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The energy oriented mine ecological restoration mode of photovoltaic+ecological restoration provides a breakthrough for alleviating the dilemma of photovoltaic land development and solving the urgent need for restoration of abandoned mining land. Taking a mining area in central Liaoning Province as an example, we established three photovoltaic+mining ecological restoration modes, including forest-photovoltaic complementary, agriculture-photovoltaic, and grass photovoltaic complementation. Combined with the life cycle assessment method, we calculated and assessed the potential of photovoltaic+mining ecological restoration in carbon reduction and sink enhancement. The average annual carbon reduction and sink increase was 514.93 t CO2·hm-2 under the photovoltaic+mining ecological restoration mode, while the average annual carbon reduction per megawatt photovoltaic power station was 1242.94 t CO2. The adoption of photovoltaic+ecological restoration mode in this mining area could make carbon reduction and sink enhancement 6.30-7.79 Mt CO2 during 25 years. The carbon reduction and sink increment mainly stemmed from the photovoltaic clean power generation induced carbon reduction, accounting for 96.4%-99.4%, while the contribution of ecosystem carbon sink increment was small, accounting for only 0.6%-3.7% of the total. Among different photovoltaic+ecological restoration modes, the carbon reduction and sink increment was the largest in forest-photovoltaic complementary (7.11 Mt CO2), followed by agriculture-photovoltaic (7.04 Mt CO2), and the least in grass photovoltaic complementation (6.98 Mt CO2). Constructing the development mode of "photovoltaic+mining ecological restoration" could effectively leverage the dual benefits of reducing emissions from photovoltaic power generation and increase sinks from mining ecological restoration, which would be helpful for achieving the goal of carbon neutrality in China.
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Sequestro de Carbono , Ecossistema , Mineração , China , Recuperação e Remediação Ambiental/métodos , Modelos Teóricos , Carbono/química , Carbono/análise , Conservação dos Recursos Naturais/métodos , Dióxido de Carbono/análise , Energia SolarRESUMO
Neurodegenerative diseases such as Parkinson's disease (PD) have complex pathogenetic mechanisms. Genetic, age, and environmental factors are all related to PD. Due to the unclear pathogenesis of PD and the lack of effective cure methods, it is urgent to find new targets for treating PD patients. Ferroptosis is a form of cell death that is reliant on iron and exhibits distinct morphological and mechanistic characteristics compared to other types of cell death. It encompasses a range of biological processes, including iron/lipid metabolism and oxidative stress. In recent years, research has found that ferroptosis plays a crucial role in the pathophysiological processes of neurodegenerative diseases and stroke. Therefore, ferroptosis is also closely related to PD, This article reviews the core mechanisms of ferroptosis and elucidates the correlation between PD and ferroptosis. In addition, new compounds that have emerged in recent years to exert anti PD effects by inhibiting the ferroptosis signaling pathway were summarized. I hope to further elaborate the relationship between ferroptosis and PD through the review of this article, and provide new strategies for developing PD treatments targeting ferroptosis.
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Ferroptose , Doença de Parkinson , Ferroptose/fisiologia , Humanos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Animais , Ferro/metabolismo , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia , Metabolismo dos Lipídeos/fisiologiaRESUMO
The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.
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Ciclo Celular , Dano ao DNA , Estruturas R-Loop , Humanos , Ciclo Celular/genética , Animais , Instabilidade Genômica , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/genética , MutaçãoRESUMO
Seeking noble-metal-free catalysts for efficient synthesis of aryl nitriles under mild conditions poses a significant challenge due to the use of hypertoxic cyanides or high-pressure/temperature NH3/O2 in conventional synthesis processes. Herein, we developed a novel framework 1 assembled by [Ni72] nanocages with excellent solvents/pH stability. To investigate the structure-activity relationship of catalytic performance, several isostructural MOFs with different molar ratios of Ni/Cu by doping Cu2+ into framework 1 (Ni0.59Cu0.41 (2), Ni0.81Cu0.19 (3), Ni0.88Cu0.12 (4), and Ni0.92Cu0.08 (5)) were prepared. Catalytic studies revealed that catalyst 3 exhibited remarkable performance in the synthesis of aryl nitriles, utilizing a formamide alternative to hypertoxic NaCN/KCN. Notably, catalyst 3 achieved an excellent TOF value of 9.8 h-1. Furthermore, catalyst 3 demonstrated its applicability in a gram-scale experiment and maintained its catalytic performance even after six recycling cycles, owing to its high stability resulting from significant electrostatic and orbital interactions between the Ni center and ligands as well as a large SOMO-LUMO energy gap supported by DFT calculations. Control experiments and DFT calculations further revealed that the excellent catalytic performance of catalyst 3 originated from the synergistic effect of Ni/Cu. Importantly, this work not only provides a highly feasible method to construct highly stable MOFs containing multinuclear nanocages with exceptional catalytic performance but also represents the first example of a heterogeneous catalyst for the synthesis of aryl nitriles using formamide as the cyanide source.
