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1.
Cell ; 182(1): 50-58.e8, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516571

RESUMO

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Camundongos Transgênicos , Pneumonia Viral/patologia , Enzima de Conversão de Angiotensina 2 , Animais , COVID-19 , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/virologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos/genética , Pandemias , Peptidil Dipeptidase A/genética , SARS-CoV-2 , Tropismo Viral , Redução de Peso
2.
J Cell Mol Med ; 28(7): e18190, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38494844

RESUMO

Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus (NPSLE). Microglial activation is observed in NPSLE patients. However, the mechanisms regulating microglia-mediated neurotoxicity in NPSLE remain elusive. Here, we showed that M1-like proinflammatory cytokine levels were increased in the cerebrospinal fluid (CSF) of SLE patients, especially those with neuropsychiatric symptoms. We also demonstrated that MRL/lpr lupus mice developed anxiety-like behaviours and cognitive deficits in the early and active phases of lupus, respectively. An increase in microglial number was associated with upregulation of proinflammatory cytokines in the MRL/lpr mouse brain. RNA sequencing revealed that genes associated with phagocytosis and M1 polarization were upregulated in microglia from lupus mice. Functionally, activated microglia induced synaptic stripping in vivo and promoted neuronal death in vitro. Finally, tofacitinib ameliorated neuropsychiatric disorders in MRL/lpr mice, as evidenced by reductions in microglial number and synaptic/neuronal loss and alleviation of behavioural abnormalities. Thus, our results indicated that classically activated (M1) microglia play a crucial role in NPSLE pathogenesis. Minocycline and tofacitinib were found to alleviate NPSLE by inhibiting micrglial activation, providing a promising therapeutic strategy.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Humanos , Camundongos , Animais , Microglia , Depressão/tratamento farmacológico , Camundongos Endogâmicos MRL lpr , Encéfalo , Lúpus Eritematoso Sistêmico/genética , Citocinas
3.
Fish Shellfish Immunol ; 149: 109600, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701991

RESUMO

Excess utilization of plant protein sources in animal feed has been found to adversely affect the antioxidant properties and immunity of animals. While the role of gut microbes in plant protein-induced inflammation has been identified in various models, the specific mechanisms regulating gut microbes in crustaceans remain unclear. Accordingly, this study was designed to investigate the effects of replacing fishmeal with soybean meal (SM) on the hepatopancreas antioxidant and immune capacities, and gut microbial functions of crayfish, as well as the potential microbial regulatory mechanisms. 750 crayfish (4.00 g) were randomly divided into five groups: SS0, SS25, SS50, SS75, and SS100, and fed diets with different levels of soybean meal substituted for fishmeal for six weeks. High SM supplementation proved detrimental to maintaining hepatopancreas health, as indicated by an increase in hemolymph MDA content, GPT, and GOT activities, the observed rupture of hepatopancreas cell basement membranes, along with the decreased number of hepatopancreatic F cells. Moreover, crayfish subjected to high SM diets experienced obvious inflammation in hepatopancreas, together with up-regulated mRNA expression levels of nfkb, alf, and tlr (p<0.05), whereas the lzm mRNA expression level exhibited the highest value in the SS25 group. Furthermore, hepatopancreas antioxidant properties highly attenuated by the level of dietary SM substitution levels, as evidenced by the observed increase in MDA content (p<0.05), decrease in GSH content (p<0.05), and inhabitation of SOD, CAT, GPx, and GST activities (p<0.05), along with down-regulated hepatopancreas cat, gpx, gst, and mmnsod mRNA expression levels via inhibiting nrf2/keap1 pathway. Functional genes contributing to metabolism identified that high SM diets feeding significantly activated lipopolysaccharide biosynthesis, revealing gut dysfunction acted as the cause of inflammation. The global microbial co-occurrence network further indicated that the microbes contributing more to serum indicators and immunity were in module eigengene 17 (ME17). A structural equation model revealed that the genes related to alf directly drove the serum enzyme activities through microbes in ME17, with OTU399 and OTU533 identified as major biomarkers and classified into Proteobacteria that secrete endotoxins. To conclude, SM could replace 25 % of fishmeal in crayfish diets without negatively affecting immunity, and antioxidant capacity. Excessive SM levels contributed to gut dysfunction and weakened the innate immune system of crayfish.


