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1.
Nature ; 630(8015): 206-213, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38778111

RESUMO

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.


Assuntos
Terapia de Alvo Molecular , Neoplasias da Próstata , Radioisótopos , Compostos Radiofarmacêuticos , Animais , Humanos , Masculino , Camundongos , Antígenos de Superfície/química , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Fluoretos/química , Fluoretos/metabolismo , Glutamato Carboxipeptidase II/química , Glutamato Carboxipeptidase II/metabolismo , Ligantes , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Terapia de Alvo Molecular/métodos , Projetos Piloto , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Compostos de Enxofre/química , Compostos de Enxofre/metabolismo , Tirosina/metabolismo , Tirosina/química , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Immunol Rev ; 313(1): 64-70, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36089768

RESUMO

The evolutionary history of complement suggests that the alternative pathway arose prior to the arrival of the classical and lectin pathways. In these pathways, target specificity is provided by antibodies and sugar specific lectins. While these efficient initiation systems dominate activation on most targets, the alternative pathway produces most of the C3b and 80%-90% of the C5b-9. While the tickover process, originally proposed by Peter Lachmann, provided ancient hosts with a crude self/non-self-discriminatory system that initiated complement attack on everything foreign, tickover clearly plays a more minor role in complement activation in modern organisms possessing classical and lectin pathways. Spontaneous activation of the alternative pathway via tickover may play a major role in human pathologies where tissue damage is complement-mediated. The molecular mechanism of tickover is still not convincingly proven. Prevailing hypotheses include (a) spontaneous hydrolysis of the thioester in C3 forming the C3b-like C3(H2 O) in solution and (b) "enhanced tickover" in which surfaces cause specific or non-specific contact activated conformational changes in C3. Theoretical considerations, including computer simulations, suggest that the latter mechanism is more likely and that more research needs to be devoted to understanding interactions between biological surfaces and C3.


Assuntos
Complemento C3 , Complemento C3b , Humanos , Complemento C3/metabolismo , Complemento C3b/metabolismo , Ativação do Complemento , Anticorpos , Compostos de Enxofre , Via Alternativa do Complemento
3.
PLoS Pathog ; 20(7): e1012410, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39038066

RESUMO

One of the greatest challenges encountered by enteric pathogens is responding to rapid changes of nutrient availability in host. However, the mechanisms by which pathogens sense gastrointestinal signals and exploit available host nutrients for proliferation remain largely unknown. Here, we identified a two-component system in Vibrio parahaemolyticus, TtrRS, which senses environmental tetrathionate and subsequently activates the transcription of the ttrRS-ttrBCA-tsdBA gene cluster to promote V. parahaemolyticus colonization of adult mice. We demonstrated that TsdBA confers the ability of thiosulfate oxidation to produce tetrathionate which is sensed by TtrRS. TtrRS autoregulates and directly activates the transcription of the ttrBCA and tsdBA gene clusters. Activated TtrBCA promotes bacterial growth under micro-aerobic conditions by inducing the reduction of both tetrathionate and thiosulfate. TtrBCA and TsdBA activation by TtrRS is important for V. parahaemolyticus to colonize adult mice. Therefore, TtrRS and their target genes constitute a tetrathionate-responsive genetic circuit to exploit the host available sulfur compounds, which further contributes to the intestinal colonization of V. parahaemolyticus.


Assuntos
Proteínas de Bactérias , Vibrioses , Vibrio parahaemolyticus , Vibrio parahaemolyticus/metabolismo , Vibrio parahaemolyticus/genética , Animais , Camundongos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Compostos de Enxofre/metabolismo , Regulação Bacteriana da Expressão Gênica , Feminino , Camundongos Endogâmicos C57BL
4.
Proc Natl Acad Sci U S A ; 119(30): e2123022119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858422

