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1.
Bioinformatics ; 40(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38715444

ABSTRACT

MOTIVATION: Exploring potential associations between diseases can help in understanding pathological mechanisms of diseases and facilitating the discovery of candidate biomarkers and drug targets, thereby promoting disease diagnosis and treatment. Some computational methods have been proposed for measuring disease similarity. However, these methods describe diseases without considering their latent multi-molecule regulation and valuable supervision signal, resulting in limited biological interpretability and efficiency to capture association patterns. RESULTS: In this study, we propose a new computational method named DiSMVC. Different from existing predictors, DiSMVC designs a supervised graph collaborative framework to measure disease similarity. Multiple bio-entity associations related to genes and miRNAs are integrated via cross-view graph contrastive learning to extract informative disease representation, and then association pattern joint learning is implemented to compute disease similarity by incorporating phenotype-annotated disease associations. The experimental results show that DiSMVC can draw discriminative characteristics for disease pairs, and outperform other state-of-the-art methods. As a result, DiSMVC is a promising method for predicting disease associations with molecular interpretability. AVAILABILITY AND IMPLEMENTATION: Datasets and source codes are available at https://github.com/Biohang/DiSMVC.


Subject(s)
Computational Biology , Humans , Computational Biology/methods , Disease , Algorithms , MicroRNAs/genetics , Software , Machine Learning
2.
Mol Cell Proteomics ; 22(4): 100525, 2023 04.
Article in English | MEDLINE | ID: mdl-36871861

ABSTRACT

Energy homeostasis of mammals during cold exposure involves complicated neural regulation and is affected by gut microbiota. However, the regulatory mechanism remains unclear partially due to a lack of comprehensive knowledge of the signaling molecules involved. Herein, we performed region-resolvable quantitative profiling of the brain peptidome using cold-exposed mouse models and interrogated the interaction between gut microbes and brain peptides in response to cold. Region-specific alterations in the brain peptidome were observed during chronic cold exposure and were correlated with gut microbiome composition. Several proSAAS-derived peptides exhibited a positive correlation with Lactobacillus. The hypothalamus-pituitary axis exhibited a sensitive response to cold exposure. We obtained a candidate pool of bioactive peptides that potentially participate in the regulation of cold-induced energy homeostasis. Intervention with cold-adapted microbiota in mice decreased the abundance of hypothalamic neurokinin B and subsequently contributed to shifting the fuel source for energy consumption from lipids to glucose. Collectively, this study demonstrated that gut microbes modulate brain peptides contributing to energy metabolism, providing a data resource for understanding the regulatory mechanism of energy homeostasis upon cold exposure.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Animals , Mice , Gastrointestinal Microbiome/physiology , Brain/metabolism , Energy Metabolism , Homeostasis , Mammals
3.
Anal Chem ; 96(8): 3662-3671, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38363802

ABSTRACT

Precise profiling of the cytokine panel consisting of different levels of cytokines can provide personalized information about several diseases at certain stages. In this study, we have designed and fabricated an "all-in-one" diagnostic tool kit to bioassay multiple inflammatory cytokines ranging from picograms per milliliter to µg/mL in a small cytokine panel. Taking advantage of the kit fabricated by the DNA-encoded assembly of nanocatalysts in dynamic regulation and signal amplification, we have demonstrated the multiplex, visual, and quantitative detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) with limits of detection of 1.6 ng/mL (61.54 pM), 20 pg/mL (1.57 pM), and 4 pg/mL (0.19 pM), respectively. This diagnostic tool kit can work well with commercial kits for detecting serum cytokines from breast cancer patients treated with immunotherapies. Furthermore, a small cytokine panel composed of CRP, PCT, and IL-6 is revealed to be significantly heterogeneous in each patient and highly dynamic for different treatment courses, showing promise as a panel of quantitative biomarker candidates for individual treatments. So, our work may provide a versatile diagnostic tool kit for the visual detection of clinical biomarkers with an adjustable broad detection range.


