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Circulating proteomes provide a snapshot of the physiological state of a human organism responding to pathogenic challenges and drug interventions. The outcomes of patients with COVID-19 and acute respiratory distress syndrome triggered by the SARS-CoV2 virus remain uncertain. Tocilizumab is an anti-interleukin-6 treatment that exerts encouraging clinical activity by controlling the cytokine storm and improving respiratory distress in patients with COVID-19. We investigate the biological determinants of therapeutic outcomes after tocilizumab treatment. Overall, 28 patients hospitalized due to severe COVID-19 who were treated with tocilizumab intravenously were included in this study. Sera were collected before and after tocilizumab, and the patient's outcome was evaluated until day 30 post-tocilizumab infusion for favorable therapeutic response to tocilizumab and mortality. Hyperreaction monitoring measurements by liquid chromatography-mass spectrometry-based proteomic analysis with data-independent acquisition quantified 510 proteins and 7019 peptides in the serum of patients. Alterations in the serum proteome reflect COVID-19 outcomes in patients treated with tocilizumab. Our results suggested that circulating proteins associated with the most significant prognostic impact belonged to the complement system, platelet degranulation, acute-phase proteins, and the Fc-epsilon receptor signaling pathway. Among these, upregulation of the complement system by activation of the classical pathway was associated with poor response to tocilizumab, and upregulation of Fc-epsilon receptor signaling was associated with lower mortality.
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Anticorpos Monoclonais Humanizados , Tratamento Farmacológico da COVID-19 , COVID-19 , Receptores de Interleucina-6 , SARS-CoV-2 , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , COVID-19/sangue , COVID-19/mortalidade , COVID-19/virologia , Receptores de Interleucina-6/sangue , Receptores de Interleucina-6/antagonistas & inibidores , Pessoa de Meia-Idade , Idoso , SARS-CoV-2/fisiologia , Proteômica/métodos , Proteoma/análise , Cromatografia Líquida/métodos , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Idoso de 80 Anos ou mais , Interleucina-6/sangueRESUMO
Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.
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Classe I de Fosfatidilinositol 3-Quinases , Mutação , Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Imunoterapia/métodos , Antígeno HLA-A11/genética , Antígeno HLA-A11/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Linhagem Celular TumoralRESUMO
Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.
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Pulmão , Metabolômica , Níquel , Humanos , Níquel/sangue , Masculino , Feminino , Adulto Jovem , China , Pulmão/efeitos dos fármacos , Estudos Transversais , Estudos de Coortes , Adulto , Testes de Função Respiratória , População do Leste AsiáticoRESUMO
BACKGROUND: Despite recent advances in locoregional, systemic, and novel checkpoint inhibitor treatment, hepatocellular carcinoma (HCC) is still associated with poor prognosis. The feasibility of potentially curative liver resection (LR) and transplantation (LT) is limited by the underlying liver disease and a shortage of organ donors. Especially after LR, high recurrence rates present a problem and circulating tumor cells are a major cause of extrahepatic recurrence. Tigecycline, a commonly used glycylcycline antibiotic, has been shown to have antitumorigenic effects and could be used as a perioperative and adjuvant therapeutic strategy to target circulating tumor cells. We aimed to investigate the effect of tigecycline on HCC cell lines and its mechanisms of action. METHODS: Huh7, HepG2, Hep3B, and immortalized hepatocytes underwent incubation with clinically relevant tigecycline concentrations, and the influence on proliferation, migration, and invasion was assessed in two- and three-dimensional in vitro assays, respectively. Bioinformatic analysis was used to identify specific targets of tigecycline. The expression of RAC1 was detected using western blot, RT-PCR and RNA sequencing. ELISA and flow cytometry were utilized to measure reactive oxygen species (ROS) generation upon tigecycline treatment and flow cytometry to detect alterations in cell cycle. Changes in mitochondrial function were detected via seahorse analysis. RNA sequencing was performed to examine involved pathways. RESULTS: Tigecycline treatment resulted in a significant reduction of mitochondrial function with concomitantly preserved mitochondrial size, which preceded the observed decrease in HCC cell viability. The sensitivity of HCC cells to tigecycline treatment was higher than that of immortalized non-cancerous THLE-2 hepatocytes. Tigecycline inhibited both migratory and invasive