RESUMO

The formation of carbon-carbon bonds from prebiotic precursors such as carbon dioxide represents the foundation of all primordial life processes. In extant organisms, this reaction is carried out by the carbon monoxide dehydrogenase (CODH)/acetyl coenzyme A synthase (ACS) enzyme, which performs the cornerstone reaction in the ancient Wood-Ljungdahl metabolic pathway to synthesize the key biological metabolite, acetyl-CoA. Despite its significance, a fundamental understanding of this transformation is lacking, hampering efforts to harness analogous chemistry. To address these knowledge gaps, we have designed an artificial metalloenzyme within the azurin protein scaffold as a structural, functional, and mechanistic model of ACS. We demonstrate the intermediacy of the NiI species and requirement for ordered substrate binding in the bioorganometallic carbon-carbon bond-forming reaction from the one-carbon ACS substrates. The electronic and geometric structures of the nickel-acetyl intermediate have been characterized using time-resolved optical, electron paramagnetic resonance, and X-ray absorption spectroscopy in conjunction with quantum chemical calculations. Moreover, we demonstrate that the nickel-acetyl species is chemically competent for selective acyl transfer upon thiol addition to biosynthesize an activated thioester. Drawing an analogy to the native enzyme, a mechanism for thioester generation by this ACS model has been proposed. The fundamental insight into the enzymatic process provided by this rudimentary ACS model has implications for the evolution of primitive ACS-like proteins. Ultimately, these findings offer strategies for development of highly active catalysts for sustainable generation of liquid fuels from one-carbon substrates, with potential for broad applications across diverse fields ranging from energy storage to environmental remediation.


Assuntos
Aldeído Oxirredutases , Azurina , Ésteres , Complexos Multienzimáticos , Níquel , Origem da Vida , Compostos de Enxofre , Aldeído Oxirredutases/química , Azurina/química , Catálise , Ésteres/síntese química , Modelos Químicos , Complexos Multienzimáticos/química , Níquel/química , Compostos de Enxofre/síntese química
5.
Infect Immun ; 92(3): e0042223, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38289071

RESUMO

Listeria monocytogenes (Lm) is a Gram-positive facultative intracellular pathogen that leads a biphasic lifecycle, transitioning its metabolism and selectively inducing virulence genes when it encounters mammalian hosts. Virulence gene expression is controlled by the master virulence regulator PrfA, which is allosterically activated by the host- and bacterially derived glutathione (GSH). The amino acid cysteine is the rate-limiting substrate for GSH synthesis in bacteria and is essential for bacterial growth. Unlike many bacteria, Lm is auxotrophic for cysteine and must import exogenous cysteine for growth and virulence. GSH is enriched in the host cytoplasm, and previous work suggests that Lm utilizes exogenous GSH for PrfA activation. Despite these observations, the import mechanism(s) for GSH remains elusive. Analysis of known GSH importers predicted a homologous importer in Lm comprised of the Ctp ABC transporter and the OppDF ATPases of the Opp oligopeptide importer. Here, we demonstrated that the Ctp complex is a high-affinity GSH/GSSG importer that is required for Lm growth at physiologically relevant concentrations. Furthermore, we demonstrated that OppDF is required for GSH/GSSG import in an Opp-independent manner. These data support a model where Ctp and OppDF form a unique complex for GSH/GSSG import that supports growth and pathogenesis. In addition, we show that Lm utilizes the inorganic sulfur sources thiosulfate and H2S for growth in a CysK-dependent manner in the absence of other cysteine sources. These findings suggest a pathoadaptive role for partial cysteine auxotrophy in Lm, where locally high GSH/GSSG or inorganic sulfur concentrations may signal arrival to distinct host niches.