Subject(s)
Breast Neoplasms , Cytokines , Humans , Female , Interleukin-6 , Breast Neoplasms/diagnosis , C-Reactive Protein , Biomarkers , Procalcitonin
4.
Small ; : e2402752, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822717

ABSTRACT

Surface modification of Cu current collectors (CCs) is proven to be an effective method for protecting lithium metal anodes. However, few studies have focused on the quality and efficiency of modification layers. Herein, a novel home-made filtered cathode vacuum arc (FCVA) co-deposition system with high modification efficiency, good repeatability and environmental friendliness is proposed to realize the wide range regulation of film composition, structure and performance. Through this system, ZnMgTiAl quaternary alloy films, which have good affinity with Li are successfully constructed on Cu CCs, and the fully enhanced electrochemical performances are achieved. Symmetrical cells constructed with modified CCs maintained a fairly low voltage hysteresis of only 13 mV after 2100 h at a current density of 1 mA cm-2. In addition, the capacity retention rate is as high as 75.0% after 100 cycles in the full cells. The influence of alloy films on the dynamic evolution process of constructing stable artificial solid electrolyte interphase (SEI) layer is revealed by in situ infrared (IR) spectroscopy. This work provides a promising route for designing various feasible modification films for LMBs, and it displays better industrial application prospects than the traditional chemical methods owing to the remarkable controllability and scale-up capacity.

5.
Opt Express ; 32(4): 6409-6422, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38439344

ABSTRACT

In this paper, a novel laser spot tracking algorithm that incorporates the Kalman filter with the continuously adaptive Meanshift algorithm (Cam-Kalm) is proposed and employed in an underwater optical wireless communication (UOWC) system. Since the Kalman filter has the advantage of predicting the state information of the target spot based on its spatial motion features, the proposed algorithm can improve the accuracy and stability of the moving laser spot tracking. A 2 m optical wireless communication experimental system with auto-tracking based on a green laser diode (LD) is built to evaluate the tracking performance of different algorithms. Experimental results verify that the proposed algorithm outperforms conventional tracking algorithms in aspects of tracking accuracy, interference resistance, and response time. With the proposed Cam-Kalm algorithm, the experimental system can establish an effective communication link, while the maximum tracking speed is 20 mm/s given the forward-error-correction (FEC) threshold.

6.
FASEB J ; 37(10): e23128, 2023 10.
Article in English | MEDLINE | ID: mdl-37651092

ABSTRACT

Alterations in DNA methylation in malignant diseases have been heralded as promising targets for diagnostic, prognostic, and predictive values. This study was based on epigenetic alterations and immune cell infiltration analysis to investigate the mechanism of CD3D methylation in uveal melanoma (UM). Bioinformatics analysis was performed on transcriptome data, 450 K methylation data, and clinical information of UM patients from the TCGA database. Stromal and immune cell infiltration was evaluated by calculating the StromalScore and ImmuneScore of UM samples. UM samples were divided into high and low StromalScore and ImmuneScore groups, followed by differential and enrichment analyses. PPI network construction and correlation analysis was used to identify the core prognosis-related genes. The bioinformatics analysis results were confirmed in UM cell experiments. StromalScore and ImmuneScore were significantly associated with the prognosis of UM patients. CD3D, IRF1, CCL3, and FN1 were identified as core genes driven by methylation that affected the prognosis of UM patients. CD3D expression showed the highest correlation with its methylation and was closely related to the four key immune cells in UM development. CD3D was hypomethylated and abundantly expressed in UM cells, while silencing of CD3D inhibited the proliferation, migration, and invasion of UM cells in vitro. In summary, this study identifies hypomethylation of CD3D promoter in UM, which was associated with immune cell infiltration of UM.


Subject(s)
Melanoma , Uveal Neoplasms , Humans , DNA Methylation , Melanoma/genetics , Phenotype , Uveal Neoplasms/genetics , Promoter Regions, Genetic
7.
FASEB J ; 37(5): e22885, 2023 05.
Article in English | MEDLINE | ID: mdl-37000492

ABSTRACT

Recent studies have reported the promising value of differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) for identifying disease biomarkers. Based on this method, this study intends to characterize the hub genes and pathways related to retinal photoreceptor cell (PRC) injury in the context of retinitis pigmentosa (RP). A total of 53 coexpression modules were identified by WGCNA, among which lightpink4, darkolivegreen, tan4, blue2, skyblue2, and navajowhite2 ranked at the top. By analyzing the RP microarrays retrieved from the GEO database, 338 differentially expressed genes (DEGs) were identified in the RP samples. Forty-five candidate genes were selected from these DEGs by intersection with the genes in the coexpression modules. These intersection genes were subjected to GO and KEGG analyses. Furthermore, the genes and pathways involved in PRC damage were identified based on analyses utilizing GeneCards and STRING tools. Transcription factor 7-like 1 (TCF7L1, also called TCF3) was suggested to participate in the RP-associated PRC damage through the Wnt signaling pathway. It was validated in a blue light-irradiated cell model that TCF7L1 overexpression boosted PRC viability and repressed apoptosis. Inhibition of the Wnt signaling pathway also contributed to protective effects. Together, the data mentioned above supported the conclusion that either elevation of TCF7L1 or blockade of the Wnt signaling pathway could prevent RP progression by protecting PRCs from damage.


