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1.
Int Immunopharmacol ; 142(Pt B): 113198, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39305891

RESUMO

Autoimmune hepatitis (AIH), an immune-mediated liver injury, plays an important role in the development and pathogenesis of several liver diseases. However, therapeutic alternatives for the treatment of AIH remain limited. Zingerone (ZIN) is a natural non-toxic phenolic compound extracted from ginger that possesses various pharmacological activities. Thus, this study aimed to investigate the effect of ZIN on AIH using a mouse model of acute liver injury induced by concanavalin A (Con A). To establish liver injury, C57BL/6J mice were intraperitoneally administered ZIN, followed by 20 mg/kg Con A after 3 h. Thereafter, the liver and serum were collected for analysis. The results revealed that ZIN pretreatment significantly suppressed the elevation of liver injury markers induced by Con A exposure and improved the survival of mice. Additionally, ZIN significantly ameliorated liver histopathological injury, hepatocyte apoptosis, and oxidative stress. Notably, ZIN inhibited hepatic M1 macrophage polarization and decreased the expression of M1 macrophage-associated pro-inflammatory genes and cytokines, including interleukin-1ß (IL-1ß), IL-12, IL-6, and tumor necrosis factor-α (TNF-α). Western blotting analysis indicated that ZIN inhibited the phosphorylation of extracellular receptor kin, c-Jun N-terminal kinase, and p65 in vitro. Taken together, these results suggest that ZIN exerts a protective effect in the Con A-induced acute liver injury model by inhibiting M1 macrophage polarization and suppressing NF-κB, mitogen-activated protein kinase, and interferon regulatory factor signaling pathways. This highlights the possibility of using ZIN as a safe drug for the treatment of liver injury and provides a novel therapeutic direction for clinical studies on liver diseases.

2.
Comput Struct Biotechnol J ; 23: 3232-3240, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39257526

RESUMO

Tylosin is an important macrolide antibiotic produced by Streptomyces fradiae. In the biosynthesis of tylosin, macrocin O-methyltransferase TylF catalyzes the conversion of the side-product tylosin C (macrocin) to the primary component tylosin A (C/A conversion). This conversion is the rate-limiting step in the biosynthesis of tylosin, and affects the quality of the end product. To find a high activity and environment-adapted TylF enzyme, a TylF variant pool has been constructed via protein evolution approach in our previous study (Fan et al., 2023 [41]). In this study, the TylF variants with higher C/A conversion rates were expressed in E. coli and purified. The variants TylFY139F, TylFQ138H, F232Y and TylFT36S, V54A were shown to have a higher C/A conversion rate at 30 °C than that of TylF at 38 °C. Moreover, they had a greater acid resistance and showed more adaptable to the pH change during fermentation. Further protein structural and substrate-binding affinity analyses revealed that the T36S, V54A, Q138H, Y139F, and F232Y mutations enlarged the volume of the substrate-binding pocket, thereby increasing the affinity of enzyme variants for their substrates of SAM and macrocin, and decreasing the inhibition of SAH. Three of the TylF variants were overexpressed in the industrial tylosin-producing S. fradiae strain, and the recombinant strains showed the highest C/A conversion at 30 °C without heating up to 38 °C during the last 24 h of fermentation. This is of great energy-saving significance for tylosin industrial production.

3.
Int Immunopharmacol ; 142(Pt B): 113136, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39293316

RESUMO

Hyper-activations of monocytes/macrophages and dendritic cells (DCs) contribute to the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus (SLE). Fatty acid synthase (FASN) is essential for the de novo synthesis of long-chain fatty acids, which play a key role in controlling the activation, differentiation, and function of immune cells. However, the role of FASN in regulating the activations of monocytes/macrophages and DCs has not been studied. In this study, we investigated the involvement of the FASN in modulating the activations of macrophages and DCs, as well as the pathogenesis of SLE. Importantly, we observed a significant upregulation of FASN expression in monocytes and DCs from patients with SLE. This increase is strongly correlated with disease severity and activation status of the immune cells. Furthermore, overexpression of FASN significantly boosts the TLR4/7/9-mediated activation of macrophages and DCs, while knockdown of FASN markedly inhibits this activation. Notably, knockdown of FASN alleviates TLR7 agonist imiquimod (IMQ)-induced lupus in mice and the activation of macrophages and DCs. It makes more sense that pharmaceutical targeting of FASN by using TVB-2640 significantly alleviates IMQ-induced lupus in mice and the activation of macrophages and DCs, as well as in spontaneous lupus MRL/lpr mice. Thus, FASN contributes to the TLRs-mediated activation of macrophages and DCs, as well as the pathogenesis of SLE. More importantly, FASN inhibitor TVB-2640 is expected to be an effective drug in the treatment of SLE.