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ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AMLâ cells in vivo, unlike the ATR inhibitor. These results suggest that the marked anti-AML activity is regulated by the kinase-independent functions of the ATR protein. Consequently, developing potent and selective ATR degraders could be a promising strategy for treating AML.
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Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/uso terapêutico , Linhagem Celular Tumoral , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Proteólise , Proteína Supressora de Tumor p53/metabolismoRESUMO
Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.
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Dihydroartemisinin (DHA), a derivative of artemisinin which is primarily used to treat malaria in clinic, also confers protective effect on lipopolysaccharide-induced nephrotoxicity. While, the activities of DHA in cisplatin (CDDP)-caused nephrotoxicity are elusive. To investigate the role and underlying mechanism of DHA in CDDP-induced nephrotoxicity. Mice were randomly separated into four groups: normal, CDDP, and DHA (25 and 50 mg/kg were orally injected 1 h before CDDP for consecutive 10 days). All mice except the normal were single injected intraperitoneally with CDDP (22 mg/kg) for once on the 7th day. Combined with quantitative proteomics and bioinformatics analysis, the impact of DHA on renal cell apoptosis, oxidative stress, biochemical indexes, and inflammation in mice were investigated. Moreover, a human hepatocellular carcinoma cells xenograft model was established to elucidate the impact of DHA on tumor-related effects of CDDP. DHA reduced the levels of creatinine (CREA) (p < 0.01) and blood urea nitrogen (BUN) (p < 0.01), reversed CDDP-induced oxidative, inflammatory, and apoptosis indexes (p < 0.01). Mechanistically, DHA attenuated CDDP-induced inflammation by inhibiting nuclear factor κB p65 (NFκB p65) expression, and suppressed CDDP-induced renal cell apoptosis by inhibiting p63-mediated endogenous and exogenous apoptosis pathways. Additionally, DHA alone significantly decreased the tumor weight and did not destroy the antitumor effect of CDDP, and did not impact AST and ALT. In conclusion, DHA prevents CDDP-triggered nephrotoxicity via reducing inflammation, oxidative stress, and apoptosis. The mechanisms refer to inhibiting NFκB p65-regulated inflammation and alleviating p63-mediated mitochondrial endogenous and Fas death receptor exogenous apoptosis pathway.
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Antineoplásicos , Artemisininas , Humanos , Camundongos , Animais , Cisplatino/toxicidade , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Artemisininas/metabolismo , Rim/metabolismo , Rim/patologia , Estresse Oxidativo , Inflamação/metabolismo , Apoptose , Antineoplásicos/toxicidadeRESUMO
The flexible and self-healing supercapacitors (SCs) are considered to be promising smart energy storage devices. Nevertheless, the SCs integrated with flexibility, lightweight, pattern editability, self-healing capabilities and desirable electrochemical properties remain a challenge. Herein, an all-in-one self-healing SC fabricated with the free-standing hybrid film (TCMP) composed of the 2,2,6,6-tetramethylpiperidin-1-yloxy-oxidized cellulose nanofibers (TOCNs) carried carbon nanotubes (CNTs), manganese dioxide (MnO2) and polyaniline (PANI) as the electrode, polyvinyl alcohol/sulfuric acid (PVA/H2SO4) gel as the electrolyte and dynamically cross-linked cellulose nanofibers/PVA/sodium tetraborate decahydrate (CNF/PB) hydrogel as the self-healing electrode matrix is developed. The TCMP film electrodes are fabricated through a facile in-situ polymerization of MnO2 and PANI in TOCNs-dispersed CNTs composite networks, exhibiting lightweight, high electrical conductivity, flexibility, pattern editability and excellent electrochemical properties. Benefited from the hierarchically porous structure and high mechanical properties of TOCNs, excellent electrical conductivity of CNTs and the desirable synergistic effect of pseudocapacitance induced by MnO2 and PANI, the assembled SC with an interdigital structure demonstrated a high areal capacitance of 1108 mF cm-2 at 2 mA cm-2, large areal energy density of 153.7 µWh cm-2 at 1101.7 µW cm-2. A satisfactory bending cycle performance (capacitance retention up to 95 % after 200 bending deformations) and self-healing characteristics (â¼90 % capacitance retention after 10 cut/repair cycles) are demonstrated for the TCMP-based symmetric SC, delivering a feasible strategy for electrochemical energy storage devices with excellent performance, designable patterns and desirable safe lifespan.