Assuntos
Ração Animal , Antioxidantes , Astacoidea , Dieta , Microbioma Gastrointestinal , Glycine max , Hepatopâncreas , Animais , Astacoidea/imunologia , Astacoidea/genética , Ração Animal/análise , Glycine max/química , Antioxidantes/metabolismo , Dieta/veterinária , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopâncreas/imunologia , Hepatopâncreas/metabolismo , Imunidade Inata/efeitos dos fármacos , Distribuição Aleatória , Intestinos/imunologia , Intestinos/efeitos dos fármacos , Suplementos Nutricionais/análise
4.
BMC Pediatr ; 24(1): 212, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528509

RESUMO

OBJECTIVE: The clinical characteristics of hospitalized children with acute poisoning were analyzed to provide a reference for preventing poisoning and seeking effective prevention and treatment. METHODS: The clinical data of 112 children with acute poisoning admitted to Qilu Hospital of Shandong University from January 1, 2018, to December 31, 2021, were collected and analyzed from different perspectives. RESULTS: The majority of acute poisoning cases that occurred in children were in early childhood and preschool age (89 cases, accounting for 79.4%). The most common types of poisoning were pesticide poisoning and drug poisoning, and the main ways of poisoning were accidental administration via the digestive tract and accidental ingestion. Poisoning occurred slightly more in spring and summer all year round, and most children had a good prognosis after timely treatment. CONCLUSION: Acute poisoning often occurs in children. Parental education and intensified child supervision are needed to prevent the incidence of unintentional poisoning.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Intoxicação , Criança , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos , Hospitalização , Criança Hospitalizada , Universidades , Intoxicação/diagnóstico , Intoxicação/epidemiologia , Intoxicação/terapia
5.
Sensors (Basel) ; 24(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38544180

RESUMO

Neural radiance fields (NeRFs) leverage a neural representation to encode scenes, obtaining photorealistic rendering of novel views. However, NeRF has notable limitations. A significant drawback is that it does not capture surface geometry and only renders the object surface colors. Furthermore, the training of NeRF is exceedingly time-consuming. We propose Depth-NeRF as a solution to these issues. Specifically, our approach employs a fast depth completion algorithm to denoise and complete the depth maps generated by RGB-D cameras. These improved depth maps guide the sampling points of NeRF to be distributed closer to the scene's surface, benefiting from dense depth information. Furthermore, we have optimized the network structure of NeRF and integrated depth information to constrain the optimization process, ensuring that the termination distribution of the ray is consistent with the scene's geometry. Compared to NeRF, our method accelerates the training speed by 18%, and the rendered images achieve a higher PSNR than those obtained by mainstream methods. Additionally, there is a significant reduction in RMSE between the rendered scene depth and the ground truth depth, which indicates that our method can better capture the geometric information of the scene. With these improvements, we can train the NeRF model more efficiently and achieve more accurate rendering results.

6.
Hepatology ; 76(2): 330-344, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34897774

RESUMO

BACKGROUND AND AIMS: Chimeric antigen receptor engineered T cells (CARTs) for HCC and other solid tumors are not as effective as they are for blood cancers. CARTs may lose function inside tumors due to persistent antigen engagement. The aims of this study are to develop low-affinity monoclonal antibodies (mAbs) and low-avidity CARTs for HCC and to test the hypothesis that low-avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects. METHODS AND RESULTS: New human glypican-3 (hGPC3) mAbs were developed from immunized mice. We obtained three hGPC3-specific mAbs that stained HCC tumors, but not the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33, the frequently used high-affinity mAb, but with approximately 17-fold lower affinity. We then compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor effects. In vitro, low-avidity 8F8 CARTs killed both hGPC3high and hGPC3low HCC tumor cells to the same extent as high-avidity GC33 CARTs. 8F8 CARTs expanded and persisted to a greater extent than GC33 CARTs, resulting in durable responses against HCC xenografts. Importantly, compared with GC33 CARTs, there were 5-fold more of 8F8-BBz CARTs in the tumor mass for a longer period of time. Remarkably, the tumor-infiltrating 8F8 CARTs were less exhausted and apoptotic, and more functional than GC33 CARTs. CONCLUSION: The low-avidity 8F8-BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high-avidity CARTs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Glipicanas , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Opt Express ; 31(17): 27082-27094, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710790

