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Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system to attack tumor cells. However, a high level of N-glycosylation can protect tumor cells, compromising the anticancer immunity of nanocatalytic immunotherapy. Here, we show a 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold for enhanced cancer piezocatalytic immunotherapy. After the implantation in the tumor, DBG generates both reactive oxygen species (ROS) and piezoelectric signals when excited with ultrasound irradiation, significantly promoting the activation of anticancer immunity. Meanwhile, 2-DG released from ROS-sensitive DBG disrupts the N-glycans synthesis, further overcoming the immunosuppressive microenvironment of tumors. The synergy effects of ultrasound-triggered and glycosylation inhibition enhanced tumor piezocatalytic immunotherapy are demonstrated on four mouse cancer models. A "hot" tumor-immunity niche is produced to inhibit tumor progress and lung metastasis and elicit strong immune memory effects. This work provides a promising piezocatalytic immunotherapy for malignant solid tumors featuring both low immunogenicity and high levels of N-glycosylation.
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Desoxiglucosa , Inmunoterapia , Especies Reactivas de Oxígeno , Glicosilación , Animales , Inmunoterapia/métodos , Ratones , Desoxiglucosa/farmacología , Desoxiglucosa/uso terapéutico , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Catálisis , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Bismuto/química , Bismuto/uso terapéutico , Femenino , Humanos , Compuestos Férricos/química , Polisacáridos/química , Ondas Ultrasónicas , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/patología , Ratones Endogámicos BALB C , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Ratones Endogámicos C57BLRESUMEN
Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with strong migratory and invasive abilities. Gas6 is closely associated with the progression of many malignant tumors; however, the role of Gas6 in the progression of esophageal cancer is unclear. Here, we report that the knockdown of Gas6 inhibited esophageal cancer cell proliferation, migration, and invasion. In addition, Gas6 knockdown downregulated the levels of P-PI3K and P-AKT. Taken together, the findings confirm that Gas6 knockdown can inhibit esophageal cancer progression and can exert anti-tumor effects on esophageal cancer through the PI3K/AKT pathway.
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BACKGROUND/OBJECTIVES: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach. METHODS: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) were searched using terms such as "acupuncture" and "metabolites" to retrieve relevant journal articles published through January 2024. Studies utilizing mass spectrometry or nuclear magnetic resonance were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool and the Newcastle-Ottawa scale. Metabolic pathway analysis was conducted using MetaboAnalyst 6.0 to identify common significant pathways affected by acupuncture. Additionally, subgroup pathway enrichment analysis identified metabolites significantly altered in more than two studies. RESULTS: Among 4019 articles, 22 studies met inclusion criteria, examining changes in metabolomic biomarkers before and after acupuncture for various diseases and symptoms. A total of 226 metabolites showed significant changes, with 14 common metabolites altered in more than two studies (glutamine, androsterone glucuronide, choline, citric acid, decanoylcarnitine, estrone, glutathione, glycine, hypoxanthine, lactic acid, pyruvic acid, serine, proline, and sn-glycero-3-phosphocholine). Common pathways affected by acupuncture were glycine, serine, and threonine metabolism, glutathione metabolism, arginine biosynthesis, and glyoxylate and dicarboxylate metabolism. CONCLUSIONS: This review provides insights of the metabolomic mechanisms underlying acupuncture, highlighting its impact on specific metabolic pathways. Recognizing these changes can enhance acupuncture's effectiveness and support the development of personalized treatments. The findings underscore metabolomics as a valuable tool for understanding and optimizing acupuncture for various diseases and symptoms.
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Soft X-ray imaging is a powerful tool to explore the structure of cells, probe material with nanometer resolution, and investigate the energetic phenomena in the universe. Conventional soft X-ray image sensors are by and large Si-based charge coupled devices that suffer from low frame rates, complex fabrication processes, mechanical inflexibility, and required cooling below -60 °C. Here, a soft X-ray photodiode is reported based on low-cost metal halide perovskite with comparable performance to commercial Si-based device. Nanothrough network electrode minimized the optical loss due to the shadowing of insensitive layers, while a multidimensional perovskite heterojunction is generated to reduce the photo-generated carrier loss. This strategy promoted a record quantum efficiency of 8 × 103% without cooling, several orders of magnitude greater than the previously achieved. Flexible and curved soft X-ray imaging arrays are fabricated based on this high-performance device structure, demonstrating stable soft X-ray response and sharp imaging capabilities. This work highlights the low-cost and efficient perovskite photodiode as a strong candidate for the next-generation soft X-ray image sensors.
