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Particulate matter (PM) undergoing various aging processes in the atmosphere changes its toxicity. However, the mechanism of toxicity evolution is not fully clarified currently. This study demonstrates that photoaging promotes an increase in the oxidative potential (OP) of atmospheric PM by about 30%, and the increased OP is mainly attributed to the production of secondary organic compounds, while water-soluble metal ions contribute only 11%. The OP of nonextractable matters (NEMs) of atmospheric PM was mostly increased after photoaging, followed by water-soluble matters (WSMs). NEM can produce quinone-like functional groups and secondary persistent free radicals during photoaging, which are most likely to produce reactive oxygen species (ROS). For WSM, the conversion of low-oxidation humic-like substances (HULIS) to high-oxidation HULIS is the main reason for the increase in OP. Quinones, nitrophenols, and N-containing heterocycles are the OP contributors produced during the conversion process. Among them, quinones are the main secondary oxidizing active compounds, while nitro-phenolic compounds and N-containing heterocyclic compounds may play a catalyst-like role, facilitating the production of oxidizing active compounds and ROS in the newly converted high-oxidation HULIS. This study clarifies the secondary OP generation mechanism and provides new insights into the uncertainty of PM toxicity during atmospheric aging.
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To explore the association between fluoride exposure and depression / anxiety in adults, the 1,169 participants were recruited. The demographic information of participants was obtained through questionnaire survey and physical measurements. Morning urine samples were collected, and urinary fluoride (UF) level was determined. Changes in depression and anxiety levels were evaluated using the Patient Health Questionnaire-2 and General Anxiety Disorder-2 scales. The association between psychiatric disorders and UF levels was analyzed. In the total population, the prevalence of depression and anxiety were 3.17% and 4.19%, respectively. These results showed no significant association between depression / anxiety scale scores and UF levels. Logistic regression suggested no significant association between depression / anxiety levels, and UF levels, but there was an interaction between UF and income on depression. Our findings highlighted the interaction between fluoride exposure and monthly income, which may affect depression in adults.
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China's nitrogen oxide (NOx) emissions have undergone significant changes over the past few decades. However, nonfossil fuel NOx emissions are not yet well constrained in urban environments, resulting in a substantial underestimation of their importance relative to the known fossil fuel NOx emissions. We developed an approach using machine learning that is accurate enough to generate a long time series of the nitrogen isotopic composition (δ15N) of atmospheric nitrate using high-level accuracies of air pollutants and meteorology data. Air temperature was found to be the critical driver of the variation of nitrate δ15N at daily resolution based on this approach, while significant reductions of aerosol and its precursor emissions played a key role in the change of nitrate δ15N on the yearly scale. Predictions from this model found a significant decrease in nitrate δ15N in Chinese megacities (Beijing and Guangzhou as representative cities in the north and south, respectively) since 2013, implying an enhanced contribution of nonfossil fuel NOx emissions to nitrate aerosols (up to 22%-26% in 2021 from 18%-22% in 2013 quantified by an isotope mixing model), as confirmed by the Weather Research and Forecasting model coupled with online chemistry (WRF-Chem) simulation. Meanwhile, the declining contribution in coal combustion (34%-39% in 2013 to 31%-34% in 2021) and increasing contribution of natural gas combustion (11%-14% in 2013 to 14%-17% in 2021) demonstrated the transformation of China's energy structure from coal to natural gas. This approach provides missing records for exploring long-term variability in the nitrogen isotope system and may contribute to the study of the global reactive nitrogen biogeochemical cycle.
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Contaminantes Atmosféricos , Nitratos , Nitratos/análisis , Gas Natural , Estaciones del Año , Monitoreo del Ambiente/métodos , China , Contaminantes Atmosféricos/análisis , Carbón Mineral/análisis , Óxido Nítrico , Isótopos de Nitrógeno/análisis , Aerosoles/análisis , Material Particulado/análisisRESUMEN
The deterioration of air quality via anthropogenic activities during the night period has been deemed a serious concern among the scientific community. Thereby, we explored the outdoor particulate matter (PM) concentration and the contributions from various sources during the day and night in winter and spring 2021 in a megacity, northwestern China. The results revealed that the changes in chemical compositions of PM and sources (motor vehicles, industrial emissions, coal combustion) at night lead to substantial PM toxicity, oxidative potential (OP), and OP/PM per unit mass, indicating high oxidative toxicity and exposure risk at nighttime. Furthermore, higher environmentally persistent free radical (EPFR) concentration and its significant correlation with OP were observed, suggesting that EPFRs cause reactive oxygen species (ROS) formation. Moreover, the noncarcinogenic and carcinogenic risks were systematically explained and spatialized to children and adults, highlighting intensified hotspots to epidemiological researchers. This better understanding of day-night-based PM formation pathways and their hazardous impact will assist to guide measures to diminish the toxicity of PM and reduce the disease led by air pollution.
