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1.
Arch Biochem Biophys ; 759: 110109, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39117070

RESUMEN

Chronic inflammation is an important pathogenetic factor that leads to the progression of Alzheimer's disease (AD), and specialized pro-resolving lipid mediators (SPMs) play critical role in regulating inflammatory responses during AD pathogenesis. Maresin1 (MaR1) is the latest discovered SPMs, and it is found that MaR1 improves AD cognitive impairment by regulating neurotrophic pathways to protect AD synapses and reduce Aß production, which made MaR1 as candidate agent for AD treatment. Unfortunately, the underlying mechanisms are still largely known. In this study, the AD mice and cellular models were subjected to MaR1 treatment, and we found that MaR1 reduced Aß production to ameliorate AD-related symptoms and increased the expression levels of ADAM10/17, sAPPα and sAPPß to exert its anti-inflammatory role. In addition, as it was determined by Western Blot analysis, we observed that MaR1 could affected the neuroprotective signal pathways. Specifically, MaR1 downregulated p57NTR and upregulated TrkA to activate the p75NTR/TrkA signal pathway, and it could increase the expression levels of p-PI3K and p-Akt, and downregulated p-mTOR to activate the PI3K/AKT/ERK/mTOR pathway. Finally, we verified the role of ADAM10/17 in regulating AD progression, and we found that silencing of ADAM10/17 inactivated the above neuroprotective signal pathways to aggravate AD pathogenesis. In conclusion, MaR1 is verified as potential therapeutic agent for AD by eliminating Aß production, upregulating ADAM10/17, sAPPα and sAPPß, and activating the neuroprotective p75NTR/TrkA pathway and the PI3K/AKT/ERK/mTOR pathway.


Asunto(s)
Proteína ADAM10 , Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Péptidos beta-Amiloides , Ácidos Docosahexaenoicos , Transducción de Señal , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Transducción de Señal/efectos de los fármacos , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/metabolismo , Péptidos beta-Amiloides/metabolismo , Ratones , Inflamación/metabolismo , Proyectos Piloto , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Masculino
2.
Kidney Int Rep ; 9(8): 2386-2398, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39156138

RESUMEN

Introduction: B-cell lymphocytes have been demonstrated to play a key role in the pathogenesis underlying membranous nephropathy (MN). The aim of this study was to evaluate the therapeutic efficacy and safety of Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody in individuals with MN. Methods: We retrospectively analyzed data from 59 consecutive patients with primary MN who provided consent to receive Obinutuzumab and were followed for at least 6 months. The primary outcomes were complete (proteinuria <0.3 g/d) or partial (proteinuria <3.5 g/d with ≥ 50% reduction) remission of proteinuria. Results: Twenty patients received Obinutuzumab as initial therapy, and 39 patients were previously treated with at least 1 immunosuppressant (second-line therapy). Fifty patients (84.7%) achieved complete remission (CR) or partial remission (PR) of proteinuria during the median follow-up of 9.4 months. The likelihood of remission was significantly higher when Obinutuzumab was used as initial therapy than as second-line therapy after adjusting for the baseline estimated glomerular filtration rate (eGFR), 24-hour urinary protein levels, and anti-phospholipase A2 receptor (PLA2R) status (adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI]: 2.1-9.5, P < 0.001). Circulating CD19+ B-cell count decreased to <5 cells/µl in all patients within 2 weeks after infusion. Serum anti-PLA2R concentrations decreased to <14 relative units (RU)/ml in 43 of 48 patients with PLA2R-related MN. After Obinutuzumab administration, a significant reduction in 24-hour urine protein and increase in serum albumin were observed. No serious adverse events were observed. Conclusion: Obinutuzumab may represent a promising and well-tolerated therapeutic option for individuals with primary MN. The potential of Obinutuzumab was highlighted as an initial therapy for primary MN.

