RESUMO
Nanomaterials are widely used in many fields for their unique physical and chemical properties and especially demonstrate irreplaceability in energy storage systems. In this paper, a novel composite of copper sulfide with hypha-like core-shell nano-structure is synthesized by in situ phase inversion method, which serves as high stability negative electrode materials of zinc-ion batteries (ZIBs). The unique structure facilitates efficient electron and ion transport, enhances the kinetics of electrochemical reactions, and effectively suppresses the undesired expansion and decomposition of transition metal compounds. As a result, the half battery exhibits high specific capacity (250.2 mAh g-1 at 0.1 A g-1), reliable rate performance, and cycle stability (98.3 mAh g-1 at 1 A g-1 after 500 cycles). Additionally, when assembled with ZnxMnO2 positive to form a full battery, it demonstrates good cycling capacity at an intermediate current density of 2 A g-1, while maintaining excellent structural stability over 5,000 cycles (61% retention).
RESUMO
Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P < 0.01). The serum neutralization antibody levels rapidly increased in sheep post-vaccination and post-challenge with OPIV3. Furthermore, viral shedding in nasal swabs and viral loads in the lungs were reduced. The results of this study suggest that vaccination with this candidate vaccine induces the production of neutralizing antibodies and provides significant protection against OPIV3 infection. These results may be helpful for further studies on prevention and control strategies for OPIV3 infections.
Assuntos
Infecções por Respirovirus , Doenças dos Ovinos , Vacinas de Produtos Inativados , Vacinas Virais , Animais , Ovinos , Infecções por Respirovirus/veterinária , Infecções por Respirovirus/prevenção & controle , Infecções por Respirovirus/virologia , Infecções por Respirovirus/imunologia , Vacinas de Produtos Inativados/imunologia , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/virologia , Doenças dos Ovinos/imunologia , Vacinas Virais/imunologia , Respirovirus/imunologia , Imunogenicidade da Vacina , Vacinação/veterináriaRESUMO
BACKGROUND: Bovine coronavirus (BCoV) is implicated in severe diarrhea in calves and contributes to the bovine respiratory disease complex; it shares a close relationship with human coronavirus. Similar to other coronaviruses, remarkable variability was found in the genome and biology of the BCoV. In 2022, samples of feces were collected from a cattle farm. A virus was isolated from 7-day-old newborn calves. In this study, we present the genetic characteristics of a new BCoV isolate. The complete genomic, spike protein, and nucleocapsid protein gene sequences of the BCoV strain, along with those of other coronaviruses, were obtained from the GenBank database. Genetic analysis was conducted using MEGA7.0 and the Neighbor-Joining (NJ) method. The reference strains' related genes were retrieved from GenBank for comparison and analysis using DNAMAN. RESULTS: The phylogenetic tree and whole genome consistency analysis showed that it belonged to the GIIb subgroup, which is epidemic in Asia and America, and was quite similar to the Chinese strains in the same cluster. Significantly, the S gene was highly consistent with QH1 (MH810151.1) isolated from yak. This suggests that the strain may have originated from interspecies transmission involving mutations of wild strains. The N gene was conserved and showed high sequence identity with the epidemic strains in China and the USA. CONCLUSIONS: Genetic characterization suggests that the isolated strain could be a new mutant from a wild-type lineage, which is in the same cluster as most Chinese epidemic strains but on a new branch.
Assuntos
Doenças dos Bovinos , Infecções por Coronavirus , Coronavirus Bovino , Genoma Viral , Filogenia , Animais , Bovinos , Coronavirus Bovino/genética , Coronavirus Bovino/isolamento & purificação , China/epidemiologia , Doenças dos Bovinos/virologia , Doenças dos Bovinos/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Infecções por Coronavirus/epidemiologia , Fezes/virologia , Glicoproteína da Espícula de Coronavírus/genética , Animais Recém-NascidosRESUMO
Chromium is a multivalent metal with great development in the energy storage field because it can effectively improve the electrochemical performance of the material. However, chromium(VI) is soluble in water and toxic, which causes serious metal pollution in the environment. In addition, nanoplastics are difficult to degrade and easy to accumulate, which is an urgent environmental problem to be solved. Therefore, we choose Zea mays to absorb chromium ions, nanopolystyrene, nanocarboxylic polystyrene, and their complexes, which can coordinate and decompose with various polymers in Z. mays, and produce coordination, conjugation, mixed valence, and adjacent group effects. Due to the above effects, the UV-vis spectrum of the material is blueshifted; the X-ray photoelectron spectroscopy peaks of Cr 2p have a chemical shift; the pore structure is optimized; the graphitization degree is improved; the content of N, O, and Cr in the material increases; and the elements are evenly distributed. The series of optimization processes makes the electrodes exhibit excellent electrochemical performance in both supercapacitors and lithium-ion batteries. At 0.5 A·g-1, the specific capacitance of the electrode reaches 490 F·g-1. After 10,000 cycles, its specific capacitance remains at 429.3 F·g-1, and the Coulombic efficiency is 89.9%. In lithium-ion batteries, the initial discharging capacity of the electrode is 1071.7 mAh·g-1 at 0.05 A·g-1. After 5000 cycles, its specific capacity can still reach 242 mAh·g-1 at 0.2 A·g-1, and the Coulombic efficiency is above 95%.
