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PURPOSE: To identify symptom clusters (SCs) in lung cancer patients undergoing chemotherapy and explore their impact on health-related quality of life (HRQoL). METHODS: Patients were invited to complete the Chinese version of the M.D. Anderson Symptom Inventory with the Lung Cancer Module and the Quality of Life Questionnaire-core 30. Network analysis was employed to identify SCs. The associations between SCs and each function of HRQoL were examined using the Pearson correlation matrix. Multiple linear regression was applied to analyze the influencing factors of each function of HRQoL. RESULTS: A total of 623 lung cancer patients who were receiving chemotherapy were recruited. The global health status of lung cancer patients was 59.71 ± 21.09, and 89.73% of patients developed symptoms. Three SCs (Somato-psychological SC, Respiratory SC, and Gastrointestinal SC) were identified, and Somato-psychological SC and Gastrointestinal SC were identified as influencing factors for HRQoL in lung cancer patients. CONCLUSION: Most lung cancer patients who undergo chemotherapy experience a range of symptoms, which can be categorized into three SCs. The Somato-psychological SC and Gastrointestinal SC negatively impacted patients' HRQoL. Health care providers should prioritize monitoring these SCs to identify high-risk patients early and implement targeted preventive and intervention measures for each SC, aiming to alleviate symptom burden and enhance HRQoL.
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Prostate cancer (PCa) is the second leading cause of cancer-related death among men in western countries. Evidence has indicated the significant role of the androgen receptor (AR) as the main driving factor in controlling the development of PCa, making androgen receptor inhibition (ARI) therapy a pivotal management approach. In addition, AR independent signaling pathways also contribute to PCa progression. One such signaling pathway that has garnered our attention is N6-Methyladenosine (m6A) signaling, which refers to a chemical modification on RNA with crucial roles in RNA metabolism and disease progression, including PCa. It is important to comprehensively summarize the role of each individual m6A regulator in PCa development and understand its interaction with AR signaling. This review aims to provide a thorough summary of the involvement of m6A regulators in PCa development, shedding light on their upstream and downstream signaling pathways. This summary sets the stage for a comprehensive review that would benefit the scientific community and clinical practice by enhancing our understanding of the biology of m6A regulators in the context of PCa.
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The co-contamination of arsenic (As) and cadmium (Cd) in the environment is of most concern. In this work, poorly crystalline CaFe-layered double hydroxide (CaFe-LDH) was synthesized with a Ca-to-Fe molar ratio of 4 to ensure effective immobilization of Cd and As in soil. The application of Ca4Fe-LDH in soil remediation demonstrated that the targeted heavy metals gradually mineralized into a relatively stable oxidizable and residual state. At a soil remediation dosage of 1.6%, the availability levels of Cd and As decreased significantly, achieving stabilization efficiencies of 99% and 85.2% respectively. Cd is trapped through isomorphic substitution and dissolution-reprecipitation of calcium (Ca) laminate, resulting in the formation of CdCaFe-LDH mineralization products. As is immobilized through ion exchange with interlayer anions, redox with Fe(III), and Fe-Cd-As complexation. Moreover, the results of the characterization and density functional theoretical (DFT) calculations demonstrate that the CdCaFe-LDH formed by isomeric substitution of Ca for Cd enhanced the adsorption of As on the (110) plane of LDH, indicating that the trap mechanism of Cd and As by Ca4Fe-LDH is synergistically promoted. Overall, the above results prove that mineralization using Ca4Fe-LDH is a promising method to remediate soils combined contaminated by both Cd and As.
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Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion capacities, as well as on the stem cell-like phenotype, within TNBC cells. Further experiments showed that YAP1 is the downstream target of SENP3, and SENP3 regulates tumorigenesis in a YAP1-dependent manner. YAP1 is found to be SUMOylated and SENP3 deconjugates SUMOylated YAP1 and promotes degradation mediated by the ubiquitin-proteasome system. More importantly, YAP1 with a mutation at the SUMOylation site impedes the capacity of wild-type YAP1 in TNBC tumorigenesis. Taken together, our findings firmly establish the pivotal role of SENP3 in the modulation of YAP1 deSUMOylation, unveiling novel mechanistic insight into the important role of SENP3 in the regulation of TNBC tumorigenesis in a YAP1-dependent manner.
