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1.
Oncologist ; 29(7): e877-e886, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38537665

RESUMO

BACKGROUND: According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. METHODS: We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. RESULTS: In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P < .001). HER2E showed increased PCR rates compared to non-HER2E (P = .004). CONCLUSIONS: Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Adulto , Imuno-Histoquímica/métodos , Idoso , Estadiamento de Neoplasias
2.
Pest Manag Sci ; 80(4): 1681-1691, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38010617

RESUMO

BACKGROUND: The endoparasitoid Cotesia marginiventris (Cresson) is a promising biological control agent of the fall armyworm (FAW) Spodoptera frugiperda (Smith). Because the application of insecticides is one of the prime choices in pest management, we evaluated the sublethal and transgenerational effects of the five key insecticides-chlorantraniliprole, emamectin benzoate, spinetoram, Bacillus thuringiensis (Bt), and Mamestra brassicae nucleopolyhedrovirus (MbNPV)-on the parasitoid. RESULTS: Exposure to five insecticides at a concentration causing 10% mortality (LC10 ) caused hormetic effects in the parent generation (F0 ) by increasing the parasitism and reducing the immature duration. Interestingly, the hormetic response was also observed in the offspring generation indirectly exposed to the insecticides. Furthermore, insecticides increased the parasitism rate by 6.32-14.73% in the F1 generation, which was similar to that of the F0 generation (3.96-11.81%) compared with the control. No significant adverse effect was observed on the number of emerged parasitoids of the F1 and F2 generations. However, insecticides had a detrimental impact on body size and fecundity in the F1 and F2 generations, which showed a small body size with shorter hind tibiae and a significant reduction in the female ratio compared with the control; the exception was that chlorantraniliprole significantly improved the female ratio in the F2 generation. CONCLUSIONS: Five insecticides at LC10 induced transgenerational hormetic and sublethal effects on C. marginiventris. Our results provide a scientific basis for a better understanding of the long-term impacts of insecticides at sublethal doses on parasitoids, facilitating the development of improved integrated pest management programs for FAW control. © 2023 Society of Chemical Industry.


Assuntos
Himenópteros , Inseticidas , Feminino , Animais , Inseticidas/toxicidade , Spodoptera , Hormese , ortoaminobenzoatos/farmacologia , Himenópteros/fisiologia , Larva
3.
Adv Sci (Weinh) ; 10(30): e2303006, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37638719

RESUMO

Immunotherapy using dendritic cell (DC)-based vaccination is an established approach for treating cancer and infectious diseases; however, its efficacy is limited. Therefore, targeting the restricted migratory capacity of the DCs may enhance their therapeutic efficacy. In this study, the effect of laponite (Lap) on DCs, which can be internalized into lysosomes and induce cytoskeletal reorganization via the lysosomal reprogramming-calcium flicker axis, is evaluated, and it is found that Lap dramatically improves the in vivo homing ability of these DCs to lymphoid tissues. In addition, Lap improves antigen cross-presentation by DCs and increases DC-T-cell synapse formation, resulting in enhanced antigen-specific CD8+ T-cell activation. Furthermore, a Lap-modified cocktail (Lap@cytokine cocktail [C-C]) is constructed based on the gold standard, C-C, as an adjuvant for DC vaccines. Lap@C-C-adjuvanted DCs initiated a robust cytotoxic T-cell immune response against hepatitis B infection, resulting in > 99.6% clearance of viral DNA and successful hepatitis B surface antigen seroconversion. These findings highlight the potential value of Lap as a DC vaccine adjuvant that can regulate DC homing, and provide a basis for the development of effective DC vaccines.


Assuntos
Cálcio , Vacinas , Linfócitos T CD8-Positivos , Antígenos , Adjuvantes Imunológicos , Citocinas , Lisossomos , Antivirais , Células Dendríticas
4.
Insects ; 14(2)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36835713

RESUMO

Trichogramma dendrolimi is one of the most successfully industrialized Trichogramma species used to control agricultural and forestry pests in China. However, the molecular mechanisms underlying its host recognition and parasitism remain largely unknown, partially due to the limited genome information of this parasitoid wasp. Here, we present a high-quality de novo assembly of T. dendrolimi through a combination of Illumina and PacBio sequencing technologies. The final assembly had a length of 215.2 Mb and contains 316 scaffolds with a scaffold N50 size of 1.41 Mb. Repetitive sequences with a length of 63.4 Mb and 12,785 protein-coding genes were identified. Significantly expanded gene families were identified to be involved in the development and regulatory processes, while remarkably contracted gene families were involved in the transport processes in T. dendrolimi. The olfactory and venom-associated genes were identified in T. dendrolimi and 24 other hymenopteran species, using uniform methods combining BLAST and HMM profiling. The identified venom genes of T. dendrolimi were enriched in antioxidant activity, tricarboxylic acid cycle, response to oxidative stress and cell redox homeostasis. Our study provides an important resource for comparative genomics and functional studies to interpret the molecular mechanisms underlying host recognition and parasitism of Trichogramma species.