4.
BMC Plant Biol ; 24(1): 748, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39103795

RESUMO

Lead affects photosynthesis and growth and has serious toxic effects on plants. Here, the differential expressed proteins (DEPs) in D. huoshanense were investigated under different applications of lead acetate solutions. Using label-free quantitative proteomics methods, more than 12,000 peptides and 2,449 proteins were identified. GO and KEGG functional annotations show that these differential proteins mainly participate in carbohydrate metabolism, energy metabolism, amino acid metabolism, translation, protein folding, sorting, and degradation, as well as oxidation and reduction processes. A total of 636 DEPs were identified, and lead could induce the expression of most proteins. KEGG enrichment analysis suggested that proteins involved in processes such as homologous recombination, vitamin B6 metabolism, flavonoid biosynthesis, cellular component organisation or biogenesis, and biological regulation were significantly enriched. Nearly 40 proteins are involved in DNA replication and repair, RNA synthesis, transport, and splicing. The effect of lead stress on D. huoshanense may be achieved through photosynthesis, oxidative phosphorylation, and the production of excess antioxidant substances. The expression of 9 photosynthesis-related proteins and 12 oxidative phosphorylation-related proteins was up-regulated after lead stress. Furthermore, a total of 3 SOD, 12 POD, 3 CAT, and 7 ascorbate-related metabolic enzymes were identified. Under lead stress, almost all key enzymes involved in the synthesis of antioxidant substances are up-regulated, which may facilitate the scavenging of oxygen-free radical scavenging. The expression levels of some key enzymes involved in sugar and glycoside synthesis, the phenylpropanoid synthesis pathway, and the terpene synthesis pathway also increased. More than 30 proteins involved in heavy metal transport were also identified. Expression profiling revealed a significant rise in the expression of the ABC-type multidrug resistance transporter, copper chaperone, and P-type ATPase with exposure to lead stress. Our findings lay the basis for research on the response and resistance of D. huoshanense to heavy metal stress.


Assuntos
Dendrobium , Chumbo , Proteínas de Plantas , Proteômica , Estresse Fisiológico , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Chumbo/toxicidade , Dendrobium/efeitos dos fármacos , Dendrobium/metabolismo , Dendrobium/genética , Estresse Fisiológico/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos
5.
Biotechnol Biofuels Bioprod ; 17(1): 109, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090744

RESUMO

BACKGROUND: The 2-phenylethanol (2-PE) tolerance phenotype is crucial to the production of 2-PE, and Pdr1p mutation can significantly increase the tolerance of 2-PE in Saccharomyces cerevisiae. However, its underlying molecular mechanisms are still unclear, hindering the rational design of superior 2-PE tolerance performance. RESULTS: Here, the physiology and biochemistry of the PDR1_862 and 5D strains were analyzed. At 3.5 g/L 2-PE, the ethanol concentration of PDR1_862 decreased by 21%, and the 2-PE production of PDR1_862 increased by 16% than those of 5D strain. Transcriptome analysis showed that at 2-PE stress, Pdr1p mutation increased the expression of genes involved in the Ehrlich pathway. In addition, Pdr1p mutation attenuated sulfur metabolism and enhanced the one-carbon pool by folate to resist 2-PE stress. These metabolic pathways were closely associated with amino acids metabolism. Furthermore, at 3.5 g/L 2-PE, the free amino acids content of PDR1_862 decreased by 31% than that of 5D strain, among the free amino acids, cysteine was key amino acid for the enhancement of 2-PE stress tolerance conferred by Pdr1p mutation. CONCLUSIONS: The above results indicated that Pdr1p mutation enhanced the Ehrlich pathway to improve 2-PE production of S. cerevisiae, and Pdr1p mutation altered the intracellular amino acids contents, in which cysteine might be a biomarker in response to Pdr1p mutation under 2-PE stress. The findings help to elucidate the molecular mechanisms for 2-PE stress tolerance by Pdr1p mutation in S. cerevisiae, identify key metabolic pathway responsible for 2-PE stress tolerance.

