RESUMO
Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood. Here, we demonstrate that NDV infection profoundly triggers LMP, leading to the translocation of cathepsin B and D and subsequent mitochondria-dependent apoptosis in various tumor and avian cells. Notably, the released cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of reactive oxygen species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents.
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Proteína HN , Vírus da Doença de Newcastle , Animais , Vírus da Doença de Newcastle/metabolismo , Proteína HN/metabolismo , Catepsina B , Apoptose , Lisossomos/metabolismoRESUMO
The pollen viability directly affects the pollination process and the ultimate grain yield of rice. Here, we identified that the MORN motif-containing proteins, OsMORN1 and OsMORN2, had a crucial role in maintaining pollen fertility. Compared with the wild type (WT), the pollen viability of the osmorn1 and osmorn2 mutants was reduced, and pollen germination was abnormal, resulting in significantly lower spikelet fertility, seed-setting rate, and grain yield per plant. Further investigation revealed that OsMORN1 was localized to the Golgi apparatus and lipid droplets. Lipids associated with pollen viability underwent alterations in osmorn mutants, such as the diacylglyceride (18:3_18:3) was 5.1-fold higher and digalactosyldiacylglycerol (18:2_18:2) was 5.2-fold lower in osmorn1, while the triacylglycerol (TG) (16:0_18:2_18:3) was 8.3-fold higher and TG (16:0_18:1_18:3) was 8.5-fold lower in osmorn2 than those in WT. Furthermore, the OsMORN1/2 was found to be associated with rice cold tolerance, as osmorn1 and osmorn2 mutants were more sensitive to chilling stress than WT. The mutants displayed increased hydrogen peroxide accumulation, reduced antioxidant enzyme activities, elevated malondialdehyde content, and a significantly decreased seedling survival rate. Lipidomics analysis revealed distinct alterations in lipids under low temperature, highlighting significant changes in TG (18:2_18:3_18:3) and TG (18:4_18:2_18:2) in osmorn1, TG (16:0_18:2_18:2) and PI (17:2_18:3) in osmorn2 compared to the WT. Therefore, it suggested that OsMORN1 and OsMORN2 regulate both pollen viability and cold tolerance through maintaining lipid homeostasis.
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Oryza , Proteínas de Plantas , Pólen , Oryza/genética , Oryza/fisiologia , Oryza/metabolismo , Pólen/genética , Pólen/fisiologia , Pólen/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Germinação/fisiologia , Regulação da Expressão Gênica de Plantas , Temperatura Baixa , Mutação , Gotículas Lipídicas/metabolismoRESUMO
Volatility of organic aerosols (OAs) significantly influences new particle formation and the occurrence of particulate air pollution. However, the relationship between the volatility of OA and the level of particulate air pollution (i.e., particulate matter concentration) is not well understood. In this study, we compared the chemical composition (identified by an ultrahigh-resolution Orbitrap mass spectrometer) and volatility (estimated based on a predeveloped parametrization method) of OAs in urban PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) samples from seven German and Chinese cities, where the PM2.5 concentration ranged from a light (14 µg m-3) to heavy (319 µg m-3) pollution level. A large fraction (71-98%) of compounds in PM2.5 samples were attributable to intermediate-volatility organic compounds (IVOCs) and semivolatile organic compounds (SVOCs). The fraction of low-volatility organic compounds (LVOCs) and extremely low-volatility organic compounds (ELVOCs) decreased from clean (28%) to heavily polluted urban regions (2%), while that of IVOCs increased from 34 to 62%. We found that the average peak area-weighted volatility of organic compounds in different cities showed a logarithmic correlation with the average PM2.5 concentration, indicating that the volatility of urban OAs increases with the increase of air pollution level. Our results provide new insights into the relationship between OA volatility and PM pollution levels and deepen the understanding of urban air pollutant evolution.
