RESUMO
Zhari Namco is situated in the alpine grassland belt of northwestern Xizang with a fragile ecological environment. As the third-largest lake in Xizang, there has been a long-term lack of research data concerning its basin water environment. In an effort to elucidate the surface water environment characteristics of the basin and the factors influencing them, an extensive investigation was conducted from August 2021 to June 2022, encompassing periods of high flow, low flow, and base flow. Further, the study also involved comprehensive assessments of the water chemistry characteristics and spatial-temporal variation in lake sampling sites of the basin that were not significant by using mathematical statistics, hydrochemical analysis, correlation analysis, and principal component analysis. The findings revealed the followingï¼ â The water in the Zhari Namco Basin exhibited an alkaline nature, with dominant ionic compositions in the lake comprising Na+, SO42-, and Cl-, whereas the rivers were primarily characterized by Ca2+, HCO3-, and SO42-. â¡ The main pollutants exceeding established standards included sulfates, arsenic, chlorides, and total phosphorus. The study identified significant spatiotemporal variations in water quality. Temporally, the exceedance of sulfates, arsenic, and total phosphorus was most pronounced during high-flow periods, followed by that during low-flow and base flow periods, with chloride levels showing less temporal variation. Spatially, river water quality surpassed that of the lakes, with arsenic, total phosphorus, TDS, sulfate, chloride, K+, and Na+ concentrations in lakes 1 to 2 orders of magnitude higher than those in rivers. Water qualities exceeding the established standard were primarily found in the lake, with less spatial variations within the lake itself. ⢠Hydrochemical processes within the basin were found to be primarily influenced by natural phenomena, including evaporation-concentration and rock weathering. Various elements entered the lakes via surface runoff, where they continuously accumulated under the influence of evaporation-concentration processes, ultimately leading to exceedances. ⣠Temporal variations in water quality were primarily attributed to increased elemental loss and intensified evaporation during high-flow periods. The spatial discrepancies in water quality were predominantly a consequence of the differing hydrodynamic conditions between flowing water bodies and enclosed water bodies.
RESUMO
This study utilized Mendelian randomization (MR) analysis and genome-wide association study (GWAS) data to investigate the association between commonly prescribed drugs and bladder cancer (BLCA) risk. Our results revealed that HMG CoA reductase (HMGCR) inhibitors, specifically simvastatin, are significantly associated with reduced BLCA risk. We further showed that simvastatin could significantly inhibit BLCA proliferation and epithelial-mesenchymal transition in animal models, with transcriptomic data identifying several pathways associated with these processes. Higher expression of HMGCR were linked with BLCA development and progression, and certain blood lipids, such as lipoprotein particles and very low density lipoprotein (VLDL) cholesterol, might influence BLCA risk. These findings suggested that HMGCR inhibitors, particularly simvastatin, could be potential treatment options or adjuvant therapies for BLCA.
Assuntos
Estudo de Associação Genômica Ampla , Inibidores de Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Sinvastatina , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Animais , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Humanos , Sinvastatina/efeitos adversos , Transcriptoma/genética , Hidroximetilglutaril-CoA Redutases/genética , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Polimorfismo de Nucleotídeo Único/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , CamundongosRESUMO
G0 arrest (G0A) is widely recognized as a crucial factor contributing to tumor relapse. The role of genes related to G0A in lung adenocarcinoma (LUAD) was unclear. This study aimed to develop a gene signature based on for LUAD patients and investigate its relationship with prognosis, tumor immune microenvironment, and therapeutic response in LUAD. We use the TCGA-LUAD database as the discovery cohort, focusing specifically on genes associated with the G0A pathway. We used various statistical methods, including Cox and lasso regression, to develop the model. We validated the model using bulk transcriptome and single-cell transcriptome datasets (GSE50081, GSE72094, GSE127465, GSE131907 and EMTAB6149). We used GSEA enrichment and the CIBERSORT algorithm to gain insight into the annotation of the signaling pathway and the characterization of the tumor microenvironment. We evaluated the response to immunotherapy, chemotherapy, and targeted therapy in these patients. The expression of six genes was validated in cell lines by quantitative real-time PCR (qRT-PCR). Our study successfully established a six-gene signature (CHCHD4, DUT, LARP1, PTTG1IP, RBM14, and WBP11) that demonstrated significant predictive power for overall survival in patients with LUAD. It demonstrated independent prognostic value in LUAD. To enhance clinical applicability, we developed a nomogram based on this gene signature, which showed high reliability in predicting patient outcomes. Furthermore, we observed a significant association between G0A-related risk and tumor microenvironment as well as drug susceptibility, highlighting the potential of the gene signature to guide personalized treatment strategies. The expression of six genes were significantly upregulated in the LUAD cell lines. This signature holds the potential to contribute to improved prognostic prediction and new personalized therapies specifically for LUAD patients.
