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Abstract Influenza (Flu) is a severe health, medical, and economic problem, but no medication that has excellent outcomes and lowers the occurrence of these problems is now available. GanghuoQingwenGranules (GHQWG) is a common Chinese herbal formula for the treatment of influenza (flu). However, its methods of action remain unknown. We used network pharmacology, molecular docking, and molecular dynamics simulation techniques to investigate the pharmacological mechanism of GHQWG in flu. TCMSP and various types of literature were used to obtain active molecules and targets of GHQWG. Flu-related targets were found in the Online Mendelian Inheritance in Man (OMIM) database, the DisFeNET database, the Therapeutic Target Database (TTD), and the DrugBank database. To screen the key targets, a protein–protein interaction (PPI) network was constructed. DAVID was used to analyze GO and KEGG pathway enrichment. Target tissue and organ distribution was assessed. Molecular docking was used to evaluate interactions between possible targets and active molecules. For the ideal core protein–compound complexes obtained using molecular docking, a molecular dynamics simulation was performed. In total, 90 active molecules and 312 GHQWG targets were discovered. The PPI network's topology highlighted six key targets. GHQWG's effects are mediated via genes involved in inflammation, apoptosis, and oxidative stress, as well as the TNF and IL-17 signaling pathways, according to GO and KEGG pathway enrichment analysis. Molecular docking and molecular dynamics simulations demonstrated that the active compounds and tested targets had strong binding capabilities. This analysis accurately predicts the effective components, possible targets, and pathways involved in GHQWG flu treatment. We proposed a novel study strategy for future studies on the molecular processes of GHQWG in flu treatment. Furthermore, the possible active components provide a dependable source for flu drug screening.

BackgroundThe antiviral activity and underlying mechanism of Patchouli alcohol remain unclear.MethodsThis study evaluated the cytotoxicity, optimal methods for drug administration, anti-influenza A activity of Patchouli alcohol. The antiviral mechanism of Patchouli alcohol was also assessed via qRT-PCR, western blot, hemagglutination inhibiting (HAI) assay, and hemolysis inhibiting assay.ResultsPatchouli alcohol was shown to have low cytotoxicity and its strongest antiviral effect was associated with premixed administration. Patchouli alcohol inhibited virus replication during the early lifecycle stages of influenza A virus infection and specifically prevented expression of the viral proteins, HA and NP. In both the HAI and hemolysis inhibiting assays, Patchouli alcohol was able to block HA2-mediated membrane fusion under low pH conditions. Patchouli alcohol had lower binding energy with HA2 than HA1.ConclusionThese findings suggest that Patchouli alcohol could be a promising membrane fusion inhibitor for the treatment of influenza A infection.

The infection of Nocardia gipuzkoensis is a relatively uncommon form of pulmonary nocardiosis seen in clinical patients. In general, nocardiosis tends to occur in patients with immune deficiency. Here, we report a 23-year-old female who was admitted to the hospital due to cough and sputum production over 10 years, diagnosed with bronchiectasis. The N. gipuzkoensis infection was identified by metagenomic next-generation sequencing and whole genome sequencing. Imipenem/cilastatin and compound sulfamethoxazole tablets were used to control the infection and the pulmonary inflammation subsided gradually.

BackgroundThe COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear.MethodsWe collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) analysis, transcription factor (TF)–gene interaction network analysis, transcription factor–miRNA co-regulatory network analysis, and candidate drug analysis prediction.ResultsWe found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF–gene and TF–miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted.ConclusionThis study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.

BackgroundDengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear.MethodsA model of dengue disease was established in IFNAR−/− C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR−/− mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury.ResultsWe observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease.ConclusionsThe interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification.

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited.Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR

BackgroundThe outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection.MethodsTo further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents.ResultsWe explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone.ConclusionsThis study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.

Background: Coronavirus disease 2019 (COVID-19) is now a worldwide public health crisis. The causative pathogen is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Novel therapeutic agents are desperately needed. Because of the frequent mutations in the virus and its ability to cause cytokine storms, targeting the viral proteins has some drawbacks. Targeting cellular factors or pivotal inflammatory pathways triggered by SARS-CoV-2 may produce a broader range of therapies. Glycyrrhizic acid (GA) might be beneficial against SARS-CoV-2 because of its anti-inflammatory and antiviral characteristics and possible ability to regulate crucial host factors. However, the mechanism underlying how GA regulates host factors remains to be determined.Methods: In our report, we conducted a bioinformatics analysis to identify possible GA targets, biological functions, protein-protein interactions, transcription-factor-gene interactions, transcription-factor-miRNA coregulatory networks, and the signaling pathways of GA against COVID-19.Results: Protein-protein interactions and network analysis showed that ICAM1, MMP9, TLR2, and SOCS3 had higher degree values, which may be key targets of GA for COVID-19. GO analysis indicated that the response to reactive oxygen species was significantly enriched. Pathway enrichment analysis showed that the IL-17, IL-6, TNF-α, IFN signals, complement system, and growth factor receptor signaling are the main pathways. The interactions of TF genes and miRNA with common targets and the activity of TFs were also recognized.Conclusions: GA may inhibit COVID-19 through its anti-oxidant, anti-viral, and anti-inflammatory effects, and its ability to activate the immune system, and targeted therapy for those pathways is a predominant strategy to inhibit the cytokine storms triggered by SARS-CoV-2 infection.

