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1.
Chem Res Toxicol ; 37(6): 1053-1061, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38847154

RESUMO

Poisoning caused by the mushroom Amanita phalloides, due to the toxin α-amanitin, accounts for approximately 90% of food poisoning deaths in China with no specific antidotes. To investigate the role of salidroside (Sal) in α-amanitin (α-AMA)-induced mitophagy, mouse liver cells AML-12 were exposed to α-AMA in the presence of Sal or not. Intracellular reactive oxygen species (ROS) levels were measured using a ROS detection kit, mitochondrial activity was evaluated using a mitochondrial red fluorescent probe kit or JC-1 dye, and protein expression levels of PINK1, Parkin, LC3 II, P62, Bax, Bcl-2, Caspase 3, Cleaved-Caspase 3, PARP I, and Cleaved-PARP I were detected through Western blot. Results demonstrated that α-AMA led to increased intracellular ROS levels, cell apoptosis, and decreased mitochondrial membrane potential. Notably, expression levels of mitophagy-related proteins PINK1, Parkin, and LC3 increased significantly while the P62 protein expression decreased remarkably. Furthermore, Sal reversed the α-AMA-induced decrease in cell viability and mitochondrial membrane potential and increase in intracellular ROS level. In addition, Sal promoted expression levels of PINK1, Parkin, and LC3 II while suppressing the Bax/Bcl-2 ratio, Cleaved-Caspase 3, and Cleaved-PARP I as well as P62. The results above proved that salidroside alleviates α-AMA-induced mouse liver cells damage via promoting PINK1/Parkin-mediated mitophagy and reducing cell apoptosis.


Assuntos
Apoptose , Glucosídeos , Mitocôndrias , Mitofagia , Fenóis , Proteínas Quinases , Espécies Reativas de Oxigênio , Ubiquitina-Proteína Ligases , Animais , Apoptose/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Fenóis/farmacologia , Fenóis/química , Glucosídeos/farmacologia , Glucosídeos/química , Camundongos , Proteínas Quinases/metabolismo , Mitofagia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos
2.
Environ Sci Technol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329046

RESUMO

Labile carbon (C) continuously delivered from the rhizosphere profoundly affects terrestrial nitrogen (N) cycling. However, nitrous oxide (N2O) and dinitrogen (N2) production in agricultural soils in the presence of continuous root C exudation with applied N remains poorly understood. We conducted an incubation experiment using artificial roots to continuously deliver small-dose labile C combined with 15N tracers to investigate N2O and N2 emissions in agricultural soils with pH and organic C (SOC) gradients. A significantly negative exponential relationship existed between N2O and N2 emissions under continuous C exudation. Increasing soil pH significantly promoted N2 emissions while reducing N2O emissions. Higher SOC further promoted N2 emissions in alkaline soils. Native soil-N (versus fertilizer-N) was the main source of N2O (average 67%) and N2 (average 80%) emissions across all tested soils. Our study revealed the overlooked high N2 emissions, mainly derived from native soil-N and strengthened by increasing soil pH, under relatively real-world conditions with continuous root C exudation. This highlights the important role of N2O and N2 production from native soil-N in terrestrial N cycling when there is a continuous C supply (e.g., plant-root exudate) and helps mitigate emissions and constrain global budgets of the two concerned nitrogenous gases.

3.
Support Care Cancer ; 32(8): 555, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066833

RESUMO

OBJECTIVE: To understand the status of spiritual well-being in patients with esophageal cancer and analyze its influencing factors. METHODS: A total of 187 patients with esophageal cancer (EC) from two grade A hospitals in Chengdu were selected and investigated by general data questionnaire, chronic disease function evaluation-spirituality scale 12 (FACIT-SP-12), general well-being scale (GWB), and Anderson symptom assessment scale gastrointestinal tract (MDASI-GI). RESULTS: The spiritual well-being score of patients with esophageal cancer was (25.13 ± 9.63). Spiritual well-being was positively correlated with general well-being and negatively correlated with symptom burden (P < 0.01). The results of multiple stepwise linear regression analysis showed that hobbies, disease stage, general well-being, and symptom burden were the main influencing factors for the spiritual well-being of esophageal cancer patients (P < 0.05), explaining 49.0% of the total variation. CONCLUSIONS: The spiritual well-being of patients with esophageal cancer is lower than the middle level, In addition, whether there is a hobby in life, disease stage, subjective well-being, and symptom burden are the main factors affecting the spiritual well-being of patients with EC. It is suggested that medical staff should take targeted care measures according to the influencing factors, so as to improve the spiritual well-being level of patients and improve the quality of life of patients.