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Aerossóis , Poluentes Atmosféricos , Poluição do Ar , Espectrometria de Massas , Material Particulado , Material Particulado/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Volatilização , Compostos Orgânicos/análise , China , Compostos Orgânicos Voláteis/análiseRESUMO
Exposure to air pollution causes adverse health outcomes, but the toxicity mechanisms remain unclear. Here, we investigated the dynamic toxicities of naphthalene-derived secondary organic aerosol (NSOA) in a human bronchial epithelial cell line (BEAS-2B) and identified the chemical components responsible for toxicities. The chemical composition of NSOA was found to vary with six simulated atmospheric aging conditions (C1-C6), as characterized by high-resolution mass spectrometry and ion mobility mass spectrometry. Global proteome profiling reveals dynamic evolution in toxicity: Stronger proteome-wide impacts were detected in fresh NSOA, but the effects declined along with atmospheric aging. While Nrf2-regulated proteins (e.g., NQO1) were significantly up-regulated, the majority (78 to 97%) of proteins from inflammation and other pathways were down-regulated by NSOA exposure (e.g., Rho GTPases). This pattern is distinct from the reactive oxygen species (ROS)-mediated toxicity pathway, and an alternative cysteine reaction pathway was revealed by the decreased abundance of proteins (e.g., MT1X) prone to posttranslational thiol modification. This pathway was further validated by observing decreased Nrf2 response in reporter cells, after preincubating NSOA with cysteine. Ethynyl-naphthalene probe was employed to confirm the alkylation of cellular proteome thiols on the proteome-wide level by fresh NSOA via in-gel fluorescence imaging. Nontarget analysis identified several unsaturated carbonyls, including naphthoquinones and hydroxylated naphthoquinones, as the toxic components responsible for cysteine reactivity. Our study provides insights into the dynamic toxicities of NSOA during atmospheric aging and identifies short-lived unsaturated carbonyls as the predominant toxic components at the posttranslational level.
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Aerossóis/toxicidade , Naftalenos/química , Naftalenos/toxicidade , Proteoma/efeitos dos fármacos , Linhagem Celular , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Processamento de Proteína Pós-Traducional , Proteômica , Regulação para CimaRESUMO
PURPOSE: Positron emission tomography (PET) with specific diagnostic probes for quantifying CD8+ T cells has emerged as a powerful technique for monitoring the immune response. However, most CD8+ T cell radiotracers are based on antibodies or antibody fragments, which are slowly cleared from circulation. Herein, we aimed to develop and assess 68 Ga-NODAGA-SNA006 for instant PET (iPET) imaging of CD8+ T cells. METHODS: A novel nanobody without a hexahistidine (His6) tag, SNA006-GSC, was designed, site-specifically conjugated with NODAGA-maleimide and radiolabelled with 68 Ga. The PET imaging profiles of 68 Ga-NODAGA-SNA006 were evaluated in BALB/c MC38-CD8+/CD8- tumour models and cynomolgus monkeys. Three volunteers with lung cancer underwent whole-body PET/CT imaging after 68 Ga-NODAGA-SNA006 administration. The biodistribution, pharmacokinetics and dosimetry of patients were also investigated. In addition, combined with immunohistochemistry (IHC), the quantitative performance of the tracer for monitoring CD8 expression was evaluated in BALB/c MC38-CD8+/CD8- and human subjects. RESULTS: 68 Ga-NODAGA-SNA006 was prepared with RCP > 98% and SA > 100 GBq/µmol. 68 Ga-NODAGA-SNA006 exhibited specific uptake in MC38-CD8+ xenografts tumours, CD8-rich tissues (such as the spleen) in monkeys and CD8+ tumour lesions in patients within 1 h. Fast washout from circulation was observed in three volunteers (t1/2 < 20 min). A preliminary quantitative linear relationship (R2 = 0.9668, p < 0.0001 for xenografts and R2 = 0.7924, p = 0.0013 for lung patients) appeared between 68 Ga-NODAGA-SNA006 uptake and CD8 expression. 68 Ga-NODAGA-SNA006 was well tolerated by all patients. CONCLUSION: 68 Ga-NODAGA-SNA006 PET imaging can instantly quantify CD8 expression with an ideal safety profile and is expected to be important for dynamically tracking CD8+ T cells and monitoring immune responses for individualised cancer immunotherapy. TRIAL REGISTRATION: NCT05126927 (19 November 2021, retrospectively registered).
