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1.
Appl Opt ; 58(12): 3310-3316, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31044811

RESUMO

Dynamic speckles, which carry information about beam parameters of a diffuse object, are produced by a moving diffuse object under illumination of a Gaussian beam. In this paper, we consider that the diffuse object moves in a plane with constant velocity and discuss the statistical properties of dynamic speckles for estimating the variation of focusing spot size. The space-time statistical properties of dynamic speckle have been revealed by analyzing the space-time cross-correlation function of speckle intensity fluctuations detected at two points in the receiving plane. We discuss the influence of the distance between two point detectors on the detection results by simulation analyses, and the theoretical analysis results are verified by experiment. This method, which applies feedback of the dynamic speckle fields for estimating the variation of focusing spot size, will help a laser focusing system optimize focusing performance.

2.
Cell Physiol Biochem ; 41(5): 1851-1864, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28376477

RESUMO

BACKGROUND: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. METHODS: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. RESULTS: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. CONCLUSION: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.


Assuntos
Apoptose , Autofagia , Movimento Celular , Neoplasias Colorretais/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas de Neoplasias/metabolismo , Osteopontina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Humanos , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Osteopontina/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
3.
Appl Opt ; 56(32): 8941-8949, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29131175

RESUMO

The speckle pattern (line by line) sequential extraction (SPSE) metric is proposed by the one-dimensional speckle intensity level crossing theory. Through the sequential extraction of received speckle information, the speckle metrics for estimating the variation of focusing spot size on a remote diffuse target are obtained. Based on the simulation, we will give some discussions about the SPSE metric range of application under the theoretical conditions, and the aperture size will affect the metric performance of the observation system. The results of the analyses are verified by the experiment. This method is applied to the detection of relative static target (speckled jitter frequency is less than the CCD sampling frequency). The SPSE metric can determine the variation of the focusing spot size over a long distance, moreover, the metric will estimate the spot size under some conditions. Therefore, the monitoring and the feedback of far-field spot will be implemented laser focusing system applications and help the system to optimize the focusing performance.

4.
Appl Opt ; 55(26): 7229-35, 2016 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-27661357

RESUMO

The images captured by an airborne range-gated imaging system are degraded by many factors, such as light scattering, noise, defocus of the optical system, atmospheric disturbances, platform vibrations, and so on. The characteristics of low illumination, few details, and high noise make the state-of-the-art restoration method fail. In this paper, we present a restoration method especially for range-gated imaging systems. The degradation process is divided into two parts: the static part and the dynamic part. For the static part, we establish the physical model of the imaging system according to the laser transmission theory, and estimate the static point spread function (PSF). For the dynamic part, a so-called light vein feature extraction method is presented to estimate the fuzzy parameter of the atmospheric disturbance and platform movement, which make contributions to the dynamic PSF. Finally, combined with the static and dynamic PSF, an iterative updating framework is used to restore the image. Compared with the state-of-the-art methods, the proposed method can effectively suppress ringing artifacts and achieve better performance in a range-gated imaging system.

5.
Opt Express ; 23(6): 7424-41, 2015 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-25837084

RESUMO

The clipped speckle autocorrelation (CSA) metric is proposed for estimating the laser beam energy concentration on a remote diffuse target in a laser beam projection system with feedback information. Using the second order statistics of the intensity distribution of the fully developed speckle and the relation of the autocorrelation functions for the clipped and unclipped speckles, we present the theoretical expression of this metric as a function of the normalized CSA function. The simulation technique based on the equivalence of the spatial average and the ensemble time average is provided. Based on this simulation technique, we analyze the influence of the surface roughness of the target on this metric and then show the influencing factors of the metric performance, for example the finite sample effect and aperture size of the observation system. Experimental results are illustrated to examine the capability of this metric and the correctness of the discussion about the metric performance.