Assuntos
Listeria monocytogenes , Animais , Cisteína/metabolismo , Dissulfeto de Glutationa/genética , Dissulfeto de Glutationa/metabolismo , Compostos de Enxofre/metabolismo , Glutationa , Enxofre/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Mamíferos
6.
J Am Chem Soc ; 146(2): 1388-1395, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38176024

RESUMO

Site-specific covalent conjugation offers a powerful tool to identify and understand protein-protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coli acyl carrier protein (AcpP) with its partner BioF, a key pyridoxal 5'-phosphate (PLP)-dependent enzyme in the early steps of biotin biosynthesis by targeting a tyrosine residue proximal to the active site. We identify the site of crosslink by MS/MS analysis of the peptide originating from both partners. We further evaluate the BioF-AcpP interface through protein crystallography and mutational studies. Among the AcpP-interacting BioF surface residues, three critical arginine residues appear to be involved in AcpP recognition so that pimeloyl-AcpP can serve as the acyl donor for PLP-mediated catalysis. These findings validate an evolutionary gain-of-function for BioF, allowing the organism to build biotin directly from fatty acid biosynthesis through surface modifications selective for salt bridge formation with acidic AcpP residues.


Assuntos
Biotina , Fluoretos , Compostos de Enxofre , Espectrometria de Massas em Tandem , Biotina/metabolismo , Escherichia coli/metabolismo , Ácidos Graxos/metabolismo
7.
Appl Environ Microbiol ; 90(2): e0201523, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38299812

RESUMO

Fungi have the capacity to assimilate a diverse range of both inorganic and organic sulfur compounds. It has been recognized that all sulfur sources taken up by fungi are in soluble forms. In this study, we present evidence that fungi can utilize gaseous carbonyl sulfide (COS) for the assimilation of a sulfur compound. We found that the filamentous fungus Trichoderma harzianum strain THIF08, which has constitutively high COS-degrading activity, was able to grow with COS as the sole sulfur source. Cultivation with 34S-labeled COS revealed that sulfur atom from COS was incorporated into intracellular metabolites such as glutathione and ergothioneine. COS degradation by strain THIF08, in which as much of the moisture derived from the agar medium as possible was removed, indicated that gaseous COS was taken up directly into the cell. Escherichia coli transformed with a COS hydrolase (COSase) gene, which is clade D of the ß-class carbonic anhydrase subfamily enzyme with high specificity for COS but low activity for CO2 hydration, showed that the COSase is involved in COS assimilation. Comparison of sulfur metabolites of strain THIF08 revealed a higher relative abundance of reduced sulfur compounds under the COS-supplemented condition than the sulfate-supplemented condition, suggesting that sulfur assimilation is more energetically efficient with COS than with sulfate because there is no redox change of sulfur. Phylogenetic analysis of the genes encoding COSase, which are distributed in a wide range of fungal taxa, suggests that the common ancestor of Ascomycota, Basidiomycota, and Mucoromycota acquired COSase at about 790-670 Ma.IMPORTANCEThe biological assimilation of gaseous CO2 and N2 involves essential processes known as carbon fixation and nitrogen fixation, respectively. In this study, we found that the fungus Trichoderma harzianum strain THIF08 can grow with gaseous carbonyl sulfide (COS), the most abundant and ubiquitous gaseous sulfur compound, as a sulfur source. When the fungus grew in these conditions, COS was assimilated into sulfur metabolites, and the key enzyme of this assimilation process is COS hydrolase (COSase), which specifically degrades COS. Moreover, the pathway was more energy efficient than the typical sulfate assimilation pathway. COSase genes are widely distributed in Ascomycota, Basidiomycota, and Mucoromycota and also occur in some Chytridiomycota, indicating that COS assimilation is widespread in fungi. Phylogenetic analysis of these genes revealed that the acquisition of COSase in filamentous fungi was estimated to have occurred at about 790-670 Ma, around the time that filamentous fungi transitioned to a terrestrial environment.