Subject(s)
Gene Regulatory Networks , Retinitis Pigmentosa , Humans , Photoreceptor Cells, Vertebrate , Microarray Analysis , Databases, Genetic , Retinitis Pigmentosa/genetics , Gene Expression Profiling/methods , Transcription Factor 7-Like 1 Protein
8.
BMC Pulm Med ; 24(1): 312, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961438

ABSTRACT

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/mortality , Male , Female , Middle Aged , China/epidemiology , Aged , Risk Factors , Hospitalization/statistics & numerical data , Adult , Prognosis , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Age Factors , Logistic Models , Neutrophils , Blood Urea Nitrogen , L-Lactate Dehydrogenase/blood
9.
Proc Natl Acad Sci U S A ; 118(36)2021 09 07.
Article in English | MEDLINE | ID: mdl-34462360

ABSTRACT

Inspired by the embodied intelligence observed in octopus arms, we introduce magnetically controlled origami robotic arms based on Kresling patterns for multimodal deformations, including stretching, folding, omnidirectional bending, and twisting. The highly integrated motion of the robotic arms is attributed to inherent features of the reconfigurable Kresling unit, whose controllable bistable deploying/folding and omnidirectional bending are achieved through precise magnetic actuation. We investigate single- and multiple-unit robotic systems, the latter exhibiting higher biomimetic resemblance to octopus' arms. We start from the single Kresling unit to delineate the working mechanism of the magnetic actuation for deploying/folding and bending. The two-unit Kresling assembly demonstrates the basic integrated motion that combines omnidirectional bending with deploying. The four-unit Kresling assembly constitutes a robotic arm with a larger omnidirectional bending angle and stretchability. With the foundation of the basic integrated motion, scalability of Kresling assemblies is demonstrated through distributed magnetic actuation of double-digit number of units, which enables robotic arms with sophisticated motions, such as continuous stretching and contracting, reconfigurable bending, and multiaxis twisting. Such complex motions allow for functions mimicking octopus arms that grasp and manipulate objects. The Kresling robotic arm with noncontact actuation provides a distinctive mechanism for applications that require synergistic robotic motions for navigation, sensing, and interaction with objects in environments with limited or constrained access. Based on small-scale Kresling robotic arms, miniaturized medical devices, such as tubes and catheters, can be developed in conjunction with endoscopy, intubation, and catheterization procedures using functionalities of object manipulation and motion under remote control.


Subject(s)
Robotics/instrumentation , Biomimetics , Equipment Design
10.
Environ Geochem Health ; 46(4): 117, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38478119

ABSTRACT

Continuous exposure to airborne pesticides causes their gradual accumulation in the human body, eventually posing a threat to human health. To the best of our knowledge, risk assessment study of pesticide non-occupational exposure to residents in agricultural areas has not been conducted in China. In this study, air samples (gas and dust) were collected from inside and outside residences of seven households and an area near the field in a grain-growing area (wheat and maize rotation) for eight months, and the pesticides present were examined both qualitatively and quantitatively. Using a 95% confidence interval, 9 out of 16 pesticides were detected, namely acetamiprid, acetochlor, atrazine, flucarbazone-sodium, imidacloprid, methyldisulfuron-methyl, nicosulfuron-methyl, pendimethalin, and beta-cyhalothrin, and their safety was subsequently evaluated. The results showed that the inhalation exposure of households to beta-cyhalothrin exceeded the acceptable range in the first residential, and the excess lifetime cancer risk of acetochlor inhalation exposure in six households and area around the field exceeds 1E-6, which highlights the need to strengthen preventive screening for cancer risk.


