Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 119
1.
Adv Sci (Weinh) ; : e2309725, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38647360

The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro-inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro-inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3-hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti-inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage.

2.
J Leukoc Biol ; 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38652703

Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases. Both diseases exhibited T cell exhaustion and senescence along with a surge in inflammatory cytokines. Significantly increased CD38+HLA-DR+CD8+T cell populations were observed in both diseases. AIH was characterized by an upregulation of CD8+TEMRA, CD4+TEM, and CD4+TEMRA cells, and a concurrent reduction in Treg cells. In contrast, PBC displayed a pronounced presence of Tfh cells and a contraction of CD4-CD8-T cell populations. Correlation analysis revealed that NKP46+NK frequency was closely tied to ALT and AST levels, and TIGIT expression on T cells was associated with GLB level in AIH. In PBC, there is a significant correlation between Tfh cells and ALP levels. Moreover, the identified immune landscapes in both diseases strongly related to disease severity. Through logistic regression analysis, γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies emerged as distinct markers capable of differentiating PBC from AIH. In conclusion, our analyses reveal that PBC and AIH share similarities and differences regarding to immune profiles. And γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies are potential noninvasive immunological markers that can differentiate PBC from AIH.

3.
Int J Mol Sci ; 25(7)2024 Mar 30.
Article En | MEDLINE | ID: mdl-38612692

Abscisic acid-responsive element-binding factor 1 (ABF1), a key transcription factor in the ABA signal transduction process, regulates the expression of downstream ABA-responsive genes and is involved in modulating plant responses to abiotic stress and developmental processes. However, there is currently limited research on the feedback regulation of ABF1 in ABA signaling. This study delves into the function of BcABF1 in Pakchoi. We observed a marked increase in BcABF1 expression in leaves upon ABA induction. The overexpression of BcABF1 not only spurred Arabidopsis growth but also augmented the levels of endogenous IAA. Furthermore, BcABF1 overexpression in Arabidopsis significantly decreased leaf water loss and enhanced the expression of genes associated with drought tolerance in the ABA pathway. Intriguingly, we found that BcABF1 can directly activate BcPYL4 expression, a critical receptor in the ABA pathway. Similar to BcABF1, the overexpression of BcPYL4 in Arabidopsis also reduces leaf water loss and promotes the expression of drought and other ABA-responsive genes. Finally, our findings suggested a novel feedback regulation mechanism within the ABA signaling pathway, wherein BcABF1 positively amplifies the ABA signal by directly binding to and activating the BcPYL4 promoter.


Abscisic Acid , Arabidopsis , Feedback , Arabidopsis/genetics , Droughts , Water
4.
Sci Adv ; 10(16): eadl4633, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38640249

Magnetic tunnel junctions (MTJs) are the core elements of spintronic devices. Now, the mainstream writing operation of MTJs mainly relies on electric current with high energy dissipation, which can be greatly reduced if an electric field is used instead. In this regard, strain-mediated multiferroic heterostructure composed of MTJ and ferroelectrics are promising with the advantages of room temperature and magnetic field-free as already demonstrated by MTJ with in-plane magnetic anisotropy. However, there is no such report on the perpendicular MTJs (p-MTJs), which have been commercialized. Here, we investigate electric-field control of resistance state of MgO-based p-MTJs in multiferroic heterostructures. A remarkable and nonvolatile manipulation of resistance is demonstrated at room temperature without magnetic field assistance. Through various characterizations and micromagnetic simulation, the manipulation mechanism is uncovered. Our work provides an effective avenue for manipulating p-MTJ resistance by electric fields and is notable for high density and ultralow power spintronic devices.