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Adenosine-to-inosine (A-to-I) editing of RNA, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is a prevalent RNA modification in mammals. It has been shown that A-to-I editing plays a critical role in multiple diseases, such as cardiovascular disease, neurological disorder, and particularly cancer. ADARs are the family of enzymes, including ADAR1, ADAR2, and ADAR3, that catalyze the occurrence of A-to-I editing. Notably, A-to-I editing is mainly catalyzed by ADAR1. Given the significance of A-to-I editing in disease development, it is important to unravel the complex roles of ADAR1 in cancer for the development of novel therapeutic interventions.In this review, we briefly describe the progress of research on A-to-I editing and ADARs in cancer, mainly focusing on the role of ADAR1 in cancer from both editing-dependent and independent perspectives. In addition, we also summarized the factors affecting the expression and editing activity of ADAR1 in cancer.
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Neoplasias , Proteínas de Ligação a RNA , Animais , Humanos , Proteínas de Ligação a RNA/genética , Neoplasias/metabolismo , Adenosina Desaminase/genética , RNA , Mamíferos/metabolismoRESUMO
Hepatocellular carcinoma (HCC) treatment is a major challenge. Although andrographolide (Andro) has an anti-proliferation effect on HCC, its underlying mechanism is not yet elucidated, and whether Andro can inhibit HCC metastasis has not been reported. The present study aimed to clarify whether Andro inhibits SK-Hep-1 cell proliferation and HCC metastasis, and the mechanisms. The results showed that Andro significantly reduced the survival of HCC cells and tumor weight and volume in tumor-bearing nude mice. Andro also triggered apoptosis of HCC cells and upregulated MIR22HG, Cleaved Caspase 9/7/3 expression levels, and downregulated BCL-2 mRNA, BCL-2 expression levels. Knockdown of MIR22HG or overexpression of HuR attenuated the effects of Andro on the signal transduction of mitochondrial apoptotic pathway and proliferation ability in HCC cells. Moreover, Andro significantly reduced the invasive ability of the cells and the level of HCC cell lung metastasis, upregulated miR-22-3p expression level and downregulated HMGB1 and MMP-9 expression levels. MIR22HG or miR-22-3p knockdown attenuated the effects of Andro on the signaling of HMGB1/MMP-9 pathway and invasive ability in HCC cells, while the overexpression of HMGB1 attenuated the inhibitory effects of Andro on the MMP-9 expression level and invasive ability in HCC cells. Thus, the regulation of MIR22HG-HuR/BCL-2 and MIR22HG/HMGB1 signaling pathways is involved in the anti-HCC proliferation and metastasis effects of Andro. This study provided a new pharmacological basis for Andro in HCC treatment and, for the first time, identified a natural product molecule capable of positively regulating MIR22HG, which has a robust biological function.
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Carcinoma Hepatocelular , Proteína HMGB1 , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Proteína HMGB1/farmacologia , Proteína HMGB1/uso terapêutico , Metaloproteinase 9 da Matriz/farmacologia , Metaloproteinase 9 da Matriz/uso terapêutico , Camundongos Nus , Linhagem Celular Tumoral , MicroRNAs/genética , Proliferação de Células , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Movimento CelularRESUMO
Genetic targeting (e.g., gene knockout and tagging) based on polymerase chain reaction (PCR) is a simple yet powerful approach for studying gene functions. Although originally developed in classic budding and fission yeast models, the same principle applies to other eukaryotic systems with efficient homologous recombination. One-step PCR-based genetic targeting is conventionally used but the sizes of the homologous arms that it generates for recombination-mediated genetic targeting are usually limited. Alternatively, gene targeting can also be performed via fusion PCR, which can create homologous arms that are orders of magnitude larger, therefore substantially increasing the efficiency of recombination-mediated genetic targeting. Here, we present GetPrimers (https://www.evomicslab.org/app/getprimers/), a generalized computational framework and web tool to assist automatic targeting and verification primer design for both one-step PCR-based and fusion PCR-based genetic targeting experiments. Moreover, GetPrimers by design runs for any given genetic background of any species with full genome scalability. Therefore, GetPrimers is capable of empowering high-throughput functional genomic assays at multipopulation and multispecies levels. Comprehensive experimental validations have been performed for targeting and verification primers designed by GetPrimers across multiple organism systems and experimental setups. We anticipate GetPrimers to become a highly useful and popular tool to facilitate easy and standardized gene modification across multiple systems.
