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1.
J Phys Chem Lett ; : 10873-10880, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39441009

RESUMO

The alternating current-driven electroluminescence (AC-EL) of Cd-based quantum dots is garnering increasing attention due to advantages such as high efficiency and an extended operating lifetime. However, the generation and transport mechanisms of charge carriers within devices still need to be more understood. Here, we construct a simple device and investigate its luminance mechanisms within a single cycle using time-resolved spectroscopy. We tested the luminance-voltage and luminance-frequency characteristics of the device as the thickness of the insulating layer varied, finding that they both exhibited a trend of initially increasing and then decreasing as the voltage or frequency increased. We subsequently investigated the transient electroluminescent characteristics of the device, which featured a P(VDF-TrFE-CFE) layer as the insulator. This layer prevents carrier injection from the Al electrode, while the ZnO layer acts as a charge-generating layer to provide additional carriers. We observed that with an increase in AC voltage, the strongest luminance peak is advanced in the cycle compared to when lower voltages were applied. The position of the strongest luminance peak is delayed with an increasing AC frequency. The C-V characteristics demonstrated that the synergistic P(VDF-TrFE-CFE)/ZnO exhibited a displacement current transforming to a conduct current, which activates the forward operation of the QLED and enables it to emit light. The mechanism we present may serve as a benchmark for improving the luminance and longevity of such devices.

2.
ACS Appl Mater Interfaces ; 16(38): 51212-51220, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39255231

RESUMO

Dual-band photodetectors (PDs) have attracted extensive research attention due to their great potential for diverse and refreshing application scenarios in full-color imaging, optical communication, and imaging detection. Here, a self-driven dual-band PD without filters and other auxiliary equipment to achieve a narrowband response in Mode 1 and a broadband response in Mode 2 was designed based on carrier-selective transmission narrowing (CSTN). The polymer material poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA), which has the appropriate energy level, was selected to be the carrier-selective transmission layer. In Mode 1, the dual-band PD exhibits a near-infrared (NIR) narrowband response in 750-900 nm, which indicates a responsivity of 360 mA/W, a full-width at half-maximum (fwhm) of 81 nm, and a specific detectivity (D*) of 7.49 × 1010 Jones at 810 nm. Simultaneously, in Mode 2, the dual-band PD exhibits a UV-visible-NIR broadband responsivity of 180 mA/W and a specific detectivity (D*) of 3.8 × 1010 Jones at 520 nm. Our study provides a reliable idea for the commercial applications of dual-function photodetectors.

3.
3 Biotech ; 14(9): 203, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39157421

RESUMO

Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM) prescription renowned for its efficacy, is specifically recognized for its therapeutic effects in managing diarrhea associated with spleen qi deficiency. Our previous research has demonstrated that a lard diet in a fatigued state induced diarrhea belonging to spleen qi deficiency in TCM. Through a comprehensive investigation, we aimed to provide insights into the intricate relationship between SLBZP and the modulation of gut microbiota in alleviating symptoms associated with spleen qi deficiency-induced diarrhea. We induced diarrhea in mice by subjecting them to continuous standing on a multiple-platform apparatus while administering lard through intragastric administration for 14 days. Subsequently, we conducted gavage administration of SLBZP at a concentration of 0.637 g/ml for seven days. We observed a therapeutic effect of SLBZP on diarrhea induced by a lard diet in a fatigued state. SLBZP mitigated disorders in lipid metabolism and diminished hepatic oxidative responses. Additionally, SLBZP reversed gut microbiota dysbiosis of diarrheic mice and notably increased the production of short-chain fatty acids (SCFAs), primarily acetic acid, butyric acid, and valeric acid. Through correlation analysis, we additionally identified Lactobacillus reuteri and Lactobacillus intestinalis as potentially pivotal species associated with the therapeutic effects of SLBZP. We demonstrated that SLBZP exerts therapeutic effects on diarrhea caused by a lard diet in a fatigued state by repairing the intestinal mucosal barrier, improving lipid metabolism disorders, and regulating gut microbiota and metabolites SCFAs.

