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2.
ISA Trans ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38839549

RESUMO

This paper proposed a prediction algorithm for the degraded actuator taking into account the impact of estimation error of hidden index in the closed-loop system. To this end, a unified prediction framework is established to evaluate the hidden degradation information and recursively update the degradation model parameters simultaneously. The advantage is that the prediction framework can comprehensively compensate the estimation error of hidden degradation index caused by system uncertainty. To jointly estimate the degradation information in avoidance of the impact of system uncertainty, a modified adaptive Kalman filter is designed, and the proof of stability is provided. With the priori estimate from the filter, the degradation model parameters are updated by the inverse filtering probability based on Bayes' theorem. It is followed by the computation of the remaining useful life (RUL) prediction utilizing aforementioned hidden degradation information and the latest degradation model. The effectiveness of the proposed RUL prediction algorithm is demonstrated by the degraded actuator in the continuous casting process.

3.
Front Immunol ; 15: 1377432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863716

RESUMO

Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Among its various complications, heart failure (HF) has been recognized as the second leading cause of cardiovascular death in RA patients. The objective of this study was to investigate the relationship between RA and HF using epidemiological and genetic approaches. Methods: The study included 37,736 participants from the 1999-2020 National Health and Nutrition Examination Survey. Associations between RA and HF in the US population were assessed with weighted multivariate logistic regression analysis. A two-sample Mendelian randomization (MR) analysis was employed to establish the causal relationship between the two variables. The primary analysis method utilized was inverse variance weighting (IVW). Additionally, horizontal pleiotropy and heterogeneity were assessed to account for potential confounding factors. In cases where multiple independent datasets were accessible during MR analysis, we combined the findings through a meta-analytical approach. Results: In observational studies, the prevalence of HF in combination with RA reached 7.11% (95%CI 5.83 to 8.39). RA was positively associated with an increased prevalence of HF in the US population [odds ratio (OR):1.93, 95% confidence interval (CI):1.47-2.54, P < 0.0001]. In a MR analysis utilizing a meta-analytical approach to amalgamate the results of the IVW method, we identified a significant causal link between genetically predicted RA and a heightened risk of HF (OR = 1.083, 95% CI: 1.028-1.141; P = 0.003). However, this association was not deemed significant for seronegative RA (SRA) (OR = 1.028, 95% CI: 0.992-1.065; P = 0.126). These findings were consistent across sensitivity analyses and did not indicate any horizontal pleiotropy. Conclusion: RA correlates with an elevated prevalence of HF within the US population. Furthermore, genetic evidence derived from European populations underscores a causal link between RA and the risk of HF. However this association was not significant in SRA.


Assuntos
Artrite Reumatoide , Insuficiência Cardíaca , Análise da Randomização Mendeliana , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Estudos Transversais , Estados Unidos/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Masculino , Feminino , Adulto , Prevalência , Pessoa de Meia-Idade
5.
Mol Biol Rep ; 51(1): 720, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824268

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) exert a significant influence on the progression and heterogeneity of various subtypes of breast cancer (BRCA). However, the roles of heterogeneous TAM within BRCA subtypes remain unclear. Therefore, this study sought to elucidate the role of TAM across the following three BRCA subtypes: triple-negative breast cancer, luminal, and HER2. MATERIALS AND METHODS: This investigation aimed to delineate the variations in marker genes, drug sensitivity, and cellular communication among TAM across the three BRCA subtypes. We identified specific ligand-receptor (L-R) pairs and downstream mechanisms regulated by VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Experimental verification of these pairs was conducted by co-culturing macrophages with three subtypes of BRCA cells. RESULTS: Our findings reveal the heterogeneity of macrophages within the three BRCA subtypes, evidenced by variations in marker gene expression, composition, and functional characteristics. Notably, heterogeneous TAM were found to promote invasive migration and epithelial-mesenchymal transition (EMT) in MDA-MB-231, MCF-7, and SKBR3 cells, activating NF-κB pathway via P38 MAPK, TGF-ß1, and AKT, respectively, through distinct VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Inhibition of these specific L-R pairs effectively reversed EMT, migration, and invasion of each cancer cells. Furthermore, we observed a correlation between ligand gene expression and TAM sensitivity to anticancer drugs, suggesting a potential strategy for optimizing personalized treatment guidance. CONCLUSION: Our study highlights the capacity of heterogeneous TAM to modulate biological functions via distinct pathways mediated by specific L-R pairs within diverse BRCA subtypes. This study might provide insights into precision immunotherapy of different subtypes of BRCA.


Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal , Macrófagos Associados a Tumor , Humanos , Feminino , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Célula Única/métodos , Células MCF-7 , Movimento Celular/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Análise de Sequência de RNA/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Transdução de Sinais/genética , Microambiente Tumoral/genética
6.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 233-237, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836656

RESUMO

Nur77 is a member of the NR4A subfamily of orphan nuclear receptors that is expressed and has a function within the immune system. This study aimed to investigate the role of Nur77 in hypoxic pulmonary hypertension. SPF male SD rats were exposed in hypobaric chamber simulating 5000 m high altitude for 0, 3, 7, 14, 21 or 28 days. Rat pulmonary artery smooth muscle cells (RPASMCs) were cultured under normoxic conditions (5% CO2-95% ambient air) or hypoxic conditions (5% O2 for 6 h, 12 h, 24 h, 48 h). Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased pulmonary arterial pressure. The levels of Nur77, HIF-1α and PNCA were upregulated in pulmonary arterial smooth muscle from hypoxic rats. Silencing of either Nur77 or HIF-1α attenuated hypoxia-induced proliferation. Silencing of HIF-1α down-regulated Nur77 protein level, but Nur77 silence did not reduce HIF-1α. Nur77 was not con-immunoprecipitated with HIF-1α. This study demonstrated that Nur77 acted as a downstream regulator of HIF-1α under hypoxia, and plays a critical role in the hypoxia-induced pulmonary vascular remodeling, which is regulated by HIF-1α. Nur77 maybe a novel target of HPH therapy.


Assuntos
Hipertensão Pulmonar , Subunidade alfa do Fator 1 Induzível por Hipóxia , Hipóxia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Artéria Pulmonar , Ratos Sprague-Dawley , Remodelação Vascular , Animais , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Remodelação Vascular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Hipóxia/metabolismo , Proliferação de Células , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Ratos , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/genética , Células Cultivadas
7.
Cancer Cell Int ; 24(1): 208, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872157

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) patients have a dismal survival rate because of cancer metastasis and drug resistance. The study aims to identify the genes that concurrently modulate EMT, metastasis and EGFR-TKI resistance, and to investigate the underlying regulatory mechanisms. METHODS: Cox regression and Kaplan-Meier analyses were applied to identify prognostic oncogenes in LUAD. Gene set enrichment analysis (GSEA) was used to indicate the biological functions of the gene. Wound-healing and Transwell assays were used to detect migratory and invasive ability. EGFR-TKI sensitivity was evaluated by assessing the proliferation, clonogenic survival and metastatic capability of cancer cells with treatment with gefitinib. Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) analyses established the level of m6A modification present on the target gene and the protein's capability to interact with RNA, respectively. Single-sample gene set enrichment (ssGSEA) algorithm used to investigate levels of immune cell infiltration. RESULTS: Our study identified dual-specificity phosphatase 5 (DUSP5) as a novel and powerful predictor of adverse outcomes for LUAD by using public datasets. Functional enrichment analysis found that DUSP5 was positively enriched in EMT and transforming growth factor-beta (TGF-ß) signaling pathway, a prevailing pathway involved in the induction of EMT. As expected, DUSP5 knockdown suppressed EMT via inhibiting the canonical TGF-ß/Smad signaling pathway in in vitro experiments. Consistently, knockdown of DUSP5 was first found to inhibit migratory ability and invasiveness of LUAD cells in in vitro and prevent lung metastasis in in vivo. DUSP5 knockdown re-sensitized gefitinib-resistant LUAD cells to gefitinib, accompanying reversion of EMT progress. In LUAD tissue samples, we found 14 cytosine-phosphate-guanine (CpG) sites of DUSP5 that were negatively associated with DUSP5 gene expression. Importantly, 5'Azacytidine (AZA), an FDA-approved DNA methyltransferase inhibitor, restored DUSP5 expression. Moreover, RIP experiments confirmed that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a m6A reader protein, could bind DUSP5 mRNA. YTHDF1 promoted DUSP5 expression and the malignant phenotype of LUAD cells. In addition, the DUSP5-derived genomic model revealed the two clusters with distinguishable immune features and tumor mutational burden (TMB). CONCLUSIONS: Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance.

