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Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance, making them an invaluable asset in the era of antibiotic resistance. Numerous depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models. Additionally, some formulation approaches have been developed for improved stability and activity of depolymerases. However, depolymerase formulation is limited to liquid dosage form and remains in its infancy, posing a significant hurdle to their clinical translation, compounded by challenges in their applicability and manufacturing. Future development must address these obstacles for clinical utility. Here, after unravelling the history, diversity, and therapeutic use of depolymerases, we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases. Finally, the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patients immunological status, and found dramatic changes in the IGH within the patients immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones during 2-3 weeks of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34 and IGHV4-39 in COVID-19 patients were more abundant than that of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.
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The atypical pneumonia (COVID-19) caused by SARS-CoV-2 is an ongoing pandemic and a serious threat to global public health. The COVID-19 patients with severe symptoms account for a majority of mortality of this disease. However, early detection and effective prediction of patients with mild to severe symptoms remains challenging. In this study, we performed proteomic profiling of urine samples from 32 healthy control individuals and 6 COVID-19 positive patients (3 mild and 3 severe). We found that urine proteome samples from the mild and severe COVID-19 patients with comorbidities can be clearly differentiated from healthy proteome samples based on the clustering analysis. Multiple pathways have been compromised after the COVID-19 infection, including the dysregulation of immune response, complement activation, platelet degranulation, lipoprotein metabolic process and response to hypoxia. We further validated our finding by directly comparing the same patients urine proteome after recovery. This study demonstrates the COVID-19 pathophysiology related molecular alterations could be detected in the urine and the potential application of urinary proteome in auxiliary diagnosis, severity determination and therapy development of COVID-19.
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Objective To compare the differences between two statistical methods for evaluating non-sensitivity of pathogenic bacteria to antimicrobial agents,and explore effect of non-consideration of clinical background on evalua-ting extent of bacterial resistance.Methods Data of Staphylococcus aureus and Acinetobacter spp .in a hospital in the first half year of 2008,2010 and 2013 were collected and conducted statistical analysis with two methods (me-thod 1 :based on all clinically isolated bacteria;method 2 :based on infection-related non-repetitive bacteria),two methods for evaluating bacterial non-sensitive rates to antimicrobial agents were compared.Results The non-sensi-tive rates of Acinetobacter spp .to various antimicrobial agents :statistical results by using method 1 were generally higher than those using method 2,absolute difference between two statistical methods was 10.46%-33.77%;the non-sensitive rates of Staphylococcus aureus to various antimicrobial agents :except compound sulfamethoxazole in 2010 and 2013(difference were 6.17% and 10.21 % respectively),penicillin G (difference was 3.86%),erythromy-cin (difference was 2.71 %),and azithromycin in 2013 (difference was 2.43%),statistical results by using method 1 were generally higher than those using method 2,absolute difference between two statistical methods was 0-18.04%.Conclusion There are deviation in the non-sensitive rates of bacterial strains to antimicrobial agents by using two different statistical methods,deviation is larger in Acinetobacter spp ..The resistance level might be incorrectly higher when evaluating the resistance status without considering clinical background of bacteria.
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Objective:To study the inhibitory effect of clarithromycin on angiogenesis induced by b-FGF. Methods:TheMatrigel implant assay was used. Matrigel (500?l) containing b-FGF and heparin were injected subcutaneously into the ab-domen of mice and were harvested 5 d later. The amount of hemoglobin and micro-vascular area present in the implant weremeasured and cotnpared. The mice were given either CAM (study group) or the same volume of glucose (vehicle group) oncea day by gastric intubation. Treatmen started 3 d before Matrigel implant and continued until the end of study. Results:Clar-ithromycin reduced hemoglobin content and micro-vascular area in Matrigel implant at high dosage(≥40 mg/(kg?d). Con-clusion:These data demonstrate that clarithromycin is a potent inhibitor of angiogenesis and may has possible therapeutic value in controlling pathologic angiogenesis.