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Contaminantes Atmosféricos , Material Particulado , Niño , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Radicales Libres/análisis , Especies Reactivas de Oxígeno , China , Monitoreo del AmbienteRESUMEN
Periodontal tissues, including gingiva, cementum, periodontal ligament, and alveolar bone, play important roles in oral health. Under physiological conditions, periodontal tissues surround and support the teeth, maintaining the stability of the teeth and distributing the chewing forces. However, under pathological conditions, with the actions of various pathogenic factors, the periodontal tissues gradually undergo some irreversible changes, that is, gingival recession, periodontal ligament rupture, periodontal pocket formation, alveolar bone resorption, eventually leading to the loosening and even loss of the teeth. Currently, the regenerations of the periodontal tissues are still challenging. Therefore, it is necessary to study the development of the periodontal tissues, the principles and processes of which can be used to develop new strategies for the regeneration of periodontal tissues. This review summarizes the development of periodontal tissues and current strategies for periodontal healing and regeneration.
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Ligamento Periodontal , Periodoncio , Ligamento Periodontal/patología , Ligamento Periodontal/fisiología , Periodoncio/fisiologíaRESUMEN
Oral squamous cell carcinoma (OSCC) and hypopharyngeal squamous cell carcinoma (HSCC) are representative of head and neck squamous cell carcinoma (HNSCC) and the molecular pathogenesis has not been completely clarified. Ubiquitin-conjugating enzyme E2 L3 (UBE2L3) is the key member of the E2 family that encodes 153 amino acid residues. Previous studies demonstrate that UBE2L3 is aberrantly overexpressed in various types of human cancers, suggesting that UBE2L3 may function as an oncogene. However, its functional role and the potential mechanisms in the OSCC and HSCC remain unclear. In the present study, we found that UBE2L3 was significantly upregulated in clinical HNSCC samples and HNSCC cell lines, and patients with lower UBE2L3 expression have a higher survival rate. Two HNSCC cell lines FaDu (HSCC cells) and CAL-27 (OSCC cells) with moderate expression of UBE2L3 were selected for in vitro experiments. We proved that UBE2L3 overexpression was positively associated with cellular malignant phenotypes in vitro, including proliferation, invasion, migration, and tumor growth in vivo. Conversely, UBE2L3 suppression diametrically yielded opposing results. Our further study demonstrated that overexpression of UBE2L3 significantly activated the nuclear factor kappa B (NF-κB) signaling pathway through promoting NF-κB p65 nuclear translocation and the ubiquitination and degradation of IκBα protein. Additionally, UBE2L3 was proved to be targeted and negatively regulated by miR-378a-5p, and UBE2L3 overexpression reversed the effects of miR-378a-5p upregulation. Collectively, the present study indicates that UBE2L3 may promote OSCC and HSCC progression via activating the NF-κB signaling by increasing IκBα degradation, indicating that UBE2L3 may be a potential therapeutic target for the treatment of HNSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , Hipofaringe/metabolismo , Hipofaringe/patología , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Boca/genética , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismoRESUMEN
Metal ions are key components in atmosphere that potentially affect the optical properties and photochemical reactivity of atmospheric humic-like substances (HULIS), while this mechanism is still unclear. In this study, we demonstrated that atmospheric HULIS coupled with Fe3+, Cu2+, Zn2+, and Al3+ exhibited distinct optical properties and reactive intermediates from that of HULIS utilizing three-dimensional fluorescence spectroscopy and electron paramagnetic resonance spectroscopy. The HULIS components showed light absorption that increased by 56% for the HULIS-Fe3+ system, fluorescence blue shift, and fluorescence quenching, showing a certain dose-effect relationship. These are mainly attributed to the fact that the highly oxidative HULIS chromophores have a stronger complexing ability with Fe3+ ions than the other metal ions. In addition, triplet organics (promoting ratio: 53%) and reactive oxygen species (promoting ratio: 82.6%) in the HULIS-Fe3+ system showed obvious generation promotion. Therefore, the main assumption of the photochemical mechanisms of atmospheric HULIS in the HULIS-Fe3+ system is that Fe3+ ions can form 3HULIS*-Fe3+ complexation with photoexcited 3HULIS* and then transition to the ground state through energy transfer, electron transfer, or nonradiative transition, accompanied by the formation of singlet oxygen and hydroxyl radicals. Our results provide references for evaluating the radiative forcing and aging effect of metal ions on atmospheric aerosols.
