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1.
Bioresour Technol ; 402: 130794, 2024 May 03.
Article En | MEDLINE | ID: mdl-38703966

Carbon deficits in inflow frequently lead to inefficient nitrogen removal in constructed wetlands (CWs) treating tailwater. Solid carbon sources, commonly employed to enhance denitrification in CWs, increase carbon emissions. In this study, MnO2 was incorporated into polycaprolactone substrates within CWs, significantly enhancing NH4+-N and NO3--N removal efficiencies by 48.26-59.78 % and 96.84-137.23 %, respectively. These improvements were attributed to enriched nitrogen-removal-related enzymes and increased plant absorption. Under high nitrogen loads (9.55 ± 0.34 g/m3/d), emissions of greenhouse gases (CO2, CH4, and N2O) decreased by 147.23-202.51 %, 14.53-86.76 %, and 63.36-87.36 %, respectively. N2O emissions were reduced through bolstered microbial nitrogen removal pathways by polycaprolactone and MnO2. CH4 accumulation was mitigated by the increased methanotrophs and dampened methanogenesis, modulated by manganese. Additionally, manganese-induced increases in photosynthetic pigment contents (21.28-64.65 %) fostered CO2 sequestration through plant photosynthesis. This research provides innovative perspectives on enhancing nitrogen removal and reducing greenhouse gas emissions in constructed wetlands with polymeric substrates.

2.
Int J Mol Sci ; 25(8)2024 Apr 15.
Article En | MEDLINE | ID: mdl-38673947

Phyllotreta striolata, the striped flea beetle, is one of the most destructive pests in Brassicaceae plants worldwide. Given the drawbacks associated with long-term use of chemical insecticides, green strategies based on chemical ecology are an effective alternative for beetle control. However, the lack of information on beetle ecology has hindered the development of effective biocontrol strategies. In this report, we identified two odorants, (S)-cis-verbenol and (-)-verbenone, which displayed significant attraction for P. striolata (p < 0.05), indicating their great potential for P. striolata management. Using the Drosophila "empty neuron" system, an antenna-biased odorant receptor, PstrOR17, was identified as responsible for the detection of (-)-verbenone and (S)-cis-verbenol. Furthermore, the interactions between PstrOR17 and (-)-verbenone or (S)-cis-verbenol were predicted via modeling and molecular docking. Finally, we used RNAi to confirm that PstrOR17 is essential for the detection of (-)-verbenone and (S)-cis-verbenol to elicit an attraction effect. Our results not only lay a foundation for the development of new and effective nonchemical insecticide strategies based on (S)-cis-verbenol and (-)-verbenone, but also provide new insight into the molecular basis of odorant recognition in P. striolata.


Bicyclic Monoterpenes , Coleoptera , Receptors, Odorant , Animals , Receptors, Odorant/genetics , Receptors, Odorant/metabolism , Bicyclic Monoterpenes/pharmacology , Coleoptera/drug effects , Arthropod Antennae/drug effects , Arthropod Antennae/physiology , Arthropod Antennae/metabolism , Molecular Docking Simulation , Odorants/analysis , Insect Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/chemistry , Monoterpenes/pharmacology , Monoterpenes/chemistry
3.
Comp Immunol Microbiol Infect Dis ; 109: 102179, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38636297

porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection, is an important swine infectious disease that causes substantial losses worldwide each year. PRRSV is a positive-sense single-stranded RNA virus that is highly susceptible to mutation and recombination, making vaccine and drug research for the disease extremely difficult. In this study, the binding of PRRSV nsp2 to HSP71 protein was detected by using the IP/MS technique. And the inhibitory effect of HSP71 on nsp2 antagonistic activity was validated by measuring NF-kB luciferase reporter. According to stress from inhibitory effects, the amino acid variation profile of PRRSV nsp2 under HSP71 stress was further analyzed using second-generation sequencing. Surprisingly, the results indicated that HSP71 pressure limits the random mutations of PRRSV nsp2 and maintains the dominant PRRSV strain within the population. Mutant strain showed weaker antagonistic activity and replication capability in cell. These results imply the binding of HSP71 with PRRSV nsp2 may lead to maintain the stability of highly virulent strains of PRRSV.

