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1.
Scand J Immunol ; 99(5): e13356, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38605549

RESUMO

In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in-depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra-tumoural T-cell ratios or in the functionality of T-cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN-γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single-agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro-immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T-cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T-cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T-cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti-tumour immunity through the application of innovative therapeutic strategies.


Assuntos
Anticorpos , Mucina-1 , Neoplasias , Receptor de Morte Celular Programada 1 , Vacinas de DNA , Animais , Camundongos , Anticorpos/metabolismo , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Mucina-1/genética , Neoplasias/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral
2.
Protein Expr Purif ; 221: 106518, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38821452

RESUMO

Chiral amino acids and their deamination products, α-keto acids, have important applications in food, medicine, and fine chemicals. In this study, two l-amino acid deaminase genes from Proteus mirabilis, PM473 of type Ⅰ and PM471 of type Ⅱ were cloned and expressed in Escherichia coli respectively, expected to achieve the chiral separation of amino acids. Extensive substrate preference testing showed that both deaminases had catalytic effects on the d-amino acid component of the D, l-amino acids, and PM473 has a wider catalytic range for amino acids. When D, L-Cys was used as the substrate, all L-Cys components and 75.1 % of D-Cys were converted to mercapto pyruvate, and the remaining D-Cys was a single chiral enantiomer. Molecular docking analysis showed that the interaction between the substrate and the key residues affected the stereoselectivity of enzymes. The compatibility of hydrophobicity between the binding pocket and substrate may be the basic factor that affects the substrate selectivity. This work provides an alternative method for the production of α-keto acids and the resolution of chiral amino acids.


Assuntos
Escherichia coli , Cetoácidos , Simulação de Acoplamento Molecular , Proteus mirabilis , Proteus mirabilis/enzimologia , Proteus mirabilis/genética , Cetoácidos/metabolismo , Cetoácidos/química , Escherichia coli/genética , Escherichia coli/metabolismo , Estereoisomerismo , Especificidade por Substrato , Aminoácidos/genética , Aminoácidos/química , Aminoácidos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/biossíntese , Clonagem Molecular
3.
Org Biomol Chem ; 22(5): 932-939, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38180250

RESUMO

A rapid and mild protocol for the exhaustive deoxygenation of various aromatic ketones to corresponding alkanes was described, which was mediated by TiCl4 and used ammonia borane (AB) as the reductant. This reduction protocol applies to a wide range of substrates in moderate to excellent yields at room temperature. The gram-scale reaction and syntheses of some key building blocks for SGLT2 inhibitors demonstrated the practicability of this methodology. Preliminary mechanistic studies revealed that the ketone is first converted into an alcohol, which then undergoes a carbocation to give the alkane via hydrogenolysis.

4.
Arch Insect Biochem Physiol ; 115(4): e22114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659314

RESUMO

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.


Assuntos
Blattellidae , Proteínas de Insetos , Oviposição , Pigmentação , Interferência de RNA , Animais , Blattellidae/genética , Blattellidae/fisiologia , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Masculino , Pigmentação/genética , Corte , Melaninas/metabolismo , Comportamento Sexual Animal
5.
J Nanobiotechnology ; 22(1): 375, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926721

RESUMO

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.


Assuntos
Carcinoma Hepatocelular , Cobre , Neoplasias Hepáticas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Cobre/química , Cobre/farmacologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Fotoquimioterapia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/química , Porfirinas/química , Porfirinas/farmacologia , Clorofilídeos , Glutationa/metabolismo , Nanopartículas/química , Catálise , Nanopartículas Metálicas/química , Liberação Controlada de Fármacos , Camundongos Nus , Antineoplásicos/farmacologia , Antineoplásicos/química
6.
Bull Entomol Res ; 114(2): 271-280, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38623047

RESUMO

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.


