Protein lysine succinylation, an emerging protein post-translational modification widespread among eukaryotic and prokaryotic cells, represents an important regulator of cellular processes. However, the extent and function of lysine succinylation in Mycobacterium tuberculosis, especially extensively drug-resistant strain, remain elusive. Combining protein/peptide prefractionation, immunoaffinity enrichment, and LC-MS/MS analysis, a total of 686 succinylated proteins and 1739 succinylation sites of M. tuberculosis were identified, representing the first global profiling of M. tuberculosis lysine succinylation. The identified succinylated proteins are involved in a variety of cellular functions such as metabolic processes, transcription, translation, and stress responses and exhibit different subcellular localization via GO, protein interaction network, and other bioinformatic analysis. Notably, proteins involved in protein biosynthesis and carbon metabolism are preferred targets of lysine succinylation. Moreover, two prevalent sequence patterns: EK(suc) and K*****K(suc), can be found around the succinylation sites. There are 109 lysine-succinylated homologues in E. coli, suggesting highly conserved succinylated proteins. Succinylation was found to occur at the active sites predicted by Prosite signature including Rv0946c, indicating that lysine succinylation may affect their activities. There is extensive overlapping between acetylation sites and succinylation sites in M. tuberculosis. Many M. tuberculosis metabolic enzymes and antibiotic resistance proteins were succinylated. This study provides a basis for further characterization of the pathophysiological role of lysine succinylation in M. tuberculosis.
ObjectivesThe study aims to investigate the state anxiety of parents of special needs children during the 2019 coronavirus disease (COVID-19) epidemic and the influence of parental stress, social support, and other related variables on the anxiety of parents.MethodsBespoke questionnaires of children’s and parent’s mental and behavioral problems during the epidemic were used in the study. We also used the State Anxiety Inventory (S-AI), the Parenting Stress Index—Short Form-15 (PSI-SF-15), the NEO Five-Factor Inventory (NEO-FFI), and the Multidimensional Scale of Perceived Social Support (MSPSS). The data used in the study were pooled from an online survey of parents of special needs children and analyzed by one-way analysis of variance (ANOVA) and multiple linear regression.ResultsOverall, 1,451 individuals were included, of which 402 were fathers (27.71%) and 1,049 were mothers (72.29%). ANOVA results showed that educational background, family monthly income, and type of their child’s disability made parents’ state anxiety significantly different. The results of multiple linear regression showed that during the epidemic, social support negatively predicted parents’ state anxiety (B = −0.15, p < 0.001), whereas parenting stress (B = 0.07, p = 0.001) and parental mental and behavioral problems (B = 0.37, p < 0.001) positively predicted parents’ state anxiety.ConclusionsDuring the outbreak of COVID-19, parents of special needs children suffered mental and behavioral problems, together with parenting stress and social support, which influenced their state anxiety. These findings can be used to develop relevant psychological interventions to improve the mental health of vulnerable groups during a pandemic like COVID-19.
Carbapenems such as imipenem and meropenem are first-line agents for the treatment of serious nosocomial infections caused by multidrug-resistant clinical isolates of bacteria belonging to the family Enterobacteriaceae. However, resistance to carbapenems has increased dramatically among members of the family Enterobacteriaceae isolated from a teaching hospital in Shanghai, China. In the present study, we investigated the prevalence and molecular characteristics of carbapenemresistant clinical isolates of Enterobacteriaceae. None of the 77 clinical isolates collected from 2002 to 2009 were susceptible to ertapenem and only 6.5 % and 1.3 % of isolates were susceptible to imipenem and meropenem, respectively. Colistin and tigecycline were found to be the most active agents against carbapenem-resistant Enterobacteriaceae isolates, inhibiting 90 % of isolates at a concentration of 1 mg ml "1 and 4 mg ml , respectively. The results of PFGE analysis suggested that many of the KPC-2-producing isolates of Citrobacter freundii and Klebsiella pneumoniae were clonally related. Most of these isolates were isolated from the same ward, namely the neurosurgical ward, suggesting horizontal transfer of the KPC-2-encoding gene in these isolates. Of the 77 isolates, 84.4 % were found, by PCR, to be capable of carbapenemase production. SDS-PAGE analysis revealed that 75.3 % (58/77) of the isolates had lost at least one porin protein. Our results suggested that the prompt detection of carbapenemase-producing strains is critical for the containment of nosocomial transmission. As no novel antimicrobials have been identified for use in the treatment of these pan-drug-resistant isolates, further studies should focus on the rational use of available antibiotics, the implementation of active antibiotic resistance surveillance and the strict implementation of infection control measures to avoid the rapid spread or outbreak of carbapenemase-producing Enterobacteriaceae in health-care facilities. INTRODUCTIONCarbapenems such as imipenem and meropenem are firstline agents for the treatment of serious healthcare-associated infections caused by clinical multidrug-resistant Enterobacteriaceae (Brink et al., 2004). However, the phenomenon of carbapenem resistance is emerging in a wide variety of these species (Yigit et al., 2001). Carbapenemases have been widely detected in recent years and predominantly contribute to carbapenem resistance among members of the family Enterobacteriaceae including Klebsiella pneumoniae and Citrobacter freundii (Peleg & Hooper, 2010). Carbapenemases including KPC, VIM, IPM, SME and OXA belong to various families of b-lactamases (Queenan & Bush, 2007). Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) have presented a great challenge to physicians in recent years (CDC, 2009;Munoz-Price & Quinn, 2009). In Shanghai, China, K. pneumoniae is the second most frequently isolated pathogen among Gram-negative bacilli according to the Shanghai Bacterial Resistance Surveillance Program (Zhu et al., 2006(Zhu et ...
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