6.
Cell Physiol Biochem ; 33(3): 747-57, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24662412

RESUMO

BACKGROUND: Salvianolic acid A (SalA) has been shown to confer robust protection against endothelial injury. VLDL receptor is expressed at high levels on the endothelial surface, however its biological effect on endothelial cells has not yet been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDL expression and barrier dysfunction under conditions of ischemia/reperfusion (IS/RP). METHODS: Human umbilical vein endothelial cells (HUVECs) treated with SalA were subjected to IS/RP stimulation. Endothelial permeability, ZO-1 distribution, actin cytoskeleton reorganization, and intracellular reactive oxygen species (ROS) generation were examined. The mRNA levels were tested by real-time RT-PCR and the protein levels were determined by immunoblot analysis. RESULTS: Pretreatment of HUVECs with SalA markedly attenuated IS/RP-induced endothelial hyperpermeability, discontinuous ZO-1 staining, actin stress fiber formation, and intracellular ROS generation. IS/RP activated p38 MAPK signaling and enhanced VLDL receptor expression, and inactivation of p38 MAPK abolished increase of VLDL receptor expression. Furthermore, siRNA experiments showed that VLDL receptor was a crucial mediator of endothelial barrier dysfunction and intracellular ROS generation induced by IS/RP. Importantly, SalA effectively suppressed IS/RP-induced activation of p38 MAPK signaling and increase of VLDL receptor expression. CONCLUSION: These results for the first time demonstrated that SalA protected against IS/RP-induced endothelial barrier dysfunction through suppression of VLDL receptor expression.


Assuntos
Alcenos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Polifenóis/farmacologia , Receptores de LDL/biossíntese , Traumatismo por Reperfusão/prevenção & controle , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , RNA Mensageiro/biossíntese , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Exp Ther Med ; 27(4): 163, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476901

RESUMO

[This retracts the article DOI: 10.3892/etm.2019.8348.].

8.
Emerg Microbes Infect ; 13(1): 2337665, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38551145

RESUMO

Coxsackievirus B4 (CVB4) is associated with a range of acute and chronic diseases such as hand, foot, and mouth disease, myocarditis, meningitis, pancreatitis, and type 1 diabetes, affecting millions of young children annually around the world. However, no vaccine is currently available for preventing CVB4 infection. Here, we report the development of inactivated viral particle vaccines for CVB4. Two types of inactivated CVB4 particles were prepared from CVB4-infected cell cultures as vaccine antigens, including F-particle (also called mature virion) consisting of VP1, VP3, VP2, and VP4 subunit proteins, and E-particle (also called empty capsid) which is made of VP1, VP3, and uncleaved VP0. Both the inactivated CVB4 F-particle and E-particle were able to potently elicit neutralizing antibodies in mice, despite slightly lower neutralizing antibody titres seen with the E-particle vaccine after the third immunization. Importantly, we demonstrated that passive transfer of either anti-F-particle or anti-E-particle sera could completely protect the recipient mice from lethal CVB4 challenge. Our study not only defines the immunogenicity and protective efficacy of inactivated CVB4 F-particle and E-particle but also reveals the central role of neutralizing antibodies in anti-CVB4 protective immunity, thus providing important information that may accelerate the development of inactivated CVB4 vaccines.


Assuntos
Vacinas , Vacinas Virais , Humanos , Criança , Animais , Camundongos , Pré-Escolar , Anticorpos Antivirais , Anticorpos Neutralizantes , Imunização , Vacinação
9.
Chem Commun (Camb) ; 60(35): 4679-4682, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38591727

RESUMO

All-inorganic perovskites have garnered significant attention in optoelectronics. Herein, square CsPb2Br5 nanosheets, with lateral dimensions of up to 200 µm and a thickness of less than 50 nm, were successfully synthesized via a straightforward aqueous method using HBr as a morphology-tailoring agent. A photodetector composed of a single nanosheet was subsequently fabricated and exhibited remarkable photodetection capabilities, demonstrating a detectivity of 5.98 × 109 Jones. These findings offer new perspectives on the synthesis and utilization of CsPb2Br5 and other perovskite nanostructures in optoelectronic devices.

