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Glutathione (GSH) plays a crucial role in several physiological processes, including anti-oxidation and heavy metal detoxification. GSH is produced endogenously in the human body and can also be obtained through diet. The development of fast, highly sensitive, and multi-application fluorescent probes remains a challenging task. In this study, we have designed and synthesized a coumarin-based fluorescent probe (NFRF) for the sensitive and rapid detection of GSH in 100 % aqueous solution. By loading probe NFRF on the filter paper, the real-time visual detection of GSH is achieved in both daylight and fluorescence modes, providing a convenient, economical and rapid on-site detection tool. Probe NFRF could be used for the detection of GSH in real samples, with recoveries rates of 81.74 %-115.12 %. Notably, the probe imaged changes in GSH concentrations in oxidative stress environments and during ferroptosis. This work provides a prospective method for GSH detection in food and complex biological systems.
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Ferroptose , Corantes Fluorescentes , Glutationa , Estresse Oxidativo , Glutationa/metabolismo , Glutationa/análise , Corantes Fluorescentes/química , Humanos , Cumarínicos/químicaRESUMO
The slaughtering environment is crucial for the food hygiene and safety of poultry products. Despite the global dominance of industrial processing, live bird slaughtering in wet markets persists due to cultural, religious, and economic reasons. This study aims to reveal the correlation between hygiene scales in wet markets and bacterial contamination levels on broiler carcasses, with a particular focus on pathobiont transmission risks and microbiome characteristics. Wet markets were categorized based on home-made ratings and the Hygiene and Biosecurity Assessment Tool (HABT). The study assessed total aerobic bacterial (TAB) levels, food spoilage and hygiene indicators (Pseudomonas and E. coli), foodborne pathogen Salmonella, and the microbiome of broiler carcasses, intestinal contents, and slaughtering facilities. Comparative analyses were conducted between market and industrial processing environments. TAB levels on broiler carcasses showed a significant negative correlation with hygiene scores, indicating that both HABT and home-made rating tools effectively assess and improve processing hygiene. Industrial processing consistently reduced bacterial contamination compared to wet markets. Although Salmonella spp. prevalence was lower in market-processed carcasses, the study identified significant cross-transmission of pathobionts and variations in bacterial composition with hygiene improvements. Notably, the microbiome analysis revealed overlaps in amplicon sequence variants (ASVs) between carcasses and contamination vectors, highlighting pathobiont transmission risks. The present study confirmed the scales of hygiene standards among wet markets reflect bacterial contamination on broiler carcasses. Enhancing slaughter practices to meet industrial hygiene standards is essential for reducing the transmission of foodborne pathogens and pathobionts, and improving food safety.
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Matadouros , Galinhas , Contaminação de Alimentos , Manipulação de Alimentos , Microbiologia de Alimentos , Microbiota , Animais , Galinhas/microbiologia , Contaminação de Alimentos/análise , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Salmonella/isolamento & purificação , Salmonella/classificação , Salmonella/genética , Higiene , Escherichia coli/isolamento & purificaçãoRESUMO
Lumbar disc herniation is usually caused by the accumulation of long-term mechanical loads and sudden overload damage. Therefore, this study aims to illustrate how fatigue failure in lumbar spine segments is influenced by both cyclic loading magnitude and pre-existing damage. Eighty-six sheep intervertebral disc samples were divided into four groups to test the fatigue responses in healthy and damaged intervertebral discs. Both before and after fatigue loading, the specimens were performed on loading-unloading tests to analyze the viscoelasticity changes, while the specimens were performed on MRI examination to analyze the geometric and morphological changes. The Stress-Failure curve (SN curve) was examined, while the number of cycles to failure of damaged specimens was much smaller than that of healthy specimens at the same stress level during cyclic loading, and the relationship was approximately linear on a logarithmic scale. In addition, the healthy specimens will not accumulate fatigue failure if the compression force remains below 50% of the ultimate compressive tolerance (UTC). Before and after fatigue loading, the loading-unloading curves do not coincide and show obvious strain-rate-dependent viscoelastic characteristics, while the elastic modulus of the damaged specimen is significantly smaller. For magnetic resonance imaging, morphological changes included the changes of nucleus pulposus (NP) shape and area, while fatigue has a more significant effect on ruptured and herniated disc specimens. The dissipated energy of the intervertebral discs under cyclic loading was then calculated based on viscoelastic constitutive equations, which show that the load and preexisting damage both have significant effects on the dissipation rate.