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Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive cognitive and physical impairment. Neuroinflammation is related to AD, and the misfolding and aggregation of amyloid protein in the brain creates an inflammatory microenvironment. Microglia are the predominant contributors to neuroinflammation, and abnormal activation of microglia induces the release of a large amount of inflammatory factors, promotes neuronal apoptosis, and leads to cognitive impairment. In this study, we used microglial membranes containing caffeic acid-coupled carbon quantum dots to prepare a novel biomimetic nanocapsule (CDs-CA-MGs) for the treatment of AD. The application of CDs-CA-MGs via nasal administration can bypass the bloodâbrain barrier (BBB) and directly target the site of inflammation. After treatment with CDs-CA-MGs, AD mice showed reduced inflammation in the brain, decreased neuronal apoptosis, and significantly improved learning and memory abilities. In addition, CDs-CA-MGs affect inflammation-related JAK-STAT and Toll-like receptor signaling pathways in AD mice. CDs-CA-MGs significantly downregulated interleukins (IL-1ß and IL-6) and tumor necrosis factor (TNF-α). This finding suggested that CDs-CA-MGs may improve cognitive impairment by modulating inflammatory responses. In conclusion, the use of CDs-CA-MGs provides a possible therapeutic strategy for the treatment of AD.
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Administración Intranasal , Enfermedad de Alzheimer , Ácidos Cafeicos , Carbono , Puntos Cuánticos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Animales , Puntos Cuánticos/química , Ratones , Carbono/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Microglía/efectos de los fármacos , Microglía/metabolismo , Masculino , Biomimética/métodos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patología , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacosRESUMEN
PROBLEM IDENTIFICATION: Previous reviews have reported the efficacy of acupuncture in managing cancer-related symptoms. However, there is a lack of comprehensive reviews examining how patients' expectancy regarding acupuncture influences treatment outcomes in the context of cancer survivorship. LITERATURE SEARCH: 9 databases were searched for articles published through August 2023. The authors included acupuncture studies that reported on patient expectancy for the effectiveness of acupuncture. DATA EVALUATION: 10 studies were included in this review. Study quality was assessed using the Cochrane risk-of-bias tool and the ROBINS-I (Risk Of Bias In Non-randomised Studies-of Interventions) tool. SYNTHESIS: 5 studies explored the relationship between expectancy and cancer-related outcomes, and in 3, expectancy was significantly associated with reduced pain, frequency of bowel movements, and severity of insomnia. Male and older patients, nonresponders to acupuncture, and those with lower education levels had lower expectancy regarding acupuncture. IMPLICATIONS FOR NURSING: Healthcare providers should assess patient expectancy to comprehensively understand its role in improving acupuncture outcomes.
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Terapia por Acupuntura , Neoplasias , Humanos , Terapia por Acupuntura/métodos , Neoplasias/complicaciones , Neoplasias/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
BACKGROUND: In recent decades, natural compounds have been considered a significant source of new antitumor medicines due to their unique advantages. Several in vitro and in vivo studies have focused on the effect of terpenoids on apoptosis mediated by mitochondria in malignant cells. RECENT FINDINGS: In this review article, we focused on six extensively studied terpenoids, including sesquiterpenes (dihydroartemisinin and parthenolide), diterpenes (oridonin and triptolide), and triterpenes (betulinic acid and oleanolic acid), and their efficacy in targeting mitochondria to induce cell death. Terpenoid-induced mitochondria-related cell death includes apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and necrosis caused by mitochondrial permeability transition. Apoptosis and autophagy interact in meaningful ways. In addition, in view of several disadvantages of terpenoids, such as low stability and bioavailability, advances in research on combination chemotherapy and chemical modification were surveyed. CONCLUSION: This article deepens our understanding of the association between terpenoids and mitochondrial cell death, presenting a hypothetical basis for the use of terpenoids in anticancer management.
