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Combined sewer overflows (CSOs) introduce microbial contaminants into the receiving water bodies, thereby posing risks to public health. This study systematically investigated the disinfection performance and mechanisms of the combined process of ultraviolet and peracetic acid (UV/PAA) in CSOs with selecting Escherichia coli (E. coli) as a target microbial contaminant. The UV/PAA process exhibited superior performance in inactivating E. coli in simulated CSOs compared with UV, PAA, and UV/H2O2 processes. Increasing the PAA dosage greatly enhanced the disinfection efficiency, while turbidity and organic matter hindered the inactivation performance. Singlet oxygen (1O2), hydroxyl (â¢OH) and organic radicals (ROâ¢) contributed to the inactivation of E. coli, with â¢OH and RO⢠playing the prominent role. Variations of intracellular reactive oxygen species, malondialdehyde, enzymes activities, DNA contents and biochemical compositions of E. coli cells suggested that UV/PAA primarily caused oxidative damage to intracellular molecules rather than the damage to the lipids of the cell membrane, therefore effectively limited the regrowth of E. coli. Additionally, the UV/PAA process displayed an outstanding performance in disinfecting actual raw CSOs, achieving a 2.90-log inactivation of total bacteria after reaction for 4 min. These results highlighted the practical applicability and effectiveness of the UV/PAA process in the disinfection of CSOs.
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Desinfecção , Escherichia coli , Ácido Peracético , Esgotos , Raios Ultravioleta , Desinfecção/métodos , Ácido Peracético/farmacologia , Escherichia coli/efeitos dos fármacos , Esgotos/microbiologia , Oxirredução , Espécies Reativas de Oxigênio/metabolismoRESUMO
Deoxynivalenol (DON) contamination in feed is a global concern that severely threatens the health of animals and humans. Taxifolin (TA) is a natural flavonoid, a member of the polyphenols, that possesses robust antioxidant properties. This study aimed to investigate the effect of TA on DON-induced damage in porcine intestinal epithelial cells (IPEC-J2). The cells were pre-incubated with a series of concentrations of TA for 24 h and exposed to DON (0.5 µg/mL) for another 24 h. The results showed that pretreatment with TA (150 µM) significantly inhibited the DON-induced decline in cell viability (p < 0.05) and cell proliferation (p < 0.01). Additionally, 150 µM TA also alleviated DON-induced apoptosis (p < 0.01). Moreover, TA decreased the production of reactive oxygen species (ROS) induced by DON (p < 0.01). In addition, TA attenuated DON-induced cell junction damage (p < 0.05). Further experiments showed that TA reversed the DON-induced reduction in antioxidant capacity in the IPEC-J2 cells, probably via activating the Nrf2 signaling pathway (p < 0.05). Collectively, these findings suggest that 150 µM TA can protect against 0.5 µg/mL DON-induced damage to IPEC-J2 cells, potentially via the activation of the Nrf2 signaling pathway. This study provides insight into TA's potential to act as a green feed additive in the pig farming industry and its efficacy in counteracting DON-induced intestinal damage.
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OBJECTIVE: To investigate the efficacy and safety of vonoprazan based bismuth-containing quadruple therapy (VBCQ) in eradicating Helicobacter pylori (Hp). MATERIALS AND METHODS: The VBCQ and the proton pump inhibitor-based bismuth-containing quadruple regimen (PBCQ) were compared by retrieving relevant studies in Pubmed, Embase, Cochrane Library, CNKI, and Wanfang data. Combined analysis was performed with risk ratio (RR) and 95% CI as effect values. RESULTS: A total of 10 studies were enrolled, including 7 randomized controlled trials and 3 cohort studies. In intention-to-treat analysis, the eradication rate of VBCQ (89.24%, 1103/1236) was significantly higher than that of PBCQ (84.03%, 1021/1215), with RR = 1.06 (95% CI: 1.03~1.10). In per-protocol analysis, the eradication rates of VBCQ and PBCQ were 92.94% (895/963) and 87.82% (829/944), respectively, with a significant difference (RR = 1.06, 95% CI: 1.03~1.09). Subgroup analysis of study design types shared similar results. VBCQ and PBCQ showed an incidence of adverse reactions of 37.30% (304/815) and 34.94% (282/807), respectively. Significant differences were not found between the two groups (RR = 1.07, 95% CI: 0.96-1.19), nor in subgroup analysis. The good compliance rates in VBCQ and PBCQ groups were 94.32% (216/229) and 95.13% (215/226), respectively, with no significant difference (RR = 0.99, 95% CI: 0.95~1.04). CONCLUSION: VBCQ has a higher eradication rate on Hp than PBCQ, while its adverse reactions and compliance are similar to PBCQ. However, we conservatively believe that in Hp eradication, the VBCQ is not inferior to PBCQ because of the small absolute difference.
