This study monitored the presence of SARS-Cov-2 RNA on environmental surfaces in hospital wards housing patients with mild, severe, and convalescent Coronavirus Disease 2019 (COVID-19), respectively. ...From 29 October to 4 December 2021, a total of 787 surface samples were randomly collected from a General Ward, Intensive Care Unit, and Convalescent Ward at a designated hospital for COVID-19 patients in China. All of the samples were used for SARS-Cov-2 detection. Descriptive statistics were generated and differences in the positivity rates between the wards were analyzed using Fisher's exact tests, Yates chi-squared tests, and Pearson's chi-squared tests. During the study period, 787 surface samples were collected, among which, 46 were positive for SARS-Cov-2 RNA (5.8%). The positivity rate of the contaminated area in the Intensive Care Unit was higher than that of the General Ward (23.5% vs. 10.4%, P<0.05). The positivity rate of the semi-contaminated area in the Intensive Care Unit (4.5%) was higher than that of the General Ward (1.5%), but this difference was not statistically significant (P>0.05). In the clean area, only one sample was positive in the Intensive Care Unit (0.5%). None of the samples were positive in the Convalescent Ward. These findings reveal that the SARS-Cov-2 RNA environmental pollution in the Intensive Care Unit was more serious than that in the General Ward, while the pollution in the Convalescent Ward was the lowest. Strict disinfection measures, personal protection, and hand hygiene are necessary to limit the spread of SARS-Cov-2.
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There is a dearth of tuberculosis (TB) drug development activity as current therapeutic treatments are inadequate due to the appearance of drug-resistant TB. The enzyme ...UDP-galactopyranose mutase (UGM) is involved in the biosynthesis of galactan which is essential for cell wall integrity and bacterial viability. Its inhibition has thus been featured as profitable strategy for anti-TB drug discovery. In this study, we report on the synthesis of amides derived from rosmarinic acid, their inhibitory effect towards purified UGM using three distinct biochemical assays: FP, HPLC and SPR. The rosmarinic amides generally showed a significantly higher affinity for UGM than the corresponding rosmarinic ester. In particular, compound 5h displayed interesting binding affinity values (Kd = 58 ± 7, 63 ± 9 µM towards KpUGM and MtUGM respectively). Furthermore, a new UGM SPR assay was established and confirmed that 5h binds to UGM with a dissociation constant of 104.8 ± 6.5 μM. Collectively, this study validates the amide bioisosteric strategy which has been successfully implemented to develop UGM inhibitors from rosmarinic acid, providing a substantial basis for further design of novel UGM inhibitors and anti-mycobacterial agents.
The multistep synthesis of a novel ADP-7-azido-7-deoxy-l-glycero-β-d-manno-heptopyranoside 2a and several analogues as heptosyltransferase ligands is described. The synthesis of the key intermediate ...heptoside-1-β-phosphate 3a involved a β-stereoselective phosphorylation of lactol 4 employing diallyl chlorophosphate as a phosphorylating reagent. Five deprotected nucleotide sugars were generated by this synthetic sequence and evaluated as heptosyltransferase substrates (K M, k cat).
The synthesis of unprecedented multimeric Kdo glycoclusters based on fullerene and calix4arene central scaffolds is reported. The compounds were used to study the mechanism and scope of multivalent ...glycosyltransferase inhibition. Multimeric mannosides based on porphyrin and pillar5arenes were also generated in a controlled manner. Twelve glycoclusters and their monomeric ligands were thus assayed against heptosyltransferase WaaC, which is an important bacterial glycosyltransferase that is involved in lipopolysaccharide biosynthesis. It was first found that all the multimers interact solely with the acceptor binding site of the enzyme even when the multimeric ligands mimic the heptose donor. Second, the novel Kdo glycofullerenes displayed very potent inhibition (Ki=0.14 μm for the best inhibitor); an inhibition level rarely observed with glycosyltransferases. Although the observed “multivalent effects” (i.e., the enhancement of affinity of a ligand when presented in a multimeric fashion) were in general modest, a dramatic effect of the central scaffold on the inhibition level was evidenced: the fullerene and the porphyrin scaffolds being by far superior to the calix‐ and pillar‐arenes. We could also show, by dynamic light scattering analysis, that the best inhibitor had the propensity to form aggregates with the heptosyltransferase. This aggregative property may contribute to the global multivalent enzyme inhibition, but probably do not constitute the main origin of inhibition.
