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1.
Cell Stem Cell ; 31(4): 554-569.e17, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579685

RESUMO

The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitro and in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitro and in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway.


Assuntos
Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Proliferação de Células , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP/agonistas , Proteínas de Sinalização YAP/efeitos dos fármacos , Proteínas de Sinalização YAP/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
3.
BMC Vet Res ; 19(1): 256, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38053140

RESUMO

BACKGROUND: Ectromelia virus (ECTV) is the causative agent of mousepox in mice. In the past century, ECTV was a serious threat to laboratory mouse colonies worldwide. Recombinase polymerase amplification (RPA), which is widely used in virus detection, is an isothermal amplification method. RESULTS: In this study, a probe-based RPA detection method was established for rapid and sensitive detection of ECTV.Primers were designed for the highly conserved region of the crmD gene, the main core protein of recessive poxvirus, and standard plasmids were constructed. The lowest detection limit of the ECTV RT- RPA assay was 100 copies of DNA mol-ecules per reaction. In addition, the method showed high specificity and did not cross-react with other common mouse viruses.Therefore, the practicability of the RPA method in the field was confirmed by the detection of 135 clinical samples. The real-time RPA assay was very similar to the ECTV real-time PCR assay, with 100% agreement. CONCLUSIONS: In conclusion, this RPA assay offers a novel alternative for the simple, sensitive, and specific identification of ECTV, especially in low-resource settings.


Assuntos
Vírus da Ectromelia , Recombinases , Animais , Camundongos , Recombinases/metabolismo , Vírus da Ectromelia/genética , Vírus da Ectromelia/metabolismo , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/veterinária , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reação em Cadeia da Polimerase em Tempo Real/métodos
4.
Mil Med Res ; 10(1): 67, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115158

RESUMO

Electroencephalography (EEG) is a non-invasive measurement method for brain activity. Due to its safety, high resolution, and hypersensitivity to dynamic changes in brain neural signals, EEG has aroused much interest in scientific research and medical fields. This article reviews the types of EEG signals, multiple EEG signal analysis methods, and the application of relevant methods in the neuroscience field and for diagnosing neurological diseases. First, three types of EEG signals, including time-invariant EEG, accurate event-related EEG, and random event-related EEG, are introduced. Second, five main directions for the methods of EEG analysis, including power spectrum analysis, time-frequency analysis, connectivity analysis, source localization methods, and machine learning methods, are described in the main section, along with different sub-methods and effect evaluations for solving the same problem. Finally, the application scenarios of different EEG analysis methods are emphasized, and the advantages and disadvantages of similar methods are distinguished. This article is expected to assist researchers in selecting suitable EEG analysis methods based on their research objectives, provide references for subsequent research, and summarize current issues and prospects for the future.


Assuntos
Eletroencefalografia , Neurologia , Humanos , Eletroencefalografia/métodos , Encéfalo
5.
J Orthop Surg Res ; 18(1): 840, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37932801

RESUMO

PURPOSE: The biomechanical capacity of "Barrel Hoop Plate (BHP)" in the treatment of the posterolateral tibial plateau (PL) depression fractures remains unknown. In this study, two kinds of posterolateral tibial plateau depression models involving mild slope-type depression fracture (MSDF) and local sink hole-type depression fracture (LSDF) were created to test and compare the biomechanical capacities of BHP with the other two conventional fixations (Anterolateral Plate and Posterolateral Plate, ALP and PLP) by finite element analysis. METHODS: The 3D models of three kinds of plate-screw systems and the two kinds of PL-depression models (MSDF and LSDF) were created. An axial force of 400N was applied from the distal femur to the tibial plateau. The maximal displacements of the posterolateral fractures (PLFs), the distribution on the PLFs articular surface and key points displacements were measured. Stresses in the fixation complex including the maximal Equivalent (von-Mises) Stress of implants, the max shear stress of PLFs and stiffness of the fixation were calculated. RESULTS: The maximal displacement of MSDF was least in Group BHP. The maximal displacement of LSDF was least in Group ALP. In MSDF, BHP showed the best rim fix effect in MSDF, but unsatisfactory results in LSDF. In both MSDF and LSDF, the greatest max Equivalent Stress of the plate and the screw occurred in the PLP system. ALP and BHP showed a comparable stiffness in MSDF and ALP had the strongest stiffness in the fixation of LSDF. CONCLUSIONS: In MSDF, the BHP has the best biomechanical capacity, especially in displacements of key points such as the PL rim, fracture line, and depression center. In LSDF, the ALP system shows the best biomechanical effect. Although the PLP has the best fixation effect on the posterior wall, it is not suitable for PL-depression fracture fixation.


