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1.
Luminescence ; 39(9): e4908, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39315636

RESUMO

A novel coumarin-naphthalimide-based ratiometric fluorescent probe, called XPT, was synthesized with the aim of achieving high sensitivity and anti-interference for N2H4 detection. The probe XPT consists of coumarin species and naphthalimide species, which act as the energy donor and acceptor, respectively. The phthalimide group functions as the recognition unit for N2H4. Without the presence of hydrazine, the naphthalimide remains in a non-fluorogenic phthalimide mode, disrupting the FRET signal. However, the phthalimide group undergoes the Gabriel reaction to an amine, which induces FRET and consequently causes a shift in the emitted fluorescence from 468 to 528 nm when N2H4 was added. The results of the study demonstrated that XPT exhibits high sensitivity with a limit of detection 2.2 µM, as well as selectivity. Furthermore, it is remarkable that the distribution of N2H4 in real water samples can be monitored by XPT.


Assuntos
Cumarínicos , Corantes Fluorescentes , Hidrazinas , Naftalimidas , Hidrazinas/análise , Hidrazinas/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Naftalimidas/química , Cumarínicos/química , Cumarínicos/síntese química , Poluentes Químicos da Água/análise , Estrutura Molecular , Água/química , Espectrometria de Fluorescência , Transferência Ressonante de Energia de Fluorescência
2.
Artigo em Inglês | MEDLINE | ID: mdl-39306766

RESUMO

Ternary metal carbide TiAlC has been proposed as a metal gate material in logic semiconductor devices. It is a hard-to-etch material due to the low volatility of the etch byproducts. Here, a simple, highly controllable, and dry etching method for TiAlC has been first presented using nonhalogen N2/H2 plasmas at low pressure (several Pa) and 20 °C. A capacitively coupled plasma etcher was used to generate N2/H2 plasmas containing active species, such as N, NH, and H to modify the metal carbide surface. The etch rate of TiAlC was obtained at 3 nm/min by using the N2/H2 plasma, whereas no etching occurred with pure N2 plasma or pure H2 plasma under the same conditions. The surface roughness of the TiAlC film etched by N2/H2 plasma was controlled at the atomic level. A smooth etched surface was achieved with a root-mean-square roughness of 0.40 nm, comparable to the initial roughness of 0.44 nm. The plasma properties of the N2/H2 plasmas were diagnosed by using a high-resolution optical emission spectrometer, detecting the NH molecular line at 336 nm. The etching behavior and plasma-surface reaction between N2/H2 plasma and TiAlC were investigated by using in situ spectroscopic ellipsometry, in situ attenuated total reflectance-Fourier transform infrared spectrometry, and X-ray photoelectron spectroscopy. The findings indicate that the N-H, C-N, and Ti(Al)-N bonds form on the TiAlC surface etched by the N2/H2 plasmas. The mechanism for etching of TiAlC involving transformation reactions between inorganic materials (metal carbides) and inorganic etchants (N2/H2 plasma) to form volatile organic compounds such as methylated, methyl-aminated, and aminated metals is proposed. Nonhalogen or nonorganic compound etchants were used during the etching process. The study provides useful insights into microfabrication for large-scale integrated circuits.

3.
Structure ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39317198

RESUMO

AlphaFold can accurately predict static protein structures but does not account for solvent conditions. Human leucine zipper EF-hand transmembrane protein-1 (LETM1) has one sequence-identifiable EF-hand but how calcium (Ca2+) affects structure and function remains enigmatic. Here, we used highly confident AlphaFold Cα predictions to guide nuclear Overhauser effect (NOE) assignments and structure calculation of the LETM1 EF-hand in the presence of Ca2+. The resultant NMR structure exposes pairing between a partial loop-helix and full helix-loop-helix, forming an unprecedented F-EF-hand with non-canonical Ca2+ coordination but enhanced hydrophobicity for protein interactions compared to calmodulin. The structure also reveals the basis for pH sensing at the link between canonical and partial EF-hands. Functionally, mutations that augmented or weakened Ca2+ binding increased or decreased matrix Ca2+, respectively, establishing F-EF as a two-way mitochondrial Ca2+ regulator. Thus, we show how to synergize AI prediction with NMR data, elucidating a solution-specific and extraordinary LETM1 F-EF-hand.

