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1.
Article in English | MEDLINE | ID: mdl-38713571

ABSTRACT

Text-to-image generation models have significantly broadened the horizons of creative expression through the power of natural language. However, navigating these models to generate unique concepts, alter their appearance, or reimagine them in unfamiliar roles presents an intricate challenge. For instance, how can we exploit language-guided models to transpose an anime character into a different art style, or envision a beloved character in a radically different setting or role? This paper unveils a novel approach named DreamAnime, designed to provide this level of creative freedom. Using a minimal set of 2-3 images of a user-specified concept such as an anime character or an art style, we teach our model to encapsulate its essence through novel "words" in the embedding space of a pre-existing text-to-image model. Crucially, we disentangle the concepts of style and identity into two separate "words", thus providing the ability to manipulate them independently. These distinct "words" can then be pieced together into natural language sentences, promoting an intuitive and personalized creative process. Empirical results suggest that this disentanglement into separate word embeddings successfully captures a broad range of unique and complex concepts, with each word focusing on style or identity as appropriate. Comparisons with existing methods illustrate DreamAnime's superior capacity to accurately interpret and recreate the desired concepts across various applications and tasks. Code is available at https://github.com/chnshx/DreamAnime.

2.
J Cell Mol Med ; 28(8): e18285, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38597406

ABSTRACT

Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive-like behaviours in chronic stress social defeat stress (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL-1ß, IL-6, and TNF-a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS-related pathological changes. Engeletin was further found to suppress the LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno-associated virus-induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS-induced depressive-like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.


Subject(s)
Antidepressive Agents , Flavonols , Glycosides , Microglia , Mice , Animals , Microglia/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/drug therapy , Depression/etiology , Signal Transduction
3.
Cancer Sci ; 115(5): 1492-1504, 2024 May.
Article in English | MEDLINE | ID: mdl-38476086

ABSTRACT

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.


Subject(s)
Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms , RNA, Long Noncoding , Transcription Factors , Tumor Suppressor Proteins , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Animals , Cell Movement/genetics , Mice , Apoptosis/genetics , Prognosis , Transcriptional Activation , RNA, Antisense/genetics , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism
4.
Nanoscale ; 16(14): 7085-7092, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38488869

ABSTRACT

A fiber-optic surface plasmon resonance (SPR) biosensor based on a silver-coated hollow fiber (HF) structure for glucose detection is presented. The sensor surface was immobilized with 4-mercaptophenylboronic acid (PMBA) acting as a glucose recognition monolayer. Then, gold nanoparticles (AuNPs) modified with 2-aminoethanethiol (2-AET) and PMBA were introduced onto the sensor surface after glucose was captured to enhance the wavelength shift of the SPR phenomenon excited by the light transmitted in the wall of the HF sensor. Instead of the conventional one-step sensitization pretreatment commonly used in the deposition process of silver films for fiber-optic SPR sensors, a sensitization-activation two-step activation method was adopted in the fabrication of the proposed sensor. Experiments for glucose detection were performed on the fabricated sensors in the concentration range of 1 nM-1 mM. Results showed that the sensor fabricated by the two-step activation method has a much larger shift of resonance wavelength than the sensor fabricated using the one-step sensitization method. The resonance wavelength shift was found to be linear to the logarithm of the concentration in the range of 1 nM-1 mM. The sensor achieved a limit of detection (LOD) of as low as 1 nM, which is at least an order of magnitude lower than that of other fiber-optic sensors for glucose detection reported previously. The presented HF glucose sensor has the potential for biosensing applications and provides a large reference value in the study of optical fiber SPR sensors for biosensing.

5.
Biomedicines ; 12(3)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38540274

ABSTRACT

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

6.
Proc Natl Acad Sci U S A ; 121(14): e2317444121, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38527208

ABSTRACT

Dust loading in West and South Asia has been a major environmental issue due to its negative effects on air quality, food security, energy supply and public health, as well as on regional and global weather and climate. Yet a robust understanding of its recent changes and future projection remains unclear. On the basis of several high-quality remote sensing products, we detect a consistently decreasing trend of dust loading in West and South Asia over the last two decades. In contrast to previous studies emphasizing the role of local land use changes, here, we attribute the regional dust decline to the continuous intensification of Arctic amplification driven by anthropogenic global warming. Arctic amplification results in anomalous mid-latitude atmospheric circulation, particularly a deepened trough stretching from West Siberia to Northeast India, which inhibits both dust emissions and their downstream transports. Large ensemble climate model simulations further support the dominant role of greenhouse gases induced Arctic amplification in modulating dust loading over West and South Asia. Future projections under different emission scenarios imply potential adverse effects of carbon neutrality in leading to higher regional dust loading and thus highlight the importance of stronger anti-desertification counter-actions such as reforestation and irrigation management.

