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1.
Nature ; 629(8011): 286, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38714811
2.
Polymers (Basel) ; 16(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38611153

RESUMO

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

3.
Molecules ; 29(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38338430

RESUMO

(1) Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the second most common cause of cancer death. However, effective anti-CRC drugs are still lacking in clinical settings. This article investigated the anti-proliferative effect of involucrasin B on CRC Caco-2 cells. (2) Methods: This study employed a sulforhodamine B (SRB) method, colony formation experiments, flow cytometry, FastFUCCI assay, dual luciferase assay, and Western blot analysis for the investigation. (3) Results: The SRB method and colony formation experiments showed that involucrasin B exhibited an inhibitory effect on the Caco-2 cells cultured in vitro. Subsequently, the flow cytometry, FastFUCCI assay, and Western blotting results showed that involucrasin B induced cell cycle arrest in the G1 phase dose-dependently. Involucrasin B significantly enhanced the TGFß RII protein level and SMAD3 phosphorylation, thus inhibiting the expression of CDK4 and cyclin D1 and causing G1 cell cycle arrest. (4) Conclusion: This study shows that involucrasin B exerts its anti-proliferative effect by regulating the TGFß/SMAD2-3-4 pathway to cause G1 cycle arrest in Caco-2 cells.


Assuntos
Fator de Crescimento Transformador beta , Humanos , Células CACO-2 , Fosforilação , Pontos de Checagem da Fase G1 do Ciclo Celular , Proliferação de Células , Fator de Crescimento Transformador beta/farmacologia , Linhagem Celular Tumoral , Proteína Smad2
4.
PLoS Pathog ; 20(1): e1011823, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38236820

RESUMO

A variety of coordinated host-cell responses are activated as defense mechanisms against pore-forming toxins (PFTs). Bacillus thuringiensis (Bt) is a worldwide used biopesticide whose efficacy and precise application methods limits its use to replace synthetic pesticides in agricultural settings. Here, we analyzed the intestinal defense mechanisms of two lepidopteran insect pests after intoxication with sublethal dose of Bt PFTs to find out potential functional genes. We show that larval intestinal epithelium was initially damaged by the PFTs and that larval survival was observed after intestinal epithelium regeneration. Further analyses showed that the intestinal regeneration caused by Cry9A protein is regulated through c-Jun NH (2) terminal kinase (JNK) and Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. JAK/STAT signaling regulates intestinal regeneration through proliferation and differentiation of intestinal stem cells to defend three different Bt proteins including Cry9A, Cry1F or Vip3A in both insect pests, Chilo suppressalis and Spodoptera frugiperda. Consequently, a nano-biopesticide was designed to improve pesticidal efficacy based on the combination of Stat double stranded RNA (dsRNA)-nanoparticles and Bt strain. This formulation controlled insect pests with better effect suggesting its potential use to reduce the use of synthetic pesticides in agricultural settings for pest control.


Assuntos
Bacillus thuringiensis , Praguicidas , Animais , Bacillus thuringiensis/genética , Janus Quinases/genética , Tirosina , Endotoxinas/genética , Insetos , Spodoptera/genética , Larva , Praguicidas/farmacologia , Regeneração , Proteínas de Bactérias/farmacologia , Proteínas de Bactérias/genética , Proteínas Hemolisinas/farmacologia , Proteínas Hemolisinas/genética , Plantas Geneticamente Modificadas , Controle Biológico de Vetores/métodos
5.
J Agric Food Chem ; 72(2): 1321-1329, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38175929

RESUMO

Bacillus thuringiensis Cry9 proteins show high insecticidal activity against different lepidopteran pests. Cry9 could be a valuable alternative to Cry1 proteins because it showed a synergistic effect with no cross-resistance. However, the pore-formation region of the Cry9 proteins is still unclear. In this study, nine mutations of certain Cry9Aa helices α3 and α4 residues resulted in a complete loss of insecticidal activity against the rice pest Chilo suppressalis; however, the protein stability and receptor binding ability of these mutants were not affected. Among these mutants, Cry9Aa-D121R, Cry9Aa-D125R, Cry9Aa-D163R, Cry9Aa-E165R, and Cry9Aa-D167R are unable to form oligomers in vitro, while the oligomers formed by Cry9Aa-R156D, Cry9Aa-R158D, and Cry9Aa-R160D are unstable and failed to insert into the membrane. These data confirmed that helices α3 and α4 of Cry9Aa are involved in oligomerization, membrane insertion, and toxicity. The knowledge of Cry9 pore-forming action may promote its application as an alternative to Cry1 insecticidal proteins.