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Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Projetos Piloto , Distribuição Tecidual , Linfócitos T CD8-Positivos , Tomografia Computadorizada por Raios X , Compostos Heterocíclicos com 1 Anel , Tomografia por Emissão de Pósitrons/métodos , Acetatos , Maleimidas , Fragmentos de Imunoglobulinas , Radioisótopos de Gálio , Linhagem Celular TumoralRESUMO
Evaluating interspecies toxicity variation is a long-standing challenge for chemical hazard assessment. This study developed a quantitative interspecies thermal shift assay (QITSA) for in situ, quantitative, and modest-throughput investigation of chemical-protein interactions in cell and tissue samples across species. By using liver fatty acid binding protein (L-FABP) as a case study, the QITSA method was benchmarked with six per- and polyfluoroalkyl substances, and thermal shifts (ΔTm) were inversely related to their dissociation constants (R2 = 0.98). The QITSA can also distinguish binding modes of chemicals exemplified by palmitic acid. The QITSA was applied to determine the interactions between perfluorooctanesulfonate (PFOS) and L-FABP in liver cells or tissues from humans, mice, rats, and zebrafish. The largest thermal stability enhancement by PFOS was observed for human L-FABP followed by the mouse, rat, and zebrafish. While endogenous ligands were revealed to partially contribute to the large interspecies variation, recombinant proteins were employed to confirm the high binding affinity of PFOS to human L-FABP, compared to the rat and mouse. This study implemented an experimental strategy to characterize chemical-protein interactions across species, and future application of QITSA to other chemical contaminants is of great interest.
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Fluorocarbonos , Proteômica , Ácidos Alcanossulfônicos , Animais , Proteínas de Ligação a Ácido Graxo , Ácidos Graxos , Humanos , Fígado , Camundongos , Ratos , Especificidade da Espécie , Peixe-ZebraRESUMO
Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (Danio rerio). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis-induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.
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Compostos Azo , Peixe-Zebra , Animais , Criança , Poeira , Embrião não Mamífero , Humanos , Mutagênicos , ToxicocinéticaRESUMO
More than 1000 per- and polyfluoroalkyl substances (PFASs) have been discovered by nontarget analysis (NTA), but their prioritization for health concerns is challenging. We developed a method by incorporating size-exclusion column co-elution (SECC) and NTA, to screen PFASs binding to human liver fatty acid binding protein (hL-FABP). Of 74 PFASs assessed, 20 were identified as hL-FABP ligands in which eight of them have high binding affinities. Increased PFAS binding affinities correlate with stronger responses in electrospray ionization (ESI-) and longer retention times on a C18 column. This is well explained by a mechanistic model, which revealed that both polar and hydrophobic interactions are crucial for binding affinities. Encouraged by this, we then developed an SECC method to identify hL-FABP ligands, and all eight high-affinity ligands were selectively captured from 74 PFASs. The method was further applied to an aqueous film-forming foam (AFFF) product in which 31 new hL-FABP ligands were identified. Suspect and nontargeted screening revealed these ligands as analogues of perfluorosulfonic acids and homologues of alkyl ether sulfates (C8- and C10/EOn, C8H17(C2H4O)nSO4-, and C10H21(C2H4O)nSO4-). The SECC method was then applied to AFFF-contaminated surface waters. In addition to perfluorooctanesulfonic acid and perfluorohexanesulfonic acid, eight other AFFF chemicals were discovered as novel ligands, including four C14- and C15/EOn. This study implemented a high-throughput method to prioritize PFASs and revealed the existence of many previously unknown hL-FABP ligands.