3.
Cell Prolif ; : e13728, 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39155403

RESUMEN

The cytoskeleton is essential for mechanical signal transduction and autophagy. However, few studies have directly demonstrated the contribution of the cytoskeleton to mechanical stress-induced autophagy. We explored the role of the cytoskeleton in response to compressive force-induced autophagy in human cell lines. Inhibition and activation of cytoskeletal polymerization using small chemical molecules revealed that cytoskeletal microfilaments are required for changes in the number of autophagosomes, whereas microtubules play an auxiliary role in mechanical stress-induced autophagy. The intrinsic mechanical properties and special intracellular distribution of microfilaments may account for a large proportion of compression-induced autophagy. Our experimental data support that microfilaments are core components of mechanotransduction signals.

4.
Clin Ther ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39112102

RESUMEN

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.

5.
Materials (Basel) ; 17(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39124346

RESUMEN

Concrete structures frequently manifest diverse defects throughout their manufacturing and usage processes due to factors such as design, construction, environmental conditions and distress mechanisms. In this paper, a multilevel convolutional neural network (CNN) combined with array ultrasonic testing (AUT) is proposed for identifying the locations of hole defects in concrete structures. By refining the detection area layer by layer, AUT is used to collect ultrasonic signals containing hole defect information, and the original echo signal is input to CNN for the classification of hole locations. The advantage of the proposed method is that the corresponding defect location information can be obtained directly from the input ultrasonic signal without manual discrimination. It effectively addresses the issue of traditional methods being insufficiently accurate when dealing with complex structures or hidden defects. The analysis process is as follows. First, COMSOL-Multiphysics finite element software is utilized to simulate the AUT detection process and generate a large amount of ultrasonic echo data. Next, the extracted signal data are trained and learned using the proposed multilevel CNN approach to achieve progressive localization of internal structural defects. Afterwards, a comparative analysis is conducted between the proposed multilevel CNN method and traditional CNN approaches. The results show that the defect localization accuracy of the proposed multilevel CNN approach improved from 85.38% to 95.27% compared to traditional CNN methods. Furthermore, the computation time required for this process is reduced, indicating that the method not only achieves higher recognition precision but also operates with greater efficiency. Finally, a simple experimental verification is conducted; the results show that this method has strong robustness in recognizing noisy ultrasonic signals, provides effective solutions, and can be used as a reference for future defect detection.

6.
ACS Nano ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177438

RESUMEN

Hybrid nanomaterials with controllable structures and diverting components have attracted significant interest in the functional materials field. Here, we develop a solvent evaporation-induced self-assembly (EISA) strategy to synthesize nanosheet-assembled phosphomolybdic acid (H3PMo)-alumina hybrid hollow spheres. The resulting nanoflowers display a high surface area (up to 697 m2 g-1), adjustable diameter, high chemical/thermal stability, and especially molecularly dispersed H3PMo species. By employing various microscopic and spectroscopic techniques, the formation mechanism is elucidated, revealing the simultaneous control of the morphology by heteropoly acids and water through the water-induced Kirkendall effect. The versatility of the synthesis method is demonstrated by varying surfactants, heteropoly acids, and metal oxide precursors for the facile synthesis of hybrid metal oxides. Spherical hybrid alumina serves as an attractive support material for constructing metal-acid bifunctional catalysts owing to its advantageous surface area, acidity, and mesoporous microenvironment. Pt-loaded hollow flowers exhibit excellent catalytic performance and exceptional stability in the hydrodeoxygenation of vanillin with recyclability for up to 10 cycles. This research presents an innovative strategy for the controllable synthesis of hybrid metal oxide nanospheres and hollow nanoflowers, providing a multifunctional platform for diverse applications.

7.
PLoS One ; 19(8): e0308636, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39116168

RESUMEN

Aiming at the characteristics that the signal noise ratio (SNR) gradually decreases from the near to far range of the swath, an adaptive phase filtering algorithm based on Goldstein filtering and combined with multiple quality-guided graphs was proposed. Firstly, the components used to determine the filtering parameters were obtained through residue density, pseudo-coherence coefficient and pseudo-SNR, the three quality-guided graphs. Then, the filter parameters were calculated by weighting the three components. Finally, the size of filtering window was determined according to the account of residues, and the interferometric phase noise was removed in frequency domain. Simulated data, TSX/TDX data and airborne interferometric imaging radar altimeter data were used to verify the performance of the new algorithm. Compared with the results of Goldstein filtering and its improved algorithms, the results showed that the proposed algorithm can effectively filter out phase noise while maintaining the edge characteristics of interferometric fringe. The section of filtering result can well match with the section of simulated pure interfeometric phase. Moreover, the algorithm proposed in this paper can effectively remove the noise in the interferogram of TSX/TDX sea ice data, and the residues' filtering rate was above 86%, which can effectively remove the phase residues of the sea ice surface while maintaining the characteristics of the sea ice edge. Experimental results showed that the new algorithm provides an effective phase noise filtering method for imaging radar altimeter data processing.


