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AIM: To assess diagnostic and prognostic value of regulator of calcineurin 3 (RCAN3) in various malignancies. METHODS: RCAN3 expression levels were assessed across pan-cancer data sets including various molecular and immune subtypes. Receiver operating characteristic (ROC) and Kaplan-Meier curves were employed to determine the diagnostic and prognostic value of RCAN3 in pan-cancer, respectively. Enrichment analyses were used to identify RCAN3-associated terms and pathways. A special focus was placed on cervical squamous cell carcinoma and endocervical adenocarcinoma cervical cancer (CESC); we assessed the prognostic value of RCAN expression within distinct clinical subgroups and its effect on m6A modifications and immune infiltration. RESULTS: RCAN3 expression varied not only in different cancer types but also in different molecular and immune subtypes of cancers. RCAN3 displayed high accuracy in diagnosing and predicting cancers, and RCAN3 expression level was associated with the prognosis of certain cancers. CESC patients with a high RCAN3 level had a worse overall survival, disease-specific survival, and progression-free interval. RCAN3 expression was related to multiple m6A modifier genes and immune cells. CONCLUSION: In general, RCAN3 can serve as a novel biomarker for the diagnosis and prognosis in pan-cancer, especially in CESC. It may represent a promising molecular target for developing new treatments. However, our analysis is limited to bioinformatic predictions, and further biological experiments are necessary to verify our results.
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Biomarcadores Tumorais , Humanos , Prognóstico , Feminino , Biomarcadores Tumorais/genética , Curva ROC , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Estimativa de Kaplan-Meier , Neoplasias/diagnóstico , Neoplasias/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genéticaRESUMO
Both soluble phosphorus (P) deficiency and petroleum hydrocarbon contamination represent challenges in soil environments. While phosphate-solubilizing bacteria and hydrocarbon-degrading bacteria have been identified and employed in environmental bioremediation, the bacteria co-adapted to soluble P deficiency and hydrocarbon contamination has rarely been reported. This study explored the ability of Acinetobacter oleivorans S4 (A. oleivorans S4) to solubilize phosphate using n-hexadecane (H), glucose (G), and a mixed carbon source (HG) in tricalcium phosphate (TCP) medium. A. oleivorans S4 exhibited robust growth in H-TCP, releasing 31 mg L-1 of soluble P. Conversely, A. oleivorans S4 barely grew in G-TCP, releasing 654 mg L-1 of soluble P. In HG-TCP, biomass surpassed that in H-TCP, with phosphate release comparable to that in G-TCP. HPLC analysis revealed a small amount of TCA cycle acids in H-TCP and a large amount of gluconate in G-TCP and HG-TCP. Transcriptomic analysis showed elevated expression of genes associated with alkane degradation, P starvation, N utilization, and trehalose synthesis in H-TCP, revealing the molecular co-adaptation mechanism of A. oleivorans S4. Furthermore, the addition of glucose enhanced alkane degradation, P and N utilization, and reduced trehalose synthesis. It indicated that incomplete glucose metabolism may provide energy for other reactions, and the increase in soluble P mediated by gluconate may alleviate oxidative stress. Overall, A. oleivorans S4 proves promising for remediating soluble P-deficient and hydrocarbon-contaminated environments, and glucose stimulates its transformation into a super phosphate-solubilizing bacterium.
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Acinetobacter , Biodegradação Ambiental , Hidrocarbonetos , Fósforo , Fósforo/deficiência , Fósforo/metabolismo , Acinetobacter/metabolismo , Hidrocarbonetos/metabolismo , Poluentes do Solo/metabolismo , Alcanos/metabolismoRESUMO
This article intends to study the asynchronous control problem for 2-D Markov jump systems (MJSs) with nonideal transition probabilities (TPs) under the Roesser model. Two practical considerations motivate the current work. First, considering that the system mode cannot always be observed accurately, a hidden Markov model (HMM) is adopted to describe the relationship between the mismatched modes. Second, considering that the TPs information related to the Markov process and the observation process is difficult to obtain, the nonideal TPs (unknown or uncertain) are simultaneously considered on the two processes. Under the considerations, several new sufficient conditions are developed for concerned closed-loop 2-D MJSs with nonideal TPs, by which the asymptotic mean square stability is ensured with an H∞ performance index. A nonconservative separation strategy is utilized to decouple the system mode TPs and the observation TPs to facilitate the analysis of nonideal TPs. An unified LMI-based condition is finally developed for the concerned closed-loop 2-D MJSs with/without nonideal TPs, showing more satisfactory conservatism than that in the literature. In the end, we present two examples to validate the superiority of the proposed design method.