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Fluorocarbonos/análise , Poluentes Químicos da Água/análise , Proteínas de Ligação a Ácido Graxo , Humanos , ÁguaRESUMO
Pyrethroids and the metabolites have been frequently observed in the environment. Animal data suggests that pyrethroids can induce adverse effect on the cardiovascular system but there are no human studies examining pyrethoids exposure as a risk for coronary heart disease (CHD). We analyzed three nonspecific pyrethroids metabolites in urine and studied the association with CHD risk. A total of 72 CHD patients and 136 healthy subjects were recruited in Shanxi province in China from 2013 to 2014 by matching age and gender. The median concentrations of urinary cis-CDDA (cis-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylic acid), trans-CDDA (trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylic acid) and 3-PBA (3-phenoxybenzoic acid) among healthy subjects were 1.03, 0.42, 0.74 µg/L respectively, while the median concentrations of the three metabolites among CHD patients were 1.93, 1.07, 1.09 µg/L respectively, significantly higher than healthy subjects. Upper tertile of urinary pyrethroid metabolites were associated with an increased risk of CHD compared with the lowest tertile (cis-CDDA: ORT3vsT1 = 6.86, 95% CI: 2.76-17.06, p-trend = 0.000; trans-CDDA: ORT3vsT1 = 6.94; 95% CI: 2.80-17.19; p-trend =0.000; 3-PBA: ORT3vsT1 = 3.62; 95% CI: 1.48-8.88; p-trend = 0.009; total pyrethroid metabolites: ORT3vsT1 = 4.55; 95% CI: 1.80-11.54; p-trend = 0.002). This study provides information on pyrethroids exposure in China and reveals a possible positive association between pyrethroids exposure and the risk of coronary heart disease.
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Doença das Coronárias/epidemiologia , Inseticidas/urina , Piretrinas/metabolismo , Animais , China/epidemiologia , Exposição Ambiental , Humanos , RiscoRESUMO
Neonicotinoids (NEOs) are currently the fastest-growing and most widely used insecticide class worldwide. Increasing evidence suggests that long-term NEO residues in the environment have toxic effects on non-target soil animals. However, few studies have conducted surveys on the effects of NEOs on soil animals, and only few have focused on global systematic reviews or meta-analysis to quantify the effects of NEOs on soil animals. Here, we present a meta-analysis of 2940 observations from 113 field and laboratory studies that investigated the effects of NEOs (at concentrations of 0.001-78,600.000 mg/kg) on different soil animals across five indicators (i.e., survival, growth, behavior, reproduction, and biochemical biomarkers). Furthermore, we quantify the effects of NEOs on different species of soil animals. Results show that NEOs inhibit the survival, growth rate, behavior, and reproduction of soil animals, and alter biochemical biomarkers. Both the survival rate and longevity of individuals decreased by 100 % with NEO residues. The mean values of juvenile survival, cocoon number, and egg hatchability were reduced by 97 %, 100 %, and 84 %, respectively. Both individual and cocoon weights were reduced by 82 %, while the growth rate decreased by 88 % with NEO residues. Our meta-analysis confirms that NEOs pose significant negative impacts on soil animals.
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Inseticidas , Neonicotinoides , Poluentes do Solo , Animais , Poluentes do Solo/toxicidade , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Resíduos de Praguicidas/toxicidade , Resíduos de Praguicidas/análise , Reprodução/efeitos dos fármacos , Solo/química , Comportamento Animal/efeitos dos fármacosRESUMO
The sustainable extraction of saponins was investigated using natural deep eutectic solvents (NADESs) combined with ultrasound-assisted extraction. A novel NADES (butyric acid-urea) that was responsive to ionic strength was designed and used as the extractant. Ultrasound treatment and a catalyst ferric chloride with plant cell wall breaking function were applied to improve the extraction efficiency.Since the solubility of the NADES varied significantly with ionic strength, 95% of NADES was readily separated from the water phase after the addition of sodium chloride, while saponins remained in the water phase for easy collection. The reuse capacity of NADES, the eco-friendliness of the extraction method, and the antioxidant activity of the extract were further evaluated.NADES was continuously recovered and used to extract Polygonatum sibiricum powder: the yield of saponins did not decrease after five cycles of recovery and re-extraction. The penalty point on the "Eco-scale" suggested that the extraction method was "green" (i.e. eco-friendly).Compared with ethanol extracts, the NADES extracts showed a higher saponin concentration and antioxidant activity.The study can contribute to the sustainable and green extraction of hydrophilic active substances in the food and pharmaceutical industries.