Assuntos
Blattellidae , Melaninas , Pigmentação , Animais , Blattellidae/genética , Blattellidae/fisiologia , Masculino , Feminino , Pigmentação/genética , Melaninas/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Comportamento Sexual Animal , Interferência de RNA
7.
Cell Mol Biol (Noisy-le-grand) ; 69(3): 1-7, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37300695

RESUMO

Diffuse large B cell lymphoma (DLBCL) is a B cell neoplasm characterized by high PIM1 expression, which is responsible for poor prognosis. Activation-induced cytidine deaminase (AID) is closely linked to PIM1 hypermutation in DLBCL. Here, we found that the DNA methyltransferase 1 (DNMT1) level decreased with AID depletion in the DLBCL cell line SU-DHL-4, and increased significantly when AID was highly expressed. The double ablation of AID and DNMT1 contributed to increased PIM1 expression, which initiated faster DLBCL cell proliferation, whereas ten-eleven translocation family member 2 (TET2) decreased with AID deficiency and increased with AID overexpression in DLBCL cell line OCI-LY7. The double depletion of AID and TET2 was associated with decreased PIM1 levels and showed slower cell division. We suggest an alternative role of AID as a co-factor of DNA methylation cooperated with DNMT1, or of DNA demethylation associated with TET2 in modulating PIM1 expression. Our findings demonstrate that AID interacts with either DNMT1 or TET2 to form a complex to bind with a PIM1 promoter and thus is responsible for the modulation of PIM1 expression. These results provide insights into an alternative role of AID to DLBCL-associated genes.


Assuntos
Citidina Desaminase , Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-pim-1 , Humanos , Linhagem Celular , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Linfoma Difuso de Grandes Células B/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo
8.
Genomics ; 114(2): 110310, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35151840

RESUMO

The German cockroach Blattella germanica is an important urban insect pest worldwide. In many insects, chemosensation is essential for guiding their behaviors for survival. Although a large number of chemosensory-related genes have been identified in B. germanica, little information on tissue-specific and developmental expression patterns has not been uncovered yet. In this study, we performed transcriptome analysis of different B. germanica tissues to reveal novel chemosensory proteins (CSPs) and sensory neuron membrane proteins (SNMPs). In addition, a phylogenetic tree and gender-specific expression of multiple chemosensory gene families have been analyzed. We identified three CSPs genes (BgerCSP11, BgerCSP12, and BgerCSP13) and five SNMP genes in B. germanica. Tissue-specific expression profiling showed that CSP1, 8, and 9 exhibited significant expression levels in both adult and 5th instar nymph antennae. The results have paved the way for further functional study of the chemosensory mechanism in B. germanica and provided potential insecticide targets.


Assuntos
Blattellidae , Receptores Odorantes , Animais , Blattellidae/genética , Blattellidae/metabolismo , Perfilação da Expressão Gênica , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos/genética , Filogenia , Receptores Odorantes/genética , Transcriptoma
9.
Nanotechnology ; 34(5)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36317264

RESUMO

A targeted drug delivery system was developed to accumulate specific drugs around tumor cells based on the redox, temperature, and enzyme synergistic responses of mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSN-NH2) and Doxorubicin (DOX) for tumor therapy were prepared and loaded into the pores of MSN- NH2 to obtain DOX@MSN(DM NPs). Hyaluronic acid (HA) was used as the backbone and disulfide bond was used as the linker arm to graft carboxylated poly (N-isopropylacrylamide)(PNIPAAm-COOH) to synthesize the macromolecular copolymer (HA-SS-PNIPAAm), which was modified to DM NPs with capped ends to obtain the nano-delivery system DOX@MSN@HA-SS-PNIPAAm(DMHSP NPs), and a control formulation was prepared in a similar way. DMHSP NPs specifically entered tumor cells via CD44 receptor-mediated endocytosis; the high GSH concentration (10 mM) of cells severed the disulfide bonds, the hyaluronidase sheared the capped HA to open the pores, and increased tumor microenvironment temperature due to immune response can trigger the release of encapsulated drugs in thermosensitive materials.In vitroandin vivoantitumor and hemolysis assays showed that DMHSP NPs can accurately target hepatocellular carcinoma cells with a good safety profile and have synergistic effects, which meant DMHSP NPs had great potential for tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Porosidade , Doxorrubicina/química , Dióxido de Silício/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Ácido Hialurônico/química , Dissulfetos , Portadores de Fármacos/química , Microambiente Tumoral
10.
Nature ; 532(7600): 522-6, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27096363