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BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). This study investigated safety and efficacy of once-daily and 3-times-weekly dosing in patients with dialysis-dependent (DD)-CKD compared with darbepoetin alfa (DA). METHODS: This phase 3b, randomized (1:1:1; vadadustat once-daily [starting dose: 300 or 450 mg], vadadustat 3-times-weekly [starting dose: 600 or 750 mg], DA), open-label, active-controlled, noninferiority trial included conversion (weeks 0-20) and maintenance (weeks 20-52) periods. Primary and secondary efficacy endpoints were mean change in hemoglobin from baseline during the primary (PEP, weeks 20-26) and secondary (SEP, weeks 46-52) evaluation periods. Other endpoints included proportion of patients requiring ESA rescue (hemoglobin <9.5 g/dL or with increases in dose ≥50% or ≥100% in DA group). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs (SAEs). RESULTS: Least squares (LS) mean treatment difference between vadadustat once-daily and DA from baseline to PEP was -0.27 g/dL (95% CI, -0.55 to 0.01); the lower bound met the noninferiority threshold (-0.75 g/dL). The LS mean treatment difference between vadadustat 3-times-weekly and DA from baseline to PEP was -0.53 g/dL (95% CI, -0.80 to -0.25), which did not meet the lower bound noninferiority threshold. The LS mean change from baseline to the SEP between DA and vadadustat once-daily was -0.40 (95% CI, -0.79 to -0.02), and for vadadustat 3-times-weekly was -0.42 (95% CI, -0.81 to -0.02). Proportion of patients who received ESA rescue during weeks 2-52 was higher in the DA group than vadadustat groups. Similar TEAEs and treatment-emergent SAEs were observed across groups. CONCLUSIONS: Vadadustat once-daily, but not 3-times-weekly, was noninferior to DA in the correction and maintenance of hemoglobin in patients with DD-CKD converted from an ESA; safety profiles were similar across groups. TRIAL REGISTRATION: EudraCT 2019-004851-36/ClinicalTrials.gov identifier: NCT04313153.
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Lead (Pb), cadmium (Cd) and arsenic (As) contamination in soils show a growing environmental concern. However, owing to the significant differences in chemical characteristics, remediating heavy metal(loid)s of Pb, Cd and As is challenging. Herein, anionic surfactant-activated electrochemical approach was proposed to realize efficient immobilization of As, Cd and Pb heavy metal(loid)s from contaminated soils. In this innovative method, calcium lignosulfonate (CL) as anionic surfactant was used to activate Cd and Pb from contaminated soils into solution, afterwards anodically generated Fe (II) ions by the electrochemical process react with Pb and Cd to form precipitates. Meanwhile, owing to the strong binding capacities of Fe (II) ions, As contaminations were remediated. Moreover, via various characterizations and cyclic voltammetric method, the reaction kinetics and phase transformation process during the electrochemical process were analyzed in detail. These findings show great potential in optimizing the design of electrochemical treatment, which will be applied in remediating multi-component heavy metal(loid) polluted soils.
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Alzheimer's disease (AD) is characterized by progressive cognitive decline and late-stage neurobehavioral issues marked by amyloid-beta plaques and Tau protein tangles. This study aims to investigate Fibulin-1(FBLN1) gene expression in the hippocampal tissue of Presenilin-1/Presenilin-2 conditional double-knockout (DKO) and double-transgenic (DTG) mice, using single-cell sequencing and experimental methods to verify abnormal methylation status and correlation with AD. Genomic DNA from DKO and DTG mice was used for genotyping. Reduced Representation Bisulfite Sequencing (RRBS) identified 10 genes with abnormal methylation changes, with protein-protein interaction (PPI) analysis highlighting five core genes, including FBLN1. Single-cell sequencing, RT-PCR, and Western blotting (WB) were used to analyze FBLN1 mRNA and protein levels in the hippocampal tissues of early-stage and mid-stage AD DKO, DTG, and CBAC57 mice. RRBS identified 10 genes with abnormal methylation, with PPI highlighting five core genes. Single-cell sequencing showed significant FBLN1 expression in AD groups. RT-PCR and WB indicated elevated FBLN1 mRNA and protein levels in mid-stage AD DKO and DTG mice compared to CBAC57 mice, with no differences in early-stage AD DKO and CBAC57 mice. RRBS revealed hypomethylation of the FBLN1 gene in mid-stage AD DKO mice. Elevated FBLN1 expression in AD models suggests an age-dependent neurodegenerative mechanism independent of amyloid-beta deposition. This study enhances our understanding of AD's epigenetic mechanisms, which will aid targeted diagnosis, treatment, and prognosis.
