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Cerebral ischemia-reperfusion injury (CI/RI) is a leading cause of disability and mortality worldwide, with limited therapeutic options available. Erianin, a natural compound derived from traditional Chinese medicine, has been reported to possess anti-inflammatory and neuroprotective properties. This study aimed to investigate the therapeutic potential of Erianin in CI/RI and elucidate its underlying mechanisms. Network pharmacology analysis predicted that Erianin could target the PI3K/AKT pathway, which are closely associated with CI/RI. In vivo experiments using a rat model of CI/RI demonstrated that Erianin treatment significantly alleviated neurological deficits, reduced infarct volume, and attenuated neuronal damage. Mechanistically, Erianin inhibited microglial cell polarization towards the pro-inflammatory M1 phenotype, as evidenced by the modulation of specific markers. Furthermore, Erianin suppressed the expression of pro-inflammatory cytokines and mediators, such as TNF-α, IL-6, and COX-2, while enhancing the production of anti-inflammatory factors, including Arg1, CD206, IL-4 and IL-10. In vitro studies using oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated microglial cells corroborated the anti-inflammatory and anti-apoptotic effects of Erianin. Notably, Erianin inhibited the NF-κB signaling pathway by inhibiting p65 phosphorylation and preventing the nuclear translocation of the p65 subunit. Collectively, these findings suggest that Erianin represents a promising therapeutic candidate for CI/RI by targeting microglial cell polarization and inflammation.
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Glioma cancer is the primary cause of cancer-related fatalities globally for both men and women. Traditional chemotherapy treatments for this condition frequently result in reduced efficacy and significant adverse effects. This investigation developed a new drug delivery system for the chemotherapeutic drug temozolomide (TMZ) using pH-sensitive drug delivery zeolitic imidazolate frameworks (ZIF-8). These nanoplatforms demonstrate excellent biocompatibility and hold potential for cancer therapy. Utilizing the favorable reaction milieu offered by ZIFs, a 'one-pot method' was employed for the fabrication and loading of drugs, leading to a good capacity for loading. TMZ@TA@ZIF-8 NPs exhibit a notable response to an acidic milieu, resulting in an enhanced drug release pattern characterized by a controlled release outcome. The effectiveness of TMZ@TA@ZIF-8 NPs in inhibiting the migration and invasion of U251 glioma cancer cells, as well as promoting apoptosis, was confirmed through various tests, including MTT (3-(4,5)-dimethylthiahiazo(-z-y1)) assay, DAPI/PI dual staining, and cell scratch assay. The biochemical fluorescent staining assays showed that TMZ@TA@ZIF-8 NPs potentially improved ROS, reduced MMP, and triggered apoptosis in U251 cells. In U251 cells treated with NPs, the p53, Bax, Cyt-C, caspase-3, -8, and -9 expressions were significantly enhanced, while Bcl-2 expression was diminished. These outcomes show the potential of TMZ@TA@ZIF-8 NPs as a therapeutic agent with anti-glioma properties. Overall, the pH-responsive drug delivery systems we fabricated using TMZ@TA@ZIF-8 NPs show great potential for cancer treatment. This approach has the potential to make significant contributions to the improvement of cancer therapy by overcoming the problems associated with TMZ-based treatments.