RESUMO

Propagation of a coherent light beam through a random medium generates speckle patterns, in which some information of media and object is hidden. Speckles produced by particles smaller than wavelength are studied thoroughly, yet it is also essential to investigate speckles produced by larger particles. In this paper, the spatial intensity correlations of transmitted speckle patterns generated by large particles are studied theoretically and experimentally. A semi-empirical expression of spatial intensity correlation function of speckle patterns is derived based on Bethe-Salpeter equation, taking particle size and concentration into account. After performing experiments with various particle sizes and concentrations, we fit the theoretical expression to experimental results and determine the introduced parameters. We analyze the variation of spatial intensity correlation function with particle size and concentration. Theoretical analyses and experimental results given in this paper have potential applications in coherent imaging through random and disordered media.

8.
Microb Ecol ; 86(3): 1575-1588, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36697746

RESUMO

Syndiniales is a diverse parasitic group, increasingly gaining attention owing to its high taxonomic diversity in marine ecosystems and inhibitory effects on the dinoflagellate blooms. However, their seasonal dynamics, host interactions, and mechanisms of community assembly are largely unknown, particularly in eutrophic waters. Here, using 18S rRNA gene amplicon sequencing, we intended to elucidate the interactions between Syndiniales and microeukaryotes, as well as community assembly processes in a eutrophic bay. The results showed that Syndiniales group II was dominating throughout the year, with substantially higher abundance in the winter and spring, whereas Syndiniales group I was more abundant in the summer and autumn. Temperature and Dinoflagellata were the most important abiotic and biotic factors driving variations of the Syndiniales community, respectively. The assembly processes of microeukaryotes and Syndiniales were completely different, with the former being controlled by a balance between homogeneous selection and drift and the latter being solely governed by drift. Network analysis revealed that Syndiniales group II had the largest number of interactions with microeukaryotes, and they primarily associated with Dinoflagellata in the winter, while interactions with Chlorophyta and Bacillariophyta increased dramatically in summer and autumn. These findings provide significant insights in understanding the interactions and assembly processes of Syndiniales throughout the year, which is critical in revealing the roles of single-celled parasites in driving protist dynamics in eutrophic waters.


Assuntos
Diatomáceas , Dinoflagellida , Ecossistema , Baías , Dinoflagellida/genética , Diatomáceas/genética , RNA Ribossômico 18S/genética , Estações do Ano
9.
Nucleic Acids Res ; 49(6): 3573-3583, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33577686

RESUMO

Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors.


Assuntos
DNA/metabolismo , Proteína Forkhead Box O1/química , Proteína Forkhead Box O1/metabolismo , DNA/química , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/metabolismo , Células HEK293 , Humanos , Sequências Repetidas Invertidas , Modelos Moleculares , Ligação Proteica , Multimerização Proteica , Transcrição Gênica
10.
Proc Natl Acad Sci U S A ; 117(17): 9490-9496, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32253318

RESUMO

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , RNA Viral , SARS-CoV-2 , Carga Viral , Soroterapia para COVID-19
11.
Neurocrit Care ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848656