Assuntos
Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Análise de Elementos Finitos , Depressão , Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Placas Ósseas , Fenômenos Biomecânicos
6.
Sci Rep ; 13(1): 16654, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789025

RESUMO

The preservation of quantum correlations requires optimal procedures and the proper design of the transmitting channels. In this regard, we address designing a hybrid channel comprising a single-mode cavity accompanied by a super-Gaussian beam and local dephasing parts based on the dynamics of quantum characteristics. We choose two-level atoms and various functions such as traced-distance discord, concurrence, and local-quantum uncertainty to analyze the effectiveness of the hybrid channel to preserve quantum correlations along with entropy suppression discussed using linear entropy. The joint configuration of the considered fields is found to not only preserve but also generate quantum correlations even in the presence of local dephasing. Most importantly, within certain limits, the proposed channel can be readily regulated to generate maximal quantum correlations and complete suppression of the disorder. Besides, compared to the individual parts, mixing the Fock state cavity, super-Gaussian beam, and local dephasing remains a resourceful choice for the prolonged quantum correlations' preservation. Finally, we present an interrelationship between the considered two-qubit correlations' functions, showing the deviation between each two correlations and of the considered state from maximal entanglement under the influence of the assumed hybrid channel.

7.
Front Immunol ; 14: 1165396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143683

RESUMO

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most threatening pathogens of swine. The nucleocapsid (N) protein is the major structural protein of the virus and has been used as a PRRSV diagnostic antigen due to its high level of inherent immunogenicity. Methods: The recombinant PRRSV N protein was generated by the prokaryotic expressing system and used to immunized mice. Monoclonal antibodies against PRRSV were produced and validated by western blot analysis and indirect immunofluorescence analysis. In this study, the linear epitope of a specific monoclonal antibody mAb (N06) was subsequently identified by enzyme-linked immunosorbent assays (ELISA) using the synthesized overlapping peptides as antigens. Results: According to the results of western blot analysis and indirect immunofluorescence analysis, mAb (N06) was capable of recognizing the native form as well as the denatured form of PRRSV N protein. The results of ELISA showed that mAb N06 recognized the epitope NRKKNPEKPHFPLATE, which was consistent with BCPREDS predictions of antigenicity. Conclusion: All the data suggested that the mAb (N06) can be used as diagnostic reagents for PRRSV detection, while the recognized linear epitope can be useful in epitope-based vaccines development, which is helpful for the control of local PRRSV infections in swine.


Assuntos
Epitopos de Linfócito B , Proteínas do Nucleocapsídeo , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Proteínas do Nucleocapsídeo/química , Proteínas do Nucleocapsídeo/metabolismo , Anticorpos Monoclonais/imunologia , Vacinas Virais/imunologia , Síndrome Respiratória e Reprodutiva Suína/diagnóstico , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico
8.
Can J Vet Res ; 87(2): 120-126, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37020572

RESUMO

Seneca Valley virus (SVV) is an oncolytic virus, which belongs to the Picornaviridae family, that causes blisters on the nose and hooves, affecting the production performance of pigs. However, the function of proinflammatory cytokines and chemokines in SVV infection is still unclear. In our study, SVV infection could induce a high expression of proinflammatory cytokines interleukin (IL)-1α, IL-1ß, and tumor necrosis factor α (TNF-α) and chemokines, including chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 5 (CCL5), and chemokine (C-X-C motif) ligand 10 (CXCL10). Interfered genes of IL-1α, IL-1ß, and TNF-α inhibited virus replication, but interfered genes of CCL2, CCL5, and CXCL10 promoted virus replication. These results indicate that proinflammatory cytokines and chemokines are involved in SVV infection; this will be beneficial to explore the pathogenesis and cytokine therapy of SVV.