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BACKGROUND: Diabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability and death in DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) plays an important role in maintaining mitochondrial respiration, but whether it is involved in regulating the progression of advanced glycation end products (AGEs)-mediated DFU is still unclear. METHODS: Firstly, the role of AGEs on cell viability, migration, and mitochondrial respiration in human umbilical vein endothelial cells (HUVECs) was explored in vitro. Next, NDUFB5 expression was detected in human samples and AGEs-treated HUVECs, and NDUFB5's effect on AGEs-induced HUVECs injury and skin wound in diabetic mice was further clarified. In addition, the role of m6A modification mediated by methyltransferase-like 3 (METTL3) in regulating NDUFB5 expression and AGEs-induced HUVECs injury was investigated. RESULTS: NDUFB5 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs, whereas mitochondrial fusion promoter M1 facilitated cell viability, migration, and mitochondrial oxiadative respiration in NDUFB5 knockdown HUVECs. Meanwhile, NDUFB5 promotes skin wound healing in diabetic mice. Besides, METTL3-mediated m6A modification and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced NDUFB5 expression in HUVECs. Furthermore, METTL3 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs by increasing NDUFB5. CONCLUSION: METTL3-mediated NDUFB5 m6A modification inhibits AGEs-induced cell injury in HUVECs. METTL3 and NDUFB5 might serve as potential targets for DFU therapy in the future.
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Movimento Celular , Pé Diabético , Células Endoteliais da Veia Umbilical Humana , Metiltransferases , Mitocôndrias , Cicatrização , Animais , Humanos , Masculino , Camundongos , Respiração Celular , Sobrevivência Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Pé Diabético/patologia , Pé Diabético/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Metiltransferases/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismoRESUMO
AIM: To develop a decision-support tool for predicting extubation failure (EF) in neonates with bronchopulmonary dysplasia (BPD) using a set of machine-learning algorithms. METHODS: A dataset of 284 BPD neonates on mechanical ventilation was used to develop predictive models via machine-learning algorithms, including extreme gradient boosting (XGBoost), random forest, support vector machine, naïve Bayes, logistic regression, and k-nearest neighbor. The top three models were assessed by the area under the receiver operating characteristic curve (AUC), and their performance was tested by decision curve analysis (DCA). Confusion matrix was used to show the high performance of the best model. The importance matrix plot and SHapley Additive exPlanations values were calculated to evaluate the feature importance and visualize the results. The nomogram and clinical impact curves were used to validate the final model. RESULTS: According to the AUC values and DCA results, the XGboost model performed best (AUC = 0.873, sensitivity = 0.896, specificity = 0.838). The nomogram and clinical impact curve verified that the XGBoost model possessed a significant predictive value. The following were predictive factors for EF: pO2, hemoglobin, mechanical ventilation (MV) rate, pH, Apgar score at 5 min, FiO2, C-reactive protein, Apgar score at 1 min, red blood cell count, PIP, gestational age, highest FiO2 at the first 24 h, heart rate, birth weight, pCO2. Further, pO2, hemoglobin, and MV rate were the three most important factors for predicting EF. CONCLUSIONS: The present study indicated that the XGBoost model was significant in predicting EF in BPD neonates with mechanical ventilation, which is helpful in determining the right extubation time among neonates with BPD to reduce the occurrence of complications.
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Extubação , Displasia Broncopulmonar , Aprendizado de Máquina , Nomogramas , Respiração Artificial , Humanos , Displasia Broncopulmonar/terapia , Recém-Nascido , Feminino , Masculino , Respiração Artificial/métodos , Curva ROC , Estudos Retrospectivos , Técnicas de Apoio para a Decisão , Falha de Tratamento , Modelos LogísticosRESUMO
PURPOSE: To evaluate the effectiveness of the PRECEDE-PROCEED model (PPM) in helping patients with liver cancer be aware of their knowledge, skills, and abilities in self-oral health behaviors and improve their oral health status. METHODS: This is a quasi-experimental study of 90 patients with liver cancer assigned to an oral health education or a control group. The intervention group was educated with the PRECEDE-PROCEED model. A brief oral scale and the knowledge, attitude, and practice oral health questionnaire were employed to measure the oral health status and cognitive behavioral ability to seek oral health in patients. RESULTS: Among 102 eligible patients, 90 (88.23%) agreed to participate in the present study and were divided to intervention (n = 45) or control (n = 45) groups. After the intervention and one month after discharge, the oral health scores of patients in the Intervention group were lower than those of the control group (P < 0.05). In addition, after the intervention and one month after discharge, the patients in the test group had higher scores on knowledge, beliefs, and behaviors of oral health than the control group (P < 0.05). One month after discharge, the mean knowledge and skills scores were significantly higher in the intervention group than in the control group. CONCLUSIONS: Our findings suggest that oral health education may be a useful health intervention for patients with liver cancer. It may also improve the knowledge and beliefs of liver cancer patients seeking oral health. Larger long-term investigations are necessary to provide more support for these preliminary conclusions.