Assuntos
Bacillus thuringiensis , Inseticidas , Animais , Bacillus thuringiensis/química , Inseticidas/química , Endotoxinas/genética , Endotoxinas/toxicidade , Endotoxinas/química , Domínios Proteicos , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias/farmacologia , Proteínas de Bactérias/toxicidade , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/toxicidade , Proteínas Hemolisinas/química , Larva/metabolismo
6.
Mol Neurobiol ; 61(1): 533-540, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37642934

RESUMO

Hypoxic-ischemic encephalopathy (HIE) is a complex pathophysiological process with multiple links and factors. It involves the interaction of inflammation, oxidative stress, and glucose metabolism, and results in acute and even long-term brain damage and impairment of brain function. Calpain is a family of Ca2+-dependent cysteine proteases that regulate cellular function. Calpain activation is involved in cerebral ischemic injury, and this involvement is achieved by the interaction among Ca2+, substrates, organelles, and multiple proteases in the neuronal necrosis and apoptosis pathways after cerebral ischemia. Many calpain inhibitors have been developed and tested in the biochemical and biomedical fields. This study reviewed the potential role of calpain in the treatment of HIE and related mechanism, providing new insights for future research on HIE.


Assuntos
Hipóxia-Isquemia Encefálica , Humanos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/metabolismo , Calpaína/metabolismo , Necrose/tratamento farmacológico , Infarto Cerebral/tratamento farmacológico
7.
Cancer Chemother Pharmacol ; 93(1): 31-39, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37740797

RESUMO

BACKGROUND: Camrelizumab combined with chemotherapy is approved across tumor types. However, only a fraction of patients benefits from immunotherapy, and biomarkers such as the expression of PD-L1, tumor mutational burden, and CXCL11 are expensive and suboptimal specificity for cancer patients. An exposure-response (E-R) relationship has been reported in many immune checkpoint inhibitors (ICIs), and the trough concentrations and other drug exposure metrics are broadly used to guide dosing decisions, assess exposure-outcomes relationships, and ultimately predict outcomes based on those relationships. However, the potential use of trough concentration levels for camrelizumab is still not clear. METHODS: Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration. RESULTS: We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05). CONCLUSIONS: Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.


Assuntos
Anticorpos Monoclonais Humanizados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Pulmonares , Humanos , Idoso , Neoplasias Pulmonares/tratamento farmacológico , População do Leste Asiático , Albuminas
8.
Health Aff (Millwood) ; 42(5): 615-621, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37126743

RESUMO

The extent to which concentration in the health insurance market affects negotiated prices paid to hospitals is of high interest to policy makers. We examined the association between insurer market share and hospital prices, using a new source of data obtained through the federal Hospital Price Transparency initiative. We found that the market-leading insurer in the least competitive (most concentrated) insurance markets pays 15 percent less to hospitals than the market-leading insurer in the most competitive (least concentrated) markets. We also found the price relationship to be more pronounced for for-profit hospitals than for not-for-profit hospitals. Our results invite the question of whether dominant insurers are passing savings on to employers in the form of lower premiums.


Assuntos
Competição Econômica , Seguradoras , Humanos , Estados Unidos , Seguro Saúde , Hospitais , Negociação/métodos
9.
Front Psychol ; 14: 1135658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895756

RESUMO

Recent academic attention on educational involution in China underpins the need for a valid and reliable instrument to precisely measure college students' academic involution behaviors. Seeing the scarcity of a proper instrument, the current study attempted to analyze the item-level psychometric properties of the newly developed Academic Involution Scale for College Students (AISCS) in China by using a Rasch model. A total of 637 college students in a public university in northern China participated in the study. Data were examined with respect to unidimensionality, rating scale functioning, item fit statistics, item polarity, item- and person-level reliability and separation, item hierarchy and invariance across educational background with Winsteps. The results show that AISCS was a single unidimensional construct with good psychometric properties. Although two items demonstrated differential item functioning, it is plausible given the differences between assessment methods for undergraduates and postgraduates. Limitations and future research directions with regard to sample selection, inclusion of more validity evidence and adding prospective additional academic involution were discussed.

10.
Front Psychol ; 14: 1062517, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935997

RESUMO

There is a gradual increase in the use of e-feedback in higher education, but issues regarding learners' anxiety remain unresolved. In light of the learners' anxiety, e-feedback would essentially become a formality if they are not proactive in providing constructive feedback. This action research examines three cycles of e-feedback activities performed by 12 doctoral students in an academic writing course in a public university in Macau, China. Specifically, the e-feedback activity involved a comprehensive use of various new educational technology tools, namely Moodle, WeChat and Rain Classroom. This study reveals that the causes of students' anxiety when using e-feedback are multi-layered, mainly from the use of smartphones as a communication medium for conducting formal learning activities and the lack of interpersonal and English skills for conveying their thoughts when providing e-feedback. The traditional Chinese culture about the importance of "face" and interpersonal harmony also has impacts on learners' e-feedback delivery. These findings shed new lights on pedagogical practice in higher education.