5.
Anal Chim Acta ; 1239: 340696, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628764

RESUMO

A highly sensitivity self-powered biosensor is developed based on T7 exonuclease (T7 Exo) and 3D DNA walker induced rolling circle amplification (RCA) for electrochemical/colorimetric dual-mode detection of microRNA-21 (miRNA-21) with improved reliability. Taking its advantage of fascinating properties, such as high structure defects and good conductivity, graphdiyne is prepared and used to prepare high-performance enzyme biofuel cell. T7 Exo-assisted 3D DNA walker target recognition triggers RCA reaction to obtain a significantly amplified signal response. A capacitor is integrated to the enzyme biofuel cell to further amplify the electrochemical output signal of the self-powered biosensor. In detection system, glucose oxidase catalyzes glucose oxidation to produce hydrogen peroxide, and 3,3',5,5'-tetramethylbenzidine (TMB) is then catalyzed to generate colored products, so as to achieve the colorimetric detection of the target. Analysis signals of diverse modes are recorded independently. Consequently, detection of microRNA with improved reliability and wider signal response range are achieved by electrochemical/colorimetric dual-mode with detection limits of 0.15 and 33 fM (S/N = 3) respectively. In addition, the proposed self-powered biosensor successfully applied for the detection of miRNA-21 in human serum samples, confirming its practical applicability in clinical diagnosis. It is powerfully anticipated the proposed self-powered biosensor possesses great potential to be applied to other biomedical domains.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Humanos , MicroRNAs/análise , Reprodutibilidade dos Testes , Limite de Detecção , DNA/genética , DNA/análise , Técnicas de Amplificação de Ácido Nucleico , Técnicas Eletroquímicas
6.
Anal Chim Acta ; 1239: 340702, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628768

RESUMO

A self-powered biosensor (SPB) was constructed for the ultra-sensitive detection of microRNA-155 (miR-155) by combining a capacitor/enzymatic biofuel cell (EBFC), a strategy of rolling circle amplification (RCA) and a digital multimeter (DMM). The experimental results show that the sensitivity of the assembled EBFC-SPB can reach 15.85 µA/pM with the action of matching capacitor, which is 513% of that without capacitor (3.09 µA/pM). This achieves the first signal amplification. Furthermore, when the target miR-155 triggers RCA, electrons are continuous generated and flow to the biocathode through the external circuit to catalyze the reduction of oxygen and release [Ru(NH3)6]3+ electron acceptor. This achieves the second signal amplification. Finally, DMM is used to convert the signal into instantaneous current and amplify it for real-time reading. This achieves the third signal amplification. Therefore, the limit of detection (LOD) of the developed biosensor is as low as 0.17 fM (S/N = 3), and the linear range is between 0.5 fM and 10,000 fM, indicating that the EBFC-SPB has a broad application prospect for cancer marker of miR-155 with ultrasensitive detection.


Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais , MicroRNAs , Limite de Detecção , Técnicas Biossensoriais/métodos , Catálise , Técnicas Eletroquímicas/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos
7.
Anal Chim Acta ; 1240: 340754, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36641150

RESUMO

A novel self-powered biosensor is engineered by the integration of DNAzyme walker and AuNPs/graphdiyne biosensing interface, realizing sensitive detection of target microRNA. The cleverly constructed DNAzyme walker with outstanding signal transduction ability to obtain an amplified signal response. In addition, the AuNPs/graphdiyne significantly improves electron transport speed of biosensing interface for improving the sensitivity of biosensor. A dynamic linear range of 0.05 fM-10 pM with a low detection limit of 0.015 fM (S/N = 3) is obtained by utilizing the self-powered biosensor. Meanwhile, the developed self-powered biosensor is capable of assaying miRNA-21 in human serum samples with satisfactory recoveries. This strategy provides a valid method for the sensitive microRNA detection, and shows great potential in point-care detection of tumor biomarker.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , MicroRNAs , Humanos , MicroRNAs/genética , Ouro , Limite de Detecção , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas
8.
Biosens Bioelectron ; 222: 114933, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36470063