Assuntos
Hypocreales , Óxidos de Enxofre , Trichoderma , Gases , Dióxido de Carbono , Solo , Filogenia , Compostos de Enxofre , Enxofre/metabolismo , Hypocreales/genética , Hypocreales/metabolismo , Hidrolases/metabolismo , Sulfatos , Trichoderma/genética , Trichoderma/metabolismo
8.
Invest New Drugs ; 42(1): 70-79, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38085423

RESUMO

In recent years, a number of novel pharmaceutical agents have received approval for the management of acute myeloid leukemia (AML). However, there is still ample opportunity for enhancing efficacy. The Wee1 inhibitor adavosertib (ADA) shows promise for the treatment of AML. Based on the effect of drugs on DNA damage, we conducted a combination study involving ADA and fimepinostat (CUDC-907), a dual inhibitor of PI3K and histone deacetylase (HDAC). We observed that the combination of CUDC-907 and ADA exhibited a synergistic effect in enhancing the antileukemic activity in both AML cell lines and primary patient samples, demonstrating through flow cytometry analysis and MTT assay, respectively. Additionally, our study revealed that CUDC-907 has the ability to augment ADA-induced DNA damage, as determined by the measurement of γH2AX levels and the implementation of the alkaline comet assay. Through the utilization of western blotting analyses, targeted inhibitors, and ectopic overexpression, we propose that the downregulation of Wee1, CHK1, RNR, and c-Myc are the potential mechanisms. Our data support the development of ADA in combination with CUDC-907 for the treatment of AML.


Assuntos
Leucemia Mieloide Aguda , Morfolinas , Pirazóis , Pirimidinas , Pirimidinonas , Compostos de Enxofre , Humanos , Dano ao DNA , Leucemia Mieloide Aguda/tratamento farmacológico
9.
Arch Biochem Biophys ; 758: 110048, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38848996

RESUMO

The inherent structural properties of enzymes are critical in defining catalytic function. Often, studies to evaluate the relationship between structure and function are limited to only one defined structural element. The two-component flavin-dependent desulfonase family of enzymes involved in bacterial sulfur acquisition utilize a comprehensive range of structural features to carry out the desulfonation of organosulfur compounds. These metabolically essential two-component FMN-dependent desulfonase systems have been proposed to utilize oligomeric changes, protein-protein interactions for flavin transfer, and common mechanistic steps for carbon-sulfur bond cleavage. This review is focused on our current functional and structural understanding of two-component FMN-dependent desulfonase systems from multiple bacterial sources. Mechanistic and structural comparisons from recent independent studies provide fresh insights into the overall functional properties of these systems and note areas in need of further investigation. The review acknowledges current studies focused on evaluating the structural properties of these enzymes in relationship to their distinct catalytic function. The role of these enzymes in maintaining adequate sulfur levels, coupled with the conserved nature of these enzymes in diverse bacteria, underscore the importance in understanding the functional and structural nuances of these systems.


Assuntos
Proteínas de Bactérias , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Bactérias/enzimologia , Compostos de Enxofre/metabolismo , Compostos de Enxofre/química , Hidrolases/química , Hidrolases/metabolismo , Mononucleotídeo de Flavina/metabolismo , Mononucleotídeo de Flavina/química , Enxofre/metabolismo , Enxofre/química , Flavinas/metabolismo , Flavinas/química , Relação Estrutura-Atividade , Carbono/metabolismo , Carbono/química
10.
J Org Chem ; 89(11): 8005-8010, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38804706

RESUMO

Trace palladium in synthetic materials can be rapidly and inexpensively semiquantified by a catalysis-based fluorometric method that converts resorufin allyl ether to resorufin. However, whether sulfur compounds would interfere with this method has not been systematically studied. Herein, we show that although thiourea in solution interferes with quantification, sulfide, thiol, and thiocarbamate do not. The fluorometric method can also detect palladium bound to sulfur-based scavenger resin and outperform inductively coupled plasma mass spectrometry for detecting trace palladium in ibuprofen.


