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BACKGROUND: Heart failure (HF), especially HF with reduced ejection fraction (HFrEF), presents complex challenges, particularly in the aging population where it often coexists with type 2 diabetes mellitus (T2DM). AIM: To analyze the effect of dapagliflozin treatment on cardiac, renal function, and safety in patients with HFrEF combined with T2DM. METHODS: Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study. The propensity score matching method was used, and a total of 102 eligible samples were scaled. The clinical efficacy of the two groups was evaluated at the end of the treatment, comparing the results of blood glucose, insulin, cardiac function, markers of myocardial injury, renal function indexes, and 6-min walk test (6MWT) before and after the treatment. We compared the occurrence of adverse effects on the treatment process of the two groups of patients. The incidence of adverse outcomes in patients within six months of treatment was counted. RESULTS: The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group (P = 0.013). After treatment, the pancreatic beta-cell function index, left ventricular ejection fraction, and glomerular filtration rate of patients in the study group were significantly higher than control group (P < 0.001), while their fasting plasma glucose, 2-h postprandial glucose, glycosylated hemoglobin, insulin resistance index, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, cardiac troponin I, creatine kinase-MB, N-terminal pro b-type natriuretic peptide, serum creatinine, and blood urea nitrogen were significantly lower than those of the control group. After treatment, patients in the study group had a significantly higher 6MWT than those in the control group (P < 0.001). Hypoglycemic reaction (P = 0.647), urinary tract infection (P = 0.558), gastrointestinal adverse effect (P = 0.307), respiratory disturbance (P = 0.558), and angioedema (P = 0.647) were not statistically different. There was no significant difference between the incidence of adverse outcomes between the two groups (P = 0.250). CONCLUSION: Dapagliflozin significantly enhances clinical efficacy, cardiac and renal function, and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.
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Electric power generation safety incidents can lead to severe consequences, including casualties and widespread power outages. Previous research has mainly focused on the mechanisms and causal relationships of accidents. However, these incidents result from multiple factors working together, lacking systematic analysis. This study examines 161 electric power generation safety incidents from 2015 to 2022, utilizing Grounded Theory for coding to construct a causal model. The derived model is used as a conditional variable for fuzzy set qualitative comparative analysis (fsQCA), with accident severity as the outcome variable. Forty-five cases are selected for assigning values, and R language and fsQCA software are integrated for univariate necessary condition analysis, followed by configurational analysis. Results show the Grounded Theory-derived causal model includes six factors: human unsafe behavior, equipment factors, enterprise safety management, on-site safety management, safety qualifications of personnel, and environmental factors. Necessary condition analysis indicates incidents result from multiple conditions. Configurational analysis identifies seven paths condensed into three types: management deficiency, low safety qualifications, and unsafe behavior. Recommendations are proposed for each type, discussing intrinsic connections between variables based on conditional variables in configurational paths. The aim is to reduce electric power generation safety incidents, ensure personnel safety, and guarantee continuous electricity supply.
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T cells play an important role in adaptive immunity. Mature T cells specifically recognize antigens on major histocompatibility complex molecules through T-cell receptors (TCRs). As the TCR repertoire is highly diverse, its analysis is vital in the assessment of T cells. Advances in sequencing technology have provided convenient methods for further investigation of the TCR repertoire. In the present review, the TCR structure and the mechanisms by which TCRs function in tumor recognition are described. In addition, the potential value of the TCR repertoire in tumor diagnosis is reviewed. Furthermore, the role of the TCR repertoire in tumor immunotherapy is introduced, and the relationships between the TCR repertoire and the effects of different tumor immunotherapies are discussed. Based on the reviewed literature, it may be concluded that the TCR repertoire has the potential to serve as a biomarker for tumor prognosis. However, a wider range of cancer types and more diverse subjects require evaluation in future research to establish the TCR repertoire as a biomarker of tumor immunity.