4.
Analyst ; 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639189

Small extracellular vesicles (sEVs), a form of extracellular vesicles, are lipid bilayered structures released by all cells. Large-scale studies on sEVs from clinical samples are necessary, but a major obstacle is the lack of rapid, reproducible, efficient, and low-cost methods to enrich sEVs. Acoustic microfluidics have the advantage of being label-free and biocompatible, which have been reported to successfully enrich sEVs. In this paper, we present a highly efficient acoustic microfluidic trap that can offer low and large volume compatible ways of enriching sEVs from biological fluids by flexible structure design. It uses the idea of pre-loading larger seed particles in the acoustic trap to enable sub-micron particle capturing. The microfluidic chip is actuated using a piezoelectric plate transducer attached to a silicon-glass bonding plate with circular cavities. Each cavity works as a resonant unit, excited at the frequency of both the half wave resonance in the main plane and inverted quarter wave resonance in the depth direction, which has the ability to strongly trap seed particles at the center, thereby improving the subsequent nanoparticle capture efficiency. Mean trapping efficiencies of 35.62% and 64.27% were obtained using 60 nm and 100 nm nanobeads, respectively. By the use of this technology, we have successfully enriched sEVs from cell culture conditioned media and blood plasma at a flow rate of 10 µL min-1. The isolated sEV subpopulations are characterized by NTA and TEM, and their protein cargo is determined by WB. This acoustic trapping chip provides a rapid and robust method to enrich sEVs from biofluids with high reproducibility and sufficient quantities. Therefore, it can serve as a new tool for biological and clinical research such as cancer diagnosis and drug delivery.

5.
Pest Manag Sci ; 2024 Mar 08.
Article En | MEDLINE | ID: mdl-38458148

BACKGROUND: The Asian tiger mosquito, Aedes albopictus, is a competent vector for the spread of several viral arboviruses including dengue, chikungunya, and Zika. Several vital mosquito behaviors linked to survival and reproduction are primarily dependent on a sophisticated olfactory system for semiochemical perception. However, a limited number of studies has hampered our understanding of the relationship between the A. albopictus acute olfactory system and the complex chemical world. RESULTS: Here, we performed a qRT-PCR assay on antennae from A. albopictus of differing sex, age and physiological states, and found that AalbOr10 was enriched in blood-fed female mosquitoes. We then undertook single sensillum recording to de-orphan AalbOr10 using a panel of physiologically and behaviorally relevant odorants in a Drosophila 'empty neuron' system. The results indicated that AalbOr10 was activated by seven aromatic compounds, all of which hampered egg-laying in blood-fed mosquitoes. Furthermore, using a post-RNA interference oviposition assay, we found that reducing the transcript level of AalbOr10 affected repellent activity mediated by 2-ethylphenol at low concentrations (10-4 vol/vol). Computational modeling and molecular docking studies suggested that hydrogen bonds to Y68 and Y150 mediated the interaction of 2-ethylphenol with AalbOr10. CONCLUSION: We reveal a potential link between aromatics-induced oviposition repellency behaviors and a specific odorant receptor in A. albopictus. Our findings provide a foundation for identifying active semiochemicals for the monitoring or controlling of mosquito populations. © 2024 Society of Chemical Industry.

6.
Water Res ; 255: 121506, 2024 May 15.
Article En | MEDLINE | ID: mdl-38552486

Constructed wetlands (CWs) have been proven to effectively immobilize plastic particles. However, little is known about the differences in the impact of varying sized plastic particles on nitrous oxide (N2O) release, as well as the intervention mechanisms in CWs. Here, we built a lab-scale wetland model and introduced plastic particles of macro-, micro-, and nano-size at 100 µg/L for 370 days. The results showed that plastic particles of all sizes reduced N2O release in CWs, with the degrees being the strongest for the Nano group, followed by Micro and Macro groups. Meanwhile, 15N- and 18O-tracing experiment revealed that the ammoxidation process contributed the most N2O production, followed by denitrification. While for every N2O-releasing process, the contributing proportion of N2O in nitrification-coupled denitrification were most significantly cut down under exposing to macro-sized plastics and had an obvious increase in nitrifier denitrification in all groups, respectively. Finally, we revealed the three mechanism pathways of N2O release reduction with macro-, micro-, and nano-sized plastics by impacting carbon assimilation (RubisCO activity), ammonia oxidation (gene amo abundance and HAO activity), and N-ion transmembrane and reductase activities, respectively. Our findings thus provided novel insights into the potential effects of plastic particles in CWs as an eco-technology.

