Exploration on pharmacological mechanisms of YZP against neuropathic pain via inhibiting spinal inflammation and the rationality of its compatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Yuanhu Zhitong Prescription (YZP) is a well-known traditional Chinese medicine (TCM) formula for neuropathic pain (NP) therapy with a satisfying clinical efficacy. However, the underlying pharmacological mechanism and its compatibility principle remain unclear. AIM OF THE STUDY: This study aims to investigate the analgesic and compatibility mechanisms of YZP on neuropathic pain (NP) at the gene and biological process levels. MATERIALS AND METHODS: The chronic constriction injury (CCI) rats were intragastrically administrated with extracts of YZP, YH and BZ separately, and then mechanical hypersensitivity were measured to evaluate the analgesic effects between YH and BZ before and after compatibility. Then, RNA-seq and bioinformatics analyses were performed to elucidate the potential mechanisms underlying YZP's analgesia and compatibility. Finally, the expression levels and significant differences of key genes were analyzed. RESULTS: Behaviorally, both YZP and YH effectively alleviated mechanical allodynia in CCI rats, with YZP being superior to YH. In contrast, we did not observe an analgesic effect of BZ. Genetically, YZP, YH, and BZ reversed the expression levels of 52, 34, and 42 aberrant genes in the spinal cord of CCI rats, respectively. Mechanically, YZP was revealed to alleviate NP mainly by modulating the inflammatory response and neuropeptide signaling pathway, which are the dominant effective processes of YH. Interestingly, the effective targets of YZP were especially enriched in leukocyte activation and cytokine-mediated signaling pathways. Moreover, BZ was found to exert an adjunctive effect in enhancing the analgesic effect of YH by promoting skeletal muscle tissue regeneration and modulating calcium ion transport. CONCLUSIONS: YH, as the monarch drug, plays a dominant role in the analgesic effect of YZP that effectively relieves NP by inhibiting the spinal inflammation and neuropeptide signaling pathway. BZ, as the minister drug, not only synergistically enhances analgesic processes of YH but also helps to alleviate the accompanying symptoms of NP. Consequently, YZP exerted a more potent analgesic effect than YH and BZ alone. In conclusion, our findings offer new insights into understanding the pharmacological mechanism and compatibility principle of YZP, which may support its clinical application in NP therapy.

Serum metabolomics analyses reveal biomarkers of osteoporosis and the mechanism of Quanduzhong capsules.

With the aging of the population, the prevalence of osteoporosis (OP) is rising rapidly, making it an important public health concern. Early screening and effective treatment of OP are the primary challenges facing the management of OP today. Quanduzhong capsule (QDZ) is a single preparation composed of Eucommia ulmoides Oliv., which is included in the Pharmacopoeia of the People's Republic of China. It is used to treat OP in clinical practice, but its mechanisms are unclear. This study involved 30 patients with OP, 30 healthy controls (HC), and 28 OP patients treated with QDZ to identify potential biomarkers for the early diagnosis of OP and to investigate the potential mechanism of QDZ in treating OP. The serum samples were analyzed using targeted amino acid metabolomics. Significant differences in amino acid metabolism were identified between the OP cohort and the HC group, as well as between OP patients before and after QDZ treatment. Compared with HC, the serum levels of 14 amino acids in OP patients changed significantly. Kynurenine, arginine, citrulline, methionine, and their combinations are expected to be potential biomarkers for OP diagnosis. Notably, QDZ reversed the changes in levels of 10 amino acids in the serum of OP patients and significantly impacted numerous metabolic pathways during the treatment of OP. This study focuses on screening potential biomarkers for the early detection of OP, which offers a new insight into the mechanism study of QDZ in treating OP.

Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery.

Recent advancements in modern science have provided robust tools for drug discovery. The rapid development of transcriptome sequencing technologies has given rise to single-cell transcriptomics and single-nucleus transcriptomics, increasing the accuracy of sequencing and accelerating the drug discovery process. With the evolution of single-cell transcriptomics, spatial transcriptomics (ST) technology has emerged as a derivative approach. Spatial transcriptomics has emerged as a hot topic in the field of omics research in recent years; it not only provides information on gene expression levels but also offers spatial information on gene expression. This technology has shown tremendous potential in research on disease understanding and drug discovery. In this article, we introduce the analytical strategies of spatial transcriptomics and review its applications in novel target discovery and drug mechanism unravelling. Moreover, we discuss the current challenges and issues in this research field that need to be addressed. In conclusion, spatial transcriptomics offers a new perspective for drug discovery.

[Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine].

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

A Multi-Modal Classification Method for Early Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease Using Three Paradigms With Various Task Difficulties.

Alzheimer's Disease (AD) accounts for the majority of dementia, and Mild Cognitive Impairment (MCI) is the early stage of AD. Early and accurate diagnosis of dementia plays a vital role in more targeted treatments and effectively halting disease progression. However, the clinical diagnosis of dementia requires various examinations, which are expensive and require a high level of expertise from the doctor. In this paper, we proposed a classification method based on multi-modal data including Electroencephalogram (EEG), eye tracking and behavioral data for early diagnosis of AD and MCI. Paradigms with various task difficulties were used to identify different severity of dementia: eye movement task and resting-state EEG tasks were used to detect AD, while eye movement task and delayed match-to-sample task were used to detect MCI. Besides, the effects of different features were compared and suitable EEG channels were selected for the detection. Furthermore, we proposed a data augmentation method to enlarge the dataset, designed an extra ERPNet feature extract layer to extract multi-modal features and used domain-adversarial neural network to improve the performance of MCI diagnosis. We achieved an average accuracy of 88.81% for MCI diagnosis and 100% for AD diagnosis. The results of this paper suggest that our classification method can provide a feasible and affordable way to diagnose dementia.

Characteristics of Damage to Brown Rice Kernels under Single and Continuous Mechanical Compression Conditions.

During the rice milling process, single and continuous compression occurs between brown rice and the processing parts. When the external load exceeds the yield limit of brown rice, brown rice kernels are damaged; with an increase in compression deformation or the extent of compression, the amount of damage to the kernels expands and accumulates, ultimately leading to the fracture and breakage of kernels. In order to investigate the mechanical compression damage characteristics of brown rice kernels under real-world working conditions, this study constructs an elastic-plastic compression model and a continuous damage model of brown rice kernels based on Hertz theory and continuous damage theory; the accuracy of this model is verified through experiments, and the relevant processing critical parameters are calculated. In this study, three varieties of brown rice kernels are taken as the research object, and mechanical compression tests are carried out using a texture apparatus; finally, the test data are analysed and calculated by combining them with the theoretical model to obtain the relevant critical parameters of damage. The results of the single compression crushing test of brown rice kernels showed that the maximum destructive forces Fc in the single compression of Hunan Early indica 45, Hunan Glutinous 28, and Southern Japonica 518 kernels were 134.77 ± 11.20 N, 115.64 ± 4.35 N, and 115.84 ± 5.89 N, respectively; the maximum crushing deformations αc in the single compression crushing test were 0.51 ± 0.04 mm, 0.43 ± 0.01 mm, and 0.48 ± 0.17 mm, respectively; and the critical average deformations αs of elasticity-plasticity deformation were 0.224 mm, 0.267 mm, and 0.280 mm, respectively. The results of the continuous compression crushing test of brown rice kernels showed that the critical deformations αd of successive compression damage formation were 0.224 mm, 0.267 mm, and 0.280 mm, and the deformation ratios δ of compression damage were 12.24%, 14.35%, and 12.84%. From the test results, it can be seen that the continuous application of compression load does not result in the crushing of kernels if the compression deformation is less than αd during mechanical compression. The continuous application of compressive loads can lead to fragmentation of the kernels if the compressive deformation exceeds αd; the larger the compression variant, the less compression is required for crushing. If the compression deformation exceeds αc, then a single compressive load can directly fragment the kernels. Therefore, the load employed during rice milling should be based on the variety of brown rice used in order to prevent brown rice deformation, which should be less than αd, and the maximum load should not exceed Fc. The results of this study provide a theoretical reference for the structure and parameter optimisation of a rice milling machine.

Scutellarin activates IDH1 to exert antitumor effects in hepatocellular carcinoma progression.

Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1-α-KG-HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.

Toxic effect and mechanism of ß-cypermethrin and its chiral isomers on HTR-8/SVneo cells.

