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1.
JACC Case Rep ; 29(18): 102552, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39359997

ABSTRACT

Coronary cameral fistulas are rare anomalous connections between coronary circulation and cardiac chambers. Coronary cameral fistulas are often asymptomatic but may cause volume overload on impacted chambers, and also create high velocity turbulent diastolic flow which may predispose patients to endocarditis. This paper presents a unique case of infective endocarditis revealed by intracerebral hemorrhage with a mycotic aneurysm in a patient who was found to have a nonvalvular infective endocarditis located on the mitral anterolateral papillary muscle, at the ventricular site of entrance of a large coronary cameral fistula.

2.
Nat Commun ; 15(1): 8494, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39353930

ABSTRACT

Increasing the molecular weight while maintaining mono-dispersity has been proved crucial in innovating high-performance photovoltaic materials in giant oligomeric acceptors. However, developing efficient giant oligomeric donors to replace the batch-varied polymers remains challenging due to a lack of design principles. Here, by designing two unique isomeric rhodanine-based linkers, we successfully regulate the assembly behaviors of giant dimeric donors (G-Dimer-Ds) and fabricate the first all-giant-oligomer OSCs pairing with giant dimeric acceptor DY. Multiple characterizations demonstrate the small homo-molecular interaction with strong thermal-driven assembly capability in G-Dimer-D2 simultaneously facilitates reducing energetic disorder, improving charge transport and obtaining stable morphology, resulting in a satisfactory efficiency of 15.70% and long-term photostability with an extrapolated T80 of ca.10,000 hours, and further enhancing thermal-driven assembly promotes efficiency of 16.05%. Our results provide construction approaches on efficient giant donors, and propose a promising type of OSC with completely definite structures, high efficiency and superior stability.

3.
Cancer Lett ; : 217284, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39366545

ABSTRACT

Chemoresistance remains a formidable challenge in pancreatic ductal adenocarcinoma (PDAC) treatment, necessitating a comprehensive exploration of underlying molecular mechanisms. This work aims to investigate the dynamic epigenetic landscape during the development of gemcitabine resistance in PDAC, with a specific focus on super-enhancers and their regulatory effects. We employed well-established gemcitabine-resistant (Gem-R) PDAC cell lines to perform high-throughput analyses of the epigenome, enhancer connectome, and transcriptome. Our findings revealed notable alterations in the epigenetic landscape and genome architecture during the transition from gemcitabine-sensitive to -resistant PDAC cells. Remarkably, we observed substantial plasticity in the activation status of super-enhancers, with a considerable proportion of these cis-elements becoming deactivated in chemo-resistant cells. Furthermore, we pinpointed the NDRG1 super-enhancer (NDRG1-SE) as a crucial regulator in gemcitabine resistance among the loss-of-function super-enhancers. NDRG1-SE deactivation induced activation of WNT/ß-catenin signaling, thereby conferring gemcitabine resistance. This work underscores a NDRG1 super-enhancer deactivation-driven ß-catenin pathway activation as a crucial regulator in the acquisition of gemcitabine-resistance. These findings advance our understanding of PDAC biology and provide valuable insights for the development of effective therapeutic approaches against chemoresistance in this malignant disease.

4.
J Ethnopharmacol ; : 118912, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39369926

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Saposhnikovia divaricata (Turcz.) Schisck, a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood. AIM OF THE STUDY: To explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model. MATERIAL AND METHODS: Surface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting. RESULTS: CHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), TNF-α, and IL-17A proteins in the joints of CHR-treated mice. CONCLUSION: CHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.

5.
Curr Pharm Des ; 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39350558

ABSTRACT

INTRODUCTION: The hormone Fibroblast Growth Factor 21 (FGF21), as a novel glucose and lipid metabolism regulator, has become a promising therapeutic target for metabolic disorders. Camel, the characteristic species adapted to arid and semi-arid desert climates, has shown exceptional ability for the regulation of lipid reserve and utilization. METHODS: This study found camel FGF21 to have a stronger regulatory effect for downstream signaling compared to human and mouse through sequence analysis and FGF21 signal downstream markers detection. FGF21 protein has been found to have one potential drug-binding pocket, which has been predicted using the CavityPlus online platform. Four small compounds, resorcinol monoacetate, tropisetron, nylidrin, and stiripentol, targeting FGF21 protein have been screened by molecular docking using the UCSF DOCK6 program. RESULTS: The inhibitory concentration 50% (IC50) values of the four small compounds have been determined by MTT assay and the values have been simulated by the software GraphPad Prism. The biological effect testing has indicated the four compounds to be involved in the regulation of the FGF21 signaling pathway and serve as agonists for FGF21 signaling transduction. While the blocking experiment of compound and protein cotreatment has indicated the four small compounds to not inhibit FGF21-induced pathway activation. Even, resorcinol monoacetate and stiripentol have shown to synergistically activate downstream signaling pathways with the FGF21 protein. CONCLUSION: This study has provided new ideas for developing therapeutic strategies based on FGF21 protein modification and exploring novel disease treatment strategies based on the compounds-protein combination.