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Ferroptosis is a regulated cell death marked by iron-dependent lipid peroxidation. Tumor cells that survive by evading chemotherapy-induced apoptosis are vulnerable to ferroptosis. Therefore, it is particularly urgent to explore active ingredients that can selectively induce ferroptosis in cancer cells. Here, we revealed that sanggenol L, the active agent of Morus Bark, predisposed non-small cell lung cancer (NSCLC) cells to ferroptosis, evidenced by reactive oxygen species (ROS) accumulation, glutathione depletion, mitochondrial shrinkage, and lipid peroxidation. Furthermore, the ferroptosis-related miRNA array showed that sanggenol L treatment upregulated the level of miR-26a-1-3p, which directly targeted the E3 ubiquitin ligase MDM2. In addition, silencing MDM2 by miR-26a-1-3p resulted in a notable increase in p53 protein levels and decrease of its downstream target SLC7A11, ultimately triggered ferroptosis. The subcutaneous xenograft model and patient-derived tumor xenograft (PDX) model of NSCLC further confirmed the anti-tumor efficacy and safety of sanggenol L in vivo. Collectively, our data suggest that miR-26a-1-3p/MDM2/p53/SLC7A11 signaling axis plays a key role in sanggenol L-induced ferroptosis, which implies that sanggenol L can serves as an anticancer therapeutic arsenal for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Camundongos Nus , MicroRNAs , Proteínas Proto-Oncogênicas c-mdm2 , Transdução de Sinais , Proteína Supressora de Tumor p53 , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Animais , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Masculino , FemininoRESUMO
Gelatin (GEL), pectin (PEC), carboxymethyl cellulose (CMC), and whey protein isolate (WPI) were employed to formulate hydrogels for stabilizing N-Acetylneuraminic Acid (NeuAc). GEL/WPI-NeuAc hydrogels, irrespective of the ratio, exhibited a flexible and smooth surface with a continuous three-dimensional network structure internally. Porosity of the three types of hydrogels increased from 3.69% to 86.92% (GEL/WPI), 41.67% (PEC/WPI), and 87.62% (CMC/WPI), rendering them suitable as carriers for NeuAc encapsulation. The dynamic swelling behavior of all hydrogels followed Schott's second-order kinetics model. The degradation performance of GEL, PEC, and CMC/WPI-NeuAc hydrogels was optimal at a 5: 5 ratio, with degradation rates of 80.39 ± 1.26%, 82.38 ± 1.96%, and 81.39 ± 1.57%, respectively. GEL, PEC, CMC/WPI-NeuAc hydrogels demonstrated decreased release rates of 44.56%, 31.04%, and 41.26%, respectively, compared to free NeuAc, post gastric digestion. The present investigation suggests the potential of GEL/WPI hydrogels as effective carriers for delivering NeuAc encapsulation.
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Preparações de Ação Retardada , Gelatina , Hidrogéis , Ácido N-Acetilneuramínico , Proteínas do Soro do Leite , Hidrogéis/química , Gelatina/química , Proteínas do Soro do Leite/química , Ácido N-Acetilneuramínico/química , Preparações de Ação Retardada/química , Cinética , Portadores de Fármacos/químicaRESUMO
BACKGROUND: Both copy number variant-sequencing (CNV-seq) and karyotype analysis have been used as powerful tools in the genetic aetiology of fetuses with congenital heart diseases (CHD). However, CNV-seq brings clinicians more confusions to interpret the detection results related to CHD with or without extracardiac abnormalities. Hence, we conducted this study to investigate the clinical value of CNV-seq in fetuses with CHD. RESULTS: A total of 167 patients with fetal CHD including 36 single CHD (sCHD), 41 compound CHD (cCHD) and 90 non-isolated CHD (niCHD) were recruited into the study. 28 cases (16.77%, 28/167) were revealed with chromosomal abnormalities at the level of karyotype. The pathogenic detection rate (DR) of CNV-seq (23.17%, 19/82) was higher than that of karyotyping (15.85%, 13/82) in 82 cases by CNV-seq and karyotyping simultaneously. The DR of pathogenic copy number variations (PCNVs) (31.43%) was higher in niCHD subgroup than that in sCHD and cCHD (9.52% and 23.08%). Conotruncal defect (CTD) was one of the most common heart malformations with the highest DR of PCNVs (50%) in 7 categories of CHD. In terms of all the pregnancy outcomes, 67 (40.12%) cases were terminated and 100 (59.88%) cases were live neonates. Only two among 34 cases with a pathogenic genetic result chose to continue the pregnancy. CONCLUSIONS: CNV-seq combined with karyotyping is a reliable and accurate prenatal technique for identifying pathogenic chromosomal abnormalities associated with fetal CHD with or without extracardiac abnormalities, which can assist clinicians to perform detailed genetic counselling with regard to the etiology and related outcomes of CHD.