7.
Vector Borne Zoonotic Dis ; 24(4): 245-248, 2024 04.
Article En | MEDLINE | ID: mdl-38441490

Japanese encephalitis virus is mainly prevalent in the tropical and subtropical regions of Asia and Oceania. Through immunoprecipitation-mass spectrometry analysis using monoclonal antibodies targeting JEV E protein, we found that mosquito Histone 2A protein could bind to JEV particles. The binding of H2A and JEV was detected in the salivary gland and supernatant of mosquito cells. Furthermore, RNA interference experiments in vitro and in vivo confirmed that H2A protein promotes JEV infection in mosquitoes. In summary, we found that mosquito H2A is a factor that supports JEV infection and can potentially facilitate cross-species transmission of JEV.


Culex , Culicidae , Encephalitis Virus, Japanese , Encephalitis, Japanese , Animals , Encephalitis Virus, Japanese/genetics , Histones , Encephalitis, Japanese/veterinary , Mosquito Vectors
8.
J Hazard Mater ; 469: 134014, 2024 May 05.
Article En | MEDLINE | ID: mdl-38503208

Plant metal uptake can occur through both soil-root and atmospheric transfer from leaves. The latter holds potential implications for development of biofiltration systems. To explore this potential, it is crucial to understand entrapment capacity and metal sources within plants. As ferns absorb materials from atmosphere, this study focuses on two abundant fern species growing in densely populated and highly polluted regions of Eastern India. Gravimetric quantification, elemental concentration and Pb isotopic analyses were performed by segregating the ferns into distinct components: foliage dusts (loose dust (LD) and wax-bound dust (WD)) and plant tissue (leaves and roots). To understand metal sources, the study analyzes soil, and atmospheric particulates (PM10 and dust fall (DF)). Results indicate that, while LDs have soil dust influence, wax entraps atmospheric particulates and translocates them inside the leaves. Furthermore, roots demonstrate dissimilar isotopic ratios from soil, while displaying close association with atmospheric particulates. Isotopic composition and subsequent mixing model reveal dominant contribution from DF in leaves (53-73%) and roots (33-86%). Apart from DF, leaf Pb is sourced from PM10 (21-38%) with minimal contribution from soil (6-10%). Conversely, in addition to dominance from DF, roots source Pb primarily from soil (12-62%) with a meagre 2-8% contribution from PM10.


Air Pollutants , Air Pollution , Ferns , Metals, Heavy , Soil Pollutants , Lead/analysis , Environmental Monitoring/methods , Metals, Heavy/analysis , Air Pollution/analysis , Dust/analysis , Isotopes/analysis , Soil , Air Pollutants/analysis , Soil Pollutants/analysis
9.
Water Res ; 254: 121386, 2024 May 01.
Article En | MEDLINE | ID: mdl-38457942

Traditional disinfection processes face significant challenges such as health and ecological risks associated with disinfection-residual-bacteria due to their single mechanism of action. Development of new disinfection processes with composite mechanisms is therefore urgently needed. In this study, we employed liquid ground-electrode dielectric barrier discharge (lgDBD) to achieve synergistic sterilization through electric field electroporation and reactive species oxidation. At a voltage of 12 kV, Pseudomonas fluorescens (ultraviolet and ozone-resistant) and Bacillus subtilis (chlorine-resistant) were completely inactivated within 8 and 6 min, respectively, surpassing a 7.0-log reduction. The lgDBD process showed good disinfection performance across a wide range of pH values and different practical water samples. Staining experiments suggest that cellular membrane damage contributes to this inactivation. In addition, we used a two-dimensional parallel streamer solver with kinetics code to fashion a representative model of the basic discharge unit, and discovered the presence of a persistent electric field during the discharge process with a peak value of 2.86 × 106 V/m. Plasma discharge generates excited state species such as O(1D) and N2(C3Πu), and further forms reactive oxygen and nitrogen species at the gas-liquid interface. The physical process, which is driven by electric field-induced cell membrane electroporation, synergizes with the bactericidal effects of reactive oxygen and nitrogen species to provide effective disinfection. Adopting the lgDBD process enhances sterilization efficiency and adaptability, underscoring its potential to revolutionize physicochemical synergistic disinfection practices.