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Enfermedad de Alzheimer , Biología Computacional , Metilación de ADN , Modelos Animales de Enfermedad , Hipocampo , Ratones Noqueados , Presenilina-2 , Animales , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Hipocampo/metabolismo , Hipocampo/patología , Ratones , Biología Computacional/métodos , Presenilina-2/genética , Presenilina-2/metabolismo , Ratones Transgénicos , Presenilina-1/genética , Presenilina-1/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Masculino , Epigénesis GenéticaRESUMEN
OBJECTIVES: This study aimed to summarize the most effective evidence on nonpharmacological interventions for the fatigue-pain-sleep disturbance symptom cluster in lung cancer patients and to provide evidence-based management methods for clinical team and lung cancer patients. METHODS: Guided by the "6S" pyramid model, we retrieved evidence on fatigue, pain, and sleep disturbance management from relevant websites and databases, and unpublished gray literature was also searched. The time frame of the search ranged from database establishment to September 30, 2023. Two researchers independently evaluated the literature quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) for guidelines, and the Assessment of Multiple Systematic Reviews II (AMSTAR II) for systematic reviews. Two people independently extracted and summarized the evidence according to the first principle of high-quality evidence and newly published evidence. The included evidence was graded by the JBI Evidence Pre-Grading System. RESULTS: A total of 52,238 articles were retrieved, of which 60 articles, including 18 guidelines, 18 JBI best practice recommendations, one Up To Date clinical practice, and 23 systematic reviews, were included. Overall, 49 pieces of evidence from six dimensions-screening, assessment, management, education, referral, and follow-up-were summarized. Forty-three pieces of evidence were level 1, three pieces of evidence were level 4, and three pieces of evidence were level 5. CONCLUSIONS: The best 49 pieces of evidence on nonpharmacological interventions for the fatigue-pain-sleep disturbance symptom cluster in lung cancer patients were summarized in this study, and these nonpharmacological interventions are scientific and comprehensive. IMPLICATIONS FOR NURSING PRACTICE: This study can provide guidance for clinical team to improve the fatigue-pain-sleep disturbance symptom cluster management. These evidence items can be implemented by clinical team to reduce the symptom burden and improve the self-management ability of symptoms in lung cancer patients.
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BACKGROUND: Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. METHODS: In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. RESULTS: GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. CONCLUSIONS: Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income.
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Depresión , Fatiga , Neoplasias Pulmonares , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/psicología , Persona de Mediana Edad , Estudios Longitudinales , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Fatiga/epidemiología , Depresión/epidemiología , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Adulto , Dolor/tratamiento farmacológico , Análisis de Clases LatentesRESUMEN
Currently, heterosis is an effective method for achieving high crop quality and yield worldwide. Owing to the challenges of breeding and the high cost of the F1 generation, the F2 generation is considered the more desirable hybrid offspring for agricultural production. The use of OJIP fluorescence provides rapid insights into various photosynthetic mechanisms. However, OJIP fluorescence has not been previously studied as an indicator of the rate of heterosis. Consequently, we investigated the relationship between photosynthetic characteristics and growth and developmental parameters in hybrid cotton cultivars. The findings showed a gradual decline in the photosynthetic performance of hybrid cotton as the number of generations increased. In comparison to the F3 generation, both the F1 and F2 generations showed minimal variations in parameters, thus maintaining hybrid dominant and emphasizing the agricultural production potential of the F2 generation. The JIP-test revealed significant differences in the relationship between ψ Eo and Ï Eo parameters, as well as variations in the connections between the photo-response center and electron transfer efficiency, and between cotton yield and fiber quality in the hybrid progeny. These variations can serve as indicators for predicting the extent of hybrid dominance in cotton. The results indicated significant differences in the light and dark responses of the hybrid offspring. By using parents with similar photosynthetic performance as genetic resources for crossbreeding, the photosynthetic capacity of the hybrid progeny can be enhanced to facilitate the efficient absorption and conversion of light energy in crops.