Subject(s)
Neoplasms , Nitriles , Pesticides , Pyrethrins , Toluidines , Humans , Pesticides/toxicity , Pesticides/analysis , Environmental Exposure/analysis , Risk Assessment
11.
J Neurochem ; 166(5): 847-861, 2023 09.
Article in English | MEDLINE | ID: mdl-37526008

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) technologies enable the profiling and analysis of the transcriptomes of single cells and hold promise for clarifying gene mechanisms at single-cell resolution. We based this study on scRNA-seq data to reveal glaucoma-related genes and downstream pathways with neuroprotection effects. The scRNA-seq datasets related to glaucoma of retinal tissue samples of human beings and Atonal Homolog 7 (ATOH7)-null mice were obtained from the GEO database. The 74 top marker genes and 20 cell clusters were obtained in human retinal tissue samples. The key gene ATOH7 was found after the intersection with genes from GeneCards data. In the ATOH7-null mouse retinal tissue samples, pseudotime inference demonstrated significant changes in cell differentiation. Moreover, mouse retinal photoreceptor cells (PRCs) were cultured and treated with lentivirus carrying oe-ATOH7 alone or in combination with Notch signaling pathway activator Jagged-1/FC, after which cell biological functions were determined. The involvement of ATOH7 in glaucoma was identified through regulating PRCs. Furthermore, ATOH7 conferred neuroprotection in PRCs in glaucoma by mediating the Notch signaling pathway. In vitro data confirmed that ATOH7 overexpression promoted the differentiation of PRCs and inhibited their apoptosis by suppressing the Notch signaling pathway. The evidence provided by our study highlighted the involvement of ATOH7 in the blockade of the Notch signaling pathway, resulting in the neuroprotection for PRCs in glaucoma.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Glaucoma , Animals , Humans , Mice , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Neuroprotection , Photoreceptor Cells/metabolism , Retina/metabolism
12.
Mol Med ; 29(1): 126, 2023 09 14.
Article in English | MEDLINE | ID: mdl-37710185

ABSTRACT

BACKGROUND: Tumor immune microenvironment regulates the growth and metastasis of uveal melanoma (UM). This study aims to reveal the possible molecular mechanism of BRCA1-associated protein 1 (BAP1) mutations in affecting the tumor immune microenvironment in UM through mediating the nuclear factor-κB (NF-κB) signaling pathway. METHODS: TCGA and cBioPortal databases jointly analyzed the genes with high mutation frequency in UM samples. Following survival analysis of UM patients, UM samples with BAP1 mutations were subjected to immune cell infiltration analysis. The signaling pathways associated with the mutated genes were screened by GSEA. Subsequently, the differential BAP1 expression was analyzed in the selected UM cell lines with wild type (WT) or mutant type (MUT) BAP1. RESULTS: Bioinformatics analysis identified 12 genes mutated in the UM samples, while only BAP1 mutations were related to the prognosis of UM patients. UM patients with BAP1 mutations had higher immune cell infiltration. BAP1 mutations inhibited the NF-κB signaling pathway, suppressing the cytokine secretion and antigen presentation by macrophages. Rescue experiments confirmed that overexpressed NF-κB could reverse the effect of BAP1 mutations on the immunosuppressive microenvironment, thus suppressing the malignant phenotypes of UM cells. CONCLUSION: BAP1 mutations may inhibit the NF-κB signaling pathway, repressing the cytokine secretion and antigen presentation by macrophages, which induces the immunosuppressive microenvironment, enhances the malignant phenotypes of UM cells and ultimately promotes the growth and metastasis of UM.


Subject(s)
Melanoma , NF-kappa B , Humans , Signal Transduction , Melanoma/genetics , Mutation , Immunosuppressive Agents , Cytokines , Tumor Microenvironment/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics
13.
J Neuroinflammation ; 20(1): 83, 2023 Mar 25.
Article in English | MEDLINE | ID: mdl-36966295

ABSTRACT

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the central nervous system (CNS). Although studies have demonstrated that microglia facilitate remyelination in demyelinating diseases, the underlying mechanisms are still not fully characterized. We found that aryl hydrocarbon receptor (AhR), an environment sensor, was upregulated within the corpus callosum in the cuprizone model of CNS demyelination, and upregulated AhR was mainly confined to microglia. Deletion of AhR in adult microglia inhibited efficient remyelination. Transcriptome analysis using RNA-seq revealed that AhR-deficient microglia displayed impaired gene expression signatures associated with lysosome and phagocytotic pathways. Furthermore, AhR-deficient microglia showed impaired clearance of myelin debris and defected phagocytic capacity. Further investigation of target genes of AhR revealed that spleen tyrosine kinase (SYK) is the downstream effector of AhR and mediated the phagocytic capacity of microglia. Additionally, AhR deficiency in microglia aggravated CNS inflammation during demyelination. Altogether, our study highlights an essential role for AhR in microglial phagocytic function and suggests the therapeutic potential of AhR in demyelinating diseases.