properties. Tigecycline application led to an increase of detected ROS and an S-phase cell cycle arrest. Bioinformatic analysis identified RAC1 as a likely target for tigecycline and the expression of this molecule was increased in HCC cells as a result of tigecycline treatment. CONCLUSION: Our study provides evidence for the antiproliferative effect of tigecycline in HCC. We show for the first time that this effect, likely to be mediated by reduced mitochondrial function, is associated with increased expression of RAC1. The reported effects of tigecycline with clinically relevant and achievable doses on HCC cells lay the groundwork for a conceivable use of this agent in cancer treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Tigeciclina/farmacologia , Tigeciclina/metabolismo , Tigeciclina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular , Células Neoplásicas Circulantes/metabolismo , Proliferação de Células/genética , Células Hep G2 , Mitocôndrias/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Apoptose , Regulação Neoplásica da Expressão Gênica , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/farmacologiaRESUMO
The polyvinylidene difluoride (PVDF) membrane has received considerable attention as a flexible surface enhanced Raman scattering (SERS) substrate due to its excellent mechanical and physicochemical properties. However, the poor fouling resistance of PVDF membrane due to its intrinsic hydrophobic property limits its practical application. To address this, in this investigation, a SERS imprinted membrane is synthesized based on W18O49/Ag composites. Firstly, to promote hydrophilicity, N-vinyl-2-pyrrolidone (NVP) and triethoxyvinylsilane (VTES) are copolymerized by hydrolysis condensation and linked with engineered polyvinypyrrolidone (PVP) chains exposed on the surface of membrane. Furthermore, W18O49/Ag composites are dispersed on the membrane under the assistance of polydopamine (pDA) to promote the pollution resistance. Subsequently, in order to demonstrate the practical detection property, W18O49/Ag/PVDF membrane is selected as the SERS substrate to synthesize SERS imprinted membrane by precipitation polymerization for the selective detection of L-tyrosine. The characteristic results reveal that the SERS-imprinted membrane exhibits satisfactory hydrophilicity, and it can effectively degrade the pollutant molecules absorbed on its surface under ultraviolet light illumination. It is proved from the detection results that the LOD of WADP-MIMs for L-tyrosine reached 10-9 mol L-1 when the concentration of L-tyrosine changed between 10-3-10-9 mol L-1. The correlation coefficient (R2) is 0.994 and the limit of detection is 10-9 mol L-1. Meanwhile, it can be applied for the selective detection of L-tyrosine in mixture samples. Overall, this study presents a novel approach for the hydrophilic modification and pollution resistance enhancement of PVDF-based SERS imprinted membrane, which can be effectively utilized for the selective detection of practical samples.
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Polivinil , Tirosina , Polímeros de Fluorcarboneto , Interações Hidrofóbicas e Hidrofílicas , Análise Espectral RamanRESUMO
BACKGROUND The anti-inflammatory drug sulfasalazine (SAS) has been confirmed to inhibit the growth of triple-negative breast cancer (TNBC), but the mechanism is not clear. The aim of this study was to use network pharmacology to find relevant pathways of SAS in TNBC patients. MATERIAL AND METHODS Through screening of the GeneCards, CTD, and ParmMapper databases, potential genes related to SAS and TNBC were identified. In addition, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed using the R programming language. Protein-protein interaction networks were constructed using Cytoscape. The Kaplan-Meier plotter screened genes related to TNBC prognosis. TNBC patient gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas database. A heatmap was generated using the R programming language that presents the expression of potential target genes in patients with TNBC. RESULTS Eighty potential target genes were identified through multiple databases. The bioinformatical analyses predicted the interrelationships, potential pathways, and molecular functions of the genes from multiple aspects, which are associated with physiological processes such as the inflammatory response, metabolism of reactive oxygen species (ROS), and regulation of proteins in the matrix metalloproteinase (MMP) family. Survival analysis showed that 12 genes were correlated with TNBC prognosis. Heatmapping showed that genes such as those encoding members of the MMP family were differentially expressed in TNBC tissues and normal tissues. CONCLUSIONS Our analysis revealed that the main reasons for the inhibitory effect of SAS on TNBC cells may be inhibition of the inflammatory response and MMP family members and activation of ROS.