4.
J Orthop Surg Res ; 19(1): 500, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39175021

RESUMO

BACKGROUND: The optimal treatment method for managing unstable Pauwels III femoral neck fractures remains undetermined. The aim of this study was to compare the biomechanical properties of two types of Femoral Neck Anti-rotation and Support System (FNAS) and a Femoral Neck System (FNS) in unstable Pauwels III femoral neck fractures. METHODS: Eighteen synthetic femoral models were implanted with one of three fixation devices: FNS, FNAS I, or FNAS II. An unstable Pauwels III (OTA/AO 31-B2.3) femoral neck fracture was simulated using a custom-made needle and osteotomy guide. Torsion and axial compression loading tests were conducted, and the torque, torsion angle, load to failure, displacement, and stiffness values were recorded. RESULTS: FNAS II exhibited significantly higher torsional stiffness (0.67 ± 0.10 Nm/°) compared to FNAS I (0.52 ± 0.07 Nm/°, P = 0.01) and FNS (0.54 ± 0.07 Nm/°, P = 0.005). FNS demonstrated significantly greater mean axial stiffness (239.24 ± 11.38 N/mm) than both FNAS I (179.33 ± 31.11 N/mm, P = 0.005) and FNAS II (190.07 ± 34.11 N/mm, P = 0.022). FNAS I (302.37 ± 33.88 N/mm, P = 0.001) and FNAS II (319.59 ± 50.10 N/mm, P < 0.001) showed significantly higher initial axial stiffness compared to FNS (197.08 ± 33.68 N/mm). Both FNAS I and II improved resistance to deforming forces at a load level before approximately 1000 N, which is sufficient to withstand the load from most daily life activities. No significant differences were observed in compression failure load among the groups. The failure patterns at the point of failure included the pull-out of the distal locking screw and reverse oblique intertrochanteric femur fracture for FNS, while for FNAS I and II, the failures were characterized by a cleft on the calcar femorale and a decrease in the load-displacement curve. CONCLUSIONS: In unstable Pauwels III femoral neck fractures, the FNAS II enhances stability and is easier to manage for reoperation. The results of the current study support the potential of FNAS II as an alternative option for treating unstable Pauwels III femoral neck fractures in young individuals.


Assuntos
Fraturas do Colo Femoral , Fixação Interna de Fraturas , Fraturas do Colo Femoral/cirurgia , Fenômenos Biomecânicos , Humanos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Rotação , Colo do Fêmur/cirurgia , Colo do Fêmur/diagnóstico por imagem
5.
J Am Chem Soc ; 146(33): 23194-23204, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39115467

RESUMO

Electrochemical hydrogenation reactions demand rapid proton-coupled electron transfer at the electrode surface, the kinetics of which depend closely on pH. Buffer electrolytes are extensively employed to regulate pH over a wide range. However, the specific role of buffer species should be taken into account when interpreting the intrinsic pH dependence, which is easily overlooked in the current research. Herein, we report the electrochemical hydrogenation of hydroxyacetone, derived from glycerol feedstock, to propylene glycol with a faradaic efficiency of 56 ± 5% on a polycrystalline Cu electrode. The reaction activities are comparable in citrate, phosphate, and borate buffer electrolytes, encompassing different buffer identities and pH. The electrokinetic profile reveals that citrate is a site-blocking adsorbate on the Cu surface, thereby decreasing buffer concentration and increasing pH will enhance the reaction rate; phosphate is an explicit proton donor, which promotes the interfacial rate by increasing buffer concentration and decreasing pH, while borate is an innocent buffer, which can be used to investigate the intrinsic pH effect. Combined with in situ SEIRAS, we demonstrate that water is the primary proton source in citrate and borate electrolytes, reiterating the rationality of the proposed mechanism based on the microkinetic modeling. Our results emphasize the intrinsic complexity of the buffer system on the kinetic activity for electrocatalysis. It calls for special care when we diagnose the mechanistic pathway in buffer electrolytes convoluted by different buffer identities and pH.