Assuntos
Adenocarcinoma de Pulmão , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Microambiente Tumoral/genética , Masculino , Feminino , Transcriptoma , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Pessoa de Meia-IdadeRESUMO
The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis.While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco = N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the DFT calculations revealed the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based hybrid materials.
RESUMO
Radionuclide diffusion will be influenced by numerous factors. Establishing a model that can elucidate the internal correlation between mesoscopic diffusion and the microscopic structure of bentonite can enhance the comprehension of radionuclide diffusion mechanisms. In this study, a light gradient boosting machine (LightGBM) was employed to predict the effective diffusion coefficients of HCrO4-, I-, and CoEDTA2- in bentonite. The model's hyperparameters were optimized using the particle swarm optimization (PSO) algorithm. Several correlated physical quantities, such as mesoscopic parameters (total porosity, rock capacity factor, and ion molar conductivity) and microscopic parameters (ionic radius and montmorillonite stacking number) were incorporated to develop a machine learning model that incorporated micro- and meso-scale features. The predictive performance of PSO-LightGBM was verified using diffusion experiments, which investigated the diffusion of HCrO4-, I-, and CoEDTA2- at compacted dry densities of 1200-1800 kg/m3 using a through-diffusion method. Spearman correlation and Shapley additive explanation analyses revealed that the compacted dry density, ionic diffusion coefficient in water, ionic radius, and total porosity were the top-four influencing factors among the 16 input features. Partial dependence plot analysis elucidated the relationship between the effective diffusion coefficient and each input feature. The analysis results were consistent with the experimental findings, demonstrating the reliability of machine learning. Due to the incorporation of multi-scale features, the PSO-LightGBM model demonstrated enhanced predictive accuracy, linking the microstructure of bentonite to radionuclide diffusion, and providing a comprehensive interpretation of the diffusion mechanism.
RESUMO
PURPOSE: This study aims to analyze the distribution of plasma aldosterone, renin activity, deoxycorticosterone (DOC), cortisol, cortisone, and 24 h urinary aldosterone (24 h-uAld) levels based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: Plasma and 24 h urine were collected from 129 healthy volunteers in Northeast China. The effect of sodium intake, age, gender, blood sampling time on plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio (ARR), DOC, cortisol, cortisone, cortisol to cortisone ratio, and 24 h-uAld were investigated by nonparametric test, multiple linear regression and Harris-Boyd's standard deviate test. RESULTS: There was no significant difference observed in 24 h-uAld, PAC (AM), PRA(AM), ARR (AM), DOC (AM), cortisol (AM), cortisone (AM), and cortisol to cortisone (AM) between high and low sodium intake group. Significant differences were observed between morning and afternoon sampling groups in terms of PAC, ARR, DOC, cortisol, and cortisone. Reference intervals (RIs) of 24 h-uAld, PAC (AM) were recommended to be partitioned by gender. RI of PRA was recommended age stratification. CONCLUSION: We recommend that the same reference interval could be used regardless of sodium intake. Gender is the main influence factor for 24 h-uAld, PAC, and ARR. Age is key influence factor for PRA.