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Photonic integrated circuits have garnered significant attention and experienced rapid development in recent years. To provide fundamental building blocks for scalable optical classical and quantum information processing, one important direction is to develop cryogenic compatible photonic integrated devices. Here, we prepare one optical filter on a lithium-niobate-on-insulator (LNOI) platform based on a multimode waveguide grating and verify its availability at temperature from 295 to 7 K. We find that the integrated optical filter still shows good quality under cryogenic conditions, and the shift of the working wavelength at different temperatures is well explained by the index variation of the material. These results advance LNOI integrated optical devices in applications under cryogenic conditions.
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Chemotherapy and targeted drugs-induced senescent ovarian cancer cells that accumulate in peritoneal adipose tissue contribute significantly to chronic inflammation, disrupt homeostasis, and may fuel various aspects of cancer progression. However, the pro-senescence effects of chemotherapy and targeted drugs on adipose derived stem cells (ADSCs) within peritoneal adipose tissue remain poorly understood. In this study, we show that the first-line chemotherapy and targeted drugs can induce the cellular senescence of ADSCs in vitro and increase the aging of peritoneal adipose tissue in vivo. These treatments significantly promoted the dysregulation of glucose and lipid metabolism, including insulin resistance and liver lipid accumulation. Our study shows that dasatinib and quercetin, as senolytics, effectively restore glucose homeostasis in mice with ovarian cancer and significantly reduce adipose tissue aging. Importantly, combining these drugs with Carboplatin or Olaparib results in a marked decrease in both peritoneal and adipose tissue metastasis of ovarian cancer cells. Mechanistically, we revealed that there is crosstalk between ovarian cancer cells and senescent ADSCs. The crosstalk increases inflammatory cytokines and chemokines production in ADSCs and notably upregulates chemokine receptors on cancer cells. Collectively, these data indicate that senescent ADSCs induced by chemotherapy and targeted therapy drugs impair adipose tissue function. However, the senolytic drugs dasatinib and quercetin, can significantly ameliorate organ aging and damage induced by these treatments. Notably, dasatinib and quercetin combined with Carboplatin or Olaparib reduced the peritoneal and adipose tissue metastasis of ovarian cancer, ultimately benefiting the mice undergoing chemotherapy and targeted therapy.