RESUMO

The CRISPR-Cas systems, as exemplified by CRISPR-Cas9, are RNA-guided adaptive immune systems used by bacteria and archaea to defend against viral infection. The CRISPR-Cpf1 system, a new class 2 CRISPR-Cas system, mediates robust DNA interference in human cells. Although functionally conserved, Cpf1 and Cas9 differ in many aspects including their guide RNAs and substrate specificity. Here we report the 2.38 Å crystal structure of the CRISPR RNA (crRNA)-bound Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1). LbCpf1 has a triangle-shaped architecture with a large positively charged channel at the centre. Recognized by the oligonucleotide-binding domain of LbCpf1, the crRNA adopts a highly distorted conformation stabilized by extensive intramolecular interactions and the (Mg(H2O)6)(2+) ion. The oligonucleotide-binding domain also harbours a looped-out helical domain that is important for LbCpf1 substrate binding. Binding of crRNA or crRNA lacking the guide sequence induces marked conformational changes but no oligomerization of LbCpf1. Our study reveals the crRNA recognition mechanism and provides insight into crRNA-guided substrate binding of LbCpf1, establishing a framework for engineering LbCpf1 to improve its efficiency and specificity for genome editing.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas Associadas a CRISPR/química , Proteínas Associadas a CRISPR/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Firmicutes/enzimologia , RNA Bacteriano/química , RNA Bacteriano/metabolismo , Sistemas CRISPR-Cas , Cristalografia por Raios X , Engenharia Genética , Modelos Moleculares , Conformação de Ácido Nucleico , Ligação Proteica , Estrutura Terciária de Proteína , Estabilidade de RNA , RNA Bacteriano/genética , RNA Guia de Cinetoplastídeos/química , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo , Especificidade por Substrato
11.
Ecotoxicol Environ Saf ; 230: 113147, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34979307

RESUMO

As the emerging contaminants, the environmental risks of drug-derived pollutants have attracted extensive attention. Citalopram (CTP) and mirtazapine (MTP) are commonly used as modern antidepressant drugs. Previous studies had proved that CTP and MTP entered the aquatic environment, but less reported the negative effects of the drugs on aquatic organisms. Herein, the effects on the feeding rate of Daphnia magna (D. magna) induced by psychotropic drugs CTP and MTP were investigated, which the possible mechanisms were analyzed with the oxidative stress and damage. Generally, the feeding rates of exposed D. magna under all concentrations of CTP and 1.03 mg/L of MTP were significantly decreased after exposure (p < 0.05 or p < 0.01). The inhibitory effect of CTP on the feeding rate of D. magna was time- and dose-dependent. The levels of reactive oxygen species (ROS) were particularly increased in D. magna after CTP and MTP exposure (p < 0.05 or p < 0.01). The level of antioxidant molecules glutathione S-transferase (GST) and the activity of scavenging enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) of D. magna were increased (p < 0.05 or p < 0.01). In consequence, the levels of malondialdehyde (MDA), protein carbonyl, and 8-hydroxydeoxyguanosine (8-OHdG) were increased (p < 0.05 or p < 0.01), which indicated oxidative damage caused by MTP and CTP, due to the imbalance of antioxidative stress system. These findings indicated that psychoactive drugs posed a high toxic threat to the aquatic organisms, and the aquatic environmental risks caused by using psychoactive drugs deserve more attention.

12.
Sensors (Basel) ; 22(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35271192

RESUMO

Unmanned aerial vehicles (UAVs) are increasingly used in instant delivery scenarios. The combined delivery of vehicles and UAVs has many advantages compared to their respective separate delivery, which can greatly improve delivery efficiency. Although a few studies in the literature have explored the issue of vehicle-assisted UAV delivery, we did not find any studies on the scenario of an UAV serving several customers. This study aims to design a new vehicle-assisted UAV delivery solution that allows UAVs to serve multiple customers in a single take-off and takes energy consumption into account. A multi-UAV task allocation model and a vehicle path planning model were established to determine the task allocation of the UAVs as well as the path of UAVs and the vehicle, respectively. The model also considered the impact of changing the payload of the UAV on energy consumption, bringing the results closer to reality. Finally, a hybrid heuristic algorithm based on an improved K-means algorithm and ant colony optimization (ACO) was proposed to solve the problem, and the effectiveness of the scheme was proven by multi-scale experimental instances and comparative experiments.