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Farmacologia Clínica/métodos , Sulfassalazina/farmacologia , Neoplasias de Mama Triplo Negativas , Anti-Inflamatórios não Esteroides/farmacologia , Biologia Computacional/métodos , Feminino , Redes Reguladoras de Genes , Humanos , Inflamação , Metaloproteinases da Matriz , Mapas de Interação de Proteínas , Espécies Reativas de OxigênioRESUMO
OBJECTIVE: To investigate the relationship between the second to the fourth digit ratio (2D:4D) and body mass index (BMI) in infertile men of the Han ethnic group in Ningxia. METHODS: Using anthropometry, we calculated the mean ratio of 2D:4D and BMI of 197 infertile men and 148 normal healthy male controls, followed by analysis of their relationship. RESULTS: The BMI was correlated positively with the 2D:4D ratio of the left hand in the infertile men (P < 0.05) and in the patients with a higher 2D:4D ratio of the left hand (P < 0.05), but negatively with the 2D:4D ratio of the righ/left (Dr-1) (left: P < 0.01; Dr-l: P < 0.05). The mean 2D: 4D ratio and BMI were both lower in the normal control than in the infertile men, with statistically significant differences in BMI (P < 0.05) and the 2D:4D ratio of the left hand (P < 0.05). CONCLUSION: There is a correlation between the 2D:4D ratio and BMI in infertile men.
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Índice de Massa Corporal , Dedos/anatomia & histologia , Infertilidade Masculina/diagnóstico , Estudos de Casos e Controles , Humanos , MasculinoRESUMO
The SDG 15.3.1 target of Land Degradation Neutrality (LDN) only has 15 years from conception (in 2015) to realization (in 2030). Therefore, investigating the effectiveness and challenges of LDN has become a priority, especially in drylands, where fragile ecosystems intersect with multiple disturbances. In this study, solutions are proposed and validated based on the challenges of LDN. We chose the Northern Slope of the Tianshan Mountains as a case study and set baselines in 2005 and 2010. The region and degree of land change (including degraded, stable, and improved) were depicted at the pixel scale (100 × 100 m), and LDN realization was assessed at the regional scale (including administrative districts and 5000 × 5000 m grids). The results showed a significant disparity between the two baselines. The number of areas that realized the LDN target was rare, regardless of the scale of the administrative districts or grids. Chord plots, Spearman's correlation, and curve estimation were employed to reveal the relationship between LDN and seven natural or socioeconomic factors. We found that substantial degradation was closely related to the expansion of unused, urban, and mining land and reduction in water, glaciers, and forests. Further evidence suggests that agricultural development both positively and negatively affects LDN, whereas urbanization and mining activities are undesirable for LDN. Notably, the adverse effects of glacier melting require additional attention. Therefore, we consider the easy-to-achieve and hard-to-achieve baselines as the mandatory and desirable targets of LDN, respectively, and focus further efforts in three aspects: preventing agricultural exploitation from occupying ecological resources, defining reasonable zones for urbanization and mining, and reducing greenhouse gas emissions to mitigate warming. Overall, this study is expected to be a beneficial addition to existing LDN theoretical systems and serve as a case validation of the challenges of LDN in drylands.