RESUMO

BACKGROUND: The objective of this research was to examine the impact of the monocyte-to-lymphocyte ratio (MLR) on the advancement of hematoma after cerebral contusion. METHODS: The clinical information and laboratory test findings of people with cerebral contusion were retrospectively analyzed. Using the tertiles of MLR, the study participants were categorized into three groups, enabling the evaluation of the correlation between MLR and the advancement of hematoma after cerebral contusion. RESULTS: Among the cohort of patients showing progression, MLR levels were significantly higher compared with the nonprogress group (P < 0.001). The high MLR group had a significantly higher proportion of patients with hematoma progression compared with the medium and low MLR groups. However, the medium MLR group had a lower proportion of patients with hematoma progression compared with the low MLR group. High MLR levels were independently linked to a higher risk of hematoma progression (Odds Ratio 3.546, 95% Confidence Interval 1.187-10.597, P = 0.024). By incorporating factors such as Glasgow Coma Scale score on admission, anticoagulant/antiplatelet therapy, white blood cell count, and MLR into the model, the predictive performance of the model significantly improved (area under the curve 0.754). CONCLUSIONS: Our study suggests that MLR may serve as a potential indicator for predicting the progression of hematoma after cerebral contusion. Further research is necessary to investigate the underlying pathological and physiological mechanisms that contribute to the association between MLR and the progression of hematoma after cerebral contusion and to explore its clinical implications.

12.
Biochem Biophys Res Commun ; 605: 9-15, 2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35306364

RESUMO

Fumarates (fumaric acid esters), primarily dimethyl fumarate (DMF) and monoethyl fumarate (MEF) and its salts, are orally administered systemic agents used for the treatment of psoriasis and multiple sclerosis. It is widely believed that the pharmaceutical activities of fumarates are exerted through the Keap1-Nrf2 pathway. Although it has been revealed that DMF and MEF differentially modify specific Keap1 cysteine residues and result in the differential activation of Nrf2, how the modification of DMF and MEF impacts the biochemical properties of Keap1 has not been well characterized. Here, we found that both DMF and MEF can only modify the BTB domain of Keap1 and that only C151 is accessible for covalent binding in vitro. Dynamic fluorescence scanning (DSF) assays showed that the modification of DMF to Keap1 BTB increased its thermal stability, while the modification of MEF dramatically decreased its thermal stability. Further crystal structures revealed no significant conformational variation between the DMF-modified and MEF-modified BTBs. Overall, our biochemical and structural study provides a better understanding of the covalent modification of fumarates to Keap1 and may suggest fundamentally different mechanisms adopted by fumarates in regulating the Keap1-Nrf2 pathway.


Assuntos
Fumarato de Dimetilo , Fator 2 Relacionado a NF-E2 , Fumarato de Dimetilo/farmacologia , Fumaratos/química , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ligação Proteica
13.
Microb Ecol ; 84(3): 746-758, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34665286

RESUMO

Diatom blooms can significantly affect the succession of microbial communities, yet little is known about the assembly processes and interactions of microbial communities during autumn bloom events. In this study, we investigated the ecological effects of an autumn diatom bloom on prokaryotic communities (PCCs) and microeukaryotic communities (MECs), focusing on their assembly processes and interactions. The PCCs were largely dominated by Alphaproteobacteria, Gammaproteobacteria, Cyanobacteria, and Flavobacteria, while the MECs primarily included Diatomea, Dinoflagellata, and Chlorophyta. The succession of both PCCs and MECs was mainly driven by this diatom bloom and environmental factors, such as nitrate and silicate. Null modeling revealed that homogeneous selection had a more pronounced impact on the structure of PCCs compared with that of MECs. In particular, drift and dispersal limitation cannot be neglected in the assembly processes of MECs. Co-occurrence network analyses showed that Litorimicrobium, Cercozoa, Marine Group I (MGI), Cryptomonadales, Myrionecta, and Micromonas may affect the bloom process. In summary, these results elucidated the complex, robust interactions and obviously distinct assembly mechanisms of PCCs and MECs during a diatom bloom and extend our current comprehension of the ecological mechanisms and microbial interactions involved in an autumn diatom bloom process.


