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1.
J Colloid Interface Sci ; 667: 282-290, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38640648

RESUMO

Se-based cathodes have caught tremendous attention owing to their comparable volumetric capacity and better electronic conductivity to S cathodes. However, its low utilization ratio and sluggish redox kinetics due to the high reaction barrier of solid-phase transformation from Se to Li2Se limit its practical application. Herein, an in-situ texturing hollow carbon host by gas-solid interface reaction anchored with Fe single-atomic catalyst is designed and prepared for advanced Li-Se batteries. This Se host presents high pore volume of 1.49 cm3 g-1, Fe single atom content of 1.53 wt%, and its specific structure protects single-atomic catalyst from the destructive reaction environment, thus balancing catalytic activity and durability. After Se loading by reduction of H2SeO3, this homogenous Se-based cathode delivers a superior rate capacity of 431.3 mA h g-1 at 4C, and great discharge capacity of 301.8 mA h g-1 after 1000 cycles at 10C, with high Li-ion diffusion coefficient and capacitance-contributed ratio. The distribution of relaxation times analysis verifies solid-phase transformation mechanism of this cathode and density functional theory calculations confirm the adsorption and bidirectionally catalysis effect of Fe single-atomic catalyst. This work provides a new strategy to prepare high-efficient Se cathode associated with non-noble metal single atoms for high-performance Li-Se batteries.

2.
Foodborne Pathog Dis ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38527171

RESUMO

Salmonella is a globally prevalent foodborne bacterium, and ceftriaxone and azithromycin have been regarded as drugs of choice for treating Salmonella infections, particularly in children. With the growing incidence of ceftriaxone and azithromycin resistance in Salmonella, there is an urgent requirement for a rapid and dependable gene testing approach to enhance the efficacy of treating Salmonella infections. Utilizing the orange to green visible dye approach, this study developed loop-mediated isothermal amplification (LAMP) assays for the sensitive and specific detection of Salmonella, ceftriaxone and azithromycin resistance genes (including CTX-M-1 group, mph(A), and ermB genes) in stool and blood samples. The specificity and sensitivity of primers during the LAMP assays for detection of Salmonella, CTX-M-1 group, mph(A), and ermB genes were determined in this study. The detection threshold for Salmonella was found to be 1.5 × 103 colony-forming units (CFU)/mL, while it was 1.5 × 102 CFU/mL for CTX-M-1 group genes (including blaCTX-M-3, blaCTX-M-15, and blaCTX-M-55), 1.5 × 102 CFU/mL for mph(A), and 1.5 × 102 CFU/mL for ermB, showing 10-103-fold, 103-fold, and 105-fold increased sensitivity compared with the polymerase chain reaction assay, respectively. Results indicated that the LAMP primers designed for Salmonella, CTX-M-1 group, mph(A), and ermB genes possess high specificity (100%) and sensitivity (over 94%). This novel approach advocates its application in detecting Salmonella, CTX-M-1 group, mph(A), and ermB genes.

3.
Chem Commun (Camb) ; 60(26): 3587-3590, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38470314

RESUMO

A novel strategy in which palladium(II)-catalyzed tandem cyclization is used to obtain N-heterocyclic architectures containing a seven-membered ring has been developed and used to synthesize a series of derivatives. The reaction uses an eco-friendly mixed solvent (water : EtOH = 2 : 1) instead of DMSO and maintains a high yield (91%). Its potential application value and reaction mechanism have also been explored.

4.
J Gastroenterol Hepatol ; 39(4): 658-666, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38251791

RESUMO

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.


Assuntos
Aminas , Esofagite Péptica , Refluxo Gastroesofágico , Úlcera Péptica , Pirróis , Humanos , Esomeprazol/efeitos adversos , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/etiologia , Resultado do Tratamento , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/complicações , Úlcera Péptica/complicações , Método Duplo-Cego , Inibidores da Bomba de Prótons/efeitos adversos
5.
J Biomed Sci ; 31(1): 8, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38229040