6.
Nurs Crit Care ; 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39308137

ABSTRACT

BACKGROUND: Hyponatraemia is a prevalent electrolyte disturbance observed in critically ill patients. The rapid correction of low plasma sodium levels by continuous renal replacement therapy (CRRT) carries the risk of developing osmotic demyelination syndrome (ODS), which can be prevented by implementing an individualized CRRT method. AIM: This study aims to introduce a CRRT protocol for the safe and gradual correction of severe hyponatraemia. STUDY DESIGN: This retrospective case series study was conducted in an intensive care unit (ICU). All four patients with severe hyponatraemia (<125 mmol/L) and renal failure between October 1, 2022, and September 30, 2023, were treated by CRRT with sterile water and regional citrate anticoagulation (RCA). Data on patient demographics, laboratory biochemical parameters, urine outputs and CRRT-related adverse events were collected. Laboratory parameters and urine outputs were compared by paired t-tests before and after CRRT. RESULTS: After CRRT, sodium levels were significantly increased (112.7 ± 6.7 vs. 141.9 ± 2.8 mmol/L, p = .005). Abnormal urine outputs, potassium, creatinine and bicarbonate were corrected (p for all <.05). Safe and gradual correction of hyponatraemia and internal environmental dysregulation was achieved in all patients without any complications related to CRRT, particularly ODS. CONCLUSION: It is a novel and simple strategy to correct severe hyponatraemia effectively while ensuring the safety of patients that can be easily implemented by experienced nurse staff. RELEVANCE TO CLINICAL PRACTICE: The sterile water-based protocol for postfilter dilution is safe to correct severe hyponatraemia with RCA and can be easily performed by experienced critical care nurses according to the precalculated formula. CRRT-trained, experienced ICU nurses are competent to initiate and adjust sterile water infusion discretely to prevent overcorrection of hyponatraemia.

7.
Article in English | MEDLINE | ID: mdl-39308450

ABSTRACT

How tissues develop distinct structures remains poorly understood. We propose herein the Lego hypothesis of tissue morphogenesis, which states that during tissue morphogenesis, the topographical properties of cell surface adhesion molecules can be dynamically altered and polarised by regulating the spatiotemporal expression and localization of orientational cell adhesion (OCA) molecules cell-autonomously and non-cell-autonomously, thus modulating cells into unique Lego pieces for self-assembling into distinct cytoarchitectures. This concept can be exemplified by epithelial morphogenesis, in which cells are coalesced into a sheet by many types of adhesions. Among them, parallel OCAs (pOCAs) at the lateral cell membranes are essential for configuring cells in parallel. Major pOCAs include Na+/K+-ATPase-mediated adhesions, Crumbs-mediated adhesions, tight junctions, adherens junctions, and desmosomes. These pOCAs align in stereotypical orders along the apical-to-basal axis, and their absolute positioning is also regulated. Such spatial organization of pOCAs underlies proper epithelial morphogenesis. Thus, a key open question about tissue morphogenesis is how to regulate OCAs to make compatible adhesive cellular Lego pieces for tissue construction.

8.
Small ; : e2405736, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39319520

ABSTRACT

Elucidating the growth mechanism of carbon nanotubes (CNTs) is critical to obtaining CNTs with desired structures and tailored properties for their practical applications. With atomic resolution imaging, in situ transmission electron microscopy (TEM) has been a key technique to reveal the microstructure and dynamics of CNTs in real time. In this review, recent advances in the development of in situ TEM with different types of environmental reactors will be introduced. The catalytic growth mechanisms of CNTs revealed by in situ TEM under realistic conditions are discussed from fundamental thermodynamics and kinetics to the detailed nucleation, growth, and termination mechanisms, including the state and phase of active catalysts, interfacial connections between catalyst and growing CNTs, and catalyst-related growth kinetics of CNTs. Great progresses have been made on how a CNT nucleates, grows and terminates, focusing on the interface dynamics and kinetic fluctuations. Finally, challenges and future directions for understanding the atomic dynamics under the real growth conditions are proposed. It is expected that breakthroughs in the fundamental growth mechanisms will pave the way to the ultimate goal of designing and controlling the atomic structures of CNTs for their applications in various devices.