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Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Hepáticas , Saúde Bucal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Saúde Bucal/educação , Educação de Pacientes como Assunto/métodos , Inquéritos e Questionários , Adulto , IdosoRESUMO
Biotic and abiotic stresses have emerged as major constraints to agricultural production, causing irreversible adverse impacts on agricultural production systems and thus posing a threat to food security. In this study, a new strain of Bacillus subtilis DNYB-S1 was isolated from soil contaminated with Fusarium wilt. It was found that artificially synthetic flora (YJ-1) [Enterobacter sp. DNB-S2 and Rhodococcus pyridinovorans DNHP-S2, DNYB-S1] could effectively mitigate both biotic (Fusarium wilt) and abiotic (phthalates) sources of stresses, with the inhibition rate of YJ-1 resistant to wilt being 71.25% and synergistic degradation of 500 mg/L PAEs was 91.23%. The adaptive difference of YJ-1 was 0.59 and the ecological niche overlap value was -0.05 as determined by Lotka-Volterra modeling. These results indicate that YJ-1 has good ecological stability. The major degradation intermediates included 2-ethylhexyl benzoate (EHBA), phthalic acid (PA), diisobutyl phthalate (DIBP), and butyl benzoate, suggesting that YJ-1 can provide a more efficient pathway for PAEs degradation. In addition, there was metabolic mutualism among the strains that will selectively utilize the provided carbon source (some metabolites of PAEs) for growth. The pot experiment showed that YJ-1 with cucumber reduced the incidence of cucumber wilt by 45.31%. YJ-1 could reduce the concentration of PAEs (DBP: DEHP = 1:1) in soil species from 30 mg/kg to 4.26 mg/kg within 35 d, with a degradation efficiency of 85.81%. Meanwhile, the concentration of PAEs in cucumber was reduced to 0.01 mg/kg, indicating that YJ-1 is directly involved in the degradation of soil PAEs and the enhancement of plant immunity. In conclusion, this study provides a new perspective for the development of customized microbiomes for phytoremediation under combined biotic-abiotic stresses in agricultural production processes.
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Cucumis sativus , Cucumis sativus/microbiologia , Ácidos Ftálicos , Microbiologia do Solo , Resistência à Doença , Estresse Fisiológico , Doenças das Plantas/microbiologia , Biodegradação Ambiental , FusariumRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq.ex Havil. was a classical medicinal plant exhibiting the properties of extinguishing wind, arresting convulsions, clearing heat and pacifying the liver. Clinically, it could be utilized for the treatment of central nervous system-related diseases, such as Alzheimer's disease. U. rhynchophylla (UR) and its major ingredient alkaloid compounds (URA) have been proved to exert significant neuroprotective effects. However, the potential mechanism aren't fully understood. AIM OF THE STUDY: This study systematically examined the therapeutic effects of URA on AD pathology in APP-PS1 mice, and revealed the potential mechanism of action. MATERIALS AND METHODS: The cognitive ability was evaluated by morris water maze test in APP-PS1 mice. The H&E staining was used to observe the tissue pathological changes. The ELISA kits were used to detect the level of inflammatory factors. The flow cytometry was used to analyze the percentage of CD4+ effector T cells (Teffs) in spleen. The immunofluorescent staining was performed to count the Teffs and microglia in brain. The protein expression was analyzed by western blot. In vitro, the lymphocyte proliferation induced by ConA was performed by CCK-8 kits. The IFN-γ, IL-17, and TNF-α production were detected by ELISA kits. The effects of URA on glycolysis and the involvement of PI3K/Akt/mTOR signaling pathway was analyzed by Lactic Acid assay kit and western blot in ConA-induced naive T cell. RESULTS: URA treatment improved AD pathology effectively as demonstrated by enhanced cognitive ability, decreased Aß deposit and Tau phosphorylation, as well as reduced neuron apoptosis. Also, the neuroinflammation was significantly alleviated as evidenced by decreased IFN-γ, IL-17 and increased IL-10, TGF-ß. Notably, URA treatment down-regulated the percentage of Teffs (Th1 and Th17) in spleen, and reduced the infiltration of Teffs and microglia in brain. Meanwhile, the Treg cell was up-regulated both in spleen and brain. In vitro, URA was capable of attenuating the spleen lymphocyte proliferation and release of inflammatory factors provoked by ConA. Interestingly, glycolysis was inhibited by URA treatment as evidenced by the decrease in Lactic Acid production and expression of HK2 and GLUT1 via regulating PI3K/Akt/mTOR signaling pathway in ConA-induced naive T cell. CONCLUSION: This study proved that URA could improve AD pathology which was possibly attributable to the restraints of CD4+ T cell mediated neuroinflammation via inhibiting glycolysis.