Assuntos
Aldosterona , Cortisona , Hidrocortisona , Renina , Espectrometria de Massas em Tandem , Humanos , Feminino , Masculino , Adulto , Cortisona/urina , Cortisona/sangue , Hidrocortisona/sangue , Hidrocortisona/urina , Pessoa de Meia-Idade , Aldosterona/sangue , Aldosterona/urina , Renina/sangue , Espectrometria de Massas em Tandem/métodos , Adulto Jovem , Cromatografia Líquida/métodos , Fatores Sexuais , Fatores Etários , Sódio na Dieta , Desoxicorticosterona/urina , Desoxicorticosterona/sangue , Idoso , China , Adolescente , Espectrometria de Massa com Cromatografia LíquidaRESUMO
The tumor recurrence and metastasis of colorectal cancer (CRC) are responsible for most of CRC-linked mortalities. It is an urgent need to deeply investigate the pathogenesis of CRC metastasis and look for novel targets for its treatment. The current study aimed to investigate the effects of ubiquitin-specific peptidase 15 (USP-15) on the CRC progression. In vivo, a mouse model of liver metastasis of CRC tumor was established to investigate the role of USP-15. In vitro, the migrated and invasive abilities of CRC cells were assessed by transwell assay. Cell stemness was evaluated by using sphere formation assay. The underlying mechanism was further explored by employing the co-immunoprecipitation, dual luciferase reporter assay, oligonucleotide pull-down assay, and chromatin immunoprecipitation assay. The results showed that USP-15 was upregulated in CRC patients with liver metastasis and high metastatic potential cell lines of CRC. Loss of USP-15 repressed the epithelial-to-mesenchymal transition (EMT), migration, invasion, and stemness properties of CRC cells in vitro. Downregulation of USP-15 reduced the liver metastasis of mice in vivo. USP-15 upregulation obtained the contrary effects. Subsequently, USP-15 deubiquitinated transcription factor AP-4 (TFAP4) and enhanced its protein stability. TFAP4 could transcriptionally activated polycomb group ring finger 1 (PCGF1). The pro-cancer effects of USP-15 were rescue by the knockdown of TFAP4 or PCGF1. In conclusions: USP-15 facilitated the liver metastasis by the enhancement of cell stemness and EMT in CRC, which was at least partly mediated by the deubiquitination of TFAP4 upon the upregulation of PCGF1.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Células-Tronco Neoplásicas , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Complexo Repressor Polycomb 1/metabolismo , Complexo Repressor Polycomb 1/genética , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genéticaRESUMO
This study aims to identify optimal parameters for using Thulium fiber lasers (TFL) in ureteral stone lithotripsy to ensure laser safety and maximize efficacy. Our goal is to improve the outcomes of single-use semi-rigid ureteroscopy for treating stones located in the proximal ureter. A clinically relevant thermal testing device was designed to investigate heating effects during TFL stone fragmentation. The device was utilized to identify safe power thresholds for TFL at various irrigation rates. Three other devices were used to assess varying pulse energy effects on stone fragmentation efficiency, dusting, retropulsion, and depth of tissue vaporization. Comparative experiments in fresh porcine renal units were performed to validate the efficacy and safety of optimal TFL parameters for semi-rigid ureteroscopy in proximal ureteral stone procedures. Our study found that the improved device generated a higher thermal effect. Furthermore, the safe power threshold for laser lithotripsy increased as the irrigation rate was raised. At an irrigation rate of 40 ml/min, it is safe to use an average power of less than 30 watts. Although increasing pulse energy has a progressively lower effect on fragmentation and dust removal efficiency, it did lead to a linear increase in stone displacement and tissue vaporization depth. Thermal testing showed 20 W (53.87 ± 2.67 °C) indicating potential urothelial damage. In our study of laser lithotripsy for proximal ureteral stones, the group treated with 0.3 J pulses had several advantages compared to the 0.8 J group: Fewer large fragments (> 4 mm): 0 vs. 1.67 fragments (1-2.25), p = 0.002, a lower number of collateral tissue injuries: 0.50 (0-1.25) vs. 2.67 (2-4), p = 0.011, and lower stone retropulsion grading: 0.83 (0.75-1) vs. 1.67 (1-2), p = 0.046. There was no significant difference in operating time between the groups (443.33 ± 78.30 s vs. 463.17 ± 75.15 s, p = 0.664). These findings suggest that TFL irradiation generates a greater thermal effect compared to non-irradiated stones. Furthermore, the thermal effect during laser lithotripsy is influenced by both power and irrigation flow rate. Our study suggests that using a power below 15 W with an irrigation flow rate of 20 ml/min is safe. Moreover, a pulse energy of 0.3 J appears to be optimal for achieving the best overall stone fragmentation effect.