9.
Ann Transplant ; 29: e943610, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39285624

ABSTRACT

BACKGROUND This study aimed to evaluate the effectiveness of implementing evidence-based preoperative nursing interventions in reducing postoperative infections and intensive care unit (ICU) length of stay among liver transplant recipients. MATERIAL AND METHODS A controlled study was conducted, comparing postoperative outcomes between an intervention group receiving standardized, evidence-based preoperative care and a control group receiving routine preoperative care. Patients undergoing elective liver transplantation from September 2020 to March 2021 were included and assigned to either the intervention or control group. The intervention group received preoperative interventions based on best available evidence, while the control group received standard preoperative care. The primary outcomes measured were postoperative infection rates and length of ICU stay. RESULTS In the control group the overall Intensive Care Unit (ICU) length of stay was 3 days and the infection rate was 33.30%, while in the intervention group it was 3 days and 13.80% (P<0.05). There was no significant difference in the length of ICU stay between the control and the intervention groups (P>0.05). There was a significant improvement in the awareness, acceptance, and compliance of doctors and nurses. CONCLUSIONS Using the best evidence-based intervention for preoperative nursing of liver transplantation patients can standardize preoperative nursing behavior. Although we did not find significant differences in outcomes before and after the intervention, it is necessary to prevent postoperative infection and improve nursing compliance.


Subject(s)
Length of Stay , Liver Transplantation , Postoperative Complications , Preoperative Care , Humans , Liver Transplantation/adverse effects , Female , Male , Preoperative Care/methods , Middle Aged , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Adult , Evidence-Based Practice , Intensive Care Units
10.
Sci Total Environ ; 954: 176482, 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39317259

ABSTRACT

Debris flows are a prevalent mountain hazard that poses severe risks to human life and property. Debris-flow hazard assessments at the regional scale are vital for risk management, which establish spatial associations between debris flows and their influencing factors based on specific evaluation units. Different spatial scales of evaluation units can influence the spatial attributes and associations obtained by statistics, and further affect the accuracy of hazard assessments. However, there is limited consensus regarding the optimal spatial scale of evaluation units for debris-flow hazard assessment. To address this issue, six different scales of grid cells and forty influencing factors related to topography, material sources, hydrology, and human activities are analyzed by the geographical detector model to assess the debris-flow hazards in the Dadu River basin, China. The results reveal that over 92 % of debris-flow points fall within hazardous zones across all spatial scales, confirming the effectiveness of the assessment model. Topography, particularly local gully topography, dominates the debris-flow occurrence in the study area, while human activities also significantly contribute. As the spatial scale of evaluation units increases, the explanatory power of the influencing factors improves, with the 90 % quantile ranging from 0.23 to 0.46. This result suggests that larger spatial scales weaken the spatial characteristics of the factors. The finer and more informative the factors are, the more sensitive to spatial scale effects. The 10 km × 10 km is identified as the optimal spatial scale, which effectively preserves the local spatial characteristics while avoiding information loss or overload. These findings provide valuable insights for enhancing the accuracy of hazard assessments and improving the efficiency of risk management.

11.
Biomed Pharmacother ; 180: 117504, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39341079

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of reproductive age. The syndrome is characterized by androgen excess, ovarian dysfunction, insulin resistance (IR) and obesity, with an elevated risk of developing long-term complications, including cardiovascular disease and type 2 diabetes mellitus (T2D). The gut microbiota plays a role in the pathogenesis of PCOS by influencing the host's endocrine, metabolic and inflammatory state, as well as the gut-brain axis. Gut microbiota-derived extracellular vesicles (GMEVs) are lipid bilayer nanoparticles secreted by the gut microbiota and contain a variety of components, including proteins, lipids and nucleic acids. They serve as signaling molecules, facilitating bacterial-bacterial and bacterial-host communications. Bacterial extracellular vesicles (BEVs) affect host cells through the delivery of bioactive substances and physical interaction through membrane components, thereby participating in the regulation of metabolic, immune, and other cellular processes. Furthermore, BEVs, which are distinguished by low toxicity, high biocompatibility and stability, and the capacity to cross biological barriers, present a promising avenue for the development of novel drug delivery systems. The isolation and characterization of BEVs also facilitate the investigation of disease-specific biomarkers. Consequently, BEVs have immense potential for a range of medical research applications, including disease diagnosis and treatment. This article discusses the potential therapeutic effects and mechanisms of GMEVs in the treatment of PCOS.