Le virus de la Vallée de Seneca (SVV) est un virus oncolytique, qui appartient à la famille des Picornaviridae, qui provoque des cloques sur le nez et les sabots, affectant les performances de production des porcs. Cependant, la fonction des cytokines pro-inflammatoires et des chimiokines dans l'infection par le SVV n'est toujours pas claire. Dans notre étude, l'infection par le SVV pourrait induire une forte expression des cytokines pro-inflammatoires interleukine (IL)-1α, IL-1ß, et du facteur de nécrose tumorale α (TNF-α) et des chimiokines, y compris la chimiokine (motif C-C) ligand 2 (CCL2), chimiokine (motif C-C) ligand 5 (CCL5) et chimiokine (motif C-X-C) ligand 10 (CXCL10). Les gènes interférés d'IL-1α, IL-1ß et TNF-α inhibent la réplication virale, mais les gènes interférents de CCL2, CCL5 et CXCL10 favorisent la réplication virale. Ces résultats indiquent que les cytokines pro-inflammatoires et les chimiokines sont impliquées dans l'infection par le SVV; cela sera bénéfique pour explorer la pathogenèse et la thérapie par cytokines du SVV.(Traduit par Docteur Serge Messier).


Assuntos
Citocinas , Picornaviridae , Animais , Suínos , Citocinas/genética , Fator de Necrose Tumoral alfa/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo
9.
Antiviral Res ; 213: 105586, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36997073

RESUMO

S-217622 (Ensitrelvir) is a reversible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro) inhibitor which obtained emergency regulatory approval in Japan for the treatment of SARS-CoV-2 infection on Nov 22, 2022. Herein, analogs of S-271622 with deuterium-for-hydrogen replacement were synthesized for comparison of the antiviral activities and pharmacokinetic (PK) profiles. Compared to the parent compound, C11-d2-S-217622 compound YY-278 retained in vitro activity against 3CLpro and SARS-CoV-2. X-ray crystal structural studies showed similar interactions of SARS-CoV-2 3CLpro with YY-278 and S-271622. The PK profiling revealed the relatively favorable bioavailability and plasma exposure of YY-278. In addition, YY-278, as well as S-217622, displayed broadly anti-coronaviral activities against 6 other coronaviruses that infect humans and animals. These results laid the foundation for further research on the therapeutic potential of YY-278 against COVID-19 and other coronaviral diseases.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Antivirais/uso terapêutico , Japão , Inibidores de Proteases/química
10.
Int J Biol Macromol ; 239: 124241, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36996959

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV), which causes severe diarrhea in newborn piglets, was first identified in Southern China in 2017. Since the Nucleocapsid (N) protein in SADS-CoV is highly conserved and plays a key role in virus replication, it is often used as a target protein in scientific research. In this study, the N protein of SADS-CoV was successfully expressed, and a new monoclonal antibody (mAb), 5G12, against the protein was generated successfully. The mAb 5G12 can be used to detect SADS-CoV strains by indirect immunofluorescence assay (IFA) and western blotting. The mAb 5G12 epitope was located to amino acids 11 EQAESRGRK 19 by evaluating the antibody for reactivity with a series of truncated N protein segments. The biological information analysis showed that the antigenic epitope had a high antigenic index and conservation. This study will help further understand the protein structure and function of SADS-CoV and in the establishment of specific SADS-CoV detection methods.


Assuntos
Infecções por Coronavirus , Proteínas do Nucleocapsídeo , Animais , Suínos , Epitopos , Anticorpos Monoclonais
11.
Eur J Med Chem ; 249: 115113, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36706621

RESUMO

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5'-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041, exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta-genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies.


Assuntos
Infecções por Coronavirus , Coronavirus , Animais , Humanos , Camundongos , Ibuprofeno/farmacologia , Linhagem Celular , Infecções por Coronavirus/tratamento farmacológico , Replicação Viral , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios/farmacologia , Nucleotídeos/farmacologia
12.
J Orthop Sci ; 28(3): 614-620, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35074294