Assuntos
Litotripsia a Laser , Túlio , Cálculos Ureterais , Cálculos Ureterais/terapia , Cálculos Ureterais/cirurgia , Litotripsia a Laser/métodos , Litotripsia a Laser/instrumentação , Litotripsia a Laser/efeitos adversos , Animais , Suínos , Lasers de Estado Sólido/uso terapêutico , Ureteroscopia/métodos , Ureteroscopia/instrumentação , Ureteroscopia/efeitos adversosRESUMO
An efficient and scalable method for the synthesis of 3,4-dihydroisoquinolin-1(2H)-ones through benzylic oxidation of tetrahydroisoquinoline derivatives using a catalytic amount of cerium ammonium nitrate (CAN) and a stoichiometric amount of NaBrO3 as oxidants was developed. The reaction is significantly influenced by the substituent groups on the phenyl ring. While electron-withdrawing groups on the phenyl ring can lower the reactivities of the substrates, electron-donating groups on the phenyl ring can dramatically promote the oxidation rate.
RESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.
RESUMO
An open challenge remained in designing an optical system to capture the aerial image with a wide field of view (FoV) and high resolution. The optical system of one camera from a single unmanned aerial vehicle (UAV) can hardly promise the FoV and resolution. The conventional swarm UAVs can form the camera array with a short or fixed baseline. They can capture the images with a wide FoV and high resolution, but the cost is the requirement of many UAVs. We aim to design a camera array with a wide and dynamic baseline to reduce the demand for UAVs to organize a synthetic optical aperture. In this thought, we propose a master-slave UAVs-based synthetic optical aperture imaging system with a wide and dynamic baseline. The system consists of one master UAV and multiple slave UAVs. Master and slave UAVs provide the global and local FoVs, respectively, and improve the efficiency of image acquisition. In such a system, fusing UAV images becomes a new challenge due to two factors: (i) the small FoV overlap of slave UAVs and (ii) the gap in resolution scale from slave to master UAV images. To deal with it, a coarse-to-fine stitching method is proposed to stitch up the multi-view images into one to obtain a wide FoV with high resolution. A video stabilization method has also been designed for the proposed imaging system. Challenges caused by wide and dynamic baselines can thus be solved by the above methods. Actual data experiments demonstrate that the proposed imaging system achieves high-quality imaging results.
RESUMO
We used Mendelian randomization (MR) to examine the relationship between smoking, various categories of blood lipids, and bladder cancer (BLCA). Data for this study were drawn from the genome-wide association studies of the GSCAN consortium (~1.2 million participants), a subset of the UK Biobank (~120,000 participants), and the FinnGen consortium (2,072 cases and 307,082 controls). Initially, we utilized inverse variance weighted (IVW), complementary and sensitivity analyses, multivariable MR, and meta-analysis to confirm the association between blood lipids and BLCA. We then performed mediation MR to elucidate the relationship between smoking, blood lipids, and BLCA. Our analysis identified five lipids, including triglycerides in very large HDL, cholesterol in small VLDL, free cholesterol in very large HDL, total free cholesterol, and apolipoprotein B, as having strong and inverse associations with BLCA. These lipids demonstrated no heterogeneity or pleiotropy and exhibited consistent direction and magnitude across IVW, weighted median, and MR-Egger analyses. Our mediation MR further revealed that triglycerides in very large HDL and cholesterol in small VLDL could reduce the impact of smoking on BLCA, mediating -4.3% and -4.5% of the effect, respectively. In conclusion, our study identified five lipids exhibiting a robust inverse relationship with BLCA, two of which can buffer the impact of smoking on BLCA.
RESUMO
Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10-8). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis.