Tubby-Like Proteins (TLPs) are important transcription factors with many functions and are found in both animals and plants. In plants, TLPs are thought to be involved in the abiotic stress response. To reveal the potential function of TLPs in the medicinal model plant Salvia miltiorrhiza, we identified 12 S. miltiorrhiza TLPs (SmTLPs) and conducted a comprehensive analysis. We examined SmTLP gene structure, protein structure, phylogenetics, and expression analysis. Our results show that all SmTLPs, except SmTLP11, have a complete typical Tub domain. Promoter analysis revealed that most SmTLPs are involved in hormone and abiotic stress responses. Expression analysis revealed that the 12 SmTLPs could be divided into three categories: those specifically expressed in roots, those specifically expressed in stems, and those specifically expressed in leaves. Additional studies have shown that SmTLP10 may play an important role in the plant cold resistance, while SmTLP12 may be involved in the S. miltiorrhiza ABA metabolic pathway. Our study represents the first comprehensive investigation of TLPs in S. miltiorrhiza. These data may provide useful clues for future studies and may support the hypotheses regarding the role of TLPs in plant abiotic stress process. All in all, we may provide a reference for improving S. miltiorrhiza quality using genetic engineering technology.

Influenza A virus (IAV) poses a severe threat to human health and is a major public health problem worldwide. As global anti-influenza virus drug resistance has increased significantly, there is an urgent need to develop new antiviral drugs, especially drugs from natural products. Isoimperatorin, an active natural furanocoumarin, exhibits a broad range of pharmacologic activities including anticoagulant, analgesic, anti-inflammatory, antibacterial, anti-tumor, and other pharmacological effects, so it has attracted more and more attention. In this study, the antiviral and mechanistic effects of isoimperatorin on influenza A virus in vitro were studied. Isoimperatorin illustrated a broad-spectrum antiviral effect, especially against the A/FM/1/47 (H1N1), A/WSN/33 (H1N1, S31N, amantadine resistant), A/Puerto Rico/8/34 (H1N1), and A/Chicken/Guangdong/1996 (H9N2) virus strains. The experimental results of different administration modes showed that isoimperatorin had the best antiviral activity under the treatment mode. Further time-of-addition experiment results indicated that when isoimperatorin was added at the later stage of the virus replication cycle (6–8 h, 8–10 h), it exhibited an effective antiviral effect, and the virus yield was reduced by 81.4 and 84.6%, respectively. In addition, isoimperatorin had no effect on the expression of the three viral RNAs (mRNA, vRNA, and cRNA). Both the neuraminidase (NA) inhibition assay and CETSA demonstrated that isoimperatorin exerts an inhibitory effect on NA-mediated progeny virus release. The molecular docking experiment simulated the direct interaction between isoimperatorin and NA protein amino acid residues. In summary, isoimperatorin can be used as a potential agent for the prevention and treatment of influenza A virus.

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

Dengue fever is a major worldwide public health problem that, as estimated by the WHO, causes epidemics in over 100 countries, resulting in hundreds of millions of dengue virus (DENV) infections every year. In China, dengue fever mainly occurs in coastal areas. Recurring dengue outbreaks were reported by Guangdong Province almost every year since the first epidemic in 1978. DENV infections persisted in Guangzhou in consecutive years since 2000, with the dengue epidemic reaching a historical peak in 2014. Because Guangzhou is one of the largest cities for opening up in China, understanding the epidemiological characteristics of dengue fever in the city can hopefully provide a significant basis for developing effective dengue prevention strategies. In this study, a total of 34 DENV strains, including 29 DENV-1 strains and 5 DENV-2 strains, were isolated from a blood samples drawn from patients who were diagnosed with dengue fever by hospitals in Guangzhou during 2018. To explore the epidemiological characteristics of dengue fever, the envelope (E) gene obtained from the isolates was amplified for phylogenetic analysis. The results from the phylogenetic analysis showed that DENV in Guangzhou was mainly imported from Southeast Asian countries. Additionally, propagation paths based on phylogeographical analysis suggested potential local dengue transmission in Guangzhou.

