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1.
PLoS Pathog ; 20(7): e1012362, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38976759

RESUMO

Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid ß-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.


Assuntos
Candida auris , Candidíase , Proteínas Fúngicas , Mutação , Candidíase/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candida auris/genética , Candida auris/metabolismo , Camundongos , Animais , Glicerol/metabolismo , Adaptação Fisiológica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação Fúngica da Expressão Gênica , Humanos
2.
JCO Precis Oncol ; 8: e2300697, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38976819

RESUMO

PURPOSE: This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). METHODS: Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. RESULTS: Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. CONCLUSION: Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.


Assuntos
Sequenciamento do Exoma , Mutação em Linhagem Germinativa , Neoplasias Urológicas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Urológicas/genética , Genômica , Predisposição Genética para Doença , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes
3.
Phys Chem Chem Phys ; 26(26): 18321-18332, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38912536

RESUMO

The biphenyl molecule (C12H10) acts as a fundamental molecular backbone in the stereoselective synthesis of organic materials due to its inherent twist angle causing atropisomerism in substituted derivatives and in molecular mass growth processes in circumstellar environments and combustion systems. Here, we reveal an unconventional low-temperature phenylethynyl addition-cyclization-aromatization mechanism for the gas-phase preparation of biphenyl (C12H10) along with ortho-, meta-, and para-substituted methylbiphenyl (C13H12) derivatives through crossed molecular beams and computational studies providing compelling evidence on their formation via bimolecular gas-phase reactions of phenylethynyl radicals (C6H5CC, X2A1) with 1,3-butadiene-d6 (C4D6), isoprene (CH2C(CH3)CHCH2), and 1,3-pentadiene (CH2CHCHCHCH3). The dynamics involve de-facto barrierless phenylethynyl radical additions via submerged barriers followed by facile cyclization and hydrogen shift prior to hydrogen atom emission and aromatization to racemic mixtures (ortho, meta) of biphenyls in overall exoergic reactions. These findings not only challenge our current perception of biphenyls as high temperature markers in combustion systems and astrophysical environments, but also identify biphenyls as fundamental building blocks of complex polycyclic aromatic hydrocarbons (PAHs) such as coronene (C24H12) eventually leading to carbonaceous nanoparticles (soot, grains) in combustion systems and in deep space thus affording critical insight into the low-temperature hydrocarbon chemistry in our universe.

4.
J Vis Exp ; (205)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38497631

RESUMO

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.


Assuntos
Artrite Psoriásica , Doenças da Unha , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/patologia , Psoríase/diagnóstico , Pele/patologia , Doenças da Unha/patologia , Eritema
5.
Open Med (Wars) ; 19(1): 20231000, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463524

RESUMO

[This corrects the article DOI: 10.1515/med-2020-0173.].

6.
Chem Commun (Camb) ; 60(25): 3445-3448, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38445390

RESUMO

Quinoline carboxylic acid-linked and Pd nanoparticle (NP)-loaded COF nanospheres were constructed via a three-component one-pot Doebner reaction and post-synthetic metalation. The obtained Pd@DhaTAPB-COOH solid stabilizer can greatly promote the pH-switched recyclable Pickering interfacial dechlorination reaction, which sheds light on the bright future of smart Pickering emulsion catalysis.

7.
Nat Commun ; 15(1): 2381, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493178

RESUMO

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.


Assuntos
Candidíase , Sepse , Animais , Camundongos , Candida/genética , Candidíase/microbiologia , Candida auris , Saccharomyces cerevisiae , Fenótipo , Antifúngicos , Testes de Sensibilidade Microbiana , Mamíferos
8.
JCO Precis Oncol ; 8: e2300453, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38412388