6.
Phys Chem Chem Phys ; 26(31): 21147-21154, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39072377

RESUMO

Quasi-two-dimensional (quasi-2D) perovskites exhibit excellent performance in light-emitting diodes (LEDs). However, the quality of perovskite films prepared via the solution method is significantly impacted by the enormous number of defects that unavoidably form at the grain boundaries and interfaces during the precursor to the crystal formation process. Here, we propose a strategy to assist perovskite crystallization and defect passivation at the buried interface through interfacial modification. The organic ammonium salt, ethylamine chloride (EACl), is added to the hole transport material and modifies the buried interface of the perovskite film. EACl introduces the nucleation sites for perovskite precursors, and promotes the crystallization process of the perovskite grains, contributing to the formation of high-quality perovskite films. At the same time, the presence of Lewis base (-NH2) groups in EACl and their lone electron pairs effectively inactivate unlocated Pb2+ ions at the buried interface, thereby reducing non-radiative recombination. In addition, chloride ions help to mitigate defects and to improve the morphology of perovskite films. Devices with this modification show a higher performance than control devices on all metrics. This work proposes a facile but efficient way for improving quasi-2D pure blue perovskite crystallization and growth.

7.
Angew Chem Int Ed Engl ; : e202412839, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075021

RESUMO

Cyclodextrin-based polyrotaxanes (CD-PRs) are gaining attention for their dynamic sliding rings along the polymer axis, enabling various applications in molecular shuttles, drug delivery, and durable polymers with slidable cross-links. However, the conventional synthesis of CD-PRs with tunable threading ratios is typically laborious, time-consuming, and complicated, which limits their scalability and cost-effectiveness. Herein, we highlight the great potential of planetary centrifugal mixing, a process that significantly accelerates and simplifies the initial synthesis of polypseudorotaxanes (PPRs), followed by a thiol-ene click reaction as an efficient end-capping reaction for the synthesis of PRs. Notably, PRs synthesized with glutathione (GSH) as the end-capping reagent are in a metastable state, where GSH act as a molecular bumper that significantly prevent de-threading of α-CD rings at room temperature. Moreover, the rate of ring de-threading can be precisely controlled by heating, enabling the preparation of metastable PRs with tunable threading ratios over a wide range. The developed strategy is of great significance to the efficient synthesis of CD-PRs, thus marking a significant step towards their practical application in advanced functional materials and devices.

8.
Front Pharmacol ; 15: 1360589, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915463

RESUMO

Background: Sishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been elucidated. Objective: This study investigated the mechanism of SSP in regulating intestinal microecology in diarrhea with DKYS. Methods: Adenine combined with Folium sennae was used to construct a mouse model of diarrhea with DKYS and administered with SSP. The behavioral changes and characteristics of gut content microbiota and short-chain fatty acids (SCFAs) of mice were analyzed to explore the potential association between the characteristic bacteria, SCFAs, intestinal inflammatory and kidney function-related indicators. Results: After SSP intervention, the body weight and anal temperature of diarrhea with DKYS gradually recovered and approached the normal level. Lactobacillus johnsonii was significantly enriched, and propionic, butyric, isobutyric and isovaleric acids were elevated. Serum creatinine (Cr), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels of the mice were reduced, while serum blood urea nitrogen (BUN) and secretory immunoglobulin A (sIgA) in the colonic tissues were increased. Moreover, there were correlations between L. johnsonii, SCFAs, intestinal inflammatory, and kidney function. Conclusion: SSP might suppress the intestinal inflammation by regulating the "L. johnsonii-propionic acid" pathway, thus achieving the effect of treating diarrhea with DKYS.