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Sexually dimorphic traits such as growth and body size are often found in various crustaceans. Methyl farnesoate (MF), the main active form of sesquiterpenoid hormone in crustaceans, plays vital roles in the regulation of their molting and reproduction. However, understanding on the sex differences in their hormonal regulation is limited. Here, we carried out a comprehensive investigation on sexual dimorphic responses to MF in the hepatopancreas of the most dominant aquacultural crustacean-the white-leg shrimp (Litopenaeus vannamei). Through comparative transcriptomic analysis of the main MF target tissue (hepatopancreas) from both female and male L. vannamei, two sets of sex-specific and four sets of sex-dose-specific differentially expressed transcripts (DETs) were identified after different doses of MF injection. Functional analysis of DETs showed that the male-specific DETs were mainly related to sugar and lipid metabolism, of which multiple chitinases were significantly up-regulated. In contrast, the female-specific DETs were mainly related to miRNA processing and immune responses. Further co-expression network analysis revealed 8 sex-specific response modules and 55 key regulatory transcripts, of which several key transcripts of genes related to energy metabolism and immune responses were identified, such as arginine kinase, tropomyosin, elongation of very long chain fatty acids protein 6, thioredoxin reductase, cysteine dioxygenase, lysosomal acid lipase, estradiol 17-beta-dehydrogenase 8, and sodium/potassium-transporting ATPase subunit alpha. Altogether, our study demonstrates the sex differences in the hormonal regulatory networks of L. vannamei, providing new insights into the molecular basis of MF regulatory mechanisms and sex dimorphism in prawn aquaculture.
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Perfilación de la Expresión Génica , Hepatopáncreas , Penaeidae , Caracteres Sexuales , Transcriptoma , Animales , Hepatopáncreas/metabolismo , Hepatopáncreas/efectos de los fármacos , Femenino , Masculino , Penaeidae/genética , Penaeidae/metabolismo , Penaeidae/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Ácidos Grasos Insaturados/farmacología , Ácidos Grasos Insaturados/metabolismoRESUMEN
OBJECTIVE: To investigate the molecular characteristics of Rb/E2F in mixed adeno-neuroendocrine carcinoma (MANEC). MATERIALS AND METHODS: The clinicopathological features of MANEC were analyzed. The protein expressions of Rb, p16, and p53 were detected by the immunohistochemical method. The infection status of high-risk human papillomavirus (HR-HPV) was evaluated by in situ hybridization (ISH) and the gene chip method. RESULTS: Thirteen cases of MANEC were divided into four molecular patterns according to Rb protein expression and HPV status. Group 1: A total of eight of the 13 cases showed positive Rb protein expression and lack of HR-HPV expression (8/13, 62%). Rb protein expression with p16 protein deletion and p53 protein abnormal expression was unique to NEC. Group 2: three cases (3/13, 23%) with negative Rb protein expression and lack of HR-HPV expression. Group 3: There was one case (1/13, 8%) with positive expression of Rb protein accompanied by HR-HPV. Group 4: There was one case of Rb protein loss with an HR-HPV-positive status. CONCLUSIONS: HR-HPV and Rb/p16/p53 pathway can be associated in MANEC pathogenesis, which provides the research basis for personalized treatment of MANEC.