Abstract Background Community-Acquired Pneumonia (CAP) remains a significant global health concern, with a subset of cases progressing to Severe Community-Acquired Pneumonia (SCAP). This study aims to develop and validate a CT-based radiomics model for the early detection of SCAP to enable timely intervention and improve patient outcomes. Methods A retrospective study was conducted on 115 CAP and SCAP patients at Southern Medical University Shunde Hospital from January to December 2021. Using the Pyradiomics package, 107 radiomic features were extracted from CT scans, refined via intra-class and inter-class correlation coefficients, and narrowed down using the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The predictive performance of the radiomics-based model was assessed through receiver operating characteristic (ROC) analysis, employing machine learning classifiers such as k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), trained and validated on datasets split 7:3, with a training set (n = 80) and a validation set (n = 35). Results The radiomics model exhibited robust predictive performance, with the RF classifier achieving superior precision and accuracy compared to LR, SVM, and KNN classifiers. Specifically, the RF classifier demonstrated a precision of 0.977 (training set) and 0.833 (validation set), as well as an accuracy of 0.925 (training set) and 0.857 (validation set), suggesting its superior performance in both metrics. Decision Curve Analysis (DCA) was utilized to evaluate the clinical efficacy of the RF classifier, demonstrating a favorable net benefit within the threshold ranges of 0.1 to 0.8 for the training set and 0.2 to 0.7 for the validation set. Conclusions The radiomics model developed in this study shows promise for early SCAP detection and can improve clinical decision-making.

Grid-forming (GFM) wind storage systems (WSSs) possess the capability of actively building frequency and phase, enabling faster frequency response. The frequency regulation power of GFM WSSs is provided by both the rotor of wind turbine and the battery storage (BS) in parallel with DC capacitor. However, with existing control strategies, the energy storage immediately responds to both small and large grid disturbances. The frequent responses significantly decrease the lifespan of energy storage. To address this issue, a cooperative strategy between rotor and energy storage is necessary. This paper proposes an advanced strategy of GFM WSSs for cooperative DC power support. The cooperative principle is that for small disturbances, the BS is disabled and total frequency regulation power is provided by the rotor, while for large disturbances, the BS is enabled to cooperatively provide power support with the rotor. The proposed cooperative strategy can decrease the charging and discharging times of BS with a small range of rotor speed fluctuation, and then the service life of BS can be significantly extended. Simulation results validate the effectiveness and superiority of the proposed strategy.

Abstract Background In 2016, the “universal two-child” policy, allowing each couple to have two children, was introduced in China. The characteristic change of the long-term period after the implementation of the universal two-child policy was unclear. We studied trends in the obstetric characteristics and their potential impact on the rates of cesarean section and preterm birth in the era of China’s universal two-child policy. Methods A tertiary center-based study (2010–2021) retrospectively focused single high-risk pregnancies who delivered from the one-child policy period (OCP, 2010–2015) to the universal two-child policy period (TCP, 2016–2021). A total of 39, 016 pregnancies were enrolled. Maternal demographics, complications, delivery mode and obstetric outcomes were analyzed. Furthermore, logistic regression analysis was used to explore the association between the cesarean section rate, preterm birth and implementation of the universal two-child policy, adjusting maternal age, parity, and fetal distress. Results Ultimately a total of 39,016 pregnant women met the criteria and were included in this analysis. The proportion of women with advanced maternal age (AMA) increased from 14.6% in the OCP to 31.6% in the TCP. The number of multiparous women increased 2-fold in the TCP. In addition, the overall rate of cesarean section significantly decreased over the policy change, regardless of maternal age, whereas the risk of preterm birth significantly increased in the TCP. Adjusting for maternal age, parity and fetal distress, the universal two-child policy showed a significantly favorable impact on the cesarean section rate (RR 0.745, 95%CI (0.714–0.777), P

CO is one of the important molecules in dense molecular clouds, and its dissociation induced by cosmic ray heavy ions is a fundamental process for molecular breaking up and rearrangement in astronomical networks. Extensive laboratory simulations are required to understand molecular evolution in astrophysical contexts. Here, we investigate the CO dissociation induced by 1 keV/u Ar2+ using cold target recoil ion momentum spectroscopy. Kinetic energy release for double electron capture Ar2++CO→Ar0+C++O+ and transfer ionization Ar2++CO→Ar++C++O++e− was obtained. The dissociation mechanisms are attributed to different KER distributions. The autoionization process is identified below the CO2+ double ionization threshold.

Magnesium potassium phosphate cement (MKPC), a clinker-free cement, was used as the recycled coarse aggregate (RCA) surface strengthening material to enhance the mechanical properties and durability of recycled aggregate concrete (RAC) under two surface treatment methods. The effect of strengthening slurry properties on RAC reinforcement was investigated by adding different types and amounts of mineral admixtures (MA). An interface model was prepared to detect the microscopic characteristics of interfaces. The results indicated that all MA-MKPC slurries improved the RAC macroscopic performances, attributed to the fact that MA-MKPC slurries effectively improved the RCA surface pore structure and promoted a secure connection with RCA or new mortar. MA-MKPC slurry properties significantly affected the performances of modified RAC, and the MA optimal dosage of 10 % was found. Furthermore, the pre-coating without pre-curing method outperformed the pre-coating plus pre-curing method, forming an enhanced new interfacial transition zone within the RAC.