7.
Front Immunol ; 15: 1324010, 2024.
Article in English | MEDLINE | ID: mdl-38370418

ABSTRACT

Triggering receptor expressed on myeloid cells 1 (TREM1), which belongs to the Ig-like superfamily expressed on myeloid cells, is reportedly involved in various diseases but has rarely been studied in glioma. In this study, the prognostic value and functional roles of TREM2 in glioma were analyzed. TERM1 was observed to be significantly upregulated in GBM compared to in other grade gliomas and was associated with poor prognosis. Increased TREM1 accompanied distinct mutation and amplification of driver oncogenes. Moreover, gene ontology and KEGG analyses showed that TREM1 might play a role in immunologic biological processes in glioma. TREM1 was also found to be tightly correlated with immune checkpoint molecules. xCell research revealed a link between TREM1 expression and multiple immune cell types, especially monocytes and macrophages. Single-cell analysis and immunofluorescence results showed that macrophages expressed TREM1. In vitro, inhibition of TREM1 signaling could result in a decrease in tumor-promoting effects of monocytes/TAMs. In summary, TREM1 may be a potential independent prognostic factor and immune target, which might provide new avenues to improve the efficacy of immunotherapy in glioma patients.


Subject(s)
Glioma , Macrophages , Humans , Triggering Receptor Expressed on Myeloid Cells-1/genetics , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Prognosis , Macrophages/metabolism , Glioma/genetics , Glioma/metabolism , Monocytes/metabolism
8.
Ultrason Sonochem ; 103: 106781, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38281445

ABSTRACT

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P < 0.05) following injection of 0.01 % activated carbon, however the average variation rate of salvia miltiorrhizae injection was dramatically decreased with the use of UACS and CACA (P > 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.


Subject(s)
Alkenes , Benzaldehydes , Benzofurans , Caffeic Acids , Catechols , Depsides , Drugs, Chinese Herbal , Polyphenols , Salvia miltiorrhiza , Drugs, Chinese Herbal/chemistry , Salvia miltiorrhiza/chemistry , Charcoal , Ultrasonics , Rosmarinic Acid , Endotoxins
9.
Soft Matter ; 20(6): 1253-1262, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38235808

ABSTRACT

Small-molecular-induced intermolecular hydrogen bonding (inter-HB) interactions were reported to increase the glass transition temperature (Tg) while decrease the dynamic fragility (m) of polymers. Herein, enthalpy relaxation parameters heat capacity jump (ΔCp) at Tg and enthalpy hysteresis (ΔHR) were investigated to help clarify the effect of macromolecular-induced inter-HB on Tg and m using amorphous polyamides as model polymers. The inter-HB strength was weakened by random copolymerization with varied chain rigidity, but was enhanced by decreasing steric hindrance. It was found that Tg and m increased after copolymerization due to the increased chain rigidity. Nevertheless, increasing steric hindrance leads to an increased Tg while anomalously reduced m. Further results found that m can be well correlated to Tg·ΔCp/ΔHR. ΔCp increases more significantly than ΔHR in co-polyamides, and thus the entropy change dominates the activation free energy of cooperative rearrangement. By contrast, ΔHR increases more significantly than ΔCp with increasing steric hindrance, and thus it is reasonable that Tg increases while m decreases. Most importantly, ΔCp and ΔHR decrease with increasing inter-HB strength regardless of the variation of Tg. These results indicate that the inter-HB strength may be very strong and insensitive to temperature in polyamides, thus behaving like physical cross-linking.