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BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.
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Colonoscopia , Intubação Gastrointestinal , Animais , Colonoscopia/métodos , Suínos , Intubação Gastrointestinal/métodos , Nutrição Enteral/métodos , Nutrição Enteral/instrumentação , Imãs , Colo/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Duração da CirurgiaRESUMO
BACKGROUND: Schisandra chinensis (Turcz.) Baill (S. chinensis), a member of the Magnoliaceae family, is renowned for its distinctive medicinal attributes and is commonly employed in the treatment of disorders affecting the CNS. PURPOSE: The potential therapeutic effects of a lignan-enriched extract derived from Schisandra chinensis (Turcz.) Baill (LSC) on PD is assessed, which focuses on its mechanisms of action in addressing neuroinflammation. METHODS: The LSC has been obtained by purifying the ethyl alcohol extract of S. chinensis. The Orbitrap-MS method has been employed to analyze the chemical composition of the LSC. In LPS-induced BV2 cells, LSC-induced changes in M1/M2 type inflammatory cytokines have been examined using the Griess reaction, Elisa, JC-1, flow cytometry, IF, and WB methods. A model of PD has been established by treatment of MPTP in C57BL/6 mice. The effect of LSC on behavioral changes, inflammatory factor levels, expression of TH and IBA-1, and production of autophagy in the midbrain has been investigated by TEM, immunohistochemistry, Elisa, and WB. RESULTS: LSC has relieved sports injuries and pathological damage, and targeted the TRPV1-AMPK-NLRP3 signaling pathway, which affected neuroinflammation and autophagy in vivo. Furthermore, in vitro investigations demonstrated that LSC has activated M1/M2 transformation, its related inflammatory factors, and protein expressions of the NLRP3-Caspase1 signaling pathway in LPS-BV2 cells. The research notably demonstrated that the LSC promoted autophagy and suppressed inflammation through targeting TRPV1. CONCLUSION: In the investigation, LSC focused on TRPV1 and controlled neuroinflammation-autophagy by regulating AMPK-NLRP3, which has been proven for the first time. The study has presented molecular data supporting the use of LSC in treating PD and offers references for developing drugs. Remarkably, LSC has the potential to be utilized as a therapeutic or health medication that could significantly decrease PD.
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AIM: To establish an innovative clustering method for predicting variable categories of diabetic complications in Chinese ≥ 65 with diabetes. MATERIALS AND METHODS: We selected and extracted data from elderly patients with diabetes (n = 4980) from a medical examination group of 51,400 people followed up annually from 2014 to date in Kunshan, China. A deep contrast clustering approach was used to cluster and predict diabetic complications. The clustering approach was further validated using data from elderly patients with diabetes (n = 397) from one medical examination cohort of 20,000 people followed up yearly from 2014 to date in Beijing Jiuhua Hospital. RESULTS: The patients were clustered into 6 categories by analysing 20 indicators. Cluster 1-Heavy smoking and a high cardiovascular disease (CVD) risk; Cluster 2-High alcohol consumption, high aminotransferase levels, the highest risk of stroke complications, and a high fatty liver disease (FLD) risk; Cluster 3-High blood lipid levels and a risk of FLD and stroke complications; Cluster 4-Good health indicators and a low risk of FLD, stroke, and CVD complications; Cluster 5-Older age, higher uric acid concentration and creatinine level, and the highest risk of CVD complications; Cluster 6-Large waist circumference, high BMI, high blood pressure, and the highest risk of FLD complications. The gene for nonalcoholic fatty liver disease in cluster 2 had the highest risk coefficient. This was consistent with cluster 2, which had a higher FLD prevalence. CONCLUSIONS: A new clustering method was developed from two large Chinese cohorts of older patients with diabetes, which may effectively predict complications by clustering into different categories.