RESUMO
Inosine could potentially become a novel antibacterial agent against Alicyclobacillus acidoterrestris as low doses of inosine can prevent its contamination. However, until now the antibacterial mechanism of inosine targeting A. acidoterrestris is still unknown. In this study, to unravel the mechanism of inosine against A. acidoterrestris puzzle, the effects of inosine on bacterial surface hydrophobicity, intracellular protein content, cell membrane damage extent, and permeability of the A. acidoterrestris were investigated. The results showed that inosine can effectively inhibit the growth and reproduction of A. acidoterrestris by destroying the integrity of cell membrane and increasing its permeability, causing the leakage of intracellular nutrients. Furthermore, the interaction networks of inosine target proteins were analyzed. The interaction networks further revealed that damage to bacterial cell membranes might be relevant to inosine's effect on bacterial DNA replication and cell energy metabolism through regulating nucleotide synthesis and metabolism and the activity of translation initiation factors. Finally, the antibacterial mechanism of inosine against A. acidoterrestris was proposed.
Assuntos
Alicyclobacillus , Antibacterianos , Antibacterianos/farmacologia , Alicyclobacillus/genética , Esporos BacterianosRESUMO
"Fast-charging" lithium-ion batteries have gained a multitude of attention in recent years since they could be applied to energy storage areas like electric vehicles, grids, and subsea operations. Unfortunately, the excellent energy density could fail to sustain optimally while lithium-ion batteries are exposed to fast-charging conditions. In actuality, the crystal structure of electrode materials represents the critical factor for influencing the electrode performance. Accordingly, employing anode materials with low diffusion barrier could improve the "fast-charging" performance of the lithium-ion battery. In this Review, first, the "fast-charging" principle of lithium-ion battery and ion diffusion path in the crystal are briefly outlined. Next, the application prospects of "fast-charging" anode materials with various crystal structures are evaluated to search "fast-charging" anode materials with stable, safe, and long lifespan, solving the remaining challenges associated with high power and high safety. Finally, summarizing recent research advances for typical "fast-charging" anode materials, including preparation methods for advanced morphologies and the latest techniques for ameliorating performance. Furthermore, an outlook is given on the ongoing breakthroughs for "fast-charging" anode materials of lithium-ion batteries. Intercalated materials (niobium-based, carbon-based, titanium-based, vanadium-based) with favorable cycling stability are predominantly limited by undesired electronic conductivity and theoretical specific capacity. Accordingly, addressing the electrical conductivity of these materials constitutes an effective trend for realizing fast-charging. The conversion-type transition metal oxide and phosphorus-based materials with high theoretical specific capacity typically undergoes significant volume variation during charging and discharging. Consequently, alleviating the volume expansion could significantly fulfill the application of these materials in fast-charging batteries.
RESUMO
The power conversion efficiency of metal halide perovskite solar cells (PSCs) has increased dramatically in recent years, but there are still major bottlenecks in the commercial application of such materials, including intrinsic instability caused by external stimuli such as water, oxygen, and radiation, as well as local stress generated inside the perovskite and external stress caused by poor interlayer contact. However, some crucial sources of instability cannot be overcome by conventional encapsulation engineering. Among them, the tensile strain can weaken the chemical bonds in the perovskite lattice, thereby reducing the defects formation energy and activation energy of ion migration and accelerating the degradation rate of the perovskite crystal. This review expounds the latest in-depth understanding of microstrain in perovskite film from the thermodynamic sources and influences on the perovskite physicochemical structure and photoelectric performance. Furthermore, it also summarizes the effective strategies for strain regulation and interlayer contact performance improvement, which are conducive to the improvement of photovoltaic performance and internal stability of PSCs. Finally, we present a prospective outlook on how to achieve more stable and higher efficiency PSCs through strain engineering.