5.
BMC Genomics ; 25(1): 425, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38684983

BACKGROUND: Purple non-heading Chinese cabbage [Brassica campestris (syn. Brassica rapa) ssp. chinensis] has become popular because of its richness in anthocyanin. However, anthocyanin only accumulates in the upper epidermis of leaves. Further studies are needed to investigate the molecular mechanisms underlying the specific accumulation of it. RESULTS: In this study, we used the laser capture frozen section method (LCM) to divide purple (ZBC) and green (LBC) non-heading Chinese cabbage leaves into upper and lower epidermis parts (Pup represents the purple upper epidermis, Plow represents the purple lower epidermis, Gup represents the green upper epidermis, Glow represents the green lower epidermis). Through transcriptome sequencing, we found that the DIHYDROFLAVONOL 4-REDUCTASE-encoding gene BcDFR, is strongly expressed in Pup but hardly in others (Plow, Gup, Glow). Further, a deletion and insertion in the promoter of BcDFR in LBC were found, which may interfere with BcDFR expression. Subsequent analysis of gene structure and conserved structural domains showed that BcDFR is highly conserved in Brassica species. The predicted protein-protein interaction network of BcDFR suggests that it interacts with almost all functional proteins in the anthocyanin biosynthesis pathway. Finally, the results of the tobacco transient expression also demonstrated that BcDFR promotes the synthesis and accumulation of anthocyanin. CONCLUSIONS: BcDFR is specifically highly expressed on the upper epidermis of purple non-heading Chinese cabbage leaves and regulates anthocyanin biosynthesis and accumulation. Our study provides new insights into the functional analysis and transcriptional regulatory network of anthocyanin-related genes in purple non-heading Chinese cabbage.


Anthocyanins , Brassica , Plant Proteins , Anthocyanins/biosynthesis , Brassica/genetics , Brassica/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Transcriptome , Laser Capture Microdissection , Gene Expression Regulation, Plant , Gene Expression Profiling , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , RNA-Seq , Promoter Regions, Genetic
6.
Article En | MEDLINE | ID: mdl-38551415

Objective: This study aims to investigate the implementation of visual management in the central sterile supply department, focusing on enhancing work efficiency, improving work quality, reducing errors and accidents, and elevating the satisfaction levels of clinical departments. Methods: Visual flow diagrams were carefully developed and classified by a dedicated team from July to August 2021, led by an established visual management team. Subsequently, department staff underwent organized training sessions to understand the concepts, requirements, and contents of these visual management flow diagrams through a related examination. The application of visual flow diagrams extended to instruments and equipment, infection control, and instrument package management. To assess the impact, a control group comprising 400 pieces of instruments used in the operating room and clinical practice in June 2021 and an observation group with 400 pieces for surgical instruments and clinical use in October 2021 were selected using a convenience sampling method. The study analyzed and compared the qualified rate of instrument cleaning, the qualified rate of instrument packaging, and clinical satisfaction between the two groups. Results: The device qualified rates for instrument cleaning in the observation and control groups were 99% and 95%, respectively; for instrument packaging, they were 96% and 92%. Clinical satisfaction rates were 99% and 90%, respectively. These findings indicate an improved qualified rate for instrument cleaning, instrument packaging, and clinical satisfaction in the observation group compared to the control group before the implementation of visual management, with statistically significant differences (P = .000). Conclusions: The application of visual flow diagrams has a significant positive impact on the work quality in the central sterile supply department and enhances clinical work satisfaction. This approach is deemed suitable for broader promotion.

7.
Arch Pharm Res ; 47(3): 219-248, 2024 Mar.
Article En | MEDLINE | ID: mdl-38485900

Type 2 diabetes mellitus (T2DM) is a persistent metabolic disorder marked by deficiencies in insulin secretion and/or function, affecting various tissues and organs and leading to numerous complications. Mitochondrial biogenesis, the process by which cells generate new mitochondria utilizing existing ones plays a crucial role in energy homeostasis, glucose metabolism, and lipid handling. Recent evidence suggests that promoting mitochondrial biogenesis can alleviate insulin resistance in the liver, adipose tissue, and skeletal muscle while improving pancreatic ß-cell function. Moreover, enhanced mitochondrial biogenesis has been shown to ameliorate T2DM symptoms and may contribute to therapeutic effects for the treatment of diabetic nephropathy, cardiomyopathy, retinopathy, and neuropathy. This review summarizes the intricate connection between mitochondrial biogenesis and T2DM, highlighting the potential of novel therapeutic strategies targeting mitochondrial biogenesis for T2DM treatment and its associated complications. It also discusses several natural products that exhibit beneficial effects on T2DM by promoting mitochondrial biogenesis.


Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Organelle Biogenesis , Mitochondria/metabolism , Muscle, Skeletal/metabolism , Insulin/metabolism
8.
Psychol Res Behav Manag ; 17: 615-625, 2024.
Article En | MEDLINE | ID: mdl-38404923

Purpose: Insomnia is related to alexithymia in adults, but the relationship between insomnia and alexithymia in adolescents with major depressive disorder remains unclear. This study aimed to investigate the sex differences and the association between insomnia and alexithymia in adolescents with major depressive disorder. Patients and Methods: From October 2020 to April 2022, adolescent patients with major depressive disorder were recruited from psychiatric departments of seven hospitals in Anhui Province, China. Their general demographic and clinical information were collected. The 20-item Toronto Alexithymia Scale, the Center for Epidemiologic Studies of Depression Scale, and the Insomnia Severity Index Scale were used to assess their alexithymia, depression, and insomnia symptoms, respectively. The analysis of variance (ANOVA), Student's t-test and Mann-Whitney U-test were used for continuous variables and chi-square tests for categorical variables. Pearson's correlation analysis and Spearman correlation analysis were used to examine the correlation between ISI and demographic and clinical variables. Multiple binary logistic regression analyses with the "Enter" method were carried out to explore the correlations of insomnia. Results: The prevalence of insomnia in female adolescent patients was similar to that of male patients (χ2=1.84, p = 0.175). Compared with those without insomnia, patients with insomnia had worse family relationships (F = 7.71, p = 0.021), perceived heavier academic stress (F = 6.32, p = 0.012), more likely to take sedative-hypnotics (F = 5.51, p = 0.019), had higher levels of depression (F = 81.57, p < 0.001) and alexithymia (F = 28.57, p < 0.001). Correlation analysis showed that alexithymia was significantly associated with insomnia in adolescent patients (r = 0.360, p < 0.01). Binary logistic regression analyses showed that, alexithymia was significantly associated with insomnia in female patients (OR = 1.050, p < 0.05) but not male patients. Conclusion: In female adolescent patients, alexithymia is a risk factor of insomnia, which is of great importance in the understanding of the psychopathological mechanisms, treatments and psychological interventions of insomnia in adolescents with major depressive disorder.

9.
Front Immunol ; 15: 1337103, 2024.
Article En | MEDLINE | ID: mdl-38352871

Background: There is a growing amount of evidence suggesting that immunity and inflammation play an important role in the pathophysiology of schizophrenia. In this study, we aimed to examine the relationship between hematological and inflammatory markers with symptom severity in Han Chinese patients with drug-free schizophrenia. Methods: This retrospective study was conducted at Chaohu Hospital of Anhui Medical University and data were extracted from the electronic medical record system over a 5-year period (May 2017 to April 2022), including participants' general and clinical information as well as Brief Psychiatric Rating Scale (BPRS) scores and hematological parameters. Results: A total of 2,899 patients with schizophrenia were identified through the initial search. After screening, 91 patients and 141 healthy controls (HCs) were included. The patients had a higher value of neutrophils/lymphocytes ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) than HCs (all P < 0.001). MLR was positively correlated with BPRS total score (r = 0.337, P = 0.001) and resistance subscale score (r = 0.350, P = 0.001). Binary logistic regression analyses revealed that severely ill was significantly associated with being male and a higher value of MLR (Natural Logaruthm, Ln) (all P < 0.05), and the receiver operating characteristic (ROC) analysis showed good performance of a regression model with an area under the curve (AUC) value of 0.787. Conclusion: Patients with drug-free schizophrenia have an unbalanced distribution of peripheral blood granulocytes, and elevated NLR, MLR and PLR. Patients with higher value of MLR tend to have more psychotic symptoms, especially those symptoms of hostility, uncooperativeness, and suspiciousness. Our study gives a preliminary indication that MLR is a potential predictor of disease severity in patients with drug-free schizophrenia.