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Previously, we found that patients with estrogen receptor (ER)-positive, HER2-low breast cancer are resistant to neoadjuvant chemotherapy (NACT) and have worse outcomes than those who achieve pathological complete response (pCR) after NACT. This study aimed to investigate the prognosis and influencing factors in these patients. A total of 618 patients with ER-positive breast cancer who received standard thrice-weekly NACT were enrolled, including 411 patients with ER-positive, HER2-low breast cancer. Data on the clinicopathological features of these patients before and after NACT were collected. Univariate and multivariate Cox regression analyses were used to identify the independent factors affecting 5-year disease-free survival (DFS). Among the ER-positive, HER2-low patients, 49 (11.9%) achieved a pCR after NACT. A significant difference in survival was observed between patients with and without residual disease after NACT. Additionally, changes in immunohistochemical markers and tumor stages before and after NACT were found to be significant. According to univariate and multivariate analyses, cN_stage (P = 0.002), ER (P = 0.002) and Ki67 (P = 0.023) expression before NACT were significantly associated with 5-year DFS, while pT_stage (P = 0.015), pN_stage (P = 0.029), ER (P = 0.020) and Ki67 (P < 0.001) levels after NACT were related to 5-year DFS in ER-positive, HER2-low patients with residual disease. Our study suggested that high proliferation, low ER expression and advanced stage before and after NACT are associated with a poor prognosis, providing useful information for developing long-term treatment strategies for ER-positive, HER2-low breast cancer in patients with residual disease in the future.
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Neoplasias da Mama , Terapia Neoadjuvante , Neoplasia Residual , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Receptor ErbB-2/metabolismo , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Prognóstico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Intervalo Livre de DoençaRESUMO
Background: CDC6 is critical in DNA replication initiation, but its expression patterns and clinical implications in cancer are underexplored. This study uses multi-omics data from The Cancer Genome Atlas (TCGA) to comprehensively analyze CDC6 across various cancers, aiming to evaluate its potential as a prognostic biomarker and explore its role in immunotherapy. Methods: By leveraging multi-omics data from TCGA, we conducted a comprehensive analysis of CDC6 expression across a variety of cancer types. Least absolute shrinkage and selection operator (LASSO) regression was employed to assess the association of CDC6 with key molecules implicated in pancreatic cancer. Results: CDC6 expression was found to be significantly upregulated across a broad spectrum of cancers. High levels of CDC6 expression were associated with poor prognosis in several cancer types. Notable associations were observed between CDC6 expression and tumor mutational burden (TMB), microsatellite instability (MSI), as well as immune cell infiltration. Co-expression analysis revealed significant associations between CDC6 and prevalent immune checkpoint genes. A risk model incorporating CDC6-related genes, including CCNA1, CCNA2, CCND1, CCND2, CDC25B, CDC6, and CDK2, was developed for pancreatic cancer. Conclusions: CDC6 emerges as a promising prognostic biomarker and a potential target for immunotherapy across various cancers, including pancreatic cancer. It appears to modulate immune responses across cancer types, highlighting its regulatory role. Further exploration into the biological functions and clinical implications of CDC6 is warranted.
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Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2-) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2- breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2- breast cancer patients.
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Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2 , Receptores de Estrogênio , Transdução de Sinais , Proteína Smad4 , Humanos , Proteína Smad4/metabolismo , Proteína Smad4/genética , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Linhagem Celular Tumoral , Animais , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Tamoxifeno/análogos & derivados , Camundongos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Receptores ErbB/metabolismo , Receptores ErbB/genéticaRESUMO
For mankind's survival and development, water, energy, and food (WEF) are essential material guarantees. In China, however, the spatial distribution of WEF is seriously unbalanced and mismatched. Here, a collaborative governance mechanism that aims at nexus security needs to be urgently established. In this paper, the Yellow River Basin in China with a representative WEF system, was selected as a case. Firstly, a comprehensive framework for WEF coupling coordination was constructed, and the relationship and mechanism between them were analyzed theoretically. Then, we investigated the spatiotemporal characteristics and driving mechanisms of the coupling coordination degree (CCD) with a composite evaluation method, coupling coordination degree model, spatial statistical analysis, and multiscale geographic weighted regression. Finally, policy implications were discussed to promote the coordinated development of the WEF system. The results showed that: 1) WEF subsystems showed a significant imbalance of spatial pattern and diversity in temporal changes; 2) the CCD for the WEF system varied little and remained at moderate coordination. Areas with moderate coordination have increased, while areas with superior coordination and mild disorder have decreased. In addition, the spatial clustering phenomenon of the CCD was significant and showed obvious characteristics of polarization; and 3) the action of each factor is self-differentiated and regionally variable. For different factors, GDP per capita was of particular importance, which contributed most to the regional development's coupling coordination. For different regions, GDP per capita, average yearly precipitation, population density, and urbanization rate exhibited differences in geographical gradients in an east-west direction. The conclusion can provide references for regional resource allocation and sustainable development by enhancing WEF system utilization efficiency.