Beta-cypermethrin (ß-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of ß-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17ß-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of ß-CYP and its specific isomers. Our results showed that ß-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 µM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and ß-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 µM 1R-trans-αS. Scratch assays revealed that ß-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor ß (ERß), ß-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of ß-CYP, its isomers, and E2 for PDE3A than for ERα or ERß. Consequently, ß-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2, and down-regulation of Myo7a and Pdgfrb, suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms.

Generation of sulfones utilizing ß-sulfinyl esters as masked aryl sulfinates under redox-neutral conditions.

A method for generation of SVI sulfones from ß-sulfinyl esters (SIV) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to excellent yields. The advantage of using ß-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the ß-sulfinyl ester. Successive ß-elimination/O-addition/sulfinate esterification/ß-elimination processes are proposed for the mechanism of generating SVI from SIV.

Proteomic study of left ventricle and cortex in rats after myocardial infarction.

Myocardial infarction (MI) induces neuroinflammation indirectly, chronic neuroinflammation may cause neurodegenerative diseases. Changes in the proteomics of heart and brain tissue after MI may shed new light on the mechanisms involved in neuroinflammation. This study explored brain and heart protein changes after MI with a data-independent acquisition (DIA) mode proteomics approach. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in the heart of rats, and the immunofluorescence of microglia in the brain cortex was performed at 1d, 3d, 5d, and 7d after MI to detect the neuroinflammation. Then proteomics was accomplished to obtain the vital proteins in the heart and brain post-MI. The results show that the number of microglia was significantly increased in the Model-1d group, the Model-3d group, the Model-5d group, and the Model-7d group compared to the Sham group. Various proteins were obtained through DIA proteomics. Linking to key targets of brain disease, 14 proteins were obtained in the brain cortex. Among them, elongation of very long chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) were verified through western blotting (WB). The results of WB were consistent with the proteomics results. Therefore, these proteins may be related to the pathogenesis of neuroinflammation after MI.

The Application of Textile Materials in Interfacial Solar Steam Generation for Water Purification and Desalination.

The global increase in population, the phenomenon of climate change, the issue of water pollution and contamination, and the inadequate management of water resources all exert heightened strain on freshwater reserves. The potential utilization of the interfacial solar steam generation (ISSG) system, which utilizes photothermal conversion to generate heat on material surfaces for wastewater purification and desalination purposes, has been successfully demonstrated. Textile-material-based ISSG devices, including (woven, nonwoven, and knitted) fabrics and electrospinning membranes, exhibit distinct properties such as a rough surface texture, high porosity, significant surface area, exceptional flexibility, and robust mechanical strength. These characteristics, combined with their affordability, accessibility, and economic viability for widespread implementation, make them extremely attractive for applications in SSG. In this review, a comprehensive analysis of the emerging concepts, advancements, and applications of textile materials, such as woven, nonwoven, and knitted fabrics and electrospun membranes, in ISSG for wastewater purification and desalination is presented. We also emphasize significant obstacles and potential prospects in both theoretical investigations and real-world implementations, aiming to contribute to future advancements in the domain of textile-material-based interfacial evaporation in wastewater purification and desalination. Furthermore, the drawbacks and the challenges of ISSG systems are also highlighted.

Meta-analytic and MaxEnt model prediction, the distribution of the Bactrocera minax (Diptera: Tephritidae), in China under changing climate.

The Tephritidae family causes damage to fruits in tropical and subtropical regions around the world, with Bactrocera minax Enderlein (Diptera: Tephritidae) widely distributed in China, causing severe economic damage to Chinese citrus. Currently, preventing the rapid spread of B. minax remains an effective strategy to control it as the climate continues to warm in the future. In this context, it is crucial to understand the potential geographic range of B. minax under climate change. We used meta-analysis to assess the survival of Tephritidae insects under temperature stress. We also used the maximum entropy (MaxEnt) model to predict the suitable regions and migration trajectories of B. minax in China under current and future climatic conditions. Through comprehensive analysis of the experimental data, we found that the survival rate of Tephritidae insects in the suitable temperature range showed an increasing trend with the increase in warming extent. Using the MaxEnt model, we observed that the highly suitable area, as well as the moderately suitable area of B. minax, were expanding in all 3 future climate scenarios, with the distribution moving toward the high latitude region and the coastal region of China. Our results also indicate that temperature and precipitation contribute more to the model in the current year. Combining multiexperiment data, our study demonstrates that the potential distribution of B. minax in China will expand under future climate warming scenarios, and these predictions will provide important information for monitoring B. minax and informing managers in developing control strategies.