RESUMO

BACKGROUND: This study aimed to evaluate the clinical outcomes of ipsilateral femoral neck and shaft fractures and identify the risk factors associated with missed diagnosis of femoral neck fractures and clinical outcomes of this fracture. METHODS: The ipsilateral femoral neck and shaft fractures from seven centers were retrospectively reviewed. Data on injury mechanism, fracture pattern, and fracture classification; surgical factors including fixation method; and timing of detection of femoral neck fracture were analyzed. The clinical outcomes, complications, and the incidence of avascular necrosis of the femoral head (AVNFH) were reviewed. Risk factors for missed femoral neck fracture and complications were analyzed. RESULTS: In total, 74 patients with an average age of 43.6 years were included. Of the femoral shaft fractures, 56.8% were type A, 21.6% were type B, and 21.6% were type C. Sixteen patients had an open fracture of the femoral shaft. Femoral neck fracture was initially missed in 27% patients and the timing of delayed diagnosis was at an average of 11.1 days after injury. For detecting femoral neck fractures, minimal displacement of the femoral neck fracture was a risk factor, whereas computed tomography (CT) was a protective factor. The incidence of AVNFH was 6.8% at an average of 36.8 months after injury. The AVNFH group had more displaced femoral neck fractures at the time of surgery, but there was no difference in the timing of diagnosis compared to non-AVNFH group. The femoral shaft showed considerable healing problems, with an average union time of 29.7 weeks and a 20.2% nonunion rate. CONCLUSION: Ipsilateral femoral neck and shaft fractures had a high rate of missed diagnosis, especially in minimally displaced fractures; however, CT was a protective factor. AVNFH occurred in 6.8% and was related to femoral neck fracture displacement, but not delayed diagnosis. The femur nonunion rate was high, which warrants attention.


Assuntos
Fraturas do Fêmur , Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Humanos , Adulto , Colo do Fêmur , Estudos Retrospectivos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/epidemiologia , Fraturas do Colo Femoral/cirurgia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/etiologia , Tomografia Computadorizada por Raios X , Necrose da Cabeça do Fêmur/etiologia
13.
Viruses ; 16(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38275950

RESUMO

Nanoparticle-assisted polymerase chain reaction (nanoPCR) is a novel method for the rapid detection of pathogens. A sensitive and specific multiple nanoPCR assay was developed for simultaneous detection of avian leucosis virus (ALV) subgroups A, B and J. In this study, three pairs of primers were designed, based on the conserved region of the gp85 gene. An exploration of the optimal primer concentration and annealing temperature were carried out, for better performance of the nanoPCR assay. According to the results, the multiple nanoPCR assay amplified 336 pb, 625 bp and 167 bp fragments of ALV-A, -B and -J, respectively, and showed no cross-reactivity with irrelevant pathogens, suggesting the excellent specificity of the assay. The constructed standard DNA templates were used to estimate the limit of detection. As shown by the results, the detection limit of the nanoPCR assay was nearly 10 copies/µL. To further evaluate the detection ability of the assay, 186 clinical samples were detected using the nanoPCR assay, among which, 14 samples were confirmed as ALV positive; the results were further confirmed by sequencing. In conclusion, a highly specific and sensitive nanoPCR assay was successfully developed, which could be a useful tool for clinical diagnosis as well as for the discrimination of ALV-A, -B and -J.


Assuntos
Vírus da Leucose Aviária , Leucose Aviária , Nanopartículas , Animais , Vírus da Leucose Aviária/genética , Sensibilidade e Especificidade , Temperatura , Reação em Cadeia da Polimerase/métodos , Leucose Aviária/diagnóstico , Galinhas
14.
Front Microbiol ; 13: 1012516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466672

RESUMO

Allicin, which is generated by the catalytic reaction between alliin and alliinase extracted from garlic, has been shown to have a wide range of antimicrobial activities, but its anti-Cryptococcus efficacy and mechanism are not quite clear. Here, we have determined that the Conversion rate of allicin in the reaction product reached 97.5%. The minimal inhibitory concentration (MIC) of allicin against Cryptococcus neoformans (C. neoformans) H99 was 2 µg/ml, which is comparable to fluconazole (FLU, 1 µg/ml). Furthermore, allicin exhibited effective antifungal activity against 46 clinical isolates of C. neoformans, and the MICs ranged from 1 to 8 µg/ml, even for AmB-insensitive strains. Interestingly, allicin also exerted additive or synergistic effects when combined with amphotericin B (AmB) and FLU. Time-killing curves and long-term live cell imaging of H99 showed that 4 MIC of allicin had fungicide activity. Additionally, allicin (4 and 8 mg/kg) exerted a dose-dependent therapeutic effect on H99-infected mice by significantly reducing the wet pulmonary coefficient and Cryptococcus load and reducing lung damage. Even the efficacy of 8 mg/kg was comparable to FLU (20 mg/kg). Transcriptomics revealed that allicin may act on the cell membrane of H99. Subsequently, transmission electron microscopy (TEM) observations showed that allicin clearly breached the cell membrane and organelles of H99. Confocal laser scanning microscopy (CLSM) results further confirmed that allicin disrupted the permeability of the cell membranes of H99 in a dose-dependent manner. Allicin exhibits strong anti-C. neoformans activity in vitro and in vivo, mainly by destroying the permeability and related functions of Cryptococcus cell membranes.