Asunto(s)
Algoritmos , Interferometría , Radar , Relación Señal-Ruido , Interferometría/métodos
8.
Sci Rep ; 14(1): 19745, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187564

RESUMEN

In practical engineering applications, factors like dust adhesion and environmental changes can cause photovoltaic arrays to exhibit multiple peaks in output power. An optimization algorithm with global optimization capability is needed to track its maximum power. In this regard, this paper proposes an improved marine predator algorithm (IMPA) to extract the maximum power point of photovoltaic system under complex solar irradiation conditions. To overcome the issues in the traditional marine predator algorithm (MPA), the opposition-based learning(OBL) strategy is introduced in IMPA, and the sine cosine algorithm (SCA) is integrated into the iteration stage to enhance the search ability of the algorithm. Furthermore, the low-order converter in the traditional MPPT control system is replaced by the Zeta converter, which increases the operating voltage range. Ultimately, simulation results demonstrate that the MPPT based on IMPA has higher tracking efficiency and shorter response time.The experimental results also indicate the practical feasibility of this method, as well as its high level of stability and robustness.

9.
Water Res X ; 24: 100243, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39188329

RESUMEN

The goal of this study was to assess the impacts or benefits of sludge in situ reduction (SIR) within wastewater treatment processes with relation to global warming potential in wastewater treatment plants, with a comprehensive consideration of wastewater and sludge treatment. The anaerobic side-stream reactor (ASSR) and the sludge process reduction activated sludge (SPRAS), two typical SIR technologies, were used to compare the carbon footprint analysis results with the conventional anaerobic - anoxic - oxic (AAO) process. Compared to the AAO, the ASSR with a typical sludge reduction efficiency (SRE) of 30 % increased greenhouse gas (GHG) emissions by 1.1 - 1.7 %, while the SPRAS with a SRE of 74 % reduced GHG emissions by 12.3 - 17.6 %. Electricity consumption (0.025 - 0.027 kg CO2-eq/m3), CO2 emissions (0.016 - 0.059 kg CO2-eq/m3), and N2O emissions (0.009 - 0.023 kg CO2-eq/m3) for the removal of secondary substrates released from sludge decay in the SIR processes were the major contributor to the increased GHG emissions from the wastewater treatment system. By lowering sludge production and the organic matter content in the sludge, the SIR processes significantly decreased the carbon footprints associated with sludge treatment and disposal. The threshold SREs of the ASSR for GHG reduction were 27.7 % and 34.6 % for the advanced dewatering - sanitary landfill and conventional dewatering - drying-incinerating routes, respectively. Overall, the SPRAS process could be considered as a cost-effective and sustainable low-carbon SIR technology for wastewater treatment.

10.
Metabolites ; 14(8)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39195513

RESUMEN

This study aimed to explore the effects of Bacillus amyloliquefaciens GSBa-1 treatment on anthracnose disease resistance and the metabolism of reactive oxygen species (ROS) and phenylpropanoids in mangoes during storage. Mangoes were soaked in a solution containing 1 × 108 CFU/mL of B. amyloliquefaciens GSBa-1. The anthracnose disease incidence, disease index, respiration intensity, ethylene release, reactive oxygen species content, and the activities of related metabolic enzymes, phenylpropanoid-related metabolic enzymes, and phenolic acids in the skin and pulp of mangoes were investigated under normal temperature storage conditions. The results showed that the antagonistic bacterial treatment (ABT) did not significantly inhibit the growth of Colletotrichum gloeosporioides in vitro. However, it significantly reduced the incidence of mango anthracnose disease when applied to the mango peel. ABT enhanced the latent resistance of mango to anthracnose disease by activating its reactive oxygen and phenylpropanoid metabolism. It maintained higher levels of ROS production and elimination in the peel. Moreover, it rapidly activated manganese superoxide dismutase, induced the accumulation of H2O2, and enhanced the activity of manganese superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase in the mango peel. Furthermore, ABT activated phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, 4-coumaroyl-CoA ligase, and cinnamyl alcohol dehydrogenase in the mango peel and pulp, promoting the accumulation of antifungal phenolic acids such as gallic acid, catechins, and ellagic acid. Bacillus amyloliquefaciens GSBa-1 may be a potent inhibitor of mango anthracnose, primarily enhancing the resistance of mangoes to anthracnose by synergistically activating ROS in the peel and phenylpropanoid metabolism in the pulp, thereby reducing the incidence of anthracnose effectively.