Ozone , Water Purification , Disinfection/methods , Bacteria , Chlorine , Nitrogen , Water Purification/methods
10.
Water Res ; 253: 121262, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38367374

Phosphorus (P) is a pivotal element responsible for triggering watershed eutrophication, and accurate source apportionment is a prerequisite for achieving the targeted prevention and control of P pollution. Current research predominantly emphasizes the allocation of total phosphorus (TP) loads from watershed pollution sources, with limited integration of source apportionment considering P species and their specific implications for eutrophication. This article conducts a retrospective analysis of the current state of research on watershed P source apportionment models, providing a comprehensive evaluation of three source apportionment methods, inventory analysis, diffusion models, and receptor models. Furthermore, a quantitative analysis of the impact of P species on watersheds is carried out, followed by the relationship between P species and the P source apportionment being critically clarified within watersheds. The study reveals that the impact of P on watershed eutrophication is highly dependent on P species, rather than absolute concentration of TP. Current research overlooking P species composition of pollution sources may render the acquired results of source apportionment incapable of assessing the impact of P sources on eutrophication accurately. In order to enhance the accuracy of watershed P pollution source apportionment, the following prospectives are recommended: (1) quantifying the P species composition of typical pollution sources; (2) revealing the mechanisms governing the migration and transformation of P species in watersheds; (3) expanding the application of traditional models and introducing novel methods to achieve quantitative source apportionment specifically for P species. Conducting source apportionment of specific species within a watershed contributes to a deeper understanding of P migration and transformation, enhancing the precise of management of P pollution sources and facilitating the targeted recovery of P resources.


Environmental Monitoring , Water Pollutants, Chemical , Environmental Monitoring/methods , Phosphorus/analysis , Retrospective Studies , Rivers , Water Quality , China , Nitrogen/analysis , Water Pollutants, Chemical/analysis
11.
Xenobiotica ; 54(3): 116-123, 2024 Mar.
Article En | MEDLINE | ID: mdl-38344757

Levetiracetam may cause acute renal failure and myoclonic encephalopathy at high plasma levels, particularly in patients with renal impairment. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict levetiracetam pharmacokinetics in Chinese adults with epilepsy and renal impairment and define appropriate levetiracetam dosing regimen.PBPK models for healthy subjects and epilepsy patients with renal impairment were developed, validated, and adapted. Furthermore, we predicted the steady-state trough and peak concentrations of levetiracetam in patients with renal impairment using the final PBPK model, thereby recommending appropriate levetiracetam dosing regimens for different renal function stages. The predicted maximum plasma concentration (Cmax), time to maximum concentration (Tmax), area under the plasma concentration-time curve (AUC) were in agreement (0.8 ≤ fold error ≤ 1.2) with the observed, and the fold error of the trough concentrations in end-stage renal disease (ESRD) was 0.77 - 1.22. The prediction simulations indicated that the recommended doses of 1000, 750, 500, and 500 mg twice daily for epilepsy patients with mild, moderate, severe renal impairment, and ESRD, respectively, were sufficient to achieve the target plasma concentration of levetiracetam.


Epilepsy , Kidney Failure, Chronic , Adult , Humans , Levetiracetam , Epilepsy/drug therapy , Kidney Function Tests , Area Under Curve , Models, Biological
13.
Sci Total Environ ; 907: 167677, 2024 Jan 10.
Article En | MEDLINE | ID: mdl-37832674

Nitrogen cycling is essential to ecosystem functioning and the overall health of our planet. Ammonia, a nitrogen-containing product, as well as a nutrient, is promoted as a low-carbon fuel for the maritime sector, with spectacular production increase in plan. Similar to any other widespread fuels in the past, it is paramount to be prepared for the potential environmental impact of ammonia fuel. Here, through our preliminary calculations using literature data, we suggest that the amount of ammonia to be produced to fulfil the maritime energy need by 2050 may entail large alterations in global nitrogen cycling. Currently, the literature based on limited known cases of ammonia excess is insufficient to quantify the environmental impacts caused by the probable increase in bunkering ammonia release at global scale. With a few knowledge gaps identified, we call on the marine science community to investigate the potential environmental impact related to substantial ammonia excess, contributing new knowledge to a more environmentally sustainable future.

14.
Int J Mol Sci ; 24(23)2023 Nov 24.
Article En | MEDLINE | ID: mdl-38069016

In order to optimize crop production and mitigate the adverse impacts associated with the utilization of chemical agents, it is necessary to explore new biocontrol agents. Bacillus velezensis has been widely studied as a biocontrol agent because of its efficient and ecofriendly plant disease control mechanisms. This study shows that the strain ZN-S10 effectively reduces the area of leaf spots caused by the pathogen Colletotrichum changpingense ZAFU0163-1, which affects conidia production and germination, inhibits mycelium growth, and induces mycelium deformation. In antifungal experiments with crude extracts, we observed a delay in the cell cycle of conidia, which may be responsible for the inhibition of conidial germination. Among the bioactive metabolites detected through integrated LC-MS- and GC-MS-based untargeted metabolomics, 7-O-Succinyl macrolactin A, telocinobufagin, and surfactin A may be the main antifungal metabolites of strain ZN-S10. The presence of 7-O-Succinyl macrolactin A could explain the cell damage in germ tubes. This is the first report of telocinobufagin detected in B. velezensis. These results are significant for understanding the inhibitory mechanisms employed by B. velezensis and should serve as a reference in the production of biocontrol agents.