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OBJECTIVE: Kleefstra syndrome (KS), formerly known as 9q subtelomeric deletion syndrome, is characterized by multiple structural abnormalities. However, most fetuses do not have obvious abnormal phenotypes. In this study, the fetus with KS presented with multiple system structural anomalies, and we aimed to explore the genotype-phenotype correlations of KS fetuses. CASE REPORT: Multiple systematic structural anomalies, including severe intrauterine growth restriction (IUGR) and cardiac defects, were detected by ultrasound in the fetus at 33 + 5 weeks' gestation. These abnormalities may be caused by the pathogenic deleted fragment at 9q34.3, including the euchromatic histone methyltransferase 1 (EHMT1) and collagen type V alpha 1 chain (COL5A1) genes, detected by copy number variation sequencing (CNV-seq). CONCLUSIONS: It is essential for clinicians to perform CNV-seq combined with multidisciplinary consultation for suspected KS fetuses, especially those with multiple systematic structural anomalies.
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Anormalidades Múltiplas , Anormalidades Craniofaciais , Cardiopatias Congênitas , Deficiência Intelectual , Humanos , Variações do Número de Cópias de DNA , Cardiopatias Congênitas/genética , Deleção Cromossômica , Deficiência Intelectual/genética , Anormalidades Múltiplas/genética , Feto/patologia , Estudos de Associação Genética , Cromossomos Humanos Par 9/genéticaRESUMO
In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.
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Sistema y+ de Transporte de Aminoácidos , Ferroptose , Metaplasia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Espécies Reativas de Oxigênio , Regeneração , Estômago , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Ferroptose/fisiologia , Estômago/patologia , Regeneração/fisiologia , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Metaplasia/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Mucosa Gástrica/metabolismo , Camundongos Endogâmicos C57BL , Celulas Principais Gástricas/metabolismo , Células Acinares/metabolismo , Camundongos Knockout , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
Background: Substantial evidence suggests an association between psychiatric disorders and chronic heart failure. However, further investigation is needed to confirm the causal relationship between these psychiatric disorders and chronic heart failure. To address this, we evaluated the potential effects of five psychiatric disorders on chronic heart failure using two-sample Mendelian Randomization (MR). Methods: We selected single nucleotide polymorphisms (SNPs) associated with chronic heart failure and five psychiatric disorders (Attention-Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Major Depression, Bipolar Disorder and Schizophrenia (SCZ)). Univariable (UVMR) and multivariable two-sample Mendelian Randomization (MVMR) were employed to assess causality between these conditions. Ever smoked and alcohol consumption were controlled for mediating effects in the multivariable MR. The inverse variance weighting (IVW) and Wald ratio estimator methods served as the primary analytical methods for estimating potential causal effects. MR-Egger and weighted median analyses were also conducted to validate the results. Sensitivity analyses included the funnel plot, leave-one-out, and MR-Egger intercept tests. Additionally, potential mediators were investigated through risk factor analyses. Results: Genetically predicted heart failure was significantly associated with ADHD (odds ratio (OR), 1.12; 95% CI, 1.04-1.20; p = 0.001), ASD (OR, 1.29; 95% CI, 1.07-1.56; p = 0.008), bipolar disorder (OR, 0.89; 95% CI, 0.83-0.96; p = 0.001), major depression (OR, 1.15; 95% CI, 1.03-1.29; p = 0.015), SCZ (OR, 1.04; 95% CI, 1.00-1.07; p = 0.024). Several risk factors for heart failure are implicated in the above cause-and-effect relationship, including ever smoked and alcohol consumption. Conclusion: Our study demonstrated ADHD, ASD, SCZ and major depression may have a causal relationship with an increased risk of heart failure. In contrast, bipolar disorder was associated with a reduced risk of heart failure, which could potentially be mediated by ever smoked and alcohol consumption. Therefore, prevention strategies for heart failure should also incorporate mental health considerations, and vice versa.