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BACKGROUND: Trigeminal neuralgia is a difficult clinical situation marked by excruciating pain that requires efficient postoperative measures. In patients with trigeminal neuralgia, this study sought to investigate the effects of ongoing rehabilitation intervention on postoperative outcomes, including psychological state, pain, and complications. The aim was to provide new perspectives and treatment strategies for the management of this crippling illness. NEW METHOD: Between January 2021 and December 2022, 120 patients receiving treatment for trigeminal neuralgia were randomized to either the observation or control groups. The observation group received a continuous and comprehensive rehabilitation intervention that included elements of the control group's regimen, while the control group received standard health education and dietary guidance interventions through the use of a digital table method. The assessment of pain scales (VAS), self-rating depression scales (SDS), self-rating anxiety scales (SAS), and complication rates were all part of the postoperative follow-up. RESULTS: At seven days following surgery, there were no appreciable variations in the observation and control groups' VAS, SAS, and SDS scores (P > 0.05). Nevertheless, the observation group showed significantly lower VAS and SAS scores than the control group at 6 months and 1 year following surgery (P < 0.05). The observation group's SDS score was significantly lower than the control group's one year after surgery (P < 0.001). In comparison to the control group, the observation group also showed a lower overall complication rate (P < 0.05), especially in the cases of facial herpes and vertigo. COMPARISON WITH EXISTING METHODS: Our ongoing, all-encompassing rehabilitation approach demonstrated better results than current approaches in terms of long-lasting pain alleviation, enhanced mental health, and lower rates of complications in patients with trigeminal neuralgia following surgery. This implies that, in comparison to traditional methods, incorporating rehabilitation strategies may provide greater therapeutic benefits. CONCLUSION: Continuous comprehensive rehabilitation intervention can effectively reduce the degree of postoperative pain in patients with trigeminal neuralgia, help to regulate their psychological state, and reduce the occurrence of complications, which has certain clinical application value.
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Reabilitação Neurológica , Neuralgia do Trigêmeo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Depressão/etiologia , Reabilitação Neurológica/métodos , Medição da Dor/métodos , Dor Pós-Operatória/reabilitação , Dor Pós-Operatória/psicologia , Dor Pós-Operatória/etiologia , Complicações Pós-Operatórias/reabilitação , Resultado do Tratamento , Neuralgia do Trigêmeo/cirurgia , Neuralgia do Trigêmeo/reabilitaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: A herbal formula Tong-Xie-Yao-Fang (TXYF) is traditionally used to treat irritable bowel syndrome (IBS), modern pharmacological evidence supports that the formula efficacy is associated with altered gut microbiota. Yet, the mechanistic role of gut microbiota in the therapy of TXYF remains unclear. We previously clarified that gut microbiota-dysregulated bile acid (BA) metabolism contribute to the pathogenesis of IBS, deriving a hypothesis that microbiota-BA metabolic axis might be a potential target of TXYF. AIM OF THE STUDY: We aim to investigate a new gut microbiota-mediated mechanism underlying anti-IBS efficacy of TXYF. MATERIALS AND METHODS: We established an IBS rat model with a combination of stressors, compared the herbal efficacy in models undergone gut bacterial manipulations, also examined BA metabolism-related microbiota, metabolites, genes and proteins by 16S rRNA gene sequencing, targeted metabolomics, qPCR and multiplex immunofluorescence staining. RESULTS: We observed that TXYF attenuated visceral hyperalgesia and diarrhea in IBS rats but not in those underwent gut bacteria depletion. Transferring gut microbiota from TXYF-treated donors also decreased visceral sensitivity and slightly relief diarrhea-like behaviors in IBS recipient rats. Fecal 16S rRNA gene sequencing revealed that TXYF modulated microbial ß-diversity and taxonomic structure of IBS rats, with a significant increase in relative abundance of bile salt hydrolase (BSH)-expressing Bacteroidaceae. qPCR and culturing data validated that TXYF had a promotive effect on the growth and BSH activity of Bacteroides species. TXYF-reshaped microbiota upregulated the expression of intestinal Fgf15, a feedback signal to control BA synthesis in the liver. As a result, the BA synthetic and excretory levels in IBS rats were decreased by TXYF, so as that colonic BA membrane receptor Tgr5 sensing and its mediated Calcitonin gene-related peptide (Cgrp)-positive neuronal response were attenuated. CONCLUSION: This study poses a new microbiota-driven therapeutic action for TXYF, highlighting the potential of developing new anti-IBS strategies from the herbal formula targeting BSH-expressing gut bacteria.
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Amidoidrolases , Ácidos e Sais Biliares , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Ratos Sprague-Dawley , Animais , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Amidoidrolases/metabolismo , Ratos , Modelos Animais de Doenças , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Additive manufacturing (AM) has attracted many attentions because of its design freedom and rapid manufacturing; however, it is still limited in actual application due to the existing defects. In particular, various defect features have been proved to affect the fatigue performance of components and lead to fatigue scatter. In order to properly assess the influences of these defect features, a defect driven physics-informed neural network (PiNN) is developed. By embedding the critical defects information into loss functions, the defect driven PiNN is enhanced to capture physical information during training progress. The results of fatigue life prediction for different AM materials show that the proposed PiNN effectively improves the generalization ability under small samples condition. Compared with the fracture mechanics-based PiNN, the proposed PiNN provides physically consistent and higher accuracy without depending on the choice of fracture mechanics-based model. Moreover, this work provides a scalable framework being able to integrate more prior knowledge into the proposed PiNN. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.