Antifungal Agents , Bacillus , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Bacillus/metabolism , Plants/metabolism , Plant Diseases/prevention & control , Plant Diseases/microbiology
15.
Plants (Basel) ; 12(20)2023 Oct 21.
Article En | MEDLINE | ID: mdl-37896099

Tomato pith necrosis (TPN) is a highly destructive disease caused by species of the Pseudomonas genus and other bacteria, resulting in a significant reduction in tomato yield. Members of the genus Bacillus are beneficial microorganisms extensively studied in the rhizosphere. However, in most cases, the potential of Bacillus members in controlling TPN and their impact on the rhizosphere microbial composition remain rarely studied. In this study, Bacillus velezensis ZN-S10 significantly inhibited the growth of Pseudomonas viridiflava ZJUP0398-2, and ZN-S10 controlled TPN with control efficacies of 60.31%. P. viridiflava ZJUP0398-2 significantly altered the richness and diversity of the tomato rhizobacterial community, but pre-inoculation with ZN-S10 mitigated these changes. The correlation analysis revealed that ZN-S10 maybe inhibits the growth of nitrogen-fixing bacteria and recruits beneficial bacterial communities associated with disease resistance, thereby suppressing the occurrence of diseases. In summary, the comparative analysis of the rhizosphere microbiome was conducted to explore the impact of ZN-S10 on the composition of rhizosphere microorganisms in the presence of pathogenic bacteria, aiming to provide insights for further research and the development of scientific and eco-friendly control strategies for this disease.

16.
Sci Total Environ ; 905: 167157, 2023 Dec 20.
Article En | MEDLINE | ID: mdl-37730035

Recently, constructed wetland-microbial fuel cells (CW-MFCs) are found to enhance the organics removal via the connection of the external circuit. Yet, it is unclear why the energy output is unmatched with the enhancement of the organics removal. This study compared the dynamic changes of the organics in a CW-MFC microcosm operated under the close circuit and open circuit. As a result, the close circuit facilitated the organics removal by 9 % before the proportional discharge of carbon metabolites. This suggested that organics entrapment should account for the huge loss of carbon recovery; and closing the external circuit could further promote the organics entrapment. Besides, polyhydroxybutyrate was found accumulated in the MFC culture experiment, evidencing that the fed-batch mode of operation could result in a feast-famine pattern of microbial metabolism. Despite the fast organics entrapment during the first hours, prolonging the operation time would lead to continuous carbon gas emission, along with the substantially elevated coulombic efficiency. Together, these results explained the substantial COD removal enhancement with low electricity yield, and cautioned the safe use of the MFC integration to spare the system from overaccumulation of organics.


Bioelectric Energy Sources , Wetlands , Wastewater , Electricity , Carbon , Electrodes
17.
Pestic Biochem Physiol ; 194: 105490, 2023 Aug.
Article En | MEDLINE | ID: mdl-37532317

Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.


Aedes , Insecticides , Pyrethrins , Animals , DDT/pharmacology , Leucine , Pyrethrins/pharmacology , Insecticides/pharmacology , Sodium Channels/genetics , Mutation , Insecticide Resistance/genetics , Aedes/genetics , Mosquito Vectors/genetics
18.
J Hazard Mater ; 459: 132283, 2023 Oct 05.
Article En | MEDLINE | ID: mdl-37591172