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Polygonatum , Saponinas , Solventes , Solventes Eutéticos Profundos , Antioxidantes , Extratos Vegetais , ÁguaRESUMO
Unreasonable application of pesticides may result in residues in the environment and foods. Chiral pesticides consist of two or more enantiomers, which may exhibit different behaviors. This Review intends to provide progress on the enantioselective residues of chiral pesticides in foods. Among the main chiral analytical methods, high performance liquid chromatography (HPLC) is the most frequently utilized. Most chiral pesticides are utilized as racemates; however, due to enantioselective dissipation, bioaccumulation, biodegradation, and chiral conversion, enantiospecific residues have been found in the environment and foods. Some chiral pesticides exhibit strong enantioselectivity, highlighting the importance of evaluation on an enantiomeric level. However, the occurrence characteristics of chiral pesticides in foods and specific enzymes or transport proteins involved in enantioselectivity needs to be further investigated. This Review could help the production of some chiral pesticides to single-enantiomer formulations, thereby reducing pesticide consumption as well as increasing food production and finally reducing human health risks.
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Praguicidas , Humanos , Praguicidas/química , Estereoisomerismo , Cromatografia Líquida de Alta Pressão , AlimentosRESUMO
A tuning fork gyroscope (TFG) with orthogonal thin-walled round holes in the driving and sensing directions is proposed to improve sensitivity. The thin walls formed by through holes produce stress concentration, transforming the small displacement of tuning fork vibration into a large concentrated strain. When piezoelectric excitation or detection is carried out here, the driving vibration displacement and detection output voltage can be increased, thereby improving sensitivity. Besides, quadrature coupling can be suppressed because the orthogonal holes make the optimal excitation and detection positions in different planes. The finite element method is used to verify the benefits of the holes, and the parameters are optimized for better performance. The experimental results show that the sensitivity of the prototype gyroscope with a driving frequency of 890.68 Hz is 100.32 mV/(°/s) under open-loop driving and detection, and the rotation rate can be resolved at least 0.016 (°/s)/Hz, which is about 6.7 times better than that of the conventional TFG. In addition, the quadrature error is reduced by 2.7 times. The gyroscope has a simple structure, high reliability, and effectively improves sensitivity, which is helpful to guide the optimization of piezoelectric gyroscopes and derived MEMS gyroscopes.
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BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. METHODS: This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson's Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. DISCUSSION: In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.
Assuntos
Moxibustão , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Qualidade de Vida , Método Simples-Cego , Constipação Intestinal , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. AIM OF THE STUDY: To explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. MATERIAL AND METHODS: 75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. RESULTS: TJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. CONCLUSION: According to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.
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Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Ratos , Masculino , Animais , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , PPAR alfa/metabolismo , LDL-Colesterol/metabolismo , Silibina/farmacologia , Ratos Sprague-Dawley , Fígado , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Etanol/farmacologia , Superóxido Dismutase/metabolismoRESUMO
The intensive use of pesticides in the North China Plain (NCP) has resulted in widespread contamination of pesticides in the local atmosphere, posing risks to air quality and human health. However, the occurrence and distribution of atmospheric pesticides in the NCP as well as their risk assessment have not been well investigated. In this study, 300 monthly samples were collected using passive air samplers with polyurethane foam at ten rural sites with different crop systems in Quzhou county, the NCP, from June 2021 to May 2022. The pesticides were quantified using mass-spectrometric techniques. Our results revealed that chlorpyrifos, carbendazim, and atrazine were the most frequently found pesticides in the air samples, with detection frequencies of ≥ 87 % across the samples. The average concentrations of atmospheric pesticides during spring (7.47 pg m-3) and summer (16.05 pg m-3) were significantly higher than those during autumn (2.04 pg m-3) and winter (1.71 pg m-3), attributable to the intensified application of pesticides during the warmer seasons. Additionally, cash crop sites exhibited higher concentrations (10.26 pg m-3) of atmospheric pesticides compared to grain crop (5.59 pg m-3) and greenhouse sites (3.81 pg m-3), primarily due to more frequent pesticides spraying events in cash crop fields. These findings indicate a distinct spatial-temporal distribution pattern of atmospheric pesticides influenced by both seasons and crop systems. Furthermore, the model-based inhalation risk assessment indicates that inhalation exposure to atmospheric pesticides is unlikely to pose a significant public concern.