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Mitocondrias , Neoplasias , Terpenos , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Terpenos/farmacología , Terpenos/uso terapéutico , Apoptosis/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Diterpenos/farmacología , Diterpenos/uso terapéuticoRESUMEN
As age increases, children will face more and more adversity. How effectively they cope with stress and difficulties of life is of great significance to the development of children's mental health and academic achievement. However, few studies have explored how different interpersonal relationships and psychological suzhi work together to influence children's healthy behaviors, particularly healthy coping in adversity. Therefore, this research focused on the teacher-student relationships and coping styles, as well as the chain-mediated effects of peer relationships and psychological suzhi. A total of 688 children (360 boys, 52.3%; Mage = 10.98 and SD = 0.89) completed questionnaires that assessed using teacher-student relationships, peer relationships, psychological suzhi, and coping styles. The results indicated that teacher-student relationships correlated positively with coping styles, peer relationships, and psychological suzhi in children. Besides, teacher-student relationships positively affected coping styles through both the mediating roles of peer relationships and psychological suzhi. This research elucidated the extrinsic and intrinsic factors impacting the coping styles of children, thus providing empirical validation of existing theoretical frameworks. In China, interventions aimed at promoting Chinese children's positive coping could benefit from strategies focused on cultivating high-quality relationships and enhancing psychological suzhi.
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BACKGROUND: HIV-related stigma continues to hinder optimal HIV care, and its determinants should be understood at multiple levels. Based on the social-ecological model, this study aimed to explore factors associated with HIV-related stigma among women living with HIV in Guangdong Province, China. METHODS: A cross-sectional study was conducted from July to August 2022 to recruit newly reported women living with HIV with a history of pregnancy or current pregnancy in 2021 in 21 cities in Guangdong Province. HIV-related stigma was assessed using an abbreviated Chinese version of Berger's HIV Stigma Scale. Univariate and multivariable hierarchical regression analyses based on the social-ecological model were conducted to explore factors associated with HIV-related stigma and its four dimensions (personalized stigma, disclosure concerns, negative self-image and concerns about public attitudes) at the community/hospital, interpersonal, and individual levels. RESULTS: A moderate level of HIV-related stigma was found among the 360 participants included, with a mean score of 45.26. Multivariable hierarchical regression analysis showed that at the community/hospital-level, individuals were more likely to experience high levels of HIV-related stigma if they had experienced the discriminatory behaviors from health care workers (aOR = 2.34, 95%CI: 1.48-3.70) and if they rated serostatus disclosure services as less helpful (aOR = 0.69, 95%CI: 0.48-0.98). At the interpersonal-level, individuals with an HIV-positive partner (aOR = 1.71, 95%CI: 1.01-2.90) were more likely to experience high levels of HIV-related stigma than those with an HIV-negative or unknown partner. Individuals with high resilience (aOR = 0.22, 95%CI: 0.13-0.35) had lower levels of HIV-related stigma at the individual-level. In addition, ever experiencing discriminatory behaviors from health care workers, thinking serostatus disclosure services helpful, having ever seen publicity about personal interest protection services and complaint channels for people living with HIV(PLHIV), knowing about care and support services for PLHIV from social organizations at the community/hospital-level, partner notification and support at the interpersonal-level, and violations of personal interests, resilience at the individual-level were also associated with different dimensions of HIV-related stigma. CONCLUSIONS: HIV-related stigma was moderate among women living with HIV. The social-ecological model can facilitate a better understanding of factors associated with HIV-related stigma. Multilevel intervention strategies need to be tailored to reduce HIV-related stigma.