Schizophrenia , Humans , Male , Female , Retrospective Studies , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Neutrophils , Lymphocytes , China
10.
Aging Dis ; 2024 Feb 17.
Article En | MEDLINE | ID: mdl-38377029

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

11.
Diabetes Metab Res Rev ; 40(1): e3762, 2024 Jan.
Article En | MEDLINE | ID: mdl-38287719

Type 2 diabetes mellitus (T2DM) is a severe, long-term condition characterised by disruptions in glucolipid and energy metabolism. Autophagy, a fundamental cellular process, serves as a guardian of cellular health by recycling and renewing cellular components. To gain a comprehensive understanding of the vital role that autophagy plays in T2DM, we conducted an extensive search for high-quality publications across databases such as Web of Science, PubMed, Google Scholar, and SciFinder and used keywords like 'autophagy', 'insulin resistance', and 'type 2 diabetes mellitus', both individually and in combinations. A large body of evidence underscores the significance of activating autophagy in alleviating T2DM symptoms. An enhanced autophagic activity, either by activating the adenosine monophosphate-activated protein kinase and sirtuin-1 signalling pathways or inhibiting the mechanistic target of rapamycin complex 1 signalling pathway, can effectively improve insulin resistance and balance glucolipid metabolism in key tissues like the hypothalamus, skeletal muscle, liver, and adipose tissue. Furthermore, autophagy can increase ß-cell mass and functionality in the pancreas. This review provides a narrative summary of autophagy regulation with an emphasis on the intricate connection between autophagy and T2DM symptoms. It also discusses the therapeutic potentials of natural products with autophagy activation properties for the treatment of T2DM conditions. Our findings suggest that autophagy activation represents an innovative approach of treating T2DM.


Biological Products , Diabetes Mellitus, Type 2 , Insulin Resistance , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Insulin/therapeutic use , Biological Products/therapeutic use , Autophagy
12.
Pest Manag Sci ; 80(6): 2587-2595, 2024 Jun.
Article En | MEDLINE | ID: mdl-38265118

BACKGROUND: Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets. RESULTS: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure. CONCLUSION: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry.


Bacillus thuringiensis Toxins , Endotoxins , Hemolysin Proteins , Larva , Malpighian Tubules , Spodoptera , Animals , Spodoptera/drug effects , Spodoptera/genetics , Spodoptera/metabolism , Spodoptera/growth & development , Malpighian Tubules/drug effects , Malpighian Tubules/metabolism , Larva/drug effects , Larva/genetics , Larva/growth & development , Larva/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Transcriptome , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Insecticides/toxicity , Proteome , Proteomics , Digestive System/drug effects , Digestive System/metabolism
13.
J Affect Disord ; 350: 110-117, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38220096

BACKGROUND: Insomnia symptoms are often associated with increased levels of inflammatory biomarkers. However, such associations have not been adequately explored in adolescents with major depressive disorder (MDD). This study aimed to examine the associations between insomnia symptoms with inflammatory cytokines in adolescents with first-episode and recurrent MDD. METHODS: From January to December 2021, this study included 164 adolescents with MDD and 76 healthy controls (HCs). The Center for Epidemiological Studies Depression Scale (CES-D) and the Insomnia Severity Index Scale (ISI) were used to assess depressive and insomnia symptoms, respectively. Also, plasma levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17 A and tumor necrosis factor-α (TNF-α) were measured. RESULTS: The prevalence of mild, moderate and severe insomnia in adolescents with MDD was 40.24 %, 36.59 % and 6.71 %, respectively. The patients had higher levels of IL-1ß, IL-6 and TNF-α than HCs (all p < 0.05). ISI score was positively correlated with CES-D score and levels of IL-1ß, IL-6 and TNF-α in first-episode patients but not in recurrent patients. A further multivariate stepwise linear regression analysis showed that ISI score was independently associated with CES-D score (beta = 0.523, t = 5.833, p < 0.001) and TNF-α levels (beta = 0.254, t = 2.832, p = 0.006). LIMITATIONS: The cross-sectional design leads to failure to make causal inferences. CONCLUSION: Insomnia symptoms are common in adolescents with MDD and associated with elevated levels of inflammatory cytokines in first-episode patients. The findings suggest that inflammatory cytokines may relate to the pathogenesis of insomnia symptoms in adolescents with MDD, but further longitudinal studies are needed to explore the causal association between insomnia symptoms and inflammatory cytokines in MDD.