RESUMO

BACKGROUND: Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications. METHODS: In the present study, we investigated a low-passage human isolate of the East/ Central/South African (ECSA) lineage of CHIKV strain LK(EH)CH6708, which exhibited a mix of small and large viral plaques. The small and large plaque variants were isolated and designated as CHIKV-SP and CHIKV-BP, respectively. CHIKV-SP and CHIKV-BP were characterized in vitro and in vivo to compare their virus production and virulence. Additionally, whole viral genome analysis and reverse genetics were employed to identify genomic virulence factors. RESULTS: CHIKV-SP demonstrated lower virus production in mammalian cells and attenuated virulence in a murine model. On the other hand, CHIKV-BP induced higher pro-inflammatory cytokine levels, compromised the integrity of the blood-brain barrier, and led to astrocyte infection in mouse brains. Furthermore, the CHIKV-SP variant had limited transmission potential in Aedes albopictus mosquitoes, likely due to restricted dissemination. Whole viral genome analysis revealed multiple genetic mutations in the CHIKV-SP variant, including a Glycine (G) to Arginine (R) mutation at position 55 in the viral E2 glycoprotein. Reverse genetics experiments confirmed that the E2-G55R mutation alone was sufficient to reduce virus production in vitro and virulence in mice. CONCLUSIONS: These findings highlight the attenuating effects of the E2-G55R mutation on CHIKV pathogenicity and neurovirulence and emphasize the importance of monitoring this mutation in natural infections.


Assuntos
Aedes , Vírus Chikungunya , Humanos , Camundongos , Animais , Vírus Chikungunya/genética , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Aminoácidos , Mutação , Mamíferos
6.
Sci Rep ; 14(1): 741, 2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38185674

RESUMO

The shear yield stress is an important parameter for the industrial application of magnetorheological (MR) fluids. A test equipment was designed and built to perform investigations on the behaviours of compression and shear after squeeze of MR fluids. Mathematical expression of magnetic flux density was further established. Furthermore, the magnetic field distribution of the test device based on two-coil mode and single-coil mode was simulated and compared using finite element analysis(ANSYS/Multiphysics). An experimental test system was fabricated and modified based on the final conditions and simulation results. The compression and shear after squeeze performances of MR fluids were tested. The results showed that a smaller initial gap distance or a larger compressive strain corresponds to a larger compressive stress under the same external magnetic field strength. The shear yield stress after the squeeze of MR fluids increases quickly with the increasing compression stress and the increasing magnetic flux density. This test equipment was thought to be suitable for studying the compression and shear after squeeze performances of MR fluids.

7.
Macromol Rapid Commun ; 45(5): e2300543, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38102953

RESUMO

Entropy is a universal concept across the physics of mixtures. While the role of entropy in other multicomponent materials has been appreciated, its effects in polymers and plastics have not. In this work, it is demonstrated that the seemingly small mixing entropy contributes to the miscibility and performance of polymer alloys. Experimental and modeling studies on over 30 polymer pairs reveal a strong correlation between entropy, morphology, and mechanical properties, while elucidating the mechanism behind: in polymer blends with weak interactions, entropy leads to homogeneously dispersed nanosized domains stabilized by highly entangled chains. This unique microstructure promotes uniform plastic deformation at the interface, thus improving the toughness of conventional brittle polymers by 1-2 orders of magnitude without sacrificing other properties, analogous to high-entropy metallic alloys. The proposed strategy also applies to ternary polymer systems and copolymers, offering a new pathway toward the development of sustainable polymers.


Assuntos
Ligas , Polímeros , Entropia , Polímeros/química , Ligas/química , Plásticos
8.
ACS Nano ; 17(21): 21639-21661, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37852618

RESUMO

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.


Assuntos
COVID-19 , Vesículas Extracelulares , Humanos , Antivirais/farmacologia , Oligonucleotídeos , Pandemias , SARS-CoV-2 , Eritrócitos
9.
Infect Drug Resist ; 16: 6175-6183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724093