15.
Carbohydr Polym ; 297: 120032, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184177

RESUMO

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.


Assuntos
Aloe , Aloe/metabolismo , Animais , Síndrome da Liberação de Citocina , Citocinas/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Mananas , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
16.
ACS Appl Mater Interfaces ; 14(40): 45178-45188, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36178205

RESUMO

Noninvasive photothermal therapy (PTT) is an emerging strategy for eliminating multidrug-resistant (MDR) bacteria that achieve sterilization by generating temperatures above 50 °C; however, such a high temperature also causes collateral damage to healthy tissues. In this study, we developed a low-temperature PTT based on borneol-containing polymer-modified MXene nanosheets (BPM) with bacteria-targeting capabilities. BPM was fabricated through the electrostatic coassembly of negatively charged two-dimensional MXene nanosheets (2DM) and positively charged quaternized α-(+)-borneol-poly(N,N-dimethyl ethyl methacrylate) (BPQ) polymers. Integrating BPQ with 2DM improved the stability of 2DM in physiological environments and enabled the bacterial membrane to be targeted due to the presence of a borneol group and the partially positive charge of BPQ. With the aid of near-infrared irradiation, BPM was able to effectively eliminate methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) through targeted photothermal hyperthermia. More importantly, BPM effectively eradicated more than 99.999% (>5 orders of magnitude) of MRSA by localized heating at a temperature that is safe for the human body (≤40 °C). Together, these findings suggest that BPM has good biocompatibility and that membrane-targeting low-temperature PTT could have great therapeutic potential against MDR infections.


Assuntos
Hipertermia Induzida , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Canfanos , Escherichia coli , Humanos , Hipertermia Induzida/métodos , Metacrilatos/farmacologia , Terapia Fototérmica , Polímeros/farmacologia , Temperatura
17.
Animals (Basel) ; 12(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36077908

RESUMO

Since 2010, a variant of porcine epidemic diarrhea virus (PEDV) has re-emerged in several provinces of China, resulting in severe economic losses for the pork industry. Here, we isolated and identified a variant PEDV strain, SC-YB73, in Guangdong Province, China. The pathological observations of jejunum showed atrophy of villi and edema in the lamina propria. The sequence analysis of the viral genome identified a six-nucleotide insertion in the E gene, which has not previously been detected in PEDV strains. Furthermore, 50 nucleotide sites were unique in SC-YB73 compared with 27 other PEDV strains. The phylogenetic analysis based on the complete genome showed that SC-YB73 was clustered in variant subgroup GII-a, which is widely prevalent in the Chinese pig population. The recombination analysis suggested that SC-YB73 originated from the recombination of GDS47, US PEDV prototype-like strains TW/Yunlin550/2018, and COL/Cundinamarca/2014. In the present study, we isolated and genetically characterized a variant PEDV strain, thus providing essential information for the control of PED outbreaks in China.