RESUMO

PURPOSE: Establishing accurate age-related penetrance figures for the broad range of cancer types that occur in individuals harboring a pathogenic germline variant in the TP53 gene is essential to determine the most effective clinical management strategies. These figures also permit optimal use of cosegregation data for classification of TP53 variants of unknown significance. Penetrance estimation can easily be affected by bias from ascertainment criteria, an issue not commonly addressed by previous studies. MATERIALS AND METHODS: We performed a maximum likelihood penetrance estimation using full pedigree data from a multicenter study of 146 TP53-positive families, incorporating adjustment for the effect of ascertainment and population-specific background cancer risks. The analysis included pedigrees from Australia, Spain, and United States, with phenotypic information for 4,028 individuals. RESULTS: Core Li-Fraumeni syndrome (LFS) cancers (breast cancer, adrenocortical carcinoma, brain cancer, osteosarcoma, and soft tissue sarcoma) had the highest hazard ratios of all cancers analyzed in this study. The analysis also detected a significantly increased lifetime risk for a range of cancers not previously formally associated with TP53 pathogenic variant status, including colorectal, gastric, lung, pancreatic, and ovarian cancers. The cumulative risk of any cancer type by age 50 years was 92.4% (95% CI, 82.2 to 98.3) for females and 59.7% (95% CI, 39.9 to 81.3) for males. Females had a 63.3% (95% CI, 35.6 to 90.1) cumulative risk of developing breast cancer by age 50 years. CONCLUSION: The results from maximum likelihood analysis confirm the known high lifetime risk for the core LFS-associated cancer types providing new risk estimates and indicate significantly increased lifetime risks for several additional cancer types. Accurate cancer risk estimates will help refine clinical recommendations for TP53 pathogenic variant carriers and improve TP53 variant classification.


Assuntos
Neoplasias da Mama , Síndrome de Li-Fraumeni , Masculino , Feminino , Humanos , Estados Unidos , Pessoa de Meia-Idade , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/genética , Genes p53/genética , Linhagem , Proteína Supressora de Tumor p53/genética , Predisposição Genética para Doença/genética , Neoplasias da Mama/genética , Fatores de Risco
9.
Chem Asian J ; 19(6): e202301103, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38288641

RESUMO

The development of effective and stable non-precious catalysts for hydrogenation of ester to diols remains a challenge. Herein, the catalytic hydrogenation of ethyl lactate (EL) to 1,2-propanediol (1,2-PDO) with supported Co catalysts derived from layered double hydroxides (LDHs) is investigated. Catalytic tests reveal that LDH-derived Co catalysts exhibit the best catalytic performance with 98 % of EL conversion and >99 % of 1,2-PDO selectivity at mild conditions, compared with other Co catalysts (supported on Al2O3, and TiO2) and LDH-derived Cu catalysts. Due to the strong interaction among Co and Al matrix, the main composition is metallic Co0 and CoO after reduction at 600 °C. Besides, the catalyst shows good recyclability in the liquid phase hydrogenation. The superior catalytic performance can be attributed to the synergistic effect between Co0 and CoO, in which H2 molecule is activated on Co0 and EL is strongly adsorbed on CoO via hydroxyl groups.

10.
Chem Commun (Camb) ; 60(11): 1404-1407, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38174640

RESUMO

A high temperature phenyl-mediated addition-cyclization-dehydrogenation mechanism to form peri-fused polycyclic aromatic hydrocarbon (PAH) derivatives-illustrated through the formation of dibenzo[e,l]pyrene (C24H14)-is explored through a gas-phase reaction of the phenyl radical (C6H5˙) with triphenylene (C18H12) utilizing photoelectron photoion coincidence spectroscopy (PEPICO) combined with electronic structure calculations. Low-lying vibrational modes of dibenzo[e,l]pyrene exhibit out-of-plane bending and are easily populated in high temperature environments such as combustion flames and circumstellar envelopes of carbon stars, thus stressing dibenzo[e,l]pyrene as a strong target for far-IR astronomical surveys.

11.
Emerg Microbes Infect ; 13(1): 2302843, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38238874

RESUMO

The emerging human fungal pathogen Candida auris has become a serious threat to public health. This pathogen has spread to 10 provinces in China as of December 2023. Here we describe 312 C. auris-associated hospitalizations and 4 outbreaks in healthcare settings in China from 2018 to 2023. Three genetic clades of C. auris have been identified during this period. Molecular epidemiological analyses indicate that C. auris has been introduced and local transmission has occurred in multiple instances in China. Most C. auris isolated from China (98.7%) exhibited resistance to fluconazole, while only a small subset of strains were resistant to amphotericin B (4.2%) and caspofungin (2.2%).