RESUMO
Oral insulin (INS) is predicted to have the most therapeutic advantages in treating diabetes to repress hepatic glucose production through its potential to mimic the endogenous insulin pathway. Many oral insulin delivery systems have been investigated. Layered double hydroxide (LDH) as an inorganic material has been widely used in drug delivery thanks to its appealing features such as good biocompatibility, low toxicity, and excellent loading capability. However, when used in oral drug delivery, the effectiveness of LDH is limited due to the acidic degradation in the stomach. In this study, to overcome these challenges, chitosan (Chi) and alginate (Alg) dual-coated LDH nanocomposites with the loading of insulin (Alg-Chi-LDH@INS) were developed by the layered-by-layered method for oral insulin delivery with dynamic size of ~ 350.8 nm, negative charge of ~ - 13.0 mV, and dispersity index 0.228. The insulin release profile was evaluated by ultraviolet-visible spectroscopy. The drug release profiles evidenced that alginate and chitosan coating partially protect insulin release from a burst release in acidic conditions. The analysis using flow cytometry showed that chitosan coating significantly enhanced the uptake of LDH@INS by Caco-2 cells compared to unmodified LDH and free insulin. Further in the in vivo study in streptozocin-induced diabetic mice, a significant hypoglycemic effect was maintained following oral administration with great biocompatibility (~ 50% blood glucose level reduction at 4 h). This research has thus provided a potential nanocomposite system for oral delivery of insulin.
Assuntos
Alginatos , Quitosana , Diabetes Mellitus Experimental , Hidróxidos , Hipoglicemiantes , Insulina , Nanocompostos , Animais , Insulina/administração & dosagem , Insulina/farmacocinética , Nanocompostos/química , Nanocompostos/administração & dosagem , Hidróxidos/química , Quitosana/química , Quitosana/administração & dosagem , Humanos , Administração Oral , Alginatos/química , Alginatos/administração & dosagem , Células CACO-2 , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Liberação Controlada de Fármacos , Masculino , Sistemas de Liberação de Medicamentos , Glicemia/efeitos dos fármacos , Glicemia/análise , Portadores de Fármacos/química , Portadores de Fármacos/administração & dosagemRESUMO
Developing non-fullerene acceptors (NFAs) by modifying the backbone, side chains and end groups is the most important strategy to improve the power conversion efficiency of organic solar cells (OSCs). Among numerous developed NFAs, Y6 and its derivatives are famous NFAs in the OSC field due to their good performance. Herein, in order to understand the mechanism of tuning the photovoltaic performance by modifying the Y6's center backbone, π-spacer and side-chains, we selected the PM6:Y6 OSC as a reference and systematically studied PM6:AQx-2, PM6:Y6-T, PM6:Y6-2T, PM6:Y6-O, PM6:Y6-1O and PM6:Y6-2O OSC systems based on extensive quantum chemistry calculations. The results indicate that introducing quinoxaline to substitute thiadiazole in the backbone induces a blue-shift of absorption spectra, reduces the charge transfer (CT) distance (Δd) and average electrostatic potential (ESP), and increases the singlet-triplet energy gap (ΔEST), CT excitation energy and the number of CT states in low-lying excitations. Inserting thienyl and dithiophenyl as π spacers generates a red-shift of absorption spectra, enlarges Δd and average ESP, and reduces ΔEST and the number of CT states. Introducing furo[3,2-b]furan for substituting one thieno[3,2-b]thiophene unit in the Y6's backbone causes a red-shift of absorption spectra and increases ΔEST, Δd and average ESP as well as CT excitation energy. Introducing alkoxyl as a side chain results in a blue-shift of absorption spectra, and increases ΔEST, Δd, average ESP, CT excitation energy and the number of CT states. The rate constants calculated using Marcus theory suggest that all the molecular modifications of Y6 reduce the exciton dissociation and charge recombination rates at the heterojunction interface, while introducing furo[3,2-b]furan and alkoxyl enlarges CT rates.