Targeted arginine metabolomics combined with metagenomics revealed the potential mechanism of Pueraria lobata extract in treating myocardial infarction.

The extraction methods for traditional Chinese medicine (TCM) may have varying therapeutic effects on diseases. Currently, Pueraria lobata (PL) is mostly extracted with ethanol, but decoction, as a TCM extraction method, is not widely adopted. In this study, we present a strategy that integrates targeted metabolomics, 16 s rDNA sequencing technology and metagenomics for exploring the potential mechanism of the water extract of PL (PLE) in treating myocardial infarction (MI). Using advanced analytical techniques like ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we comprehensively characterized PLE's chemical composition. Further, we tested its efficacy in a rat model of MI induced by ligation of the left anterior descending branch of the coronary artery (LAD). We assessed cardiac enzyme levels and conducted echocardiograms. UPLC-MS/MS was used to compare amino acid differences in serum. Furthermore, we investigated fecal samples using 16S rDNA sequencing and metagenomic sequencing to study intestinal flora diversity and function. This study demonstrated PLE's effectiveness in reducing cardiac injury in LAD-ligated rats. Amino acid metabolomics revealed significant improvements in serum levels of arginine, citrulline, proline, ornithine, creatine, creatinine, and sarcosine in MI rats, which are key compounds in the arginine metabolism pathway. Enzyme-linked immunosorbent assay (ELISA) results showed that PLE significantly improved arginase (Arg), nitric oxide synthase (NOS), and creatine kinase (CK) contents in the liver tissue of MI rats. 16 s rDNA and metagenome sequencing revealed that PLE significantly improved intestinal flora imbalance in MI rats, particularly in taxa such as Tuzzerella, Desulfovibrio, Fournierella, Oscillibater, Harryflintia, and Holdemania. PLE also improved the arginine metabolic pathway in the intestinal microorganisms of MI rats. The findings indicate that PLE effectively modulates MI-induced arginine levels and restores intestinal flora balance. This study, the first to explore the mechanism of action of PLE in MI treatment considering amino acid metabolism and intestinal flora, expands our understanding of the potential of PL in MI treatment. It offers fresh insights into the mechanisms of PL, guiding further research and development of PL-based medicines.

[Mechanism of Xinshubao Tablets in exerting anti-inflammatory, vasodilation, and cardioprotective effects based on network pharmacology].

This study aims to explore the anti-inflammatory, vasodilation, and cardioprotective effects of the intestinal absorption liquids containing Xinshubao Tablets or single herbs, and to elucidate the potential mechanism based on network pharmacology. Western blot was then conducted to validate the expression changes of core proteins. Lipopolysaccharide(LPS)-stimulated RAW264.7 cells were used to observe the anti-inflammatory effect. The vasodilation activity was examined by the microvessel relaxation assay in vitro. Oxygen-glucose deprivation(OGD)-induced H9c2 cells were used to investigate the cardioprotective effect. The chemical components were retrieved from Herb databases and composition of Xinshubao Tablets drug-containing intestinal absorption solution. Drug targets were retrieved from SwissTargetPrediction databases. GeneCards was searched for the targets associated with the anti-inflammatory, vasodilation, and cardioprotective effects. The common targets shared by the drug and the effects were used to establish the protein-protein interaction(PPI) network, from which the core targets were obtained. Finally, the core targets were imported into Cytoscape 3.9.1 for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses. The anti-inflammatory experiment showed that both Xinshubao Tablets and the single herbs constituting this formula had anti-inflammatory effects. Curcumae Radix had the strongest inhibitory effect on the production of tumor necrosis factor-α(TNF-α), and Salviae Miltiorrhizae Radix et Rhizoma had the strongest inhibitory effect on the generation of interleukin-6(IL-6). Xinshubao Tablets, Curcumae Radix, and Crataegi Fructus had vasodilation effect, and Crataegi Fructus had the strongest effect. Xinshubao Tablets, Salviae Miltiorrhizae Radix et Rhizoma, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, and Paeoniae Radix Alba had cardioprotective effects, and Salviae Miltiorrhizae Radix et Rhizoma had the strongest cardioprotective effect. Network pharmacology results demonstrated that except the whole formula, Salviae Miltiorrhizae Radix et Rhizoma had the most components with anti-inflammatory effect, and Curcumae Radix had the most components with vasodilation and cardioprotective effects, followed by Salviae Miltiorrhizae Radix et Rhizoma. The nitric oxide synthase 3(NOS3) was predicted as the core target for the anti-inflammatory, vasodilation, and cardioprotective effects. Western blot results showed that Xinshubao Tablets significantly up-regulated the expression of NOS3 in OGD-induced H9c2 cells. GO enrichment analysis showed that the effects were mainly related to lipid exported from cell, regulation of blood pressure, and inflammatory response. KEGG pathway enrichment predicted AGE-RAGE and HIF-1 signaling pathways as the key pathways.