8.
Environ Sci Pollut Res Int ; 31(28): 41290-41300, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38849617

RESUMO

As a crucial hydrolytic enzyme, urease plays a vital role in anaerobic biological treatment. It is well-known that manganese ions are abundant in landfill leachate, but their concentration fluctuates significantly. However, few studies have investigated the effect and mechanism of different concentrations of Mn2+ on urease activity during anaerobic biological treatment of landfill leachate. This paper aimed to investigate the effects and mechanisms of different concentrations of Mn2+ on urease activity. The results showed that an appropriate amount of Mn2+ could significantly enhance urease activity, while a high concentration of Mn2+ could inhibit it. Insight into the mechanisms behind this phenomenon, various methods such as Zeta potential, particle size, ultraviolet spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and statistical analysis were employed in our study. Research suggested that, on one hand, Mn2+ may form hydrogen bonds with the side chain amino or carboxyl groups of urease amino acid residues, affecting the structure of urease through hydrogen bonding. Additionally, Mn2+ also binds to urease through hydrophobic interactions. On the other hand, the C-OH and C-N functional groups in urease have a strong affinity for Mn2+, and changes in these functional groups can greatly enhance the activity of urease. Furthermore, under the action of high concentrations of Mn2+, while the structure of urease becomes more stable, there is also a steric hindrance phenomenon that affects the substrate from entering the catalytic center. Therefore, studying the mechanism of Mn2+ affecting urease activity has significant biological significance and provides a new perspective for exploring the impact of metals on anaerobic bioprocessing of landfill leachate.


Assuntos
Manganês , Urease , Poluentes Químicos da Água , Urease/metabolismo , Poluentes Químicos da Água/metabolismo , Anaerobiose
9.
Environ Sci Pollut Res Int ; 31(28): 41155-41166, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38849618

RESUMO

Zinc and cadmium ions are usually found in livestock breeding wastewater, and the mixed ions will have an impact on the biological nitrogen removal. Nitrification performance plays an important role in biological nitrogen removal. In order to investigate the combined effect of zinc and cadmium ions on nitrification performance and to reveal the interactions between zinc and cadmium ions, three concentration ratios of zinc and cadmium ions, as well as 18 different concentration gradients were designed with the direct equipartition ray and the dilution factor method. The effect of pollutants on the nitrification performance of biological nitrogen removal was analyzed by the nonlinear regression equation, and the concentration-addition model was conducted to probe into the relationship between the mixed pollutants and the nitrification performance. The results showed that the effect on nitrification performance increased significantly with the increase of reaction duration and pollutant concentration, which indicated that the effects are concentration-dependent and time-dependent. The concentration-addition model suggested that the interactions between zinc and cadmium ions with different concentration ratios were mainly antagonistic, and as the percentage of cadmium ions in the mixtures increased, the antagonism between the mixtures became stronger. This study will provide a relevant theoretical basis for the regulation of the ratios and concentrations of heavy metal ions during the biological treatment of livestock breeding wastewater.


Assuntos
Cádmio , Gado , Nitrificação , Nitrogênio , Águas Residuárias , Zinco , Animais , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água
10.
Polymers (Basel) ; 16(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891444

RESUMO

Plasma-initiated polymerization (PIP) is generally attributed to a radical process due to its inhibiting property. However, its unique polymerization behaviors like long-lived radical and solvent effect do not comply well with the traditional radical mechanism. Herein, the PIP of methyl methacrylate (MMA) was conducted in a high-voltage DC electric field to investigate the charged nature of its radicals. Consequently, the polymerization presented a preferential distribution of polymers at the anode but not the cathode, revealing the negatively charged nature of the growing radicals. An acceleration phenomenon, accompanied by the growth in molecular weights and the reduction in molecular weight distributions (Ð), was observed at the voltages above 16 kV, suggesting the dissociation of ion pairs of growing radicals. The PIP yielded PMMA with analogous chemical and steric structures to those of PMMA from traditional radical initiation, whether in the presence or absence of the external electric field. This work offers new insights into the PIP of vinyl monomers, wherein a one-electron transfer reaction is inferred to be involved in the monomer activation.