RESUMO

Purpose: Metagenomic next-generation sequencing (mNGS) has been widely used to diagnose infectious diseases. However, there are few studies on its diagnostic performance in the central nervous system (CNS) cryptococcosis. This study examined the diagnostic efficacy of mNGS in identifying Cryptococcus spp. in cerebrospinal fluid (CSF) samples. Patients and Methods: From March 2021 to March 2023, 290 patients with suspected CNS infection were recruited from the First Affiliated Hospital, School of Medicine, Zhejiang University, and 74 patients were ultimately included in the study. Lastly, 22 patients with CNS cryptococcosis were included. Of these patients, 25 CSF samples were enrolled. The diagnostic performance of conventional assays [including India ink, cryptococcal antigen (CrAg) testing, and culture] and mNGS was evaluated for CNS cryptococcosis. Results: In the 25 samples collected, the coincidence rates of mNGS with India ink, CrAg, and culture were 64.0% (16/25), 80.0% (20/25), and 80.0% (20/25), respectively. Without antifungal drug exposure, the coincidence rates were increased to 66.7% (10/15), 100.0% (15/15), and 93.3% (14/15), respectively. The coincidence rates after antifungal therapy were all decreased to 60.0% (6/10), 50.0% (5/10), and 60.0% (6/10), respectively. Moreover, in the 25 samples, the sensitivity of mNGS reached 80.0%, and of India ink, CrAg testing, and culture were 68.0, 100.0, and 60.0%, respectively. The mNGS showed an excellent positive rate (100.0%) in the 15 samples collected without antifungal drug exposure, which was significantly higher than the antifungal drug-exposed group (n = 10) (50.0%) (P = 0.005). The reads of Cryptococcus spp. before antifungal therapy were significantly higher than after it (median, 25,915 vs 2, P = 0.008). Conclusion: mNGS is an effective tool for diagnosing CNS cryptococcosis using CSF; however, its sensitivity decreases considerably in patients who have been effectively treated with antifungal drugs.

11.
Infect Drug Resist ; 16: 4137-4145, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37396070

RESUMO

Purpose: Metagenomic next-generation sequencing (mNGS) has been extensively used in the diagnosis of infectious diseases but has rarely been applied in non-tuberculous mycobacterial pulmonary disease (NTMPD). This study analyzed the diagnostic performance of mNGS in bronchoalveolar lavage fluid (BALF) samples to identify non-tuberculous mycobacteria (NTM). Patients and Methods: A total of 231 patients with suspected NTMPD were recruited from the First Affiliated Hospital, School of Medicine, Zhejiang University, from March 2021 to October 2022. A total of 118 cases were ultimately included. Of these patients, 61 cases were enrolled in the NTMPD group, 23 cases were enrolled in the suspected-NTMPD group, and 34 cases were enrolled in the non-NTMPD group. The diagnostic performance of traditional culture, acid-fast staining (AFS), and mNGS for NTMPD was assessed. Results: Patients in the NTMPD group had a higher proportion of bronchiectasis (P=0.007). Among mNGS-positive samples in the NTMPD group, a significantly higher reads number of NTM was observed in AFS-positive patients [61.50 (22.00, 395.00) vs 15.50 (6.00, 36.25), P=0.008]. Meanwhile, mNGS demonstrated a sensitivity of 90.2%, which was far superior to AFS (42.0%) and culture (77.0%) (P<0.001). The specificity of mNGS in detecting NTM was 100%, which was the same as that of traditional culture. The area under the receiver operating characteristic curve of mNGS was 0.951 (95% CI 0.906-0.996), which was higher than that of culture (0.885 [95% CI 0.818-0.953]) and AFS (0.686 [95% CI 0.562-0.810]). In addition to NTM, other pulmonary pathogens were also found by mNGS. Conclusion: mNGS using BALF samples is a rapid and effective diagnostic tool for NTMPD, and mNGS is recommended for patients with suspected NMTPD or NTM coinfected pneumonia.

12.
Nat Commun ; 14(1): 4474, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491340

RESUMO

High-performance Li-ion/metal batteries working at a low temperature (i.e., <-20 °C) are desired but hindered by the sluggish kinetics associated with Li+ transport and charge transfer. Herein, the temperature-dependent Li+ behavior during Li plating is profiled by various characterization techniques, suggesting that Li+ diffusion through the solid electrolyte interface (SEI) layer is the key rate-determining step. Lowering the temperature not only slows down Li+ transport, but also alters the thermodynamic reaction of electrolyte decomposition, resulting in different reaction pathways and forming an SEI layer consisting of intermediate products rich in organic species. Such an SEI layer is metastable and unsuitable for efficient Li+ transport. By tuning the solvation structure of the electrolyte with a lower lowest unoccupied molecular orbital (LUMO) energy level and polar groups, such as fluorinated electrolytes like 1 mol L-1 lithium bis(fluorosulfonyl)imide (LiFSI) in methyl trifluoroacetate (MTFA): fluoroethylene carbonate (FEC) (8:2, weight ratio), an inorganic-rich SEI layer more readily forms, which exhibits enhanced tolerance to a change of working temperature (thermodynamics) and improved Li+ transport (kinetics). Our findings uncover the kinetic bottleneck for Li+ transport at low temperature and provide directions to enhance the reaction kinetics/thermodynamics and low-temperature performance by constructing inorganic-rich interphases.