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Tecido Adiposo , Carboplatina , Senescência Celular , Dasatinibe , Neoplasias Ovarianas , Neoplasias Peritoneais , Ftalazinas , Piperazinas , Quercetina , Dasatinibe/farmacologia , Dasatinibe/administração & dosagem , Feminino , Animais , Quercetina/farmacologia , Quercetina/administração & dosagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/farmacologia , Ftalazinas/administração & dosagem , Carboplatina/farmacologia , Carboplatina/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Piperazinas/farmacologia , Piperazinas/administração & dosagem , Senescência Celular/efeitos dos fármacos , Camundongos , Humanos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Senoterapia/farmacologia , Linhagem Celular Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Glutamine (Gln) is a critical nutrient required by neonatal mammals for intestinal growth, especially for newborn piglets. However, the mechanisms underlying the role of Gln in porcine intestinal epithelium development are not fully understood. The objective of the current study was to explore the possible signaling pathway involved in the promotion of porcine intestinal epithelial cell (IPEC-J2) proliferation by Gln. The results showed that 1 mM Gln promoted IPEC-J2 cell proliferation, and tandem mass tag proteomics revealed 973 differentially expressed proteins in Gln-treated IPEC-J2 cells, 824 of which were upregulated and 149 of which were downregulated. Moreover, gene set enrichment analysis indicated that the Wnt signaling pathway is activated by Gln treatment. Western blotting analysis further confirmed that Gln activated the Wnt/ß-catenin signaling pathway. In addition, Gln increased not only cytosolic ß-catenin but also nuclear ß-catenin protein expression. LF3 (a ß-catenin/TCF4 interaction inhibitor) assay and ß-catenin knockdown demonstrated that Gln-mediated promotion of Wnt/ß-catenin signaling and cell proliferation were blocked. Furthermore, the inhibition of TCF4 expression suppressed Gln-induced cell proliferation. These findings further confirmed that Wnt/ß-catenin signaling is involved in the promotion of IPEC-J2 cell proliferation by Gln. Collectively, these findings demonstrated that Gln positively regulated IPEC-J2 cell proliferation through the Wnt/ß-catenin pathway. These data greatly enhance the current understanding of the mechanism by which Gln regulates intestinal development.
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Glutamina , Via de Sinalização Wnt , Animais , Suínos , Glutamina/farmacologia , Glutamina/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Intestinos , Mucosa Intestinal/metabolismo , Proliferação de Células , Mamíferos/metabolismoRESUMO
Regulation of fluorescence and self-assembly of a salicylaldehyde azine-containing amphiphile by a water-soluble pillar[5]arene via host-guest recognition in water was realized. The fluorescence and the self-assembled aggregates of the bola-type amphiphile G can be tailored by adding different amounts of water-soluble pillar[5]arene (WP5). In addition, the emission property and self-assembly behavior of G and WP5 are responsive to pH conditions. Furthermore, the fluorescence emission property of G and the regulation by WP5 or pH conditions was applied as information encryption material, rewritable paper, and erasable ink. We believe that this fluorescence regulation strategy is promising for the construction of advanced fluorescent organic materials.
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Deoxynivalenol (DON) is a common mycotoxin that is widely found in various foods and feeds, posing a potential threat to human and animal health. This study aimed to investigate the protective effect of the natural polyphenol piceatannol (PIC) against DON-induced damage in porcine intestinal epithelial cells (IPEC-J2 cells) and the underlying mechanism. The results showed that PIC promotes IPEC-J2 cell proliferation in a dose-dependent manner. Moreover, it not only significantly relieved DON-induced decreases in cell viability and proliferation but also reduced intracellular reactive oxygen species (ROS) production. Further studies demonstrated that PIC alleviated DON-induced oxidative stress damage by increasing the protein expression levels of the antioxidant factors NAD(P)H quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase modifier subunit (GCLM), and the mRNA expression of catalase (CAT), Superoxide Dismutase 1 (SOD1), peroxiredoxin 3 (PRX3), and glutathione S-transferase alpha 4 (GSTα4). In addition, PIC inhibited the activation of the nuclear factor-B (NF-κB) pathway, downregulated the mRNA expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) to attenuate DON-induced inflammatory responses, and further mitigated DON-induced cellular intestinal barrier injury by regulating the protein expression of Occludin. These findings indicated that PIC had a significant protective effect against DON-induced damage. This study provides more understanding to support PIC as a feed additive for pig production.
