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Scalable and highly efficient bamboo whitening remains a great challenge. Herein, an effective bamboo whitening strategy is proposed based on photocatalyzed oxidation, which involves H2O2 infiltration and UV illumination. The as-prepared white bamboo well maintains the nature structure of natural bamboo and demonstrates high whiteness and superior mechanical properties. The absorbance value is significantly decreased to 3.5 and the transmittance is increased to 0.04 % in UV-visible wavelength range due to the removal of light-absorbing chromospheres of lignin, resulting in a high whiteness when the UV illumination time is 8 h. In addition, the white bamboo displays a high tensile strength of 30 MPa and a high flexural strength of 36 MPa due to the well-preserved lignin units (lignin preservation is about 89 %). XRD patterns and analysis show that photocatalyzed oxidation has no effect on the crystal parameters of cellulose. Compared with the traditional bamboo whitening technology, our photocatalyzed oxidation strategy demonstrates significant advantage including chemical and time conservation, high efficiency, environment friendliness, and mechanical robustness. This highly efficient and environmentally friendly photocatalyzed oxidation strategy for the fabrication of white bamboo may pave the way of bamboo-based energy-efficient structural materials for engineering application.
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Lignina , Oxirredução , Lignina/química , Catálise , Sasa/química , Peróxido de Hidrogênio/química , Resistência à Tração , Raios Ultravioleta , Processos Fotoquímicos , Cor , Poaceae/químicaRESUMO
The antibiotic oxytetracycline (OTC) can be detected in contemporary natural aquatic environments and has been implicated in causing intestinal damage in humans exposed to OTC-contaminated food or water. The irreversible damage caused by high concentrations of OTC to the intestine suggests that treatment through dietary means could still be necessary. This study proved the effectiveness of kefir extract (KE) in reversing intestinal damage caused by oxytetracycline (OTC) exposure. Following a 24-hour KE treatment subsequent to OTC exposure from 3 to 8 days post-fertilization of zebrafish larvae, molecular-level and microbiomic assessments revealed significant improvements. These included reduced expression of proinflammatory factors (IL-8 and IL-1ß), increased antioxidant levels, and reversed unhealthy distribution of intestinal microbiota. Furthermore, KE supplementation showed potential in enhancing intestinal motility in the experiment of Nile red staining and fluorescent microbead transit. However, histological analysis showed that this short-term treatment with KE only partially reversed the intestinal morphological changes induced by OTC, suggesting that a longer treatment period might be necessary for complete restoration.
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Microbioma Gastrointestinal , Intestinos , Kefir , Larva , Oxitetraciclina , Peixe-Zebra , Animais , Oxitetraciclina/farmacologia , Larva/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacosRESUMO
Metastasis and recurrence are notable contributors to mortality associated with breast cancer. Although immunotherapy has shown promise in mitigating these risks after conventional treatments, its effectiveness remains constrained by significant challenges, such as impaired antigen presentation by dendritic cells (DCs) and inadequate T cell infiltration into tumor tissues. To address these limitations, we developed a multifunctional nanoparticle platform, termed GM@P, which consisted of a hydrophobic shell encapsulating the photosensitizer MHI148 and a hydrophilic core containing the STING agonist 2'3'-cGAMP. This design elicited robust type I interferon responses to activate antitumor immunity. The GM@P nanoparticles loaded with MHI148 specifically targeted breast cancer cells. Upon exposure to 808 nm laser irradiation, the MHI148-loaded nanoparticles produced toxic reactive oxygen species (ROS) to eradicate tumor cells through photodynamic therapy (PDT). Notably, PDT stimulated immunogenic cell death (ICD) to foster the potency of antitumor immune responses. Furthermore, the superior photoacoustic imaging (PAI) capabilities of MHI148 enabled the simultaneous visualization of diagnostic and therapeutic procedures. Collectively, our findings uncovered that the combination of PDT and STING activation facilitated a more conducive immune microenvironment, characterized by enhanced DC maturation, infiltration of CD8+ T cells, and proinflammatory cytokine release. This strategy stimulated local immune responses to augment systemic antitumor effects, offering a promising approach to suppress tumor growth, inhibit metastasis, and prevent recurrence.
