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1.
IEEE Trans Vis Comput Graph ; 30(5): 2337-2346, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38437098

RESUMO

VR headsets have limited rendering capability, which limits the size and detail of the virtual environment (VE) that can be used in VR applications. One solution is cloud VR, where the "thin" VR clients are assisted by a server. This paper describes Cio VR, a cloud VR system that provides fast loading times, as needed to let users see and interact with the VE quickly at session startup or after teleportation. The server reduces the original VE to a compact representation through near-far partitioning. The server renders the far region to an environment map which it sends to the client together with the near region geometry, from which the client renders quality frames locally, with low latency. The near region starts out small and grows progressively, with strict visual continuity, minimizing startup time. The low-latency and fast-startup advantages of CloVR have been validated in a user study where groups of 8 participants wearing all-in-one VR headsets (Quest 2's) were supported by a laptop server to run a collaborative VR application with a 25 million triangle VE.

2.
J Chem Phys ; 160(12)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38526106

RESUMO

This study focuses on the recognition and isolation of fullerenes, which are crucial for further exploration of their physical and chemical properties. Our goal is to investigate the potential recognition of the D5h-C70 fullerene using crown-shaped metal compositions through density functional theory calculations. We assess the effectiveness of fullerene C70 recognition by studying the binding energy. Additionally, various analyses were conducted, including natural bond order charge analysis and reduced density gradient analysis, to understand the interaction mechanism between the host and guest molecules. These investigations provide valuable insights into the nature of the interaction and the stability of the host-guest system. To facilitate the release of the fullerene guest molecule, the vis-NIR spectra were simulated for the host-guest structures. This analysis offers guidance on the specific wavelengths that can be utilized to release the fullerene guest from the host-guest structures. Overall, this work proposes a new strategy for the effective recognition of various fullerene molecules and their subsequent release from host-guest systems. These findings could potentially be applied in assemblies involving fullerenes, advancing their practical applications.

3.
Heliyon ; 10(5): e26140, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449635

RESUMO

Background: Tactile sensors are utilized to measure multichannel pulse signals in pulse wave analysis (PWA). Owing to noise interferences, researchers have applied various denoising algorithms on multichannel pulse signals. To comprehensively assess these algorithms, numerous evaluation metrics have been proposed. However, these studies did not investigate the noise mechanisms in depth and lacked reference pulse signals, thus making the evaluations insufficiently objective. Materials and methods: An applicable denoising evaluation approach for multichannel pulse signal algorithms based on an arterial pulse acquisition system is established by superimposing real-world multichannel noise to the reference signals. The system, comprising a SphygmoCor and a uniaxial noise acquisition device, allows us to acquire single-reference pulse signals as well as real-world multichannel noise. Results: We assess eight popular denoising algorithms with three evaluation metrics, including amplitude relative error (ARE), mean square error (MSE) and increased percentage signal-noise ratio (SNR%). Our proposed approach provides accurate and objective evaluations of multichannel pulse signal denoising. Notably, classic algorithms for single-channel denoising are not recommended for multichannel denoising. Comparatively, RPCA-based algorithms can denoise pulse signals independently for each channel. Conclusion: This study sets the stage for the establishment of accurate and objective pulse signal denoising evaluations and provides insights for data-driven clinical diagnoses in cardiovascular medicine.

4.
Inorg Chem ; 63(2): 1188-1196, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38175718

RESUMO

Metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have attracted extensive research attention from researchers due to their potential applications in information encryption, anticounterfeiting technology, and security logic. In contrast to short-lived fluorescent materials, LPL materials offer a visible response that can be easily distinguished by the naked eye, thereby facilitating a much clearer visualization. However, there are few reports on functional LPL MOF materials as probes. In this article, two amino-functional LPL MOFs (VB4-2D and VB4-1D) were synthesized. They both exhibited adjustable fluorescence and phosphorescence from blue to green and from cyan to green, respectively. Notably, the MOFs emitted bright and adjustable LPL upon the removal of the different radiation sources. The basic amino functional groups in the MOFs exhibited acid and ammonia sensitivity, and fluorescence and phosphorescence emission intensities can be burst and restored in two atmospheres, respectively, which can be cycled multiple times. Furthermore, LPL intensity undergoes switching between two different conditions as well, which can be visually discerned by the naked eye, enabling visual sensing of volatiles by LPL. This combination of photoluminescence and the visual LPL switching behavior of acids and bases in functional MOFs may provide an effective avenue for stimulus response, anticounterfeiting, and encryption applications.