10.
Sci Total Environ ; 916: 170253, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38253097

ABSTRACT

Root exudates are pivotal in plant stress responses, however, the impact of microplastics (MPs) on their release and characteristics remains poorly understood. This study delves into the effects of 0.05 % and 0.1 % (w/w) additions of polyethylene (PE) MPs on the growth and physiological properties of lettuce (Lactuca sativa L.) following 28 days of exposure. The release characteristics of root exudates were assessed using UV-vis and 3D-EEM. The results indicated that PE increased leaf number but did not significantly affect other agronomic traits or pigment contents. Notably, 0.05 % PE increased the total root length and surface area compared to the 0.1 % addition, while a non-significant trend towards decreased root activity was observed with PE MPs. PE MPs with 0.1 % addition notably reduced the DOC concentration in root exudates by 37.5 %, while 0.05 % PE had no impact on DOC and DON concentrations. PE addition increased the SUVA254, SUVA260, and SUVA280 values of root exudates, with the most pronounced effect seen in the 0.05 % PE treatment. This suggests an increase of aromaticity and hydrophobic components induced by PE addition. Fluorescence Regional Integration (FRI) analysis of 3D-EEM revealed that aromatic proteins (region I and II) were dominant in root exudates, with a slight increase in fulvic acid-like substances (region III) under 0.1 % PE addition. Moreover, prolonged PE exposure induced ROS damage in lettuce leaves, evidenced by a significant increase in content and production rate of O2·-. The decrease in CAT and POD activities may account for the lettuce's response to environmental stress, potentially surpassing its tolerance threshold or undergoing adaptive regulation. These findings underscore the potential risk of prolonged exposure to PE MPs on lettuce growth.


Subject(s)
Microplastics , Plastics , Microplastics/metabolism , Plastics/metabolism , Polyethylene/metabolism , Lactuca , Hydroponics , Oxidative Stress
11.
J Orthop Res ; 42(3): 685-699, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37794686

ABSTRACT

Traditional growing rod (TGR) provides a corrective moment for deformed segments to straighten the spine, whose clinical efficacy has proven positive and growth-friendly. However, an insufficient understanding of orthopedic mechanisms can affect the development of clinical strategies. This research attempts to analyze the spine that has undergone four distraction operations: exploring the spinal orthopedic mechanism, including alignment, growth, and morphology. In this study, the spinal morphology curves were illustrated in three human planes to exhibit the changes in spinal alignment. The spinal growth characteristics were measured to discuss the unsynchronized and diminishing growth rate. The spinal deformations were evaluated to indicate asymmetric growth. As a result, the spinal alignment changes indicated the orthopedic process improved, but the re-unbalance occurred after multiple distractions. Then, unsynchronized growth existed in the superior and inferior segments, and the growth rate over every distraction diminished. Finally, asymmetric growth was indicated as the axial/circumferential growth ratio getting greater and the cuneate level approaching normal. Accordingly, a TGR is growth-friendly, but combining the osteotomy fusion of lumbar segments for severe early-onset scoliosis may be an excellent choice to solve the insufficient corrective stimulation. Regarding the distraction process, reshaping before the final fusion can fix the balance loss, and a prolonged distraction frequency fits the law of diminishing return. In conclusion, studying orthopedic mechanisms based on morphological measurement can guide clinical strategy optimization.


Subject(s)
Orthopedic Procedures , Osteogenesis, Distraction , Scoliosis , Humans , Scoliosis/surgery , Spine/surgery , Treatment Outcome , Osteotomy , Retrospective Studies
12.
Biomed Tech (Berl) ; 69(2): 151-165, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-37823389

ABSTRACT

OBJECTIVES: Fatigue has a considerable impact on the driver's vehicle and even the driver's own operating ability. METHODS: An intelligent algorithm is proposed for the problem that it is difficult to classify the degree of drowsiness generated by the driver during the driving process. By studying the driver's electrocardiogram (ECG) during driving, two models were established to jointly classify the ECG signals as awake, stress, and fatigue or drowsiness states for drowsiness levels. Firstly, the deep learning method was used to establish the model_1 to predict the drowsiness of the original ECG, and model_2 was developed using the combination of principal component analysis (PCA) and weighted K-nearest neighbor (WKNN) algorithm to classify the heart rate variability characteristics. Then, the drowsiness prediction results of the two models were weighted according to certain rules, and the hybrid learning model combining dilated convolution and bidirectional long short-term memory network with PCA and WKNN algorithm was established, and the mixed model was denoted as DiCNN-BiLSTM and PCA-WKNN (DBPW). Finally, the validity of the DBPW model was verified by simulation of the public database. RESULTS: The experimental results show that the average accuracy, sensitivity and F1 score of the test model in the dataset containing multiple drivers are 98.79, 98.81, and 98.79 % respectively, and the recognition accuracy for drowsiness or drowsiness state is 99.33 %. CONCLUSIONS: Using the proposed algorithm, it is possible to identify driver anomalies and provide new ideas for the development of intelligent vehicles.