11.
J Am Chem Soc ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196310

RESUMEN

Nanoparticle (NP) delivery systems have been actively exploited for cancer therapy and vaccine development. Nevertheless, the major obstacle to targeted delivery lies in the substantial liver sequestration of NPs. Here we report a DNA-engineered approach to circumvent liver phagocytosis for enhanced tumor-targeted delivery of nanoagents in vivo. We find that a monolayer of DNA molecules on the NP can preferentially adsorb a dysopsonin protein in the serum to induce functionally invisibility to livers; whereas the tumor-specific uptake is triggered by the subsequent degradation of the DNA shell in vivo. The degradation rate of DNA shells is readily tunable by the length of coated DNA molecules. This DNA-engineered invisibility cloaking (DEIC) is potentially generic as manifested in both Ag2S quantum dot- and nanoliposome-based tumor-targeted delivery in mice. Near-infrared-II imaging reveals a high tumor-to-liver ratio of up to ∼5.1, approximately 18-fold higher than those with conventional nanomaterials. This approach may provide a universal strategy for high-efficiency targeted delivery of theranostic agents in vivo.

12.
Res Sq ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39108475

RESUMEN

This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating® (CDR®). Using the SOMAscan assay, we detected subtle increases in specific ubiquitin enzymes associated with proteostasis in mutation carriers (MCs) up to two decades before the estimated symptom onset. This was followed by more pronounced elevations of UPS-activating enzymes, including E2 and E3 proteins, and ubiquitin-related modifiers. Our findings also demonstrated consistent correlations between UPS proteins and CSF biomarkers such as Aß42/40 ratio, total tau, various phosphorylated tau species to total tau ratios (ptau181/T181, ptauT205/T205, ptauS202/S202, ptauT217/T217), and MTBR-tau243, alongside Neurofilament light chain (NfL) and the CDR®. Notably, a positive association was observed with imaging markers (PiB PET, tau PET) and a negative correlation with markers of neurodegeneration (FDG PET, MRI), highlighting a significant link between UPS dysregulation and neurodegenerative processes. The correlations suggest that the increase in multiple UPS proteins with rising tau levels and tau-tangle associated markers, indicating a potential role for the UPS in relation to misfolded tau/neurofibrillary tangles (NFTs) and symptom onset. These findings indicate that elevated CSF UPS proteins in DIAD MCs could serve as early indicators of disease progression and suggest a link between UPS dysregulation and amyloid plaque, tau tangles formation, implicating the UPS as a potential therapeutic target in AD pathogenesis.