Abstract Background The morbidity and mortality of community-acquired pneumonia (CAP) remain high among infectious diseases. It was reported that angiopoietin-like 4 (ANGPTL4) could be a diagnostic biomarker and a therapeutic target for pneumonia. This study aimed to develop a more objective, specific, accurate, and individualized scoring system to predict the severity of CAP. Methods Totally, 31 non-severe community-acquired pneumonia (nsCAP) patients and 14 severe community-acquired pneumonia (sCAP) patients were enrolled in this study. The CURB-65 and pneumonia severity index (PSI) scores were calculated from the clinical data. Serum ANGPTL4 level was measured by enzyme-linked immunosorbent assay (ELISA). After screening factors by univariate analysis and receiver operating characteristic (ROC) curve analysis, multivariate logistic regression analysis of ANGPTL4 expression level and other risk factors was performed, and a nomogram was developed to predict the severity of CAP. This nomogram was further internally validated by bootstrap resampling with 1000 replications through the area under the ROC curve (AUC), the calibration curve, and the decision curve analysis (DCA). Finally, the prediction performance of the new nomogram model, CURB-65 score, and PSI score was compared by AUC, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results A nomogram for predicting the severity of CAP was developed using three factors (C-reactive protein (CRP), procalcitonin (PCT), and ANGPTL4). According to the internal validation, the nomogram showed a great discrimination capability with an AUC of 0.910. The Hosmer–Lemeshow test and the approximately fitting calibration curve suggested a satisfactory accuracy of prediction. The results of DCA exhibited a great net benefit. The AUC values of CURB-65 score, PSI score, and the new prediction model were 0.857, 0.912, and 0.940, respectively. NRI comparing the new model with CURB-65 score was found to be statistically significant (NRI = 0.834, P

This paper presents an evaluation of the bearing capacity of cross-bracing in steel transmission tower structures. Design guidelines (ASCE 10-15, BS EN 50341-1, GB 50017-2017, and DL/T 5486-2020) related to the buckling capacity of the cross-bracing are summarized and compared with the experimental results. The current design provisions obtained the bearing capacity from the equivalent slenderness ratio, and then the stability coefficient and buckling capacity were derived. The calculated bearing capacity based on the design code tends to be overly progressive for smaller slenderness ratios (particularly those below 100), except for EN 50341-1-2012. Conversely, for larger slenderness ratios, ASCE 10-15 and DL/T 5486-2020 Class A design codes lean towards being overly progressive, while GB 50017-2017 and EN 50341-1-2012 codes tend to be more conservative. The design standard appears to exhibit unsafe predictions for Class A and B connections with low slenderness ratios and Class C connections. It needs to be noted that the effects of torsional stiffness and joint connection type are not considered in the current design codes, which are proved to be nonnegligible by the test results. In this paper, the bearing capacity calculation formula is proposed by introducing a modified effective length coefficient (K), and both the torsional stiffness and joint connection type are taken into account. The modified bearing capacity is verified with the test results; the correlation coefficient is 0.997, and the coefficient of variation is 0.04. It can provide a reference for the engineering design of steel lattice transmission tower structures.

The relationship between gut microbiota and its metabolites with cardiovascular disease (CVD) has been proven. In this review, we aim to conclude the potential mechanism of gut microbiota and its metabolites on inducing the formation of vulnerable atherosclerotic plaque, and to discuss the effect of intestinal metabolites, including trimethylamine-N-oxide (TMAO), lipopolysaccharide (LPS), phenylacetylglutamine (PAG), short-chain fatty acids (SCFAs) on plaque stability. Finally, we include the impact of gut microbiota and its metabolites on plaque stability, to propose a new therapeutic direction for coronary heart disease. Gut microbiota regulation intervenes the progress of arteriosclerosis, especially on coronary atherosclerosis, by avoiding or reducing the formation of vulnerable plaque, to lower the morbidity rate of myocardial infarction.

Key Clinical Message There was an 83‐year‐old man having coronary artery disease associated with coronary artery ectasia who occurred ventricular fibrillation suddenly during coronary artery angiography. As Kawasaki disease was suspected to the most likely reason which led to coronary artery lesion.

Substitution of cement clinker with steel slag (SS) is an effective approach for solving the problems of environmental contamination and resource consumption caused by cement manufacturing. This study aimed to improve the mechanical properties of cement–SS mortar by incorporating water glass (WG) to promote the optimal utilization of SS waste. In this study, the setting time, mechanical strength, and microstructure of cement–SS systems were investigated. From the experimental results, it was found that the incorporation of WG effectively shortened their setting times and enhanced their mechanical strengths, particularly early strengths. The enhancement in these properties was mainly due to the acceleration effect of WG on the cement–SS system hydration process by expediting the dissolution of the tetrahedron [SiO4] and [AlO4] units in SS to produce H3SiO4− and H3AlO42−. This facilitated the formation of more stable zeolite-like hydration products. Furthermore, the soluble Si4+ supplied by WG reacted with Ca (OH)2 to form a calcium silicate hydrate (C–S–H) gel. Both the high hydration degree of SS at early ages and C–S–H gel formation appeared to be the primary mechanisms for the strength improvement of the cement–SS systems by WG addition.