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BACKGROUND: Acute kidney injury (AKI) is a common adverse outcome following nephrectomy. The progression from AKI to acute kidney disease (AKD) and subsequently to chronic kidney disease (CKD) remains a concern; yet, the predictive mechanisms for these transitions are not fully understood. Interpretable machine learning (ML) models offer insights into how clinical features influence long-term renal function outcomes after nephrectomy, providing a more precise framework for identifying patients at risk and supporting improved clinical decision-making processes. OBJECTIVE: This study aimed to (1) evaluate postnephrectomy rates of AKI, AKD, and CKD, analyzing long-term renal outcomes along different trajectories; (2) interpret AKD and CKD models using Shapley Additive Explanations values and Local Interpretable Model-Agnostic Explanations algorithm; and (3) develop a web-based tool for estimating AKD or CKD risk after nephrectomy. METHODS: We conducted a retrospective cohort study involving patients who underwent nephrectomy between July 2012 and June 2019. Patient data were randomly split into training, validation, and test sets, maintaining a ratio of 76.5:8.5:15. Eight ML algorithms were used to construct predictive models for postoperative AKD and CKD. The performance of the best-performing models was assessed using various metrics. We used various Shapley Additive Explanations plots and Local Interpretable Model-Agnostic Explanations bar plots to interpret the model and generated directed acyclic graphs to explore the potential causal relationships between features. Additionally, we developed a web-based prediction tool using the top 10 features for AKD prediction and the top 5 features for CKD prediction. RESULTS: The study cohort comprised 1559 patients. Incidence rates for AKI, AKD, and CKD were 21.7% (n=330), 15.3% (n=238), and 10.6% (n=165), respectively. Among the evaluated ML models, the Light Gradient-Boosting Machine (LightGBM) model demonstrated superior performance, with an area under the receiver operating characteristic curve of 0.97 for AKD prediction and 0.96 for CKD prediction. Performance metrics and plots highlighted the model's competence in discrimination, calibration, and clinical applicability. Operative duration, hemoglobin, blood loss, urine protein, and hematocrit were identified as the top 5 features associated with predicted AKD. Baseline estimated glomerular filtration rate, pathology, trajectories of renal function, age, and total bilirubin were the top 5 features associated with predicted CKD. Additionally, we developed a web application using the LightGBM model to estimate AKD and CKD risks. CONCLUSIONS: An interpretable ML model effectively elucidated its decision-making process in identifying patients at risk of AKD and CKD following nephrectomy by enumerating critical features. The web-based calculator, found on the LightGBM model, can assist in formulating more personalized and evidence-based clinical strategies.
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Lesión Renal Aguda , Aprendizaje Automático , Nefrectomía , Insuficiencia Renal Crónica , Humanos , Nefrectomía/efectos adversos , Nefrectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Estudios Retrospectivos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/diagnóstico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/diagnóstico , Pronóstico , Algoritmos , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnósticoRESUMEN
BACKGROUND: Compound 861 (Cpd861) is a traditional Chinese herbal compound for the treatment of hepatic fibrosis (HF). In the current investigation, Cpd861 has been demonstrated to have an underlying molecular mechanism and material foundation for the treatment of HF through network pharmacology, Mendelian randomization (MR), and molecular docking. METHODS: Public databases were consulted for Cpd861 constituents and HF targets. Protein-protein interactions (PPIs) were established using STRING software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To elucidate the causal relationship between potential targets and liver injury, MR was used as a methodological tool. Finally, a molecular docking analysis was conducted between the active compound and the key target. RESULTS: We obtained 174 active ingredients and 113 intersecting genes. Through the PPI network, high-degree targets were identified, namely CTNNB1, ESR1, FOS, MDM2, CCND1, TP53, RELA, and BCL2. As shown by GO and KEGG pathway enrichment analyses, Cpd861 functions through xenobiotic stimulus and oxidative stress-related genes, as well as the PI3K-AKT and non-alcoholic fatty liver disease (NAFLD) signaling pathways. The results of MR showed that MDM2 and BCL2 had a causal relationship with liver injury. Molecular docking results showed that several active compounds in Cpd861 were stably bound to BCL2. CONCLUSION: This study made predictions regarding the efficacious components, as well as potential targets and pathways of Cpd861 in the therapy of HF. This will open up a new perspective for further investigation of the molecular mechanism of Cpd861 in the treatment of HF.
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Cirrosis Hepática , Análisis de la Aleatorización Mendeliana , Simulación del Acoplamiento Molecular , Farmacología en Red , Proteínas Proto-Oncogénicas c-bcl-2 , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/químicaRESUMEN
Compulsive shopping, a behavioral disorder with significant personal and social repercussions, necessitates reliable assessment tools, especially within different cultural contexts. While several scales exist to measure compulsive buying behavior, there is a lack of validated instruments tailored to the Chinese population. This study aimed to examine the psychometric properties of the Chinese version of the Compulsive Shopping Scale (CSS) using Item Response Theory (IRT). A total of 637 young healthy participants (42.5 % males and 57.5 % females), with a mean age of 21.32 years (SD = 2.06), both undergraduate and postgraduate students, were recruited from various cities in China. Sixty-four participants were retested after a two-week interval to assess test-retest reliability. The results indicated that a one-dimensional factor structure was appropriate. The reliability analyses, including test-retest reliability, ω, α, and λ6 tests, demonstrated good internal consistency. The rating scale model analysis showed infit and outfit MNSQ values between 0.6 and 1.4, indicating a good fit. The item information curve and test information curve indicated a normal distribution of scores. Differential item functioning was observed in two items, suggesting potential gender-related differences. These findings indicate that the Chinese version of the CSS is a reliable and valid instrument for measuring compulsive shopping behaviors in Chinese populations.