Assuntos
Aeronaves , Algoritmos , Fenômenos Físicos
13.
Molecules ; 27(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35335266

RESUMO

Hyperlipidemia is a chronic metabolic disease caused by the abnormal metabolism of lipoproteins in the human body. Its main hazard is to accelerate systemic atherosclerosis, which causes cerebrovascular diseases such as coronary heart disease and thrombosis. At the same time, although the current hypolipidemic drugs have a certain therapeutic effect, they have side effects such as liver damage and digestive tract discomfort. Many kinds of polysaccharides from natural resources possess therapeutic effects on hyperlipidemia but still lack a comprehensive understanding. In this paper, the research progress of natural polysaccharides on reducing blood lipids in recent years is reviewed. The pharmacological mechanisms and targets of natural polysaccharides are mainly introduced. The relationship between structure and hypolipidemic activity is also discussed in detail. This review will help to understand the value of polysaccharides in lowering blood lipids and provide guidance for the development and clinical application of new hypolipidemic drugs.


Assuntos
Hiperlipidemias , Hipolipemiantes , Humanos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Recursos Naturais , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico
14.
Environ Monit Assess ; 194(10): 723, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056993

RESUMO

During COVID-19, Shenyang implemented strict household isolation measures, resulting in a sharp reduction in anthropogenic emission sources, providing an opportunity to explore the impact of human activities on air pollution. The period from January to April of 2020 was divided into normal period, blockade period and resumption period. Combined with meteorological and pollutant data, mathematical statistics and spatial analysis methods were used to compare with the same period of 2015-2019. The results showed that PM2.5, PM10, NO2 and O3 increased by 32.6%, 13.2%, 4.65% and 22.7% in the normal period, among which the western area changed significantly. During the blockade period, the concentration of pollutants decreased by 35.79%, 35.87%, 32.45% and -4.84%, of which the central area changed significantly. During the resumption period, the concentration of pollutants increased by 21.8%, 8.7%, 5.7% and -6.3%, and the area with the largest change was located in the western. During the blockade period, a heavy pollution occurred with PM2.5 as the main pollutant. The WRF-Chem model and the HYSPLIT model were used to reproduce the pollution occurrence process. The result showed that winds circulated as zonal winds during the pollution process at high altitudes. These winds were controlled by straight westerly and weak northwesterly airflows in front of the high pressure, and the ground was located behind the warm low pressure. Weather conditions were relatively stable. Thus, high temperatures (average > 10 ℃), high humidity (40%-60%) and slow wind (2 m/s) conditions prevailed for a long time in the Shenyang area. The unfavorable meteorological conditions lead to the occurrence of pollution. The backward trajectory showed that the potential source areas were concentrated in the urban agglomeration around Shenyang, and sporadic contributions came from North Korea.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , COVID-19/epidemiologia , China/epidemiologia , Monitoramento Ambiental/métodos , Humanos , Material Particulado/análise
15.
Cancer Sci ; 112(7): 2679-2691, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33949040