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Cadmium (Cd) and arsenic (As), two toxic elements to humans, are ubiquitously coexisting contaminant found in paddy fields. The accumulation of Cd and As in rice, a major food source for many people around the world, can pose a serious threat to food safety and human health. Therefore, it is crucial to be aware of these contaminants and take adequate measures to reduce the accumulation of these two elements in rice. Developing an effective method to simultaneously reduce the accumulation of Cd) and As in rice is challenging. In this study, a pot experiment was conducted to investigate the synergistic effects of selenium (Se), iron (Fe) and phosphorus (P) on the uptake, transport and accumulation of cadmium and arsenic in rice by analyzing the physical and chemical properties of the soil, the elemental concentrations and their interrelationships in the rice tissues, and the composition and morphology of the iron plaque (IP). The results showed that the combined treatments of Se, Fe and P had positive effects on reducing Cd and As accumulation in rice, reducing Cd concentrations in brown rice by 3.86-51.88 % and As concentrations by 25.37-40.81 %. The possible mechanisms for the reduction of As and Cd concentrations in rice grains were: (i) Combined application of Fe, P and Se can effectively reduce the soil available Cd and As concentration. (ii) Combined application significantly improved the formation of IP at the tillering stage and increased the crystalline iron oxides in IP, promoting the deposition of SiO2 in rice roots, thereby effectively inhibiting the uptake of Cd and As by rice roots. (iii) Interplay and interaction between elements facilitated by transporter proteins could contribute to the synergistic mitigation of Cd and As by Se, Fe and P. This study provides a valuable new approach for effective control of Cd and As concentration of rice grown in co-contaminated soil.
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Arsénico , Cadmio , Hierro , Oryza , Fósforo , Selenio , Contaminantes del Suelo , Cadmio/metabolismo , Arsénico/análisis , Contaminantes del Suelo/análisis , Fósforo/análisis , Suelo/químicaRESUMEN
Here, Fe- and Mn-modified biochar (BC-Fe-Mn) was applied to simultaneously stabilize As and Cd in the contaminated soil. The removal efficiencies for NaHCO3-extractable As and DTPA-extractable Cd by BC-Fe-Mn were 60.8% and 49.6%, respectively. The speciation analyses showed that the transformation to low-crystallinity Fe-bound (F3) As, Fe-Mn oxide-bound (OX) of Cd, and residual As and Cd was primarily attributed to stabilizing the two metal(loid)s. Moreover, the correlation analyses showed that the increase of As in F3 fraction was significantly and positively associated with the increase of OX fraction Mn (r = 0.64). Similarly, OX fraction Cd was increased notably with increasing OX fraction Fe (r = 0.91) and OX fraction Mn (r = 0.76). In addition, a novel dialysis experiment was performed to separate the reacted BC-Fe-Mn from the soil for intensively investigating the stabilization mechanisms for As and Cd by BC-Fe-Mn. The characteristic crystalline compounds of (Fe0.67Mn0.33)OOH and Fe2O3 on the surface of BC-Fe-Mn were revealed by SEM-EDS and XRD. And FTIR analyses showed that α-FeOOH, R-COOFe/Mn+, and O-H on BC-Fe-Mn potentially served as the reaction sites for As and Cd. A crystalline compound of MnAsO4 was found in the soil treated by BC-Fe-Mn in the dialysis experiment. Thus, our results are beneficial to deeper understand the mechanisms of simultaneous stabilization of As and Cd by BC-Fe-Mn in soil and support the application of the materials on a large scale.