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Complicações do Diabetes , Humanos , Masculino , Idoso , Feminino , Análise por Conglomerados , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/etiologia , Complicações do Diabetes/diagnóstico , China/epidemiologia , Fatores de Risco , Seguimentos , Prognóstico , Idoso de 80 Anos ou mais , População do Leste AsiáticoRESUMO
Six new highly oxidized seco-terpenoids, including three 3-nor-labdane type diterpenes, talaroterpenoids A-C (1-3), and three meroterpenoids containing an orthoester group, talaroterpenoids D-F (6-8), together with five known compounds (4-5 and 9-11), were isolated from the marine-derived fungus Talaromyces aurantiacus. Their chemical structures were elucidated through 1D, 2D NMR, HRESIMS, J-based configuration analysis (JBCA), computational ECD calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 contain an unusual 6,20-γ-lactone-bridged scaffold. Compounds 10 and 11 presented inhibitory effects on NO release in lipopolysaccharide (LPS)-induced BV-2 cells with IC50 values of 11.47 and 11.32 µM, respectively. Talaroterpenoid C (3) showed moderate antifungal activity against A. alternata and P. theae Steyaert.
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Talaromyces , Talaromyces/química , Animais , Terpenos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Camundongos , Organismos Aquáticos , Estrutura Molecular , Linhagem Celular , Óxido Nítrico/metabolismo , Cristalografia por Raios XRESUMO
BACKGROUND: Angiotensin 1-7 (Ang1-7) is the classical end product of angiotensin II, which has the effects of dilating blood vessels, protecting endothelial cells, anti-hypertension, improving cardiac function, and inhibiting atherosclerosis. We hypothesize that Ang1-7 inhibits human umbilical vein endothelial cells (HUVEC) ferroptosis through NF-κB/P53 signal pathway, and reduces extracorporeal membrane oxygenation (ECMO) vascular injury. METHODS: Cultured HUVEC were seeded into 15 wells and randomly divided into five groups: the control group and four experimental groups (erastin, erastin + Ang1-7, erastin + Ang1-7 + Betulinic acid, erastin + Betulinic acid). After stimulation, cell viability, lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were measured. The effects of Ang1-7 on HUVEC microstructure, antioxidant enzymes (ferritin heavy chain 1 (FTH1), cystine/glutamic acid reverse transport solute carrier family 7 members 11 (SLC7A11 or XCT), superoxide dismutase-2 (SOD-2) and glutathione peroxidase 4 (GPX4)), NF-κB, P-NF-κB, P53, and P-P53). RESULTS: Erastin stimulation promoted HUVEC lipid peroxidation, decreased antioxidant enzyme expression, increased P-NF-κB, P53, and P-P53 expressions, and damaged HUVEC mitochondrial structure. Ang1-7 alleviated the effect of erastin on HUVEC, which was destroyed by Betulinic acid. CONCLUSION: Angiotensin1-7 pretreatment inhibited vascular endothelial cells' ferroptosis and alleviated ECMO vessel injury through NF-κB /P53 signal pathway.
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Angiotensina I , Oxigenação por Membrana Extracorpórea , Ferroptose , Fragmentos de Peptídeos , Humanos , Angiotensina I/farmacologia , Angiotensina I/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ferroptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Lesões do Sistema Vascular/tratamento farmacológico , Lesões do Sistema Vascular/metabolismoRESUMO
Two sulfur-containing heterodimers of a cytochalasan and a macrolide, sucurchalasins A and B (1 and 2), and four known cytochalasan monomers (3-6), as well as four known macrolide derivatives (7-10), were obtained from the endophytic fungus Aspergillus spelaeus GDGJ-286. Sucurchalasins A and B (1 and 2) are the first cytochalasan heterodimers formed via a thioether bridge between cytochalasan and curvularin macrolide units. Their structures were elucidated by detailed analysis of NMR, LC-MS/MS, and X-ray crystallography. In bioassays, 1 and 2 exhibited cytotoxic effects on A2780 cells, with IC50 values of 3.9 and 8.3 µM, respectively. They also showed antibacterial activities against E. faecalis and B. subtilis with MIC values of 3.1 and 6.3 µg/mL, respectively.
