Baicalin Downregulates RLRs Signaling Pathway to Control Influenza A Virus Infection and Improve the Prognosis

The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg. The results showed that IAV infection led to low body weight and high viral load and high expression of RIG-I, IRF3, IRF7, and NF-κB mRNA, as well as RIG-I and NF-κB p65 protein. However, baicalin reduced the rate of body weight loss, inhibited virus replication, and downregulated the key factors of the RLRs signaling pathway. Besides, baicalin reduced the high expression inflammatory cytokines in lung and decreased the ratios of Th1/Th2 and Th17/Treg to arouse a brief but not overviolent inflammatory response. Therefore, baicalin activated a balanced host inflammatory response to limit immunopathologic injury, which was helpful to the improvement of clinical and survival outcomes

Effectiveness of Shuxuening injection in coronary heart disease: a systematic review and meta-analysis

Background: Coronary heart disease (CHD) poses a serious threat to public health, and the current medical management still faces significant challenges. Reliable evidence on the efficacy of Shuxuening injection (SXNI) in CHD is still lacking, even though it is widely used in China.Purpose: To evaluate the efficacy of SXNI combination therapy in treating CHD.Methods: A systematic search of eight databases was conducted to identify relevant randomized controlled trials (RCTs) from the inception of each database until June 2023. ROB 2.0, RevMan 5.4, and Stata 15.1 were used for quality evaluation and data analysis. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the quality of evidence.Results: A total of 3,779 participants from 39 studies were included. The results showed SXNI combination therapy increased the clinical efficacy and decreased the frequency and duration of angina. Furthermore, SXNI combination therapy improved cardiac function of patients by decreasing LVEDD, and increased CI, CO, and LVEF. It also improved blood lipid profiles by increasing HDL, decreasing TC, TG, and LDL. The thrombosis factors of patients were also improved by decreasing FIB, PV, HCT, and HS. Moreover, SXNI combination therapy was superior to the conventional treatment in improving CRP levels, increasing ECG efficacy and BNP. However, due to the limited safety information, reliable safety conclusions could not be drawn. Furthermore, the levels of evidence ranged from very low to moderate due to publication bias and heterogeneity.Conclusion: SXNI can effectively improve angina symptoms, clinical efficacy, cardiac function, blood lipid indicators, and thrombosis factors of patients with CHD. However, more multi-center and large-sample studies are needed to confirm the conclusions due to the limitations of this study.Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399606; Identifier: CRD42023433292

Adsorption of Per- and Polyfluoroalkyl Substances (PFAS) and Microcystins by Virgin and Weathered Microplastics in Freshwater Matrices

Microplastics and per- and polyfluoroalkyl substances (PFAS) both represent persistent groups of environmental contaminants that have been associated with human health risks. Microcystin toxins are produced and stored in the cells of cyanobacteria and may be released into sources of drinking water. Recent concerns have emerged regarding the ability of microplastics to adsorb a range of organic contaminants, including PFAS and microcystins. This study examined the adsorption of two long-chain and two short-chain PFAS, as well as two common microcystins, by both virgin and weathered microplastics in freshwater. Natural weathering of microplastic surfaces may decrease adsorption by introducing hydrophilic oxygen-containing functional groups. Up to 50% adsorption of perfluorooctanesulfonic acid (PFOS) was observed for virgin PVC compared to 38% for weathered PVC. In contrast, adsorption capacities for microcystins by virgin LDPE were approximately 5.0 µg/g whereas no adsorption was observed following weathering. These results suggest that adsorption is driven by specific polymer types and dominated by hydrophobic interactions. This is the first known study to quantify PFAS and microcystins adsorption when considering environmentally relevant concentrations as well as weathered microplastics