Subject(s)
Algorithms , Wakefulness , Humans , Wakefulness/physiology , Computer Simulation , Electrocardiography , Fatigue
13.
Neural Netw ; 169: 378-387, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37924607

ABSTRACT

The effective use of temporal relationships while extracting fertile spatial features is the key to video action understanding. Video action understanding is a challenging visual task because it generally necessitates not only the features of individual key frames but also the contextual understanding of the entire video and the relationships among key frames. Temporal relationships pose a challenge to video action understanding. However, existing 3D convolutional neural network approaches are limited, with a great deal of redundant spatial and temporal information. In this paper, we present a novel two-stream approach that incorporates Spatial Residual Attention and Temporal Markov (SRATM) to learn complementary features to achieve stronger video action understanding performance. Specifically, the proposed SRATM consists of spatial residual attention and temporal Markov. Firstly, the spatial residual attention network captures effective spatial feature representation. Further, the temporal Markov network enhances the model by learning the temporal relationships via conducting probabilistic logic calculation among frames in a video. Finally, we conduct extensive experiments on four video action datasets, namely, Something-Something-V1, Something-Something-V2, Diving48, and Mini-Kinetics, show that the proposed SRATM method achieves competitive results.


Subject(s)
Learning , Neural Networks, Computer , Physics
14.
Sci Rep ; 13(1): 21592, 2023 12 07.
Article in English | MEDLINE | ID: mdl-38062071

ABSTRACT

Ferroptosis is a form of cell death that is triggered by iron-dependent lipid peroxidation and is closely associated with osteoarthritis. The primary interventions for inhibiting ferroptosis in osteoarthritis are anti-lipid peroxidation and iron chelation. The objective of our study is to investigate the characteristics of ferroptosis in osteoarthritis and identify the optimal time points for inhibiting ferroptosis to alleviate disease progression. Ferroptosis-related alterations and markers of OA were analyzed in paired intact and damaged cartilages from OA patients by immunofluorescence, qRT-PCR, mitochondrial membrane potential and immunohistochemistry. We also compared Ferroptosis-related alterations in cartilage of mild, moderate, and severe OA (according to the modified Mankin score). In addition, we compared the effect of Fer-1 on ferroptosis and the protection of chondrocytes by detecting markers of both ferroptosis and OA by immunofluorescence, CCK8 and qRT-PCR. Ferroptosis-related alterations (GPX4 downregulation, ACSL4 upregulation, MDA, LPO accumulation, Mitochondrial membrane potential decreased) in the damaged area cartilage were more severe than those in the intact area and increased with the progression of OA. Compared with mild OA group, the activity of chondrocytes treated with Fer-1 (a ferroptosis inhibitor) was increased, mitochondrial function was improved, and ferroptosis was reduced (GPX4 upregulation, SLC7A11 upregulation, ACSL4 downregulation,), and promoted the expression of COL2A1 and inhibited the expression of MMP13. However, these changes were not observed in moderate and severe OA chondrocytes. Ferroptosis occurs in a region-specific manner and is exacerbated with the progression of human OA cartilage degeneration. Inhibition of ferroptosis might had a therapeutic effect on chondrocytes with mild OA but had no significant therapeutic effect on chondrocytes with moderate to severe OA.


Subject(s)
Cartilage, Articular , Ferroptosis , Osteoarthritis , Humans , Cartilage, Articular/metabolism , Cells, Cultured , Osteoarthritis/metabolism , Chondrocytes/metabolism
15.
J Cell Mol Med ; 27(23): 3928-3938, 2023 12.
Article in English | MEDLINE | ID: mdl-37799103

ABSTRACT

Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first-line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side-effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Engeletin, a natural Smilax glabra rhizomilax derivative, is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The effects of engeletin were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Engeletin was also investigated in the chronic restraint stress (CRS) mouse model of depression with fluoxetine (FLX) as the positive control. Changes in prefrontal cortex (PFC) spine density, synaptic plasticity-linked protein expressions and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB)- mammalian target of rapamycin complex 1 (mTORC1) signalling pathway after chronic stress and engeletin treatment were then investigated. The TrkB and mTORC1 selective inhibitors, ANA-12 and rapamycin, respectively, were utilized to assess the engeletin's antidepressive mechanisms. Our data shows that engeletin exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. Furthermore, it exhibited efficiency against the depression of CRS model. Moreover, it enhanced the BDNF-TrkB-mTORC1 pathway in the PFC during CRS and altered the reduction in dendritic spine density and levels of synaptic plasticity-linked protein induced by CRS. In conclusion, engeletin has antidepressant activity via activation of the BDNF-TrkB-mTORC1 signalling pathway and upregulation of PFC synaptic plasticity.