Abstract Background Wear resistance affects dental ceramics longevity and the functions of the opposing teeth. However, data for the effect of aqueous environment on wear resistance of dental ceramics are lacking. This study evaluated the effect of aqueous environment on wear resistance of typical dental glass–ceramics. Methods Disk specimens were prepared from lithium disilicate glass–ceramics (LD) and leucite reinforced glass–ceramics (LEU). The disk specimens paired with steatite antagonists were tested in a pin-on-disk tribometer under both wet and dry conditions with 10 N up to 500,000 wear cycles. The wear analysis of glass–ceramics was performed using a 3D profilometer after 100,000, 300,000 and 500,000 wear cycles. Wear morphologies were analyzed by employing scanning electron microscopy (SEM). The crystalline compositions of specimens stored in a dry environment and subsequently immersed in distilled water for 40 h were separately determined using X-ray diffraction (XRD). The chemical states of the wear surfaces for LD were analyzed by X-ray photoelectron spectroscopy (XPS). The data analysis and multiple pair-wise comparisons of means were performed by using one-way analysis of variance (ANOVA) and Tukey’s post-hoc test. Results LEU in a wet environment exhibited less wear volume loss than that in a dry environment (p

Nano-SiO2 (NS) is widely used in cement-based materials due to its excellent physical properties. To study the influence of NS content on a cement paste and the interfacial transition zone (ITZ), cement paste samples containing nano content ranging from 0 to 2% (by weight of cement) were prepared, and digital image correlation (DIC) technology was applied to test the mechanical properties. Finally, the optimal NS content was obtained with statistical analysis. The mini-slump cone test showed that, with the help of superplasticizer and ultrasonic treatment, the flowability decreased continuously, as the NS content increased. The DIC experimental results showed that NS could effectively improve the mechanical properties of the cement paste and the ITZ. Specifically, at the content level of 1%, the elastic modulus of cement paste and ITZ was 20.95 GPa and 3.20 GPa, respectively. When compared to that without nanomaterials, the increased amplitude was 73.50% and 90.50%, respectively. However, with the further increase in NS content, the mechanical properties decreased, which was mainly caused by the agglomeration of nanomaterials. Additionally, the NS content did not exhibit a significant effect on the thickness of the ITZ, and its value was maintained at 76.91–91.38 μm. SEM confirmed that NS would enhance the microstructure of both cement paste and ITZ.

Industrial structure adjustment is an important component of China’s supply-side structural reforms. This study examines the effect and action path of regional industrial structure transformation, through the lens of advancement and rationalization, on the economic fluctuation and quality of the marine fishery industry. The results show that regional industrial structure advancement (rationalization) promotes (reduces) economic fluctuation. Regarding the action paths, regional industrial structure advancement (rationalization) has a U-shaped (inverted U-shaped) relationship with economic quality. The regional industrial structure advancement level is greater than 5.108 in China’s coastal areas and on the right side of the U shape. Thus, the evolution of the industrial structure in these areas is conducive to improving the economic quality of marine fisheries. Meanwhile, The degree of regional industrial structure rationalization has not reached the optimum level, and most areas are far from optimum level. This suggests that the structural dividends from industrial structure rationalization not fully released and need further regulation. In terms of the overall effect, regional industrial structure transformation can cause economic fluctuations in marine fisheries, with the main force originating from industrial structure advancement. The path of regional industrial structure transformation affecting economic quality of marine fisheries is non-linear. At present, the industrial structure advancement transformation can improve economic quality, but the industrial structure rationalization needs to be further adjusted.

ObjectiveTo investigate the correlation of trends in lipid profiles from first to second trimester with trends in insulin indices and gestational diabetes mellitus (GDM).MethodsSecondary analysis of an ongoing prospective cohort study was conducted on 1234 pregnant women in a single center. Lipid profiles, glucose metabolism and insulin indices were collected in the first and second trimesters. Trends in lipid profiles were divided into four subgroups: low-to-low, high-to-high, high-to-low and low-to-high group. Insulin indices including homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were calculated to evaluate insulin resistance (IR). Trends in insulin indices were described as: no IR, persistent IR, first-trimester IR alone and second-trimester IR alone. Pearson correlation analysis and multivariate logistic regression were performed to assess the associations of lipid profiles subgroups with insulin indices and GDM.ResultsFirst- and second-trimester total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol were strongly correlated to first- and second-trimester insulin indices. Only TG had a sustained correlation with glucose metabolism indices. High-to-high low-density lipoprotein cholesterol (LDL-c) was an independent risk factor for GDM. High-to-high TG and high-to-low TG groups were independent risk factors for persistent IR. High-to-high TG and low-to-high TG groups were independent risk factors for second-trimester IR alone.ConclusionTG has a sustained correlation with insulin indices and glucose metabolism indices. Persistently high TG is an independent risk factor for persistent IR and second-trimester IR alone. Regardless of whether pregnant women have first-trimester IR, lower TG levels help reduce the risk for persistent IR or subsequent development of IR. These results highlight the benefit of lowering TG levels in early and middle pregnancy to prevent the development of IR.