5.
J Am Med Inform Assoc ; 31(2): 426-434, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37952122

RESUMO

OBJECTIVE: To construct an exhaustive Complementary and Integrative Health (CIH) Lexicon (CIHLex) to help better represent the often underrepresented physical and psychological CIH approaches in standard terminologies, and to also apply state-of-the-art natural language processing (NLP) techniques to help recognize them in the biomedical literature. MATERIALS AND METHODS: We constructed the CIHLex by integrating various resources, compiling and integrating data from biomedical literature and relevant sources of knowledge. The Lexicon encompasses 724 unique concepts with 885 corresponding unique terms. We matched these concepts to the Unified Medical Language System (UMLS), and we developed and utilized BERT models comparing their efficiency in CIH named entity recognition to well-established models including MetaMap and CLAMP, as well as the large language model GPT3.5-turbo. RESULTS: Of the 724 unique concepts in CIHLex, 27.2% could be matched to at least one term in the UMLS. About 74.9% of the mapped UMLS Concept Unique Identifiers were categorized as "Therapeutic or Preventive Procedure." Among the models applied to CIH named entity recognition, BLUEBERT delivered the highest macro-average F1-score of 0.91, surpassing other models. CONCLUSION: Our CIHLex significantly augments representation of CIH approaches in biomedical literature. Demonstrating the utility of advanced NLP models, BERT notably excelled in CIH entity recognition. These results highlight promising strategies for enhancing standardization and recognition of CIH terminology in biomedical contexts.


Assuntos
Algoritmos , Unified Medical Language System , Processamento de Linguagem Natural , Idioma
6.
Plant Physiol Biochem ; 206: 108263, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38100887

RESUMO

The supply level of exogenous nitrogen has a very important influence on the growth and development of cucumber. Insufficient or excessive nitrogen application will lead to metabolic disorders in the body and affect the formation of yield. Therefore, it is of great scientific and practical significance to explore the corresponding mitigation measures. Melatonin (MT) is a multi-regulatory molecule with pleiotropic effects on plant growth and development. A large number of studies have shown that the appropriate amount of melatonin supplementation is beneficial to plant growth and development by promoting root development, delaying leaf senescence, and improving fruit yield. However, the study of MT function combined with a detailed physiological analysis of nitrogen (N) absorption and metabolism in cucumber plants needs further strengthening. We performed hydroponic tests at different nitrogen levels to determine the metabolic processes associated with the enhanced tolerance to nitrogen in melatonin-treated cucumber (Cucucumis sativus L.) seedlings. Cucumber seedlings were sprayed with 100 µM melatonin or water and treated with different nitrogen in the growth chamber for 7 days. Nitrogen deficiency significantly inhibited seedling growth, and this growth inhibition was partially alleviated by melatonin. The expression analysis of related carbon and nitrogen genes showed that the genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. By enzyme activity and reactive oxygen content data analysis, melatonin-treated cucumber seedlings showed relatively stable carbon and nitrogen levels compared to untreated ones. In conclusion, MT can repair the impaired growth and development situation by regulating the nitrogen assimilation capacity and the balance between oxidation and oxidative metabolism and carbon metabolism in the cucumber under different nitrogen levels.


Assuntos
Cucumis sativus , Melatonina , Plântula/metabolismo , Cucumis sativus/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Nitrogênio/metabolismo , Carbono/metabolismo
7.
ACS Appl Mater Interfaces ; 15(50): 58994-59004, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38079597