Mining Software Repositories for Automatic Interface Recommendation

There are a large number of open source projects in software repositories for developers to reuse. During software development and maintenance, developers can leverage good interfaces in these open source projects and establish the framework of the new project quickly when reusing interfaces in these open source projects. However, if developers want to reuse them, they need to read a lot of code files and learn which interfaces can be reused. To help developers better take advantage of the available interfaces used in software repositories, we previously proposed an approach to automatically recommend interfaces by mining existing open source projects in the software repositories. We mainly used the LDA (Latent Dirichlet Allocation) topic model to construct the Feature-Interface Graph for each software project and recommended the interfaces based on the Feature-Interface Graph. In this paper, we improve our previous approach by clustering the recommending interfaces on the Feature-Interface Graph, which can recommend more accurate interfaces for developers to reuse. We evaluate the effectiveness of the improved approach and the results show that the improved approach can be more efficient to recommend more accurate interfaces for reuse over our previous work

A Collaborative Emergency Drill System for Urban Tunnels Using BIM and an Agent-Based Model

With the rapid development of smart cities, the refined management of urban highway tunnels has put forward higher requirements for the emergency disposal ability of operation and maintenance personnel. This paper proposed a collaborative emergency drill system for urban tunnels using building information modeling (BIM) and an agent-based model. The objectives of this paper are as follows: (1) To help address the challenge of multi-person collaborative intelligent drills in complex emergency scenarios, this system constructed an emergency collaborative drill model and a virtual emergency scenario description method based on trait-based objects (TBOs). (2) To help address the challenge of the organization and integration of multi-source heterogeneous data in complex emergency scenarios, the system established an emergency scenario generation method through lightweight BIM data, standard emergency plan documents, and virtual emergency scenario data. The system was successfully applied to the Hongmei South Road Tunnel in Shanghai, China. The feasibility of the proposed system provided practical help for tunnel emergency management and was extended to other urban tunnels in Shanghai

Mitochondrial dysfunction induced by bedaquiline as an anti-Toxoplasma alternative

Abstract Toxoplasma gondii is a zoonotic parasite that infects one-third of the world’s population and nearly all warm-blooded animals. Due to the complexity of T. gondii’s life cycle, available treatment options have limited efficacy. Thus, there is an urgent need to develop new compounds or repurpose existing drugs with potent anti-Toxoplasma activity. This study demonstrates that bedaquiline (BDQ), an FDA-approved diarylquinoline antimycobacterial drug for the treatment of tuberculosis, potently inhibits the tachyzoites of T. gondii. At a safe concentration, BDQ displayed a dose-dependent inhibition on T. gondii growth with a half-maximal effective concentration (EC50) of 4.95 μM. Treatment with BDQ significantly suppressed the proliferation of T. gondii tachyzoites in the host cell, while the invasion ability of the parasite was not affected. BDQ incubation shrunk the mitochondrial structure and decreased the mitochondrial membrane potential and ATP level of T. gondii parasites. In addition, BDQ induced elevated ROS and led to autophagy in the parasite. By transcriptomic analysis, we found that oxidative phosphorylation pathway genes were significantly disturbed by BDQ-treated parasites. More importantly, BDQ significantly reduces brain cysts for the chronically infected mice. These results suggest that BDQ has potent anti-T. gondii activity and may impair its mitochondrial function by affecting proton transport. This study provides bedaquiline as a potential alternative drug for the treatment of toxoplasmosis, and our findings may facilitate the development of new effective drugs for the treatment of toxoplasmosis

Potential Molecular Mechanisms of Plantain in the Treatment of Gout and Hyperuricemia Based on Network Pharmacology