Depressive Disorder, Major , Sleep Initiation and Maintenance Disorders , Humans , Adolescent , Cytokines , Depressive Disorder, Major/complications , Tumor Necrosis Factor-alpha , Interleukin-6 , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/complications , Cross-Sectional Studies , Interleukin-1beta
14.
Biosci Biotechnol Biochem ; 88(3): 322-332, 2024 Feb 21.
Article En | MEDLINE | ID: mdl-38066695

This study was to investigate the inhibitory activity of small hairtail-related peptides (VFEVFW, LPNSLYQQ, LPNSLYQK, and FADAME) on intracellular monoamine oxidase-A (MAO-A) and their protective effects in a cell model. Specifically, the inhibition activity in SH-SY5Y cells indicated that VFEVFW and LPNSLYQK reduced ∼50% of MAO-A activity in cells, at 0.5 m m. The survival experiment demonstrated that the toxic effect of dexamethasone (DEX) on cells can be significantly alleviated in the presence of peptides, and these peptides can restore (>20%) the mitochondrial membrane potential of SH-SY5Y cells reduced by DEX. Circular dichroism displayed that peptides affected the secondary structure of MAO-A in a concentration-dependent manner. Finally, the real-time quantitative polymerase chain reaction assay revealed that the MAO-A inhibitory activity of the peptides was associated with the upregulation of brain derived neurotrophic factor/cAMP (Cyclic adenosine monophosphate) response element binding protein)/B-cell lymphoma-2 mRNA levels.


Monoamine Oxidase , Neuroblastoma , Humans , Monoamine Oxidase/genetics , Monoamine Oxidase/metabolism , Monoamine Oxidase/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/metabolism , Cell Line, Tumor , Neuroblastoma/genetics , Neuroblastoma/metabolism , Neurons , Peptides/pharmacology
15.
Phytother Res ; 38(1): 196-213, 2024 Jan.
Article En | MEDLINE | ID: mdl-37850242

Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high-fat-high-glucose diet (HFD)-induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD-induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate-activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet-induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.


Chalcones , Diabetes Mellitus, Experimental , Insulin Resistance , Mice , Animals , Chalcones/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diet, High-Fat/adverse effects , Homeostasis , Liver , Mice, Inbred C57BL , AMP-Activated Protein Kinases/metabolism , Energy Metabolism , Mammals/metabolism
17.
Small ; : e2307379, 2023 Dec 12.
Article En | MEDLINE | ID: mdl-38084463

Rheumatoid arthritis (RA) is the most prevalent inflammatory joint disease worldwide, leading to irreversible disability and even mortality. Unfortunately, current treatment regimens fail to cure RA due to low therapeutic responses and off-target side effects. Herein, a neutrophil membrane-cloaked, natural anti-arthritic agent leonurine (Leo), and catalase (CAT) co-loaded nanoliposomal system (Leo@CAT@NM-Lipo) is constructed to remodel the hostile microenvironment for RA remission. Due to the inflammation tropism inherited from neutrophils, Leo@CAT@NM-Lipo can target and accumulate in the inflamed joint cavity where high-level ROS can be catalyzed into oxygen by CAT to simultaneously accelerate the drug release and alleviate hypoxia at the lesion site. Besides, the neutrophil membrane camouflaging also enhances the anti-inflammatory potentials of Leo@CAT@NM-Lipo by robustly absorbing pro-arthritogenic cytokines and chemokines. Consequently, Leo@CAT@NM-Lipo successfully alleviated paw swelling, reduced arthritis score, mitigated bone and cartilage damage, and reversed multiple organ dysfunctions in adjuvant-induced arthritis rats (AIA) rats by synergistic effects of macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief. Furthermore, Leo@CAT@NM-Lipo manifested excellent biocompatibility both at the cellular and animal levels. Taken together, the study provided a neutrophil-mimetic and ROS responsive nanoplatform for targeted RA therapy and represented a promising paradigm for the treatment of a variety of inflammation-dominated diseases.