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Alcaloides , Doença de Alzheimer , Linfócitos T CD4-Positivos , Glicólise , Doenças Neuroinflamatórias , Uncaria , Animais , Uncaria/química , Glicólise/efeitos dos fármacos , Camundongos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Alcaloides/farmacologia , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Camundongos Transgênicos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-Hâ¯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.
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Cristalização , Pirazinas , Molhabilidade , Pirazinas/química , Estabilidade de Medicamentos , Ligação de Hidrogênio , Cristalografia por Raios X , Estrutura Molecular , Difração de Raios XRESUMO
This work was designed to investigate the neurotoxic effects of the typical plasticizer dibutyl phthalate (DBP) using zebrafish larvae as a model. The results of exhibited that zebrafish larvae exposed to DBP at concentrations of 5 µg/L and 10 µg/L exhibited brain malformations (24 h) and behavioral abnormalities (72 h). After 72 h of exposure to DBP, microglia in the brain were over-activated, reactive oxygen species (ROS) formation was increased, and apoptosis was observed. Meanwhile, it was found that neurons exhibited impaired mitochondrial structure, absent mitochondrial membrane potential and up-regulated autophagy. Further comprehensive biochemical analyses and RNA-Seq, validated by RT-qPCR, glutamate metabolism and PPAR signaling pathway were significantly enriched in the DBP stress group, this may be the main reason for the disruption of glycolysis/gluconeogenesis processes and the reduction of energy substrates for the astrocyte-neuron lactate shuttle (ANLS). In addition, the DBP-exposed group showed aberrant activation of endoplasmic reticulum (ER) stress signaling pathway, which may be related to ROS as well as neuronal apoptosis and autophagy. In conclusion, DBP-induced neurotoxicity may be the combined result of insufficient neuronal energy acquisition, damage to mitochondrial structure, apoptosis and autophagy. These results provide a theoretical basis for understanding the neurotoxic effects of DBP.
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Apoptose , Dibutilftalato , Larva , Neurônios , Peixe-Zebra , Animais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Dibutilftalato/toxicidade , Larva/efeitos dos fármacos , Larva/metabolismo , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Metabolismo Energético/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Autofagia/efeitos dos fármacos , Plastificantes/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
OBJECTIVE: This study aimed to use machine learning to evaluate the risk factors of seizures and develop a model and nomogram to predict seizures in children with coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: A total of 519 children with COVID-19 were assessed to develop predictive models using machine learning algorithms, including extreme gradient boosting (XGBoost), random forest (RF) and logistic regression (LR). The performance of the models was assessed using area under the receiver operating characteristic curve (AUC) values. Importance matrix plot and SHapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance and to show the visualization results. The nomogram and clinical impact curve were used to validate the final model. RESULTS: Two hundred and seventeen children with COVID-19 had seizures. According to the AUC, the RF model performed the best. Based on the SHAP values, the top three most important variables in the RF model were neutrophil percentage, cough and fever duration. The nomogram and clinical impact curve also verified that the RF model possessed significant predictive value. CONCLUSIONS: Our research indicates that the RF model demonstrates excellent performance in predicting seizures, and our novel nomogram can facilitate clinical decision-making and potentially offer benefit for clinicians to prevent and treat seizures in children with COVID-19.