Removal of Cr(VI) from aqueous solution using ball mill modified biochar: multivariate modeling, optimization and experimental study.

Chromium (Cr(VI)) pollution has attracted wide attention due to its high toxicity and carcinogenicity. Modified biochar has been widely used in the removal of Cr(VI) in water as an efficient and green adsorbent. However, the existing biochar prepared by chemical modification is usually complicated in process, high in cost, and has secondary pollution, which limits its application. It is urgent to explore modified biochar with simple process, low cost and environmental friendliness. Therefore, ball milling wheat straw biochar (BM-WB) was prepared by ball milling technology in this paper. The adsorption characteristics and mechanism of Cr(VI) removal by BM-WB were analyzed by functional group characterization, adsorption model and response surface method. The results showed that ball milling effectively reduced the particle size of biochar, increased the specific surface area, and more importantly, enhanced the content of oxygen-containing functional groups on the surface of biochar. After ball milling, the adsorption capacity of Cr(VI) increased by 3.5-9.1 times, and the adsorption capacity reached 52.21 mg/g. The adsorption behavior of Cr(VI) follows the pseudo-second-order kinetics and Langmuir isotherm adsorption model rate. Moreover, the Cr(VI) adsorption process of BM-WB is endothermic and spontaneous. Under the optimized conditions of pH 2, temperature 45 °C, and adsorbent dosage 0.1 g, the removal rate of Cr(VI) in the solution can reach 100%. The mechanism of Cr(VI) adsorption by BM-WB is mainly based on electrostatic attraction, redox and complexation. Therefore, ball milled biochar is a cheap, simple and efficient Cr(VI) removal material, which has a good application prospect in the field of remediation of Cr(VI) pollution in water.

Transcriptomics and Metabolomics Unveil the Neuroprotection Mechanism of AnGong NiuHuang (AGNH) Pill Against Ischaemic Stroke Injury.

As a famous prescription in China, AnGong NiuHuang (AGNH) pill exerts good neuroprotection for ischaemic stroke (IS), but its mechanism is still unclear. In this study, the neuroprotection of AGNH was evaluated in the rat IS model which were established with the surgery of middle cerebral artery occlusion (MCAO), and the potential mechanism was elucidated by transcriptomic analysis and metabolomic analysis. AGNH treatment obviously decreased the infarct volume and Zea-Longa 5-point neurological deficit scores, improved the survival percentage of rats, regional cerebral blood flow (rCBF), and rat activity distance and activity time. Transcriptomics showed that AGNH exerted its anti-inflammatory effects by affecting the regulatory network including Tyrobp, Syk, Tlr2, Myd88 and Ccl2 as the core. Integrating transcriptomics and metabolomics identified 8 key metabolites regulated by AGNH, including L-histidine, L-serine, L-alanine, fumaric acid, malic acid, and N-(L-arginino) succinate, 1-pyrroline-4-hydroxy-2-carboxylate and 1-methylhistamine in the rats with IS. Additionally, AGNH obviously reduced Tyrobp, Syk, Tlr2, Myd88 and Ccl2 at both the mRNA and protein levels, decreased IL-1ß, KC-GRO, IL-13, TNF-α, cleaved caspase 3 and p65 nucleus translocation, but increased IκBα expression. Network pharmacology analysis showed that quercetin, beta-sitosterol, baicalein, naringenin, acacetin, berberine and palmatine may play an important role in protecting against IS. Taken together, this study reveals that AGNH reduced neuroinflammation and protected against IS by inhibiting Tyrobp/Syk and Tlr2/Myd88, as well as NF-κB signalling pathway and regulating multiple metabolites.