Assuntos
Neoplasias Esofágicas , Espiritualidade , Humanos , Masculino , Estudos Transversais , Feminino , Neoplasias Esofágicas/psicologia , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Qualidade de Vida , Adulto , Modelos Lineares , China , Idoso de 80 Anos ou mais
4.
Biochem Genet ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429602

RESUMO

BACKGROUND: Solamargine (SM) has been shown to play anti-tumor role in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of SM in HCC progression deserve further exploration. METHODS: HCC cell proliferation and apoptosis were assessed by cell counting kit 8 assay, colony formation assay and flow cytometry. Ferroptosis was evaluated by detecting the levels of Fe2+, iron, MDA, ROS and GSH in HCC cells. In addition, mitochondrial carrier 1 (MTCH1) mRNA level was detected by quantitative real-time PCR. Western blot was used to test MTCH1 and signal transduction and activation of transcription 1 (STAT1) protein levels. Dual-luciferase reporter assay was employed to analyze the interaction between STAT1 and MTCH1. A mouse xenograft model was also constructed to explore the role of SM in vivo. RESULTS: SM could potentially suppress HCC cell growth by inducing ferroptosis. MTCH1 was highly expressed in HCC tissues and cells, and its silencing inhibited HCC cell proliferation, promoted apoptosis and ferroptosis. MTCH1 expression was reduced by SM, and its overexpression reversed SM-induced HCC cell apoptosis and ferroptosis. Furthermore, STAT1 facilitated MTCH1 transcription and promoted its expression. Besides, STAT1 expression could be reduced by SM, and its overexpression abolished the decreasing effect of SM on MTCH1 expression. In vivo, SM suppressed HCC tumor growth by reducing MTCH1 expression. CONCLUSION: SM promoted HCC cell apoptosis and ferroptosis via the STAT1/MTCH1 axis.

5.
Pediatr Emerg Care ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38718806

RESUMO

OBJECTIVE: Persistent pulmonary hypertension of the newborn (PPHN) is one of the critical neonatal diseases associated with high morbidity and mortality. This study attempted to conduct a nomogram prediction model for performing early identification of PPHN and providing effective information for clinical practice. METHODS: A total of 456 newborns who first admitted to the hospital after birth were included in the analysis, including 138 newborns with PPHN and 318 newborns without PPHN (as controls). The optimal predictive variables selection was performed based on LASSO (least absolute shrinkage and selection operator) regression and multivariate logistic regression. Using the selected variables, a nomogram prediction model was developed. To validate the model, the model was assessed using the receiver operating characteristic curve, calibration plot, and clinical impact curve. RESULTS: Six predictors, namely, gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pao2, were identified by LASSO and multivariate logistic regression analysis from the original 30 variables studied. The constructed model, using these predictors, exhibited favorable predictive ability for PPHN, with an area under the receiver operating characteristic of 0.897 (sensitivity = 0.876, specificity = 0.785) in the training set and 0.871 (sensitivity = 0.902, specificity = 0.695) in the validation set, and was well calibrated, as indicated by the PHosmer-Lemeshow test values of 0.233 and 0.876 for the training and validation sets, respectively. CONCLUSIONS: The model included gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pao2 had good prediction performance for predicting PPHN among newborns first admitted to the hospital after birth.

6.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338959

RESUMO

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doenças das Aves Domésticas , Animais , Masculino , Galinhas , Interferon-alfa/farmacologia , Interferon-alfa/genética , Sorogrupo , Adenoviridae/genética , Antivirais/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico
7.
Int J Mol Sci ; 25(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000096

RESUMO

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.