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Marcação de Genes , Schizosaccharomyces , Recombinação Homóloga , Técnicas de Inativação de Genes , Sequência de Bases , Schizosaccharomyces/genética , Reação em Cadeia da PolimeraseRESUMO
Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to angiotensin II, which has vasoconstrictive effects. Previous studies have shown that certain compounds of natural origin can inhibit the activity of angiotensin-converting enzymes and exert blood pressure-regulating effects. Surface Plasmon Resonance (SPR) biosensor technology is the industry standard method for observing biomolecule interactions. In our study, we used molecular simulation methods to investigate the docking energies of various herbal metabolites with ACE1 proteins, tested the real-time binding affinities between various herbal metabolites and sACE1 by SPR, and analyzed the relationship between real-time binding affinity and docking energy. In addition, to further explore the connection between inhibitor activity and real-time binding affinity, several herbal metabolites' in vitro inhibitory activities were tested using an ACE1 activity test kit. The molecular docking simulation technique's results and the real-time affinity tested by the SPR technique were found to be negatively correlated, and the virtual docking technique still has some drawbacks as a tool for forecasting proteins' affinities to the metabolites of Chinese herbal metabolites. There may be a positive correlation between the enzyme inhibitory activity and the real-time affinity detected by the SPR technique, and the results from the SPR technique may provide convincing evidence to prove the interaction between herbal metabolites and ACE1 target proteins.
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Inibidores da Enzima Conversora de Angiotensina , Técnicas Biossensoriais , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Simulação de Acoplamento Molecular , Ressonância de Plasmônio de Superfície , Técnicas Biossensoriais/métodos , AngiotensinasRESUMO
Wind turbine blades are often covered with ice and snow, which inevitably reduces their power generation efficiency and lifetime. Recently, a superhydrophobic surface has attracted widespread attention due to its potential values in anti-icing/deicing. However, the superhydrophobic surface can easily transition from Cassie-Baxter to Wenzel at low temperature, limiting its wide applications. Herein, inspired by the excellent water resistance and cold tolerance of Trifolium repens L. endowed by its micronano structure and low surface energy, a fresh structure was prepared by combining femtosecond laser processing technology and a boiling water treatment method. The prepared icephobic surface aluminum alloy (ISAl) mainly consists of a periodic microcrater array, nonuniform microclusters, and irregular nanosheets. This three-scale structure greatly promotes the stability of the Cassie-Baxter state. The critical Laplace pressure of ISAl is up to 1437 Pa, and the apparent water contact angle (CA) is higher than 150° at 0 °C. Those two factors contribute to its excellent anti-icing and deicing performances. The results show that the static icing delay time reaches 2577 s, and the ice adhesion strength is only 1.60 kPa. Furthermore, the anti-icing and deicing abilities of the proposed ISAl were examined under the environment of low temperature and high relative humidity to demonstrate its effectiveness. The dynamic anti-icing time of ISAl in extreme environments is up to 5 h, and ice can quickly fall with a speed of 34 r/min when it is in a horizontal rotational motion. Finally, ISAl has excellent reusability and mechanical durability, with the ice adhesion strength still being less than 6 kPa and the CA greater than 150° after 15 cycles of icing-deicing tests. The proposed structure would offer a promising strategy for the efficient anti-icing and deicing of wind turbine blades.
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The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are crucial electrochemical reactions that play vital roles in energy conversion and storage technologies, such as fuel cells and metal-air batteries. Typically, noble-metal-based catalysts are required to enhance the sluggish kinetics of the ORR and OER, but their high costs restrict their practical commercial applications. Thus, highly active and strong non-noble metal catalysts are essential to address the cost and durability challenge. Based on previous research, carbon-based catalysts may present the best alternatives to these precious metals in the future owing to their affordability, very large surface areas, and superior mechanical and electrical qualities. In particular, carbon aerogels prepared using biomass as the precursors are referred to as biomass-derived carbon aerogels. They have sparked broad attention and demonstrated remarkable performance in the energy conversion and storage sectors as they are ecologically beneficial, affordable, and have an abundance of precursors. Therefore, this review focuses on various nanostructured materials based on biomass-derived carbon aerogels as ORR/OER catalysts, including metal atoms, metal compounds, and alloys.