13.
Sci Total Environ ; 950: 175425, 2024 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-39134261

RESUMEN

Plant non-structural carbohydrates (NSCs), which largely comprise starch and soluble sugars, are essential energy reserves to support plant growth and physiological functions. While it is known that increasing global deposition of nitrogen (N) affects plant concentration of NSCs, quantification of seasonal responses and drivers of woody species leaf and root NSCs to N addition at larger spatial scales remains lacking. Here, we systematically analyzed data from 53 field experiments distributed across China, comprising 1202 observations, to test for effects of N addition on woody plant leaf and root NSCs across and within growing and non-growing seasons. We found (1) no overall effects of N addition on the concentrations of leaf and root NSCs, soluble sugars or starch during the growing season or the non-growing season for leaves. However, N addition decreased root NSC and starch concentrations by 13.8 % and 39.0 %, respectively, and increased soluble sugars concentration by 15.0 % during the non-growing season. (2) Shifts in leaf NSC concentration under N addition were driven by responses by soluble sugars in both seasons, while shifts in root NSC were driven by soluble sugars in the non-growing season and starch and soluble sugars in the growing season. (3) Relationships between N, carbon, and phosphorus stoichiometry with leaf and root NSCs indicated effects of N addition on woody plant NSCs allocation through impacts on plant photosynthesis, respiration, and growth. (4) Effects of N addition on leaf and root NSCs varied with plant functional types, where effects were more pronounced in roots than in leaves during the non-growing season. Overall, our results reveal divergent responses of woody plant leaf and root NSCs to N addition within non-growing season and highlight the role of ecological stoichiometry and plant functional types in woody plant allocation patterns of NSCs in response to ongoing N deposition under global change.


Asunto(s)
Nitrógeno , Hojas de la Planta , Raíces de Plantas , Estaciones del Año , China , Carbohidratos/análisis , Metabolismo de los Hidratos de Carbono
14.
Res Sq ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39108494

RESUMEN

Initially focused on the European population, multiple genome-wide association studies (GWAS) of complex diseases, such as type-2 diabetes (T2D), have now extended to other populations. However, to date, few ancestry-matched omics datasets have been generated or further integrated with the disease GWAS to nominate the key genes and/or molecular traits underlying the disease risk loci. In this study, we generated and integrated plasma proteomics and metabolomics with array-based genotype datasets of European (EUR) and African (AFR) ancestries to identify ancestry-specific muti-omics quantitative trait loci (QTLs). We further applied these QTLs to ancestry-stratified T2D risk to pinpoint key proteins and metabolites underlying the disease-associated genetic loci. We nominated five proteins and four metabolites in the European group and one protein and one metabolite in the African group to be part of the molecular pathways of T2D risk in an ancestry-stratified manner. Our study demonstrates the integration of genetic and omic studies of different ancestries can be used to identify distinct effector molecular traits underlying the same disease across diverse populations. Specifically, in the AFR proteomic findings on T2D, we prioritized the protein QSOX2; while in the AFR metabolomic findings, we pinpointed the metabolite GlcNAc sulfate conjugate of C21H34O2 steroid. Neither of these findings overlapped with the corresponding EUR results.

15.
J Neuroinflammation ; 21(1): 197, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39113081

RESUMEN

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined. METHODS: Using microarray analysis, we analyzed the lncRNA levels in MG. By bioinformatics analysis, LINC01566 was found to potentially play an important role in MG. First, qRT‒PCR was performed to verify the LINC1566 expressions in MG patients. Then, fluorescence in situ hybridization was conducted to determine the localization of LINC01566 in CD4 + T cells. Finally, the impact of LINC01566 knockdown or overexpression on CD4 + T-cell function was also analyzed using flow cytometry and CCK-8 assay. A dual-luciferase reporter assay was used to validate the binding of the TF FOSL1 to the LINC01566 promoter. RESULTS: Based on the lncRNA microarray and differential expression analyses, we identified 563 differentially expressed (DE) lncRNAs, 450 DE mRNAs and 19 DE TFs in MG. We then constructed a lncRNA-TF-mRNA network. Through network analysis, we found that LINC01566 may play a crucial role in MG by regulating T-cell-related pathways. Further experiments indicated that LINC01566 is expressed at low levels in MG patients. Functionally, LINC01566 is primarily distributed in the nucleus and can facilitate CD4 + T-cell apoptosis and inhibit cell proliferation. Mechanistically, we hypothesized that LINC01566 may negatively regulate the expressions of DUSP3, CCR2, FADD, SIRPB1, LGALS3 and SIRPB1, which are involved in the T-cell activation pathway, to further influence the cellular proliferation and apoptosis in MG. Moreover, we found that the effect of LINC01566 on CD4 + T cells in MG was mediated by the TF FOSL1, and in vitro experiments indicated that FOSL1 can bind to the promoter region of LINC01566. CONCLUSIONS: In summary, our research revealed the protective roles of LINC01566 in clinical samples and cellular experiments, illustrating the potential roles and mechanism by which FOSL1/LINC01566 negatively regulates CD4 + T-cell activation in MG.