19.
Materials (Basel) ; 16(20)2023 Oct 23.
Article En | MEDLINE | ID: mdl-37895800

Magnetorheological damper (MRD) has been successfully applied to vehicle suspension systems as an intelligent core component. Most conventional MRDs have closed rectangle-shaped magnetic circuits, resulting in a short effective working length and negligible damping force. To address the above issues, a novel full-channel effective MRD with trapezoidal magnetic rings (FEMRD_TMR) is proposed. The trapezoidal magnetic ring can shunt the magnetic circuit, distributing it evenly along the damping channel and increasing the effective working length. Additionally, which has the same variation trend as the magnetic flux through it, makes the magnetic induction intensity distribution more uniform to reduce the magnetic saturation problem. Theoretically analyzing the damping characteristics of the FEMRD_TMR, a quasi-static model is developed to forecast the output damping force. The structural design of MRD is challenging since conventional quasi-static models rely on the yield stress of magnetorheological fluid (MRF) to reflect the rheological property, which cannot be directly observed and is challenging to calculate. The Takagi-Sugeno (T-S) fuzzy neural network and a unique magnetic circuit computation are offered as a novel quasi-static modeling approach to address the issue. The MRF's yield stress is linearized into magnetic induction intensity functions by the T-S fuzzy neural network and then converted into the MRD's structural size by the special magnetic circuit calculation. Therefore, the proposed quasi-static model can directly reflect the relationship between the damping force and structure size, simplifying MRD's structure design. The novel quasi-static model is shown to be more straightforward and understandable than the conventional Bingham quasi-static model and to have approximately accurate damping force prediction when compared to experimental data.

20.
J Med Internet Res ; 25: e45767, 2023 09 19.
Article En | MEDLINE | ID: mdl-37725432

BACKGROUND: While scientific knowledge of post-COVID-19 condition (PCC) is growing, there remains significant uncertainty in the definition of the disease, its expected clinical course, and its impact on daily functioning. Social media platforms can generate valuable insights into patient-reported health outcomes as the content is produced at high resolution by patients and caregivers, representing experiences that may be unavailable to most clinicians. OBJECTIVE: In this study, we aimed to determine the validity and effectiveness of advanced natural language processing approaches built to derive insight into PCC-related patient-reported health outcomes from social media platforms Twitter and Reddit. We extracted PCC-related terms, including symptoms and conditions, and measured their occurrence frequency. We compared the outputs with human annotations and clinical outcomes and tracked symptom and condition term occurrences over time and locations to explore the pipeline's potential as a surveillance tool. METHODS: We used bidirectional encoder representations from transformers (BERT) models to extract and normalize PCC symptom and condition terms from English posts on Twitter and Reddit. We compared 2 named entity recognition models and implemented a 2-step normalization task to map extracted terms to unique concepts in standardized terminology. The normalization steps were done using a semantic search approach with BERT biencoders. We evaluated the effectiveness of BERT models in extracting the terms using a human-annotated corpus and a proximity-based score. We also compared the validity and reliability of the extracted and normalized terms to a web-based survey with more than 3000 participants from several countries. RESULTS: UmlsBERT-Clinical had the highest accuracy in predicting entities closest to those extracted by human annotators. Based on our findings, the top 3 most commonly occurring groups of PCC symptom and condition terms were systemic (such as fatigue), neuropsychiatric (such as anxiety and brain fog), and respiratory (such as shortness of breath). In addition, we also found novel symptom and condition terms that had not been categorized in previous studies, such as infection and pain. Regarding the co-occurring symptoms, the pair of fatigue and headaches was among the most co-occurring term pairs across both platforms. Based on the temporal analysis, the neuropsychiatric terms were the most prevalent, followed by the systemic category, on both social media platforms. Our spatial analysis concluded that 42% (10,938/26,247) of the analyzed terms included location information, with the majority coming from the United States, United Kingdom, and Canada. CONCLUSIONS: The outcome of our social media-derived pipeline is comparable with the results of peer-reviewed articles relevant to PCC symptoms. Overall, this study provides unique insights into patient-reported health outcomes of PCC and valuable information about the patient's journey that can help health care providers anticipate future needs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1101/2022.12.14.22283419.


COVID-19 , Social Media , Humans , Natural Language Processing , Reproducibility of Results , Fatigue , Patient Reported Outcome Measures
...