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Proteínas de Membrana , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Proteínas de Membrana/metabolismo , Feminino , Humanos , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Camundongos Endogâmicos BALB C , Nucleotídeos Cíclicos/química , Nucleotídeos Cíclicos/farmacologiaRESUMO
SCOPE: Palmitoleic acid (POA) is an omega-7 monounsaturated fatty acid that has been suggested to improve metabolic disorders. However, it remains unclear whether gut microbiota plays a role in the amelioration of metabolic disorders by POA. This study aims to investigate the regulation of POA on metabolism, as well as systemic inflammation in HFD-fed mice from the perspective of serum metabolome and gut microbiome. METHODS AND RESULTS: Thirty-six C57BL/6 male mice are randomly assigned to either a normal chow diet containing 1.9% w/w lard or an HFD containing 20.68% w/w lard or 20.68% w/w sea buckthorn pulp oil for 16 weeks. The study finds that POA significantly attenuated hyperlipidemia, insulin resistance, and inflammation in HFD-fed mice. POA supplementation significantly alters the composition of serum metabolites, particularly lipid metabolites in the glycerophospholipid metabolism pathway. POA obviously increases the abundance of Bifidobacterium and decreases the abundance of Allobaculum. Importantly, the study finds that glycerophosphocholine mediates the effect of Bifidobacterium on LDL-C, sphingomyelin mediates the effect of Bifidobacterium on IL-6, and maslinic acid mediates the effect of Allobaculum on IL-6. CONCLUSION: The results suggest that exogenous POA can improve metabolic disorders and inflammation in HFD-fed mice, potentially by modulating the serum metabolome and gut microbiome.
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Microbioma Gastrointestinal , Doenças Metabólicas , Masculino , Animais , Camundongos , Interleucina-6 , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Ácidos Graxos Monoinsaturados/farmacologia , Firmicutes , Dieta Hiperlipídica/efeitos adversosRESUMO
Chromium (VI) in soil poses a significant threat to the environment and human health. Despite efforts to remediate Cr contaminated soil (Cr-soil), instances of re-yellowing have been observed over time. To understand the causes of re-yellowing as well as the influence of overdosed chemical reductant in remediating Cr-soil, experiments on excess reducing agent interference and soil re-yellowing mechanisms under different extreme conditions were conducted. The results show that the USEPA method 3060A & 7196A combined with K2S2O8 oxidation is an effective approach to eliminate interference from excess FeSO4 reducing agents. The main causes of re-yellowing include the failure of reducing agents, disruption of soil lattice, and interactions between manganese oxides and microorganisms. Under various extreme conditions simulated across the four seasons, high temperature and drought significantly accelerated the failure of reducing agents, resulting in the poorest remediation effectiveness for Cr-soil (91.75 %). Dry-wet cycles promoted the formation of soil aggregates, negatively affecting Cr(VI) removal. While these extreme conditions caused relatively mild re-yellowing (9.46 %-16.79 %) due to minimal soil lattice damage, the potential risk of re-yellowing increases with the failure of reducing agents and the release of Cr(VI) within the lattice. Prolonged exposure to acid rain leaching and freeze-thaw cycles disrupted soil structure, leading to substantial leaching and reduction of insoluble Cr, resulting in optimal remediation effectiveness (94.37 %-97.73 %). As reducing agents gradually and the involvement of the water medium, significant re-yellowing occurred in the remediated soil (51.52 %). Mn(II) in soil enriched relevant microorganisms, and the Mn(IV)-mediated biological oxidation process was also one of the reasons for soil re-yellowing.