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Contaminantes Atmosféricos , Sustancias Húmicas , Sustancias Húmicas/análisis , Especies Reactivas de Oxígeno/química , Compuestos Férricos , Aerosoles/química , Radical Hidroxilo , Material Particulado/análisis , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisisRESUMEN
Brucellosis is one of the most serious and widespread zoonotic diseases, which seriously threatens human health and the national economy. This study was based on the T/B dominant epitopes of Brucella outer membrane protein 22 (Omp22), outer membrane protein 19 (Omp19) and outer membrane protein 28 (Omp28), with bioinformatics methods to design a safe and effective multi-epitope vaccine. The amino acid sequences of the proteins were found in the National Center for Biotechnology Information (NCBI) database, and the signal peptides were predicted by the SignaIP-5.0 server. The surface accessibility and hydrophilic regions of proteins were analysed with the ProtScale software and the tertiary structure model of the proteins predicted by I-TASSER software and labelled with the UCSF Chimera software. The software COBEpro, SVMTriP and BepiPred were used to predict B cell epitopes of the proteins. SYFPEITHI, RANKpep and IEDB were employed to predict T cell epitopes of the proteins. The T/B dominant epitopes of three proteins were combined with HEYGAALEREAG and GGGS linkers, and carriers sequences linked to the N- and C-terminus of the vaccine construct with the help of EAAAK linkers. Finally, the tertiary structure and physical and chemical properties of the multi-epitope vaccine construct were analysed. The allergenicity, antigenicity and solubility of the multi-epitope vaccine construct were 7.37-11.30, 0.788 and 0.866, respectively. The Ramachandran diagram of the mock vaccine construct showed 96.0% residues within the favoured and allowed range. Collectively, our results showed that this multi-epitope vaccine construct has a high-quality structure and suitable characteristics, which may provide a theoretical basis for future laboratory experiments.
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Vacuna contra la Brucelosis/química , Brucella/inmunología , Epítopos de Linfocito B/química , Epítopos de Linfocito T/química , Secuencia de Aminoácidos , Antígenos Bacterianos/química , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacuna contra la Brucelosis/inmunología , Brucelosis/prevención & control , Biología Computacional , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Humanos , Inmunogenicidad Vacunal , Modelos Moleculares , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Solubilidad , Vacunas de Subunidad/química , Vacunas de Subunidad/inmunologíaRESUMEN
Nitrogen oxides (NOx) are a key precursor in O3 formation. Although stringent anthropogenic NOx emission controls have been implemented since the early 2000s in the United States, several rural regions of California still suffer from O3 pollution. Previous findings suggest that soils are a dominant source of NOx emissions in California; however, a statewide assessment of the impacts of soil NOx emission (SNOx) on air quality is still lacking. Here we quantified the contribution of SNOx to the NOx budget and the effects of SNOx on surface O3 in California during summer by using WRF-Chem with an updated SNOx scheme, the Berkeley Dalhousie Iowa Soil NO Parameterization (BDISNP). The model with BDISNP shows a better agreement with TROPOMI NO2 columns, giving confidence in the SNOx estimates. We estimate that 40.1% of the state's total NOx emissions in July 2018 are from soils, and SNOx could exceed anthropogenic sources over croplands, which accounts for 50.7% of NOx emissions. Such considerable amounts of SNOx enhance the monthly mean NO2 columns by 34.7% (53.3%) and surface NO2 concentrations by 176.5% (114.0%), leading to an additional 23.0% (23.2%) of surface O3 concentration in California (cropland). Our results highlight the cobenefits of limiting SNOx to help improve air quality and human health in rural California.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , California , Humanos , Iowa , Óxidos de Nitrógeno/análisis , Ozono/análisis , Suelo , Estados UnidosRESUMEN
Exploring the molecular mechanism of oral squamous cell carcinoma (OSCC) pathogenesis is of great significance for its improvement and therapy. Non-structural maintenance of chromatin condensin I complex subunit G (NCAPG) is responsible for chromatin condensation and is associated with the progression of many malignant tumors. This study was aimed to investigate the role of NCAPG on OSCC pathogenesis. NCAPG mRNA expression data in OSCC tissues were obtained from the Gene Expression Omnibus (GEO) database and NCAPG protein expression in OSCC cell lines was determined by western blotting analysis. The results demonstrated that NCAPG expression in OSCC tissues and cells was higher than that of normal control. Following the short interfering RNA (siRNA) knockdown of NCAPG in two OSCC cell lines, we observed that NCAPG depletion notably inhibited OSCC proliferation and cell cycle progression, as well as promoted apoptosis in vitro. Besides, silencing of NCAPG specifically inhibited the GSK-3ß/ß-catenin signaling. Furthermore, we demonstrated that NCAPG was a downstream target of miR-378a-3p. NCAPG silencing counteracted the effect of the miR-378a-3p inhibitor on cell proliferation/cycle induction. Collectively, these findings suggest that NCAPG is crucial in OSCC progression and development, and may serve as a potential therapeutic target for OSCC.