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Transtorno do Espectro Autista , Insuficiência Cardíaca , Transtornos Mentais , Humanos , Análise da Randomização Mendeliana , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Saúde Mental , Doença Crônica , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genéticaRESUMO
In recent years, the total nitrogen concentration in Taihu Lake has decreased significantly. Denitrification, as the main nitrogen removal process, is the key reason for the decrease. Here, the denitrification parameter values in the Environmental Fluid Dynamic Code (EFDC) model were calculated based on isotope-labeled denitrification experiment instead of selecting the recommended values directly. This study further focused on EFDC denitrification parameter derivation with an experimental denitrification rate (Dtot) to reduce simulation errors. According to the EFDC nitrate deposition flux mechanism, the conversion equation between the denitrification rate of the first sediment layer ([Formula: see text]) in EFDC and Dtot was successfully derived. The results revealed a linear correlation between [Formula: see text] and (Dtot)1/2. The [Formula: see text] values of sampling points ranged from 0.25 to 0.27 m·day-1, within the range of model parameters. After substituting [Formula: see text] into the Taihu Lake EFDC model, the average percentage bias and determination coefficient of total nitrogen were 16.25% and 0.87, respectively. The average total nitrogen concentration reduction caused by denitrification at water quality calibration points ranged from 0.027 to 0.305 mg·L-1.
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Desnitrificação , Lagos , Nitrogênio/análise , Qualidade da Água , Isótopos , ChinaRESUMO
Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.
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Gastrite Atrófica , Lesões Pré-Cancerosas , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/genética , Lesões Pré-Cancerosas/patologia , Biomarcadores , Metaplasia , Mucosa Gástrica/patologiaRESUMO
Background: The diagnosis of benign and malignant solitary pulmonary nodules based on personal experience has several limitations. Therefore, this study aims to establish a nomogram for the diagnosis of benign and malignant solitary pulmonary nodules using clinical information and computed tomography (CT) results. Methods: Retrospectively, we collected clinical and CT characteristics of 1,160 patients with pulmonary nodules in Guang'an People's Hospital and the hospital affiliated with North Sichuan Medical College between 2019 and 2021. Among these patients, data from 773 patients with pulmonary nodules were used as the training set. We used the least absolute shrinkage and selection operator (LASSO) to optimize clinical and imaging features and performed a multivariate logistic regression to identify features with independent predictive ability to develop the nomogram model. The area under the receiver operating characteristic curve (AUC), C-index, decision curve analysis, and calibration plot were used to evaluate the performance of the nomogram model in terms of predictive ability, discrimination, calibration, and clinical utility. Finally, data from 387 patients with pulmonary nodules were utilized for validation. Results: In the training set, the predictors for the nomogram were gender, density of the nodule, nodule diameter, lobulation, calcification, vacuole, vascular convergence, bronchiole, and pleural traction, selected through LASSO and logistic regression analysis. The resulting model had a C-index of 0.842 (95% CI [0.812-0.872]) and AUCs of 0.842 (95% CI [0.812-0.872]). In the validation set, the C-index was 0.856 (95% CI [0.811-0.901]), and the AUCs were 0.844 (95% CI [0.797-0.891]). Results from the calibration curve and clinical decision curve analyses indicate that the nomogram has a high fit and clinical benefit in both the training and validation sets. Conclusion: The establishment of a nomogram for predicting the benign or malignant diagnosis of solitary pulmonary nodules by this study has shown good efficacy. Such a nomogram may help to guide the diagnosis, follow-up, and treatment of patients.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico , Estudos Retrospectivos , Nomogramas , Nódulo Pulmonar Solitário/diagnóstico , Pulmão/patologia , Nódulos Pulmonares Múltiplos/diagnósticoRESUMO
BACKGROUND: Ankyrin repeat domain 49 (ANKRD49) has been found to be highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. METHODS: Real-time qPCR was employed to test ANKRD49 expression levels in nine pairs of fresh NSCLC tissues and the corresponding adjacent normal tissues. The function of ANKRD49 was investigated using overexpression and RNA interference assays in lung adenocarcinoma cell line (NCI-H1299) and lung squamous carcinoma cell line (NCI-H1703) through gelatin zymography, cell counting kit-8, colony formation, wound healing, migration and invasion assays mmunoprecipitation was performed to in vitro. Immunoprecipitation was performed to test the interaction of c-Jun and ATF2. Chromatin immunoprecipitation was conducted to assess the transcriptional regulation of ATF2/c-Jun on MMP-2/9. Moreover, the tumorigenicity of ANKRD49 was evaluated in nude mice models and the involved signal molecular was also measured by immunohistochemical method. RESULTS: We found that the levels of ANKRD49 in cancerous tissues were higher than those in adjacent normal tissues. in vitro assay showed that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9. In vivo assay showed that ANKRD49 promoted lung metastasis of injected-NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. CONCLUSION: The present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9. The molecular mechanisms of ANKRD49's function is different from those found in A549 cells. The current study is a supplement and improvement to the previous research.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Animais , Camundongos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Nus , Proliferação de Células/genética , Linhagem Celular Tumoral , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologiaRESUMO
Long-term application of nitrogen (N) fertilizer adversely degrades soil and decreases crop yield. Biochar amendment with N fertilizer not only can increase yield but also can improve the soil. A 3-year field experiment was conducted to determine the effect of biochar doses with N fertilizer on maize yield and soil N and water dynamics under border irrigation (BI) and drip irrigation (DI) methods. Treatments were 260 kg N ha-1 without biochar addition and combined with low, medium, and high doses of biochar, namely, 15.5 t ha-1, 30.7 t ha-1, and 45.3 t ha-1 (NB0, NB1, NB2, and NB3), respectively. The biochar doses and irrigation methods significantly (p < 0.05) increased maize growth and yield characteristics, irrigation water use efficiency (IWUE), and fertilizer N use efficiency (FNUE) and enhanced the soil properties. In the BI and DI method, the NB1, NB2, and NB3 treatments increased yield by 4.96%-6.10%, 8.36%-9.85%, and 9.65%-11.41%, respectively, compared to NB0. In terms of IWUE and FNUE, the non-biochar treatment had lower IWUE and FNUE compared to biochar combined with N fertilizer treatments under both BI and DI methods. In the BI method, the IWUE in NB2 and NB3 ranged from 3.36 to 3.43 kg kg-1, and in DI, it was maximum, ranging from 5.70 to 5.94 kg kg-1. Similarly, these medium and high doses of biochar increased the FNUE of maize. The FNUEs in NB2 and NB3 under BI ranged from 38.72 to 38.95 kg kg-1 and from 38.89 to 39.58 kg kg-1, while FNUEs of these same treatments under DI ranged from 48.26 to 49.58 kg kg-1 and from 48.92 to 50.28 kg kg-1. The effect of biochar was more obvious in DI as compared to the BI method because soil water content (SWC) and soil N concentrations (SNCs) were higher at rhizosphere soil layers under DI. Biochar improved SWC and SNC at 0-20 cm and 20-40 cm soil layers and decreased below 60-cm soil layers. In contrast, despite biochar-controlled SWC and SNCs, still, values of these parameters were higher in deeper soil layers. In the BI method, the SNCs were higher at 60-80 cm and 80-100 cm compared to the top and middle soil layers. Depth-wise results of SNC demonstrated that the biochar's ability to store SNC was further enhanced in the DI method. Moreover, biochar increased soil organic matter (OM) and soil aggregate stability and maintained pH. The NB0 treatment increased soil OM by 11.11%-14.60%, NB2 by 14.29%-19.42%, and NB3 by 21.98%-23.78% in both irrigation methods. This increased OM resulted in improved average soil aggregates stability by 2.45%-11.71% and 4.52%-14.66% in the BI and DI method, respectively. The results of our study revealed that combined application of N fertilizer with a medium dose of biochar under the DI method would be the best management practice, which will significantly increase crop yield, improve SWC, enrich SNC and OM, improve soil structure, and maintain pH.
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The present study aimed to investigate the role and mechanism of action of ribonucleotide reductase M2 (RRM2) in lung adenocarcinoma and its potential as a therapeutic target. Data of patients with lung adenocarcinoma from The Cancer Genome Atlas database were collected and analyzed to evaluate the potential of RRM2 as a biomarker. The expression of RRM2 was evaluated in the A549 cell line and its cisplatin-resistant A549/DDP cell line derivative by western blot and reverse transcription-quantitative PCR. The study also investigated cell proliferation and the mechanism by which RRM2 controls cellular cisplatin resistance using CCK-8 and colony-formation assays. In addition, cell migration was assessed using Transwell assays, and the cell cycle and apoptosis were examined using flow cytometry. RRM2 was highly expressed in lung adenocarcinoma and was associated with the clinical TMN stage. Functional enrichment analysis showed that RRM2 was enriched in the cell cycle. Immune cell infiltration analysis identified 12 types of immune cell that exhibited differences between patients expressing different levels of RRM2. Cellular assays revealed higher levels of RRM2 expression in A549/DDP cells than A549 cells, and its expression was induced by cisplatin. RRM2 knockdown decreased cell proliferation and migration, accelerated apoptosis and caused cell cycle arrest in the S-phase, increasing the sensitivity of A549 and A549/DDP cells to cisplatin through the Wnt/ß-catenin signaling pathway. Overexpression of ß-catenin reduced the effects of RRM2 knockdown on A549 cells. Lung adenocarcinoma growth may be influenced by RRM2 through the Wnt/ß-catenin signaling pathway, suggesting a potential pathway for cancer progression.