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BACKGROUND: Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. METHODS: A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. RESULTS: The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47-2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74-36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85-2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19-1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34-1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204-3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001-1.009, p = 0.014). CONCLUSIONS: Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.
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Artrite Reumatoide , Doenças Autoimunes , Endometriose , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Artrite Reumatoide/complicações , Artrite Reumatoide/genética , Endometriose/epidemiologia , Endometriose/genética , Endometriose/complicações , Estudos Transversais , Análise da Randomização Mendeliana , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Estudo de Associação Genômica AmplaRESUMO
Chitosan, as a natural nontoxic biomaterial, has been demonstrated to inhibit fungal growth and enhance plant defense against pathogen infection. However, the antifungal pattern and mechanism of how chitosan application evokes plant defense are poorly elucidated. Herein, we provide evidence that chitosan exposure is fungicidal to C. heterostrophus. Chitosan application impairs conidia germination and appressorium formation of C. heterostrophus and has a pronounced effect on reactive oxygen species production, thereby preventing infection in maize. In addition, the toxicity of chitosan to C. heterostrophus requires Mkk1 and Mps1, two key components in the cell wall integrity pathway. The Δmkk1 and Δmps1 mutants were more tolerant to chitosan than the wild-type. To dissect chitosan-mediated plant defense response to C. heterostrophus, we conducted a metabolomic analysis, and several antifungal compounds were upregulated in maize upon chitosan treatment. Taken together, our findings provide a comprehensive understanding of the mechanism of chitosan-alleviated infection of C. heterostrophus, which would promote the application of chitosan in plant protection in agriculture.
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Ascomicetos , Bipolaris , Quitosana , Virulência , Quitosana/farmacologia , Quitosana/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Ascomicetos/metabolismo , Proteínas Fúngicas/metabolismo , Zea mays/metabolismo , Doenças das Plantas/microbiologiaRESUMO
Endometriosis has been reported in epidemiological studies to be associated with certain types of cancer. However, the presence of reverse causality and residual confounding due to common risk factors introduces uncertainty regarding the extent to which endometriosis itself contributes to the development of cancer. We performed the Mendelian randomization (MR) to investigate the causal associations between endometriosis and 34 different types of cancers. The results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for ovarian cancer (OR = 3.2913; p-value = .0320). The genetic liabilities to endometriosis had causal associations with the decreased risk for skin cancer (OR = 0.9973; p-value = .0219), hematological cancer (OR = 0.9953; p-value = .0175) and ER- breast cancer (OR = 0.6960; p-value = .0381). The causal association of the above combinations were robust by test of heterogeneity and pleiotropy. Together, our study suggests that endometriosis had causal effect on cancer risk.
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Neoplasias da Mama , Endometriose , Feminino , Humanos , Endometriose/complicações , Endometriose/epidemiologia , Endometriose/genética , Análise da Randomização Mendeliana , Causalidade , Fatores de Risco , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Estudo de Associação Genômica AmplaRESUMO
In this study, polyphenols were extracted from walnut green husk, an agricultural waste, and were incorporated into curdlan (CD) and methyl cellulose (MC) to create a novel edible composite film. For structural character, the film matrix was tightly bound primarily by non-covalent bonds and the addition of walnut green husk polyphenols (WGHP) significantly reduced the surface roughness of the composite film. For mechanical properties, the addition of WGHP improve the flexibility of films, and it significantly improved the barrier ability of ultraviolet rays and water-vapor. Furthermore, the incorporation of WGHP to the CD-MC film resulted in enhanced antioxidant and antibacterial effects, which effectively retards lipid oxidation in fried walnuts. Consequently, the fabricated CD-MC-WGHP composite film bears immense potential for use in food preservation applications, particularly in extending the shelf life of fried walnuts.