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In order to further promote the application and development of unmanned aviation in the manned field, and reduce the difficulty that airlines cannot avoid due to unexpected factors such as bad weather, aircraft failure, and so on, the problem of restoring aircraft routes has been studied. To reduce the economic losses caused by flight interruption, this paper divides the repair problem of aircraft operation plans into two sub problems, namely, the generation of flight routes and the reallocation of aircraft. Firstly, the existing fixed-point iteration method proposed by Dang is used to solve the feasible route generation model based on integer programming. To calculate quickly and efficiently, a segmentation method that divides the solution space into mutually independent segments is proposed as the premise of distributed computing. The feasible route is then allocated to the available aircraft to repair the flight plan. The experimental results of two examples of aircraft fault grounding and airport closure show that the method proposed in this paper is effective for aircraft route restoration.
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Vegetation restoration can effectively improve the ecological environment of mining areas, enhance the ecological service function, and promote the carbon sequestration and sink increase in the ecosystem. The soil carbon cycle plays an important role in the biogeochemical cycle. The abundance of functional genes can predict the material cycling potential and metabolic characteristics of soil microorganisms. Previous studies on functional microorganisms have mainly focused on large ecosystems such as farmland, forest, and wetland, but relatively little attention has been paid to complex ecosystems with great anthropogenic interference and special functions, such as mines. Clarifying the succession and driving mechanism of functional microorganisms in reclaimed soil under the guidance of vegetation restoration is helpful to fully explore how functional microorganisms change with the change in abiotic and biotic conditions. Therefore, 25 topsoil samples were collected from grassland (GL), brushland (BL), coniferous forests (CF), broadleaf forests (BF), and mixed coniferous and broadleaf forests (MF) in the reclamation area of the Heidaigou open pit waste dump on the Loess Plateau. The absolute abundance of soil carbon cycle functional genes was determined using real-time fluorescence quantitative PCR to explore the effect of vegetation restoration on the abundance of carbon cycle-related functional genes in soil and its internal mechanism. The results showed that:â the effects of different vegetation restoration types on the chemical properties of reclaimed soil and the abundance of functional genes related to the carbon cycle were significantly different (P<0.05). GL and BL showed significantly better accumulation of soil organic carbon, total nitrogen, and nitrate nitrogen (P<0.05) than that in CF. â¡ The gene abundance of rbcL, acsA, and mct was the highest among all carbon fixation genes. The abundance of functional genes related to carbon cycle in BF soil was higher than that in other types, which was closely related to the high activity of ammonium nitrogen and BG enzymes and the low activity of readily oxidized organic carbon and urease in BF soil. The functional gene abundance of carbon degradation and methane metabolism was positively correlated with ammonium nitrogen and BG enzyme activity and negatively correlated with organic carbon, total nitrogen, readily oxidized organic carbon, nitrate nitrogen, and urease activity (P<0.05). ⢠Different vegetation types could directly affect soil BG enzyme activity or affect soil nitrate nitrogen content, thus indirectly affecting BG enzyme activity, in turn manipulating the abundance of functional genes related to the carbon cycle. This study is helpful to understand the effects of different vegetation restoration types on the functional genes related to the carbon cycle in the soil of mining areas on the Loess Plateau and provides a scientific basis for ecological restoration and ecological carbon sequestration and sink enhancement in mining areas.