9.
COPD ; 21(1): 2329282, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38622983

RESUMO

COPD is an inflammatory lung disease that limits airflow and remodels the pulmonary vascular system. This study delves into the therapeutic potential and mechanistic underpinnings of Panax notoginseng Saponins (PNS) in alleviating inflammation and pulmonary vascular remodeling in a COPD rat model. Symmap and ETCM databases provided Panax notoginseng-related target genes, and the CTD and DisGeNET databases provided COPD-related genes. Intersection genes were subjected to protein-protein interaction analysis and pathway enrichment to identify downstream pathways. A COPD rat model was established, with groups receiving varying doses of PNS and a Roxithromycin control. The pathological changes in lung tissue and vasculature were examined using histological staining, while molecular alterations were explored through ELISA, RT-PCR, and Western blot. Network pharmacology research suggested PNS may affect the TLR4/NF-κB pathway linked to COPD development. The study revealed that, in contrast to the control group, the COPD model exhibited a significant increase in inflammatory markers and pathway components such as TLR4, NF-κB, HIF-1α, VEGF, ICAM-1, SELE mRNA, and serum TNF-α, IL-8, and IL-1ß. Treatment with PNS notably decreased these markers and mitigated inflammation around the bronchi and vessels. Taken together, the study underscores the potential of PNS in reducing lung inflammation and vascular remodeling in COPD rats, primarily via modulation of the TLR4/NF-κB/HIF-1α/VEGF pathway. This research offers valuable insights for developing new therapeutic strategies for managing and preventing COPD.


Assuntos
Panax notoginseng , Doença Pulmonar Obstrutiva Crônica , Saponinas , Ratos , Animais , Saponinas/farmacologia , Saponinas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , NF-kappa B/metabolismo , Panax notoginseng/metabolismo , Receptor 4 Toll-Like/genética , Fator A de Crescimento do Endotélio Vascular/genética , Remodelação Vascular , Pulmão , Inflamação/tratamento farmacológico
10.
Adv Healthc Mater ; 13(19): e2400293, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38426417

RESUMO

Exosomes, nanoparticles secreted by various cells, composed of a bilayer lipid membrane, and containing bioactive substances such as proteins, nucleic acids, metabolites, etc., have been intensively investigated in tissue engineering owing to their high biocompatibility and versatile biofunction. However, there is still a lack of a high-quality review on bone defect regeneration potentiated by exosomes. In this review, the biogenesis and isolation methods of exosomes are first introduced. More importantly, the engineered exosomes of the current state of knowledge are discussed intensively in this review. Afterward, the biomaterial carriers of exosomes and the mechanisms of bone repair elucidated by compelling evidence are presented. Thus, future perspectives and concerns are revealed to help devise advanced modalities based on exosomes to overcome the challenges of bone regeneration. It is totally believed this review will attract special attention from clinicians and provide promising ideas for their future works.


Assuntos
Regeneração Óssea , Exossomos , Engenharia Tecidual , Exossomos/metabolismo , Humanos , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/química
11.
Polymers (Basel) ; 16(6)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38543369

RESUMO

The performance of silicone rubber gel elastomers is affected by the composition and structure of the crosslinker. In this work, a two-component addition liquid silicone rubber gel material was developed, and the effects of the contents of two methyl hydro-silicone oils on the compression modulus and breakdown strength of the silicone rubber gel insulating material, as well as the performance change after hot air aging at different times (24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h), were studied. The results showed that the breakdown strength and compression modulus exhibited an upward trend with the increase in the hydrogen silicone oil content. The best performance was achieved in the silicone rubber gel with Si-H:Si-Vi = 1.4:1. Moreover, with the increase in aging time, the breakdown strength decreased and the compression modulus increased.

12.
Mol Med ; 30(1): 34, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448811

RESUMO

BACKGROUND: Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear. METHODS: The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells. RESULTS: POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance. CONCLUSION: Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.