Assuntos
Movimento Celular , Proteína Duplacortina , Neurogênese , Neurônios , Animais , Ratos , Neurônios/metabolismo , Neurônios/citologia , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/citologia , Hipotálamo/metabolismo , Hipotálamo/citologia , Arginina Vasopressina/metabolismo
8.
J Environ Manage ; 355: 120504, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38447513

RESUMO

Ammonia-oxidation process directly contribute to soil nitrous oxide (N2O) emissions in agricultural soils. However, taxonomy of the key nitrifiers (within ammonia oxidising bacteria (AOB), archaea (AOA) and complete ammonia oxidisers (comammox Nitrospira)) responsible for substantial N2O emissions in agricultural soils is unknown, as is their regulation by soil biotic and abiotic factors. In this study, cumulative N2O emissions, nitrification rates, abundance and community structure of nitrifiers were investigated in 16 agricultural soils from major crop production regions of China using microcosm experiments with amended nitrogen (N) supplemented or not with a nitrification inhibitor (nitrapyrin). Key nitrifier groups involved in N2O emissions were identified by comparative analyses of the different treatments, combining sequencing and random forest analyses. Soil cumulative N2O emissions significantly increased with soil pH in all agricultural soils. However, they decreased with soil organic carbon (SOC) in alkaline soils. Nitrapyrin significantly inhibited soil cumulative N2O emissions and AOB growth, with a significant inhibition of the AOB Nitrosospira cluster 3a.2 (D11) abundance. One Nitrosospira multiformis-like OTU phylotype (OTU34), which was classified within the AOB Nitrosospira cluster 3a.2 (D11), had the greatest importance on cumulative N2O emissions and its growth significantly depended on soil pH and SOC contents, with higher growth at high pH and low SOC conditions. Collectively, our results demonstrate that alkaline soils with low SOC contents have high N2O emissions, which were mainly driven by AOB Nitrosospira cluster 3a.2 (D11). Nitrapyrin can efficiently reduce nitrification-related N2O emissions by inhibiting the activity of AOB Nitrosospira cluster 3a.2 (D11). This study advances our understanding of key nitrifiers responsible for high N2O emissions in agricultural soils and their controlling factors, and provides vital knowledge for N2O emission mitigation in agricultural ecosystems.


Assuntos
Ecossistema , Solo , Solo/química , Amônia/química , Carbono , Oxirredução , Archaea , Nitrificação , Microbiologia do Solo
9.
Front Med (Lausanne) ; 11: 1396625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799153

RESUMO

Background: Reasonable and effective time allocation can promote the improvement of medical care service quality. This study aimed to translate, cross-culturally adapt and validate the Chinese Nursing Time Management Scale (NTMS). Methods: Using a cross-sectional survey, 345 clinical nurses were selected from June to September 2023 for a general information questionnaire and Nursing Time Management Scale (NTMS) study. Item analysis, exploratory factor analysis and validation factor analysis were used to verify the reliability and validity of the Chinese version of Nursing Time Management Scale. Results: The Chinese version of the Nurses' Time Management Competency Scale includes 17 entries in 3 dimensions: planning activities and setting goals, coordinating activities and procedures, and organizing nursing activities. The Cronbach's alpha coefficient for the total scale was 0.966. Exploratory factor analysis showed that the cumulative variance contribution of the three male factors was 97.44%. Conclusion: The NTMS has acceptable validity and reliability and can be used to evaluate the nursing time management skills of Chinese clinical nurses.

10.
Biochim Biophys Acta Mol Cell Res ; 1871(7): 119787, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38879133

RESUMO

The WhiB-Like (Wbl) proteins are a large family of iron-sulfur (Fe-S) cluster-containing transcription factors exclusively found in the phylum Actinobacteria, including the notable genera like Mycobacteria, Streptomycetes and Corynebacteria. These proteins play pivotal roles in diverse biological processes, such as cell development, redox stress response and antibiotic resistance. Members of the Wbl family exhibit remarkable diversity in their sequences, structures and functions, attracting great attention since their first discovery. This review highlights the most recent breakthroughs in understanding the structural and mechanistic aspects of Wbl-dependent transcriptional regulation.