11.
Anal Chem ; 96(24): 9834-9841, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38832651

RESUMO

Complexed and tiresome pretreatment processes have significantly impeded in-field analysis of environmental specimens. Herein, an all-in-one sample separation and enrichment strategy based on a compact charge-selective capture/nanoconfined enrichment (CSC/NCE) device is exploited for marker-free surface-enhanced Raman spectroscopy (SERS) detection of charged pesticides in matrix specimens. This tactic incorporating in situ separations, seizing, and nanoconfined enhancement can greatly elevate the effectiveness of sample pretreatment. Importantly, CSC/NCE with excellent adsorption performances and excellent plasmonic features facilitates concentration and signal amplification of electrically charged pesticides. With the introduction of an electric field on this integrated CSC/NCE, the matrix effect in samples could be significantly eradicated, and a distinct SERS response is witnessed for targeted analytes. Accurate quantification of multipesticides is achieved by synergizing the CSC/NCE chip and chemometrics, and the contents found by the CSC/NCE-based sensing strategy agree with those obtained from chromatography assays with relative deviations lower than 10%. The facile and versatile all-in-one tactic infused in a compact chip exhibits enormous potential for field-test application in chemical measurement and food safety.


Assuntos
Praguicidas , Análise Espectral Raman , Praguicidas/análise , Miniaturização , Nanopartículas Metálicas/química , Propriedades de Superfície
12.
Opt Express ; 32(10): 17581-17592, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858939

RESUMO

The development of solid-state nonlinear optical limiting (NOL) materials is crucial for advancing the practicality in the field of optical limiting. In this paper, we innovatively prepare a new solid NOL material which is spiral carbon nanotubes doped epoxy resin (SCNTs-doped ER, SER) with a simple physical mixing method, and achieve an excellent nonlinear optical limiting performance. We experimentally measured optical limiting of SER with different SCNTs concentrations (0.14, 0.28, and 0.43 mg/mL) and obtained the nonlinear absorption coefficient, nonlinear refractive index, and third-order nonlinear susceptibility at the wavelength 1064 nm. Z-scan experiment results show that the SER exhibits a large nonlinear absorption coefficient (5.07 ± 0.38) × 10-9 m/W. We also measure the transmittance of the SER to evaluate its nonlinear optical limiting performance. For the SER with 0.43 mg/mL concentration, the linear transmittance and minimum transmittance with NOL effects at 1064 nm are 54.8% and 26.2%, respectively. In addition, the SER also has prominent features such as a high damage threshold and easy fabrication, indicating that the SER is a promising solid material for nonlinear optical limiting.

13.
J Gene Med ; 26(6): e3693, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860366

RESUMO

BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.


Assuntos
Carcinoma Hepatocelular , Células Estreladas do Fígado , Interleucina-17 , Neoplasias Hepáticas , Ratos Sprague-Dawley , Células Estreladas do Fígado/metabolismo , Animais , Interleucina-17/metabolismo , Interleucina-17/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Ratos , Masculino , Microambiente Tumoral , Endopeptidases/metabolismo , Endopeptidases/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Animais de Doenças , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Linhagem Celular Tumoral
14.
Nat Commun ; 15(1): 5216, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890331

RESUMO

Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating charges past the charge transfer center is accompanied by concomitant unwinding of the inner end of the S4 and S5 helices, disrupting the tight gating interface observed in the Closed state structure. This helix-coil transition at the intracellular gating interface accompanies a concerted iris-like dilation of the pore helices and underlies the reversed voltage dependence of HCN channels.


Assuntos
Microscopia Crioeletrônica , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Ativação do Canal Iônico , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/química , Humanos , Canais de Potássio/química , Canais de Potássio/metabolismo , Modelos Moleculares , Potenciais da Membrana/fisiologia
15.
Sensors (Basel) ; 24(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38894189