RESUMO

A real-time self-powered biosensor is designed for ultrasensitive detection of microRNA-21 based on electrochemical energy device capacitor and target-induced recycling double amplification strategy, which greatly improves the output signal by converting a small number of targets into two glucose oxidase labeled output strand DNAs, and the squeezed-out output strand is recycled by the cathode to fix more signal [Ru(NH3)6]3+ to further improve the detection signal. A digital multimeter (DMM) is connected to computer for real-time displaying the output signal of the self-powered biosensing system, which improves the accuracy of the sensing platform. The sensitivity of the proposed biosensor is 116.15 µA/pM for target microRNA-21, which is 32.26 times higher than that of pure EBFC (3.6 µA/pM). The target concentration is proportional to the open-circuit voltage value in a wide linear range of 0.1-10000 fM with a low detection limit of 0.04 fM (S/N = 3). The method shows high sensitivity and excellent selectivity, and can be applied to detect tumor marker microRNA-21 in biological matrix.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , DNA , Eletrodos , Limite de Detecção
9.
Anal Chem ; 94(49): 16980-16986, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36445725

RESUMO

Realization of a highly sensitive analysis and sensing platform is important for early-stage tumor diagnosis. In this work, a self-powered biosensor with a novel sandwich graphdiyne (SGDY) combined with an aptamer-specific recognition function was developed to sensitively and accurately detect tumor markers. Results indicated that the detection limits of microRNA (miRNA)-21 and miRNA-141 were 0.15 and 0.30 fM (S/N = 3) in the linear range of 0.05-10000 and 1-10000 fM, respectively. The newly designed platform has great promise for early-stage tumor diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias , Humanos , Biomarcadores Tumorais , MicroRNAs/análise , Técnicas Biossensoriais/métodos , Neoplasias/diagnóstico , Limite de Detecção , Técnicas Eletroquímicas
10.
Analyst ; 147(15): 3396-3414, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35748818

RESUMO

Rolling circle amplification (RCA) is a simple and isothermal DNA amplification technique that is used to generate thousands of repeating DNA sequences using circular templates under the catalysis of DNA polymerase. Compared to alternating temperature nucleic acid amplification such as polymerase chain reaction (PCR) amplification, RCA is more suitable for on-spot detection without the need for an expensive thermal cycler. In this study, the principle and classification of RCA are introduced, and the applications of RCA in the detection of pathogenic bacteria, nucleic acid tumor markers, viruses, and proteins are reviewed. Finally, the perspectives of RCA in biological detection are anticipated. The RCA method has a great potential for biological detection. This review aims to provide references for the further development and application of the RCA technique in biosensors.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Técnicas Biossensoriais/métodos , DNA Polimerase Dirigida por DNA , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase
11.
Micromachines (Basel) ; 13(4)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35457910

RESUMO

In this paper, numerical simulations were used to study the decomposition and combustion processes inside the 0.2 N-class ADN-based thruster, and the effects of two geometrical parameters (length and diameter) of the combustion chamber on the combustion performance were evaluated. The decomposition and combustion processes of the thruster were simulated using a reduced chemical reaction mechanism with 22 components and 20 reactions steps. According to the distribution of the basic physical fields, the variation patterns of the pressure field, velocity field, temperature field, and key component parameters caused by different combustion chamber geometrical parameters were observed and analyzed. The results show that the specific impulse and thrust of the thruster increased and then decreased with the increase of the combustion chamber diameter. When the combustion chamber diameter is 7.9 mm, the specific impulse reaches the maximum value of 206.6 s. Additionally, the specific impulse increased from 186 s to 206 s when the combustion chamber length was changed from 7 mm to 11 mm; the specific impulse increased gradually but not significantly, and the growth trend started to flatten out. The results from the paper can serve as a reference for the design and vacuum testing of an ADN-based thruster.