Subject(s)
Demyelinating Diseases , Receptors, Aryl Hydrocarbon , Remyelination , Animals , Mice , Corpus Callosum/metabolism , Cuprizone/toxicity , Demyelinating Diseases/drug therapy , Disease Models, Animal , Mice, Inbred C57BL , Microglia/metabolism , Myelin Sheath/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Remyelination/physiology
14.
J Neurooncol ; 163(1): 71-82, 2023 May.
Article in English | MEDLINE | ID: mdl-37173511

ABSTRACT

PURPOSE: Classification and grading of central nervous system (CNS) tumours play a critical role in the clinic. When WHO CNS5 simplifies the histopathology diagnosis and places greater emphasis on molecular pathology, artificial intelligence (AI) has been widely used to meet the increased need for an automatic histopathology scheme that could liberate pathologists from laborious work. This study was to explore the diagnosis scope and practicality of AI. METHODS: A one-stop Histopathology Auxiliary System for Brain tumours (HAS-Bt) is introduced based on a pipeline-structured multiple instance learning (pMIL) framework developed with 1,385,163 patches from 1038 hematoxylin and eosin (H&E) slides. The system provides a streamlined service including slide scanning, whole-slide image (WSI) analysis and information management. A logical algorithm is used when molecular profiles are available. RESULTS: The pMIL achieved an accuracy of 0.94 in a 9-type classification task on an independent dataset composed of 268 H&E slides. Three auxiliary functions are developed and a built-in decision tree with multiple molecular markers is used to automatically formed integrated diagnosis. The processing efficiency was 443.0 s per slide. CONCLUSION: HAS-Bt shows outstanding performance and provides a novel aid for the integrated neuropathological diagnostic workflow of brain tumours using CNS 5 pipeline.


Subject(s)
Artificial Intelligence , Brain Neoplasms , Humans , Algorithms , Supervised Machine Learning , World Health Organization
15.
Macromol Rapid Commun ; 44(13): e2200974, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37153967

ABSTRACT

Volatile organic compounds (VOCs) may have short- and long-term adverse health effects. Especially, aromatic VOCs including benzene, toluene, ethylbenzene, and xylene (BTEX) are important indoor air pollutants. Developing highly efficient porous adsorbents with broad applicability remains a major challenge. In this study, a perchlorinated covalent-triazine framework (ClCTF-1-400) is prepared for adsorbing BTEX. ClCTF-1-400 is confirmed as a partially oxidized/chlorinated microporous covalent triazine framework through a variety of characterization. It is found that ClCTF-1-400 is reversible VOCs absorbent with very high absorption capacities, which can adsorb benzene (693 mg g-1 ), toluene (621 mg g-1 ), ethylbenzene (603 mg g-1 ), o-xylene (500 mg g-1 ), m-xylene (538 mg g-1 ), and p-xylene (592 mg g-1 ) at 25 °C and their saturated vapor pressure (≈ 1 kPa). ClCTF-1-400 is of higher adsorption capacities for all selected VOCs than activated carbon and other reported adsorbents. The adsorption mechanism is also inferred through theoretical calculation and in-site Fourier Transform Infrared (FTIR) spectroscopy. The observed excellent BTEX adsorption performance is attributed to the multiple weak interactions between the ClCTF-1-400 frameworks and aromatic molecules through multiple weak interactions (CH… π and CCl… π). The breakthrough experiment demonstrates ClCTF-1-400 has the potential for real VOCs pollutant removal in air.