Assuntos
Fluorometria , Ibuprofeno , Paládio , Paládio/química , Ibuprofeno/química , Ibuprofeno/análise , Catálise , Fluorometria/métodos , Estrutura Molecular , Compostos de Enxofre/química , Compostos de Enxofre/análise
11.
Environ Sci Technol ; 58(17): 7357-7366, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38568220

RESUMO

Although sulfur cycling in acid mine drainage (AMD)-contaminated rice paddy soils is critical to understanding and mitigating the environmental consequences of AMD, potential sources and transformations of organosulfur compounds in such soils are poorly understood. We used sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy to quantify organosulfur compounds in paddy soils from five AMD-contaminated sites and one AMD-uncontaminated reference site near the Dabaoshan sulfide mining area in South China. We also determined the sulfur stable isotope compositions of water-soluble sulfate (δ34SWS), adsorbed sulfate (δ34SAS), fulvic acid sulfur (δ34SFAS), and humic acid sulfur (δ34SHAS) in these samples. Organosulfate was the dominant functional group in humic acid sulfur (HAS) in both AMD-contaminated (46%) and AMD-uncontaminated paddy soils (42%). Thiol/organic monosulfide contributed a significantly lower proportion of HAS in AMD-contaminated paddy soils (8%) compared to that in AMD-uncontaminated paddy soils (21%). Within contaminated soils, the concentration of thiol/organic monosulfide was positively correlated with cation exchange capacity (CEC), moisture content (MC), and total Fe (TFe). δ34SFAS ranged from -6.3 to 2.7‰, similar to δ34SWS (-6.9 to 8.9‰), indicating that fulvic acid sulfur (FAS) was mainly derived from biogenic S-bearing organic compounds produced by assimilatory sulfate reduction. δ34SHAS (-11.0 to -1.6‰) were more negative compared to δ34SWS, indicating that dissimilatory sulfate reduction and abiotic sulfurization of organic matter were the main processes in the formation of HAS.


Assuntos
Mineração , Oryza , Poluentes do Solo , Solo , Solo/química , Oryza/química , Substâncias Húmicas , Enxofre , Compostos de Enxofre
12.
Anal Bioanal Chem ; 416(11): 2871-2882, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581531

RESUMO

Antarctic seaweeds are vital components of polar marine ecosystems, playing a crucial role in nutrient cycling and supporting diverse life forms. The sulfur content in these organisms is particularly interesting due to its implication in biogeochemical processes and potential impacts on local and global environmental systems. In this study, we present a comprehensive characterization of seaweed collected in the Antarctic in terms of their total sulfur content and its distribution among different classes of species, including thiols, using various methods and high-sensitivity techniques. The data presented in this paper are unprecedented in the scientific literature. These methods allowed for the determination of total sulfur content and the distribution of sulfur compounds in different fractions, such as water-soluble and proteins, as well as the speciation of sulfur compounds in these fractions, providing valuable insights into the chemical composition of these unique marine organisms. Our results revealed that the total sulfur concentration in Antarctic seaweeds varied widely across different species, ranging from 5.5 to 56 g kg-1 dry weight. Furthermore, our investigation into the sulfur speciation revealed the presence of various sulfur compounds, including sulfate, and some thiols, which were quantified in all ten seaweed species evaluated. The concentration of these individual sulfur species also displayed considerable variability among the studied seaweeds. This study provides the first in-depth examination of total sulfur content and sulfur speciation in brown and red Antarctic seaweeds.


Assuntos
Alga Marinha , Alga Marinha/química , Regiões Antárticas , Peso Molecular , Ecossistema , Enxofre/metabolismo , Compostos de Enxofre/metabolismo , Verduras , Compostos de Sulfidrila/metabolismo
13.
Nature ; 561(7721): 109-112, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30111837