18.
Front Physiol ; 13: 902513, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812330

RESUMO

Background: Atrial appendage tachycardia (AAT) originating from the atrial appendage (AA) is extremely difficult to eliminate using radiofrequency catheter ablation (RFCA). The optimal management strategy for AAT refractory to RFCA remains unclear. Objective: This study aims to investigate the long-term result of ablative therapy and the optimal alternative management for AAT refractory to RFCA. Methods: A total of 51 patients with AAT originating from the AA undergoing RFCA were recruited. Video-assisted atrial appendectomy and oral ivabradine were performed on those with AATs refractory to RFCA, and this study aimed to evaluate their safety and long-term efficacy. Results: We included 51 patients (51/586, 8.7%) with AATs confirmed by activation mapping and contrast venography. Among them, there were 28 (54.9%) AATs originating from the distal AA. In total, 14 (27.4%) AATs were refractory to RFCA, including 13 originating from the distal AA and one arising from the proximal AA. Ten of 11 (90.9%) AATs originating from the distal AA were eliminated after an atrial appendectomy, and the other three AATs were suppressed using oral ivabradine. Origins from the distal AA refractory to RFCA and early age of AAT onset ≤26.5 years indicated the need for atrial appendectomy. No major complications occurred, and nine patients with tachycardia-induced cardiomyopathy fully recovered. Long-term success was achieved in 98.0% of patients with multiple treatment managements. Conclusion: AATs originating from the distal AA were more refractory to RFCA. RFCA was the cornerstone of AAT catheter ablation. Video-assisted thoracoscopic atrial appendectomy was an effective strategy for those origins at the distal AA and the age of AAT onset ≤26.5 years. Ivabradine represents a promising treatment for AAT temporarily in pediatric and young adult patients.

19.
Sci Transl Med ; 14(661): eabm7621, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-35579533

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus driving the ongoing coronavirus disease 2019 (COVID-19) pandemic, continues to rapidly evolve. Because of the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOCs), orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously, we showed that the parent nucleoside of remdesivir, GS-441524, has potent anti-SARS-CoV-2 activity. Here, we report that esterification of the 5'-hydroxyl moieties of GS-441524 markedly improved antiviral potency. This 5'-hydroxyl-isobutyryl prodrug, ATV006, demonstrated excellent oral bioavailability in rats and cynomolgus monkeys and exhibited potent antiviral efficacy against different SARS-CoV-2 VOCs in vitro and in three mouse models. Oral administration of ATV006 reduced viral loads and alleviated lung damage when administered prophylactically and therapeutically to K18-hACE2 mice challenged with the Delta variant of SARS-CoV-2. These data indicate that ATV006 represents a promising oral antiviral drug candidate for SARS-CoV-2.


Assuntos
Tratamento Farmacológico da COVID-19 , Pró-Fármacos , Adenosina/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Camundongos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Ratos , SARS-CoV-2
20.
Can J Vet Res ; 86(2): 102-107, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35388228

RESUMO

Vesicular disease caused by Seneca Valley virus (SVV) has recently emerged throughout China and caused certain industry losses. We used immunofluorescence and western blotting to confirm that 3 new SVV strains (CH-GDSG-2018-1, CH-GDSG-2018-2, and CH-GDSG-2018-3) were from 1 pig farm. Phylogenetic analysis revealed the following: i) all 3 strains belong to USA-GBI29-2015-like clades, ii) CH-GDSG-2018-3 might have diverged from CH-GDSG-2018-1 and CH-GDSG-2018-2, and iii) CH-GDSG-2018-3 is a recombinant of the CHhb17 and HeNKF-1 strains. Virus growth curves showed that CH-GDSG-2018-3 had stronger proliferation ability in vitro. Seneca Valley virus has evolved extensively within China and this study has furthered our understanding of SVV epidemiology.


La maladie vésiculeuse causée par le virus de la vallée de Seneca (SVV) est récemment apparue dans toute la Chine et a causé certaines pertes dans l'industrie. Nous avons utilisé l'immunofluorescence et l'immunobuvardage pour confirmer que trois nouvelles souches de SVV (CH-GDSG-2018-1, CH-GDSG-2018-2 et CH-GDSG-2018-3) provenaient d'un seul élevage de porcs. L'analyse phylogénétique a révélé ce qui suit : i) les trois souches appartiennent à des clades de type USA-GBI29-2015, ii) CH-GDSG-2018-3 pourrait avoir divergé de CH-GDSG-2018-1 et CH-GDSG-2018-2, et iii) CH-GDSG-2018-3 est un recombinant des souches CHhb17 et HeNKF-1. Les courbes de croissance virale ont montré que CH-GDSG-2018-3 avait une capacité de prolifération in vitro plus forte. Le virus SVV a considérablement évolué en Chine et cette étude a approfondi notre compréhension de l'épidémiologie de ce virus.(Traduit par Docteur Serge Messier).


Assuntos
Infecções por Picornaviridae , Doenças dos Suínos , Animais , Fazendas , Filogenia , Picornaviridae , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/veterinária , Suínos , Doenças dos Suínos/epidemiologia
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