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Poluentes Atmosféricos , Poluição do Ar , Praguicidas , Humanos , Praguicidas/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar/análise , China , Estações do AnoRESUMO
Background: More patients with lung diseases were identified with low-dose computed tomography (CT) popularization and increasing physical examination awareness. Day surgery was routinely conducted in many departments as a relatively mature diagnosis and treatment mode. Thus, this study aimed to assess the feasibility of day surgery in thoracic surgery for pulmonary surgery and provide guidance for selecting suitable patients. Methods: This study retrospectively analyzed the clinical data of patients with pulmonary nodule surgeries. Patients were divided into the day and routine surgery groups following chest tube removal within 48â h postoperatively and the discharge criteria. Each group was further divided into the wedge and anatomic lung resection groups. The feasibility and applicability of day surgery in thoracic surgery was evaluated by calculating the percentage of the day surgery group and comparing the clinical data of the two groups, and corresponding guidance was given for selecting suitable patients for day surgery. Results: The day surgery group accounted for 53.4% of the total number of patients in both groups. Data comparison revealed differences in age, hypertension, coronary heart disease, pulmonary function index, nodule localization, pleural adhesion, total postoperative drainage, and complications in the wedge resection and age, gender, smoking history, pulmonary function indexes, intraoperative adhesions, operative duration, total postoperative drainage volume, and complications in the anatomic lung resection (P < 0.05). There were no significant differences in the rates of re-hospitalization (1/172 ratio 1/150) and re-drainage (0/172 ratio 1/150) (P > 0.05). Conclusion: This study concluded that more than half of the pulmonary surgery can be applied to the treatment mode of day surgery, and day surgery can be applied to the screened patients. It conforms to the concept of accelerated rehabilitation and can speed up bed turnover so that more patients can receive high-level medical treatment promptly.
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BACKGROUND: In segmentectomy, in addition to the anatomy of the segmental hilum, the identification and separation of the intersegmental plane is also an important step of the operation. Because of its simplicity and high efficiency, most thoracic surgeons choose the staplers. But the energy devices also have its unique advantages in the separation of the intersegmental plane. This study compared the clinical efficacy of staplers and energy devices in the separation of the intersegmental planes during the uniport thoracoscopic segmentectomy through the clinical data. METHODS: Clinical data of 89 patients undergoing uniport VATS lung segmentectomy from January 2019 to October 2020 at the First Affiliated Hospital of Soochow University were analyzed retrospectively. According to the different treatment methods of intersegmental plane, the patients were divided into two groups, 55 in the stapler group and 34 in the energy device group. The clinical data of the two groups were compared and analyzed statistically. And the univariate and multivariate logistic regression were also used to explore the influencing factors of postoperative complications. RESULTS: Lung segmentectomy was successfully operated in both groups. There were statistically significant differences in operative duration, number of staplers used, surgical expenses and postoperative complications (P < 0.05). In terms of general data, including tumor location, operative hemorrhage, drainage volume on the first postoperative day, total postoperative drainage volume, postoperative chest tube retention duration, postoperative hospital stay, postoperative blood routine indexes, and postoperative pulmonary function indexes after 3 months, no significant differences were observed (P > 0.05). Smoking history (OR 5.08, 95% CI 1.05-24.56, P = 0.043) and intersegmental plane treatment (OR 3.18, 95% CI 1.11-9.14, P = 0.031) were risk factors for postoperative complications. Patients of the energy device group had a higher incidence of postoperative complications. CONCLUSIONS: In uniport thoracoscopic segmentectomy, the use of energy devices to treat the intersegmental plane will result in longer operative duration and higher postoperative complication rate, but it does not affect postoperative recovery and can help reduce surgical expenses. Both methods are safe and reliable. Clinically, the two methods can be reasonably selected according to the specific situation.