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Aspergillus , Citocalasinas , Macrolídeos , Aspergillus/química , Citocalasinas/farmacologia , Citocalasinas/química , Citocalasinas/isolamento & purificação , Macrolídeos/farmacologia , Macrolídeos/química , Estrutura Molecular , Humanos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Enxofre/química , Cristalografia por Raios X , Bacillus subtilis/efeitos dos fármacosRESUMO
BACKGROUND: In recent years, the advancement of computational chemistry has offered new insights into the rational design of molecularly imprinted polymers (MIPs). From this aspect, our study tried to give quantitative parameters for evaluating imprinting efficiency and exploring the formation mechanism of MIPs by combining simulation and experiments. METHODS: The pre-polymerization system of sulfadimethoxine (SDM) was investigated using a combination of quantum chemical (QC) calculations and molecular dynamics (MD) simulations. MIPs were prepared on the surface of silica gel by a surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP). RESULTS: The results of the QC calculations showed that carboxylic monomers exhibited higher bonding energies with template molecules than carboxylic ester monomers. MD simulations confirmed the hydrogen bonding sites predicted by QC calculations. Furthermore, it was observed that only two molecules of monomers could bind up to one molecule of SDM, even when the functional monomer ratio was up to 10. Two quantitative parameters, namely, the effective binding number (EBN) and the maximum hydrogen bond number (HBNMax), were defined. Higher values of EBN and HBNMax indicated a higher effective binding efficiency. Hydrogen bond occupancies and RDF analysis were performed to analyze the hydrogen bond formation between the template and the monomer from different perspectives. Furthermore, under the influence of the EBN and collision probability of the template and the monomers, the experimental results show that the optimal molar ratio of template to monomer is 1:3. CONCLUSIONS: The method of monomer screening presented in this study can be extended to future investigations of pre-polymerization systems involving different templates and monomers.
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Cross conjugation, though prevalent in many organic compounds, is typically considered less effective for electron delocalization compared to linear conjugation. Consequently, it is rarely used as the backbone structure for semiconducting conjugated polymers. In this study, we designed and synthesized a novel building block, TIDP, which features a central cyclic dipeptide with cross conjugation characteristics. Strong intramolecular hydrogen bonding interactions confer TIDP with a highly rigid and coplanar conformation. Importantly, theoretical calculations reveal that π electrons are well delocalized across the entire structure, despite its low aromaticity. Conjugated polymers incorporating TIDP exhibit high charge carrier mobilities, demonstrating the effective π electrons delocalization of this innovative building block. Our findings show that with rational design, cross conjugation can achieve effective π electrons delocalization, providing a valuable approach for developing high-performance conjugated polymers for organic electronic materials.
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The purified neutral polysaccharide fraction, namely SBP-1, was isolated and characterized from Schisandra chinensis (Turcz.) Baill crude polysaccharides, which have anti-Parkinson's disease activity were investigated in vivo and in vitro. Experiments have shown that the main chain of SBP-1 was Glcp-(1â, â4)-Glcp-(1â and â4,6)-Glcp-(1â. We also revealed the effect of SBP-1 on the PD mice model and the potential underlying molecular mechanism. The results showed that SBP-1 administration improved behavioral deficits, increased tyrosine hydroxylase-positive cells, attenuated loss of dopaminergic neurons in MPTP-exposed mice, and reduced cell death induced by MPP+. The MCL-1 was identified as the target of SBP-1 by the combination of docking-SPR-ITC, WB, and IF experiments. Subsequently, the study showed that SBP-1 could target MCL-1 to enhance autophagy with a change in the apoptotic response, which was further demonstrated by a change in LC3/P62, PI3K/AKT/mTOR, and possesses a change in the expression of BCL2/BAX/Caspase3. These results demonstrate that SBP-1 may protect neurons against MPP+ or MPTP-induced damage in vitro and in vivo through enhancing autophagy. In summary, these findings indicate that SBP-1 and S. chinensis show potential as effective candidates for further investigation in the prevention and treatment of PD or associated illnesses, specifically through autophagy apoptotic-based mechanisms.