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The thermocapillary flow instabilities of silicon melt in a cylindrical pool with a rotating disk on the free surface (a simplified model of the Czochralski crystal growth) are numerically investigated by using the linear stability analysis. The complete neutral or critical stability curves are determined. Results show that the neutral stability curves form a closed region in the parameter plane, in which the steady axisymmetric flow is linearly stable. Two types of rotating wave (RW1 and RW2) instabilities and two types of hydrothermal wave (HTW1 and HTW2) instabilities are found. The energy analysis shows that all the instabilities are hydrodynamic (inertial) in nature. Specifically, RW1 and RW2 are caused by the azimuthal shear induced by the crystal rotation, while HTW1 and HTW2 are caused by the radial shear induced by the thermocapillary force.
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The instabilities of the steady axisymmetric thermocapillary-buoyancy flow in a rotating annular pool were investigated by linear stability analysis. The critical instability parameters for the thermocapillary-buoyancy flow (normal gravity) and the pure thermocapillary flow (microgravity) were compared under different pool depths and rotation rates. The results show that the thermocapillary-buoyancy flow is more stable than the pure thermocapillary flow due to the stabilizing effect of the gravity (buoyancy) force. Two types of oscillatory instabilities were observed depending on the different rotation rates, and the propagation direction of the hydrothermal wave is also affected by the rotation rate.
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The discrepancy of indoleamine 2, 3-dioxygenase 1 (IDO1) function in atherosclerosis has been noted. Compared to the protective effect of IDO1 against established atherogenesis, the role of IDO1 in the developmental process of atherosclerosis is still unclear. Here, the expression patterns and activities of IDO1 and its isoenzyme tryptophan 2,3-dioxygenase (TDO) in aortas and blood samples of patients with atherosclerosis were investigated. IDO1 and TDO were colocalized with CD3-positive lymphocytes and CD68-positive macrophages in atherosclerotic lesions. The expression and activity of IDO1 and TDO increased with the grade of the histological classification in early atherosclerosis (grade I, II), but the increase did not continue in advanced atherosclerosis (grade III). Treatment of THP-1 macrophages (THP-M) with oxidized low-density lipoprotein (oxLDL) induced the expression of IDO1 via the PI3K/Akt/NF-κB pathway, indicating the potential function of IDO1 in foam cells. Before and after treatment with oxLDL on THP-M, IFN-γ-induced IDO1 exhibited different degrees of promotion on foaming, inflammatory factor production and cell apoptosis. Finally, we found that the IDO1 inhibitor 1-methyl-tryptophan could elevate the high-density lipoprotein cholesterol level in serum and reduce the area of the aortic atherosclerotic lesions in high-fat diet-fed ApoE-/- mice. Our study indicated that IDO1 played a complicated and unfixed role in the entire process of atherogenesis, despite the atheroprotective role in established atherosclerosis. IDO1 also had proatherosclerotic functions in the developmental stages of atherosclerosis. Modulation of IDO1 could be a good method for alleviating atherosclerosis.