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Growing research has demonstrated that exposure to fine particulate matter (PM2.5) was associated with decreased pulmonary function and obvious inflammatory response. However, few pieces of research focus on the effects of PM2.5-bound metals on people with asthma. Here, we assessed whether PM2.5 and PM2.5-bound metals exposure could worsen pulmonary function in asthmatic patients and further elucidate the possible mechanisms. Thirty-four asthmatic patients were recruited to follow up for one year with eight visits in 2019-2020 in Taiyuan City, China. The index of pulmonary function was detected and blood and nasal epithelial lining fluid (ELF) samples were acquired for biomarkers measurement at each follow-up. Linear mixed-effect (LME) models were used to evaluate the relations between PM2.5, PM2.5-bound metals, and blood metals with lung function and biomarkers of Th17/Treg balance. The individual PM2.5 exposure concentration varied from 37 µg/m3 to 194 µg/m3 (mean: 59.63 µg/m3) in the present study. An interquartile range (IQR) increment of PM2.5 total mass was associated with a faster decline in maximal mid-expiratory flow (MMEF) and higher interleukin-23 (IL-23). PM2.5-bound metals [e.g. copper (Cu), nickel (Ni), manganese (Mn), titanium (Ti), and zinc (Zn)] were significantly associated with IL-23 (Cu: 5.1126%, 95% CI: 9.3708, 0.8544; Mn: 14.7212%, 95% CI: 27.926, 1.5164; Ni: 1.0269%, 95% CI: 2.0273, 0.0264; Ti: 16.7536%, 95% CI: 31.6203, 1.8869; Zn: 24.5806%, 95% CI: 46.609, 2.5522). Meanwhile, blood lead (Pb) and Cu were associated with significant declines of 0.382-3.895% in MMEF and maximum ventilatory volume (MVV). Blood Pb was associated with descending transforming growth factor ß (TGF-ß). In conclusion, exposure to PM2.5-bound metals and blood metals is a risk factor for decreased pulmonary function, especially in small airways. These alterations might be partially attributed to the imbalance of Th17/Treg.
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Asma , Chumbo , Humanos , Adulto , Linfócitos T Reguladores , Zinco , Manganês , Níquel , Titânio , Interleucina-23 , PulmãoRESUMO
For 17 consecutive years, the outbreak of Ulva prolifera in the South Yellow Sea area of China has caused significant negative impacts on coastal ecological environment. However, its specific influence on fish immunity is rare. In this study, the juvenile Paralichthys olivaceus was exposed to fresh U. prolifera algae (FU) and decomposing algal effluent (DU). After short-term stress for 14 days, the histopathological and transcriptome analysis were performed to study the effect of U. prolifera decay on P. olivaceus. Histopathological analysis found that the liver, spleen and head kidneys of P. olivaceus were damaged after the short-term stress. The transcriptome results showed that the steroid biosynthesis signaling pathway and the PI3K-Akt signaling pathway were significantly enriched. Some immune related genes, including c1qc-like, dusp1, dusp16, HSP90 and metabolic related genes serotransferrin, were differentially expressed. These results highlighted the harmfulness of U. prolifera on marine fish, setting a solid foundation for further analyses.