RESUMO

BCR-ABL1 gene fusion associated with additional DNA lesions involves the pathogenesis of chronic myelogenous leukemia (CML) from a chronic phase (CP) to a blast crisis of B lymphoid (CML-LBC) lineage and BCR-ABL1+ acute lymphoblastic leukemia (BCR-ABL1+ ALL). The recombination-activating gene RAG1 and RAG2 (collectively, RAG) proteins that assemble a diverse set of antigen receptor genes during lymphocyte development are abnormally expressed in CML-LBC and BCR-ABL1+ ALL. However, the direct involvement of dysregulated RAG in disease progression remains unclear. Here, we generate human wild-type (WT) RAG and catalytically inactive RAG-expressing BCR-ABL1+ and BCR-ABL1- cell lines, respectively, and demonstrate that BCR-ABL1 specifically collaborates with RAG recombinase to promote cell survival in vitro and in xenograft mice models. WT RAG-expressing BCR-ABL1+ cell lines and primary CD34+ bone marrow cells from CML-LBC samples maintain more double-strand breaks (DSB) compared to catalytically inactive RAG-expressing BCR-ABL1+ cell lines and RAG-deficient CML-CP samples, which are measured by γ-H2AX. WT RAG-expressing BCR-ABL1+ cells are biased to repair RAG-mediated DSB by the alternative non-homologous end joining pathway (a-NHEJ), which could contribute genomic instability through increasing the expression of a-NHEJ-related MRE11 and RAD50 proteins. As a result, RAG-expressing BCR-ABL1+ cells decrease sensitivity to tyrosine kinase inhibitors (TKI) by activating BCR-ABL1 signaling but independent of the levels of BCR-ABL1 expression and mutations in the BCR-ABL1 tyrosine kinase domain. These findings identify a surprising and novel role of RAG in the functional specialization of disease progression in BCR-ABL1+ leukemia through its endonuclease activity.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Proteínas de Fusão bcr-abl/metabolismo , Proteínas de Homeodomínio/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Proteínas Nucleares/metabolismo , Hidrolases Anidrido Ácido/metabolismo , Animais , Crise Blástica/genética , Crise Blástica/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Progressão da Doença , Proteínas de Fusão bcr-abl/genética , Instabilidade Genômica , Xenoenxertos , Histonas/análise , Proteínas de Homeodomínio/genética , Humanos , Técnicas In Vitro , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Proteína Homóloga a MRE11/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico
16.
Opt Express ; 29(18): 29138-29148, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34615030

RESUMO

We report on the crystal growth, spectroscopic properties and laser performance of Tm3+-doped Bi4Si3O12 (BSO) crystal. The crystal was grown by the vertical Bridgeman method. The spectroscopic properties are investigated based on absorption and luminescence spectroscopy. Judd - Ofelt (JO) analysis is performed to calculate the spontaneous emission probabilities, branching ratio and the radiative lifetimes. The absorption spectrum, emission spectrum and gain cross-section spectra of Tm3+: BSO crystal are determined for the 2 µm transition. Luminescence decay kinetic of 3F4 upper level was analysed in detail. The continuous-wave 2 µm laser with a maximum output power of 650 mW and a slope efficiency of 29.7% is demonstrated for the first time. The beam quality factor (M2) of Tm3+: BSO laser was about 1.03 at the maximum output level.

17.
Opt Lett ; 46(20): 5244-5247, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34653163

RESUMO

Environmental factors include sample temperature, ambient gas composition, and pressure, which have a significant impact on the accuracy and stability of the analysis results of laser-induced breakdown spectroscopy (LIBS). In this study, a method for simultaneously correcting the influence of several environmental factors is proposed. When the calibration and application environment are different, only one sample is needed to be measured in the application environment to correct the influence of environmental factors, so that the calibration model can obtain good analytical accuracy in this environment. When using one to four samples to correct the influence of environmental factors, the application of the calibration models constructed under solid-state conditions at atmosphere pressure to analyze seven elements in molten alloys in vacuum demonstrated the average root mean square error of prediction (RMSEP) of 0.57%, 0.51%, 0.41%, and 0.30% respectively. The accuracy of using only one sample to correct the influence of environmental factors was much higher than using two samples to establish calibration models in the application environment. This proved the effectiveness of the developed method for reducing the difficulty and cost of calibration in the metallurgical processes.

18.
Pestic Biochem Physiol ; 171: 104726, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357547

RESUMO

Insect antennae play a fundamental role in perceiving and recognizing a broad spectrum of conventional semiochemicals and host plant-derived odors. As such, genes that are tightly associated with the antennae are thought to have olfactory-related roles related to signal transduction mechanisms. Several mechanisms suggest that enzymatic inactivation could contribute to the signal termination process, such as odorant-degrading enzymes (ODEs). To date, a few ODEs have been identified and characterized in detail in insect herbivores, but little is known about aldehyde oxidases (AOXs); moreover, direct in vivo experimental evidence is needed. AOXs are a major family of metabolic enzymes that oxidize a variety of aromatic aldehydes, and they may also play a significant role in detoxification and degradation of environmental chemical cues. Here, we report on the identification and characterization of a novel cDNA encoding the putative odorant-degrading enzyme, PxylAOX3, from the antennae of the diamondback moth, (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae). The purified recombinant protein showed a wide-range of substrate zymography oxidizing both sex pheromone compounds as well as plant-derived aldehydes with distinct activities. Our data suggest PxylAOX3 might be involved in the degradation of many structurally diverse aldehyde odorants. Furthermore, PxylAOX3 could participate in olfactory neuron protection by inactivation of redundant odorants and xenobiotic detoxification, making it a potential target for pesticide development as well.