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidíase/microbiologia , Candida auris , Surtos de Doenças , China/epidemiologia , Testes de Sensibilidade Microbiana
12.
Huan Jing Ke Xue ; 45(1): 555-566, 2024 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-38216504

RESUMO

Agricultural utilization of reclaimed water is considered to be an effective way to solve water shortage and reduce water environmental pollution. Silicon fertilizer can improve crop yield and quality and enhance crop resistance. The effect of foliar spray with silicon fertilizer on phyllosphere microbial communities remains lacking. In this study, a pot experiment was conducted to explore the effects of different types of silicon fertilizer on the composition and diversity of a phyllosphere bacterial community and the abundances of related functional genes in rice irrigated with reclaimed water. The results showed that Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota, and Verrucomicrobiota dominated the phyllosphere bacteria of rice. The relative abundance of Bacillus was higher than that of other treatments in RIS3. Reclaimed water irrigation significantly increased the relative abundances of the potential pathogens Pantoea and Enterobacter. The unclassified bacteria were also an important part of the bacterial community in the rice phyllosphere. Bacillus, Exiguobacterium, Aeromonas, and Citrobacter were significantly enriched by silicon fertilizer treatments. Functional prediction analysis showed that indicator species were mainly involved in metabolism and degradation functions, and the predicted functional groups of phyllosphere bacteria were attributed to chemoheterotrophy, aerobic chemoheterotrophy, nitrate reduction, and fermentation. Quantitative PCR results showed that AOA, AOB, and nifH genes were at low abundance levels in all treatments, and nirK genes was not significantly different among treatments. These results contribute to the in-depth understanding of the effects of foliar spray silicon fertilizer on the bacterial community structure and diversity of rice phyllosphere and provide a theoretical basis for the application of silicon fertilizer in reclaimed water irrigation agriculture.


Assuntos
Bacillus , Oryza , Fertilizantes/análise , Silício/farmacologia , Solo/química , Água/análise , Bactérias/genética , Microbiologia do Solo
13.
Arthritis Care Res (Hoboken) ; 76(3): 421-425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37691268

RESUMO

OBJECTIVE: We aimed to create a question bank about clinical factors for predicting the diagnoses of psoriatic arthritis in patients with psoriasis of various ancestries and skin tones, which can be completed entirely by patients. METHODS: Utah Psoriasis Initiative participants without a psoriatic arthritis diagnosis at enrollment were observed for diagnosis during the study period. We inferred ancestry from exome sequencing data and performed Cox proportional hazards regression to identify clinical predictors of psoriatic arthritis in different ancestry groups. Based on results and literature review, we developed a question bank for assessing psoriatic arthritis risk among patients with psoriasis in various ancestries. RESULTS: Patient-reported untreated psoriasis induration and history of fingernail psoriasis were associated with psoriatic arthritis in participants of European and non-European ancestry. We developed the Psoriatic Arthritis Prediction and Identification Question Bank for Diverse Ancestries (PAPRIKA) version 1.0, which included questions regarding psoriasis characteristics, arthritis symptoms, comorbidities, family history, and demographics. PAPRIKA is accessible at http://bjfenglab.org/. CONCLUSION: The clinical features (untreated psoriasis induration and history of fingernail psoriasis) that can predict psoriatic arthritis in European individuals also work for non-European individuals. PAPRIKA can be used to gather psoriatic arthritis predictive data from patients with psoriasis without provider assistance and is relevant for patients across ancestries.


Assuntos
Artrite Psoriásica , Capsicum , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/tratamento farmacológico , Psoríase/diagnóstico , Psoríase/epidemiologia , Psoríase/tratamento farmacológico , Comorbidade
14.
Microbiol Spectr ; 11(6): e0178923, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37933972

RESUMO

IMPORTANCE: Candida albicans is a human commensal and frequent pathogen that encounters a wide range of pH stresses. The ability of C. albicans to adapt to changes in extracellular pH is crucial for its success in colonization and pathogenesis. The Rim101 pH sensing pathway is well known to govern neutral-alkaline pH responses in this pathogen. Here, we report a novel Rfg1-Bcr1 regulatory pathway that governs acidic pH responses and regulates filamentous growth in C. albicans. In addition, the Rim101-Phr1 pathway, cAMP signaling pathway, transcription factors Efg1 and Flo8, and hyphal-specific G1 cyclin Hgc1 cooperate with this regulation. Our findings provide new insights into the regulatory mechanism of acidic pH response in C. albicans.