4.
J Mol Model ; 30(10): 339, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287820

RESUMO

CONTEXT: Ammonium Tutton salts have been widely studied in recent years due to their thermostructural properties, which make them promising compounds for application in thermochemical energy storage devices. In this work, a detailed experimental study of the Tutton salt with the formula (NH4)2Zn(SO4)2(H2O)6 is carried out. Its structural, vibrational, and thermal properties are analyzed and discussed. Powder X-ray diffraction (PXRD) studies confirm that the compound crystallizes in a structure of a Tutton salt, with monoclinic symmetry and P21/a space group. The Hirshfeld surface analysis results indicate that the main contacts stabilizing the material crystal lattice are H···O/O···H, H···H, and O···O. In addition, a typical behavior of an insulating material is confirmed based on the electronic bandgap calculated from the band structure and experimental absorption coefficient. The Raman and infrared spectra calculated using DFT are in a good agreement with the respective experimental spectroscopic results. Thermal analysis in the range from 300 to 773 K reveals one exothermic and several endothermic events that are investigated using PXRD measurements as a function of temperature. With increasing temperature, two new structural phases are identified, one of which is resolved using the Le Bail method. Our findings suggest that the salt (NH4)2Zn(SO4)2(H2O)6 is a promising thermochemical material suitable for the development of heat storage systems, due to its low dehydration temperature (≈ 330 K), high enthalpy of dehydration (122.43 kJ/mol of H2O), and hydration after 24 h. METHODS: Computational studies using Hirshfeld surfaces and void analysis are conducted to identify and quantify the intermolecular contacts occurring in the crystal structure. Furthermore, geometry optimization calculations are performed based on density functional theory (DFT) using the PBE functional and norm-conserving pseudopotentials implemented in the Cambridge Serial Total Energy Package (CASTEP). The primitive unit cell optimization was conducted using the Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithm. The electronic properties of band structure and density of states, and vibrational modes of the optimized crystal lattice are calculated and analyzed.

5.
Mol Cell ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39303720

RESUMO

Cys2-His2 zinc-finger proteins (C2H2-ZNFs) constitute the largest class of DNA-binding transcription factors (TFs) yet remain largely uncharacterized. Although certain family members, e.g., GTF3A, have been shown to bind both DNA and RNA, the extent to which C2H2-ZNFs interact with-and regulate-RNA-associated processes is not known. Using UV crosslinking and immunoprecipitation (CLIP), we observe that 148 of 150 analyzed C2H2-ZNFs bind directly to RNA in human cells. By integrating CLIP sequencing (CLIP-seq) RNA-binding maps for 50 of these C2H2-ZNFs with data from chromatin immunoprecipitation sequencing (ChIP-seq), protein-protein interaction assays, and transcriptome profiling experiments, we observe that the RNA-binding profiles of C2H2-ZNFs are generally distinct from their DNA-binding preferences and that they regulate a variety of post-transcriptional processes, including pre-mRNA splicing, cleavage and polyadenylation, and m6A modification of mRNA. Our results thus define a substantially expanded repertoire of C2H2-ZNFs that bind RNA and provide an important resource for elucidating post-transcriptional regulatory programs.

6.
Antiviral Res ; 231: 106006, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293594

RESUMO

Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 are effective against COVID-19 and might mitigate future pandemics. However, their efficacy is challenged by the emergence of antibody-resistant virus variants. We developed a method to efficiently identify such resistant mutants based on selection from mutagenized virus pools. By inducing mutations with the active compound of Molnupiravir, N4-hydroxycytidine (NHC), and subsequently passaging the virus in the presence of antibodies, we identified specific Spike mutations linked to resistance. Validation of these mutations was conducted using pseudotypes and immunofluorescence analysis. From a Wuhan-like strain of SARS-CoV-2, we identified the following mutations conferring strong resistance towards the corresponding antibodies: Bamlanivimab - E484K, F490S and S494P; Sotrovimab - E340K; Cilgavimab - K444R/E and N450D. From the Omicron B.1.1.529 variant, the strongly selected mutations were: Bebtelovimab - V445A; Sotrovimab - E340K and K356M; Cilgavimab - K444R, V445A and N450D. We also identified escape mutations in the Wuhan-like Spike for the broadly neutralizing antibodies S2K146 - combined G485S and Q493R - and S2H97 - D428G, K462E and S514F. Structural analysis revealed that the selected mutations occurred at antibody-binding residues within the receptor-binding domains of the Spike protein. Most of the selected mutants largely maintained ACE2 binding and infectivity. Notably, many of the identified resistance-conferring mutations are prevalent in real-world SARS-CoV-2 variants, but some of them (G485S, D428G, and K462E) have not yet been observed in circulating strains. Our approach offers a strategy for predicting the therapeutic efficacy of antibodies against emerging virus variants.