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Juglans , Polifenóis , beta-Glucanas , Juglans/química , Embalagem de Alimentos/métodos , Celulose/química , MetilceluloseRESUMO
Southern corn leaf blight (SCLB) caused by Cochliobolus heterostrophus is a destructive disease that threatens global maize (Zea mays) production. Despite many studies being conducted, very little is known about molecular processes employed by the pathogen during infection. There is a need to understand the fungal arms strategy and identify novel functional genes as targets for fungicide development. Transcriptome analysis based on RNA sequencing was carried out across conidia germination and host infection by C. heterostrophus. The present study revealed major changes in C. heterostrophus gene expression during host infection. Several differentially expressed genes (DEGs) induced during C. heterostrophus infection could be involved in the biosynthesis of secondary metabolites, peroxisome, energy metabolism, amino acid degradation and oxidative phosphorylation. In addition, histone acetyltransferase, secreted proteins, peroxisomal proteins, NADPH oxidase and transcription factors were selected for further functional validation. Here, we demonstrated that histone acetyltransferases (Hat2 and Rtt109), secreted proteins (Cel61A and Mep1), peroxisomal proteins (Pex11A and Pex14), NADPH oxidases (NoxA, NoxD and NoxR) and transcription factors (Crz1 and MtfA) play essential roles in C. heterostrophus conidiation, stress adaption and virulence. Taken together, our study revealed major changes in gene expression associated with C. heterostrophus infection and identified a diverse repertoire of genes critical for successful infection.
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Ascomicetos , Bipolaris , Zea mays , Virulência/genética , Zea mays/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Doenças das Plantas/microbiologiaRESUMO
BACKGROUD: Two-component histidine kinase (HK) phosphorelay signaling systems play important roles in differentiation, virulence, secondary metabolite production and response to environmental signals. Allyl isothiocyanate (A-ITC) is a hydrolysis product of glucosinolates with excellent antifungal activity. Our previous study indicated that the mycelial growth of Cochliobolus heterostrophus was significantly hindered by A-ITC. However, the function of HK in regulating A-ITC sensitivity was not clear in C. heterostrophus, the causal agent of Southern corn leaf blight. RESULTS: In this study, the role of HKs was investigated in C. heterostrophus. Deletion of the HK coding gene ChNIK1 resulted in dramatically increased sensitivity of C. heterostrophus to A-ITC. In addition, ΔChnik1 mutant exhibited significantly decreased conidiation and increased sensitivity to NaCl, KCl, tebuconazole and azoxystrobin, but deletion of the other five HK genes did not affect the A-ITC sensitivity of C. heterostrophus. ChSLN1, ChNIK4, ChNIK8 and ChMAK2 are essential for conidiation and response to H2 O2 and sodium dodecyl sulfate. However, deletion of NIKs had on effect on significant virulence. CONCLUSION: Our findings demonstrate that the HKs play different roles in A-ITC sensitivity in C. heterostrophus. © 2023 Society of Chemical Industry.
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Ascomicetos , Bipolaris , Histidina , Histidina Quinase/genética , Ascomicetos/genética , Isotiocianatos , Zea mays/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
Isothiocyanates (ITCs) that are found in Brassicaceae exhibited obvious antifungal activity against Cochliobolus heterostrophus, which is the causal agent of southern corn leaf blight. However, the underlying antifungal mechanism of allyl-ITCs (A-ITCs) against C. heterostrophus remains largely unknown. Here, we used transcriptomic analysis to find that the high osmolarity pathway was upregulated significantly when treated with A-ITCs. To investigate the roles of the high osmolarity pathway in adaption to A-ITCs, we constructed Δssk2, Δpbs2, and Δhog1 mutant strains. Deletion of three genes (ChSSK2, ChPBS2, and ChHOG1) involved in the high osmolarity pathway resulted in significantly increased sensitivity of C. heterostrophus to ITCs. In addition, the phosphorylation level of ChHog1 was induced by A-ITC and was dependent on the presence of ChSsk2 and ChPbs2. Moreover, Δssk2, Δpbs2, and Δhog1 mutants exhibited a dramatically decreased virulence on maize leaves. Our findings demonstrated that the high osmolarity pathway played a positive role in ITC tolerance and virulence, which may provide novel insights into developing ITCs as a new fungicide against C. heterostrophus.