12.
Insects ; 13(1)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35055913

RESUMO

The Asian corn borer (ACB), Ostrinia furnicalis, is a serious corn pest in south-east Asia, causing huge economic losses every year. Trichogramma dendrolimi and Trichogramma ostriniae, two egg parasitoids, have previously been identified as key biological control agents. To determine the age impact of ACB eggs on their effective biocontrol potential, herein we compared the biological parameters (i.e., number of parasitized eggs, emergence, developmental time, and sex ratio) of both parasitoids on ACB eggs of various ages (i.e., 0-4, 4-8, 8-12, 12-16, 16-24, 24-36, and 36-48 h old), respectively. Our results showed that the age of ACB eggs had a significant impact on the parasitization activity of T. dendrolimi in both choice and no-choice conditions. Trichogramma dendrolimi preferred to parasitize 0-8-h-old ACB eggs, and its parasitization dramatically declined on ACB eggs older than 8 h under choice and no-choice conditions. On the other hand, T. ostriniae showed high preference to parasitize all tested ACB egg ages. The age of ACB eggs had no significant impact on the parasitization of T. ostriniae under choice and no-choice conditions. Furthermore, the female progeny of T. dendrolimi decreased as the age of ACB increased, while no differences were found in female progeny of T. ostriniae. Trichogramma ostriniae also developed faster on each ACB egg age group in comparison with T. dendrolimi. Overall, the age of ACB eggs had a significant impact on T. dendrolimi performance, leading us to conclude that T. ostriniae is more effective than T. dendrolimi as a biocontrol agent of the ACB.

13.
Nanoscale ; 14(3): 815-822, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34984426

RESUMO

A self-powered microRNA biosensor with triple signal amplification systems was assembled through the integration of three-dimensional DNA walkers, enzymatic biofuel cells and a capacitor. The DNA walker is designed from an enzyme-free target triggered catalytic hairpin assembly of modified gold nanoparticles. When triggered by the target microRNA, the DNA walker will move along the catalytic hairpin track, resulting in a payload release of glucose oxidase. The enzymatic biofuel cell contains the glucose oxidase bioanode and a bilirubin oxidase biocathode that bring a dramatic open circuit voltage to realize the self-powered bioassays of microRNA. A capacitor is further coupled with the enzymatic biofuel cell to further amplify the electrochemical signal, and the sensitivity increases 28.82 times through optimizing the matching capacitor. Based on this design, the present biosensor shows high performance, especially for detection limit and sensitivity. Furthermore, the present biosensor was successfully applied for serum samples, directly demonstrating its good application in clinical biomedicine and disease diagnosis.


Assuntos
Fontes de Energia Bioelétrica , Nanopartículas Metálicas , MicroRNAs , Bioensaio , DNA , Ouro , Limite de Detecção , MicroRNAs/genética
14.
Materials (Basel) ; 16(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36614486

RESUMO

As a new type of energy-containing material, Ammonium dinitramide based liquid propellant has the advantages of being green, having low toxicity, good stability, and high safety performance. Traditional catalytic combustion methods require preheating of the catalytic bed and deactivation of the catalytic particles at high temperatures, while microwave ignition methods can effectively solve these problems. To study the combustion characteristics of ADN-based liquid propellants during microwave ignition, the influence of microwave power and gas flow rates on the combustion process are analyzed using experimental methods. A high-speed camera was used to observe the enhanced effects of microwave power and gas flow on plasma and flame. Combined with temperature measurement, the combustion process of ADN-based liquid propellants under the action of plasma was analyzed. The combustion process in the presence of microwaves was observed by comparing parameters such as flame length, flame temperature, and radical intensity. Those results show that, with the increase in microwave power, the luminous burning area of the flame grows significantly. The microwave power is increased by 250 W each, and the flame jet length is increased by nearly 20%. The increase in microwave power also leads to an increase in propellant combustion temperature, however, this increase gradually slows down. At a gas flow rate of 20 L/min, the ADN-based liquid propellant showed the best combustion performance with a maximum jet length of 14.51 cm and an average jet length increase of approximately 85.9% compared to 14 L/min. Too much gas flow rate will hinder the development of the jet, while the high-velocity airflow will have a cooling effect on the flame temperature. The results provide a basis for the specific parameter design of microwave ignition and promote the application of ADN-based liquid propellants in the aerospace field.