7.
J Colloid Interface Sci ; 678(Pt C): 506-514, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39305618

RESUMO

Electrocatalytic CO2 reduction reaction (CO2RR) is a process in which CO2 is reduced to high-value-added C1 and C2 energy sources, particularly ethylene (C2H4), thereby supporting carbon-neutral recycling with minimal consumption. This makes it a promising technology with significant potential. Nevertheless, the low selectivity for C2H4 remains a significant challenge in practical applications. In this paper, a strategy based on Cu-Sn bimetallic catalysts is proposed to improve the selectivity of electrocatalytic conversion of CO2 to C2H4 over Cu-based catalysts. The experimental results show that the Faradaic efficiency (FE) of C2H4 can reach up to 48.74 %, and the FE of C2 product reaches 60 %, at which time the local current density is 11.99 mA/cm2. Compared with pure Cu catalyst, the FE and local current density of C2H4 increased by 55.27 % and 35.33 %, respectively. Moreover, the FE of C2H4 remained above 40 % after 8 h over Cu10-Sn catalyst. The addition of Sn facilitates the transfer of local electrons from Cu to Sn, stabilizes the *CO intermediate, promotes CC coupling, significantly lowers the reaction energy barrier, and enables highly efficient CO2RR catalysis for C2H4 production.

8.
Plant Mol Biol ; 114(5): 103, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316185

RESUMO

Members of the glycosyltransferase 8 (GT8) family play an important role in regulating gene expression in response to many kinds of biotic and abiotic stress. In this study, 56 members of the apple GT8 family were identified, and their gene structure, phylogenetic relationships, chromosomal localization, and promoter cis-acting elements were comprehensively analyzed. Subsequently, 20 genes were randomly selected from the evolutionary tree for qRT-PCR detection, and it was found that MhGolS2 was significantly overexpressed under stress conditions. MhGolS2 was isolated from M.halliana and transgenic Arabidopsis thaliana, tobacco and apple callus tissues were successfully obtained. The transgenic plants grew better under stress conditions with higher polysaccharide, chlorophyll and proline content, lower conductivity and MDA content, significant increase in antioxidant enzyme activities (SOD, POD, CAT) and maintenance of low Na+/K+ as compared to the wild type. Meanwhile, the expression levels of reactive oxygen species-related genes (AtSOD, AtPOD, and AtCAT), Na+ transporter genes (AtCAX5, AtSOS1, and AtHKT1), H+-ATPase genes (AtAHA2 and AtAHA8), and raffinose synthesis-related genes (AtSTS, AtRFS1, and AtMIPS) were significantly up-regulated, while the expression levels of K+ transporter genes (AtSKOR, AtHAK5) were reduced. Finally, the Y2H experiment confirmed the interaction between MhGolS2 and MhbZIP23, MhMYB1R1, MhbHLH60, and MhNAC1 proteins. The above results indicate that MhGolS2 can improve plant saline-alkali tolerance by promoting polysaccharide synthesis, scavenging reactive oxygen species, and increasing the activity of antioxidant enzymes. This provides excellent stress resistance genes for the stress response regulatory network in apple.


Assuntos
Regulação da Expressão Gênica de Plantas , Malus , Filogenia , Proteínas de Plantas , Plantas Geneticamente Modificadas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Família Multigênica , Arabidopsis/genética , Estresse Fisiológico/genética , Tolerância ao Sal/genética , Álcalis , Nicotiana/genética , Nicotiana/metabolismo , Genoma de Planta
9.
J Neurogenet ; : 1-10, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39321203