13.
J Orthop Surg Res ; 18(1): 510, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37464433

RESUMO

BACKGROUND: Postoperative anemia is a risk factor for adverse surgical outcomes. Our study aimed to assess the role of intravenous iron and erythropoietin therapy for the rapid correction of anemia following orthopedic surgery. METHODS: Patients undergoing elective orthopedic surgery were prospectively enrolled and randomly divided into three groups: Control (placebo), Group 1 (IV iron monotherapy), and Group 2 [combined IV iron and recombinant human erythropoietin (rHuEPO) therapy]. Blood tests were performed preoperative (baseline) and on postoperative days (PODs) 1, 3, and 7. RESULTS: All groups demonstrated significantly lower hemoglobin (Hb) concentrations compared to baseline, with no significant inter-group differences in postoperative Hb concentrations (p > 0.05). Serum erythropoietin, ferritin, and vitamin B12 levels, and reticulocyte count increased beyond normal ranges in all groups. Significantly lower serum iron levels were observed postoperatively in all groups (p < 0.05). No significant inter-group differences in hepcidin level were observed (p > 0.05). CONCLUSION: Postoperative treatment with combined intravenous iron and rHuEPO was ineffective in correcting postoperative anemia among orthopedic surgery patients, besides achieving higher reticulocyte counts in the first week of surgery. No improvement in mobilization of storage iron was achieved with rHuEPO. We further suggest against vitamin B12 administration during the early postoperative period.


Assuntos
Anemia , Eritropoetina , Procedimentos Ortopédicos , Humanos , Ferro , Anemia/tratamento farmacológico , Anemia/etiologia , Procedimentos Ortopédicos/efeitos adversos , Vitaminas/uso terapêutico , Proteínas Recombinantes/uso terapêutico
14.
Viruses ; 15(6)2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37376676

RESUMO

Dengue virus (DENV) is the cause of dengue fever, infecting 390 million people worldwide per year. It is transmitted to humans through the bites of mosquitoes and could potentially develop severe symptoms. In spite of the rising social and economic impact inflicted by the disease on the global population, a conspicuous lack of efficacious therapeutics against DENV still persists. In this study, catechin, a natural polyphenol compound, was evaluated as a DENV infection inhibitor in vitro. Through time-course studies, catechin was shown to inhibit a post-entry stage of the DENV replication cycle. Further investigation revealed its role in affecting viral protein translation. Catechin inhibited the replication of all four DENV serotypes and chikungunya virus (CHIKV). Together, these results demonstrate the ability of catechin to inhibit DENV replication, hinting at its potential to be used as a starting scaffold for further development of antivirals against DENV infection.


Assuntos
Catequina , Vírus da Dengue , Dengue , Animais , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Replicação Viral
15.
Braz J Microbiol ; 54(2): 1093-1102, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37145298

RESUMO

Heracleum vicinum Boiss., a perennial plant of Angelica in Umbelliferae, is mainly distributed in Sichuan and Hunan of China. Trichophyton rubrum is a common skin fungus causing dermatophyte. The previous experimental study found that the ethanol extract from Heracleum vicinum Boiss. had excellent anti-Trichophyton rubrum activity, especially the ethanol extract further extracted with petroleum ether and dichloromethane has the best antibacterial effect and has good potential for treating dermatophytes. In this study, Heracleum vicinum Boiss. was extracted with ethanol by microwave-assisted ultrasonic extraction method and isolated with silica gel column to obtain a coumarin compound M1-1 by the guidance of anti-Trichophyton rubrum activity, which was characterized by nuclear magnetic resonance spectroscopy(13C-NMR), hydrogen nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy (FTIR), high-resolution mass spectrometry (HR-ESI-MS), and ultraviolet (UV) and identified as imperatorin and belonged to coumarins, with the minimum inhibitory concentration (MIC) against Trichophyton rubrum of 12.5 µg/mL. According to the discussion on the inhibitory mechanism of the compound, we found that the compound may exert its inhibitory effect by destroying the mycelial membrane and inhibiting the mycelial growth of Trichophyton rubrum. In a word, imperatorin isolated from Heracleum vicinum Boiss. is expected to be used as an antibacterial agent to treat dermatophytes a potential natural compound against Trichophyton rubrum, and a template for drug development of dermatophytes the future.