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Arsénico , Cadmio , Carbón Orgánico , Restauración y Remediación Ambiental , Manganeso , Contaminantes del Suelo , Suelo , Carbón Orgánico/química , Contaminantes del Suelo/química , Cadmio/química , Restauración y Remediación Ambiental/métodos , Suelo/química , Manganeso/química , Arsénico/química , Hierro/químicaRESUMEN
Selenium (Se) fortification is witnessed to simultaneously inhibit absorbing Cadmium (Cd) and Arsenic (As) by rice plants, but the mechanism is unclear. Here, the effects of Se on the root morphology, iron plaque (IP) content, soil Fe2+ content, radial oxygen loss (ROL), and enzyme activities of the rice plants in the soil contaminated by Cd and As were intensively investigated through the hydroponic and soil experiments. Se effectively alleviated the toxic effects of Cd and As on the plants and the dry weight, root length, and root width were increased by 203.18%, 33.41%, and 52.81%, respectively. It also elucidated that ROL was one of the key factors to elevate IP formation by Se and the specific pathways of Se enhancing ROL were identified. ROL of the plants in the experiment group treated by Se was increased 36.76%, and correspondingly IP was magnified 50.37%, compared to the groups with Cd and As. It was owing to Se significantly increased the root porosity (62.11%), facilitating O2 transport to the roots. Additionally, Se enhanced the activities of catalase (CAT) and superoxide dismutase (SOD) to promote the catalytic degradation of ROS induced by Cd and As stress. It indirectly increased O2 release in the rhizosphere, which benefit to form more robust IP serve as stronger barrier to Cd and As. The results of our study provide a novel molecular level insight for Se promoting root IP to block Cd and As uptake by the rice plants.
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Arsénico , Cadmio , Hierro , Oryza , Raíces de Plantas , Selenio , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/metabolismo , Oryza/metabolismo , Oryza/efectos de los fármacos , Arsénico/metabolismo , Arsénico/toxicidad , Selenio/farmacología , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Hierro/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Suelo/química , Catalasa/metabolismo , Rizosfera , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.
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Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.
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Anticuerpos Antivirales , Formación de Anticuerpos , Linfocitos B , Vacunas contra la COVID-19 , COVID-19 , Centro Germinal , Inmunización Secundaria , SARS-CoV-2 , Células T Auxiliares Foliculares , Animales , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Linfocitos B/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Ratones , COVID-19/inmunología , COVID-19/prevención & control , Células T Auxiliares Foliculares/inmunología , Centro Germinal/inmunología , Formación de Anticuerpos/inmunología , Femenino , Hipermutación Somática de Inmunoglobulina , Vacunación , Ratones Endogámicos BALB C , Humanos , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
Drugs often target specific metabolic pathways to produce a therapeutic effect. However, these pathways are complex and interconnected, making it challenging to predict a drug's potential effects on an organism's overall metabolism. The mapping of drugs with targeting metabolic pathways in the organisms can provide a more complete understanding of the metabolic effects of a drug and help to identify potential drug-drug interactions. In this study, we proposed a machine learning hybrid model Graph Transformer Integrated Encoder (GTIE-RT) for mapping drugs to target metabolic pathways in human. The proposed model is a composite of a Graph Convolution Network (GCN) and transformer encoder for graph embedding and attention mechanism. The output of the transformer encoder is then fed into the Extremely Randomized Trees Classifier to predict target metabolic pathways. The evaluation of the GTIE-RT on drugs dataset demonstrates excellent performance metrics, including accuracy (>95%), recall (>92%), precision (>93%) and F1-score (>92%). Compared to other variants and machine learning methods, GTIE-RT consistently shows more reliable results.
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Biología Computacional , Aprendizaje Automático , Redes y Vías Metabólicas , Humanos , Biología Computacional/métodos , Preparaciones Farmacéuticas/metabolismo , Algoritmos , Modelos Biológicos , Redes Neurales de la Computación , Interacciones FarmacológicasRESUMEN
Nature experience is a relatively easy and beneficial measure for improving emotions. Individuals experience nature through proximal senses (tactile, gustatory, and olfactory) and distal senses (vision and audition). This study examined the relationships between diverse natural senses experience and individuals' positive and negative emotions, along with the mediating role of nature connectedness. We recruited 978 college students (Mage = 20.09 ± 1.09 years old) from Beijing, China. The results showed that tactile experience (e.g. touching trees and water) was negatively related to negative emotions, while gustatory experience (e.g. tasting fresh fruits) was positively correlated with positive emotions. Furthermore, nature connectedness mediated the relationship between other natural sensory experiences and positive and negative emotions, except for the insignificant mediation between olfactory experiences and negative emotions. Therefore, individuals should emphasize the role of the proximal senses (especially tactile and gustatory experiences) during nature experiences and increase nature connectedness to maintain positive emotions.
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The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.