Assuntos
Estudo de Associação Genômica Ampla , Urolitíase , Humanos , Análise da Randomização Mendeliana , Estilo de Vida , Urolitíase/etiologia , Urolitíase/genética , CháRESUMO
OBJECTIVES: To compare the efficacy and safety of thulium fiber laser (TFL) to holmium: YAG (Ho: YAG) laser in ureteroscopic lithotripsy for urolithiasis. METHODS: PubMed, Web of Science, Embase, CENTRAL, SinoMed, CNKI database, VIP and Wanfang Database were systematically searched for all relevant clinical trials until September 2023. References were explored to identify the relevant articles. Meta-analysis was carried out for the retrieved studies using RevMan5.4.1 software, and the risk ratio, mean difference and 95% confidence interval were expressed. Statistical significance was set at p < 0.05. The main outcomes of this meta-analysis were stone-free rate (SFR), perioperative outcomes and intraoperative or postoperative complications. RESULTS: Thirteen studies, including 1394 patients, were included. According to the results of pooled analysis, TFL was associated with significantly higher stone-free rate (SFR) [0.52, 95% CI (0.32, 0.85), P = 0.009], shorter operation time [-5.47, 95% CI (-8.86, -2.08), P = 0.002], and less stone migration [0.17, 95% CI (0.06, 0.50), P = 0.001]. However, there was no significant difference in terms of the laser time, duration of hospital stay, drop of hemoglobin level, total energy, postoperative ureteral stenting, the incidence of intraoperative complications or postoperative complications between TFL and Ho: YAGs. CONCLUSION: The findings of this study demonstrated several advantages of TFL in terms of higher SFR, shorter operative time and less stone migration. TRIAL REGISTRATION: The protocol of this systematic review was listed in PROSPERO ( www.crd.york.ac.uk/PROSPERO ) (Protocol number: CRD42022362550).
Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Túlio , Ureteroscopia , Humanos , Ureteroscopia/métodos , Lasers de Estado Sólido/uso terapêutico , Litotripsia a Laser/métodos , Resultado do Tratamento , Urolitíase/cirurgia , Urolitíase/terapiaAssuntos
Cistadenoma Mucinoso , Neoplasias Renais , Humanos , Universidades , Pelve Renal , Neoplasias Renais/cirurgia , ChinaRESUMO
Gibberella ear rot (GER) caused by Fusarium graminearum (teleomorph Gibberella zeae) is one of the most destructive diseases in maize, which severely reduces yield and contaminates several potential mycotoxins in the grain. However, few efforts had been devoted to dissecting the genetic basis of maize GER resistance. In the present study, a genome-wide association study (GWAS) was conducted in a maize association panel consisting of 303 diverse inbred lines. The phenotypes of GER severity were evaluated using kernel bioassay across multiple time points in the laboratory. Then, three models, including the fixed and random model circulating probability unification model (FarmCPU), general linear model (GLM), and mixed linear model (MLM), were conducted simultaneously in GWAS to identify single-nucleotide polymorphisms (SNPs) significantly associated with GER resistance. A total of four individual significant association SNPs with the phenotypic variation explained (PVE) ranging from 3.51 to 6.42% were obtained. Interestingly, the peak SNP (PUT-163a-71443302-3341) with the greatest PVE value, was co-localized in all models. Subsequently, 12 putative genes were captured from the peak SNP, and several of these genes were directly or indirectly involved in disease resistance. Overall, these findings contribute to understanding the complex plant-pathogen interactions in maize GER resistance. The regions and genes identified herein provide a list of candidate targets for further investigation, in addition to the kernel bioassay that can be used for evaluating and selecting elite germplasm resources with GER resistance in maize.
RESUMO
Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, has been shown to be effective for patients with ALK-positive non-small cell lung cancer (NSCLC). However, alectinib resistance is a serious problem worldwide. To the best of our knowledge, little information is available on its molecular mechanisms using the Gene Expression Omnibus (GEO) database. In this study, the differentially expressed genes (DEGs) were selected from the gene expression profile GSE73167 between parental and alectinib-resistant human lung adenocarcinoma (LUAD) cell samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). The construction of protein-protein interaction (PPI) network was performed to visualize DEGs. The hub genes were extracted based on the analysis of the PPI network using plug-in cytoHubba of Cytoscape software. The functional roles of the key genes were investigated using Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer (UALCAN), Gene Set Enrichment Analysis (GSEA), and Tumor Immune Estimation Resource (TIMER) analysis. The networks of kinase, miRNA, and transcription-factor targets of SFTPD were explored using LinkedOmics. The drug sensitivity analysis of SFTPD was analyzed using the RNAactDrug database. Results showed a total of 144 DEGs were identified. Five hub genes were extracted, including mucin 5B (MUC5B), surfactant protein D (SFTPD), deleted in malignant brain tumors 1 (DMBT1), surfactant protein A2 (SFTPA2), and trefoil factor 3 (TFF3). The survival analysis using GEPIA displayed that low expression of SFTPD had a significantly negative effect on the prognosis of patients with LUAD. GSEA revealed that low expression of SFTPD was positively correlated with the pathways associated with drug resistance, such as DNA replication, cell cycle, drug metabolism, and DNA damage repair, including mismatch repair (MMR), base excision repair (BER), homologous recombination (HR), and nucleotide excision repair (NER). The SFTPD expression was negatively correlated with the drug sensitivity of alectinib according to RNAactDrug database. The expression of SFTPD was further validated in parental H3122 cells and alectinib-resistant H3122 cells by quantitative reverse transcription PCR (RT-qPCR). In conclusion, our study found that the five hub genes, especially low expression of SFTPD, are closely related to alectinib resistance in patients with LUAD.