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Linguado , Ulva , Animais , Transcriptoma , Fosfatidilinositol 3-Quinases , Perfilação da Expressão Gênica , ChinaRESUMO
BACKGROUND: Atherosclerosis is now the main cause of cardiac-cerebral vascular diseases around the world. Disturbances in lipid metabolism have an essential role in the development and progression of atherosclerosis. Thus, we aimed to investigate lipid metabolism-related molecular clusters and develop a diagnostic model for atherosclerosis. METHODS: First, we used the GSE100927 and GSE43292 datasets to screen differentially expressed lipid metabolism-related genes (LMRGs). Subsequent enrichment analysis of these key genes was performed using the Metascape database. Using 101 atherosclerosis samples, we investigated the LMRG-based molecular clusters and the corresponding immune cell infiltration. After that, a diagnostic model for atherosclerosis was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a series of bioinformatics techniques, including CIBERSORT, gene set variation analysis, and single-cell data analysis, were used to analyze the potential mechanisms of the model genes in atherosclerosis. RESULTS: A total of 29 LMRGs were found to be differentially expressed between atherosclerosis and normal samples. Functional and DisGeNET enrichment analyses indicated that 29 LMRGs are primarily engaged in cholesterol and lipid metabolism, the PPAR signaling pathway, and regulation of the inflammatory response and are also closely associated with atherosclerotic lesions. Two LMRG-related molecular clusters with significant biological functional differences are defined in atherosclerosis. A three-gene diagnostic model containing ADCY7, SCD, and CD36 was subsequently constructed. Receiver operating characteristic curves, decision curves, and an external validation dataset showed that our model exhibits good predictive performance. In addition, three model genes were found to be closely associated with immune cell infiltration, especially macrophage infiltration. CONCLUSIONS: Our study comprehensively highlighted the intricate association between lipid metabolism and atherosclerosis and created a three-gene model for future clinical diagnosis.
Assuntos
Aterosclerose , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/genética , Aterosclerose/diagnóstico , Aterosclerose/genética , Biomarcadores , Antígenos CD36/genética , Biologia ComputacionalRESUMO
BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine cancer with a high risk of early mortality (i.e., survival time less than 1 month). This study aimed to identify relevant risk factors and predict early mortality in SCLC patients. METHODS: A total of 27,163 SCLC cases registered between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) data. Significant independent risk factors were identified by univariate and multivariate logistic regression analyses. Nomograms for all-causes and cancer-specific early death were constructed and evaluated. RESULTS: Age, sex, clinical stage, presence of metastasis (liver and lung), and absence of treatment (surgery, radiotherapy and chemotherapy) were identified for significant association with all-causes and cancer-specific early death. Nomograms based on these predictors exhibited high accuracy (area under ROC curve > 0.850) and potential clinical practicality in the prediction of early mortality. CONCLUSION: We identified a set of factors associated with early mortality from SCLC and developed a clinically useful nomogram to predict high-risk patients. This nomogram could aid oncologists in the administration of individualized treatment regimens, potentially improving clinical outcomes of SCLC patients.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/terapia , Estudos Retrospectivos , Fatores de Risco , Bases de Dados Factuais , Nomogramas , Neoplasias Pulmonares/terapia , Programa de SEER , PrognósticoRESUMO
Around the world, cancer-related death is primarily caused by lung cancer all the time. MiR-654-3p plays an outstanding role in the development of cancer, but the mechanism of miR-654-3p in non-small cell lung cancer (NSCLC) is uncertain. For this purpose, a quantitative real-time polymerase chain reaction(qRT-PCR) was carried out to detect the expression of miR-654-3p and SRC mRNA. Western blot was used to estimate the level of SRC protein. The mimics enhanced miR-654-3p, while inhibitors knocked it down. Functional experiments were performed to evaluate the proliferation and migration capacities of cells. Flow cytometry assay was utilized to measure apoptosis rates and cell cycles of cells. TargetScan bioinformatics database was queried to identify the probable target gene for miR-654-3p. Dual-fluorescence assay was implemented to verify whether miR-654-3p targets SRC. Subcutaneous tumorigenesis was used to estimate the function of miR-654-3p in vivo. Results showed that low expression of miR-654-3p was found in NSCLC tissues and cells. Up-regulated miR-654-3p suppressed cell proliferation and migration, promoted apoptosis, and blocked cells in the G1 phase, while down-regulated miR-654-3p created the opposite results. Dual-fluorescence assay confirmed that miR-654-3p was directly bound to SRC. Compared with the control group, the effects of miR-654-3p were neutralized in the group, which was co-transfected with miR-654-3p mimics and SRC over-expression plasmids. In vivo, the tumor volume in the LV-miR-654-3p group was smaller than that in the control group. It was concluded that miR-654-3p acts in an anti-cancer role and suppresses tumor progression via regulating SRC, which lays a theoretical foundation for targeted therapy of NSCLC. MiR-654-3p is expected to be a new miRNA-based therapeutic target.