The contact type between graphene and semiconducting two-dimensional materials is a crucial factor in determining the performance of nanoscale electronic devices based on two-dimensional materials. Recently, SiCP4 is proposed to have high charge mobility plus high stability. In this work, we study the contact type between graphene and SiCP4. The Schottky barrier is formed between graphene and SiCP4. By changing the interlayer distance, the Schottky barrier can be tuned in a wide range. The charge transfer at the interface induces a reverse shift between the bands of graphene and SiCP4. The amount of charge transfer can be used to explain the change in the Schottky barrier. Furthermore, the Schottky barrier can be controlled by applying a vertical electric field. The tunable Schottky barrier provides a guide for the design of the nanodevice based on graphene and SiCP4.

The output of renewable energy is strongly uncertain and random, and the distribution of voltage and reactive power in regional power grids is changed with the access to large-scale renewable energy. In order to quantitatively evaluate the influence of renewable energy access on voltage and reactive power operation, a novel combinational evaluation method of voltage and reactive power in regional power grids containing renewable energy is proposed. Firstly, the actual operation data of renewable energy and load demand are clustered based on the K-means algorithm, and several typical scenarios are divided. Then, the entropy weight method (EWM) and the analytic hierarchy process (AHP) are combined to evaluate the voltage qualified rate, voltage fluctuation, power factor qualified rate and reactive power reserve in typical scenarios. Besides, the evaluation results are used as the training samples for back-propagation (BP) neural networks. The proposed combinational evaluation method can calculate the weight coefficient of the indexes adaptively with the change of samples, which simplifies the calculation process of the indexes’ weight. At last, the case simulation of an actual regional power grid is provided, and the historical data of one year is taken as the sample for training, evaluating and analyzing. And finally, the effectiveness of the proposed method is verified based on the comparison with the existing method. The evaluated results could provide reference and guidance to the operation analysis and planning of renewable energy.

Abstract Background Circular RNAs (circRNAs) has emerged as vital regulator involved in various diseases. In this study, we identified and investigated the potential circRNAs involved in gestational diabetes mellitus (GDM). Methods High-throughput sequencing was used to collect the plasma circRNAs expression profiles of GDM patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to measure the expressions of circ_0008285 and circ_0001173 in the plasma specimens. The Pearson’s correlation test was employed to assess the correlation between 2 circRNAs expression and the clinicopathologic data. Two circRNAs expression was verified in high glucose (HG)-induced HTR-8/SVneo cells. MTS, transwell assay was used to evaluate the effects of circ_0008285 expression on HG-induced HTR-8/SVneo cells. The network of circ_0008285 was constructed using cytocape. Results In GDM patients, the expression of circ_0008285 was significantly upregulated, while that of circ_0001173 was decreased. Circ_0008285 was significantly correlated with the total cholesterol and LDL-C levels. Circ_0001173 was significantly correlated with glycated hemoglobin. HG promoted the proliferation, invasion, and migration in HTR-8/SVneo cells, while the knockdown of circ_0008285 exerted reverse effects. In addition, network construction exhibited that circ_0008285 had 45 miRNA binding sites, which correlated with 444 mRNA. Conclusions circ_0008285 plays an important role and provides a clue for the usage of therapeutic targets in the development of GDM.

The human body is thoroughly colonized by a wide variety of microorganisms, termed microbiota. Pancreatic cancer, one of the most aggressive forms of cancer, is no exception. The microbiota of pancreatic cancer largely influences and even dominates the occurrence, development and outcome of pancreatic cancer in many ways. Studies have shown that microbiota could change the malignant phenotype and prognosis of pancreatic cancer by stimulating persistent inflammation, regulating the antitumor immune system, changing the tumor microenvironment and affecting cellular metabolism. This is why the association of the microbiota with pancreatic cancer is an emerging area of research that warrants further exploration. Herein, we investigated the potential microbial markers of pancreatic cancer, related research models, the mechanism of action of microbiota in pancreatic cancer, and pancreatic cancer-microbiota-related treatment.

There are multiple ways by which energy and charge transfer occur in weakly bound systems. Here the authors reveal a heavy ion N+ transfer in a doubly charged Van der Waals cluster produced in collisions of the highly charged Ne8+ ion with N2Ar, leading to fragmentation of N+ and NAr+ via Coulomb explosion.

We investigate the fragmentation of the CH4 cluster by fast electron impact at stagnation pressures from 0.5 bar to 16 bar. By measuring the time of flight spectrum (TOF), two types of ions, including (CH4)n−1CH5+ and (CH4)n−2(C2Hm)+, are observed. In the 1D TOF spectrum, it is shown that for the stagnation pressure larger than 4 bar, the former ion is predominant for each n, similar to the previous experimental result. However, as the pressure decreases to 0.5 or 2 bar, the contribution of the C2Hm+ ion is dominant over that of the CH4CH5+ ion. In the 2D coincident TOF spectrum, the above two patterns of ions are also distinguished, and the enhancement of C2Hm+ is observed at 4 bar pressure. The phenomena appearing in 2D and 1D TOF spectra imply that the C2Hm+ ion prefers to survive in a smaller cluster, while the stabilization of the protonated ion needs a more massive cluster environment.