Better together? The synthesis of unprecedented multimeric Kdo glycoclusters based on fullerene and calixarene central scaffolds is reported (see figure). The compounds were used to study the mechanism and the scope of multivalent heptosyltransferase inhibition, which is an important bacterial enzyme. The novel Kdo glycofullerenes displayed very potent inhibition (Ki=0.14 μm), at a level that is rarely observed with glycosyltransferases.
Enzyme assays involving coupled pyruvate kinase (PK) have been used for many years to monitor the activity of major classes of enzymes including glycosyltransferases. Numerous potent inhibitors have ...been discovered and kinetically characterized thanks to this technology. However, when inhibitors of these important enzymes are screened, PK inhibitors or activators are very often observed. In this study we report solutions to resolve the problems encountered either during the screening or during the kinetic characterization of glycosyltransferase inhibitors by means of PK‐coupled assays. The enzyme under study—WaaC—is an important glycosyltransferase involved in the bacterial lipopolysaccharide (LPS) biosynthesis pathway. Firstly we showed that alternative kinases such as nucleoside 5‐diphosphate kinase (NDPK), myokinase (MK), and ADPdependent hexokinase that catalyze similar reactions to PK are prone to the same troubles. Moreover, an ADP chemosensor was used as an alternative but the sensitivity was not sufficient to allow a proper screening. Finally, we found that a stepwise PK/luciferase assay resolved the problems encountered with PK inhibitors and that a WaaC HPLC assay allowed the identification of WaaC inhibitors acting as PK activators, thus allowing false positive and false negative results linked to the coupling to PK to be eliminated.
No longer out of WaaC: Pyruvate‐kinase‐coupled (PK‐coupled) glycosyltransferase assays can be troublesome when the compound under study inhibits or activates the PK. Thanks to the development of new kinetic protocols, potent inhibitors of the heptosyltransferase WaaC were discovered and characterized even when the standard PK‐coupled procedures failed.
This study monitored the presence of SARS-Cov-2 RNA on environmental surfaces in hospital wards housing patients with mild, severe, and convalescent Coronavirus Disease 2019 (COVID-19), respectively. ...From 29 October to 4 December 2021, a total of 787 surface samples were randomly collected from a General Ward, Intensive Care Unit, and Convalescent Ward at a designated hospital for COVID-19 patients in China. All of the samples were used for SARS-Cov-2 detection. Descriptive statistics were generated and differences in the positivity rates between the wards were analyzed using Fisher’s exact tests, Yates chi-squared tests, and Pearson’s chi-squared tests. During the study period, 787 surface samples were collected, among which, 46 were positive for SARS-Cov-2 RNA (5.8%). The positivity rate of the contaminated area in the Intensive Care Unit was higher than that of the General Ward (23.5% vs. 10.4%, P<0.05). The positivity rate of the semi-contaminated area in the Intensive Care Unit (4.5%) was higher than that of the General Ward (1.5%), but this difference was not statistically significant (P>0.05). In the clean area, only one sample was positive in the Intensive Care Unit (0.5%). None of the samples were positive in the Convalescent Ward. These findings reveal that the SARS-Cov-2 RNA environmental pollution in the Intensive Care Unit was more serious than that in the General Ward, while the pollution in the Convalescent Ward was the lowest. Strict disinfection measures, personal protection, and hand hygiene are necessary to limit the spread of SARS-Cov-2.
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•A statistic framework and nonlinear detrend method are used in this study.•The relative contributions of climate variability on drought are quantified.•The dependence of drought ...trend on climate change varies in region and timescale.
Exploring the impact of climate change on drought under changing environmental conditions is crucial for agriculture, ecology, and human society. To evaluate the role of climate change on drought, this study selected the Songnen Plain (SNP) in Northeast China as a study area in which to quantify the relative contributions of climatic variables to the drought trend in accordance with the Standardized Precipitation and Evapotranspiration Index (SPEI). A series of SPEI-based numerical experiments, using combinations of observational and nonlinear detrended climatic variable data series, was used as a synthetic approach with which to analyze the relative impact of the individual climatic variables. Results indicated that drought on the SNP has been mitigated marginally during 1961–2016, mainly during spring, winter, the growing season, and on the annual timescale. Significant trends were detected in relation to temperature, sunshine duration, and wind speed, and these variables had differing roles in drought evolution. An increasing trend in temperature was found to aggravate drought tendency at all investigated timescales; however, decreasing trends in net radiation and wind speed offset the drought tendency caused by rising temperature. The positive contribution of wind speed was larger than the negative contribution of temperature, especially in areas around 46°N. Although the change of precipitation was not significant, it promoted drought mitigation on the SNP in spring, winter, the growing season, and on the annual timescale. The analysis framework used in this study was shown useful for improving understanding of the relationship between climate change and drought evolution, and it could prove helpful in providing rational and regulatory policy strategies regarding drought relief.