RESUMO
Skin wound healing is a multifaceted and intricate process involving inflammation, tissue proliferation, and scar formation, all of which are accompanied by the continuous application of mechanical forces. Mechanotransduction is the mechanism by which the skin receives and reacts to physical signals from the internal and external environment, converting them into intracellular biochemical signals. This intricate process relies on specialized proteins known as mechanotransducers, with Piezo1 being a critical mechanosensitive ion channel that plays a central role in this process. This article provides an overview of the structural characteristics of Piezo1 and summarizes its effects on corresponding cells or tissues at different stages of skin trauma, including how it regulates skin sensation and skin-related diseases. The aim is to reveal the potential diagnostic and therapeutic value of Piezo1 in skin trauma and skin-related diseases. Piezo1 has been reported to be a vital mediator of mechanosensation and transduction in various organs and tissues. Given its high expression in the skin, Piezo1, as a significant cell membrane ion channel, is essential in activating intracellular signaling cascades that trigger several cellular physiological functions, including cell migration and muscle contraction. These functions contribute to the regulation and improvement of wound healing.
Assuntos
Canais Iônicos , Mecanotransdução Celular , Membrana Celular/metabolismo , Movimento Celular , Mecanotransdução Celular/fisiologia , Transdução de Sinais , HumanosRESUMO
Type I interferon has great broad-spectrum antiviral ability and immunomodulatory function, and its receptors are expressed in almost all types of cells. Bovine viral diarrhea virus (BVDV) is an important pathogen causing significant economic losses in cattle. In this study, a recombinant expression plasmid carrying bovine interferon-α(BoIFN-α)gene was constructed and transformed into E. coli BL21 (DE3) competent cells. SDS-PAGE and Westernblotting analysis showed that the recombinant BoIFN-α protein (rBoIFN-α) was successfully expressed. It is about 36KD and exists in the form of inclusion body. When denatured, purified and renatured rBoIFN-α protein stimulated MDBK cells, the expression of interferon stimulating genes (ISGs) such as ISG15, OAS1, IFIT1, Mx1 and IFITM1 were significantly up-regulated, and reached the peak at 12 h (P< 0.001). MDBK cells were infected with BVDV with moi of 0.1 and 1.0, respectively. The virus proliferation was observed after pretreatment with rBoIFN-α protein and post-infection treatment. The results showed that the denatured, purified and renatured BoIFN-α protein had good biological activity and could inhibit the replication of BVDV in MDBK cells in vitro, which provided a basis for BoIFN-α as an antiviral drug, immune enhancer and clinical application of BVDV.
Assuntos
Vírus da Diarreia Viral Bovina , Interferon Tipo I , Animais , Bovinos , Escherichia coli , Interferon-alfa/genética , Interferon-alfa/farmacologia , Interferon-alfa/metabolismo , Antivirais/uso terapêutico , Interferon Tipo I/metabolismo , Vírus da Diarreia Viral Bovina/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/metabolismoRESUMO
Listeria monocytogenes is a Gram-positive bacterium frequently involved in food-borne disease outbreaks and is widely distributed in the food-processing environment. This work aims to depict the impact of nutrition deficiency on the survival strategy of L. monocytogenes both in planktonic and biofilm states. In the present study, cell characteristics (autoaggression, hydrophobicity and motility), membrane fatty acid composition of MRL300083 (Lm83) in the forms of planktonic and biofilm-associated cells cultured in TSB-YE and 10-fold dilutions of TSB-YE (DTSB-YE) were investigated. Additionally, the relative expression of related genes were also determined by RT-qPCR. It was observed that cell growth in different bacterial life modes under nutritional stress rendered the cells a distinct phenotype. The higher autoaggression (AAG) and motility of the planktonic cells in DTSB-YE is associated with better biofilm formation. An increased proportion of unsaturated fatty acid/saturated fatty acid (USFA/SFA) indicates more fluidic biophysical properties for cell membranes of L. monocytogenes in planktonic and biofilm cells in DTSB-YE. Biofilm cells produced a higher percentage of USFA and straight fatty acids than the corresponding planktonic cells. An appropriate degree of membrane fluidity is crucial for survival, and alteration of membrane lipids is an essential adaptive response. The adaptation of bacteria to stress is a multifactorial cellular process, the expression of flagella-related genes fliG, fliP, flgE and the two-component chemotactic system cheA/Y genes of planktonic cells in DTSB-YE significantly increased compared to that in TSB-YE (p < 0.05). This study provides new information on the role of the physiological adaptation and gene expression of L. monocytogenes for planktonic and biofilm growth under nutritional stress.