RESUMO

SMA (spinal muscular atrophy) is an autosomal recessive neuromuscular disease that causes muscle atrophy and weakness. SMA is diagnosed by a homozygous deletion in exon 7 of the SMN1 gene. However, mutations in genes located in the SMA region, such as SMN2, NAIP, SERF1, and GTF2H2, may also contribute to the severity of the disease. Within our study's scope, 58 SMA patients who applied in 2018-2021 and 40 healthy controls were analyzed. The study retrospectively included the SMN1 and SMN2 copy numbers previously determined by the MLPA method. Then, NAIP gene analyses with the multiplex PCR method and GTF2H2 gene analyses with the RFLP method were performed. There was a significant correlation (p = 0.00001) between SMN2 copy numbers and SMA subtypes. Also, the NAIP gene (p = 0.01) and the GTF2H2 gene (p = 0.0049) revealed a significant difference between healthy and SMA subjects, whereas the SMA subtypes indicated no significant differences. We detected a significant correlation between clinical subtypes and HFMSE scores in 32 pediatric SMA patients compared (p = 0.01). While pediatric patients with GTF2H2 deletions demonstrated higher motor functions, and those with NAIP deletions demonstrated lower motor functions. In this study, we examined the relationship between NAIP and GTF2H2, called SMN region modifier genes, and the clinical severity of the disease in Turkish SMA patients. Despite its small scale, this research will benefit future investigations into the pathogenesis of SMA disease.

10.
Food Chem X ; 23: 101722, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39229615

RESUMO

This study examined the impact of varying salt concentrations on microbiota, physicochemical properties, and metabolites in a secondary fortified fermentation process using multi-omics techniques. It aimed to determine the influence of salt stress on microbiota shifts and metabolic activities. The findings demonstrated that moderate salt reduction (MS) was found to enhance moromi's flavor and quality, while mitigating the negative effects of excessive low salt (LS). MS samples had 1.22, 1.13, and 2.92 times more amino acid nitrogen (AAN), non-volatiles, and volatiles, respectively, than high salt (HS) samples. In contrast, lactic acid and biogenic amines in LS samples were 1.56 g/100 g and 4115.11 mg/kg, respectively, decreasing to 0.15 g/100 g and 176.76 mg/kg in MS samples. Additionally, the contents of ethanol and small peptides increased in MS due to the growth of specific functional microorganisms such as Staphylococcus gallinarum, Weissella confusa, and Zygosaccharomyces rouxii, while food-borne pathogens were inhibited. Network analysis revealed that the core microbial interactions were enhanced in MS samples, promoting a balanced fermentation environment. Redundancy analysis (RDA) and correlation analyses underscored that the physicochemical properties significantly impacted bacterial community structure and the correlations between key microbes and flavor compounds. These findings provided a theoretical foundation for developing innovative reduced-salt fermentation techniques, contributing to the sustainable production of high-quality soy sauce.

11.
R Soc Open Sci ; 11(9): 230975, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39263456

RESUMO

Recent work on the diazonium ion metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKDI) suggests that 5-(pyridin-3-yl)-3,4-dihydro-2H-furan-1-ium (NNKFI) may form from NNKDI via an intramolecular reaction. NNKDI is an important carcinogen whose role as an alkylating agent has received significant attention. While there is some experimental evidence supporting NNKFI's production in vitro, it has not yet been directly observed. Little is known about NNKFI's structure and reactivity. We report the first in silico examination of this ion. Our study utilized Kohn-Sham density functional theory (B3LYP/6-311G**) and coupled cluster theory (CCSD/6-31G*) to produce energy-optimized structures, vibrational normal modes and molecular orbitals for NNKFI. To gain insight into the chemical properties of this species, we calculated electrostatic potential surfaces, natural population analysis charges and local Fukui indices. We report data and results for NNKFI's cis and trans conformers. Our work confirms C5 as the preferred site for nucleophilic attack in NNKFI. Stretching motions and predicted bond lengths near O1 are consistent with a somewhat weakened carbonyl structure in this ion. Partial charges, electrostatic potential surfaces and local Fukui indices reveal delocalization of cationic charge on the furanium moiety and notable carbocation character at C5.