12.
Gels ; 10(9)2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39330159

ABSTRACT

The application of fish gelatin (FG) is limited due to its poor mechanical properties and thermal stability, both of which could be significantly improved by gellan gum (GG) found in previous research. However, the FG/GG composite hydrogel was brittle and easily damaged by external forces. It was found that the composite hydrogel with Fe2(SO4)3 showed good flexibility and self-healing properties in the pre-experiment. Thus, the synergistic effect of FG, GG and Fe2(SO4)3 on the mechanical properties of the composite hydrogel was investigated in this study. According to one-way experiments, response surface tests and Texture Profile Analysis, it was found that under the optimum condition of FG concentration 186.443 g/L, GG concentration 8.666 g/L and Fe2(SO4)3 concentration 56.503 g/L, the springiness of the composite cylindrical hydrogel with the height of 25 mm formed in 25 mL beakers (bottom diameter 30 mm) was 7.602 mm. Determination of the rheological properties, compression performance, adhesive performance and self-healing properties showed that the composite hydrogel had good thermal stability, flexibility and self-healing properties with good adhesion, skin compliance and compressive strength, and it was easy to remove. The composite hydrogel showed strong antimicrobial activity against A. salmonicida and V. parahaemolyticus. All hydrogels showed a uniform and porous structure. The 3D structure of the composite hydrogel was much looser and more porous than the pure FG hydrogel. The flexible and self-healing composite hydrogel with some antimicrobial activity is suitable for the development of medical dressings, which broadens the applications of the composite hydrogel.

13.
Chem Commun (Camb) ; 60(78): 10890-10893, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39253791

ABSTRACT

Three ball-milling methodologies were developed to synthesize bespoke multi-metallic K-doped Cu-Fe/ZnO-Al2O3 catalysts for the hydrogenation of carbon dioxide. The catalytic performance of the catalysts was benchmarked against their solution-based counterparts. The catalysts synthesized by ball milling are greener, showing smaller particles, with different selectivity towards oxygenate products.

14.
Food Chem ; 463(Pt 1): 141029, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39241428

ABSTRACT

The enhancement of saltiness induced by odrants perceived from the retronasal cavity during Larou oral processing was analyzed. During the oral processing of Xiangtan Larou, the smoky attribute was the dominant when chewing 0-15 times, followed by the savory (15-24 times) and meaty (24-42 times). Partial least squares analysis predicted 33 aroma compounds from the retronasal cavity significantly (p < 0.05) contributing to the aroma perception. A total of 12 aroma compounds with saltiness-enhancement ability were confirmed by odorant-NaCl mixture model experiments. Results revealed that 2-methoxy-4-vinylphenol (1.00-1000.00 µg/L) had the strongest enhancing effect on saltiness at NaCl (2969.85 mg/L), followed by diallyl sulfide (0.156-2.50 µg/L), 2,5-dimethylthiophene (0.156-50.00 µg/L), 2,6-dimethylphenol (1.00-100.00 µg/L), 2,5-dimethylpyrazine (0.391-50.00 µg/L), and 2,3-butanedione (0.50-100.0 µg/L). The sulfur-containing, nitrogen-containing, and phenolic odorants with savory, roasty, sulfide, meaty or smoky, attributes showed the better ability in saltiness enhancement.

15.
J Multidiscip Healthc ; 17: 4373-4382, 2024.
Article in English | MEDLINE | ID: mdl-39262823

ABSTRACT

Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

16.
bioRxiv ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39253493

ABSTRACT

Deciphering cell identity genes is pivotal to understanding cell differentiation, development, and many diseases involving cell identity dysregulation. Here, we introduce SCIG, a machine-learning method to uncover cell identity genes in single cells. In alignment with recent reports that cell identity genes are regulated with unique epigenetic signatures, we found cell identity genes exhibit distinctive genetic sequence signatures, e.g., unique enrichment patterns of cis-regulatory elements. Using these genetic sequence signatures, along with gene expression information from single-cell RNA-seq data, enables SCIG to uncover the identity genes of a cell without a need for comparison to other cells. Cell identity gene score defined by SCIG surpassed expression value in network analysis to uncover master transcription factors regulating cell identity. Applying SCIG to the human endothelial cell atlas revealed that the tissue microenvironment is a critical supplement to master transcription factors for cell identity refinement. SCIG is publicly available at https://github.com/kaifuchenlab/SCIG , offering a valuable tool for advancing cell differentiation, development, and regenerative medicine research.