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Antifúngicos , Ascomicetos , Antifúngicos/farmacologia , Glicerol , Ascomicetos/genética , Concentração Osmolar , IsotiocianatosRESUMO
The use of global standards, and the placement of barcodes and data matrix codes on vaccine labels and other levels of packaging are crucial elements for the traceability of finished vaccine products. Vaccine manufacturers are committed to improving health through their products, as vaccine production offers opportunities that can be leveraged to benefit immunization systems. In 2019 the Developing Countries Vaccine Manufacturers Network (DCVMN) created the Supply Chain Initiative aimed at prioritize and explore traceability opportunities; concomitantly procurement agencies announced traceability requirements for vaccine global supply. Vaccine traceability brings benefits including supply chain reliability and safety through enhanced product movement visibility, and a reduction of falsified and expired vaccines circulating in the supply chain. DCVMN has coordinated the development and implementation of global traceability standards, at both primary and secondary vaccine packaging levels, to encourage and enable sharing these experiences. Six pilot studies in four different countries showed successful implementation, and constituted part of larger vaccine traceability work within the respective organizations. The main findings from these pilot studies indicated that stepwise approaches to the adoption of traceability standards allowed vaccine manufacturers to learn by doing, initially with lower risk, and to spread their investments over time. Because the value of traceability is in its scale of adoption and the use of the data, it remains important for all stakeholders to engage in and prioritize the journey of vaccine traceability, but also to suitably manage the financial risks. The DCVMN Supply Chain Initiative has demonstrated that its members are committed to driving supply system changes that benefit immunization, while recognizing that supply chain traceability is part of a larger healthcare ecosystem and should be adopted by countries and immunization programmes as well.
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The black-boned silky fowl (BSF) muscle protein hydrolysate was gained by alcalase. The hydrolysate could stimulate MC3T3-E1 cell proliferation, as well as enhance alkaline phosphatas (ALP) activity and deposits of minerals. After isolation and purification, 55 peptide sequences with Mascot score over 40 were identified. Combined with molecular docking simulation and molecular dynamics analysis, two novel peptides (PASTGAAK and PGPPGTPF) were identified with the lowest binding energy of -4.99 kcal/mol and -3.07 kcal/mol with receptor BMPR1A of BMP-2/Smad pathway, showing the ability to increase BMPR1A stability. Moreover, both PASTGAAK and PGPPGTPF revealed strong anti-osteoporosis activities in the zebrafish model induced by dexamethasone. Additionally, the identified peptides could be beneficial for the differentiation of MC3T3-E1 cell for upregulating the expression of some osteoblast-related genes and proteins by stimulating BMP-2/Smad pathway. Overall, the two newly identified peptides could be the potential candidate to prevent osteoporosis.
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Hidrolisados de Proteína , Peixe-Zebra , Animais , Galinhas , Larva , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , Hidrolisados de Proteína/farmacologiaRESUMO
BACKGROUND: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer's disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. METHODS: To investigate the effect and mechanism of the cholinergic circuit in Alzheimer's disease-related hippocampal memory, overexpression of human wild-type Tau (hTau) in medial septum (MS)-hippocampus (HP) cholinergic was achieved by specifically injecting pAAV-EF1α-DIO-hTau-eGFP virus into the MS of ChAT-Cre mice. Immunostaining, behavioral analysis and optogenetic activation experiments were used to detect the effect of hTau accumulation on cholinergic neurons and the MS-CA1 cholinergic circuit. Patch-clamp recordings and in vivo local field potential recordings were used to analyze the influence of hTau on the electrical signals of cholinergic neurons and the activity of cholinergic neural circuit networks. Optogenetic activation combined with cholinergic receptor blocker was used to detect the role of cholinergic receptors in spatial memory. RESULTS: In the present study, we found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. In addition to an inhibitory effect on neuronal excitability, theta synchronization between the MS and CA1 subsets was significantly disrupted during memory consolidation after overexpressing hTau in the MS. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm-dependent manner. CONCLUSIONS: Our study not only reveals the vulnerability of a novel MS-CA1 cholinergic circuit to AD-like tau accumulation but also provides a rhythm- and time window-dependent strategy to target the MS-CA1 cholinergic circuit, thereby rescuing tau-induced spatial cognitive functions.