Assuntos
Candida albicans , Fatores de Transcrição , Humanos , Candida albicans/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Transdução de Sinais , Concentração de Íons de Hidrogênio , Regulação Fúngica da Expressão Gênica , Hifas/metabolismo
15.
Int J Antimicrob Agents ; 62(6): 107010, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37863341

RESUMO

OBJECTIVES: Infections caused by azole-resistant Candida tropicalis strains are increasing in clinical settings. The reason for this epidemical change and the mechanisms of C. tropicalis azole resistance are not fully understood. METHODS: In this study, we performed biological and genomic analyses of 239 C. tropicalis strains, including 115 environmental and 124 human commensal isolates. RESULTS: Most (99.2%) of the isolates had a baseline diploid genome. The strains from both environmental and human niches exhibit similar abilities to survive under stressful conditions and produce secreted aspartic proteases. However, the human commensal isolates exhibited a stronger ability to filament than the environmental strains. We found that 19 environmental isolates (16.5%) and 24 human commensal isolates (19.4%) were resistant to fluconazole. Of the fluconazole-resistant strains, 37 isolates (86.0%) also exhibited cross-resistance to voriconazole. Whole-genome sequencing and phylogenetic analyses revealed that both environmental and commensal isolates were widely distributed in a number of genetic clusters, but the two populations exhibited a close genetic association. The majority of fluconazole-resistant isolates were clustered within a single clade (X). CONCLUSIONS: The combination of hotspot mutations (Y132F and S154F) and genomic expansion of ERG11, which encodes the azole target lanosterol 14-α-demethylase and represents a major target of azole drugs, was a major mechanism for the development of azole resistance. The isolates carrying both hotspot mutations and genomic expansion of ERG11 exhibited cross-resistance to fluconazole and voriconazole. Moreover, the azole-resistant isolates from both the environmental and human commensal niches showed similar genotypes.


Assuntos
Azóis , Candida tropicalis , Farmacorresistência Fúngica , Fluconazol , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Azóis/farmacologia , Candida tropicalis/genética , Farmacorresistência Fúngica/genética , Fluconazol/farmacologia , Proteínas Fúngicas/genética , Genômica , Testes de Sensibilidade Microbiana , Mutação , Filogenia , Voriconazol/farmacologia
16.
Emerg Infect Dis ; 29(7): 1425-1428, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347816

RESUMO

Candida vulturna belongs to the Candida haemulonii species complex and is phylogenetically related to C. auris. We report a C. vulturna outbreak among persons in Shanxi Province, China, during 2019-2022. Isolates were resistant to multiple antifungal drugs and exhibited enhanced adhesion and biofilm formation properties.


Assuntos
Candida , Candidíase , Candidíase/epidemiologia , Candidíase/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , China/epidemiologia , Testes de Sensibilidade Microbiana
17.
Front Microbiol ; 14: 1174878, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37350781

RESUMO

Introduction: Candida auris is a newly emerging pathogenic fungus of global concern and has been defined by the World Health Organization (WHO) as a member of the critical group of the most health-threatening fungi. Methods: This study reveals and reports for the first time that a rough morphotype C. auris strain causes urinary tract infections in non-intensive care unit (ICU) inpatients. Furthermore, the morphology, the scanning electronmicroscopy (SEM), Whole-genome resequencing and RNA sequencing of C. auris possessing rough morphotype colonies compared to their smooth morphotype counterparts. Results: The newly identified phenotypic variation of C. auris appears round, convex, dry, and burr-like with a rough texture. SEM shows that rough type C. auris has a rough and uneven colony surface with radial wrinkles and irregular spore arrangement. Cells of the rough morphotype C. auris naturally aggregate into clusters with tight connections in the liquid, and it seems that the cell division is incomplete. A genome-wide analysis of the rough type C. auris confirmed its genetic association with the smooth type of C. auris prevalent in China (Shenyang) two years ago; however, single nucleotide polymorphism (SNP) mutations of five genes (ACE2, IFF6, RER2, UTP20, and CaO19.5847) were identified more recently. RNA-seq revealed IFF2/HYR3, DAL5, PSA31, and SIT1 were notably up-regulated, while multiple cell wall-associated genes (ALS1, MNN1, PUL1, DSE1, SCW11, PGA38, RBE1, FGR41, BGLI, GIT3, CEP3, and SAP2) were consistently down-regulated in rough morphotype C. auris. Discussion: The rough phenotypic variation of C. auris is likely to be related to the structural and functional changes in cell wall proteins. This novel rough morphotype C. auris will provide a basis for further studies concerning the evolutionary characteristics of C. auris.