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Conducta Compulsiva , Psicometría , Humanos , Femenino , Masculino , Psicometría/instrumentación , Psicometría/normas , China , Reproducibilidad de los Resultados , Adulto Joven , Conducta Compulsiva/diagnóstico , Conducta Compulsiva/psicología , Adulto , Escalas de Valoración Psiquiátrica/normasRESUMEN
BACKGROUND: Low albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients. METHODS: This study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software. RESULTS: There were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P < 0.01) and a higher rate of autoimmune disease (P = 0.03) than the low-albumin group. Membranous nephropathy (MN) was the most frequent pathological type of NS in patients with thromboembolic events, regardless of their albumin level. There were significantly fewer patients with anti-PLA2R (M-type phospholipase A2 receptor)-positive MN in the high-albumin group than in the low-albumin group (P < 0.01). CONCLUSIONS: Our study found that there was still a high risk for patients with NS and relatively high albumin levels to develop thromboembolic events.
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Síndrome Nefrótico , Albúmina Sérica , Tromboembolia , Humanos , Masculino , Femenino , Síndrome Nefrótico/sangre , Síndrome Nefrótico/complicaciones , Tromboembolia/sangre , Tromboembolia/etiología , Tromboembolia/epidemiología , Persona de Mediana Edad , Albúmina Sérica/metabolismo , Albúmina Sérica/análisis , Factores de Riesgo , Adulto , Anciano , Estudios RetrospectivosRESUMEN
Efforts to stabilize the global climate change while also continuing human development depend upon "decoupling" economic growth from fossil fuel CO2 emissions. However, evaluations of such decoupling have typically relied on production-based emissions, which do not account for emissions embodied in international trade. Yet international trade can greatly change emissions accounting and reshape the decoupling between emissions and economic growth. Here, we evaluate decoupling of economic growth from different accounts of emissions in each of the 159 countries and analyze the drivers of decoupling. We find that between 1995 and 2015, although 29 countries exhibited strong decoupling of territorial emissions (growing economies and decreasing emissions), only 19 countries achieved economic growth while their consumption-based emissions decreased. Most developed countries have achieved decoupling of emissions related to domestic goods and services, but have not achieved decoupling of emissions related to imported goods and services. The U-test confirms that the domestic component of consumption-based emissions exhibits a stronger decoupling trend from gross domestic product (GDP) growth than consumption-based emissions, and emissions from imports continue to rise with GDP per capita without a corresponding decline, providing a statistical validation of the decoupling analysis. Moreover, in the countries where economic growth and consumption-based emissions are most decoupled, a key driver is decreasing emissions intensity due to technological progressâand especially reductions in the intensity of imported goods and services. Our results reveal the importance of assessing decoupling using consumption-based emissions; successful decoupling may require international cooperation and coordinated mitigation efforts of trading partners.