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Doença de Alzheimer , Consolidação da Memória , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Colinérgicos/metabolismo , Colinérgicos/farmacologia , Neurônios Colinérgicos , Hipocampo/metabolismo , Transtornos da Memória/metabolismo , Proteínas tau/metabolismoRESUMO
Excessive reductants are used in engineering to ensure a reliable remediation effect of chromite ore processing residue (COPR), however, re-yellowing phenomenon of remediated COPR occurs after some time though the Cr(VI) content meets regulatory requirements after curing period. This problem is due to a negative bias on Cr(VI) determination using USEPA method 3060A. To address this issue, this study tried to reveal the interference mechanisms and proposed two methods to amend the bias. Results of ion concentrations, UV-Vis spectrum, XRD, and XPS together showed that Cr(VI) was reduced by ions (Fe2+, S52-) in the digestion stage of USEPA method 3060A, and as a result, method 7196A would not reflect the true Cr(VI) concentration. The interference on Cr(VI) determination generated by excess reductants mainly occurs during the curing period of remediated COPR, but it decreases over time as reductants being oxidized gradually by the air. Compared with the thermal oxidation, the chemical oxidation with K2S2O8 prior to alkaline digestion performs better to eliminate the masking effect brought by excess reductants. This study provides an approach on how to accurately determine the Cr(VI) concentration in the remediated COPR. It might be helpful to reduce the occurrence possibility of re-yellowing phenomenon.
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Cigarette smoke (CS)-induced oxidative stress drives the pathogenesis of respiratory diseases, in which the activation and accumulation of reactive oxygen species (ROS) play an important role. Ferroptosis, a regulated cell death induced by Fe2+-dependent, lipid peroxidation, and ROS, is closely related to CS-induced airway injury disease, but its mechanism remains unclear. We found that bronchial epithelial ferroptosis and expression of iNOS in smoking patients were significantly higher than that in non-smokers. The iNOS, induced by CS exposure, was involved in bronchial epithelial cell ferroptosis, whereas genetic depletion or pharmacologic inactivation of iNOS attenuated the CS-induced ferroptosis and mitochondrial dysfunction. Our mechanistic studies found that SIRT3 directly bound to and negatively regulated iNOS to mediate ferroptosis. Moreover, we found that the Nrf-2/SIRT3 signal was deactivated by cigarette smoke extract (CSE)-induced ROS. Collectively, these results linked CS to human bronchial epithelial cell ferroptosis through ROS deactivation of the Nrf-2/SIRT3 signal to promote iNOS expression. Our study provides new insights into the pathogenesis of CS-induced tracheal injury diseases such as chronic bronchitis, emphysema, and chronic obstructive pulmonary disease.