Subject(s)
Depressive Disorder, Major , Neuronal Plasticity , Receptor, trkB , Animals , Humans , Mice , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Brain-Derived Neurotrophic Factor/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Depressive Disorder, Major/drug therapy , Hippocampus/metabolism , Mammals/metabolism , Mechanistic Target of Rapamycin Complex 1/drug effects , Mechanistic Target of Rapamycin Complex 1/metabolism , Protein-Tyrosine Kinases/metabolism , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Neuronal Plasticity/drug effects , Receptor, trkB/drug effects , Receptor, trkB/metabolism
16.
China CDC Wkly ; 5(35): 779-784, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37745265

ABSTRACT

Introduction: Over the latter half of the previous century, pulmonary heart disease (PHD) emerged as a significant public health issue in China. However, the current mortality rate is unknown. Utilizing the Multiple Cause of Death database, the present study aims to investigate the current state and progression of PHD-associated death in China. Methods: Data from the China National Mortality Surveillance System were used to analyze progression in mortality rates attributable to PHD from 2014 to 2021. To standardize population structure for each year during the investigation period, demographic information from the 2020 census was employed as the reference population. Age-standardized mortality rates (ASMR) were determined based on sex, urban-rural area, and region. To identify trends in ASMR, a joinpoint regression analysis was executed. Results: The ASMR of PHD exhibited a marked decrease, falling from 61.68 per 100,000 in 2014 to 28.53 per 100,000 in 2021. This downward trend was observable in both genders, all regions, and both urban and rural settings. The greatest ASMR values were documented in the western region. Comparative observations revealed a higher ASMR in rural areas versus urban ones and in males versus females. PHD-associated deaths predominantly occurred among older individuals, particularly those aged 80 and above. Chronic obstructive pulmonary disease (COPD) emerged as the principal underlying cause of death PHD-associated mortalities, accounting for between 87.41% and 93.42% of cases throughout the period 2014-2021. Conclusions: There was a declining trend in PHD mortality in China from 2014 to 2021, with COPD accounting for a significant proportion of these deaths. Given the high prevalence of COPD and the escalating population aging in China, PHD remains a significant health concern that warrants further attention.

17.
BMC Cancer ; 23(1): 893, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37735368

ABSTRACT

BACKGROUND: Pancreatic cancer is a growing public health concern in China, and depicting it from different perspectives would provide a comprehensive understanding of its epidemiological characteristics. METHODS: Data from the National Mortality Surveillance System (NMSS) in China was used to estimate the number of deaths, years of life lost (YLL), age-standardized mortality rate (ASMR) and age-standardized YLL rate in China, its provinces and urban-rural areas from 2005 to 2020. Joinpoint regression analysis was employed to explore the temporal trends of ASMR and age-standardized YLL rate. Decomposition analysis was conducted to assess the contribution of population growth, population aging and cause-specific mortality rate to the increment of pancreatic cancer deaths. RESULTS: A total of 100,427 pancreatic cancer deaths and 2,166,355 pancreatic cancer related YLL were estimated in China in 2020. The overall ASMR significantly increased from 6.6/100 000 in 2005 to 7.4/100 000 in 2020, and was higher in men than that in women. Age-standardized YLL rate showed a similar trend. The mortality rates of pancreatic cancer were generally higher in northeast China than in southwest China. The highest ASMRs were found in Jilin, Zhejiang, Inner Mongolia and Anhui, and the lowest ones in Guangxi, Yunnan, Tibet, and Hainan. The disease burden due to pancreatic cancer presented a significant upward trend in rural areas and a downward trend in urban areas. CONCLUSIONS: The burden associated with pancreatic cancer had been increasing in China from 2005 to 2020. The escalating disease burden of pancreatic cancer in rural areas necessitates the implementation of effective control and prevention measures. Relevant provinces should pay greater attention to the prevailing of pancreatic cancer, particularly those exhibiting higher mortality rates.