Assuntos
Ácidos Graxos , Listeria monocytogenes , Ácidos Graxos/metabolismo , Microbiologia de Alimentos , Plâncton/genética , Biofilmes , Expressão GênicaRESUMO
An antibiotic produced by Paenibacillus polymyxa 7F1 was studied. The 7F1 strain was isolated from the rhizosphere of a wheat field. Response surface methodology was used to optimize the physicochemical parameters. The strain showed broad-spectrum activity against several plant pathogens. Identification of the strain was realized based on 16s rRNA gene and gyrB gene sequencing. The antibiotic was optimized by one-factor-at-a-time (OFAT) and response surface methodology (RSM) approaches. The suitable antibiotic production conditions were optimized using the one-factor-at-a-time method. The individual and interaction effects of three independent variables: culture temperature, initial pH, and culture time, were optimized by Box-Behnken design. The 16SrRNA gene sequence (1239 nucleotides) and gyrB gene (1111 nucleotides) were determined for strain 7F1 and shared the highest identities to those of Paenibacillus polymyxa. The results showed the optimal fermentation conditions for antibiotics produced by Paenibacillus polymyxa 7F1 were a culture temperature of 38 °C, initial pH of 8.0, and culture time of 8 h. The antibiotics produced by Paenibacillus polymyxa 7F1 include lipopeptides such as iturin A and surfactin. The results provide a theoretical basis for the development of bacteriostatic biological agents and the control of mycotoxins.
Assuntos
Fusarium , Paenibacillus polymyxa , Paenibacillus polymyxa/genética , Fusarium/genética , Antibacterianos , RNA Ribossômico 16S/genética , FermentaçãoRESUMO
Dysregulated epigenetic modifications play a critical role in cancer development where TRMT112 is a member of the transfer RNA (tRNA) methyltransferase family. Till now, no studies have revealed the linkage between TRMT112 expression and diverse types of tumors. Based on TCGA data, we first probed into the relation between TRMT112 and prognosis and the potential role of TRMT112 in tumor microenvironment across 33 types of tumor. TRMT112 presented with increased expression in most cancers, which was significantly prognostic. Furthermore, TRMT112 was associated with tumor-associated fibroblasts in a variety of cancers. Additionally, a positive relationship was identified between TRMT112 expression and multiple tumor-related immune infiltrations, such as dendritic cells, CD8+ T cells, macrophages, CD4+ T cells, neutrophils, and B cells in lung adenocarcinoma and breast invasive carcinoma. In summary, our results suggest that TRMT112 might be a potential prognostic predictor of cancers and involved in regulating multiple cancer-related immune responses to some extent.
RESUMO
Oncolytic viral therapy is a promising treatment approach for a variety of tumor forms. Although a number of studies have demonstrated that the pseudorabies virus (PRV) may be applied as an oncolytic carrier, the anti-colorectal cancer impact of the virus and the mechanism of its cytotoxic effect remain elusive. In this study, the replication capacity and cell activity of PRV attenuated live vaccines Bartha K61 and HB98 in HCT-8 cells in vitro were investigated. Next, the antitumor ability and safety were evaluated in a mouse model of HCT-8 tumor transplantation. Both PRV strains were able to suppress tumor growth and HB98 showed higher safety and efficiency than the Bartha K61 strain. Finally, flow cytometry and immunohistochemistry examination were performed to investigate its possible cytotoxic mechanism. The results showed that PRV inhibited tumor proliferation both in vitro and in vivo by inducing apoptosis. In summary, our study discovered for the first time that the live attenuated PRV has an oncolytic effect on HCT-8 cells with high efficacy and safety.
RESUMO
BACKGROUND: The outbreak of Lumpy skin disease (LSD) in cattle caused by LSD virus (LSDV) was first reported in August 2019 in China. Since then, several LSD outbreaks have been reported in seven different provinces of China. Until now, several Lumpy skin disease virus (LSDV) strains from China have been reported and sequenced including LSDV/Xinjiang/2019 (MN598005.1), China/GD01/2020 (MW355944.1), and LSDV/Hongkong/2021 (MW732649.1). In October 2020, more than 1,700 cattle imported from Chile arrived in Xilingol, Inner Mongolia, and were diagnosed with LSD. Currently, limited data on the origin of the virus is available. METHODS: Nucleotide sequences of the ORF11, ORF36, ORF74, ORF117, ORF126 genes and the complete genome of LSDV strains and isolates were downloaded from NCBI database. MEGA7.0 was used to perform phylogenetic analysis with Neighbor-Joining (NJ). DNASTAR software is used to analyze homologous comparison analysis with related genes of reference strains included in Genbank. RESULTS: Compared with other strains isolated from China, the results of full genome sequence analysis showed the LSDV/NMG/2020 strain belonged to the recombinant strains. The LSDV/NMG/2020 strain is different from the current LSDV field isolates in Africa, the Middle East, Europe, and the newly emerged LSDV Russia variants. Based on the identities of P32, RPO30, EEV, GPCR and LSDV117 genes (99.8%, 99%, 99.8%, 99% and 98.7%), the sub-cluster recombinant containing LSDV/NMG/2020 strain is phylogenetically closer to the Russia strain (Saratov/2017). CONCLUSIONS: In this study, we reported a new isolated LSDV strain named LSDV/NMG/2020. The results of genomic characterization and phylogenetic analysis demonstrated that the LSDV/NMG/2020 isolate was a vaccine-like recombinant strain.