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Desarrollo Económico , Comercio , Producto Interno Bruto , Cambio Climático , Dióxido de Carbono/análisis , Humanos , Combustibles FósilesRESUMEN
Background: The understanding of molecular characteristics of HER2-low breast cancer is evolving since the establishment of trastuzumab deruxtecan. Here, we explore the differences in expression patterns of immune-related genes in the tumor immune microenvironment (TME) and survival between HER2-low and HER2-zero breast cancers. Methods: Comprehensive genomic and immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on FFPE samples from 129 patients with advanced HER2-negative (immunohistochemistry (IHC) 0, 1+ or 2+ with negative ERBB2 amplification by in-situ hybridization) breast cancer. Both estrogen receptor (ER) and HER2 statuses were obtained from available pathology reports. mRNA expressions of immune biomarkers, except for PD-L1 IHC and TMB, were derived from RNA-seq. Statistical comparisons were performed using the Kruskal-Wallis or Wilcoxon Rank-Sum test or the two-sample test for equality of proportions with continuity correction (p≤0.05 for significance). Survival differences were calculated using Kaplan-Meier analysis (p≤0.05 for significance). Results: There were no significant differences in mRNA expressions of immune-related genes between HER2-low and HER2-zero breast cancers. However, HER2-low breast cancers were associated with a higher proportion of ER-positivity. When ER was analyzed along with HER2, we observed a significantly higher tumor immunogenic signature (TIGS) expression in HER2-zero/ER-negative tumors than in HER2-low/ER-positive tumors (p=0.0088). Similarly, lower expression of PD-L1 and T cell immunoglobulin and ITIM domain (TIGIT) mRNA was observed in HER2-low/ER-positive tumors when compared to HER2-zero/ER-negative tumors (p=0.014 and 0.012, respectively). Patients with HER2-low tumors had a longer median OS than those with HER2-zero tumors (94 months vs 42 months, p=0.0044). Conclusion: Patients with HER2-low breast cancer have longer survivals yet display no differences in immune-related gene expression when compared to those with HER2-zero cancers. The differences in survival can be attributed to the higher rate of ER-positivity seen in HER2-low breast cancers, compared to HER2-zero tumors.
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Cancer and depression are closely interrelated, particularly in patients with advanced cancer, who often present with comorbid anxiety and depression for various reasons. Recently, there has been a growing interest in the study of depression in cancer patients, with the aim of assessing the possible triggers, predictors, adverse events, and possible treatment options for depression in several common cancers. The objective of this narrative review is to synthesize the extant literature on the relationship between the occurrence and progression of depression in several common patient categories. The authors conducted a comprehensive review of 75 articles published in PubMed over the past five years. This review was further evaluated in the present paper. Ultimately, it was determined that depression is a prevalent and detrimental phenomenon among cancer patients, particularly those with advanced disease. Consequently, there is a pressing need to prioritize research and interventions aimed at improving the quality of life and psychosocial well-being of cancer patients, including those with advanced disease. The relationship between cancer and depression has been evolving dynamically in recent times. The current research findings indicate a strong association between cancer and depression. However, the direction of causality remains unclear. Focusing on depression in cancer patients may, therefore, be beneficial for these patients.
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Comorbilidad , Depresión , Neoplasias , Humanos , Neoplasias/epidemiología , Neoplasias/complicaciones , Neoplasias/psicología , Depresión/epidemiología , Depresión/psicología , Calidad de VidaRESUMEN
Air quality in China has significantly improved owing to the effective implementation of pollution control measures. However, mutation events caused by short-term spikes in PM2.5 in urban agglomeration regions continue to occur frequently. Identifying the spatial sources and influencing factors, as well as improving the prediction accuracy of high PM2.5 during mutation events, are crucial for public health. In this study, we firstly introduced discrete wavelet transform (DWT) to identify the mutation events with high PM2.5 concentration in the four key urban agglomerations, and evaluated the spatial sources for the polluted scenario using Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model. Additionally, DWT was combined with a widely used artificial neural network (ANN) to improve the prediction accuracy of PM2.5 concentration seven days in advance (seven-day forecast). Results indicated that mutation events commonly occurred in the northern regions during winter time, which were under the control of both short-range transportation of dirty airmass as well as negative meteorology conditions. Compared with the ANN model alone, the average band errors decreased by 9% when using DWT-ANN model. The average correlation coefficient (R) and root mean square error (RMSE) obtained using the DWT-ANN improved by 10% and 12% compared to those obtained using the ANN, indicating the efficiency and accuracy of simulating PM2.5, by combining the DWT and ANN. The short-term mortality during mutation events was then calculated, with the total averted all-cause, cardiovascular, and respiratory deaths in the four regions, being 4751, 2554, and 582 persons, respectively. A declining trend in prevented deaths from 2018 to 2020 demonstrated that the pollution intensity during mutation events gradually decreased owing to the implementation of the Three-Year Action Plan to Win the Blue Sky Defense War. The method proposed in this study can be used by policymakers to take preventive measures in response to a sudden increase in PM2.5, thereby ensuring public health.