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COVID-19 , Aprendizado de Máquina , Nomogramas , SARS-CoV-2 , Convulsões , Humanos , COVID-19/complicações , COVID-19/diagnóstico , Convulsões/etiologia , Convulsões/diagnóstico , Feminino , Masculino , Criança , Pré-Escolar , Fatores de Risco , Curva ROC , Modelos Logísticos , LactenteRESUMO
A large amount of metal tailings causes many environmental issues. Thus, the techniques for their ecological restoration have garnered extensive attention. However, they are still in the exploratory stage. Biological soil crusts (BSCs) are a coherent layer comprising photoautotrophic organisms, heterotrophic organisms and soil particles. They are crucial in global terrestrial ecosystems and play an equal importance in metal tailings. We summarized the existing knowledge on BSCs growing on metal tailings. The main photosynthetic organisms (cyanobacteria, eukaryotic algae, lichens, and mosses) of BSCs exhibit a high heavy metal(loid) (HM) tolerance. BSCs also have a strong adaptability to other adverse conditions in tailings, such as poor structure, acidification, and infertility. The literature about tailing BSCs has been rapidly increasing, particularly after 2022. The extensive literature confirms that the BSCs distributed on metal tailings, including all major types of metal tailings in different climatic regisions, are common. BSCs perform various ecological functions in tailings, including HM stress reduction, soil structure improvement, soil nutrient increase, biogeochemical cycle enhancement, and microbial community restoration. They interact and accelerate revegetation of tailings (at least in the temperate zone) and soil formation. Restoring tailings by accelerating/inducing BSC formation (e.g., resource augmentation and inoculation) has also attracted attention and achieved small-scale on-site application. However, some knowledge gaps still exist. The potential areas for further research include the relation between BSCs and HMs, large-scale quantification of tailing BSCs, application of emerging biological techniques, controlled laboratory experiments, and other restoration applications.
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Recuperação e Remediação Ambiental , Microbiologia do Solo , Poluentes do Solo , Solo , Solo/química , Poluentes do Solo/análise , Recuperação e Remediação Ambiental/métodos , Metais Pesados/análise , Ecossistema , Metais/análise , MineraçãoRESUMO
The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4+ and CD8+ T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4+ T cells, and memory CD8+ T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection. IMPORTANCE: There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection. CLINICAL TRIAL: This study is registered with ClinicalTrials.gov as NCT05680896.
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COVID-19 , Imunidade nas Mucosas , Vacinas de Produtos Inativados , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , Infecções Irruptivas , Linfócitos T CD8-Positivos , Estudos Prospectivos , Imunoglobulina G , Imunoglobulina A , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.
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Objective: Diabetic foot ulcer (DFU) impairs the quality of life of diabetic patients and overburdens healthcare systems and society. It is crucial to comprehend the pathophysiology of DFU and develop effective treatment strategies. The aim of this study was to to evaluate the therapeutic potential of Lactobacillus Plantarum (LP) on wound healing in DFU and to explore the underlying mechanisms. Methods: To investigate the effects of LP on wound healing, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) and used to assess cell viability, migration, and pyroptosis using CCK-8, cell scratch, and flow cytometry. The levels of IL-1ß and IL-18 were measured by ELISA. The expression of NLRP3, caspase-1 p20, and GSDMD-N was detected by Western blot. Additionally, NLRP3 inhibitor MCC950 was used to treat a diabetic rat model established by streptozotocin (STZ). Pearson correlation analysis was performed to analyze the relationship between LP and NLRP3, IL-1ß, IL-18 in ulcer tissue. Results: Our data mechanistically demonstrate that AGEs activate the NLRP3/Caspase-1/GSDMD pathway, leading to an increase in the levels of IL-1ß and IL-18 and ultimately promoting cell pyroptosis. Furthermore, we identified that LP inhibits the effects of AGEs by downregulating NLRP3 inflammasome activity. LP facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20. Finally, we observed a negative correlation between LP and NLRP3, IL-1ß, IL-18 in diabetic foot skin tissue. Conclusion: Our findings uncovered a novel role of LP in diabetic foot wound healing via regulation of the NLRP3 inflammasome, suggesting this link as a therapeutic target. In future research, it would be valuable to explore the signaling cascades involved in LP-mediated inhibition of NLRP3 inflammasome activation.