Assuntos
Doenças dos Bovinos , Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/veterinária , Doença Nodular Cutânea/epidemiologia , FilogeniaRESUMO
The water body environment is related to ecological and human health. Adsorption is an effective means to remove pollutants from water bodies. Currently, the common adsorbents suffer from disadvantages such as structural instability and poor adsorption performance under acidic conditions, which not only affect the adsorption efficiency but also cause secondary pollution of water bodies. In this study, a novel aminated multiwalled carbon nanotube-doped flower-like nanocomposite was designed, where the anionic or neutral groups were protonated under acidic conditions, and it displayed a higher adsorption capacity for dyes by ion exchange, represented by methylene blue (MB) and rhodamine B (RB). WSe2 in the composite increases its adsorption sites. The adsorption efficiency of pollutants in acidic wastewater was enhanced while avoiding secondary contamination. The synthesized composites showed maximum adsorptions of 27.55 and 27.47 mg/g for MB and RB, respectively. The current work offers a novel approach to treating acidic wastewater.
Assuntos
Nanotubos de Carbono , Poluentes Químicos da Água , Adsorção , Corantes/química , Humanos , Cinética , Fenômenos Magnéticos , Azul de Metileno/química , Nanotubos de Carbono/química , Águas Residuárias , Água , Poluentes Químicos da Água/análiseRESUMO
Akt has emerged as an exciting target in oncology due to its critical roles in proliferation, survival, metabolism, metastasis, and invasion in tumor cells. Herein, we describe the discovery and optimization of a series of ATP-competitive Akt inhibitors that possess new chemical scaffolds and exhibit potent enzymatic activities and improved in vivo pharmacokinetic profiles. Remarkably, NTQ1062 (compound 22b) exhibited potent antitumor efficacies in vitro and in vivo, which was accomplished through the optimization of the hinge binder region and the linkage. Subsequent studies of NTQ1062 demonstrated that it possesses good oral pharmacokinetic characteristics and dose-dependent pharmacodynamic effects on downstream biomarkers. In addition, NTQ1062 exhibits a robust antitumor efficacy in xenograft models in which the PI3K-Akt-mTOR pathway was activated. Based on its ideal druglike properties, NTQ1062 is currently being evaluated in a phase I clinical trial for the treatment of advanced solid tumors (CTR20211999).
Assuntos
Antineoplásicos , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Chromobox protein homolog 3 (CBX3) has been recognized as a member of the heterochromatin protein 1 family and participate in transcriptional activation or inhibition, cell differentiation and growth. Despite more and more evidence shows that CBX3 has a critical function in the development of some tumors, no systematic extensive analysis of CBX3 has been reported. Thus, we intended to examine the prognostic significance of CBX3 in 33 tumors and investigate its potential immune function. We employed several bioinformatics methods to explore the potential carcinogenic impact of CBX3 premised on the data sets collected from tumor genome maps, human protein maps, cBioPortal, and genotype tissue expression. The approaches include assessing the link between CBX3 and prognosis of different tumors, immune cell infiltration, micro-satellite instability (MSI), DNA methylation, and tumor mutational burden (TMB). The outcomes illustrated that CBX3 was increasingly expressed in 29 tumors. Moreover, CBX3 exhibited a negative correlation with the prognosis of many tumors. The expression of CBX3 was linked to MSI in 12 tumors and TMB in 16 tumors. In 24 tumors, the expression of CBX3 was linked to DNA methylation. Moreover, the CBX3 expression exhibited a negative relationship with the infiltration level of the majority of immune cells, but showed a positive link to T gamma delta cells, central memory T cells, and T helper cells, especially when invading breast carcinoma, thymic carcinoma, colon carcinoma, cutaneous melanoma, endometrial carcinoma, and lung squamous carcinoma. Our research indicates that CBX3 might be used as a prognostic indicator for different malignant tumors due to its function in tumor genesis as well as tumor immunity.