6.
Food Res Int ; 192: 114833, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39147522

RESUMO

This study examined the suppressive effects of 16 selected plant-based foods on α-glucosidase and pancreatic lipase and their antioxidant properties. Among these, the bark of Cinnamomum cassia (Cinnamon, WLN-FM 15) showed the highest inhibitory activity against α-glucosidase and the highest antioxidant activity. Additionally, WLN-FM 15 showed promising results in the other tests. To further identify the bioactive constituents of WLN-FM 15, a multi-bioactivity-labeled molecular networking approach was used through a combination of GNPS-based molecular networking, DPPH-HPLC, and affinity-based ultrafiltration-HPLC. A total of nine procyanidins were identified as antioxidants and inhibitors of α-glucosidase and pancreatic lipase in WLN-FM 15. Subsequently, procyanidins A1, A2, B1, and C1 were isolated, and their efficacy was confirmed through functional assays. In summary, WLN-FM 15 has the potential to serve as a functional food ingredient with the procyanidins as its bioactive constituents. These results also suggest that the multi-bioactivity-labeled molecular networking approach is reliable for identifying bioactive constituents in plant-based foods.


Assuntos
Antioxidantes , Biflavonoides , Catequina , Cinnamomum aromaticum , Inibidores de Glicosídeo Hidrolases , Lipase , Casca de Planta , Proantocianidinas , Proantocianidinas/farmacologia , Proantocianidinas/química , Proantocianidinas/análise , Lipase/antagonistas & inibidores , Lipase/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/análise , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Casca de Planta/química , Cinnamomum aromaticum/química , Biflavonoides/farmacologia , Biflavonoides/análise , Biflavonoides/química , Catequina/análise , Catequina/química , Catequina/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cromatografia Líquida de Alta Pressão , Pâncreas/enzimologia , alfa-Glucosidases/metabolismo , Farmacologia em Rede , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química
7.
Nat Commun ; 15(1): 7202, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39169018

RESUMO

Flexible frequency controls are crucial in many photonic and electronic applications, ranging from communications systems, spectroscopy, and metrology to quantum information processing. However, the state-of-the-art solutions based on nonlinear bulk media, electro-optic effect, and nonlinear metasurfaces incur very limited spectral controllability, and merely a couple of harmonic orders can be independently manipulated. Here, we theoretically propose and experimentally demonstrate synthetic moving-envelope metasurface antennas capable of simultaneously generating arbitrary harmonic orders and independently manipulating their wave properties in a software-defined manner. As proof-of-principle examples, we demonstrate unidirectional frequency transition, frequency comb generation, arbitrary harmonic orders independent control, and their applications in frequency-division multiplexing communications. All these complicated functionalities are achieved by the 1-bit spatiotemporally ON-OFF switching of meta-atoms of the waveguide-integrated metasurface antenna. Our proposed synthetic metasurface antenna solution greatly expands the frontiers of wave engineering and information manipulation, showing promising potential in wireless communications, spectroscopy, metrology, and quantum science.

8.
Foods ; 13(16)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39200518

RESUMO

This study focused on improving the flavor quality of seasonings, and enzymatic hydrolysis of soybean protein isolate (SPI) seasoning via traditional technology may lead to undesirable flavors. Herein, we aimed to develop a new type of SPI seasoning through microbial fermentation to improve its flavor quality. The effect of Corynebacterium glutamicum fermentation on the flavoring compounds of seasonings in SPI enzymatic hydrolysate was examined. Sensory evaluation showed that the SPI seasoning had mainly aromatic and roasted flavor, and the response signals of S18 (aromatic compounds), S24 (alcohols and aldehydes), and S25 (esters and ketones) sensors of the electronic nose differed significantly. Overall, 91 volatile compounds were identified via gas chromatography-mass spectrometry. SPI seasonings contained a higher number of alcohols, ketones, aromatics, and heterocyclic compounds than traditional seasonings, which had stronger cheese, fatty, and roasted aromas. According to the relative odor activity value (ROAV) analysis, n-pentylpyrzine, 2,6-dimethylpyrazine, and tetramethylpyrazine are the key flavoring compounds (ROAV ≥ 1) of SPI seasoning, which may impart a unique roasted and meaty aroma. Therefore, the fermentation of SPI enzymatic hydrolysate with C. glutamicum may improve the flavor quality of its products, providing a new method for the development and production of new seasoning products.