Assuntos
Alphaproteobacteria , Diatomáceas , Dinoflagellida , Gammaproteobacteria , Baías/microbiologia
14.
World J Surg Oncol ; 20(1): 402, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36529739

RESUMO

Bladder cancer is a common malignant tumor of the genitourinary system, with the primary cause of death being metastasis. The most common metastatic sites are the lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland, and the intestine. Brain and heart metastases are rare. In this report, we describe a patient who had pulmonary lymph node metastases more than a year after being diagnosed with bladder cancer, followed by brain and cardiac metastases more than two years later. Following the failure of standard first-line chemotherapy, the patient accepted 6 cycles of tislelizumab immunotherapy. The re-examination revealed that the bilateral frontal brain metastases had vanished, the right temporal lobe metastases had been greatly decreased, the neurological symptoms had been alleviated, and the cardiac metastases had disappeared. This is a rare clinical case with encouraging effects of tislelizumab and can serve as a model for the treatment of similar patients.


Assuntos
Linfonodos , Neoplasias da Bexiga Urinária , Humanos , Linfonodos/patologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Pulmão/patologia , Imunoterapia , Encéfalo/patologia
15.
Sensors (Basel) ; 22(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35591077

RESUMO

Most traditional agricultural traceability systems are centralized, which could result in the low reliability of traceability results, enterprise privacy data leakage vulnerabilities, and the generation of information islands. To solve the above problems, we propose a trusted agricultural product traceability system based on the Ethereum blockchain in this paper. We designed a dual storage model of "Blockchain+IPFS (InterPlanetary File System)" to reduce the storage pressure of the blockchain and realize efficient information queries. Additionally, we propose a data privacy protection solution based on some cryptographic primitives and the Merkle Tree that can avoid enterprise privacy and sensitive data leakage. Furthermore, we implemented the proposed system using the Ethereum blockchain platform and provided the cost, performance, and security analysis, as well as compared it with the existing solutions. The results showed that the proposed system is both efficient and feasible and can meet the practical application requirements.


Assuntos
Blockchain , Segurança Computacional , Privacidade , Reprodutibilidade dos Testes
16.
Biochem Biophys Res Commun ; 571: 152-158, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34325131

RESUMO

Potent neutralizing antibodies (Abs) have been proven with therapeutic efficacy for the intervention against SARS-CoV-2. Majority of these Abs function by directly interfering with the virus entry to host cells. Here, we identified a receptor binding domain (RBD) specific monoclonal Ab (mAb) 82A6 with efficient neutralizing potency against authentic SARS-CoV-2 virus. As most Abs targeting the non-receptor binding motif (RBM) region, 82A6 was incapable to block the RBD-ACE2 interaction. In particular, it actively promoted the S1 subunit shedding from the S protein, which may lead to effective reduction of intact SARS-CoV-2 viruses. Importantly, it could block potential syncytia formation associated with post-infectious cell surface expression of S proteins. Our study evidenced a RBD specific Ab with unique beneficial efficacy against SARS-CoV-2 infection, which might bring informative significance to understand the collective effects of neutralizing Abs elicited in COVID-19 patients.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/uso terapêutico , Especificidade de Anticorpos , Sítios de Ligação/imunologia , COVID-19/imunologia , COVID-19/virologia , Células Gigantes/imunologia , Células Gigantes/virologia , Células HEK293 , Humanos , Imunização Passiva , Técnicas In Vitro , Domínios Proteicos , Subunidades Proteicas , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/química , Eliminação de Partículas Virais , Soroterapia para COVID-19
17.
Opt Express ; 29(2): 1340-1359, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33726352