11.
Neural Netw ; 173: 106182, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38387203

RESUMO

Radiology images of the chest, such as computer tomography scans and X-rays, have been prominently used in computer-aided COVID-19 analysis. Learning-based radiology image retrieval has attracted increasing attention recently, which generally involves image feature extraction and finding matches in extensive image databases based on query images. Many deep hashing methods have been developed for chest radiology image search due to the high efficiency of retrieval using hash codes. However, they often overlook the complex triple associations between images; that is, images belonging to the same category tend to share similar characteristics and vice versa. To this end, we develop a triplet-constrained deep hashing (TCDH) framework for chest radiology image retrieval to facilitate automated analysis of COVID-19. The TCDH consists of two phases, including (a) feature extraction and (b) image retrieval. For feature extraction, we have introduced a triplet constraint and an image reconstruction task to enhance discriminative ability of learned features, and these features are then converted into binary hash codes to capture semantic information. Specifically, the triplet constraint is designed to pull closer samples within the same category and push apart samples from different categories. Additionally, an auxiliary image reconstruction task is employed during feature extraction to help effectively capture anatomical structures of images. For image retrieval, we utilize learned hash codes to conduct searches for medical images. Extensive experiments on 30,386 chest X-ray images demonstrate the superiority of the proposed method over several state-of-the-art approaches in automated image search. The code is now available online.


Assuntos
Algoritmos , COVID-19 , Humanos , Raios X , COVID-19/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Bases de Dados Factuais
12.
J Mater Chem B ; 12(15): 3614-3635, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38511264

RESUMO

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.


Assuntos
Doenças Inflamatórias Intestinais , Neoplasias , Humanos , Biomimética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Previsões , Neoplasias/tratamento farmacológico
13.
Mol Biotechnol ; 66(5): 1266-1278, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38206528

RESUMO

The objective of this study was to investigate the mechanism of curcumin in diabetic foot ulcer (DFU) wound healing. A DFU rat model was established, and fibroblasts were cultured in a high-glucose (HG) environment to create a cell model. Various techniques, including Western blot, RT‒qPCR, flow cytometry, Transwell, cell scratch test and H&E staining, were employed to measure the levels of relevant genes and proteins, as well as to assess cell proliferation, apoptosis, migration, and pathological changes. The results showed that miR-152-3p was overexpressed in DFU patients, while FBN1 was underexpressed. Curcumin was found to inhibit fibroblast apoptosis, promote proliferation, migration, and angiogenesis in DFU rats, and accelerate wound healing in DFU rats. In addition, overexpression of miR-152-3p weakened the therapeutic effect of curcumin, while overexpression of FBN1 reversed the effects of the miR-152-3p mimic. Further investigations into the underlying mechanisms revealed that curcumin expedited wound healing in DFU rats by restoring the FBN1/TGF-ß pathway through the inhibition of miR-152-3p. In conclusion, curcumin can suppress the activity of miR-152-3p, which, in turn, leads to the rejuvenation of the FBN1/TGF-ß pathway and accelerates DFU wound healing.


Assuntos
Curcumina , Pé Diabético , MicroRNAs , Transdução de Sinais , Cicatrização , Animais , Feminino , Humanos , Masculino , Ratos , Adipocinas , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Pé Diabético/metabolismo , Pé Diabético/genética , Pé Diabético/tratamento farmacológico , Pé Diabético/patologia , Modelos Animais de Doenças , Fibrilina-1/genética , Fibrilina-1/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Cicatrização/efeitos dos fármacos , Cicatrização/genética
14.
Front Pharmacol ; 15: 1412231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933681

RESUMO

Introduction: Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks. Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses. Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport. Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application. Conclusion: B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38954584

RESUMO

Brain functional network (BFN) analysis has become a popular method for identifying neurological diseases at their early stages and revealing sensitive biomarkers related to these diseases. Due to the fact that BFN is a graph with complex structure, graph convolutional networks (GCNs) can be naturally used in the identification of BFN, and can generally achieve an encouraging performance if given large amounts of training data. In practice, however, it is very difficult to obtain sufficient brain functional data, especially from subjects with brain disorders. As a result, GCNs usually fail to learn a reliable feature representation from limited BFNs, leading to overfitting issues. In this paper, we propose an improved GCN method to classify brain diseases by introducing a self-supervised learning (SSL) module for assisting the graph feature representation. We conduct experiments to classify subjects with mild cognitive impairment (MCI) and autism spectrum disorder (ASD) respectively from normal controls (NCs). Experimental results on two benchmark databases demonstrate that our proposed scheme tends to obtain higher classification accuracy than the baseline methods.