RESUMO

Intensive agriculture currently relies on pesticides to maximize crop yield1,2. Neonicotinoids are the most widely used insecticides globally3, but increasing evidence of negative impacts on important pollinators4-9 and other non-target organisms10 has led to legislative reassessment and created demand for the development of alternative products. Sulfoximine-based insecticides are the most likely successor11, and are either licensed for use or under consideration for licensing in several worldwide markets3, including within the European Union12, where certain neonicotinoids (imidacloprid, clothianidin and thiamethoxam) are now banned from agricultural use outside of permanent greenhouse structures. There is an urgent need to pre-emptively evaluate the potential sub-lethal effects of sulfoximine-based pesticides on pollinators11, because such effects are rarely detected by standard ecotoxicological assessments, but can have major impacts at larger ecological scales13-15. Here we show that chronic exposure to the sulfoximine-based insecticide sulfoxaflor, at dosages consistent with potential post-spray field exposure, has severe sub-lethal effects on bumblebee (Bombus terrestris) colonies. Field-based colonies that were exposed to sulfoxaflor during the early growth phase produced significantly fewer workers than unexposed controls, and ultimately produced fewer reproductive offspring. Differences between the life-history trajectories of treated and control colonies first became apparent when individuals exposed as larvae began to emerge, suggesting that direct or indirect effects on a small cohort may have cumulative long-term consequences for colony fitness. Our results caution against the use of sulfoximines as a direct replacement for neonicotinoids. To avoid continuing cycles of novel pesticide release and removal, with concomitant impacts on the environment, a broad evidence base needs to be assessed prior to the development of policy and regulation.


Assuntos
Abelhas/efeitos dos fármacos , Abelhas/fisiologia , Inseticidas/efeitos adversos , Piridinas/efeitos adversos , Compostos de Enxofre/efeitos adversos , Animais , Feminino , Inseticidas/administração & dosagem , Masculino , Dinâmica Populacional , Piridinas/administração & dosagem , Reprodução/efeitos dos fármacos , Compostos de Enxofre/administração & dosagem
14.
Nature ; 563(7731): 412-415, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30429546

RESUMO

Algae produce massive amounts of dimethylsulfoniopropionate (DMSP), which fuel the organosulfur cycle1,2. On a global scale, several petagrams of this sulfur species are produced annually, thereby driving fundamental processes and the marine food web1. An important DMSP transformation product is dimethylsulfide, which can be either emitted to the atmosphere3,4 or oxidized to dimethylsulfoxide (DMSO) and other products5. Here we report the discovery of a structurally unusual metabolite, dimethylsulfoxonium propionate (DMSOP), that is synthesized by several DMSP-producing microalgae and marine bacteria. As with DMSP, DMSOP is a low-molecular-weight zwitterionic metabolite that carries both a positively and a negatively charged functional group. Isotope labelling studies demonstrate that DMSOP is produced from DMSP, and is readily metabolized to DMSO by marine bacteria. DMSOP was found in near nanomolar amounts in field samples and in algal culture media, and thus represents-to our knowledge-a previously undescribed biogenic source for DMSO in the marine environment. The estimated annual oceanic production of oxidized sulfur from this pathway is in the teragram range, similar to the calculated dimethylsulfide flux to the atmosphere3. This sulfoxonium metabolite is therefore a key metabolite of a previously undescribed pathway in the marine sulfur cycle. These findings highlight the importance of DMSOP in the marine organosulfur cycle.


Assuntos
Organismos Aquáticos/metabolismo , Bactérias/metabolismo , Microalgas/metabolismo , Compostos de Enxofre/metabolismo , Bactérias/crescimento & desenvolvimento , Dimetil Sulfóxido/metabolismo , Marcação por Isótopo , Microalgas/crescimento & desenvolvimento , Oxirredução , Fitoplâncton/citologia , Fitoplâncton/metabolismo , Sulfetos/metabolismo , Compostos de Sulfônio/metabolismo , Compostos de Enxofre/química
15.
Ecotoxicology ; 33(6): 546-559, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38649545

RESUMO

Wild bees are crucial pollinators of flowering plants and concerns are rising about their decline associated with pesticide use. Interspecific variation in wild bee response to pesticide exposure is expected to be related to variation in their morphology, physiology, and ecology, though there are still important knowledge gaps in its understanding. Pesticide risk assessments have largely focussed on the Western honey bee sensitivity considering it protective enough for wild bees. Recently, guidelines for Bombus terrestris and Osmia bicornis testing have been developed but are not yet implemented at a global scale in pesticide risk assessments. Here, we developed and tested a new simplified method of pesticide exposure on wild bee species collected from the field in Belgium. Enough specimens of nine species survived in a laboratory setting and were exposed to oral and topical acute doses of a sulfoximine insecticide. Our results confirm significant variability among wild bee species. We show that Osmia cornuta is more sensitive to sulfoxaflor than B. terrestris, whereas Bombus hypnorum is less sensitive. We propose hypotheses on the mechanisms explaining interspecific variations in sensitivity to pesticides. Future pesticide risk assessments of wild bees will require further refinement of protocols for their controlled housing and exposure.