15.
Anal Chem ; 93(46): 15225-15230, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34752059

RESUMO

The detection of microRNA (miRNA) in human serum has great significance for cancer prevention. Herein, a novel self-powered biosensing platform is developed, which effectively integrates an enzymatic biofuel cell (EBFC)-based self-powered biosensor with a matching capacitor for miRNA detection. A catalytic hairpin assembly and hybrid chain reaction are used to improve the analytical performance of EBFC. Furthermore, the matching capacitor is selected as an auxiliary signal amplifying device, and graphdiyne is applied as substrate material for EBFC. The results confirm that the developed method obviously increases the output current of EBFC, and the sensitivity can reach 2.75 µA/pM, which is 786% of pure EBFC. MiRNA can be detected in an expanded linear range of 0.1-100000 fM with a detection limit of 0.034 fM (S/N = 3). It can offer a selective and sensitive platform for nucleotide sequence detection with great potential in clinical diagnostics.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Técnicas Eletroquímicas , Grafite , Humanos , Limite de Detecção , MicroRNAs/isolamento & purificação
16.
ACS Omega ; 6(35): 22937-22944, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34514264

RESUMO

Microwave-assisted ignition is a new ignition method, which has the advantages of reliable ignition and high ignition energy and requires no preheating. In this study, experimental methods were used to study the microwave-assisted ignition and combustion characteristics of ADN-based liquid propellant, and the effects of microwave power and propellant flow rate on combustion flame structure, spectral emission characteristics, and flame temperature were investigated. In the experiment, a microwave-assisted ignition experimental device was established first. The ADN-based liquid propellant was injected into the microwave high-energy region from the bottom of the resonator through a hollow straight tube with an inner diameter of 1 mm, and the gas was introduced in a coaxial manner. The research results demonstrated that when the microwave power increased from 1000 to 2000 W, the flame height increased from 11.12 to 17.32 mm; the free radical intensity of C2*, NH2, and HNO* increased significantly; the flame temperature increased by about 28.9%. The increase in microwave power is helpful to the generation of intermediate products and the combustion performance of propellant is better. When the propellant flow rate was increased from 25 to 45 mL/min, it was found that the spray combustion effect was the best when the propellant flow rate was 30 mL/min, the flame height increased by 25.2%, and the flame temperature increased by about 11.3%.

17.
Adv Mater ; 33(40): e2102528, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34396603

RESUMO

Dendritic cell (DC) vaccines are used for cancer and infectious diseases, albeit with limited efficacy. Modulating the formation of DC-T-cell synapses may greatly increase their efficacy. The effects of graphene oxide (GO) nanosheets on DCs and DC-T-cell synapse formation are evaluated. In particular, size-dependent interactions are observed between GO nanosheets and DCs. GOs with diameters of >1 µm (L-GOs) demonstrate strong adherence to the DC surface, inducing cytoskeletal reorganization via the RhoA-ROCK-MLC pathway, while relatively small GOs (≈500 nm) are predominantly internalized by DCs. Furthermore, L-GO treatment enhances DC-T-cell synapse formation via cytoskeleton-dependent membrane positioning of integrin ICAM-1. L-GO acts as a "nanozipper," facilitating the aggregation of DC-T-cell clusters to produce a stable microenvironment for T cell activation. Importantly, L-GO-adjuvanted DCs promote robust cytotoxic T cell immune responses against SARS-CoV-2 spike 1, leading to >99.7% viral RNA clearance in mice infected with a clinically isolated SARS-CoV-2 strain. These findings highlight the potential value of nanomaterials as DC vaccine adjuvants for modulating DC-T-cell synapse formation and provide a basis for the development of effective COVID-19 vaccines.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Células Dendríticas/imunologia , Grafite/uso terapêutico , Nanoestruturas/uso terapêutico , Adjuvantes Imunológicos/química , Animais , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Células Dendríticas/efeitos dos fármacos , Grafite/química , Humanos , Camundongos , Nanoestruturas/química , SARS-CoV-2/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
18.
J Neurochem ; 158(2): 358-372, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025573

RESUMO

Molecular abnormalities within the Glucocorticoid Receptor (GR) stress signaling pathway involved in dysfunction of mitochondria and confer vulnerability to stress-related psychiatric disorders. Bcl-2 associated athanogene (Bag-1) is a target for the actions of mood stabilizers. Bag-1 interacts with GR, thereby regulating glucocorticoid function. In this study, we investigate the potential role of Bag-1 in regulating GR translocation into mitochondria. Corticosterone (CORT) treatment significantly enhanced Bag-1/GR complex formation and GR mitochondrial translocation in cultured rat cortical neurons after treatment for 30 min and 24 hr. By contrast, after stimulation with CORT for 3 days, localization of the Bag-1/GR complex and mitochondrial GR were reduced. Similar results were obtained in mice, in which administrated CORT in drinking water for 21 days significantly impaired the GR levels in the mitochondria, while Bag-1 over-expression rescued this reduction. Furthermore, chronic CORT exposure led to anhedonia-like and depression-like behaviors in the sucrose-consumption test and forced swimming test, and these behaviors were rescued by Bag-1 over-expression. These results suggest that Bag-1 mediates GR trafficking to mitochondria and regulates affective resilience in response to a CORT increase and provide potential insight into the mechanisms by which Bag-1 and GR could contribute to the physiology and pathogenesis of psychiatric disorders in response to the change of stress hormone.