RESUMO

Light propagation in turbulent media is conventionally studied with the help of the spatio-temporal power spectra of the refractive index fluctuations. In particular, for natural water turbulence several models for the spatial power spectra have been developed based on the classic, Kolmogorov postulates. However, as currently widely accepted, non-Kolmogorov turbulent regime is also common in the stratified flow fields, as suggested by recent developments in atmospheric optics. Until now all the models developed for the non-Kolmogorov optical turbulence were pertinent to atmospheric research and, hence, involved only one advected scalar, e.g., temperature. We generalize the oceanic spatial power spectrum, based on two advected scalars, temperature and salinity concentration, to the non-Kolmogorov turbulence regime, with the help of the so-called "Upper-Bound Limitation" and by adopting the concept of spectral correlation of two advected scalars. The proposed power spectrum can handle general non-Kolmogorov, anisotropic turbulence but reduces to Kolmogorov, isotropic case if the power law exponents of temperature and salinity are set to 11/3 and anisotropy coefficient is set to unity. To show the application of the new spectrum, we derive the expression for the second-order mutual coherence function of a spherical wave and examine its coherence radius (in both scalar and vector forms) to characterize the turbulent disturbance. Our numerical calculations show that the statistics of the spherical wave vary substantially with temperature and salinity non-Kolmogorov power law exponents and temperature-salinity spectral correlation coefficient. The introduced spectrum is envisioned to become of significance for theoretical analysis and experimental measurements of non-classic natural water double-diffusion turbulent regimes.

18.
Appl Opt ; 60(15): 4462-4468, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34143139

RESUMO

Underwater polarization differential imaging requires the estimation of different parameters, and the parameters can be accurately obtained by using optical correlation. However, optical correlation as a criterion function to estimate parameters takes a lot of time. To expedite the parameters' estimation process, we propose two operations to process underwater polarization images. One operation is to update the analyzer angle range to reduce the number of processed images. The other is image downsampling, which reduces the amount of calculation for the corresponding images. In experiments, we confirmed the feasibility of our method. We have obtained an average of 42 times the calculation speed increase under the conditions of updating the analyzer angle range 3 times and reducing the image scale by 16 times. The results of our method are consistent with those of traditional methods. This established method is conducive to the practical application of underwater polarization differential imaging.

19.
J Med Internet Res ; 23(8): e29529, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397393

RESUMO

BACKGROUND: Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. OBJECTIVE: This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. METHODS: This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes. RESULTS: A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005). CONCLUSIONS: The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-032949.


Assuntos
Qualidade de Vida , Varfarina , Anticoagulantes/uso terapêutico , Valvas Cardíacas , Humanos , Coeficiente Internacional Normatizado , Internet , Estudos Prospectivos , Resultado do Tratamento , Varfarina/efeitos adversos
20.
J Card Surg ; 36(6): 1864-1871, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33604903

RESUMO

OBJECTIVE: To compare the midterm outcomes of patients with isolated left anterior descending disease (iLAD) who underwent robotically assisted coronary artery bypass graft (R-CABG) and percutaneous coronary intervention (PCI) with drug eluting stents (DES). METHOD: Clinic data was collected in 223 patients who underwent R-CABG in our hospital between July, 2007 to November, 2014. Cardiology Database System of our hospital was used to identify 4047 patients who underwent PCI with DES for LAD lesion between April, 2011 to November, 2014. Total 496 patients received DES and 108 patients underwent R-CABG after screening. Patients were propensity matched into 108 R-CABG and DES pairs according to vital statistic. Mortality, myocardial infarction (MI), stroke, repeat target lesion revascularization (r-TLR), main adverse cardiac and cerebral events (MACCE), and angina relief were compared across pairs. RESULT: Kaplan-Meier estimates for R-CABG and DES had no significant difference in mortality (p = 1.00), MI (p = .32), Stroke (p = .80), and MACCE (p = .47), but the rate of r-TLR (p = .03) were lower in R-CABG group. Patients who underwent R-CABG had better angina relief (p = .02), lower rate of arrhythmia (p < .001), and recurrent angina (p = .02) after operation compared patients received DES. CONCLUSION: R-CABG offers lower r-TLR rate and better angina relief compared with DES for revascularization in patients with isolated proximal LAD stenosis and there was no difference in mortality, MI, stroke, and MACCE between them.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Procedimentos Cirúrgicos Robóticos , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Humanos , Resultado do Tratamento
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