10.
J Opt Soc Am A Opt Image Sci Vis ; 30(12): 2502-9, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24323010

RESUMO

The linear equations method is proposed to calculate the complete modal content of the partially coherent laser beam using only the intensity information. This method could give not only the incoherent expansion coefficients of the modal decomposition but also the cross-correlation expansion coefficients using the intensity profiles in several planes of finite distance along the propagation direction. A simulation is also presented to verify the validity of this theory. In our algorithm, the minimum and maximum mode orders should be known a priori, so we provide an estimation method for the two parameters.

11.
Tissue Cell ; 81: 102032, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36701898

RESUMO

Ellagic acid (EA), found in fruits and foods, has been shown to be effective in the treatment of breast, colon and bladder cancer. However, due to the complexity of colon cancer, the therapeutic mechanism of EA for colon cancer is still unclear. Cell Counting Kit-8 (CCK-8) assay were employed to investigate the cell proliferation. Western blotting and flow cytometry assays were utilized to investigate apoptosis and autophagy in CRC cells (HCT116), respectively. Moreover, western blotting and luciferase reporter assays were evaluated the effect of EA on AMPK/mTOR pathway. Through flow cytometry analysis, EA could promote the apoptosis of HCT116 cells. In addition, EA can reduce the phosphorylation of mTOR, promoted phosphorylation of AMPK, and induced autophagy in HCT116 cells. Also, Dorsomorphin pretreatment can reduce the expression of autophagy protein, which indicates that EA induces autophagy through AMPK/mTOR pathway. These results suggest that EA inhibits the growth of colon cancer through AMPK/mTOR pathway and induces apoptosis and protective autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP , Neoplasias do Colo , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Ácido Elágico/farmacologia , Ácido Elágico/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo/tratamento farmacológico , Apoptose , Autofagia
12.
ACS Appl Mater Interfaces ; 15(4): 5172-5179, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36650087

RESUMO

CuO has been regarded as a promising catalyst for the electrochemical reduction of nitrate (NO3-RR) to ammonium (NH3); however, the intrinsic activity is greatly restricted by its poor electrical property. In this work, self-supported Zn-doped CuO nanosheet arrays (Zn-CuO NAs) are synthesized for NO3-RR, where the Zn dopant regulates the electronic structure of CuO to significantly accelerate the interfacial charge transfer and inner electron transport kinetics. The Zn-CuO NAs are constructed by a one-step etching of commercial brass (Cu64Zn36 alloy) in 0.1 M NaOH solution, which experiences a corrosion-oxidation-reconstruction process. Initially, the brass undergoes a dealloying procedure to produce nanosized Cu, which is immediately oxidized to the Cu2O unit with a low valence state. Subsequently, Cu2O is further oxidized to the CuO unit and reconstructed into nanosheets with the coprecipitation of Zn2+. For NO3-RR, Zn-CuO NAs show a high NH3 production rate of 945.1 µg h-1 cm-2 and a Faradaic efficiency of up to 95.6% at -0.7 V in 0.1 M Na2SO4 electrolyte with 0.01 M NaNO3, which outperforms the majority of the state-of-the-art catalysts. The present work offers a facile yet very efficient strategy for the scale-up synthesis of Zn-CuO NAs for high-performance NH3 production from NO3-RR.