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Recent electronics-tissues biointefacing technology has offered unprecedented opportunities for long-term disease diagnosis and treatment. It remains a grand challenge to robustly anchor the pressure sensing bioelectronics onto specific organs, since the periodically-varying stress generated by normal biological processes may pose high risk of interfacial failures. Here, a general yet reliable approach is reported to achieve the robust hydrogel interface between wireless pressure sensor and biological tissues/organs, featuring highly desirable mechanical compliance and swelling resistance, despite the direct contact with biofluids and dynamic conditions. The sensor is operated wirelessly through inductive coupling, characterizing minimal hysteresis, fast response times, excellent stability, and robustness, thus allowing for easy handling and eliminating the necessity for surgical extraction after a functional period. The operation of the wireless sensor has been demonstrated with a custom-made pressure sensing model and in vivo intracranial pressure monitoring in rats. This technology may be advantageous in real-time post-operative monitoring of various biological inner pressures after the reconstructive surgery, thus guaranteeing the timely treatment of lethal diseases.
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Hidrogéis , Tecnologia sem Fio , Animais , Tecnologia sem Fio/instrumentação , Ratos , Hidrogéis/química , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Pressão , Pressão Intracraniana , Fenômenos MecânicosRESUMO
BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.
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The only existing approach for assessing the risk of developing acute ischemic stroke (AIS) necessitates that individuals possess a strong understanding of their health status. Our research gathered compelling evidence in favor of our hypothesis, suggesting that the likelihood of developing AIS can be assessed by analyzing the green autofluorescence (AF) of the skin and fingernails. Utilizing machine learning-based analyses of AF images, we found that the area under the curve (AUC) for distinguishing subjects with three risk factors from those with zero, one, or two risk factors was 0.79, 0.76, and 0.75, respectively. Our research has revealed that green AF serves as an innovative biomarker for assessing the risk of developing AIS. Our method is objective, non-invasive, efficient, and economic, which shows great promise to boost a technology for screening natural populations for risk of developing AIS.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Unhas , Fatores de Risco , BiomarcadoresRESUMO
Widespread application of the typical phthalate plasticizers, di (2-ethylhexyl) phthalate (DEHP), poses a serious potential threat to the health of animals and even humans. Previous studies have confirmed the mechanism of DEHP-induced cardiac developmental defects in zebrafish larvae. However, the mechanism of cardiac dysfunction is still unclear. Thus, this work aimed to comprehensively investigate the mechanisms involved in DEHP-induced cardiac dysfunction through computational simulations, in vivo assays in zebrafish, and in vitro assays in cardiomyocytes. Firstly, molecular docking and western blot initially investigated the activating effect of DEHP on Pparg in zebrafish. Although GW9662 (PPARG antagonist) effectively alleviated DEHP-induced cardiac dysfunction and lipid metabolism disorders, it did not restore significant decreases in mitochondrial membrane potential and ATP levels. In vitro assays in cardiomyocytes, DEHP caused overexpression of PPARG and proteins involved in the regulation of Ca2+ homeostasis, and the above abnormalities were effectively alleviated by GW9662, suggesting that the Ca2+ homeostatic imbalance caused by activation of PPARG by DEHP seems to be the main cause of DEHP-induced cardiac dysfunction. To sum up, this work not only refines the mechanism of toxic effects of cardiotoxicity induced by DEHP, but provides an important theoretical basis for enriching the toxicological effects of DEHP.
Assuntos
Anilidas , Dietilexilftalato , Cardiopatias , Ácidos Ftálicos , Humanos , Animais , Dietilexilftalato/toxicidade , Dietilexilftalato/metabolismo , Peixe-Zebra/metabolismo , PPAR gama/metabolismo , Simulação de Acoplamento Molecular , Plastificantes/toxicidade , Plastificantes/metabolismoRESUMO
The quick progress of epigenetic study has kindled new hope for treating many cancers. When it comes to RNA epigenetics, the ac4C acetylation modification is showing promise, whereas N-acetyltransferase 10 plays a wide range of biological functions, has a significant impact on cellular life events, and is frequently highly expressed in many malignant tumors. N-acetyltransferase 10 is an acetyltransferase with important biological involvement in cellular processes and lifespan. Because it is highly expressed in many malignant tumors, it is considered a pro-carcinogenic gene. The review aims to introduce NAT10, summarize the effects of ac4C acetylation on tumor growth from multiple angles, and discuss the possible therapeutic targeting of NAT10 and the future directions of ac4C acetylation investigations.