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Neoplasias Pulmonares , Pneumonectomia , Humanos , Pneumonectomia/métodos , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Pulmão , Complicações Pós-Operatórias/etiologia , Cirurgia Torácica VídeoassistidaRESUMO
Background: With the popularization of mobile phones and the development of the Internet, many patients use social media platforms to seek health information. Currently, TikTok, iQiyi, Bilibili, and Weibo are the most popular video platforms in China. Therefore, based on the above facts, this study estimated the quality of lung nodule videos taken in China using these platforms. Methods: The term "lung nodule" was searched on these platforms. Then, the first 30 videos were selected. Subsequently, some videos were excluded after they had been reviewed and analyzed, after which information on the features and sources of these videos was finally assessed using DISCERN, the Journal of the American Medical Association (JAMA) Benchmark Criteria, and the Hexagonal Radar Schema. Analysis was performed according to different groups. Results: 101 videos were included in this study. According to the different sources, although most videos were from physicians (71.3%), comprising those with shorter durations; faster updates; and more likes, comments, and shares; no significant difference in the scores were obtained. Moreover, regarding the different platforms, while Weibo had the highest update, TikTok had more likes, comments, and shares. Investigations also revealed that while score differences were recorded, most videos were rated "very poor" and "poor." Besides, hexagonal radar charts showed a severe deficiency of video information. Conclusions: Although the quality of most videos on the understudied social media platforms was poor, these platforms have huge potential. Therefore, caution should be exercised when using the platforms as information sources about lung nodules, and a better review and push system is needed.
RESUMO
Background: Primary mediastinal germ cell tumors (PMGCT) represent a rare but sometimes highly aggressive type of mediastinal tumors. The current prognostic models for PMGCT are insufficient. This study was undertaken to establish and validate an individualized nomogram for predicting the overall survival (OS) of patients with PMGCT. Methods: We conducted a retrospective analysis of patients with PMGCT diagnosed between 2000 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Clinical variables included surgery subtype, gender, treatment regimens, age, histology, tumor size, stage, chemotherapy, radiation, race, and survival-related information. The main outcome measure was survival duration. The Kaplan-Meier method along with the log-rank test were utilized to estimate the OS. Independent prognostic factors were identified by performing the univariate and multivariate Cox proportional hazards regression analyses, from which an individualized nomogram was constructed to predict 3-, 5-, and 10-year OS of patients with PMGCT. The concordance index (C-index) and calibration curve were used to verify the discrimination and accuracy of the nomogram. Results: A total of 845 patients with PMGCT were recruited from the SEER database and further randomly assigned to a training set (n=635) and a validation set (n=210) at a ratio of 7:3. The 3-, 5-, and 10-year OS for overall PMGCT was 70.0%, 67.1%, and 63.9%, respectively. Cox regression analysis indicated that age, tumor size, stage, chemotherapy, radiation, histology, and surgery type were as independent factors for OS in patients with PMGCT (P<0.05). An individualized nomogram for OS was constructed utilizing these variables, with the C-index of 0.714 [95% confidence interval (CI): 0.695 to 0.743] and 0.756 (95% CI: 0.735 to 0.787) in the training and validation groups. Moreover, good levels of agreement were observed according to the calibration curve between the predicted and actual 3-, 5-, and 10-year survival rates both in the training and validated cohorts, showing that the model could accurately predict patient prognosis. Conclusions: This study documented the first attempt at establishing and validating a novel nomogram for predicting the 3-, 5-, and 10-year OS probabilities of PMGCT. The prognostic nomogram was demonstrated to have good performance for predicting individualized OS of patients with PMGCT.