Asunto(s)
Linfocitos T CD4-Positivos , Activación de Linfocitos , Miastenia Gravis , Proteínas Proto-Oncogénicas c-fos , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Miastenia Gravis/metabolismo , Miastenia Gravis/inmunología , Miastenia Gravis/genética , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Adulto
16.
Diabetes Metab Syndr Obes ; 17: 2955-2966, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135891

RESUMEN

Background: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied. Methods: A total of 615 patients with T2D were selected by convenient sampling. The patients were investigated with the International Physical Activity Questionnaire (IPAQ-S). Moreover, biochemical indices were collected, and the progression of the body composition of the subjects was determined via dual-energy X-ray absorptiometry (DXA). The variables included lumbar bone mineral density (LSBMD), femoral neck bone mineral density (FNBMD), hip bone mineral density (HBMD), whole-body bone mineral density (TBMD), limb skeletal muscle mass index (ASMI), whole-body fat percentage (B-FAT) and trunk fat percentage (T-FAT). Moreover, the levels of physical activity (high level of physical activity [H-PA], medium level of physical activity [M-PA] and low level of physical activity [L-PA]) were divided into three groups to analyze the changes in patient body composition with changes in physical activity level. Results: One-way analysis of variance showed that ß-CTX, TP1NP, HbA1c, B-FAT and T-FAT increased significantly (p<0.05), while 25(OH)D, LSBMD, FNBMD, HBMD, TBMD and ASMI decreased significantly (p<0.001) with the decrease of physical activity. However, there was no significant difference in serum lipids between lnHOMA-ir and lnHOMA-ß (p>0.05). Multiple linear regression model was established to gradually adjust for clinical confounding factors. It was found that physical activity level was independently positively correlated with LSBMD, FNBMD, HBMD, TBMD, and ASMI, and was independently negatively correlated with B-FAT and T-FAT in patients with type 2 diabetes. Conclusion: A lack of physical activity is an independent risk factor for decreased bone mineral density, decreased skeletal muscle content and increased fat content in patients with T2D.

18.
Adv Healthc Mater ; : e2401451, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39021319

RESUMEN

Meticulously engineered nanomaterials achieve significant advances in the diagnosis and therapy of solid tumors by improving tumor delivery efficiency; and thereby, enhancing imaging and therapeutic efficacy. Currently, polydopamine (PDA) attracts widespread attention because of its biocompatibility, simplicity of preparation, abundant surface groups, and high photothermal conversion efficiency, which can be applied in drug delivery, photothermal therapy, theranostics, and other nanomedicine fields. Inspired by PDA structures that are rich in catechol and amino functional groups that can coordinate with various metal ions, which have charming qualities and characteristics, metal-coordinated PDA structures are exploited for tumor theranostics, but are not thoroughly summarized. Herein, this review summarizes the recent progress in the fabrication of metal-coordinated PDA structures and their availabilities in tumor imaging and therapy, with further in-depth discussion of the challenges and future perspectives of metal-coordinated PDA structures, with the aim that this systematic review can promote interdisciplinary intersections and provide inspiration for the further growth and clinical translation of PDA materials.

20.
Sci Rep ; 14(1): 16646, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025944

RESUMEN

This paper proposed a frequency reconfigurable antenna that utilizes a multilayer structure of liquid crystal (LC) material. This antenna design incorporates a three-layer stacked structure to create an LC-injected cavity. The inverted microstrip line structure is designed to be in contact with the LC, serving as both a radiating element and a bias electrode. A parasitic patch is placed at the top of the antenna to enhance bandwidth. To prevent interference with DC and RF sources, a bias tee is integrated into the microstrip line input. Experimental results demonstrate that the proposed antenna exhibits excellent impedance matching and stable radiation patterns within the operational frequency range. By comparing the simulated performance of the existing LC antenna with our proposed design, the bandwidth is tripled at a center frequency of 30.3 GHz. In addition, the effective area of the proposed reconfigurable antenna (154 mm2) is 24.6% of the area of the previous reconfigurable antenna (625 mm2).

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