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Células Epiteliais , NF-kappa B , Estilbenos , Tricotecenos , Suínos , Animais , Humanos , NF-kappa B/metabolismo , Linhagem Celular , RNA Mensageiro/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos (Schw.) Wolf (Polyporaceae, P.cocos), which is born on the pine root, has a history of more than two thousand years of medicine in China. P.cocos was first recorded in the Shennong's Herbal Classic, studies have proved its lipid-lowering effect. AIM OF STUDY: The aim of study was to investigate the underlying mechanism of P.cocos extract on hyperlipidemia. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats aged 9-12 weeks were intraperitoneally (IP) injected with Triton-WR 1339 to establish an acute hyperlipidemia model. At 0 h and 20 h after the model was established, low and high doses of P.cocos extract or simvastatin were given twice. After 48 h, the rats were sacrificed, and liver and serum samples were collected for analysis. The cell model was constructed by treating L02 cells with 1% fat emulsion-10% FBS-RPMI 1640 medium for 48 h. At the same time, low and high doses of P.cocos extract and simvastatin were administered. Oil red O staining was used to evaluate the lipid accumulation in the cells, and H&E staining was used to evaluate the liver lesions of rats. Real-time quantitative PCR and western blotting were used to detect the expressions of lipid metabolism-related genes. RESULTS: P.cocos extract relieved lipid accumulation in vitro and alleviated hyperlipidemia in vivo. Both gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα) were shown to be up-regulated by P.cocos extract. Additionally, P.cocos extract down-regulated the expressions of fatty acid synthesis-related genes sterol regulatory element-binding protein-1 (SREBP-1), Acetyl-CoA Carboxylase 1 (ACC1) and fatty acid synthase (FAS), while up-regulated the expressions of cholesterol metabolism-related genes liver X receptor-α (LXRα), ATP-binding cassette transporter A1 (ABCA1), cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein receptor (LDLR), which were reversed by the treatment with the PPARα inhibitor GW6471. CONCLUSION: P.cocos extract ameliorates hyperlipidemia and lipid accumulation by regulating cholesterol homeostasis in hepatocytes through PPARα pathway. This study provides evidence that supplementation with P.cocos extract could be a potential strategy for the treatment of hyperlipidemia.
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Hiperlipidemias , Wolfiporia , Lobos , Ratos , Masculino , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , Lobos/metabolismo , Ratos Sprague-Dawley , Fígado , Metabolismo dos Lipídeos , Hiperlipidemias/metabolismo , Hepatócitos/metabolismo , Lipídeos , Colesterol/metabolismo , Homeostase , Sinvastatina/farmacologia , Sinvastatina/uso terapêuticoRESUMO
A simple and mild stimulus-responsive fluorescent supramolecular polymer network was constructed from a pillararene-based multi-functional monomer through multiple noncovalent interactions and used as a rewritable paper.
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This study provided an in-depth understanding of enhanced algae inactivation by combining ultraviolet and peracetic acid (UV/PAA) and selecting Microcystis aeruginosa as the target algae species. The electron paramagnetic resonance (EPR) tests and scavenging experiments provided direct evidence on the formed reactive species (RSs) and indicated the dominant role of RSs including singlet oxygen (1O2) and hydroxyl (HOâ¢) and organic (ROâ¢) radicals in algae inactivation. Based on the algae inactivation kinetic model and the determined steady-state concentration of RSs, the contribution of RSs was quantitatively assessed with the second-order rate constants for the inactivation of algae by HOâ¢, ROâ¢, and 1O2 of 2.67 × 109, 3.44 × 1010, and 1.72 × 109 M-1 s-1, respectively. Afterward, the coexisting bi/carbonate, acting as a shuttle, that promotes the transformation from HO⢠to RO⢠was evidenced to account for the better performance of the UV/PAA system in algae inactivation under the natural water background. Subsequently, along with the evaluation of the UV/PAA preoxidation to modify coagulation-sedimentation, the possible application of the UV/PAA process for algae removal was advanced.