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Carcinoma de Células Escamosas , Proteínas de Ciclo Celular , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Apoptosis/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glucógeno Sintasa Quinasa 3 beta/genética , Humanos , MicroARNs/genética , Neoplasias de la Boca/genética , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello , beta Catenina/metabolismoRESUMEN
It is unclear whether patients with hypertension are more likely to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and whether there is a difference in the severity of coronavirus disease (COVID-19) pneumonia in patients who have taken ACEI/ARB drugs compared with those who have not.This observational study included data from all patients with clinically confirmed COVID-19 admitted to Hankou Hospital, Wuhan, China, between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cut off on March 8, 2020.A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older and were more likely to have preexisting comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Moreover, patients with hypertension tended to have higher positive rate for SARS-CoV-2 PCR detection. Multivariate logistic regression analysis showed that age (P = 0.005) and gender (P = 0.019) were independent risk factors associated with the severity of pneumonia in patients on admission, whereas ACEI/ARB treatment (P = 0.184) was not.Patients with COVID-19 with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. ACEI/ARB drugs did not influence the severity of pneumonia in patients with SARS-CoV-2. In future studies, a larger sample size and multi-center clinical data would be needed to support these conclusions.
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COVID-19/epidemiología , Hospitalización , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , COVID-19/complicaciones , COVID-19/diagnóstico , China , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores SexualesRESUMEN
This study focuses on analyzing the physicochemical properties, structural characteristics and dominant epitopes of Brucella outer membrane protein 2b (Omp2b), periplasmic binding protein (P39) and Brucella lumazine synthase (BLS) proteins by bioinformatics methods, and to provide a theoretical basis for constructing multi-epitope vaccines. The amino acid sequences of three kinds of proteins were obtained from the UniProt database. The highest frequency alleles in northern China were obtained from the AlleleFrequencies database. Analysis of the physicochemical properties of the proteins by ProtParam online software. Analysis of the secondary structure of the proteins were predicted by SOMPA online software. Using SWISS-MODEL online software constructed and analyzed the tertiary structure of the proteins. Using ABCpred, BepiPred, BCPred and SVMTrip online software analyzed linear B cell epitopes of proteins, The T cell dominant epitope of the protein was analyzed using SYFPEITHI, RANKPEP and IEDB online software. Omp2b was identified three linear B cell dominant epitopes, five CD8+ T cell dominant epitopes, and three CD4+ T cell dominant epitopes. P39 was identified three linear B cell dominant epitopes, two CD8+ T cell dominant epitopes, and two CD4+ T cell dominant epitopes. BLS was identified one linear B cell dominant epitope, one CD8+ T cell dominant epitope, and two CD4+ T cell dominant epitopes. The results indicated that epitope prediction of three Brucella vaccine candidate proteins can provide a theoretical basis for the construction of an ideal multivalent epitope vaccine against Brucella.
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Brucella , Vacunas , Brucella/genética , China , Biología Computacional , Epítopos de Linfocito B/genética , Epítopos de Linfocito T/genética , Proteínas de la Membrana , Complejos Multienzimáticos , Vacunas CombinadasRESUMEN
It remains unclear whether melatonin and its analogues prevent postoperative delirium (POD). Therefore, we conducted a systematic review and meta-analysis to evaluate the effect of melatonin and its analogues on POD prevention. PubMed, Cochrane Library, Web of Science, Embase and CINAHL databases were searched. Primary outcome was the incidence of POD. Six randomized controlled trials, 2 cohort studies and 1 case-control study were included in this meta-analysis. Results showed that melatonin and its analogue ramelteon decreased the incidence of POD in the entire adult surgical population (odds ratio [OR] = 0.45, 95% confidence interval [CI] 0.24-0.84, P = .01). When administered at a higher dose (5 mg), melatonin was effective in reducing the POD incidence (OR = 0.32, 95% CI 0.20-0.52, P < .00001). Melatonin administered less than 5 elimination half-lives before the surgery significantly reduced the POD incidence (OR = 0.31, 95% CI 0.19-0.49, P < .00001). Current literature supports the effectiveness of melatonin and its analogue ramelteon in POD prevention. However, the present study was limited by the significant heterogeneity of the included studies. More studies are needed to ascertain the preventive effect of melatonin and its analogues on the incidence of delirium after cardiac and noncardiac surgeries.