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Autofagia , Proteína de Sequência 1 de Leucemia de Células Mieloides , Doença de Parkinson , Polissacarídeos , Schisandra , Transdução de Sinais , Animais , Schisandra/química , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Autofagia/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Regulação da Expressão Gênica/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismoRESUMO
Balancing the trade-off between accuracy and speed for obtaining higher performance without sacrificing the inference time is a challenging topic for object detection task. Knowledge distillation, which serves as a kind of model compression techniques, provides a potential and feasible way to handle above efficiency and effectiveness issue through transferring the dark knowledge from the sophisticated teacher detector to the simple student one. Despite demonstrating promising solutions to make harmonies between accuracy and speed, current knowledge distillation for object detection methods still suffer from two limitations. Firstly, most of the methods are inherited or refereed from the frameworks in image classification task, and deploy an implicit manner by imitating or constraining the features from the intermediate layers or the output predictions between the teacher and student models. While little consideration has been raised to the intrinsic relevance of the classification and localization predictions in object detection task. Besides, these methods fail to investigate the relationship between detection and distillation tasks in knowledge distillation pipeline, and they train the whole network by simply integrating losses from these two different tasks through hand-crafted designation parameters. For addressing the aforementioned issues, we propose a novel Relation Knowledge Distillation by Auxiliary Learning for Object Detection (ReAL) method in this paper. Specifically, we first design a prediction relation distillation module which makes the student model directly mimic the output predictions from the teacher one, and conduct self and mutual relation distillation losses to excavate the relation information between teacher and student models. Moreover, for better devolving into the relationship between different tasks in distillation pipeline, we introduce the auxiliary learning into knowledge distillation for object detection and develop a dynamic weight adaptation strategy. Through regarding detection task as primary task and treating distillation task as auxiliary task in auxiliary learning framework, we dynamically adjust and regularize the corresponding weights of the losses for these tasks during the training process. Experiments on MS COCO dataset are conducted using various detector combinations of teacher and student models and the results show that our proposed ReAL can achieve obvious improvement on different distillation model configurations, while performing favorably against state-of-the-arts.
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Intact autophagy-lysosomal pathway (ALP) in neuronal survival is crucial. However, it remains unclear whether ALP is intact after subarachnoid hemorrhage (SAH). Ten-eleven translocation (TET) 3 primarily regulates genes related to autophagy in neurons in neurodegenerative diseases. This study aims to investigate the role of TET3 in the ALP following SAH. The results indicate that the ALP is impaired after SAH, with suppressed autophagic flux and an increase in autophagosomes. This is accompanied by a decrease in TET3 expression. Activation of TET3 by α-KG can improve ALP function and neural function to some extent. Silencing TET3 in neurons significantly inhibited the ALP function and increased apoptosis. Inhibition of miR-93-5p, which is elevated after SAH, promotes TET3 expression. This suggests that the downregulation of TET3 after SAH is, at least in part, due to elevated miR-93-5p. This study clarifies the key role of TET3 in the functional impairment of the ALP after SAH. The preliminary exploration revealed that miR-93-5p could lead to the downregulation of TET3, which could be a new target for neuroprotective therapy after SAH.
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Autofagia , Lisossomos , MicroRNAs , Hemorragia Subaracnóidea , Animais , Masculino , Camundongos , Autofagia/fisiologia , Dioxigenases , Lisossomos/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/genéticaRESUMO
In this Letter, an omni-directional reflector (ODR) with a thin hybrid dielectric layer (hybrid-ODR) is proposed to enhance the light extraction efficiency (LEE) for inclined-sidewall-shaped AlGaN-based deep ultraviolet light-emitting diode (DUV LED) by inserting a thin diamond with high refraction index into a conventional Al/Al2O3-based ODR. The three-dimensional finite-difference time-domain (3D FDTD) simulation results show that the LEE of TM-polarized light for the DUV LED with hybrid-ODR is enhanced by 18.5% compared with Al/Al2O3-based ODR. It is because the diamond can transform the evanescent wave in Al2O3 into the propagating light wave in diamond, thereby preventing effective excitation of the surface plasmon polariton (SPP) on the surface of the metal Al. Moreover, the Brewster's angle effect causes the TM-polarized light in diamond to propagate effectively into AlGaN. Furthermore, decreasing the total thickness of the dielectric layer also improves the scattering effect of the inclined sidewall. However, the utilization of hybrid-ODR results in a slight reduction in the LEE for transverse electric (TE) polarized light because the light is confined to the diamond layer and eventually absorbed by the metal Al.