RESUMO

Global positioning systems often fall short in dense forest environments, leading to increasing demand for innovative localization methods. Notably, existing methods suffer from the following limitations: (1) traditional localization frameworks necessitate several fixed anchors to estimate the locations of targets, which is difficult to satisfy in complex and uncertain forestry environments; (2) the uncertain environment severely decreases the quality of signal measurements and thus the localization accuracy. To cope with these limitations, this paper proposes a new method of trajectory localization for forestry environments with the assistance of UAVs. Based on the multi-agent DRL technique, the topology of UAVs is optimized in real-time to cater for high-accuracy target localization. Then, with the aid of RSS measurements from UAVs to the target, the least squares algorithm is used to estimate the location, which is more flexible and reliable than existing localization systems. Furthermore, a shared replay memory is incorporated into the proposed multi-agent DRL system, which can effectively enhance learning performance and efficiency. Simulation results show that the proposed method can obtain a flexible and high-accuracy localization system with the aid of UAVs, which exhibits better robustness against high-dimensional heterogeneous data and is suitable for forestry environments.

16.
Mol Ther ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38879753

RESUMO

Osteoarthritis (OA) is a painful and debilitating disease affecting over 500 million people worldwide. Intraarticular injection of mesenchymal stromal cells (MSCs) shows promise for the clinical treatment of OA, but the lack of consistency in MSC preparation and application makes it difficult to further optimize MSC therapy and to properly evaluate the clinical outcomes. In this study, we used Sox9 activation and RelA inhibition, both mediated by the CRISPR/dCas9 technology simultaneously, to engineer MSCs with enhanced chondrogenic potential and downregulated inflammatory responses. We found that both Sox9 and RelA could be fine-tuned to the desired levels, which enhances the chondrogenic and immunomodulatory potentials of the cells. Intraarticular injection of modified cells significantly attenuated cartilage degradation and palliated OA pain, compared to the injection of cell culture medium or unmodified cells. Mechanistically, the modified cells promoted the expression of factors beneficial to cartilage integrity, inhibited the production of catabolic enzymes in osteoarthritic joints, and suppressed immune cells. Interestingly, a substantial number of modified cells could survive in the cartilaginous tissues including articular cartilage and meniscus. Together, our results suggest that CRISPR/dCas9-based gene regulation is useful for optimizing MSC therapy for OA.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38898423

RESUMO

Flexible electronics toward high integration, miniaturization, and multifunctionality, leading to a dramatic increase in power density. However, the low thermal conductivity of flexible substrates impedes efficient heat dissipation and device performance improvement. In this work, we propose a template-assisted chemical conversion strategy for obtaining boron nitride nanotube (BNNT) films with high thermal conductivity and great flexibility. Aligned carbon nanotube (CNT) films have been adopted as templates; a low-temperature chemical conversion followed by a high-temperature annealing has been carried out to produce a highly ordered BNNT film. Benefiting from the high orientation order, the BNNT film exhibits an exceptional thermal conductivity of 45.5 W m-1 K-1 and presents excellent heat dissipation capability, much superior to the commonly used polyimide film. Furthermore, the BNNT film demonstrated excellent flexibility and high insulation resistance. The test of integration with film resistors demonstrated its potential as a thermally conductive substrate for electronics cooling. This work provides a solution for the effective thermal management of flexible electronics.

18.
Nutrients ; 16(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38794687

RESUMO

It has been strongly suggested that selenium deficiency and T-2 toxin contamination have a strong relationship with the occurrence and development of Kashin-Beck disease (KBD). In order to provide information for understanding the high prevalence of KBD in Tibet, this study collected the responses to a cubital venous blood and dietary questionnaire of 125 subjects including 75 KBD patients and 50 healthy controls in a KBD-prevalent county (Luolong County) in Tibet, China. A total of 10 household local families were randomly selected in this area, and local diet samples of brick tea, Zanba powder, milk residue, and hulless Barley were collected from these residents. Selenium content in blood was detected by inductively coupled plasma mass spectrometry (ICP-MS). The T-2 toxin contamination level in food sample was assayed using an ELISA kit. The selenium levels of patients and controls were 42.0 ± 19.8 and 56.06 ± 22.4 µg/L, respectively. The serum selenium level in controls was higher than that in patients, but there was no significant difference, and the serum selenium level both in patients and controls in Tibet was lower than the normal range. The results of the dietary survey showed that the number of respondents who consumed butter tea was large; 46.67% of patients indicated that they drank buttered tea every day, which was significantly higher than in controls. The contents of T-2 toxin in Zanba powder, milk residue, hulless barley and drinking water samples were below the detection limit (0.05 µg/kg); this result was labeled Tr. Unexpectedly, the contents of T-2 toxin in brick tea were higher, with average levels of 424 ± 56 µg/kg in Detong village and 396 ± 24 µg/kg in Langcuo village. For the first time, we report the presence of an extremely high concentration of T-2 toxin in brick tea of Tibet.