Assuntos
Resistência à Insulina , Animais , Camundongos , Glucose , Hipotálamo , Resistência à Insulina/genética , Neurônios , Pró-Opiomelanocortina/genética , Receptor Tipo 4 de Melanocortina/genética
13.
Heliyon ; 10(3): e25315, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38322883

RESUMO

Ventricular septal rupture (VSR) is a catastrophic mechanical complication of acute myocardial infarction (AMI) that can result in acute heart failure. Delaying operative intervention frequently leads to cardiogenic shock and multi-organ failure. Here we report a case of massive anterior MI complicated with VSR that was discovered through cardiac Doppler ultrasound and suspected multiple organ hemorrhage. The patient showed signs of rapid cardiogenic shock and eventually died. The morphological changes of VSR and MI were identified during necropsy, and microscopic examinations of the heart, brain, and kidney revealed multiple organ hemorrhage. This autopsy case suggested that the complication of VSR caused by AMI results in a reduction of oxygen and nutrient content of the circulating blood throughout the body and, eventually, functional failure of multiple organs. We provide clinical and pathological evidence elucidating changes in multiple organs under the severe condition of post-infarction VSR and demonstrate the consequences of a lack of immediate surgery and sufficient medical intervention for a patient suffering from AMI with VSR.

14.
Nanoscale ; 16(8): 3838-3880, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38329288

RESUMO

Lead halide perovskites (LHPs) are emerging semiconductor materials for light-emitting diodes (LEDs) owing to their unique structure and superior optoelectronic properties. However, defects that initiate degradation of LHPs through external stimuli and prompt internal ion migration at the interfaces remain a significant challenge. The electric field (EF), which is a fundamental driving force in LED operation, complicates the role of these defects in the physical and chemical properties of LHPs. A deeper understanding of EF-induced defect behavior is crucial for optimizing the LED performance. In this review, the origins and characterization of defects are explored, indicating the influence of EF-induced defect dynamics on LED performance and stability. A comprehensive overview of recent defect passivation approaches for LHP bulk films and nanocrystals (NCs) is also provided. Given the ubiquity of EF, a summary of the EF-induced defect behavior can enhance the performance of perovskite LEDs and related optoelectronic devices.

15.
Angew Chem Int Ed Engl ; 63(17): e202401602, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38345598

RESUMO

Electrochemical biomass conversion holds promise to upcycle carbon sources and produce valuable products while reducing greenhouse gas emissions. To this end, deep insight into the interfacial mechanism is essential for the rational design of an efficient electrocatalytic route, which is still an area of active research and development. Herein, we report the reduction of dihydroxyacetone (DHA)-the simplest monosaccharide derived from glycerol feedstock-to acetol, the vital chemical intermediate in industries, with faradaic efficiency of 85±5 % on a polycrystalline Cu electrode. DHA reduction follows preceding dehydration by coordination with the carbonyl and hydroxyl groups and the subsequent hydrogenation. The electrokinetic profile indicates that the rate-determining step (RDS) includes a proton-coupled electron transfer (PCET) to the dehydrated intermediate, revealed by coverage-dependent Tafel slope and isotopic labeling experiments. An approximate zero-order dependence of H+ suggests that water acts as the proton donor for the interfacial PCET process. Leveraging these insights, we formulate microkinetic models to illustrate its origin that Eley-Rideal (E-R) dominates over Langmuir-Hinshelwood (L-H) in governing Cu-mediated DHA reduction, offering rational guidance that increasing the concentration of the adsorbed reactant alone would be sufficient to promote the activity in designing practical catalysts.

16.
Ageing Res Rev ; 93: 102160, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38065225

RESUMO

Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.


Assuntos
Doenças do Sistema Nervoso Central , Microglia , Humanos , Microglia/patologia , Doenças do Sistema Nervoso Central/terapia , Doenças do Sistema Nervoso Central/patologia , Fenótipo
17.
Heliyon ; 9(12): e23010, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38076060