12.
Mol Phylogenet Evol ; 201: 108195, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260627

RESUMO

Members of the plant specific family of C1-1i zincfinger transcriptionfactors (ZF-TFs), such as SUPERMAN, JAGGED, KNUCKLES or GIS,regulatediversedevelopmental processes including sexual reproduction. C1-1is consist of one zinc-finger and one to two EAR domains, connected by large intrinsically disordered regions (IDR). While the role of C1-i1 ZF-TFs in development processes is well known for some genes in Arabidopsis, rice or tomatoa comprehensive and broadphylogenetic background is lacking, yet knowledge of orthology is a requirement for a better understanding of C1-1i-Zf-TFs diverse roles in plants. Here, we provide a fine-grained and land plant wide classification of C1-1i sub-families and their known co-repressors TOPLESS and TOPLESS RELATED. Our work combines the identification of orthologous groups with Maximum-Likelihood phylogeny reconstructions and digital gene expression analyses mining high quality land plant genomes and transcriptomes to generate a comprehensive framework of C1-1i ZF-TF evolution. We show that C1-1i's are low to moderate copy genesand that orthologous genesonly partiallyhaveconserved sub-family and life cycle stage dependent expression pattern across land plants while others are highly diverged. Our workprovides the phylogenetic framework for C1-1i ZF-TFs, s and strengthen C1-1 ZF-TFs as a potential model for IDR-research in plants.

13.
Front Oncol ; 14: 1448890, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246323

RESUMO

Background: Rapidly developed chemoresistance to dacarbazine (DTIC) is a major obstacle in the clinical management of melanoma; however, the roles and mechanisms of epi-transcriptomic RNA modification in this process have not been investigated. Method: DTIC-resistant (DR) melanoma cells were established for bulk RNA sequencing. The expressions of mRNAs were detected using qRT-PCR, and protein levels were determined using Western blotting and immunohistochemistry. Acetylated RNAs were detected by dot blotting and immunoprecipitation sequencing (acRIP-seq). A lung metastasis mouse model of melanoma was established to evaluate the anti-melanoma effects in vivo. Results: We identified that the expression of N-acetyltransferase 10 (NAT10), a catalytic enzyme for the N 4-acetylcytidine (ac4C) modification of RNA, was significantly upregulated in the DR cells. Clinically, NAT10 expression was elevated in disease progression samples and predicted a poor outcome. Using ac4C RNA immunoprecipitation (ac4C-RIP), we found that the mRNAs of two C2H2 zinc finger transcriptional factors, DDX41 and ZNF746, were targets of NAT10-mediated ac4C modification. Gain- and loss-of-function experiments in NAT10, or in DDX41 and ZNF746, altered the chemosensitivity of melanoma accordingly, and the two target genes also negatively correlated with clinical outcomes. Finally, pharmacological inhibition of NAT10 with Remodelin sensitized melanoma cells to DTIC treatment in vitro and in a mouse xenograft model. Conclusion: Our study elucidates the previously unrecognized role of NAT10-mediated ac4C modification in the chemoresistance of melanoma and provides a rationale for developing new strategies to overcome chemoresistance in melanoma patients.

14.
Future Med Chem ; 16(16): 1685-1703, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39105606

RESUMO

Cardiovascular diseases (CVDs) and cancer are the top two leading causes of death globally. Vasodilators are commonly used to treat various CVDs. In cancer treatment, targeted anticancer agents have been developed to minimize side effects compared with traditional chemotherapy. Many hypertension patients are more prone to cancer, a case known as reverse cardio-oncology. This leads to the search for drugs with dual activity or repurposing strategy to discover new therapeutic uses for known drugs. Recently, medicinal chemists have shown great interest in synthesizing pyridazinone derivatives due to their significant biological activities in tackling these critical health challenges. This review will concentrate on pyridazin-3(2H)-one-containing compounds as vasodilators and anticancer agents, along with a brief overview of various methods for their synthesis.


[Box: see text].


Assuntos
Antineoplásicos , Doenças Cardiovasculares , Neoplasias , Piridazinas , Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Doenças Cardiovasculares/tratamento farmacológico , Piridazinas/química , Piridazinas/farmacologia , Piridazinas/uso terapêutico , Vasodilatadores/farmacologia , Vasodilatadores/química , Vasodilatadores/uso terapêutico , Animais , Estrutura Molecular
15.
Dokl Biol Sci ; 518(1): 133-136, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128960

RESUMO

The transcription factor Z4 (putzig) is one of the key proteins that determine the chromatin structure in Drosophila. Z4 is found at the boundaries of bands on polytene chromosomes, and the bands are currently thought to correlate with chromatin domains. Z4 is a component of a protein complex that additionally includes Chromator and BEAF-32, and a conserved domain is necessary to occur at the N end of Z4 to ensure its interaction with the two proteins. In this study, a zinc finger-associated domain (ZAD) domain was identified in Z4. The capability of dimerization was confirmed for the domain by biochemical methods. A dimer model of the domain was obtained using AlphaFold2, and the model structure was confirmed using small-angle X-ray scattering (SAXS). The dimer structure shows a fold typical of ZAD domains.