Assuntos
Inseticidas , Piridinas , Compostos de Enxofre , Animais , Abelhas/efeitos dos fármacos , Abelhas/fisiologia , Inseticidas/toxicidade , Piridinas/toxicidade , Compostos de Enxofre/toxicidade , Especificidade da Espécie , Bélgica , Medição de Risco
16.
Pestic Biochem Physiol ; 204: 106061, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277377

RESUMO

Aphis gossypii Glover is one of the most agriculturally important phloem-feeding economic pests, causing tremendous loss in crop yield annually. The hormesis is an important cause of A. gossypii resistance formation, population resurgence, and re-outbreak. However, whether the hormesises induced by different insecticides interact mutually remain largely unclear. In the study, four-generation A. gossypii experiment found that the 24-h sublethal-dose (LC20) sulfoxaflor treatment on G0 significantly increased the net reproductive rate (R0) and fecundity of G1 and G2 generation A. gossypii, but it did not significantly affect the fecundity of G3 and G4 individuals. Transcriptomic analyses revealed that the insecticide-induced significant up-regulation of pathways ribosome, energy metabolism, and the DNA replication and reparation might be responsible for the enhancement of fecundity in G1 and G2 A. gossypii. Notably, G0 exposure to LC20 sulfoxaflor followed by G1 exposure to LC30 deltamethrin resulted in a stronger reproductive stimulation than sulfoxaflor or deltamethrin exposure alone. Our findings provide valuable reference for optimizing sulfoxaflor application in integrated pest management strategies.


Assuntos
Afídeos , Hormese , Inseticidas , Piridinas , Reprodução , Compostos de Enxofre , Animais , Compostos de Enxofre/toxicidade , Compostos de Enxofre/farmacologia , Reprodução/efeitos dos fármacos , Afídeos/efeitos dos fármacos , Afídeos/genética , Hormese/efeitos dos fármacos , Piridinas/toxicidade , Piridinas/farmacologia , Inseticidas/toxicidade , Inseticidas/farmacologia , Piretrinas/toxicidade , Nitrilas/toxicidade , Nitrilas/farmacologia , Fertilidade/efeitos dos fármacos
17.
Clin Oral Investig ; 28(6): 341, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801476

RESUMO

OBJECTIVES: The purpose of this systemic review and meta-analysis was to explore the association between halitosis and periodontitis in observational studies. MATERIALS AND METHODS: A systematic search covered PubMed, Web of Science, Embase, Scopus, and Cochrane Library until August 18, 2023. Nine observational studies (585 cases, 1591 controls) were analyzed using Stata 17, with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses considered halitosis assessment methods. RESULTS: The review found a positive association between halitosis and periodontitis. Significant differences were observed with organoleptic test (OR = 4.05, 95% CI: 1.76, 9.30, p < 0.01) and volatile sulfur compound readings (OR = 4.52, 95% CI: 1.89, 10.83, p < 0.01). CONCLUSIONS: A positive association was observed between halitosis and periodontitis, supported by significant differences in both organoleptic and volatile sulfur compound readings. However, conclusive findings are limited by statistical heterogeneity, emphasizing the need for additional research. CLINICAL RELEVANCE: Understanding the halitosis and periodontitis association is clinically significant, informing potential interventions for improved oral health. Further research is vital to refine understanding and guide effective clinical strategies, acknowledging the limitations in current findings.