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Poluentes Químicos da Água , Purificação da Água , Raios Ultravioleta , Ácido Peracético/farmacologia , Água , Peróxido de Hidrogênio , OxirreduçãoRESUMO
Targeted drug delivery systems have gained great attention from the chemistry and biomedical fields in recent years due to the minimized harm to normal cells. When designing targeted drug delivery systems, the property of harmlessness to normal cells and the tracking ability of the whole process are quite crucial. These two characters can be brought into the related systems by applying a drug carrier that is self-luminescent and its drug release can be induced by the microenvironment of cancer cells. Therefore, the design and synthesis of drug delivery vehicles are significant for the fabrication of target drug delivery systems. Herein, we have synthesized a cysteine-responsive and fluorescent molecule, maleic acid-modified tetraphenylethylene derivative (MATPE), by a facile method. In addition, a drug delivery system with self-luminescence and cysteine-responsiveness based on the self-assembly of MATPE was fabricated. In this system, MATPE and cysteine both played dual roles as cysteine probe/drug carrier and emission-enhanced inducement/drug-release stimulus. The drug-release process was successfully realized in cancer cells and can be visualized, exhibiting great potential in the field of theranostics.
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Cisteína , Doxorrubicina , Doxorrubicina/farmacologia , Doxorrubicina/química , Liberação Controlada de Fármacos , Luminescência , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/toxicidade , Portadores de Fármacos/químicaRESUMO
BACKGROUND: QTc prolongation is one of the possible complications in patients with schizophrenia taking antipsychotics, which leads to malignant cardiac arrhythmia. No meta-analysis has been reported assessing the prevalence and correlated risk factors for QTc prolongation. METHODS: This meta-analysis aimed to assess the evidence for the prevalence of QTc prolongation and correlated risk factors in patients with schizophrenia taking antipsychotics. Web of Science and PubMed were searched according to preset strategy. The quality of research was assessed by the Newcastle-Ottawa Scale (NOS). RESULTS: In all, 15 studies covering 15,540 patients with schizophrenia taking antipsychotics were included. Meta-analysis showed that the prevalence of QTc prolongation in patients with schizophrenia taking antipsychotics was about 4.0% (95% confidence interval (CI): 3.0%-5.0%, p < 0.001). The prevalence was about 4.0% in Asia (95%CI: 3.0%-6.0%, p < 0.001), about 5.0% in Europe (95%CI: 2.0%-7.0%, p < 0.001), and about 2.0% in America (95%CI: 1.0%-3.0%, p < 0.001). Sensitivity analyses indicated the robustness of the result. Publication bias analysis reported a certain publication bias (t = 3.37, p = 0.012). Meta-regression suggested that female and elderly patients were clinically associated with a higher prevalence of QTc prolongation. According to included studies, smoking, comorbidity of cardiovascular disease, and abnormal levels of high-density lipoprotein/low-density lipoprotein might be related to QTc prolongation in patients with schizophrenia taking antipsychotics. CONCLUSIONS: The prevalence of QTc prolongation in patients with schizophrenia taking antipsychotics was about 4.0%. Female and elderly patients were more likely to experience QTc prolongation. Close electrocardiogram monitoring was suggested in these at-risk populations.
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Antipsicóticos , Síndrome do QT Longo , Esquizofrenia , Idoso , Feminino , Humanos , Antipsicóticos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Prevalência , Fatores de Risco , Esquizofrenia/induzido quimicamente , MasculinoRESUMO
Environmental-friendly and low-cost catalysts for peracetic acid (PAA) activation are vital to promote their application for micropollutant degradation in water. In this study, powdered activated carbon (PAC) was reported to improve the degradation of sulfamethoxazole (SMX). The improvement of SMX degradation in the PAC/PAA system was expected to be because of the PAA activation rather than the co-existing H2O2 activation. Non-radical oxidation pathways, including the mediated electron-transfer process and singlet oxygen (1O2), were evidenced to play the dominant roles in the degradation of micro-organic pollutants. The graphitization of PAC, persistent free radicals, and electron-donating groups like C-OH were proposed to contribute to the activation of PAA. High SMX degradation could be achieved in the acidic and neutral conditions in the PAC/PAA system. Overall, higher dosages of PAC (0-0.02 g/L) and PAA (0-100 µM) benefited the degradation of SMX. The presence of HCO3- could lower the SMX degradation significantly, while Cl-, PO43-, and humic acid (HA) only reduced the SMX degradation efficiency a little. Overall, this study offered an efficient non-radical PAA activation method using PAC, which can be effectively used to degrade micro-organic pollutants.