Assuntos
Proteínas de Drosophila , Multimerização Proteica , Fatores de Transcrição , Animais , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Domínios Proteicos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo
16.
Cells ; 13(16)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39195277

RESUMO

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling mechanisms in mast and basophil cells. This systematic review aims to study common signaling pathways of the anti-allergic or anti-inflammatory compounds on RBL-2H3 cells. We selected the relevant research articles published after 2015 from the PubMed, Scopus, Science Direct and Web of Science databases. The risk of bias of the studies was assessed based on the modified CONSORT checklist for in vitro studies. The cell lines, treatments, assay, primary findings, and signaling pathways on RBL-2H3 cells were extracted to synthesize the results. Thirty-eight articles were included, and FCεRI and its downstream pathways, such as Lyn, Sky, PLCγ, and MAPK, were commonly studied. Moreover, the JAK/STAT pathway was a potential signaling mechanism in RBL-2H3 cells. However, the findings based on RBL-2H3 cells needed to be tested along with human mast cells to confirm its relevance to human health. In conclusion, a single plant extract may act as an anti-inflammatory reagent in RBL-2H3 cells via multiple signaling pathways besides the MAPK signaling pathway.


Assuntos
Antialérgicos , Anti-Inflamatórios , Transdução de Sinais , Animais , Ratos , Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Linhagem Celular , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Mastócitos/imunologia , Receptores de IgE/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
17.
mSphere ; 9(9): e0040924, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39189776

RESUMO

Verticillium dahliae causes Verticillium wilt in more than 200 plant species worldwide. As a soilborne fungus, it forms melanized microsclerotia and colonizes the xylem of host plants. Our previous study revealed a subfamily of C2H2-homeobox transcription factors in V. dahliae, but their biological roles remain unknown. In this study, we systematically characterized the functions of seven C2H2-homeobox transcription factors in V. dahliae. Deletion of VdChtf3 and VdChtf6 significantly decreased the production of melanized microsclerotia, and knockout of VdChtf1 and VdChtf4 enhanced virulence. Loss of VdChtf2 and VdChtf6 increased conidium production, whereas loss of VdChtf5 and VdChtf7 did not affect growth, conidiation, microsclerotial formation, or virulence. Further research showed that VdChtf3 activated the expression of genes encoding pectic enzymes to participate in microsclerotial formation. In addition, VdChtf4 reduced the expression of VdSOD1 to disturb the scavenging of superoxide radicals but induced the expression of genes related to cell wall synthesis to maintain cell wall integrity. These findings highlight the diverse roles of different members of the C2H2-homeobox gene family in V. dahliae. IMPORTANCE: Verticillium dahliae is a soilborne fungus that causes plant wilt and can infect a variety of economic crops and woody trees. The molecular basis of microsclerotial formation and infection by this fungus remains to be further studied. In this study, we analyzed the functions of seven C2H2-homobox transcription factors. Notably, VdChtf3 and VdChtf4 exhibited the most severe defects, affecting phenotypes associated with critical developmental stages in the V. dahliae disease cycle. Our results indicate that VdChtf3 is a potential specific regulator of microsclerotial formation, modulating the expression of pectinase-encoding genes. This finding could contribute to a better understanding of microsclerotial development in V. dahliae. Moreover, VdChtf4 was associated with cell wall integrity, reactive oxygen species (ROS) stress resistance, and increased virulence. These discoveries shed light on the biological significance of C2H2-homeobox transcription factors in V. dahliae's adaptation to the environment and infection of host plants.