9.
Angew Chem Int Ed Engl ; : e202410744, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177424

RESUMO

Molecular spherical nucleic acids (m-SNAs) are a second generation of spherical nucleic acids (SNAs), which are of significance in potential application of targeted delivery of nucleic acids or gene regulation due to their defined molecular structures. Nevertheless, m-SNAs typically involve a single DNA sequence which greatly limits its functions as either targeting purpose or gene regulation. In response, we proposed here a third generation, supramolecular spherical nucleic acids (Supra-SNAs) with two different sequences to achieve both above-mentioned functions. Specifically, we constructed a series of supramolecular self-assembly structures by coupling a cell membrane receptor (i.e., nucleolin)-recognizing aptamer (AS1411)-modified adamantine as targeting probe and human epithelial growth factor receptor 2 (HER2) antisense-functionalized ß-cyclodextrin to specifically inhibit the overexpression of HER2 proteins for gene regulations. In comparison to the m-SNA precursors, such Supra-SNA structures exhibited enhanced levels of resistance to nuclease degradation, cellular uptake, gene regulation capabilities and tumor retention capacity. We demonstrated that Supra-SNAs exhibited optimal cell suppression rates and cell apoptosis via a phosphatidylinositol 3-kinase/protein kinase B signaling pathway. The well-defined molecular structures provide an attractive platform for investigating interrelationship between structure and property at the molecular level.

10.
J Dent ; 149: 105284, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39122206

RESUMO

OBJECTIVES: To demonstrate the potential application of mixed reality (MR) holographic imaging technology in subgingival scaling and root planing (SRP) for patient with advanced periodontitis. METHODS: This case series comprised the analysis of 1566 sites from 261 teeth of 10 patients with advanced periodontitis. Digital CBCT scans and intraoral scans of the patients were digitally acquired preoperatively and aligned to create a three-dimensional periodontal visualization model. Through rendering, interactive holographic images were displayed using MR. The surgeon first used MR images to communicate with the patients, and then facilitated SRP under their guidance. Probing pocket depth (PPD), clinical attachment loss (CAL), Plaque index (PI), and bleeding on probing (BOP) parameters were recorded at baseline and at 8-week postoperatively. Patient-reported outcome indicator questionnaires on self-efficacy were also collected. RESULTS: PPD, CAL, PI, and BOP significantly decreased at 8-week following MR hologram-assisted SRP (p<0.001). For sites with PPD≥4 mm, PPD and CAL declined by 2.33±1.23 mm and 0.69±1.07 mm, respectively. PI significantly decreased from 1.94±0.61 to 0.82±0.58 (p < 0.001) and BOP sites decreased significantly from 84.11% to 40.25%. After receiving MR holograms for condition communication, most patients had a better perception of the effectiveness of SRP treatment and the benefits it brings. 80% of the subjects expressed their willingness to undergo MR-assisted periodontal treatment in the future. CONCLUSION: These results provide preliminary support for MR hologram-assisted digital SRP. With this technology, images of the gingiva and alveolar bone can be displayed in real time, accurately and three-dimensionally. This improves SRP effectiveness, diminishes complications, and enhances patients' confidence in the treatment. CLINICAL SIGNIFICANCE: MR holographic imaging-based digital SRP is a clinically feasible and promising adjunctive periodontal treatment option. It may contribute to improved non-surgical treatment efficacy in patients with severe periodontitis.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Raspagem Dentária , Holografia , Índice Periodontal , Periodontite , Aplainamento Radicular , Humanos , Holografia/métodos , Aplainamento Radicular/métodos , Raspagem Dentária/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Feixe Cônico/métodos , Periodontite/diagnóstico por imagem , Periodontite/terapia , Adulto , Bolsa Periodontal/terapia , Bolsa Periodontal/diagnóstico por imagem , Perda da Inserção Periodontal/terapia , Perda da Inserção Periodontal/diagnóstico por imagem , Imageamento Tridimensional/métodos , Índice de Placa Dentária , Estudo de Prova de Conceito , Resultado do Tratamento , Autoeficácia , Medidas de Resultados Relatados pelo Paciente
11.
mBio ; 15(9): e0066824, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39105586

RESUMO

The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.IMPORTANCEAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine was highly effective in preclinical trials, generating strong immune responses and ensuring protection against both matching and heterologous strains of influenza viruses and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , SARS-CoV-2 , Vacinas de mRNA , Animais , COVID-19/prevenção & controle , COVID-19/imunologia , Camundongos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Influenza Humana/virologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/administração & dosagem , Camundongos Endogâmicos BALB C , Feminino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Virus da Influenza A Subtipo H5N1/imunologia , Virus da Influenza A Subtipo H5N1/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/genética
13.
Adv Healthc Mater ; : e2304108, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979870

RESUMO

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1O2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.