Assuntos
Mariposas , Atrativos Sexuais , Aldeído Oxidase/genética , Animais , Mariposas/genética , Feromônios , Xenobióticos
19.
Ecotoxicol Environ Saf ; 197: 110573, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32278825

RESUMO

Antibiotics had been paid more and more attention to their toxicity to non-target aquatic organisms in the aquatic environment. As azithromycin (AZI) was an important antibiotic pollutant in water, its toxicity to aquatic organisms had been investigated. In this study, the potential aquatic ecological risk of AZI was identified by assessing the toxicity on the feeding behavior and physiological function of Daphnia magna (D. magna) under the different exposure pathways (aqueous phase exposure vs. food phase exposure). For the food Chlorella pyrenoidosa (C. pyrenoidosa), AZI could inhibit the growth and nutrition accumulation with concentration- and time-response relationship. For D. magna, the feeding behavior was inhibited by AZI under the aqueous phase exposure pathway. However, the feeding behavior was inhibited firstly and then reversed into promotion in the low and medium concentration groups and was continually promoted in the high concentration group under the food phase exposure pathway. The accumulation of polysaccharides and total protein were decreased in D. magna n the high concentration group under the aqueous phase exposure pathway, while the accumulation of polysaccharides and crude fat were decreased in the high concentration group under the food phase exposure pathway. The activity of amylase (AMS) and trypsin in D. magna were decreased after exposure to AZI under the aqueous phase exposure pathway. On the other hand, the activity of AMS in the medium and high concentration groups was decreased under the food phase exposure pathway, but the activity of trypsin was decreased in the medium concentration group and increased in the high concentration group. The levels of ROS in D. magna were also measured and increased in both exposure pathways except in the low concentration group under the food phase exposure pathway, indicating the oxidative stress injury of D. magna. Our results showed that AZI could affect the digestive enzyme activities and oxidative stress-antioxidative system, ultimately leading to the change of D. magna's feeding behavior and nutrition accumulation. These results also provided a comprehensive perspective to evaluate the toxic effects of non-lethal dose antibiotics to non-target aquatic organisms via different exposure pathways.


Assuntos
Azitromicina/toxicidade , Daphnia/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Nutrientes/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Azitromicina/metabolismo , Chlorella/metabolismo , Daphnia/metabolismo , Daphnia/fisiologia , Exposição Dietética/efeitos adversos , Exposição Ambiental/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/metabolismo
20.
Environ Monit Assess ; 193(1): 9, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33319343

RESUMO

To find out the characteristics and sources of atmospheric pollutants during heating period in Shenyang, the study investigated the temporal and spatial distribution of pollutants, using data of six typical atmospheric pollutants (SO2, NO2, PM10, PM2.5, O3, and CO) from November 2017 to March 2018 in 11 monitoring stations in Shenyang. These features were combined with the HYSPLIT model for backward trajectory simulation of heavily polluted weather. PM10 and PM2.5 are the main pollutants during heating period in Shenyang, with average concentrations of 90.26 µg/m3 and 56.92 µg/m3, respectively. The concentrations of various types of contaminants at the Taiyuan Street station were relatively high. PM10 and PM2.5 were relatively high in the southwestern area of Shenyang, gradually decreasing to the northeast. Only one heavy pollution event occurred during heating period in 2018. The results of the backward trajectory analysis of this heavy pollution event using HYSPLIT show that air masses from inland areas such as the southwest and northwest brought some particulate matter and atmospheric pollutants, which exacerbated Shenyang Air pollution in the city.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Monitoramento Ambiental , Calefação , Material Particulado/análise
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