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The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs' evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner's gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method.
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Artificial modification of Bacillus thuringiensis (Bt) proteins can effectively improve their resistance to target pests, but the effect of such modification on the diversity of rhizosphere microorganisms remains unclear. Transgenic maize 2A-7 contains two artificially modified Bt proteins, mCry1Ab and mCry2Ab. These proteins can enter soil and pose a potential threat to soil microbial diversity. To assess their impacts on rhizosphere bacteria communities, the contents of the two Bt proteins and changes in bacterial community diversity in the rhizosphere soils of transgenic maize 2A-7 and its control variety were analyzed at different growth stages in 2020. The results showed that the two Bt proteins were detected at low levels in the rhizosphere soils of 2A-7 plants. No significant differences in soil bacterial diversity were detected between 2A-7 and its control variety at any of the growth stages. Bioinformatics analysis indicated that the growth stage, rather than the cultivar, was the main factor causing changes in bacterial communities. This research provides valuable data for understanding the impact of Bt crops on the soil microbiome, and establishes a theoretical basis for evaluation of their safety.
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INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/diagnóstico por imagem , Imageamento Tridimensional , Método Simples-Cego , Colonoscopia/métodos , Adenoma/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagemRESUMO
To remove ammonium and tetracycline (TC) from wastewater, a new strain, DX-21, was isolated and exhibited simultaneous removal ability. The performance of DX-21 in TC removal, its removal mechanism, and the potential toxicities of the degradation products were investigated with genomics, mass spectrometry, density functional theory calculations, quantitative structure-activity relationship analyses, and Escherichia coli exposure experiments. DX-21 exhibited removal of ammonium (9.64 mg·L-1·h-1) via assimilation, and TC removal (0.85 mg·L-1·h-1) primarily occurred through cell surface bio-adsorption and biodegradation. Among the 12 identified degradation products, the majority exhibited lower toxicities than TC. Moreover, potential degradation pathways were proposed, including hydroxylation and deamination. Furthermore, DX-21 possessed TC resistance genes, various oxygenases and peroxidases that could potentially contribute to TC degradation. DX-21 colonized activated sludge and significantly enhanced the biodegradation of TC. Therefore, DX-21 showed potential for treating wastewater containing both ammonium and TC.
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Compostos de Amônio , Compostos Heterocíclicos , Águas Residuárias , Pseudomonas/metabolismo , Compostos de Amônio/análise , Tetraciclina/farmacologia , Tetraciclina/química , Antibacterianos/análiseRESUMO
A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC50 = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs. Kinase panel assays demonstrated that compound I10 was the selective VEGFR-2 inhibitor. The prediction of 3D modeling unveiled a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable anti-angiogenesis and anti-proliferation in HUVEC at low nanomolar concentrations. PK studies indicated that the lead compound possessed adequate oral bioavailability in various species. In vivo subcutaneous tumor model demonstrated that oral administration of I10 demonstrated potent efficacy in inhibiting tumor growth and angiogenesis. All these results suggested compound I10 is a potential drug candidate for cancer treatment.
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Antineoplásicos , Neoplasias , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Neoplasias/tratamento farmacológico , Fosforilação , Inibidores de Proteínas Quinases/química , Proliferação de Células , Antineoplásicos/química , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Estrutura MolecularRESUMO
This study investigated the removal characteristics of tetracycline (TC) in the presence of copper ions (Cu2+) in aerobic granular sludge by analyzing the TC removal pathway, composition and functional group changes of extracellular polymeric substances (EPS), and microbial community structure. The TC removal pathway changed from cell biosorption to EPS biosorption, and the microbial degradation rate of TC was reduced by 21.37% in the presence of Cu2+. Cu2+ and TC induced enrichment of denitrifying bacteria and EPS-producing bacteria by regulating the expression of signaling molecules and amino acid synthesis genes to increase the content of EPS and -NH2 groups in EPS. Although Cu2+ reduced the content of acidic hydroxyl functional groups (AHFG) in EPS, an increase in TC concentration stimulated the secretion of more AHFG and -NH2 groups in EPS. The long-term presence of TC presence of the relative abundances of Thauera, Flavobacterium and Rhodobacter and improved the removal efficiency.