral high-performance liquid chromatography resolution gave enantiomers (+)- and (−)-4, respectively. The structures and absolute configurations of compounds 1–6 were determined by the comprehensive analyses of nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) calculation. All isolated compounds were selected for the virtual screening on the coronavirus 3-chymoretpsin-like protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the docking scores of compounds 1–2, 5, 6, 8 and 17 were top among all screened molecules, may be helpful in fighting with Corona Virus Disease-19 (COVID-19) after further studies.

A new type of network-combination synchronization is proposed between two drive networks, small-world and scale-free, and one response community network based on the model of multiple system combination. According to Lyapunov Stability Theorem, combined controllers are designed to control three disparate networks with different topological structures. A realistic combination model of multiple inhomogeneous networks and a universal controller are devised in the combination design. The paper is characterized by two parts of one response community network loaded from the combined signals of two drive networks. Numerical simulations are presented to show the full and partial control of the proposed method.

Experimental investigations on the heat transfer performance of supercritical water flowing in the subchannel of supercritical water-cooled reactor (SCWR) simulated by a triangular channel were conducted at pressures of 23−28 MPa, mass flow rates of 700−1300 kg·m−2·s−1, and inner wall surface heat fluxes of 200−600 kW·m−2. An 8 mm diameter fuel rod with a 1.4 pitch to diameter ratio was used. The effects of pressure, mass flow rate, and heat flux on the heat transfer performance under the resistance of a standard grid spacer were analyzed. Experimental results showed the significant positive influence of the grid spacer on the supercritical water in the subchannel. Moreover, in the presence of the grid spacer, the parameters influenced the heat transfer with different degrees of strengthening reaction. In view of the phenomenon in the tests, the rule of the supercritical heat transfer was further revealed by the comparison between empirical formulas and experimental data. This paper mainly studied the positioning grid function and the fluid flow characteristics downstream of the subchannel under the influence of the standard grid spacer and the impact mechanism of each parameter on the whole heat transfer process coefficient.

Six new depsidones, curdepsidones B−G (1−6), were obtained from the marine-derived fungus Curvularia sp. IFB-Z10. Their planar structures were determined by comprehensive analysis of HRESIMS and 1D/2D-NMR data. The absolute configuration of curdepsidones B−C (1−2) were established by synergistic use of DFT/NMR (density functional theory/nuclear magnetic resonance) and TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations. Partial isolated compounds were tested for their anti-inflammatory activities in Propionibacterium acnes-induced THP-1 cells. Curdepsidone C (2) displayed significant anti-inflammatory properties with an IC50 value of 7.47 ± 0.35 μM, and reduced the P. acnes-induced phosphorylation levels of JNK and ERK in a dose-dependent mechanism. The possible anti-inflammatory mechanism of 2 was also investigated by molecular docking.

A pre-column derivatization high-performance liquid chromatography (HPLC) method was developed and optimized to characterize and quantify the monosaccharides present in tea polysaccharides (TPS) isolated from Yingshuang green tea. TPS sample was hydrolyzed with trifluoroacetic acid, subjected to pre-column derivatization using 1-phenyl-3-methyl-5-pyrazolone (PMP), and separated on an Agilent TC-C18 column (4.6 mm × 250 mm, 5 μm) with UV detection at 250 nm. A mixture of ten PMP derivatives of standard monosaccharides (mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, xylose, galactose, arabinose, and fucose) could be baseline separated within 20 min. Moreover, quantitative analysis of the component monosaccharides in Yingshuang green tea TPS was achieved, indicating the TPS consisted of mannose, ribose, rhamnose, glucuronic acid, galacturonic acid, glucose, xylose, galactose, and arabinose in the molar contents of 0.72, 0.78, 0.89, 0.13, 0.15, 0.36, 0.39, 0.36, 0.36, and 0.38 μM, respectively. Recovery efficiency for component monosaccharides from TPS ranged from 93.6 to 102.4% with RSD values lower than 2.5%. In conclusion, pre-column derivatization HPLC provides a rapid, reproducible, accurate, and quantitative method for analysis of the monosaccharide composition and contents in TPS, which may help to further explore the relationship between TPS monosaccharides isolated from different tea varieties and their biological activity.