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Ecossistema , Solo , Carbono , Nitratos , Urease , Ciclo do Carbono , Florestas , NitrogênioRESUMO
Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with favorable outcomes in breast cancer patients. Identifying reliable predictors for pCR can assist in selecting patients who will derive the most benefit from NAC. The prognostic nutritional index (PNI) serves as an indicator of nutritional status and systemic immune competence. It has emerged as a prognostic biomarker in several malignancies; however, its predictive value for pCR in breast cancer remains uncertain. The objective of this study is to assess the predictive value of pretreatment PNI for pCR in breast cancer patients. Methods: A total of 1170 patients who received NAC in two centers were retrospectively analyzed. The patients were divided into three cohorts: a training cohort (n=545), an internal validation cohort (n=233), and an external validation cohort (n=392). Univariate and multivariate analyses were performed to assess the predictive value of PNI and other clinicopathological factors. A stepwise logistic regression model for pCR based on the smallest Akaike information criterion was utilized to develop a nomogram. The C-index, calibration plots and decision curve analysis (DCA) were used to evaluate the discrimination, calibration and clinical value of the model. Results: Patients with a high PNI (≥53) had a significantly increased pCR rate (OR 2.217, 95% CI 1.215-4.043, p=0.009). Tumor size, clinical nodal status, histological grade, ER, Ki67 and PNI were identified as independent predictors and included in the final model. A nomogram was developed as a graphical representation of the model, which incorporated the PNI and five other factors (AIC=356.13). The nomogram demonstrated satisfactory calibration and discrimination in the training cohort (C-index: 0.816, 95% CI 0.765-0.866), the internal validation cohort (C-index: 0.780, 95% CI 0.697-0.864) and external validation cohort (C-index: 0.714, 95% CI 0.660-0.769). Furthermore, DCA indicated a clinical net benefit from the nomogram. Conclusion: The pretreatment PNI is a reliable predictor for pCR in breast cancer patients. The PNI-based nomogram is a low-cost, noninvasive tool with favorable predictive accuracy for pCR, which can assist in determining individualized treatment strategies for breast cancer patients.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Avaliação Nutricional , Nomogramas , Prognóstico , Estudos RetrospectivosRESUMO
Anthropogenic climate change and species invasion are two major threats to biodiversity, affecting the survival and distribution of many species around the world. Studying the responses of invasive species under climate change can help better understand the ecological and genetic mechanisms of their invasion. However, the effects of warming and phosphorus deposition on the phenotype of native and invasive plants are unknown. To address the problem, we applied warming (+2.03 °C), phosphorus deposition (4 g m-2 yr-1 NaH2PO4), and warming × phosphorus deposition to Solidago canadensis and Artemisia argyi to measure the direct effects of environmental changes on growth and physiology at the seedling stage. Our results reveal that the physiology parameters of A. argyi and S. canadensis did not change significantly with the external environment. Under phosphorus deposition, S. canadensis had higher plant height, root length, and total biomass compared to A. argyi. Interestingly, warming has an inhibitory effect on the growth of both A. argyi and S. canadensis, but overall, the reduction in total biomass for S. canadensis (78%) is significantly higher than A. argyi (52%). When the two plants are treated with warming combined with phosphorus deposition, the advantage gained by S. canadensis from phosphorus deposition is offset by the negative effects of warming. Therefore, under elevated phosphorus, warming has a negative effect on the invasive S. canadensis and reduces its growth advantage.
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The legacy effects of invasive plant species can hinder the recovery of native communities, especially under nitrogen deposition conditions, where invasive species show growth advantages and trigger secondary invasions in controlled areas. Therefore, it is crucial to thoroughly investigate the effects of nitrogen deposition on the legacy effects of plant invasions and their mechanisms. The hypotheses of this study are as follows: (1) Nitrogen deposition amplifies the legacy effects of plant invasion. This phenomenon was investigated by analysing four potential mechanisms covering community system structure, nitrogen metabolism, geochemical cycles, and microbial mechanisms. The results suggest that microorganisms drive plant-soil feedback processes, even regulating or limiting other factors. (2) The impact of nitrogen deposition on the legacy effects of plant invasions may be intensified primarily through enhanced nitrogen metabolism via microbial anaerobes bacteria. Essential insights into invasion ecology and ecological management have been provided by analysing how nitrogen-fixing bacteria improve nitrogen metabolism and establish sustainable methods for controlling invasive plant species. This in-depth study contributes to our better understanding of the lasting effects of plant invasions on ecosystems and provides valuable guidance for future ecological management.