Assuntos
Halitose , Periodontite , Halitose/etiologia , Humanos , Periodontite/complicações , Compostos de Enxofre/análise , Estudos Observacionais como Assunto
18.
Int J Mol Sci ; 25(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39125961

RESUMO

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.


Assuntos
Compostos Alílicos , Antioxidantes , Dissulfetos , Alho , Fenóis , Extratos Vegetais , Sulfetos , Ácidos Sulfínicos , Alho/química , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Fenóis/farmacologia , Fenóis/química , Dissulfetos/farmacologia , Dissulfetos/química , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ácidos Sulfínicos/farmacologia , Ácidos Sulfínicos/química , Sulfetos/farmacologia , Sulfetos/química , Compostos Alílicos/farmacologia , Compostos Alílicos/química , Compostos de Enxofre/farmacologia , Compostos de Enxofre/química , Cisteína/análogos & derivados , Cisteína/química , Cisteína/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo
19.
J Environ Manage ; 351: 119954, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169252

RESUMO

Bioleaching technologies have been shown to be an environmentally friendly and economically beneficial tool for extracting metals from spent lithium-ion batteries (LIBs). However, conventional bioleaching methods have exhibited low efficiency in recovering metals from spent LIBs. Therefore, relied on the sustainability principle of using waste to treat waste, this study employed pyrite (FeS2) as an energy substance with reducing properties and investigated its effects in combination with elemental sulfur (S0) or FeSO4 on metals bioleaching from spent LIBs. Results demonstrated that the bioleaching efficiency was significantly higher in the leaching system constructed with FeS2 + S0, than in the FeS2 + FeSO4 or FeS2 system. When the pulp densities of FeS2, S0 and spent LIBs were 10 g L-1, 5 g L-1 and 10 g L-1, respectively, the leaching efficiency of Li, Ni, Co and Mn all reached 100%. Mechanistic analysis reveals that in the FeS2 + S0 system, the activity and acid-producing capabilities of iron-sulfur oxidizing bacteria were enhanced, promoting the generation of Fe (Ⅱ) and reducible sulfur compounds. Simultaneously, bio-acids were shown to disrupt the structure of the LIBs, thereby increasing the contact area between Fe (Ⅱ) and sulfur compounds containing high-valence metals. This effectively promoted the reduction of high-valence metals, thereby enhancing their leaching efficiency. Overall, the FeS2 + S0 bioleaching process constructed in this study, improved the leaching efficiency of LIBs while also effectively utilizing waste, providing technical support for the comprehensive and sustainable management of solid waste.


Assuntos
Ferro , Lítio , Sulfetos , Lítio/química , Metais , Enxofre , Compostos de Enxofre , Fontes de Energia Elétrica , Reciclagem
20.
J Environ Manage ; 354: 120321, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377755

RESUMO

Due to the malodorous effects and health risks of volatile sulfur compounds (VSCs) emitted from wastewater treatment plants (WWTPs), odor collection devices have been extensively utilized; however, their effectiveness has rarely been tested. In the present investigation, the characteristics of VSCs released in a WWTP equipped with gas collection hoods are methodically examined by gas chromatography. The obtained results indicate that the concentration of VSCs in the ambient air can be substantially reduced, and the primary treatment unit still achieves the highest concentration of VSCs. Compared to WWTPs without odor collection devices, the concentration of H2S in this WWTP is not dominant, but its sensory effects and health risks are still not negligible. Additionally, research on the emission of VSCs from sludge reveals that the total VSCs emitted from dewatering sludge reaches the highest level. Volatile organic sulfur compounds play a dominant role in the component and sensory effects of VSCs released by sludge. This study provides both data and theoretical support for analyzing the effectiveness of odor collection devices in WWTPs, as well as reducing the source of VSCs. The findings can be effectively employed to optimize these devices and improve their performance.


Assuntos
Compostos Orgânicos Voláteis , Purificação da Água , Compostos de Enxofre/análise , Compostos de Enxofre/química , Esgotos , Odorantes/análise , Medição de Risco , Compostos Orgânicos Voláteis/análise
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