Subject(s)
Pancreatic Neoplasms , Male , Female , Humans , China/epidemiology , Pancreatic Neoplasms/epidemiology , Tibet , Pancreas , Aging
18.
Virol Sin ; 38(6): 911-921, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37659477

ABSTRACT

African swine fever (ASF) is originally reported in East Africa as an acute hemorrhagic fever. African swine fever virus (ASFV) is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response. S273R protein (pS273R), as a SUMO-1 specific cysteine protease, can affect viral packaging by cutting polymeric proteins. In this study, we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon (IFN-I) production. A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3 (IRF3). Subsequently, we showed that pS273R disrupted the association between TBK1 and IRF3, leading to the repressed IRF3 phosphorylation and dimerization. Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity. These findings will help us further understand ASFV pathogenesis.


Subject(s)
African Swine Fever Virus , African Swine Fever , Cysteine Proteases , Interferon Type I , Swine , Animals , African Swine Fever Virus/genetics , Protein Serine-Threonine Kinases/genetics , Interferon Regulatory Factor-3 , Interferon Type I/metabolism , Cysteine Proteases/metabolism
19.
Opt Express ; 31(16): 26398-26409, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37710502

ABSTRACT

A dielectric/Ag-coated hollow fiber (HF) temperature sensor based on long-range surface plasmon resonance (LRSPR) is proposed and experimentally demonstrated. The structural parameters, including the dielectric material and layer thicknesses, are optimized through comprehensive theoretical analysis to achieve the best performance. By filling it with a high refractive index (RI) thermosensitive liquid, the GK570/Ag-coated HF temperature sensor with optimal structural parameters is fabricated. Due to the high sensitivity of the LRSPR sensor and the optimized design, the fabricated sensor achieves a temperature sensitivity of 3.6∼20.5 nm/°C, which is almost the highest among the optical fiber temperature sensors based on surface plasmon resonance reported experimentally. Moreover, the detection range of the proposed sensor can be easily tuned up to 170°C by varying the RI of the filled thermosensitive liquid, and the sensor performance remains stable. Considering that most temperature sensors using polydimethylsiloxane have a fixed detection range, this is an outstanding advantage that could expand the application field of the optical fiber temperature sensor.

20.
J Orthop Surg Res ; 18(1): 620, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620972

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is a prevalent disease plaguing the elderly. Recently, chondrocyte ferroptosis has been demonstrated to promote the progression of OA. Peroxisome proliferator-activated receptor-γ (PPARγ) is an important factor in maintaining cartilage health. However, the relationship between PPARγ and chondrocyte ferroptosis in OA and its mechanism is completely unclear. METHODS: We established a surgically induced knee OA rat model to investigate PPARγ and chondrocyte ferroptosis in OA. Rat knee specimens were collected for Safranin O/Fast Green staining and immunohistochemical staining after administered orally placebo or pioglitazone (PPARγ agonist) for 4 weeks. We used RSL3 to establish a chondrocyte ferroptosis model cultured in vitro to study the role of PPARγ activation toward ferroptosis, mitochondrial function, and PTEN-induced putative kinase 1 (Pink1)/Parkin-dependent mitophagy. GW9662 (PPARγ antagonist), Mdivi-1 (mitophagy inhibitor), and chloroquine (mitophagy inhibitor) were employed to investigate the mechanism of PPARγ-Pink1/Parkin-dependent mitophagy in the inhibition of ferroptosis. RESULTS: We found that PPARγ activation by pioglitazone attenuated not only OA but also inhibited the expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 (ACSL4) at the same time in rats. Furthermore, in vivo and in vitro data indicated that PPARγ activation restored Pink1/Parkin-dependent mitophagy, improved mitochondrial function, inhibited chondrocyte ferroptosis, and delayed the progression of OA. CONCLUSIONS: The present study demonstrated that PPARγ activation attenuates OA by inhibiting chondrocyte ferroptosis, and this chondroprotective effect was achieved by promoting the Pink1/Parkin-dependent mitophagy pathway.


Subject(s)
Ferroptosis , Mitophagy , Osteoarthritis, Knee , PPAR gamma , Animals , Rats , Chondrocytes , Pioglitazone/pharmacology , PPAR gamma/metabolism , Protein Kinases
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