The addition of conductive fillers to the carbon fiber bar reduces its resistivity and improves electrical stability. Unstable conductivity and susceptibility to ambient temperature change impede the application of this technique in engineering, unless such influence can be eliminated by technical means or precisely predict. In this paper, modified epoxy Resin based carbon fiber bars with 4 sets of different mixed fillers have been designed to evaluate the temperature-resistance effect under different temperature cycles. Results show that the initial volume resistivity reduces due to the incorporation of carbon powder(CP) and nano-silica(NS), and meets the lowest when the CP and NS mass ratio is 1:0.6. The volume resistivity increases linearly with the temperature rising, and reaches the maximum temperature sensitivity coefficient of 78.8%. During the temperature cycle process, the volume resistivity of all specimens first decreases and then increases with the increasing temperature uniformly. The three groups (CP/NS ratio 1:0.2, 1:0.6, and 1:0) share the same PTC effect transition temperature range, from 30 to 60 °C. And for the 1:1 group, the transition temperature is about 0 °C, which is the lowest. Altogether, these enhancements provide avenues for future self-sensing carbon fiber composites in engineering structures.

IntroductionAsymptomatic coronavirus disease 2019 (COVID-19) and moderate COVID-19 may be the most common COVID-19 cases. This study was designed to develop a diagnostic model for patients with asymptomatic and moderate COVID-19 based on demographic, clinical, and laboratory variables.MethodsThis retrospective study divided the subjects into 2 groups: asymptomatic COVID-19 (without symptoms, n = 15) and moderate COVID-19 (with symptoms, n = 57). Demographic characteristics, clinical data, routine blood tests, other laboratory tests, and inpatient data were collected and analyzed to compare patients with asymptomatic COVID-19 and moderate COVID-19.ResultsComparison of the asymptomatic COVID-19 group with the moderate COVID-19 group yielded the following results: the patients were younger (P = 0.045); the cluster of differentiation (CD)8+ (cytotoxic) T cell level was higher (P = 0.017); the C-reactive protein (CRP) level was lower (P = 0.001); the white blood cell (WBC, P < 0.001), neutrophil (NEU, P = 0.036), lymphocyte (LYM, P = 0.009), and eosinophil (EOS, P = 0.036) counts were higher; and the serum iron level (P = 0.049) was higher in the asymptomatic COVID-19 group. The multivariate analysis showed that the NEU count (odds ratio [OR] = 2.007, 95% confidence interval (CI): 1.162 - 3.715, P = 0.014) and LYM count (OR = 9.380, 95% CI: 2.382 - 36.934, P = 0.001) were independent factors for the presence of clinical symptoms after COVID-19 infection. The NEU count and LYM count were diagnostic predictors of asymptomatic COVID-19. This diagnostic prediction model showed high discriminatory power, consistency, and net clinical benefits.ConclusionsThe proposed model can distinguish asymptomatic COVID-19 from moderate COVID-19, thereby helping clinicians identify and distinguish patients with potential asymptomatic COVID-19 from those with moderate COVID-19.

Abstract The unbound concentrations of 14 commercial drugs, including five non‐efflux/uptake transporter substrates—Class I, five efflux transporter substrates—class II and four influx transporter substrates—Class III, were simultaneously measured in rat liver, muscle, and blood via microanalysis. Kpuu,liver and Kpuu,muscle were calculated to evaluate the membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver. For Class I compounds, represented by antipyrine, unbound concentrations among liver, muscle and blood are symmetrically distributed when compound hepatic clearance is low. And when compound hepatic clearance is high, unbound concentrations among liver, muscle and blood are asymmetrically distributed, such as Propranolol. For Class II and III compounds, overall, the unbound concentrations among liver, muscle, and blood are asymmetrically distributed due to a combination of hepatic metabolism and efflux and/or influx transporter activity.

The wave function of an atom, which passed through a diffraction grating, is characterized by a regular space structure. Correspondingly, the interaction of another particle with this atom can be viewed as scattering on an ‘atomic quantum grating’ made of just a single atom. Probing this ‘grating’ by collisions with a charged projectile reveals few-body interference phenomena caused by the coherent contributions of its ‘slits’ to the transition amplitude (the superposition principle) and quantum entanglement of the particles involved. In particular, the spectra of electrons emitted from the atom in collisions with swift ions exhibit a pronounced interference pattern whose shape can be extremely sensitive to the collision velocity.

Grain size is one of the most important physical parameters for randomly packed granular (RPG) materials. Its estimation, especially in situ, plays a key role in many natural and industrial processes. Here, the application of laser-induced breakdown spectroscopy (LIBS) was investigated experimentally to estimate the grain size in RPG materials. The experiment was performed by taking sieved copper microspheres with discrete median diameters ranging from 53 to 357 μm as examples and by measuring the plasma emissions induced by 1064 nm laser pulses with a duration of 7 ns in an air environment. It was found that the plasma emission measurements were successful in estimating the grain median diameter via monitoring the variations in plasma temperature (electron density) at the range of median diameter below (above) a critical value. In addition, it was demonstrated that, when plasma temperature serves as an indicator of grain size, the intensity ratio between two spectral lines from different upper energy levels of the same emitting species can be used as an alternative indicator with higher sensitivity. The results show the potential of using LIBS for in situ estimation of grain size in RPG materials for the first time.