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Delirio del Despertar/prevención & control , Indenos/uso terapéutico , Melatonina/uso terapéutico , HumanosRESUMEN
Breast cancer (BC) is the most common type of fatal cancer in women. New therapeutic strategies need to be explored to enhance the efficacy of doxorubicin by overcoming the resistance of BC cells. NUF2 is a component of the Ndc80 centromere complex and is a key substance in mediating mitosis and affects the progression of multiple tumors. However, the role as well as mechanisms of NUF2 resistance in BC remain unclear. This study aims to reveal the role of NUF2 in drug resistance in BC. We here revealed that NUF2 was highly expressed in human BC. NUF2 depletion-derived exosomes blocked the growth of BC cells. Further, NUF2 ablation-derived exosomes inhibited autophagy in BC cells. Also, NUF2 ablation-derived exosomes improved doxorubicin resistance in BC cells. Mechanically, NUF2 ablation-derived exosomes blocked PI3K/AKT/mTOR axis in BC cells. In summary, NUF2 ablation-derived exosomes blocked the autophagy of BC cells and improved doxorubicin resistance via mediating PI3K/AKT/mTOR axis.
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Autofagia , Neoplasias de la Mama , Movimiento Celular , Doxorrubicina , Resistencia a Antineoplásicos , Exosomas , Humanos , Doxorrubicina/farmacología , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Autofagia/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
ABSTRACT: Sepsis-induced acute kidney injury (SAKI) poses a significant clinical challenge with high morbidity and mortality. Excessive mitochondrial fission has been identified as the central pathogenesis of sepsis-associated organ damage, which is also implicated in the early stages of SAKI. Sirtuin 5 (SIRT5) has emerged as a central regulator of cellular mitochondrial function; however, its role in the regulation of sepsis-induced excessive mitochondrial fission in kidney and the underlying mechanism remains unclear. In this study, SAKI was modeled in mice through cecal ligation and puncture, and in human renal tubular epithelial (HK-2) cells stimulated with lipopolysaccharide (LPS), to mimic the cell SAKI model. Our findings revealed that septic mice with a SIRT5 knockout exhibited shortened survival times and elevated levels of renal injury compared to wild-type mice, suggesting the significant involvement of SIRT5 in SAKI pathophysiology. Additionally, we observed that SIRT5 depletion led to increased renal mitochondrial fission, while the use of a mitochondrial fission inhibitor (Mdivi-1) reversed the detrimental effects caused by SIRT5 depletion, emphasizing the pivotal role of SIRT5 in preventing excessive mitochondrial fission. In vitro experiments demonstrated that the overexpression of SIRT5 effectively mitigated the adverse effects of LPS on HK-2 cells viability and mitochondrial fission. Conversely, downregulation of SIRT5 decreased HK-2 cells viability and exacerbated LPS-induced mitochondrial fission. Mechanistically, the protective function of SIRT5 may be in part, ascribed to its desuccinylating action on ATPase inhibitory factor 1. In conclusion, this study provides novel insights into the underlying mechanisms of SAKI, suggesting the possibility of identifying future drug targets in terms of improved mitochondrial dynamics by SIRT5.