16.
Comput Struct Biotechnol J ; 23: 369-383, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38226313

RESUMO

Background: Inflammatory responses influence the outcome of immunotherapy and tumorigenesis by modulating host immunity. However, systematic inflammatory response assessment models for predicting cancer immunotherapy (CIT) responses and survival across human cancers remain unexplored. Here, we investigated an inflammatory response score model to predict CIT responses and patient survival in a pan-cancer analysis. Methods: We retrieved 12 CIT response gene expression datasets from the Gene Expression Omnibus database (GSE78220, GSE19423, GSE100797, GSE126044, GSE35640, GSE67501, GSE115821 and GSE168204), Tumor Immune Dysfunction and Exclusion database (PRJEB23709, PRJEB25780 and phs000452.v2.p1), European Genome-phenome Archive database (EGAD00001005738), and IMvigor210 cohort. The tumor samples from six cancers types: metastatic urothelial cancer, metastatic melanoma, gastric cancer, primary bladder cancer, renal cell carcinoma, and non-small cell lung cancer.We further established a binary classification model to predict CIT responses using the least absolute shrinkage and selection operator (LASSO) computational algorithm. Findings: The model had high predictive accuracy in both the training and validation cohorts. During sub-group analysis, area under the curve (AUC) values of 0.82, 0.80, 0.71, 0.7, 0.67, and 0.64 were obtained for the non-small cell lung cancer, gastric cancer, metastatic urothelial cancer, primary bladder cancer, metastatic melanoma, and renal cell carcinoma cohorts, respectively. CIT response rates were higher in the high-scoring training cohort subjects (51%) than the low-scoring subjects (27%). The five-year survival rates in the high- and low score groups of the training cohorts were 62% and 21%, respectively, while those of the validation cohorts were 54% and 22%, respectively (P < 0·001 in all cases). Inflammatory response signature score derived from on-treatment tumor specimens are highly predictive of response to CIT in patients with metastatic melanoma. A significant correlation was observed between the inflammatory response scores and tumor purity. Regardless of the tumor purity, patients in the low score group had a significantly poorer prognosis than those in the high score group. Immune cell infiltration analysis indicated that in the high score cohort, tumor-infiltrating lymphocytes were significantly enriched, particularly effector and natural killer cells. Inflammatory response scores were positively correlated with immune checkpoint genes, suggesting that immune checkpoint inhibitors may have benefited patients with high scores. Analysis of signature scores across different cancer types from The Cancer Genome Atlas revealed that the prognostic performance of inflammatory response scores for survival in patients who have not undergone immunotherapy can be affected by tumor purity. Interleukin 21 (IL21) had the highest weight in the inflammatory response model, suggesting its vital role in the prediction mode. Since the number of metastatic melanoma patients (n = 429) was relatively large among CIT cohorts, we further performed a co-culture experiment using a melanoma cell line and CD8 + T cell populations generated from peripheral blood monocytes. The results showed that IL21 therapy combined with anti-PD1 (programmed cell death 1) antibodies (trepril monoclonal antibodies) significantly enhanced the cytotoxic activity of CD8 + T cells against the melanoma cell line. Conclusion: In this study, we developed an inflammatory response gene signature model that predicts patient survival and immunotherapy response in multiple malignancies. We further found that the predictive performance in the non-small cell lung cancer and gastric cancer group had the highest value among the six different malignancy subgroups. When compared with existing signatures, the inflammatory response gene signature scores for on-treatment samples were more robust predictors of the response to CIT in metastatic melanoma.