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In this paper, a dual-frequency wireless power transfer method is proposed, capable of achieving controllable routing and providing power through magnetic coupling resonance to various positions on a two-dimensional plane. The plane is composed of multiple power supply units with a uniform structure. Every unit has two different resonant states to switch, an activated state to power the receiver and a low-power inactive state adopted to maintain power required for state-switching. By switching and combining units in different states through wireless control circuits, directional wireless transfer of power on the plane can be realized. The circuit of power transfer through coupling is modelled and analysed. Electromagnetic simulations are conducted, followed by implementation and test of an experimental system. Both single-receiver and multiple-receiver situations are applicable in this method. The highest transmission efficiency can reach 93.3% under single receiver situation after coupling 5 units, which reveals satisfactory ability in flexibility and efficiency. Embedded in multiple application scenes, we envision further possibilities of this method such as indoor-device wireless charging and free-moving robot charging systems in factories.
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Background: The importance of pyroptosis in tumorigenesis and cancer progression is becoming increasingly apparent. However, the efficacy of using pyroptosis-related genes (PRGs) in predicting the prognosis of pancreatic adenocarcinoma (PAAD) patients is unknown. Methods: This investigation used two databases to obtain expression data for PAAD patients. Differentially expressed PRGs (DEPRGs) were identified between PAAD and control samples. Several bioinformatic approaches were used to analyze the biological functions of DEPRGs and to identify prognostic DERPGs. A miRNA-prognostic DEPRG-transcription factor (TF) regulatory network was created via the miRNet online tool. A risk score model was created after each patient's risk score was calculated. The microenvironments of the low- and high-risk groups were assessed using xCell, the expression of immune checkpoints was determined, and gene set variation analysis (GSVA) was performed. Finally, the efficacy of certain potential drugs was predicted using the pRRophetic algorithm, and the results in the high- and low-risk groups were compared. Results: A total of 13 DEPRGs were identified between PAAD and control samples. Functional enrichment analysis showed that the DEPRGs had a close relationship with inflammation. In univariate and multivariate Cox regression analyses, GSDMC, IRF1, and PLCG1 were identified as prognostic biomarkers in PAAD. The results of the miRNA-prognostic DEPRG-TF regulatory network showed that GSDMC, IRF1, and PLCG1 were regulated by both specific and common miRNAs and TFs. Based on the risk score and other independent prognostic indicators, a nomogram with a good ability to predict the survival of PAAD patients was developed. By evaluating the tumor microenvironment, we observed that the immune and metabolic microenvironments of the two groups were substantially different. In addition, individuals in the low-risk group were more susceptible to axitinib and camptothecin, whereas lapatinib might be preferred for patients in the high-risk group. Conclusion: Our study revealed the prognostic value of PRGs in PAAD and created a reliable model for predicting the prognosis of PAAD patients. Our findings will benefit the prognostication and treatment of PAAD patients.
Assuntos
Adenocarcinoma , MicroRNAs , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Proteínas Citotóxicas Formadoras de Poros , Prognóstico , Piroptose , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
The polyacrylonitrile/fly ash composite was synthesized through solution polymerization and was modified with NH2OH·HCl. The amidoxime-modified polyacrylonitrile/fly ash composite demonstrated excellent adsorption capacity for Zn2+ in an aqueous medium. Fourier transform-Infrared spectroscopy, thermogravimetric analysis, nitrogen adsorption, X-ray diffraction, and scanning electron microscopy were used to characterize the prepared materials. The results showed that the resulting amidoxime-modified polyacrylonitrile/fly ash composite was able to effectively remove Zn2+ at pH 4-6. Adsorption of Zn2+ was hindered by the coexisting cations. The adsorption kinetics of Zn2+ by Zn2+ followed the pseudo-second order kinetic model. The adsorption process also satisfactorily fit the Langmuir model, and the adsorption process was mainly single layer. The Gibbs free energy ΔG0, ΔH0, and ΔS0 were negative, indicating the adsorption was a spontaneous, exothermic, and high degree of order in solution system.