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Ácido Peracético , Poluentes Químicos da Água , Sulfametoxazol , Peróxido de Hidrogênio , Carvão Vegetal , OxirreduçãoRESUMO
Metabolic reprogramming plays a pivotal role in the differentiation and function of immune cells including dendritic cells (DCs). Regulatory DCs can be generated in regional tissue niches like splenic stroma and act as an important part of stromal control of immune response for the maintenance of immune tolerance. However, the metabolic alterations during splenic stroma-driven regulatory DCs differentiation and the metabolic enzyme involved in regulatory DCs function remain poorly understood. By combining metabolomic, transcriptomic, and functional investigations of mature DCs (maDCs) and diffDCs (regulatory DCs differentiated from activated mature DCs through coculturing with splenic stroma), here we identified succinate-CoA ligase subunit beta Suclg2 as a key metabolic enzyme that reprograms the proinflammatory status of mature DCs into a tolerogenic phenotype via preventing NF-κB signaling activation. diffDCs downregulate succinic acid levels and increase the Suclg2 expression along with their differentiation from mature DCs. Suclg2-interference impaired the tolerogenic function of diffDCs in inducing T cell apoptosis and enhanced activation of NF-κB signaling and expression of inflammatory genes CD40, Ccl5, and Il12b in diffDCs. Furthermore, we identified Lactb as a new positive regulator of NF-κB signaling in diffDCs whose succinylation at the lysine 288 residue was inhibited by Suclg2. Our study reveals that the metabolic enzyme Suclg2 is required to maintain the immunoregulatory function of diffDCs, adding mechanistic insights into the metabolic regulation of DC-based immunity and tolerance.
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Células Dendríticas , NF-kappa B , Diferenciação Celular , Células Dendríticas/imunologia , Regulação da Expressão Gênica , Tolerância Imunológica , NF-kappa B/metabolismo , Transdução de Sinais , Succinato-CoA Ligases/imunologia , beta-Lactamases/imunologiaRESUMO
In this study, Fe(â ¡)/peracetic acid (PAA) and Fe(â ¡)/sodium hypochlorite (NaClO) systems were applied as the combined preoxidation and coagulation process to enhance algae removal. A high removal rate of algae and turbidity could be achieved, with most algal cells keeping intact when adding reasonable concentrations of PAA and NaClO to enhance Fe(â ¡) coagulation. The variations of chlorophyll a, malondialdehyde, and intracellular reactive oxygen species suggested that moderate oxidation with only destroying surface-adsorbed organic matter rather than cell integrity was realized. The generated organic radicals, Fe(â £), and hydroxy radical played the major roles in the Fe(â ¡)/PAA system for the moderate oxidation of algal cells, but direct oxidation by NaClO rather than producing reactive species in the Fe(â ¡)/NaClO process contributed to the preoxidation. Concurrently, the in-situ formed Fe(â ¢) greatly promoted the agglomerating and settling of algae. The analysis of cell integrity, biochemical compositions, and fluorescence excitation-emission matrices spectra demonstrated that excess NaClO but not PAA would seriously damage the algal cells. This might be because that NaClO would directly oxidize the cell wall/membrane, while PAA mainly permeates into the cell to inactivate algae. These results suggest that Fe(â ¡)/PAA is an efficient strategy for algae-laden water treatment without serious algae lysis.