Assuntos
Arthrodermataceae , Heracleum , Cumarínicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Etanol/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana
16.
Clin Transl Gastroenterol ; 14(7): e00602, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37235793

RESUMO

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.


Assuntos
Antiulcerosos , Úlcera Duodenal , Humanos , Lansoprazol/efeitos adversos , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/induzido quimicamente , Antiulcerosos/efeitos adversos , Método Duplo-Cego
17.
Environ Sci Pollut Res Int ; 30(31): 76606-76616, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37243766

RESUMO

A scientific evaluation of the carbon emission efficiency is crucial for ensuring the sustainable development of wastewater treatment plants (WWTPs). In this paper, we applied a non-radial data envelopment analysis (DEA) model to calculate the carbon emission efficiency of 225 WWTPs located in China. The results showed that the average carbon emission efficiency of China's WWTPs was 0.59, indicating that the efficiencies of most samples still require improvement. The carbon emission efficiency of WWTPs from 2015 to 2017 decreased because of the decrease in technology efficiency. Among the influencing factors, different treating scales had positive impact on carbon emission efficiency improvement. WWTPs with anaerobic oxic process and the first-class A standard were likely to have higher carbon emission efficiency in the 225 WWTPs. By incorporating direct and indirect carbon emissions into WWTP efficiency evaluation, this study helped decision-makers and related water authorities to better understand the contribution of WWTPs to the aquatic and atmospheric environments.


Assuntos
Águas Residuárias , Purificação da Água , Eliminação de Resíduos Líquidos/métodos , China , Eficiência , Carbono
18.
Pharmaceutics ; 15(3)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36986786

RESUMO

The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.

19.
Nat Immunol ; 24(4): 690-699, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36914890

RESUMO

The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent of such escape in nine convalescent patients infected with the wild-type SARS-CoV-2 during the first wave of the pandemic. Among the total of 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, we identified seven mAbs with broad neutralizing activity to all variants tested, including various omicron subvariants. Biochemical and structural analysis indicated the majority of these mAbs bound to the receptor-binding domain, mimicked the receptor ACE2 and were able to accommodate or inadvertently improve recognition of omicron substitutions. Passive delivery of representative antibodies protected K18-hACE2 mice from infection with omicron and beta SARS-CoV-2. A deeper understanding of how the memory B cells that produce these antibodies could be selectively boosted or recalled can augment antibody immunity against SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Camundongos , Anticorpos Monoclonais , Anticorpos Antivirais , Anticorpos Neutralizantes
20.
Eur J Clin Microbiol Infect Dis ; 42(6): 681-689, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36997767

RESUMO

Rickettsia and Coxiella burnetii are zoonotic tick-borne pathogens that cause febrile illnesses in humans. Metagenomic next-generation sequencing (mNGS) is a new technology used to diagnose infectious diseases. However, clinical experience with applying the test to rickettsioses and Q fever is relatively limited. Therefore, this study aimed to explore the diagnostic performance of mNGS in detecting Rickettsia and C. burnetii. We retrospectively studied patients with rickettsioses or Q fever between August 2021 and July 2022. Peripheral blood mNGS and polymerase chain reaction (PCR) were performed for all patients. Clinical data were retrieved for analysis. Thirteen patients were included in this study (eleven confirmed cases and two suspected cases). Signs and symptoms included fever (13, 100%), rash (7, 53.8%), muscle soreness (5, 38.5%), headache (4, 30.8%), skin eschar (3, 23.1%), and disturbance of consciousness (2, 15.4%). In addition, eight patients (61.6%) had thrombocytopenia, ten (76.9%) had liver function impairment, and two (15.4%) had renal function impairment. The results of mNGS revealed seven patients with R. japonica (53.8%), five with C. burneti (38.5%), two with R. heilongjiangensis (15.4%), and one with R. honei (7.7%). PCR results were positive in 11 patients (84.6%). After receiving doxycycline-based treatment, 12 (92.3%) patients returned to a normal temperature within 72 h. All patients were discharged in better health. Therefore, mNGS can help diagnose Rickettsia and C. burnetii and shorten the diagnosis time, especially for patients with atypical clinical manifestations and unclear epidemiologic evidence of a tick bite or exposure.


Assuntos
Coxiella burnetii , Febre Q , Infecções por Rickettsia , Rickettsia , Humanos , Rickettsia/genética , Coxiella burnetii/genética , Febre Q/diagnóstico , Estudos Retrospectivos , Infecções por Rickettsia/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala
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