11.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166586, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36374802

RESUMO

Lenvatinib, a multitarget tyrosine kinase inhibitor (TKI), increases the incidence of severe hypertension and thus the incidence of cardiovascular complications. Inhibition of ferroptosis, a newly recognized type of cell death, alleviates endothelial dysfunction. Here, we report that lenvatinib-induced hypertension is associated with ferroptosis of endothelial cells. RNA sequencing (RNA-seq) showed that lenvatinib led to ferroptosis of endothelial cells and that administration of mouse with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, dramatically ameliorated lenvatinib-induced hypertension and reversed lenvatinib-induced impairment of endothelium-dependent relaxation (EDR). Furthermore, lenvatinib significantly reduced glutathione peroxidase 4 (GPX4) expressions in the mouse aorta and human umbilical vein endothelial cells (HUVECs) and increased lipid peroxidation, lactate dehydrogenase (LDH) release, and malondialdehyde (MDA) levels in HUVECs. Immunofluorescence and Western blotting showed that lenvatinib significantly reduced Yes-associated protein (YAP) nuclear translocation but not cytoplasmic YAP expression in HUVECs. The data, generated from both in vivo and in vitro, showed that lenvatinib reduced total YAP (t-YAP) expression and increased the phosphorylation of YAP at both Ser127 and Ser397, without affecting YAP mRNA levels in HUVECs. XMU-MP-1 mediated YAP activation or YAP overexpression effectively attenuated the lenvatinib-induced decrease in GPX4 expression and increases in LDH release and MDA levels. In addition, overexpression of YAP in HUVECs ameliorated lenvatinib-induced decrease in the mRNA and protein levels of spermidine/spermine N (1)-acetyltransferase-1 (SAT1), heme oxygenase-1 (HO-1), and ferritin heavy chain 1 (FTH1). Taken together, our data suggest that lenvatinib-induced inhibition of YAP led to ferroptosis of endothelial cells and subsequently resulted in vascular dysfunction and hypertension.


Assuntos
Ferroptose , Hipertensão , Humanos , Camundongos , Animais , Pressão Sanguínea , Células Endoteliais da Veia Umbilical Humana , RNA Mensageiro
12.
Front Aging Neurosci ; 14: 1035086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425321

RESUMO

Transcranial Doppler (TCD) is a rapid and non-invasive diagnostic technique that can provide real-time measurements of the relative changes in cerebral blood velocity (CBV). Therefore, TCD is a useful tool in the diagnosis and treatment of clinical cerebrovascular diseases (CVDs). In this review, the basic principles of TCD and its application in CVD were outlined. Specifically, TCD could be applied to evaluate occlusive CVD, assess collateral circulation in patients with ischemic stroke, and monitor cerebral vascular occlusion before and after thrombolysis as well as cerebral vasospasm (VSP) and microembolization signals after aneurysmal subarachnoid hemorrhage (SAH). Moreover, TCD could predict short-term stroke and transient cerebral ischemia in patients with anterior circulation occlusion treated with endovascular therapy and in patients with anterior circulation vascular occlusion. Additionally, TCD not only could monitor blood velocity signals during carotid endarterectomy (CEA) or carotid artery stenting (CAS) but also allowed earlier intervention through early recognition of sickle cell disease (SCD). Presently, TCD is a useful prognostic tool to guide the treatment of CVD. On the one hand, TCD is more commonly applied in clinical research, and on the other hand, TCD has an increasing role in the management of patients. Collectively, we review the principles and clinical application of TCD and propose some new research applications for TCD.

13.
Front Psychol ; 13: 1038878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262446

RESUMO

This study examined the longitudinal reciprocal relations between students' grit and their perceptions of social relationships (teacher-student and peer relationships) in studying English as a foreign language (EFL). A total of 2,435 students from Grades 10-11 in China (Mage = 16.40 years old, 54.2% female) participated in the study on three occasions across 1 year. The three-wave cross-lagged analytic model results indicated that (a) peer relationship and grit reciprocally enhanced each other across both intervals; (b) the teacher-student relationship at Time 2 was influenced by Time 1 grit, but not vice versa. Nevertheless, the teacher-student relationship transactionally facilitated each other during the second interval (from Time 2 to Time 3). The multiple-group confirmatory factor analysis (MG-CFA) results indicated that such relations remained stable across gender. The study's findings contribute to ongoing research delineating the dynamic system between social relationships and grit in EFL learning. It also reveals that males and females benefit similarly during social communications with peers and their English language teachers. Implications for educational practices were discussed.