13.
Cureus ; 15(10): e46603, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37937018

RESUMO

PURPOSES: The primary aim of this clinical study is to identify the factors associated with rapid glycemic, bodyweight, and lipid profile remission in young obese patients following bariatric surgery. MATERIALS AND METHODS: In a total of 131 Chinese in-patients at Shanghai Pudong Hospital, China, we retrospectively analyzed in-patient data of metabolic parameters, including BMI, waist circumference, blood pressure (BP), and blood laboratory tests, such as plasma lipids and lipoprotein, hemoglobulin A1c (HbA1c), and oral glucose tolerance tests (OGTT) before bariatric surgery. We followed up these indices at the first month, third months, half-year, and one year later. RESULTS: The results showed that bodyweight, BP, fasting plasma glucose (FPG), HbA1c, and triglyceride (TG) levels decreased significantly in one to three months following surgery in both male and female patients (p<0.05). We demonstrated that age (male: ß=-0.181; female: ß=-0.292) and the pre-operation HbA1c levels (male: ß=0.935; female: ß=0.919) were independent predictors of HbA1c reduction in both young obese male and female patients in three months after surgery. For body weight loss, age (ß=-0.229) and pre-operation bodyweight (ß=0.735) are the predictors in females, but only pre-operation body weight (ß=0.798) is the independent predictor in obese young male patients. CONCLUSION:  This study discovered that changes in bodyweight were determined by age, pre-operation status of bodyweight, and HbA1C in obese young Chinese.

14.
Adv Mater ; 35(48): e2307017, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37821238

RESUMO

Nanoarray electrocatalysts with unique advantage of facilitating gas bubble detachment have garnered significant interest in gas evolution reactions (GERs). Existing research is largely based on a static hypothesis, assuming that buoyancy is the only driving force for the release of bubbles during GERs. However, this hypothesis overlooks the effect of the self-dynamic electrolyte flow, which is induced by the release of mature bubbles and helps destabilize and release the smaller, immature bubbles nearby. Herein, the enhancing effect of self-dynamic electrolyte flow on nanoarray structures is examined. Phase-field simulations demonstrate that the flow field of electrode with arrayed surface focuses shear force directly onto the gas bubble for efficient detachment, due to the flow could pass through voids and channels to bypass the shielding effect. The flow field therefore has a more substantial impact on the arrayed surface than the nanoscale smooth surface in terms of reducing the critical bubble size. To validate this, superaerophobic ferrous-nickel sulfide nanoarrays are fabricated and employed for water splitting, which display improved efficiency for GERs. This study contributes to understanding the influence of self-dynamic electrolyte on GERs and emphasizes that it should be considered when designing and evaluating nanoarray electrocatalysts.

15.
Updates Surg ; 74(3): 1117-1127, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35426604

RESUMO

To compare outcomes between single-incision laparoscopic totally extra-peritoneal sub-lay (SIL-TES) mesh repair and laparoscopic intraperitoneal onlay mesh (IPOM) repair of ventral hernia (VH). A retrospective selection of 104 patients who underwent VH repair (50 and 54 in the SIL-TES and IPOM groups, respectively) was made. Patient data were collected, and quality of life was evaluated using Carolinas Comfort Scale (CCS) 1 month and 3 months after surgery. There were no significant differences in sex, American Society of Anesthesiologists class, defect size, mesh area, estimated blood loss, and complication rate between the groups. Age was lower, body mass index was higher, prevalence of primary VH was significantly higher (p < 0.0001), and pain was less at 24 and 48 h post procedure (p < 0.0001) in the SIL-TES group. Drainage placement was more (p < 0.0001), operation time was shorter (p = 0.012), and hospitalization duration and total hospitalization cost were greater in the IPOM group than that in SIL-TES group (8.3 ± 0.3 vs 4.3 ± 0.4 days, p < 0.0001; $7126.9 ± 141.4 vs $2937.3 ± 58.3, p < 0.0001, respectively). Pain and movement limitation scores evaluated by CCS were significantly worse at 1 month (4.93 ± 0.28 vs 1.75 ± 0.28: p < 0.0001; 2.52 ± 0.24 vs 1.15 ± 0.18: p < 0.0001, respectively) and 3 months (4.32 ± 0.37 vs 0.9 ± 0.29: p < 0.0001; 2.06 ± 0.25 vs 0.69 ± 0.11: p < 0.0001, respectively) in IPOM group, compared with the according scores in SIL-TES group. There was no readmission within 30 days and no hernia recurrence at mean follow-up of 12 months. SIL-TES mesh repair is safe and effective and is superior to IPOM repair.