RESUMO

This study explored the effects of different doses of adenine intake on mice in terms of kidney function, oxidative stress and gut content microbiota to elucidate interactions between adenine-induced kidney function impairment and gut content microbiota disorder. Mice were gavaged with low-dosage adenine suspension (NML), middle-dosage adenine suspension (NMM), high-dosage adenine suspension (NMH) and sterile water (NC). Behaviour, kidney structure and function, colonic structure, oxidative stress and gut content microbiota were detected. Mice in NML, NMM, and NMH groups had significantly lower body weight, anal temperature and food intake, increased water intake, the mice had loose and deformed feces with obvious water stains through the paper. NMM mice presented significantly structural damage to kidney and colonic tissues, considerably higher BUN and Cr, MDA and lower SOD. MDA and SOD levels in NMM and NMH groups were closely associated with Cr and BUN. Moreover, different doses of adenine intake effected the mice gut content microbiota, and enriched the different characteristic bacteria. Characteristic bacteria Lactobacillus and Bifidobacterium presented significant correlations with MDA. Eventually, Lactobacillus and Bifidobacterium mediated oxidative stress pathway involved in the process of adenine-induced kidney injure in mice.

18.
J Biol Chem ; 299(12): 105476, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37981207

RESUMO

Circadian rhythm disruption leads to dysregulation of lipid metabolism, which further drive the occurrence of insulin resistance (IR). Exosomes are natural carrier systems that advantageous for cell communication. In the present study, we aimed to explore whether and how the exosomal microRNAs (miRNAs) in circulation participate in modulating skeletal muscle IR induced by circadian rhythm disruption. In the present study, 24-h constant light (12-h light/12-h light, LL) was used to establish the mouse model of circadian rhythm disruption. Bmal1 interference was used to establish the cell model of circadian rhythm disruption. And in clinical experiments, we chose a relatively large group of rhythm disturbance-shift nurses. We showed that LL-induced circadian rhythm disruption led to increased body weight and visceral fat volume, as well as occurrence of IR in vivo. Furthermore, exosomal miR-22-3p derived from adipocytes in the context of circadian rhythm disruption induced by Bmal1 interference could be uptaken by skeletal muscle cells to promote IR occurrence in vitro. Moreover, miR-22-3p in circulation was positively correlated with the clinical IR-associated factors. Collectively, these data showed that exosomal miR-22-3p in circulation may act as potential biomarker and therapeutic target for skeletal muscle IR, contributing to the prevention of diabetes in the context of rhythm disturbance.


Assuntos
Ritmo Circadiano , Exossomos , Resistência à Insulina , MicroRNAs , Animais , Camundongos , Adipócitos/metabolismo , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo
19.
Curr Med Sci ; 43(5): 1051-1060, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37806993

RESUMO

OBJECTIVE: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis. METHODS: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). RESULTS: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002. CONCLUSION: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Osteogênese , Farmacologia em Rede , Diferenciação Celular , Transdução de Sinais
20.
Mol Nutr Food Res ; 67(18): e2300452, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37622564

RESUMO

SCOPE: Preliminary research finds that a high-fat diet (HFD) in a fatigued state triggers diarrhea, but the exact mechanism has not been clarified. To address concerns about the pathogenesis of diarrhea, the study evaluates the composition and metabolomics of the gut microbiota. METHODS AND RESULTS: The study uses the multiple platform apparatus device to induce fatigue in mice, combined with intragastric administration of lard-caused diarrhea. Subsequently, the characteristics and interaction relationship of gut microbiota, short-chain fatty acids (SCFAs), inflammatory biomarkers, brain-gut peptides, and lipid metabolism are analyzed at the end of the experiment. HFD in a fatigued state results in a significant increase in interleukin-17, interleukin-6, cholecystokinin, somatostatin, and malondialdehyde content in mice (p < 0.05), along with a substantial decrease in high-density lipoprotein (p < 0.05). Additionally, an HFD in a fatigued state causes changes in the structure and composition of the gut microbiota, with Lactobacillus murinus as its characteristic bacteria, and reduces the production of SCFAs. CONCLUSIONS: An HFD in a fatigued state triggers diarrhea, possibly associated with gut content microbiota dysbiosis, SCFAs deprivation, increased inflammation, and dysregulated lipid metabolism.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Diarreia/etiologia , Fadiga , Ácidos Graxos Voláteis
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