RESUMO
Cyclic peptides are polypeptide chains formed by cyclic sequences of amide bonds between protein-derived or non-protein-derived amino acids. Compared to linear peptides, cyclic peptides offer several unique advantages, such as increased stability, stronger affinity, improved selectivity, and reduced toxicity. Cyclic peptide has been proved to have a promising application prospect in the medical field. In addition, this paper mainly describes that cyclic peptides play an important role in anti-cancer, anti-inflammatory, anti-virus, treatment of multiple sclerosis and membranous nephropathy through immunomodulation. In order to know more useful information about cyclic peptides in clinical research and drug application, this paper also summarizes cyclic peptides currently in the clinical trial stage and cyclic peptide drugs approved for marketing in the recent five years. Cyclic peptides have many advantages and great potential in treating various diseases, but there are still many challenges to be solved in the development process of cyclic peptides.
RESUMO
[This corrects the article DOI: 10.1016/j.isci.2023.106024.].
RESUMO
The release of nitrogen and phosphorus from sediments into lake water will exacerbate the eutrophication of lakes and endanger ecological safety and human health. Microorganisms are indispensable in nitrogen and phosphorus conversion, and accurate analysis of the distribution characteristics and sources of nitrogen and phosphorus in sediments as well as their relationship with microorganisms is an important prerequisite for lake eutrophication control. Taking Taihu Lake as the study area, 30 surface sediment samples were collected, and the grain size, pH, organic matter (OM), dissolved organic carbon (DOC), total phosphorus (TP), total nitrogen (TN), nitrate nitrogen (NO3--N), and dissolved organic nitrogen (DON) along with some other index contents were measured and analyzed; accordingly, spatial distribution characteristics were analyzed. While using nutrient agar (NA), the number of aerobic bacteria (AB) was determined by plate counting in the medium. Combined with principal component analysis (PCA) and Pearson correlation analysis, the spatial distribution characteristics and sources of sediments and AB in Taihu Lake were explored. The characteristics of sediment pollution in Taihu Lake were studied using the comprehensive pollution index and the organic pollution index methods. The results revealed that the average sediment indicators of the surface layer of Taihu Lake were as follows:AB was 9.25×104 CFU·g-1, average particle size (MZ) was 17.59 µm, pH was 7.62, ω(OM) was 15.05 g·kg-1, ω(DOC) was 71.60 mg·kg-1, ω(TP) was 598.13 mg·kg-1, ω(TN) was 1113.92 mg·kg-1, ω(NO3--N) was 3.22 mg·kg-1, and ω(DON) was 22.60 mg·kg-1. The comprehensive pollution index (FF) showed that 13% of the Taihu Lake was moderately polluted, while 87% was heavily polluted. Excluding the area in the center of the lake, the southern lake area, and some lakes in the western part of the East Taihu Lake, TN in the rest of the area was moderately and severely polluted. In addition to the heavy pollution of Zhushan Bay, the TP in Taihu Lake was generally at light and moderate pollution. The organic pollution index (OI) showed that the organic pollution of the sediments of Taihu Lake was relatively light, majorly caused by organic nitrogen (ON) pollution. DOC, DON, TN, and OM in Taihu Lake were primarily derived from the influence of aquatic plants, and TP And AB were primarily derived from the influence of the external input of rivers. This research will provide theoretical support for lake eutrophication treatment and also provide new ideas for further analysis of AB to remove nitrogen and phosphorus pollution from sediments.