14.
Light Sci Appl ; 13(1): 172, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025829

RESUMO

Independent controls of various properties of electromagnetic (EM) waves are crucially required in a wide range of applications. Programmable metasurface is a promising candidate to provide an advanced platform for manipulating EM waves. Here, we propose an approach that can arbitrarily control the polarization direction and phases of reflected waves in linear and nonlinear ways using a stacked programmable metasurface. Further, we extend the space-time-coding theory to incorporate the dimension of polarization, which provides an extra degree of freedom for manipulating EM waves. As proof-of-principle application examples, we consider polarization rotation, phase manipulation, and beam steering at linear and nonlinear frequencies. For validation, we design, fabricate, and measure a metasurface sample. The experimental results show good agreement with theoretical predictions and simulations. The proposed approach has a wide range of applications in various areas, such as imaging, data storage, and wireless communication.

15.
Rheumatol Adv Pract ; 8(3): rkae080, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055542

RESUMO

Objective: To characterize BMI in Chinese patients with RA vs US patients and examine its association with joint damage in Chinese patients. Methods: Each of the 1318 patients from a real-world Chinese RA population was first stratified by gender and then individually age-matched with one American RA patient from the US National Health and Nutritional Examination Survey 1999-2018. Data on BMI, bilateral hand radiographs and risk factors at enrolment were collected but radiographs were unavailable for the American patients. Logistic regression was used to evaluate the association of BMI with radiographic joint damage (RJD) in Chinese patients. Results: Chinese patients had a significantly lower BMI [(weighted) median 21.8 vs 29.8 kg/m2; P < 0.001] and a higher prevalence of being underweight (15.2% vs 1.1%; P < 0.05) than their American counterparts. Underweight Chinese patients (BMI <18.5) had higher modified total Sharp scores (median 17 vs 10) and joint space narrowing (JSN) subscores (median 6 vs 2) (both P < 0.05) than normal-weight patients (BMI ≥18.5-<24). After controlling for confounding, continuous BMI was cross-sectionally negatively associated with RJD [adjusted prevalence odds ratio (OR) 0.90 (95% CI 0.85, 0.96)] and JSN [adjusted prevalence OR 0.92 (95% CI 0.87, 0.96)]; being underweight vs normal weight was associated with RJD [adjusted prevalence OR 2.14 (95% CI 1.37, 3.35)] and JSN [adjusted prevalence OR 1.77 (95% CI 1.10, 2.84)]. Conclusion: Low BMI and being underweight were cross-sectionally associated with joint damage in Chinese RA patients, especially JSN, suggesting the clinical importance of identifying underweight patients and focusing on weight gain to prevent joint damage.

16.
Virus Res ; 347: 199437, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39002567

RESUMO

The global monkeypox virus (MPXV) outbreak in 2022 emphasizes the urgent need for effective and accessible new-generation vaccines and neutralizing antibodies. Herein, we identified MPXV-neutralizing antibodies using high-throughput single-cell RNA and V(D)J sequencing of antigen-sorted B cells from patients with convalescent monkeypox. IgG1-expressing B cells were obtained from 34 paired heavy- and light-chain B cell receptor sequences. Subsequently, three potent neutralizing antibodies, MV127, MV128, and MV129, were identified and reacted with the MPXV A35 protein. Among these, MV129, which has a half-maximal inhibitory concentration of 2.68µg/mL against authentic MPXV, was considered to be the putative candidates for MPXV neutralization in response to monkeypox disease.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos B , Sequenciamento de Nucleotídeos em Larga Escala , Monkeypox virus , Mpox , Anticorpos Neutralizantes/imunologia , Humanos , Anticorpos Antivirais/imunologia , Monkeypox virus/imunologia , Monkeypox virus/genética , Mpox/imunologia , Mpox/virologia , Linfócitos B/imunologia , Imunoglobulina G/imunologia , Feminino , Masculino , Adulto , Testes de Neutralização , Pessoa de Meia-Idade
17.
Sci Bull (Beijing) ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39084926