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Hipoclorito de Sódio , Purificação da Água , Hipoclorito de Sódio/farmacologia , Hipoclorito de Sódio/química , Ácido Peracético/farmacologia , Compostos Férricos , Clorofila A , Oxirredução , Purificação da Água/métodos , Compostos Ferrosos/químicaRESUMO
Background: Helicobacter pylori (H. pylori) infection is one of the most important public health issues, and bismuth-containing quadruple therapy (BQT) is the first-line therapeutic option. This study aimed to compare the efficacy and safety of high-dose dual therapy (HDDT) and BQT in eradicating H. pylori. Methods: Randomized controlled trials (RCTs) were retrieved from Pubmed, Embase, and Cochrane Library to evaluate the effects of HDDT and BQT on H. pylori infection from 2002 to August 31, 2022 (last 20 years). A meta-analysis was conducted using Review Manager 5.4 and dichotomous data were estimated by the risk ratio (RR) and the 100% confidence interval (CI). A heterogeneity test and publication bias adjustment were carried out using Stata 12.0. Results: 5604 participants from 14 RCTs were included in this meta-analysis. The eradication rates of H. pylori in the HDDT group and the BQT group were 87.46% and 85.70%, respectively. There was a bordered significant difference (RR = 1.02, 95% CI: 1.00 ~ 1.04, P = 0.03) in the intention-to-treat (ITT) analysis. Inconsistently, in per-protocol (PP) analysis, HDDT showed similar efficacy to BQT (89.97% vs 89.82%, RR = 1.00, 95% CI: 0.99 ~ 1.02, P = 0.67). HDDT showed fewer frequent adverse events than BQT (13.00% vs 31.05%, RR = 0.41, 95% CI: 0.33 ~0.50, P < 0.00001). After adjusting for publication bias, the tendency did not change (RR = 0.49, 95% CI: 0.44 ~ 0.55, P < 0.00001). The compliance of the HDDT group has no significant difference compared with the BQT group (95.88% vs 93.84%, RR = 1.01, 95% CI: 1.00 ~ 1.03, P = 0.14). Conclusion: HDDT achieved a non-inferiority eradication rate, fewer side effects, and similar compliance compared with BQT.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Bismuto/uso terapêutico , Antibacterianos/uso terapêutico , Inibidores da Bomba de Prótons , Quimioterapia Combinada , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/farmacologia , Resultado do TratamentoRESUMO
Establishing scaling laws for amorphous alloys is of critical importance for describing their mechanical behavior at different size scales. In this paper, taking Ni2Ta amorphous metallic alloy as a prototype materials system, we derive the scaling law of impact resistance for amorphous alloys. We use laser-induced supersonic micro-ballistic impact experiments to measure for the first time the size-dependent impact response of amorphous alloys. We also report the results of molecular dynamics (MD) simulations for the same system but at much smaller scales. Comparing these results, we determined a law for scaling both length and time scales based on dimensional analysis. It connects the time and length scales of the experimental results on the impact resistance of amorphous alloys to that of the MD simulations, providing a method for bridging the gap in comparing the dynamic behavior of amorphous alloys at various scales and a guideline for the fabrication of new amorphous alloy materials with extraordinary impact resistance.
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CCR7-triggered DC migration toward draining lymph nodes is critical for the initiation of protective immunity and maintenance of immune tolerance. How to promote CCR7-mediated DC migration to determine T cell responses under inflammatory and homeostatic conditions remains poorly understood. Here we demonstrate that the Extl1 (Exostosin like glycosyltransferase 1) promotes CCR7-triggered DC migration in a heparan sulfate proteoglycans (HSPG)-dependent manner. Mechanistically, Extl1 mediates HSPG production via its glycosyltransferase domain to inhibit C1q expression. Extl1/HSPG axis relieves C1q-mediated restriction of CCR7 surface expression and internalization, and thus enhances CCR7-dependent migratory signaling activation. Consequently, Extl1 is required for DC-mediated Th1 and Th17 responses in immune defense against bacterial infection and for Treg cell development in the prevention of autoimmunity. Our study adds mechanistic insights to the regulation of CCR7-triggered DC migration in immunity and tolerance and provides a potential target for the treatment of infectious and autoimmune diseases.