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Fumar Cigarros , Ferroptose , Doença Pulmonar Obstrutiva Crônica , Sirtuína 3 , Humanos , Fumar Cigarros/efeitos adversos , Fumar Cigarros/metabolismo , Células Epiteliais/metabolismo , Epitélio/metabolismo , Ferroptose/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Nicotiana/efeitos adversosRESUMO
PURPOSE: Health disparities are driven by a complex interplay of determinants operating across multiple levels of influence. However, while recognized conceptually, much disparities research fails to capture this inherent complexity in study focus and/or design; little of such work accounts for the interplay across the multiple levels of influence from structural (contextual) to biological or clinical. We developed a novel modeling framework that addresses these challenges and provides new insights. METHODS: We used data from the Florida Cancer Data System on endometrial cancer patients and geocoded-derived social determinants of health to demonstrate the applicability of a new modeling paradigm we term PRISM regression. PRISM is a new highly interpretable tree-based modeling framework that allows for automatic discovery of potentially non-linear hierarchical interactions between health determinants at multiple levels and differences in survival outcomes between groups of interest, including through a new specific area-level disparity estimate (SPADE) incorporating these multilevel influences. RESULTS: PRISM demonstrates that hierarchical influences on racial disparity in endometrial cancer survival appear to be statistically relevant and that these better predict survival differences than only using individual level determinants. The interpretability of the models allows more careful inspection of the nature of these hierarchical effects on disparity. Additionally, SPADE estimates show distinct geographical patterns across census tracts in Florida. CONCLUSION: PRISM can provide a powerful new modeling framework with which to better understand racial disparities in cancer survival.
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Neoplasias do Endométrio , Grupos Raciais , Feminino , Humanos , Fatores Raciais , Florida/epidemiologia , EndométrioRESUMO
Octyl and decyl glycerate (ODG), a medium-chain triglyceride (MCT), is widely used as a food additive. Medium-chain monoglycerides, such as glycerol monolaurate and glycerol monocaprylate, were found to change the composition of the gut microbiota and influence glucose and lipid metabolism and inflammation. However, whether ODG influences the gut microbiota and whether the alteration in the gut microbiota contributes to the metabolic phenotype remain unknown. Under a normal-chow diet, mice were treated with or without different dosages of ODG (150, 800, 1600 mg kg-1) for 22 weeks. All doses of ODG significantly decreased the ratio of HDL to LDL cholesterol, improved the inflammation and insulin resistance, and increased the α-diversity of the gut microbiota and the abundance of Bifidobacterium and Turicibacter. Under a high-fat diet, mice were treated with or without 1600 mg kg-1 ODG for 16 weeks. The results demonstrated that ODG significantly alleviated the increase in the ratio of HDL to LDL cholesterol, insulin resistance, and inflammation caused by HFD. The expression of related genes was consistent with the above observations. ODG also altered the composition of the gut microbiota and increased the Bifidobacterium abundance under HFD. Our findings indicated that ODG similarly improved glucose metabolism and inflammation but exhibited differential effects on lipid metabolism under different dietary patterns. Furthermore, changes in the gut microbiota caused by ODG supplementation might contribute to the alteration in glucose and lipid metabolism and inflammation, which might be influenced by dietary patterns.
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Microbioma Gastrointestinal , Resistência à Insulina , Animais , Camundongos , LDL-Colesterol , Inflamação/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Glucose/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Considering the high toxicity of arsenic (As), its contamination of soil represents an alarming environmental and public health issue. Existing soil heavy metal concentration estimation models based on hyperspectral data ignore the spatial nonstationarity of the relationship between the soil spectrum and heavy metal concentration. A novel model (geographically weighted eXtreme gradient boosting or GW-XGBoost model) combining geographically weighted regression (GWR) method with XGBoost algorithm was proposed. The northeast district of Beijing, China, was chosen as a case study area to assess the effectiveness of the proposed model. The GW-XGBoost model was established to estimate the As concentration based on the typical spectrum of As and the spatial correlation between the spectrum and As concentration obtained using the GWR method, and the result was compared to that obtained with the XGBoost and GWR models. The accuracy of the GW-XGBoost model was obviously better than that of the other models (R2GW-XGBoost = 0.90, R2XGBoost = 0.48, and R2GWR = 0.74). Therefore, the proposed model is reliable, as it considers the spatial correlation between the spectrum and As concentration.