Biochar-based materials have been widely used to remove Cr(VI). However, current strategies mainly focus on slow adsorption through electrostatic and functional group properties, ignoring the confinement catalytic fast kinetics caused by inherent porous properties. Herein, we designed a confinement strategy to achieve high-efficiency Cr(VI) reduction by encapsulating the catalytic reaction of Cr(VI) and oxalic acid (OA) in the micropore of PCRN-3-10-2-800. The results showed that the removal rate constant of the PCRN-3-10-2-800/OA system was 14.3 and 146.8 times higher than that of the BC-800/OA system (low porosity) and PCRN-3-10-2-800 alone (adsorption), which was highest removal rate constant in the current reported materials under the same system. The structure-activity relationship indicated that the catalytic activity of Cr(VI) depended on the micropore characteristics of the catalyst. Density functional theory calculations confirmed that nanoscale space could enhance Cr(VI) adsorption and reduce the energy barrier of the rate-determining step. The electron paramagnetic resonance spectrum demonstrated the rapid conversion of Cr(VI) to Cr(III). Furthermore, the PCRN-3-10-2-800/OA system showed good applicability and high efficiency for Cr(VI) removal (nearly 100% in 5 min) in industrial electroplating wastewater treatment. This work first proposes a nanoconfinement-induced heavy metal reduction strategy and guides biochar's universality design in wastewater treatment.

19.
Front Pharmacol ; 14: 1157437, 2023.
Article En | MEDLINE | ID: mdl-37168994

One of the major limitations in the clinical use of existing oxazolidinone antibiotics is their characteristic adverse reactions, in particular thrombocytopenia. In anti-infective treatment, if patients are suspected of having drug-induced thrombocytopenia, the first step is to immediately discontinue the offending drug. Even in patients with severe infections, the antibacterial drug may need to be changed or the antibacterial treatment may need to be discontinued because thrombocytopenia may have a more serious clinical prognosis. In addition, if the patient needs to continue antibacterial treatment after discharge, the lack of conditions for monitoring platelet levels may also pose hidden dangers to the patient. Contezolid is an orally administered oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021. We found that contezolid may have an improved safety profile with a significantly reduced potential for myelosuppression based on the results of our observational clinical study. In this article, we review the advantages of contezolid as a new oxazolidinone antibiotic and describe three typical clinical cases of patients who experienced drug-induced thrombocytopenia after using linezolid. The platelet levels of these different patients were all significantly improved to varying degrees after initiation of contezolid treatment.

20.
Microbiol Spectr ; 11(3): e0092823, 2023 06 15.
Article En | MEDLINE | ID: mdl-37212713

Lipids are prominent components of the mycobacterial cell wall, and they play critical roles not only in maintaining biofilm formation but also in resisting environmental stress, including drug resistance. However, information regarding the mechanism mediating mycobacterial lipid synthesis remains limited. PatA is a membrane-associated acyltransferase and synthesizes phosphatidyl-myo-inositol mannosides (PIMs) in mycobacteria. Here, we found that PatA could regulate the synthesis of lipids (except mycolic acids) to maintain biofilm formation and environmental stress resistance in Mycolicibacterium smegmatis. Interestingly, the deletion of patA significantly enhanced isoniazid (INH) resistance in M. smegmatis, although it reduced bacterial biofilm formation. This might be due to the fact that the patA deletion promoted the synthesis of mycolic acids through an unknown synthesis pathway other than the reported fatty acid synthase (FAS) pathway, which could effectively counteract the inhibition by INH of mycolic acid synthesis in mycobacteria. Furthermore, the amino acid sequences and physiological functions of PatA were highly conserved in mycobacteria. Therefore, we found a mycolic acid synthesis pathway regulated by PatA in mycobacteria. In addition, PatA also affected biofilm formation and environmental stress resistance by regulating the synthesis of lipids (except mycolic acids) in mycobacteria. IMPORTANCE Tuberculosis, caused by Mycobacterium tuberculosis, leads to a large number of human deaths every year. This is so serious, which is due mainly to the drug resistance of mycobacteria. INH kills M. tuberculosis by inhibiting the synthesis of mycolic acids, which are synthesized by the FAS pathway. However, whether there is another mycolic acid synthesis pathway is unknown. In this study, we found a PatA-mediated mycolic acid synthesis pathway that led to INH resistance of in patA-deleted mutant. In addition, we first report the regulatory effect of PatA on mycobacterial biofilm formation, which could affect the bacterial response to environmental stress. Our findings represent a new model for regulating biofilm formation by mycobacteria. More importantly, the discovery of the PatA-mediated mycolic acid synthesis pathway indicates that the study of mycobacterial lipids has entered a new stage, and the enzymes might be new targets of antituberculosis drugs.


Mycobacterium tuberculosis , Mycolic Acids , Humans , Mycolic Acids/metabolism , Mycolic Acids/pharmacology , Isoniazid/pharmacology , Mycobacterium smegmatis/metabolism , Biofilms , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
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