14.
Psychol Res Behav Manag ; 15: 2543-2559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124335

RESUMO

Background: In recent years, temporal leadership has gradually attracted academic attention. Purpose: This paper discussed the impact of temporal leadership on team innovation performance. Methodology: Through the sample analysis of 385 team members in 98 teams. The measurements of temporal leadership, team innovation performance, transactive memory system, and team reflection were used to measure the relationships between temporal leadership, transactive memory systems and team innovation performance. Findings/Results: It is found that temporal leadership has a positive impact on team innovation performance, which is transmitted through the credibility dimension and coordination dimension of transactive memory systems. Positive team reflection regulates the relationship between temporal leadership and transactive memory systems. Value: This paper reveals the specific impact mechanism of temporal leadership on team innovation performance and provides a new perspective on how to improve team innovation performance in limited time resources.

15.
Polymers (Basel) ; 14(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35745985

RESUMO

A series of novel crosslinked polyphosphazene-aromatic ether organic-inorganic hybrid microspheres with different structures were prepared via precipitation polycondensation between hexachlorocyclotriphosphazene (HCCP) and bisphenol monomers. The bisphenol monomers have different numbers of -CF3 in the side group, which correspond to distinct oligomeric species-absorbing mechanisms. The wetting behavior of the microsphere surface was evaluated using a water contact angle (CA) measurement, which increased with the increase in the content of -CF3 in polyphosphazene. We also investigated the effects of HCCP concentration and ultrasonic power on the morphology of the microspheres.

16.
Work ; 72(4): 1289-1298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35754248

RESUMO

BACKGROUND: The rapid development of science and technology and the swift improvement of people's material living standards enabled smartphones to be indispensable of people's daily lives. OBJECTIVE: The purpose of this paper was to examine the influence of self-control in adolescents' participation in physical activity on cell phone dependence. METHODS: The Physical Activity Rating Scale (PARS-3), the Self-Control Scale, and the Cell Phone Dependence Scale were used to measure the influence of self-control in adolescents' participation in physical activity on cell phone dependence among 649 adolescents. RESULTS: The results show: (1) There were significant differences (p < 0.01) in the physical activity levels of adolescents under different gender, birthplace, and education background. (2) Each dimensional variable of physical activity was negatively correlated with the cell phone dependence variable, and positively correlated with each variable of self-control, and the self-control variables were negatively correlated with cell phone dependence. (3) Self-control was partially mediating the effects of physical activity on cell phone dependence, with the mediating effect accounting for 39.68%. CONCLUSIONS: Adolescents' participation in physical exercise activities will improve self-control and ultimately reduce cell phone dependence. Curbing the negative and malignant events of cell phone addiction among adolescents, timely investigation of mobile phone and Internet addiction, pathological formation mechanisms and intervention measures are important measures to reshape the healthy lifestyle of adolescents and have great practical significance for the prosperity and development of families, society, nation and country.


Assuntos
Comportamento Aditivo , Telefone Celular , Autocontrole , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Exercício Físico , Humanos , Smartphone
17.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34864886

RESUMO

Gene expression is directly controlled by transcription factors (TFs) in a complex combination manner. It remains a challenging task to systematically infer how the cooperative binding of TFs drives gene activity. Here, we quantitatively analyzed the correlation between TFs and surveyed the TF interaction networks associated with gene expression in GM12878 and K562 cell lines. We identified six TF modules associated with gene expression in each cell line. Furthermore, according to the enrichment characteristics of TFs in these TF modules around a target gene, a convolutional neural network model, called TFCNN, was constructed to identify gene expression level. Results showed that the TFCNN model achieved a good prediction performance for gene expression. The average of the area under receiver operating characteristics curve (AUC) can reach up to 0.975 and 0.976, respectively in GM12878 and K562 cell lines. By comparison, we found that the TFCNN model outperformed the prediction models based on SVM and LDA. This is due to the TFCNN model could better extract the combinatorial interaction among TFs. Further analysis indicated that the abundant binding of regulatory TFs dominates expression of target genes, while the cooperative interaction between TFs has a subtle regulatory effects. And gene expression could be regulated by different TF combinations in a nonlinear way. These results are helpful for deciphering the mechanism of TF combination regulating gene expression.