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Contaminantes Atmosféricos , Contaminación del Aire , Monitoreo del Ambiente , Redes Neurales de la Computación , Material Particulado , Material Particulado/análisis , China , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Humanos , Exposición a Riesgos Ambientales/estadística & datos numéricos , CiudadesRESUMEN
The electron extraction from perovskite/C60 interface plays a crucial role in influencing the photovoltaic performance of inverted perovskite solar cells (PSCs). Here, we develop a one-stone-for-three-birds strategy via employing a novel fullerene derivative bearing triple methyl acrylate groups (denoted as C60-TMA) as a multifunctional interfacial layer to optimize electron extraction at the perovskite/C60 interface. It is found that the C60-TMA not only passivates surface defects of perovskite via coordination interactions between C=O groups and Pb2+ cations but also bridge electron transfer between perovskite and C60. Moreover, it effectively induces the secondary grain growth of the perovskite film through strong bonding effect, and this phenomenon has never been observed in prior art reports on fullerene related studies. The combination of the above three upgrades enables improved perovskite film quality with increased grain size and enhanced crystallinity. With these advantages, C60-TMA treated PSC devices exhibit a much higher power conversion efficiency (PCE) of 24.89 % than the control devices (23.66 %). Besides, C60-TMA benefits improved thermal stability of PSC devices, retaining over 90 % of its initial efficiency after aging at 85 °C for 1200â h, primarily due to the reinforced interfacial interactions and improved perovskite film quality.
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Two important plant enzymes are 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27), which is necessary for biosynthesis of plastoquinone and tocopherols, and phytoene dehydrogenase (PDS; EC 1.3.99.26), which plays an important role in colour rendering. Dual-target proteins that inhibit pigment synthesis will prevent resistant weeds and improve the spectral characteristics of herbicides. This study introduces virtual screening of pharmacophores based on the complex structure of the two targets. A three-dimensional database was established by screening 1,492,858 compounds based on the Lipinski principle. HPPD&PDS dual-target receptor-ligand pharmacophore models were then constructed, and nine potential dual-target inhibitors were obtained through pharmacophore modeling, molecular docking, and molecular dynamics simulations. Ultimately, ADMET prediction software yielded three compounds with high potential as dual-target herbicides. The obtained nine inhibitors were stable when combined with both HPPD and PDS proteins. This study offers guidance for the development of HPPD&PDS dual-target inhibitors with novel skeletons.
Asunto(s)
4-Hidroxifenilpiruvato Dioxigenasa , Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , 4-Hidroxifenilpiruvato Dioxigenasa/antagonistas & inhibidores , 4-Hidroxifenilpiruvato Dioxigenasa/química , 4-Hidroxifenilpiruvato Dioxigenasa/metabolismo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Herbicidas/química , Herbicidas/farmacología , Simulación de Dinámica Molecular , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , Oxidorreductasas/química , Evaluación Preclínica de MedicamentosRESUMEN
In recent years, China has adopted numerous policies and regulations to control NOx emissions to further alleviate the adverse impacts of NO3--N deposition. However, the variation in wet NO3--N deposition under such policies is not clear. In this study, the southeastern area, with highly developed industries and traditional agriculture, was selected to explore the variation in NO3--N deposition and its sources changes after such air pollution control through field observation and isotope tracing. Results showed that the annual mean concentrations of NO3--N in precipitation were 0.67 mg L-1 and 0.54 mg L-1 in 2014-2015 and 2021-2022, respectively. The average wet NO3--N depositions in 2014-2015 and 2021-2022 was 7.76 kg N ha-1 yr-1 and 5.03 kg N ha-1 yr-1, respectively, indicating a 35% decrease. The δ15N-NO3- and δ18O-NO3- values were lower in warm seasons and higher in cold seasons, and both showed a lower trend in 2021-2022 compared with 2014-2015. The Bayesian model results showed that the NOx emitted from coal-powered plants contributed 53.6% to wet NO3--N deposition, followed by vehicle exhaust (22.9%), other sources (17.1%), and soil emissions (6.4%) during 2014-2015. However, the contribution of vehicle exhaust (33.3%) overpassed the coal combustion (32.3%) and followed by other sources (25.4%) and soil emissions (9.0%) in 2021-2022. Apart from the control of air pollution, meteorological factors such as temperature, precipitation, and solar radiation are closely related to the changes in atmospheric N transformation and deposition. The results suggest phased achievements in air pollution control and that more attention should be paid to the control of motor vehicle exhaust pollution in the future, at the same time maintaining current actions and supervision of coal-powered plants.