•A synchrotron TXM tomography system was used to obtain morphology data of NMC electrodes.•Geometric and electrochemical characteristics of the electrodes were analyzed.•SEI and charge transfer ...resistances decrease with increasing NMC density.•Increasing calendering causes crashing of NMC particles and decrease rate capability.•Optimum performance is achieved at 3.0g/cm3 NMC density.
The impact of calendering process on the geometric characteristics and electrochemical performance of LiNi1/3Mn1/3Co1/3O2 (NMC) electrode was investigated in this study. The geometric properties of NMC electrodes with different calendering conditions, such as porosity, pore size distribution, particle size distribution, specific surface area and tortuosity were calculated from the computed tomography data of the electrodes. A synchrotron transmission X-ray microscopy tomography system at the Advanced Photon Source of the Argonne National Laboratory was employed to obtain the tomography data. The geometric and electrochemical analysis show that calendering can increase the electrochemically active area, which improves rate capability. However, more calendering will result in crushing of NMC particles, which can reduce the electrode capacity at relatively high C rates. This study shows that the optimum electrochemical performance of NMC electrode at 94:3:3 weight ratio of NMC:binder:carbon black can be achieved by calendering to 3.0g/cm3 NMC density.
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•Sericite 40Ar/39Ar dating constrains the Ag-Au mineralization in the main-stage India-Asia collision.•Different types of fluid inclusion dominate in ore-barren quartz, ore-related ...quartz and sphalerite.•Fluid mixing may have been the main ore precipitation mechanism.•Guqiong is classified as an orogenic-type Ag-Au deposit.
Guqiong is an Ag–Au polymetallic deposit located in the eastern part of the Au–Sb ore belt along the Indus-Yarlung Zangbo suture in the North Himalaya. In this study, we have identified three major alteration/mineralization stages for Guqiong based on the mineral assemblages and their paragenetic relationships, namely the (I) pre-ore alteration, forming mainly ore-barren thick quartz veins and vuggy quartz; (II) main ore stage that comprises quartz veins with sulfide mineralization including Ag (-Au)-bearing minerals. In this stage, sericite occurs closely associated with sulfides; (III) the post-ore stage characterized by the formation of calcite and quartz with trace sulfides. Fluid inclusion assemblage (FIA) microthermometry was conducted on barren and mineralized quartz, and sphalerite. Three types of inclusions are identified based on their petrographic features and laser Raman spectra, i.e., the pure carbonic (PC), aqueous-carbonic (three-phase C1 and two-phase C2) and aqueous (W) types. The FIAs in stage I ore-barren quartz are mainly PC-type and C1-type, which are characterized by being high temperatures (260 to 300 °C), low salinities (0.8 to 3.5 wt% NaCl eqv.) and with abundant CO2. Sphalerite of main ore stage contains mainly W-type (with limited C2-type) of low temperatures (158 to 180 °C) and medium salinities (5.6 to 6.7 wt% NaCl eqv.). Meanwhile, the FIA in mineralized quartz is featured by the general coexistence of C2-type and W-type (with local PC-type and C1-type) inclusions. The fluid system may have been a mixture of the two aforementioned fluids in barren quartz and sphalerite, as indicated by two significantly different FIAs (C-type and W-type) with contrasting homogenization temperatures (260 to 290 °C and 180 to 220 °C, respectively) but comparable salinities (0.2 to 8.2 and 0.2 to 8.1 wt% NaCl eqv., respectively). The fluid δD, δ18O and δ13C values of the main ore stage quartz are −172 to −114%, 8.8 to 13.1% and −13.4 to −7.7%, respectively. The negative δ13C values are interpreted as devolatilization products of biogenic carbon with a metamorphic origin, while the δD and δ18O values likely reflect meteoric water involvement into metamorphic fluids. We propose that fluid mixing had occurred and caused sulfide precipitation at the main ore stage. Additionally, the estimated fluid trapping depth of 5 to 6 km (obtained using 3-D phase diagram) is consistent with the formation depth of many orogenic-type deposits worldwide. 40Ar/39Ar dating on sericite yielded a well-defined plateau age of 42.03 ± 0.42 Ma, with normal and inverse isochron ages of 42.8 ± 1.6 Ma and 42.9 ± 1.9 Ma, respectively. These ages bracket the Ag–Au mineralization at Guqiong, place it in the main-stage India-Asia collision and further support its orogenic-type origin.
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