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BACKGROUND: Over-expression and over-activation of immunosuppressive enzyme indoleamine 2, 3 -dioxygenase 1 (IDO1) is a key mechanism of cancer immune escape. However, the regulation of IDO1 has not been fully studied. The relation between hydrogen sulfide (H2S) and IDO1 is unclear. METHODS: The influences of endogenous and exogenous H2S on the expression of IDO1, iNOS and NF-κB and STAT3 signaling proteins were investigated using qPCR or western blot, and the production of nitric oxide (NO) was analyzed by nitrate/nitrite assay in Cse-/- mice and MCF-7 and SGC-7901 cells. The effect of H2S on IDO1 activity was investigated by HPLC and in-vitro enzymatic assay. The effect of H2S on tryptophan metabolism was tested by luciferase reporter assay in MCF-7 and SGC-7901 cells. The correlation between H2S-generating enzyme CSE and IDO1 was investigated by immunostaining and heatmaps analysis in clinical specimens and tissue arrays of hepatocellular carcinoma (HCC) patients. The immunotherapeutic effects of H2S on H22 HCC-bearing mice were investigated. RESULTS: Using Cse-/- mice, we found that H2S deficiency increased IDO1 expression and activity, stimulated NF-κB and STAT3 pathways and decreased the expression of NO-generating enzyme Inos. Using IDO1-expressing MCF-7 and SGC-7901 cells, we found that exogenous H2S inhibited IDO1 expression by blocking STAT3 and NF-κB pathways, and decreased IDO1 activity via H2S/NO crosstalk, and combinedly decreased the tryptophan metabolism. The negative correlation between H2S-generating enzyme CSE and IDO1 was further validated in clinical specimens and tissue arrays of HCC patients. Additionally, H2S donors effectively restricted the tumor development in H22 HCC-bearing mice via downregulating IDO1 expression, inducing T-effector cells and inhibiting MDSCs. CONCLUSIONS: Thus, H2S, as a novel negative regulator of IDO1, shows encouraging antitumor immunotherapeutic effects and represents a novel therapeutic target in cancer therapy.
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Carcinoma Hepatocelular/enzimologia , Sulfeto de Hidrogênio/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Neoplasias Hepáticas/enzimologia , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Imunoterapia/métodos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Células Tumorais CultivadasRESUMO
We developed a new sludge reduction HA-A/A-MCO (Hydrolysis-Acidogenosis-Anaerobic/Anoxic -Multistep Continuous Oxic tank) process, which has improved phosphate (P) and nitrogen (N) removal. Its biological treatment unit uses an A2/O P & N removal process with hydrolysis acidification, multistep continuous aeration, and continuous flow, coupled with sidestream P removal by draining out anaerobic P-bearing wastewater. The process has advanced synchronization of P and N removal and sludge reduction. The improved performance is closely associated with the population structure of P-accumulating organisms (PAOs). This study investigated the relationship between P removal performance and the population structure of PAOs. The results show that the average effluent P content of HA-A/A-MCO process was only 0.44 mg/L, when the influent P concentration was 8â¼12 mg/L. The effluent met the A standard set by GB18918-2002. PAOs were able to effectively release 1 mg of P and absorb 2.8 mg of P. The system removed P by draining out anaerobic P-rich wastewater, as P had been reduced in the aerobic absorption process. This reduced the need for excess P uptake ability of the PAOs. The bacterial pure culture method was applied to isolate 5 PAOs with typical P absorption and removel features. 16SrDNA amplification and sequence analysis revealed that Acinetobacter sp. and Lampropedia sp played dominant roles in anaerobic P-releasing process. Moreover, Devosia sp. and Bdellovibrio sp were the primary strains in the aerobic tank, and, they were the major stains for P absorption. Uncultured Bacterium and other uncultured strains were detected in the anoxic tank.
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Bactérias/metabolismo , Reatores Biológicos/microbiologia , Fósforo/isolamento & purificação , Esgotos/química , Acinetobacter/metabolismo , Aerobiose , Anaerobiose , Bactérias/isolamento & purificação , Bdellovibrio/metabolismo , DNA Bacteriano/genética , Desenho de Equipamento , Nitrogênio/metabolismo , Fosfatos/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Recommending news stories to users, based on their preferences, has long been a favourite domain for recommender systems research. Traditional systems strive to satisfy their user by tracing users' reading history and choosing the proper candidate news articles to recommend. However, most of news websites hardly require any user to register before reading news. Besides, the latent relations between news and microblog, the popularity of particular news, and the news organization are not addressed or solved efficiently in previous approaches. In order to solve these issues, we propose an effective personalized news recommendation method based on microblog user profile building and sub class popularity prediction, in which we propose a news organization method using hybrid classification and clustering, implement a sub class popularity prediction method, and construct user profile according to our actual situation. We had designed several experiments compared to the state-of-the-art approaches on a real world dataset, and the experimental results demonstrate that our system significantly improves the accuracy and diversity in mass text data.