Sustainable development of environmental protection talents training: Research on the behavior decision of government, university and enterprise under the background of evolutionary game.

Environmental protection talents training (EPTT) is recognized as a key prerequisite for maintaining environmental sustainability, and in order to study the influence of each player on EPTT. This paper innovatively constructs a tripartite evolutionary game model of government, university and enterprise. The equilibrium points and evolutionary stabilization strategies of each participant are solved by replicating the dynamic equations, and the behaviors of each subject in EPTT are analyzed so as to clarify the behavioral characteristics and optimal strategies of the government's participation in EPTT. The results show that enterprises occupy a more important position in influencing government decisions. The government should reduce the financial incentives for enterprises and replace them with greater policy support. Meanwhile, the government should actively promote the cultivation mechanism that integrates universities and enterprises. The results of the study can provide a decision-making basis for the government to promote the sustainable development of EPTT.

Xinshubao tablet rescues cognitive dysfunction in a mouse model of vascular dementia: Involvement of neurogenesis and neuroinflammation.

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.

Severe disseminated Nocardia brasiliensis pneumonia with normal immune function: A case report.

RATIONALE: Members of the genus Nocardia brasiliensis are Gram-positive, aerobic bacteria and exist ubiquitously in most environments. In recent years, the incidence of Nocardia brasiliensis has increased significantly and become a global concern. It may be predominantly caused pulmonary infections in immunocompromised hosts. Interestingly, however, we found that it can be present not only on immunocompromised hosts, but also to infect patients with a normal immune system. PATIENT CONCERNS: We report a very rare case of a 49-year-old immunocompetent man with disseminated Nocardia brasensis pneumonia. He had a fever for 14 days (maximum temperature about 38°C) and a history of mass rupture. DIAGNOSES: Severe Disseminated Nocardia brasiliensis pneumonia with normal immune function. INTERVENTIONS: No. OUTCOMES: The patient was finally diagnosed with Severe Disseminated Nocardia brasiliensis pneumonia and received compound sulfamethoxazole treatment for 4 months. LESSONS SUBSECTIONS: Our report highlights when cold pus appears in soft tissues such as the lower limbs, neck, nose, scalp, etc, should prompt timely evaluation and biopsy for definitive diagnosis. Be alert to a normally immunocompetent, disseminated Nocardia brasiliensis infection. Early recognition and effective treatment are necessary conditions for successful results. This would allow for better disease prognostication while enabling physicians to develop more effective treatment strategies.

Multiphoton emission of single CdZnSe/ZnS quantum dots coupled with plasmonic Au nanoparticles.

The fluorescence blinking and low multiphoton emission of quantum dots (QDs) have limited their application in lasing, light-emitting diodes, and so on. Coupling of single QDs to plasmonic nanostructures is an effective approach to control the photon properties. Here plasmon-exciton systems including Au nanoparticles and CdZnSe/ZnS QDs were investigated at the single particle level. With the modulation of the local electromagnetic field, the fluorescence intensity of single QDs is increased, accompanied by a significant suppression in blinking behavior, and the lifetime is shortened from 15 ns to 2 ns. Moreover, the second-order photon intensity correlation at zero lag time g2(0) of coupled single QDs is larger than 0.5, indicating an increased probability of multiphoton emission. The enhancement factors of radiative and nonradiative decay rates of QDs coupled with Au nanoparticles are calculated. The sharply increased radiative decay rate can be comparable to the nonradiative Auger rate, leading to dominated multiple exciton radiative recombination with PL intensity enhancement, suppressed blinking, lifetime shortening, and multiphoton emission. The results of the exciton decay dynamics and emission properties of single QDs in this work are helpful in exploring the mechanism of plasmon-exciton interaction and optoelectronic application of single QDs.