Assuntos
Afeto/efeitos dos fármacos , Corticosterona/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Mitocôndrias/metabolismo , Receptores de Glucocorticoides/metabolismo , Resiliência Psicológica/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Anedonia , Animais , Depressão/psicologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Neurônios/efeitos dos fármacos , Gravidez , Cultura Primária de Células , Transporte Proteico , Ratos , Ratos Sprague-Dawley , Estimulação Química , Natação/psicologia
19.
Biol Pharm Bull ; 43(8): 1159-1171, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32448843

RESUMO

Regulating synaptic formation and transmission is critical for the physiology and pathology of psychiatric disorders. The adenosine A2A receptor subtype has attracted widespread attention as a key regulator of neuropsychiatric activity, neuroprotection and injury. In this study, we systematically investigated the regulatory effects of a novel A2A receptor agonist, PSB-0777, on the expression of synaptic proteins and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPA receptors) at the cellular level in a time- and dose-dependent manner. After 30 min of high-dose PSB-0777 stimulation, the expression of Synapsin-1 (Syn-1), postsynaptic density protein 95 (PSD95), and AMPA receptors and the number of synapses were rapidly and significantly increased in rat primary cortical neurons compared with the control. Sustained elevation was found in the low and medium-dose groups after 24 h and 3 d of treatment. In contrast, after stimulation with PSB-0777 for 3 consecutive days, the expression of Syn-1 was decreased, and PSD95, AMPA receptors and the number of synapses were no longer increased in the high-dose group. Our study focuses on the detailed and systematic regulation of synaptic proteins and AMPA receptors by an A2A receptor agonist, PSB-0777, which may result in both beneficial and detrimental effects on neurotransmission and neuroprotection and may contribute to the pathophysiology of psychiatric disorders related to A2A receptors. These experimental data may contribute to understanding of the mechanisms for neuroprotective and therapeutic effect of A2A receptor agonists.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Furanos/farmacologia , Fármacos Neuroprotetores/farmacologia , Receptor A2A de Adenosina/fisiologia , Receptores de AMPA/genética , Animais , Células Cultivadas , Córtex Cerebral/metabolismo , Proteína 4 Homóloga a Disks-Large/genética , Relação Dose-Resposta a Droga , Feminino , Ratos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos , Sinapses/fisiologia , Sinapsinas/genética , Transmissão Sináptica/efeitos dos fármacos
20.
PLoS One ; 15(4): e0231098, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315304

RESUMO

Trichogramma leucaniae is believed to be an efficient biological control agent for controlling the soybean pod borer [SPB; Leguminivora glycinivorella]. The large eggs of Chinese oak silkworm, Antheraea pernyi, are one of the best alternative host for mass production of Trichogramma. However, they are considered poor host for the growth and development of T. leucaniae. Here, we determine the feasibility of successive rearings of T. leucaniae on the large eggs for eight generations and evaluated their capacity of parasitizing SPB eggs of different ages. In the first four generations, the suitability of T. leucaniae reared on large eggs exhibited a significant increasing tendency and then decreased with the successive generations thereafter. The percentage of parasitized eggs and number of emerged adults per egg were increased from 40.0% and 10.8 adults/egg in F1 generation to 86.7% and 36.4 adults/egg in F4 generation respectively. In addition, T. leucaniae reared on A. pernyi for four generations significantly parasitized more SPB eggs regardless of egg age compared with those reared on Corcyra cephalonica eggs. These results provided useful information on the feasibility of mass production of T. leucaniae by reared for successive generations on A. pernyi large eggs.


Assuntos
Bombyx/parasitologia , Ovos/parasitologia , Himenópteros/crescimento & desenvolvimento , Controle Biológico de Vetores/métodos , Animais , Feminino , Interações Hospedeiro-Parasita , Humanos , Himenópteros/patogenicidade , Masculino , Óvulo/parasitologia , Glycine max/parasitologia
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