17.
ACS Appl Mater Interfaces ; 16(15): 19529-19536, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38564290

RESUMO

Flexible and stretchable transparent heaters (THs) have been widely used in various applications, including deicing and defogging of flexible screens as well as thermotherapy pads. Ionic THs based on ionogels have emerged as a promising alternative to conventional electronic THs due to their unique advantages in terms of transparency-conductance conflict, uniform heating, and interfacial adhesion. However, the commonly used hydrophilic ionogels inevitably introduce a moisture-sensitive issue. In this work, we present a stretchable and transparent hydrophobic ionogel-based heater that utilizes ionic current-induced Joule heating under high-frequency alternating current. This ionogel-based TH exhibits exceptional multifunctional properties with low hysteresis, a fracture strain of 840%, transmittance of 93%, conductivity of 0.062 S m-1, temperature resistance up to 165 °C, voltage resistance up to 120 V, heating rate of 0.1 °C s-1, steady-state temperature at 115 °C, and uniform heating even when bent or stretched (up to 200%). Furthermore, it maintains its heating performance when it is directly exposed to water. This hydrophobic ionogel-based TH expands the range of materials available for ionic THs and paves the way for their practical applications.

18.
Int J Biol Macromol ; 270(Pt 1): 132310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38740162

RESUMO

With multiscale hierarchical structure, wood is suitable for a range of high-value applications, especially as a chromatographic matrix. Here, we have aimed to provide a weak anion-exchange polymeric monolithic column based on natural wood with high permeability and stability for effectively separating the targeted protein. The wood-polymeric monolithic column was synthesized by in situ polymerization of glycidyl methacrylate and ethylene glycol dimethacrylate in wood, and coupled with diethylaminoethyl hydrochloride. The wood-polymeric monolithic column can be integrated with fast-protein liquid chromatography for large-scale protein purification. According to the results, the wood-polymeric monolithic column showed high hydrophilicity, permeability and stability. Separation experiments verified that the wood-polymeric monolithic column could purify the targeted protein (spike protein of SARS-COV-2 and ovalbumin) from the mixed proteins by ion exchange, and the static adsorption capacity was 33.04 mg mL-1 and the dynamic adsorption capacity was 24.51 mg mL-1. In addition, the wood-polymerized monolithic column had good stability, and a negligible decrease in the dynamic adsorption capacity after 20 cycles. This wood-polymerized monolithic column can provide a novel, efficient, and green matrix for monolithic chromatographic columns.


Assuntos
Madeira , Madeira/química , Adsorção , Metacrilatos/química , Cromatografia por Troca Iônica/métodos , Polímeros/química , Ovalbumina/química , Ovalbumina/isolamento & purificação , Interações Hidrofóbicas e Hidrofílicas , SARS-CoV-2 , Polimerização , Compostos de Epóxi
19.
Environ Pollut ; 359: 124757, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153537

RESUMO

In the troposphere, ozone (O3) formation can be limited by NOx, VOCs, or both, complicating efforts to reduce O3 by controlling its precursors. This study used formaldehyde (HCHO) data and nitrogen dioxide (NO2) data from the Ozone Monitoring Instrument (OMI) to analyze O3 formation sensitivity in Fujian from 2012 to 2021. Over the past decade, an 8.7% reduction in NO2 VCDs and a 9.91% increase in HCHO VCDs were observed. Due to differences in the primary driving factors, HCHO VCDs exhibit a characteristic seasonal pattern with higher in summer and lower in winter, whereas NO2 VCDs show the opposite trend. O3 formation chemistry was accurately diagnosed by combining satellite-based data and ground-based O3 data. A new threshold value (3.3-4.6) was derived to determine the transition from VOC-limited to NOx-limited O3 formation regimes. Results showed that O3 sensitivity exhibited pronounced seasonal variations. The VOC-limited regime predominates throughout the entire Fujian region in winter, whereas it occupies only 5% of the area in summer. A VOC-limited region was found widely across Fujian on an annual average, but it decreased by 24% over 10 years. Transitional areas experienced a 19% increase. In two natural emission reduction cases (reductions during the Chinese Lunar New Year holiday and reductions in weekend traffic emissions compared to weekdays), ground-level O3 effectively captured the impacts of sensitivity changes. The impact suggests that when Fujian is in the VOC control region, a significant reduction in NOx, without effective VOC control, might lead to an O3 increase. The importance of controlling VOC emissions is highlighted in Fujian. This study enhances the understanding of O3 formation regimes in southeastern China, which is crucial for developing O3 prevention and control strategies.

20.
Oncol Lett ; 28(4): 461, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39119230

RESUMO

Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.

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