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BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.
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Lesões Encefálicas Traumáticas , Ferroptose , Glucosídeos , Monoterpenos , Proteína Supressora de Tumor p53 , Glucosídeos/farmacologia , Ferroptose/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Animais , Monoterpenos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Camundongos , Masculino , Neurônios/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Paeonia/química , Fármacos Neuroprotetores/farmacologiaRESUMO
Three new compounds 1-glyceryl 9(ß), 10(α), 11(ß)-trihydroxy-12(Z)-octadecenoate, 2'S-20-O-p-hydroxyphenylpropionyloxy-20-hyd-roxyarachidic acid glycerol ester (2), 3-O-α-l-arabinopyranosyl-(1â6)-ß-d-glucopyranoside of ethyl (3S)-hydroxybutanoate (3), as well as a new natural product (4) were isolated from the fruits of Solanum virginianum L. The structures of 26 compounds were determined by comprehensive spectroscopic analyses, NMR calculation, chemical methods, and comparisons of spectroscopic data. Compounds 2 and 16 exhibited good anti-inflammatory activity in the LPS-induced RAW 264.7 inflammatory model with IC50 values of 16.75 ± 1.54 and 22.43 ± 2.01 µM, respectively.
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Cadmium (Cd) accumulates in rice and then moves up the food chain, causing serious health problems for humans. Glutathione S-transferase (GST) binds exogenous hazardous compounds to glutathione (GSH), which performs a variety of roles in plant responses to Cd stress. Here, Cd stimulated the transcripts of a novel OsGST gene, and the OsGST protein, which was localized in the nucleus and cytoplasm, was also induced by Cd. In OsGST deletion mutant lines generated by CRISPR/Cas9, more Cd was accumulated, and Cd hypersensitive phenotypes were observed, while transgenic lines overexpressing OsGST exhibited enhanced Cd tolerance and less Cd accumulation. Further analysis indicated that the osgst mutants exhibited considerably greater reactive oxygen species (ROS) and higher GSH level, and the antioxidant activity associated genes' expression were down-regulated, imply that OsGST controlled rice Cd accumulation and resistance through preserving the equilibrium of the GSH and redox in rice.
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Cádmio , Glutationa , Oryza , Plantas Geneticamente Modificadas , Oryza/genética , Oryza/metabolismo , Cádmio/metabolismo , Cádmio/toxicidade , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Glutationa/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio/metabolismo , Glutarredoxinas/genética , Glutarredoxinas/metabolismoRESUMO
Purpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity. Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis. Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually. Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.
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In this work, we hybridize an air cavity reflector and a nanopatterned sapphire substrate (NPSS) for making an inclined-sidewall-shaped deep ultraviolet micro light-emitting diode (DUV micro-LED) array to enhance the light extraction efficiency (LEE). A cost-effective hybrid photolithography process involving positive and negative photoresist (PR) is explored to fabricate air-cavity reflectors. The experimental results demonstrate a 9.88% increase in the optical power for the DUV micro-LED array with a bottom air-cavity reflector when compared with the conventional DUV micro-LED array with only a sidewall metal reflector. The bottom air-cavity reflector significantly contributes to the reduction of the light absorption and provides more escape paths for light, which in turn increases the LEE. Our investigations also report that such a designed air-cavity reflector exhibits a more pronounced impact on small-size micro-LED arrays, because more photons can propagate into escape cones by experiencing fewer scattering events from the air-cavity structure. Furthermore, the NPSS can enlarge the escape cone and serve as scattering centers to eliminate the waveguiding effect, which further enables the improved LEE for the DUV micro-LED array with an air-cavity reflector.