Abstract In clinical pharmacology, the free drug hypothesis has been widely applied in the interpretation of the relationship between pharmacokinetics and pharmacodynamics (PK/PD). The free drug hypothesis assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state. The objective of this study is to demonstrate whether the free drug hypothesis is universally applicable for all drugs. The unbound concentrations of the 18 compounds in blood and in brain interstitial fluids (ISF) at steady state following constant intravenous infusion were simultaneously monitored up to 6 hours via in vivo microdialysis technique. Based on the permeability and efflux ratio (ER), the test compounds can be divided into two classes. Class I includes the compounds with good membrane permeability that are not substrates of efflux transporters (eg, P‐gp, BCRP, and MRPs), whereas Class II includes the compounds that are substrates of efflux transporters. The steady‐state unbound drug concentrations in blood, brain, and CSF are quantitatively very similar for Class I compounds, whereas the steady‐state unbound concentrations in the brain and CSF are significantly lower than those in blood for Class II compounds. These results strongly suggest that the free drug hypothesis is not universal for all drugs but is only applicable for drugs with good permeability that are not substrates of efflux transporters.

High-purity solanesol can be used for pharmaceutical applications, but the current method for purifying solanesol has high cost and difficult continuous operation, and the use of molecular imprinting to purify natural products is a hot research topic of current research. Solanesol molecularly imprinted polymers were synthesized via emulsion polymerization for the first time. The morphology of the SSO-MIPs was observed with a scanning electron microscope, and the effects of the synthesis time, initiator dosage, functional monomer dosage, and cross-linking agent dosage on the adsorption effects under high-temperature and rapid synthesis conditions were discussed. The results demonstrate that the optimum synthesis conditions were a ratio of the template molecules to the functional monomers to the cross-linking agents of 1:8:30 (mol:mol:mol), 10 mg of the initiator, and a synthesis temperature of 70 °C. The imprinting factor of SSO-MIPs synthesized under the optimized process was found to reach 2.51, and the SSO-MIPs synthesized by this method exhibited a good adsorption effect, emitted less pollution during the synthesis process, and are convenient for demulsification. This research reports a reliable method for the synthesis of solanesol molecularly imprinted polymers.

BACKGROUND: Removable dentures are subject to plaque and/or staining problems. Denture hygiene habits and risk factors differ among countries and regions. The aims of this study were to assess hygiene habits and denture plaque and staining risk factors in Chinese removable denture wearers aged >40 years in Xi'an through multiple logistic regression analysis (MLRA). METHODS: Questionnaires were administered to 222 patients whose removable dentures were examined clinically to assess wear status and levels of plaque and staining. Univariate analyses were performed to identify potential risk factors for denture plaque/staining. MLRA was performed to identify significant risk factors. RESULTS: Brushing (77.93%) was the most prevalent cleaning method in the present study. Only 16.4% of patients regularly used commercial cleansers. Most (81.08%) patients removed their dentures overnight. MLRA indicated that potential risk factors for denture plaque were the duration of denture use (reference, ≤0.5 years; 2.1-5 years: OR = 4.155, P = 0.001; >5 years: OR = 7.238, P5 years: OR = 27.226, P

OBJECTIVE: Chronic respiratory inflammation has been associated with lung cancer. Tumor-associated macrophages (TAMs) play a critical role in the formation of inflammation microenvironment. We sought to characterize the role of TAMs in coal tar pitch extract (CTPE)-induced tumorigenic transformation of human bronchial epithelial cells and the underlying mechanisms. METHODS: The expression of TAMs-specific CD68 in lung cancer tissues and paired adjacent tissues from cancer patients was determined using immunostaining. Co-culture of human bronchial epithelial cells (BEAS-2B) and macrophage-like THP-1 cells were conducted to evaluate the promotive effect of macrophages on CTPE-induced tumorigenic transformation of BEAS-2B cells. BEAS-2B cells were first treated with 2.4 µg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured either with or without THP-1 cells and passaged using trypsin-EDTA. Alterations of cell cycle, karyotype, colony formation in soft agar and tumor xenograft growth in nude mice of BEAS-2B cells at passages 10, 20 and 30, indicative of tumorigenecity, were determined, respectively. In addition, mRNA and protein levels of NF-κB in BEAS-2B cells were measured with RT-PCR and western blot, respectively. B(a)P was used as the positive control. RESULTS: The over-expression of TAMs-specific CD68 around lung tumor tissues was detected and associated with lung cancer progression. The tumorigenic alterations of BEAS-2B cells including increase in cell growth rate, number of cells with aneuploidy, clonogenicity in soft agar, and tumor size in nude mice in vivo occurred at passage 10, becoming significant at passages 20 and 30 of the co-culture following CTPE removal in compared to BEAS-2B cells alone. In addition, the expression levels of NF-κB in BEAS-2B cells were positively correlated to the malignancy of BEAS-2B cells under different conditions of treatment. CONCLUSION: The presence of macrophages facilitated CTPE-induced tumorigenic transformation of BEAS-2B cells, which may be mediated by NF-κB.