Background. The incidence of gout and hyperuricemia is increasing year by year in the world. Plantain is a traditional natural medicine commonly used in the treatment of gout and hyperuricemia, but the molecular mechanism of its active compounds is still unclear. Based on network pharmacology, this article predicts the targets and pathways of effective components of plantain for gout and hyperuricemia and provides effective reference for clinical medication. Method. Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SymMap databases were used to screen out the active compounds and their targets in plantain. GeneCards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM) databases were used to find the targets corresponding to gout and hyperuricemia. Venn diagram was used to obtain the intersection targets of plantain and diseases. The interaction network of the plantain active compounds-targets-pathways-diseases was constructed by using Cytoscape 3.7.2 software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. Result. Seven active compounds were identified by network pharmacological analysis, including dinatin, baicalein, baicalin, sitosterol, 6-OH-luteolin, stigmasterol, and luteolin. Plantain plays a role in gout and hyperuricemia diseases by regulating various biological processes, cellular components, and molecular functions. The core targets of plantain for treating gout are MAPK1, RELA, TNF, NFKBIA, and IFNG, and the key pathways are pathways in cancer, hypoxia-inducible factor-1 (HIF-1) signaling pathway, interleukin (IL)-17 signaling pathway, Chagas disease (American trypanosomiasis), and relaxin signaling pathway. The core targets of plantain for hyperuricemia are RELA, MAPK1, NFKBIA, CASP3, CASP8, and TNF, and the main pathways are pathways in cancer, apoptosis, hepatitis B, IL-17 signaling pathway, and toxoplasmosis. Conclusion. This study explored the related targets and mechanisms of plantain for the treatment of gout and hyperuricemia from the perspective of network pharmacological analysis, reflecting the characteristics of multiple components, multiple targets, and multiple pathways, and it provides a good theoretical basis for the clinical application of plantain

Characterization, Stability and Antioxidant Activity of Vanilla Nano-Emulsion and Its Complex Essential Oil

As a natural flavoring agent, vanilla essential oil has a special aroma and flavor, but its volatility and instability limit its value. Therefore, in this study, vanilla essential oil was compounded with cinnamon essential oil to prepare nano-emulsions (composite nano-emulsions called C/VT and C/VM), and the stability of the composite essential oil emulsions was investigated. Transmission electron microscopy (TEM) images showed that the nano-emulsions were spherical in shape and some flocs were observed in C/VM and C/VT. The results showed that the average droplet sizes of C/VM and C/VT increased only by 14.99% and 15.01% after heating at 100 °C for 20 min, and the average droplet sizes were less than 120 nm after 24 days of storage at 25 °C. Possibly due to the presence of reticulated flocs, which have a hindering effect on the movement of individual droplets, the instability indices of C/VM and C/VT were reduced by 34.9% and 39.08%, respectively, in comparison to the instability indices of C/VM and C/VT. In addition, the results of antioxidant experimental studies showed that the presence of composite essential oil flocs had no significant effect on the antioxidant capacity. These results indicate that the improved stability of the composite essential oil nano-emulsions is conducive to broadening the application of vanilla essential oil emulsions

Prediction Model of Hemorrhage Transformation in Patient with Acute Ischemic Stroke Based on Multiparametric MRI Radiomics and Machine Learning

Intravenous thrombolysis is the most commonly used drug therapy for patients with acute ischemic stroke, which is often accompanied by complications of intracerebral hemorrhage transformation (HT). This study proposed to build a reliable model for pretreatment prediction of HT. Specifically, 5400 radiomics features were extracted from 20 regions of interest (ROIs) of multiparametric MRI images of 71 patients. Furthermore, a minimal set of all-relevant features were selected by LASSO from all ROIs and used to build a radiomics model through the random forest (RF). To explore the significance of normal ROIs, we built a model only based on abnormal ROIs. In addition, a model combining clinical factors and radiomics features was further built. Finally, the models were tested on an independent validation cohort. The radiomics model with 14 All-ROIs features achieved pretreatment prediction of HT (AUC = 0.871, accuracy = 0.848), which significantly outperformed the model with only 14 Abnormal-ROIs features (AUC = 0.831, accuracy = 0.818). Besides, combining clinical factors with radiomics features further benefited the prediction performance (AUC = 0.911, accuracy = 0.894). So, we think that the combined model can greatly assist doctors in diagnosis. Furthermore, we find that even if there were no lesions in the normal ROIs, they also provide characteristic information for the prediction of HT

Research progress on the role of endoplasmic reticulum stress in osteoarthritis

Osteoarthritis is a common degenerative disease in which endoplasmic reticulum stress(ER stress) plays an important role in the pathogenesis of chondrocyte apoptosis. To limit the adverse effects of endoplasmic reticulum stress, cells activate the unfolded protein response (UPR). However, when endoplasmic reticulum stress persists beyond the maximum tolerance of UPR, cells may trigger endoplasmic reticulum dysfunction through three pathways of UPR leading to chondrocyte apoptosis