Sterols are essential components of eukaryotic cells whose biosynthesis and function has been studied extensively. Sterols are also recognized as the diagenetic precursors of steranes preserved in sedimentary rocks where they can function as geological proxies for eukaryotic organisms and/or aerobic metabolisms and environments. However, production of these lipids is not restricted to the eukaryotic domain as a few bacterial species also synthesize sterols. Phylogenomic studies have identified genes encoding homologs of sterol biosynthesis proteins in the genomes of several additional species, indicating that sterol production may be more widespread in the bacterial domain than previously thought. Although the occurrence of sterol synthesis genes in a genome indicates the potential for sterol production, it provides neither conclusive evidence of sterol synthesis nor information about the composition and abundance of basic and modified sterols that are actually being produced. Here, we coupled bioinformatics with lipid analyses to investigate the scope of bacterial sterol production. We identified oxidosqualene cyclase (Osc), which catalyzes the initial cyclization of oxidosqualene to the basic sterol structure, in 34 bacterial genomes from five phyla (Bacteroidetes, Cyanobacteria, Planctomycetes, Proteobacteria, and Verrucomicrobia) and in 176 metagenomes. Our data indicate that bacterial sterol synthesis likely occurs in diverse organisms and environments and also provides evidence that there are as yet uncultured groups of bacterial sterol producers. Phylogenetic analysis of bacterial and eukaryotic Osc sequences confirmed a complex evolutionary history of sterol synthesis in this domain. Finally, we characterized the lipids produced by Osc-containing bacteria and found that we could generally predict the ability to synthesize sterols. However, predicting the final modified sterol based on our current knowledge of sterol synthesis was difficult. Some bacteria produced demethylated and saturated sterol products even though they lacked homologs of the eukaryotic proteins required for these modifications emphasizing that several aspects of bacterial sterol synthesis are still completely unknown.
Mass spectrometry (MS) is one of the most widely used analytical techniques in many fields. Recent developments in chemical and biological researches have drawn much attention to the measurement of substances with low abundances in samples. Continuous efforts have been made consequently to further improve the sensitivity of MS. Modifications on the mass analyzers of mass spectrometers offer a direct, universal and practical way to obtain higher sensitivity. This review provides a comprehensive overview of the latest developments in mass analyzers for the improvement of mass spectrometers’ sensitivity, including quadrupole, ion trap, time-of-flight (TOF) and Fourier transform ion cyclotron (FT-ICR), as well as different combinations of these mass analyzers. The advantages and limitations of different mass analyzers and their combinations are compared and discussed. This review provides guidance to the selection of suitable mass spectrometers in chemical and biological analytical applications. It is also beneficial to the development of novel mass spectrometers.
DNA G-quadruplexes (G4s) in vivo have been linked to cancer and other diseases such as neurological disorders. Nondestructive fast detection of endogenous DNA G4s can provide specific real-time information, which is of particular interest for clinic accurate diagnosis. However, tools to probe live-cell endogenous DNA G4s in real time are very limited. Herein, we report the design and development of a fluorescent molecule QIN for the real-time detection of endogenous DNA G4s in live cells with the aid of a new spiropyran in situ switching (SIS) strategy. The lipophilic spiropyran-linked QIN differs from the other probes in that it can enter live cells readily within 15 s and can be in situ induced by DNA G4s to adopt its charged open form, causing a large red shift in the fluorescent emission wavelength. Live-cell super-resolution fluorescent imaging suggests that the SIS-based probe has high photostability and can be applied for the accurate detection of DNA G4s in complex biosystems with very high sensitivity and selectivity.
Objective With the epidemic of coronavirus disease 2019 (COVID-19), the healthcare workers (HCWs) require proper respiratory personal protective equipment (rPPE) against viral respiratory infectious diseases (VRIDs). It is necessary to evaluate which type of mask and manner of wearing is the best suitable rPPE for preventing the VRID. Study design A Bayesian network meta-analysis was performed to comprehensively analyze the protective efficacy of various rPPE. Methods This network meta-analysis protocol was registered in an international prospective register of systematic reviews (CRD42020179489). Electronic databases were searched for cluster randomized control trials (RCTs) of comparing the effectiveness of rPPE and wearing manner in preventing HCWs from VRID. The primary outcome was the incidence of laboratory-confirmed viral respiratory infection reported as an odds ratio (OR) with the associated 95% credibility interval (CrI). The secondary outcome was the incidence of clinical respiratory illness (CRI) reported as an OR with the associated 95% CrI. Surface under the cumulative ranking curve analysis (SUCRA) provided a ranking of each rPPE according to the primary outcome and the secondary outcome as data supplement. Results Six studies encompassing 12,265 HCWs were included. In terms of the incidence of laboratory-confirmed viral respiratory infection, the continuous wearing of N95 respirators (network OR, 0.48; 95% CrI: 0.27 to 0.86; SUCRA score, 85.4) showed more effective than the control group. However, in terms of reducing the incidence of CRI, there was no rPPE showing superior protective effectiveness. Conclusions There are significant differences in preventive efficacy among current rPPE. Our result suggests that continuous wearing of N95 respirators on the whole shift can serve as the best preventive rPPE for HCWs from the VRID.
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