Assuntos
Doença de Kashin-Bek , Selênio , Toxina T-2 , Humanos , Tibet/epidemiologia , Doença de Kashin-Bek/epidemiologia , Doença de Kashin-Bek/sangue , Toxina T-2/sangue , Toxina T-2/análogos & derivados , Toxina T-2/análise , Feminino , Masculino , Selênio/sangue , Adulto , Pessoa de Meia-Idade , Prevalência , Bebidas , Contaminação de Alimentos/análise , Chá/química , Dieta/estatística & dados numéricos , Estudos de Casos e Controles , Inquéritos sobre Dietas
19.
Am J Hematol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38800953

RESUMO

Pathogenic variants in HFE and non-HFE genes have been identified in hemochromatosis in different patient populations, but there are still a certain number of patients with unexplained primary iron overload. We recently identified in Chinese patients a recurrent p.(Arg639Gln) variant in SURP and G-patch domain containing 2 (SUGP2), a potential mRNA splicing-related factor. However, the target gene of SUGP2 and affected iron-regulating pathway remains unknown. We aimed to investigate the pathogenicity and underlying mechanism of this variant in hemochromatosis. RNA-seq analysis revealed that SUGP2 knockdown caused abnormal alternative splicing of CIRBP pre-mRNA, resulting in an increased normal splicing form of CIRBP V1, which in turn increased the expression of BMPER by enhancing its mRNA stability and translation. Furthermore, RNA-protein pull-down and RNA immunoprecipitation assays revealed that SUGP2 inhibited splicing of CIRBP pre-mRNA by a splice site variant at CIRBP c.492 and was more susceptible to CIRBP c.492 C/C genotype. Cells transfected with SUGP2 p.(Arg639Gln) vector showed up-regulation of CIRBP V1 and BMPER expression and down-regulation of pSMAD1/5 and HAMP expression. CRISPR-Cas9 mediated SUGP2 p.(Arg622Gln) knock-in mice showed increased iron accumulation in the liver, higher total serum iron, and decreased serum hepcidin level. A total of 10 of 54 patients with hemochromatosis (18.5%) harbored the SUGP2 p.(Arg639Gln) variant and carried CIRBP c.492 C/C genotype, and had increased BMPER expression in the liver. Altogether, the SUGP2 p.(Arg639Gln) variant down-regulates hepcidin expression through the SUGP2/CIRBP/BMPER axis, which may represent a novel pathogenic factor for hemochromatosis.

20.
Anal Chem ; 96(21): 8566-8575, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38748451

RESUMO

Unraveling bacterial identity through Raman scattering techniques has been persistently challenging due to homogeneously amplified Raman signals across a wide variety of bacterial molecules, predominantly protein- or nucleic acid-mediated. In this study, we present an approach involving the use of silver nanoparticles to completely and uniformly "mask" adsorption on the surface of bacterial molecules through sodium borohydride and sodium chloride. This approach enables the acquisition of enhanced surface-enhanced Raman scattering (SERS) signals from all components on the bacterial surface, facilitating rapid, specific, and label-free bacterial identification. For the first time, we have characterized the identity of a bacterium, including its DNA, metabolites, and cell walls, enabling the accurate differentiation of various bacterial strains, even within the same species. In addition, we embarked on an exploration of the origin and variability patterns of the main characteristic peaks of Gram-positive and Gram-negative bacteria. Significantly, the SERS peak ratio was found to determine the inflection point of accelerated bacterial death upon treatment with antimicrobials. We further applied this platform to identify 15 unique clinical antibiotic-resistant bacterial strains, including five Escherichia coli strains in human urine, a first for Raman technology. This work has profound implications for prompt and accurate identification of bacteria, particularly antibiotic-resistant strains, thereby significantly enhancing clinical diagnostics and antimicrobial treatment strategies.


Assuntos
Nanopartículas Metálicas , Prata , Análise Espectral Raman , Análise Espectral Raman/métodos , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/análise , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Escherichia coli/química , Humanos
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