18.
ACS Appl Mater Interfaces ; 15(22): 26650-26659, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37226049

RESUMO

The rational design of advanced catalysts for sodium-sulfur (Na-S) batteries is important but remains challenging due to the limited understanding of sulfur catalytic mechanisms. Here, we propose an efficient sulfur host consisting of atomic low-coordinated Zn-N2 sites dispersed on N-rich microporous graphene (Zn-N2@NG), which realizes state-of-the-art sodium-storage performance with a high sulfur content of 66 wt %, high-rate capability (467 mA h g-1 at 5 A g-1), and long cycling stability for 6500 cycles with an ultralow capacity decay rate of 0.0062% per cycle. Ex situ methods combined with theoretical calculations demonstrate the superior bidirectional catalysis of Zn-N2 sites on sulfur conversion (S8 ↔ Na2S). Furthermore, in situ transmission electron microscopy was applied to visualize the microscopic S redox evolution under the catalysis of Zn-N2 sites without liquid electrolytes. During the sodiation process, both surface S nanoparticles and S molecules in the mircopores of Zn-N2@NG quickly convert into Na2S nanograins. During the following desodiation process, only a small part of the above Na2S can be oxidized into Na2Sx. These results reveal that, without liquid electrolytes, Na2S is difficult to be decomposed even with the assistance of Zn-N2 sites. This conclusion emphasizes the critical role of liquid electrolytes in the catalytic oxidation of Na2S, which was usually ignored by previous works.

19.
Toxicol Res (Camb) ; 12(2): 282-295, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125334

RESUMO

Background: Although many studies have shown that herbs containing aristolochic acids can treat various human diseases, AAΙ in particular has been implicated as a nephrotoxic agent. Methods and results: Here, we detail the nephrotoxic effect of AAΙ via an approach that integrated 1H NMR-based metabonomics and network pharmacology. Our findings revealed renal injury in mice after the administration of AAΙ. Metabolomic data confirmed significant differences among the renal metabolic profiles of control and model groups, with significant reductions in 12 differential metabolites relevant to 23 metabolic pathways. Among them, there were seven important metabolic pathways: arginine and proline metabolism; glycine, serine, and threonine metabolism; taurine and hypotaurine metabolism; ascorbate and aldehyde glycolate metabolism; pentose and glucosinolate interconversion; alanine, aspartate, and glutamate metabolism; and glyoxylate and dicarboxylic acid metabolism. Relevant genes, namely, nitric oxide synthase 1 (NOS1), pyrroline-5-carboxylate reductase 1 (PYCR1), nitric oxide synthase 3 (NOS3) and glutamic oxaloacetic transaminase 2 (GOT2), were highlighted via network pharmacology and molecular docking techniques. Quantitative real-time PCR findings revealed that AAI administration significantly downregulated GOT2 and NOS3 and significantly upregulated NOS1 and PYCR1 expression and thus influenced the metabolism of arginine and proline. Conclusion: This work provides a meaningful insight for the mechanism of AAΙ renal injury.

20.
Sci China Life Sci ; 66(8): 1915-1929, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37118508

RESUMO

Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity. Environmental factors often have a direct impact on the occurrence and frequency of sexual reproduction in fungi. The regulatory effects of atmospheric relative humidity (RH) on sexual reproduction and pathogenesis in plant fungal pathogens and in soil fungi have been extensively investigated. However, the knowledge of how RH regulates the lifecycles of human fungal pathogens is limited. In this study, we report that low atmospheric RH promotes the development of mating projections and same-sex (homothallic) mating in the human fungal pathogen Candida albicans. Low RH causes water loss in C. albicans cells, which results in osmotic stress and the generation of intracellular reactive oxygen species (ROS) and trehalose. The water transporting aquaporin Aqy1, and the G-protein coupled receptor Gpr1 function as cell surface sensors of changes in atmospheric humidity. Perturbation of the trehalose metabolic pathway by inactivating trehalose synthase or trehalase promotes same-sex mating in C. albicans by increasing osmotic or ROS stresses, respectively. Intracellular trehalose and ROS signal the Hog1-osmotic and Hsf1-Hsp90 signaling pathways to regulate the mating response. We, therefore, propose that the cell surface sensors Aqy1 and Gpr1, intracellular trehalose and ROS, and the Hog1-osmotic and Hsf1-Hsp90 signaling pathways function coordinately to regulate sexual mating in response to low atmospheric RH conditions in C. albicans.


Assuntos
Candida albicans , Proteínas Fúngicas , Humanos , Candida albicans/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Trealose/metabolismo , Umidade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Reprodução/fisiologia
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