Assuntos
Hérnia Ventral , Laparoscopia , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Humanos , Laparoscopia/métodos , Dor , Qualidade de Vida , Recidiva , Estudos Retrospectivos , Telas Cirúrgicas
16.
Iran J Public Health ; 51(2): 327-335, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35866106

RESUMO

Background: Colorectal cancer (CRC) has not only seriously affected people's lives, but also burdened the government healthcare system. Long non-coding RNAs (lncRNA) have attracted more and more attention in the cancer study field. Methods: Experiments were completed in the Medical Research and Innovation Center of Shanghai Pudong Hospital, China from 2019 to 2020. Cell cycle was detected by western blot analyzing and flow cytometry. Apoptosis analysis were determined using flow cytometry or western blot analysis. LncRNA CKMT2-AS1 was knocked down by shRNA transfection. Results: We found CKMT2-AS1 was the most significant=0.0105 for SW480 and P=0.0071 for HCT116) difference lncRNA between colorectal cancer treated with autophagy inducer and colorectal cancer without any treatment. Effective shRNA-CKMT2-AS1 was also designed. Following, we found the treatment of autophagy inducer and autophagy inducer + shRNA-NC were able to suppress the proliferation of both SW480 and HCT116 cells. In addition, the treatment of autophagy inducer + shRNA-CKMT2-AS1 significantly reduced the apoptosis of SW480 and HCT116 cells induced by autophagy. Furthermore, we found the phosphorylation of mTOR, AKT was enhanced in SW480, and HCT116 cells treated with autophagy inducer + shRNA-CKMT2-AS1 compared to the cells treated with autophagy inducer of autophagy inducer + shRNA-NC. Conclusion: Enhancing the expression of CKMT2-AS1 will become a promising strategy to prevent the progress of colorectal cancer.

17.
Adv Mater ; 34(37): e2204624, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35866182

RESUMO

Developing high-efficiency electrocatalysts for the hydrogen evolution and oxidation reactions (HER/HOR) in alkaline electrolytes is of critical importance for realizing renewable hydrogen technologies. Ruthenium phosphides (RuPx ) are promising candidates to substitute Pt-based electrodes; however, great challenges still remain in their electronic structure regulation for optimizing intermediate adsorption. Herein, it is reported that a homologous RuP@RuP2 core-shell architecture constructed by a phosphatization-controlled phase-transformation strategy enables strong electron coupling for optimal intermediate adsorption by virtue of the emergent interfacial functionality. Density functional theory calculations show that the RuP core and RuP2 shell present efficient electron transfer, leading to a close to thermoneutral hydrogen adsorption Gibbs free energy of 0.04 eV. Impressively, the resulting material exhibits superior HER/HOR activities in alkaline media, which outperform the benchmark Pt/C and are among the best reported bifunctional hydrogen electrocatalysts. The present work not only provides an efficient and cost-effective bifunctional hydrogen electrocatalyst, but also offers a new synthetic protocol to rationally synthesize homologous core-shell nanostructures for widespread applications.

18.
Emerg Microbes Infect ; 11(1): 351-367, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34964428

RESUMO

The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop477-489, and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.


Assuntos
COVID-19/virologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Mapeamento de Epitopos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
19.
Opt Express ; 19(19): 18216-28, 2011 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-21935188

RESUMO

In order to research the statistical properties of Gaussian beam propagation through an arbitrary thickness random phase screen for adaptive optics and laser communication application in the laboratory, we establish mathematic models of statistical quantities, which are based on the Rytov method and the thin phase screen model, involved in the propagation process. And the analytic results are developed for an arbitrary thickness phase screen based on the Kolmogorov power spectrum. The comparison between the arbitrary thickness phase screen and the thin phase screen shows that it is more suitable for our results to describe the generalized case, especially the scintillation index.

20.
Nat Commun ; 12(1): 264, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431876

RESUMO

The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Anticorpos Antivirais/química , Anticorpos Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , SARS-CoV-2/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Microscopia Crioeletrônica , Mapeamento de Epitopos , Epitopos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Ligação Proteica/efeitos dos fármacos , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia
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