17.
Qual Life Res ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240422

ABSTRACT

PURPOSE: To identify symptom clusters (SCs) in lung cancer patients undergoing chemotherapy and explore their impact on health-related quality of life (HRQoL). METHODS: Patients were invited to complete the Chinese version of the M.D. Anderson Symptom Inventory with the Lung Cancer Module and the Quality of Life Questionnaire-core 30. Network analysis was employed to identify SCs. The associations between SCs and each function of HRQoL were examined using the Pearson correlation matrix. Multiple linear regression was applied to analyze the influencing factors of each function of HRQoL. RESULTS: A total of 623 lung cancer patients who were receiving chemotherapy were recruited. The global health status of lung cancer patients was 59.71 ± 21.09, and 89.73% of patients developed symptoms. Three SCs (Somato-psychological SC, Respiratory SC, and Gastrointestinal SC) were identified, and Somato-psychological SC and Gastrointestinal SC were identified as influencing factors for HRQoL in lung cancer patients. CONCLUSION: Most lung cancer patients who undergo chemotherapy experience a range of symptoms, which can be categorized into three SCs. The Somato-psychological SC and Gastrointestinal SC negatively impacted patients' HRQoL. Health care providers should prioritize monitoring these SCs to identify high-risk patients early and implement targeted preventive and intervention measures for each SC, aiming to alleviate symptom burden and enhance HRQoL.

18.
Food Chem X ; 23: 101756, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39295963

ABSTRACT

Studies have demonstrated the protective effect of milk fat globule membrane (MFGM) on probiotics in harsh environments. However, currently, there are no reports on the encapsulation of probiotics using MFGM. In this study, MFGM and pullulan (PUL) polysaccharide fibers were prepared by electrostatic spinning and used to encapsulate probiotics, with whey protein isolates (WPI)/PUL as the control. The morphology, physical properties, mechanical properties, survival, and stability of the encapsulated Lacticaseibacillus rhamnosus GG (LGG) were studied. The results showed that the MFGM/PUL solution had significant effects on pH, viscosity, conductivity, and stability. Electrostatic spinning improved the mechanical properties and encapsulation ability of the polymer formed by MFGM/PUL. LGG encapsulated in MFGM/PUL nanofibers survived rate was higher than WPI/PUL nanofibers in mimic intestinal juice, which could be attributed to the phospholipid content contained in MFGM. These results demonstrate that MFGM is a promising material for probiotic encapsulation, providing an important basis for the potential use of MFGM/PUL nanofibers as a robust encapsulation matrix.

19.
Int Immunopharmacol ; 142(Pt B): 113136, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39293316

ABSTRACT

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.

20.
Carbohydr Polym ; 345: 122566, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39227121

ABSTRACT

Flexible electronic sensing and energy storage technology impose heightened demands on the mechanical and stable properties of gel electrolyte materials. Lignocellulosic nanofiber (LCNF) present a promising avenue for improving the properties of electrolyte networks and mechanical strength. In this study, LCNF derived from hemp fibers was prepared using lactic acid/choline chloride deep eutectic solvent (DES) through a combination of cooking and colloid mill mechanical treatment to achieve nanocellulose with a high aspect ratio and uniform dimensions. The outcomes demonstrated that LCNF, a width of below 20 nm and a length of over 5 µm, can be effectively produced through the DES cooking pretreatment in conjunction with colloid mill mechanical treatment. Meanwhile, DES lignin possessed a purity of ∼90 % and was obtained as a by-product. Subsequently, the as-prepared LCNF was integrated as a nanofiller into gel electrolyte. Ag-L NPs/LCNF/DES/PAA exhibited dense porous structures and showcased exceptional properties, including a high conductivity exceeding 10 mS/cm and remarkable adhesion strength surpassing 100 KPa. The presence of LCNF allowed Ag-L NPs/LCNF/DES/PAA to achieve strains above 1000 % and compression properties over 1000 KPa. The supercapacitor based on this assembly had a high specific capacitance of 271 F g-1 at 0.5 A g-1), along with an impressive capacity retention rate reaching ∼100 % after 3000 cycles. This investigation offers valuable insights into the utilization of lignocellulosic multi-component approaches in the development of flexible electronic devices.

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