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Lesión Renal Aguda , Dinámicas Mitocondriales , Sepsis , Sirtuinas , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Animales , Sepsis/complicaciones , Sepsis/metabolismo , Ratones , Sirtuinas/metabolismo , Humanos , Proteína Inhibidora ATPasa , Masculino , Ratones Noqueados , Ratones Endogámicos C57BL , Lipopolisacáridos/toxicidad , Línea CelularRESUMEN
Inflammatory osteolysis poses a significant worldwide threat to public health. However, current monotherapies, which target either the prevention of the inflammatory response or the attenuation of osteoclast (OC) formation, have limited efficacy due to the complexity of the bone immune system being overlooked. Herein, by means of modifying salmon calcitonin (sCT), a multifunctional nano-system (AuNDs-sCT) was designed to synergistically inhibit OC differentiation and reverse the inflammatory microenvironment against inflammatory osteolysis. On the one hand, AuNDs-sCT effectively restrained OC differentiation by binding to the calcitonin receptors on the surface of OC precursors, resulting in the down-regulation of OC-specific genes and proteins. The targeted capacity of AuNDs-sCT provided a more durable and precise therapeutic effect. On the other hand, AuNDs-sCT exhibited antioxidant and anti-inflammatory effects, which regulated the polarization "switch" from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype in macrophages by the inhibition of NF-κB p65 phosphorylation, thereby effectively reversed the local inflammatory microenvironment. Additionally, AuNDs-sCT served as a promising fluorescent probe, enabling real-time visualization of the therapeutic process. This capability is expected to optimize drug administration and evaluate therapeutic effects. In summary, by inhibiting OC differentiation and reprogramming macrophages, AuNDs-sCT successfully realized drug repurposing and achieved the "one arrow two eagles" therapeutic strategy, which offers a synergistic and effective treatment option for the clinical management of inflammatory osteolysis.
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As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.
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Multiple primary tumors of the parotid gland refer to the occurrence of 2 or more primary tumors in the ipsilateral or bilateral parotid gland metachronously or synchronously, which do not originate from postoperative recurrence or metastasis. Multiple primary tumors of the parotid gland, especially synchronous benign and malignant tumors, are extremely uncommon. A rare case of multiple Warthin tumors with epithelial-myoepithelial carcinoma of the ipsilateral parotid gland is reported as follows.
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Carcinoma , Neoplasias Primarias Múltiples , Neoplasias de la Parótida , Humanos , Glándula Parótida/patología , Neoplasias de la Parótida/cirugía , Neoplasias de la Parótida/patología , Carcinoma/cirugía , Carcinoma/patología , Neoplasias Primarias Múltiples/patologíaRESUMEN
Ferroptosis is a type of non-apoptotic cell death, which demonstrates a definite iron-dependent expression pattern and is associated with lipid peroxidation. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis. Ferroptosis is involved in the development and progression of various diseases, such as cancer, tissue ischemia-reperfusion injury, neurological diseases, and respiratory diseases. It has been established previously that ferroptotic cells trigger the innate immune system by releasing inflammation-linked damage-related molecules, and immune cells stimulate the inflammatory response by recognizing the operational mechanism of ferroptosis. Some anti-inflammatory drugs have been shown to inhibit ferroptosis in certain cell models. Conversely, some ferroptosis inhibitors also exert anti-inflammatory effects in certain diseases. The present review evaluated the relationship between ferroptosis and inflammation, as well as the underlying internal mechanism, and provided valuable insights into developing novel treatment strategies for inflammatory diseases and cancer.
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Ferroptosis , Neoplasias , Humanos , Hierro/metabolismo , InflamaciónRESUMEN
Road dust pollution is still an important environmental problem in the cities of northwest China. To better understand the risk exposure and sources of unhealthy metals in road dust and foliar dust, the dust samples were collected in Xi'an city, Northwest China. The sampling period was during December 2019 and 53 metals in the dust were analyzed using Inductive Coupled Plasma Emission Spectrometer (ICPA-RQ). Compared to road dust, most metals are found in relatively higher concentrations in foliar dust, especially water-soluble metals, with Mn being 3710 times more abundant in foliar dust. However, the regional characteristics of road dust are more pronounced, i.e., the concentrations of Co and Ni are six times higher in industrial manufacturing areas than in residential areas. The results of the non-negative matrix factorization and principal component analysis source analyses demonstrate this difference, the dust in Xi'an is mainly from transportation (63 %) and natural sources (35 %). From the emission characteristics of the traffic source dust, brake wear is the main cause of traffic source, accounting for 43 %. However, the metal sources in each principal component of foliar dust show a more mixed state, which is consistent with the results of regional characterization. The health risk evaluation shows that traffic sources are the main risk source and contribute 67 % to the total risk. Among them, Pb from tire wear is the main contribution to the total non-carcinogenic risk for children, which is close to the risk threshold. In addition, Cr and Mn are also worthy of attention. The above results all emphasize the contribution of traffic emissions, especially the non-tailpipe emission component, to dust emissions and health risks. Therefore, controlling vehicle wear and tear and exhaust emissions should be the main way to improve air quality, such as traffic control and improvement of vehicle component materials.