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Meios de Comunicação , Internet , Modelos Teóricos , Algoritmos , HumanosRESUMO
In this study, we describe the quenching of electrochemiluminescence (ECL) of tris(2,2'-bipyridine)-ruthenium(II)(Ru(bpy)(3)(2+))/tri-n-propylamine(TPA) at pristine multiwall carbon nanotube (MWNT) modified glassy carbon (GC) electrode. Even though the faradic current of the Ru(bpy)(3)(2+)/TPA system and the oxidation of TPA obtained at pristine MWNT-modified GC electrode is enhanced compared with those at the bare GC electrode, the intensity of ECL produced at MWNT electrode is smaller than that at GC electrode. For testing the possible reason of quenching, a comparison of ECL behavior of Ru(bpy)(3)(2+)/TPA at pristine MWNT and acid-treated, heat-treated, and polyethylene glycol (PEG)-wrapped MWNT-modified GC electrode is studied. The results demonstrate that the oxygen-containing groups at the surface of MWNT and the intrinsic electron properties of MWNT are considered to be the major reason for the suppression of ECL. The comparison also demonstrates that this quenching is related to the distance between MWNT and Ru(bpy)(3)(2+)/TPA. Utilizing this essential quenching mechanism, a new signal-on DNA hybridization assay is proposed on the basis of the MWNT modified electrode, where single-stranded DNA (ssDNA) labeled with Ru(bpy)(3)(2+) derivatives probe (Ru-ssDNA) at the distal end is covalently attached onto the MWNT electrode. ECL signal is quenched where Ru-ssDNA is self-organized on the surface of MWNT electrode; however, the quenched ECL signal returns in case of the presence of complementary ssDNA. The developed approach for sequence-specific DNA detection has good selectivity, sensitivity, and signal-to-background ratio. Therefore, the quenching of the ECL of Ru(bpy)(3)(2+)/TPA system by the pristine MWNT can be an excellent platform for nucleic acid studies and molecular sensing.
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DNA/análise , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , Nanotubos de Carbono/química , Compostos de Piridínio/química , Rutênio/químicaRESUMO
There is great interest in utilization of silicon-containing nanostructures as anode materials for lithium-ion batteries but usually limited by manufacturing cost, their intrinsic low electric conductivity, and large volume changes during cycling. Here we present a facile process to fabricate graphene-wrapped silicon nanowires (GNS@Si NWs) directed by electrostatic self-assembly. The highly conductive and mechanical flexible graphene could partially accommodate the large volume change associated with the conversion reaction and also contributed to the enhanced electronic conductivity. The as-prepared GNS@Si NWs delivered a reversible capacity of 1648 mAh·g(-1) with an initial Coulombic efficiency as high as 80%. Moreover, capacity remained 1335 mAh·g(-1) after 80 cycles at a current of 200 mA·g(-1), showing significantly improved electrochemical performance in terms of rate capability and cycling performance.
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Bovine pancreatic trypsin inhibitor (BPTI) is a natural non-specific serine protease inhibitor and possesses the ability to inhibit trypsin, chymotrypsin, plasmin and plasma kallikrein. The expression of BPTI in Escherichia coli and other systems has been reported. However, the preparation of recombinant BPTI (rBPTI) with correct N-terminus in Pichia pastoris has not been successful. A previous study showed that the preBPTI with the prepro leader sequence of alpha mating factor (AMF) was not processed into natural BPTI in P. pastoris. Now, we introduce a new method to prepare rBPTI, which carries a natural N-terminal amino acid residue, Arg-Pro-Asp, in P. pastoris using human serum albumin signal peptide corresponding to the pre sequence. The concentration of rBPTI in an 80 l fermentor reached 900 mg/l. We also explored a rapid and simple purification protocol for rBPTI and the purity of rBPTI reached 95-98% as evaluated by SDS-PAGE analysis. The sequencing results showed that the sequence of N-terminal 15 amino acids of rBPTI was consistent with that of natural BPTI. The inhibitory activity of rBPTI against trypsin was the same as natural BPTI and its K(i) was 2.6+/-0.1 x 10(-9). The therapeutic effect of rBPTI on acute pancreatitis was identified in rats.