Assuntos
Ascomicetos , Proteínas Fúngicas , Regulação Fúngica da Expressão Gênica , Doenças das Plantas , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ascomicetos/genética , Ascomicetos/patogenicidade , Ascomicetos/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Virulência , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Verticillium/genética , Verticillium/patogenicidade
18.
Z Rheumatol ; 2024 Aug 14.
Artigo em Alemão | MEDLINE | ID: mdl-39143256

RESUMO

Given the ever-increasing number of approved therapies for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA), head-to-head (H2H) comparative studies are essential. These are aimed primarily at a comparative analysis of treatment effectiveness. In both PsO and PsA, biological disease-modifying antirheumatic drugs (bDMARD) have been shown to be superior to conventional therapies in H2H studies. In PsO interleukin 17 (IL-17) and IL-23 inhibitors proved superiority compared to tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) in several studies. Ustekinumab was more effective than etanercept, but less effective than IL-17 and IL-23 inhibitors. Only a few H2H studies have been published on the treatment of PsA. In the Spirit H2H study ixekizumab was superior to adalimumab using a combined endpoint of arthritis and psoriasis response (ACR-50 and PASI-100). When looking at arthritic symptoms only (ACR-20), secukinumab was not significantly superior to adalimumab in the EXCEED study but was superior in terms of the effect on skin involvement (PASI90). Other H2H studies focused on the treatment of enthesitis (ECLIPSA study), the efficacy of Janus kinase (JAK) inhibition (SELECT-PSA-1) or the additional administration of methotrexate to bDMARD treatment (MUST study). The H2H data have been incorporated into the treatment guidelines and have led to IL-17 and IL-23 inhibition being preferred over TNF inhibition in cases of relevant skin involvement in PsA.

19.
ACS Appl Mater Interfaces ; 16(33): 44077-44093, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39120144

RESUMO

Wood, as a natural biomass material, has long been a research focus. Superhydrophobic modified wood, in particular, has shown great promise in a myriad of engineering applications such as architecture, landscape, and shipbuilding. However, commercial development has encountered significant resistance due to preparation difficulties and sometimes unsatisfactory performance. In this study, hydrophobic/superhydrophobic wood comodified with methyltrimethoxysilane (MTMS) and 1H,1H,2H,2H-perfluorodecyltrimethoxysilane (PFDTMS) was fabricated by a one-step sol-gel method that uses an in situ growth process. Low-molecular-weight MTMS was allowed to permeate the three-dimensional porous wood interior. Then, acid-base catalysts were used to regulate the hydrolytic condensation process of MTMS and PFDTMS composite silanes to generate micro/nano hierarchical structures with low surface energy on the wood surface. The physicochemical characteristics of modified wood were investigated and the reaction mechanism established. The modified wood displayed excellent internal hydrophobicity/surface superhydrophobicity, water-moisture resistance, and dimensional stability at low fluorine concentrations. The resulting superhydrophobic surface provided stain resistance, self-cleaning ability, and loading capacity in water while exhibiting good mechanochemical stability; wood mechanical strength was also enhanced. This methodology created a superhydrophobic surface and bulk hydrophobization of wood in one step. Beyond wood, this approach is expected to provide a promising approach for functional modification of other porous composite materials.

20.
Small ; : e2402382, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39118549

RESUMO

Developing high-performance porous materials to separate ethane from ethylene is an important but challenging task in the chemical industry, given their similar sizes and physicochemical properties. Herein, a new type of ultra-strong C2H6 nano-trap, CuIn(3-ain)4 is presented, which utilizes multiple guest-host interactions to efficiently capture C2H6 molecules and separate mixtures of C2H6 and C2H4. The ultra-strong C2H6 nano-trap exhibits the high C2H6 (2.38 mmol g-1) uptake at 6.25 kPa and 298 K and demonstrates a remarkable selectivity of 3.42 for C2H6/C2H4 (10:90). Additionally, equimolar C2H6/C2H4 exhibited a superior high separation potential ∆Q (2286 mmol L-1) at 298 K. Kinetic adsorption tests demonstrated that CuIn(3-ain)4 has a high adsorption rate for C2H6, establishing it as a new benchmark material for the capture of C2H6 and the separation of C2H6/C2H4. Notably, this exceptional performance is maintained even at a higher temperature of 333 K, a phenomenon not observed before. Theoretical simulations and single-crystal X-ray diffraction provide critical insights into how selective adsorption properties can be tuned by manipulating pore dimensions and geometry. The excellent separation performance of CuIn(3-ain)4 has been confirmed through breakthrough experiments for C2H6/C2H4 gas mixtures.

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