Assuntos
Aprendizado Profundo , Fatores de Transcrição , Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Ann Thorac Surg ; 113(4): 1325-1332, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33961817

RESUMO

BACKGROUND: This study evaluated the effects of single low-dose preoperative methylprednisolone (MP) on the immunologic function and postoperative pain of patients undergoing elective video-assisted thoracoscopic surgery under general anesthesia. METHODS: The study randomly assigned 81 patients who underwent elective video-assisted thoracoscopic surgery to the MP group or the control group. The T-lymphocyte subsets of CD3+, CD4+, and CD8+, and the CD4+/CD8+ ratio at T0 (before anesthesia), T1 (after operation), and T2 (24 hours after operation) were recorded. Also recorded were postoperative rest and cough pain scores and postoperative adverse effects and surgery complications. RESULTS: Compared with T0, the levels of CD3+ and CD4+ subsets and CD4+/CD8+ were significantly decreased, and the level of CD8+ was increased after surgery in both groups. There was no significant difference in the variation of CD3+, CD4+, CD8+, and CD4+/CD8+ between the MP group and the control group. The rest and cough pain of patients in the MP group was significantly lower compared with the control group at 2, 4, 6, and 24 hours after surgery. The incidences of nausea and vomiting and dizziness were also significantly higher in the control group than those in the MP group. CONCLUSIONS: A preoperative single low dose of MP (1 mg/kg) had no effect on immune function but had effective analgesic effects and could reduce the incidence of dizziness and postoperative nausea and vomiting.


Assuntos
Metilprednisolona , Cirurgia Torácica , Tosse , Tontura , Humanos , Imunidade , Metilprednisolona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Cirurgia Torácica Vídeoassistida
19.
Front Psychol ; 13: 1048143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36710807

RESUMO

The purpose of the current study is to propose and examine a comprehensive model that uses motivational and self-regulated variables to explain factors affecting environment management in technology-based physics learning among Chinese secondary school students. Data were collected from 726 grade-eight secondary school students in Southeast China, who were learning physics. Structural equation modeling was used to analyze the relationships among students' goal orientations, environment management, and time management. Results suggest that students were more likely to manage their environment if they had learning-oriented goals and if they managed their time, but they were less likely to do so if they had social-oriented goals. Implications for teachers' technology integration in physics class were discussed.

20.
Insect Biochem Mol Biol ; 137: 103635, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34363975

RESUMO

Resistance evolution of target pests reduces efficacy of Bacillus thuringiensis Cry toxins used in insect-pest control. Mutations in Cadherin (CAD) or ATP-binding cassette (ABC) transporters genes are linked to Cry resistance in different pests. Also, it has been shown that ABCC2 and CAD have synergistic interaction on Cry toxicity when co-express in cell lines, which we confirmed here by Helicoverpa armigera HaABCC2 and HaCAD expression in Hi5 cells. To confirm that CAD and ABC transporters interact in vivo, we constructed nearly H. armigera isogenic lines such as LFC2 and 96CAD strains, linked to HaABCC2 and HaCAD mutations that showed 512- and 396-fold Cry1Ac resistance-ratios, respectively. Interestingly, Fusion-1 strain linked to both HaABCC2 and HaCAD mutations, showed 6273-fold resistance-ratio, significantly higher than the single mutant strains. To confirm the interaction of HaABCC2 and CAD in Cry1Ac resistance, we analyzed the Cry1Ac susceptibility in CRISPR/Cas9 knockdown strains, C2-KO (ABCC2-gene knockout-strain) and CAD-KO (CAD-gene knockout-strain), that showed 112- and 531-fold Cry1Ac resistance-ratios, respectively. However, the resistance-ratio of Fusion-2 strain obtained from crossing C2-KO and CAD-KO strains, was only 816-fold. The analysis of HaABCC3 gene transcript levels showed nearly 4-fold lower expression in LFC2 and Fusion-1 strains compared to the susceptible strain, suggesting that additional mutations in these strains resulted in low HaABCC3 expression, which contribute to their enhanced Cry1Ac resistance. Our data show that the CAD and ABCC2/ABCC3 interact synergistically to induce high Cry1Ac resistance in H. armigera. These results can be helpful for Bt resistance monitoring and pest management.


Assuntos
Toxinas de Bacillus thuringiensis/farmacologia , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Mariposas/efeitos dos fármacos , Mariposas/genética , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Bacillus thuringiensis/química , Caderinas/genética , Caderinas/metabolismo , Proteínas de Insetos/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento , Mariposas/crescimento & desenvolvimento , Mutação
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