Subject(s)
Volatile Organic Compounds , Benzene , Adsorption , Xylenes , Toluene
16.
Phys Chem Chem Phys ; 25(18): 12565-12586, 2023 May 10.
Article in English | MEDLINE | ID: mdl-37102210

ABSTRACT

Catalyst activity affects the reaction rate, and an increasing number of studies have shown that strain can significantly increase the electrocatalytic activity. Catalysts such as alloys and core-shell structures can modulate their properties through strain effects. Reasonable simulation techniques can be used to predict and design the catalytic performance based on understanding the strain action mechanism. Therefore, the methodological flow of theoretical simulations is summarised in this review. The mechanism underlying the strain-adsorption-reaction relationship is discussed using density functional theory (DFT) calculations. An introduction to DFT is given first, followed by a quick rundown of the strain classification and application. Typical electrocatalytic reactions, namely, the hydrogen and oxygen evolution reactions and oxygen reduction reaction, are taken as examples. After briefly explaining these reactions, the relevant studies on simulating the strain to tune the catalyst performance are covered. The simulation methods are summarised and analysed to observe the effects of strain on electrocatalytic properties. Finally, a summary of the issues with simulated strain-assisted design and a discussion on the perspectives and forecasts for the future design of effective catalysts are provided.

17.
Acta Pharmacol Sin ; 44(4): 766-779, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36229601

ABSTRACT

The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin (CAP), the main component of chili pepper. Despite studies in several neurological diseases, the role of TRPV1 in demyelinating diseases remains unknown. Herein, we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone (CPZ)-induced demyelination mouse model. TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice, whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination. TRPV1 was predominantly expressed in Iba1+ microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions. TRPV1 deficiency decreased microglial recruitment to the corpus callosum, with an associated increase in the accumulation of myelin debris. Conversely, the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance. Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment. In addition, the expression of the scavenger receptor CD36 was increased, and that of the glycolysis regulators Hif1a and Hk2 was decreased. We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.


Subject(s)
Demyelinating Diseases , Multiple Sclerosis , Animals , Humans , Mice , Cuprizone , Demyelinating Diseases/chemically induced , Demyelinating Diseases/drug therapy , Disease Models, Animal , Mice, Inbred C57BL , Microglia/metabolism , Multiple Sclerosis/drug therapy , Multiple Sclerosis/metabolism , Myelin Sheath/metabolism , TRPV Cation Channels , Capsaicin/pharmacology
18.
J Nanobiotechnology ; 21(1): 307, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37644442

ABSTRACT

A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion "recruitment" properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized "homing" target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized ß-cyclodextrin (ß-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE-/- mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Animals , Mice , Foam Cells , Biomimetics , Atherosclerosis/drug therapy , Biological Transport
19.
Proc Natl Acad Sci U S A ; 117(39): 24096-24101, 2020 09 29.
Article in English | MEDLINE | ID: mdl-32929033

ABSTRACT

Deployability, multifunctionality, and tunability are features that can be explored in the design space of origami engineering solutions. These features arise from the shape-changing capabilities of origami assemblies, which require effective actuation for full functionality. Current actuation strategies rely on either slow or tethered or bulky actuators (or a combination). To broaden applications of origami designs, we introduce an origami system with magnetic control. We couple the geometrical and mechanical properties of the bistable Kresling pattern with a magnetically responsive material to achieve untethered and local/distributed actuation with controllable speed, which can be as fast as a tenth of a second with instantaneous shape locking. We show how this strategy facilitates multimodal actuation of the multicell assemblies, in which any unit cell can be independently folded and deployed, allowing for on-the-fly programmability. In addition, we demonstrate how the Kresling assembly can serve as a basis for tunable physical properties and for digital computing. The magnetic origami systems are applicable to origami-inspired robots, morphing structures and devices, metamaterials, and multifunctional devices with multiphysics responses.

20.
Anim Biotechnol ; 35(1): 2276717, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37934003

ABSTRACT

The objective of this study was to assess the genetic diversity, phylogenetic relationship and population structure of five goat breeds in Shanxi, China. High genetic diversities were found in the five populations, among which, Licheng big green goat (LCBG) has the highest genetic diversity, while Jinlan cashmere goat (JLCG) population has the lowest genetic diversity. Bottleneck analysis showed the absence of recent genetic bottlenecks in the five goat populations. Genetic differentiation analysis shows that the closest genetic relationship between LCBG and LLBG (Lvliang black goat) was found, and the genetic distance between JLCG and the other four populations is the largest. The population structure of JLCG is different from the other four populations with K = 2, while LCBG and LLBG have high similarity population structure as the K value changes. Knowledge about genetic diversity and population structure of indigenous goats is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of goat breeds.


Subject(s)
Genetic Variation , Genetics, Population , Animals , Genetic Variation/genetics , Phylogeny , Goats/genetics , Microsatellite Repeats/genetics
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