RESUMO

Two-dimensional noble transition metal chalcogenide (NTMC) semiconductors represent compelling building blocks for fabricating flexible electronic and optoelectronic devices. While binary and ternary compounds have been reported, the existence of quaternary NTMCs with a greater elemental degree of freedom remains largely unexplored. This study presents the pioneering experimental realization of a novel semiconducting quaternary NTMC material, AuPdNaS2, synthesized directly on Au foils through chemical vapor deposition. The ribbon-shaped morphology of the AuPdNaS2 crystal can be finely tuned to a thickness as low as 9.2 nm. Scanning transmission electron microscopy reveals the atomic arrangement, showcasing robust anisotropic features; thus, AuPdNaS2 exhibits distinct anisotropic phonon vibrations and electrical properties. The field-effect transistor constructed from AuPdNaS2 crystal demonstrates a pronounced anisotropic conductance (σmax/σmin = 3.20) under gate voltage control. This investigation significantly expands the repertoire of NTMC materials and underscores the potential applications of AuPdNaS2 in nano-electronic devices.

18.
Small ; : e2400179, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031523

RESUMO

With the rapid development of micro/nano machining, there is an elevated demand for high-performance microdevices with high reliability and low cost. Due to their outstanding electrochemical, optical, electrical, and mechanical performance, carbon materials are extensively utilized in constructing microdevices for energy storage, sensing, and optoelectronics. Carbon micro/nano machining is fundamental in carbon-based intelligent microelectronics, multifunctional integrated microsystems, high-reliability portable/wearable consumer electronics, and portable medical diagnostic systems. Despite numerous reviews on carbon materials, a comprehensive overview is lacking that systematically encapsulates the development of high-performance microdevices based on carbon micro/nano structures, from structural design to manufacturing strategies and specific applications. This review focuses on the latest progress in carbon micro/nano machining toward miniaturized device, including structural engineering, large-scale fabrication, and performance optimization. Especially, the review targets an in-depth evaluation of carbon-based micro energy storage devices, microsensors, microactuators, miniaturized photoresponsive and electromagnetic interference shielding devices. Moreover, it highlights the challenges and opportunities in the large-scale manufacturing of carbon-based microdevices, aiming to spark further exciting research directions and application prospectives.

19.
BMC Microbiol ; 24(1): 281, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068412

RESUMO

BACKGROUND: Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles. RESULTS: Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse. CONCLUSIONS: The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.


Assuntos
Adenomiose , Ciclo Menstrual , Microbiota , Vagina , Humanos , Feminino , Vagina/microbiologia , Ciclo Menstrual/fisiologia , Adulto , Adenomiose/microbiologia , Adenomiose/fisiopatologia , Adenomiose/complicações , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Estudos de Casos e Controles , RNA Ribossômico 16S/genética , Lactobacillus/isolamento & purificação
20.
J Exerc Sci Fit ; 22(4): 322-328, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38947123

RESUMO

Background: The perceived benefits and barriers to physical activity play crucial roles in determining daily physical activity levels. However, previous studies have employed tools lacking adequate validation, leading to inconsistent conclusions about the impact of these two factors. Therefore, this national, population-based study was conducted to assess the psychometric properties, measurement invariance, and predictive validity of the Chinese versions of the perceived benefits (C-PBEPA) and barriers to physical activity (C-PBAPA) scales. Methods: The final sample (N = 2942, 49.3 % for boys) was randomly split into two subsamples. The first subsample was used for exploratory factor analysis and the second subsample was used for confirmatory factor analysis. Measurement invariance across gender and age groups were examined. Structural equation models were developed to examine the predictive validity of the revised C-PBEPA and C-PBAPA on moderate to vigorous PA. Results: The results showed that both scales were unidimensional, had excellent model fit (e.g., X 2/df < 3, CFI >0.9, RMSEA <0.06) and demonstrated convergent validity. Findings also revealed lack of scalar invariance for C-PBAPA between preadolescents and adolescents' groups (ΔCFI >0.01) and supported the predictive validity of both scales (p < 0.001). Conclusion: The study demonstrated that the revised C-PBEPA and C-PBAPA are valid scales for measuring Chinese adolescents' perceived benefits and barriers to PA.

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