RESUMO

In various countries worldwide, the issue of wastewater contamination poses a significant threat due to its intricate composition of heavy metals, organic dyes, and microorganisms, thereby complicating the purification process. Consequently, researchers have expressed considerable interest in materials capable of eliminating organic, heavy metal, and microbial pollutants. This study focuses on the fabrication of a water purification membrane (PDA/ZnO-NWs/PVDF) with a hierarchical structure and the ability to remove multiple pollutants. The membrane was created by modifying poly(vinylidene fluoride) (PVDF) nanofiber with zinc oxide nanowires (ZnO-NWs) and reinforcing it with polydopamine (PDA). The experimental results demonstrate that the PDA/ZnO-NWs/PVDF membrane exhibits a range of functionalities, including long-lasting superhydrophilicity, Cu(II) adsorption, photocatalytic degradation, and antibacterial ability. The manipulation of the DA synthesis procedure allows for the adjustment of the wettability, adsorption, and photocatalytic and antibacterial activities of the PDA/ZnO-NWs/PVDF composite. According to the Langmuir isotherm, the maximum Cu(II) adsorption capacity of the PDA/ZnO-NWs/PVDF membrane is determined to be 65.75 mg/g, which is significantly higher (27.26 mg/g) than that of the ZnO-NWs/PVDF membrane (38.49 mg/g). The PDA/ZnO-NWs/PVDF composite exhibited a notable degradation capacity toward rhodamine B under natural sunlight, reaching a maximum of 5.97 mg/g. Additionally, the degradation rate achieved during daylight hours was as high as 90.42%. Furthermore, the antibacterial efficacy of the PDA/ZnO-NWs/PVDF composite against both Gram-positive and Gram-negative bacteria approached 100%. This work presents a promising approach for the treatment of wastewater containing various coexisting contaminants.


Assuntos
Poluentes Ambientais , Metais Pesados , Nanofibras , Nanofios , Óxido de Zinco , Esgotos , Antibacterianos/farmacologia , Antibacterianos/química , Óxido de Zinco/química , Nanofios/química , Nanofibras/química , Águas Residuárias , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Bactérias , Corantes
8.
Front Microbiol ; 14: 1291242, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053549

RESUMO

A central question in microbial ecology is how immense microbes are assembled in changing natural environments while executing critical ecosystem functions. Over the past decade, effort has been made to unravel the contribution of stochasticity and determinism to the compositional of microbial communities. However, most studies focus on microbial taxa, ignoring the importance of functional traits. By employing shotgun metagenomic sequencing and state-of-the-art bioinformatics approaches, this study comprehensively investigated the microbially mediated nitrogen (N) cycling processes in two geographically distant coastal locations. Both shotgun and 16S rRNA gene amplicon sequencing demonstrated significantly differed taxonomic compositions between the two sites. The relative abundance of major microbial phyla, such as Pseudomonadota, Thaumarchaeota, and Bacteroidota, significantly differed. In contrast, high homogeneity was observed for N-cycling functional traits. Statistical analyses suggested that N-cycling taxonomic groups were more related to geographic distance, whereas microbial functional traits were more influenced by environmental factors. Multiple community assembly models demonstrated that determinism strongly governed the microbial N-cycling functional traits, whereas their carrying taxonomic groups were highly stochastic. Such discordant patterns between N-cycling functional traits and taxa demonstrated an important mechanism in microbial ecology in which essential ecosystem functions are stably maintained despite geographic distance and stochastic community assembly.

9.
PLoS Pathog ; 19(12): e1011853, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38100526

RESUMO

Engineered T cells hold great promise to become part of an effective HIV cure strategy, but it is currently unclear how best to redirect T cells to target HIV. To gain insight, we generated engineered T cells using lentiviral vectors encoding one of three distinct HIV-specific T cell receptors (TCRs) or a previously optimized HIV-targeting chimeric antigen receptor (CAR) and compared their functional capabilities. All engineered T cells had robust, antigen-specific polyfunctional cytokine profiles when mixed with artificial antigen-presenting cells. However, only the CAR T cells could potently control HIV replication. TCR affinity enhancement did not augment HIV control but did allow TCR T cells to recognize common HIV escape variants. Interestingly, either altering Nef activity or adding additional target epitopes into the HIV genome bolstered TCR T cell anti-HIV activity, but CAR T cells remained superior in their ability to control HIV replication. To better understand why CAR T cells control HIV replication better than TCR T cells, we performed a time course to determine when HIV-specific T cells were first able to activate Caspase 3 in HIV-infected targets. We demonstrated that CAR T cells recognized and killed HIV-infected targets more rapidly than TCR T cells, which correlates with their ability to control HIV replication. These studies suggest that the speed of target recognition and killing is a key determinant of whether engineered T cell therapies will be effective against infectious diseases.


Assuntos
Infecções por HIV , HIV-1 , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos de Linfócitos T/genética , Infecções por HIV/terapia , Replicação Viral
10.
J Nanobiotechnology ; 21(1): 354, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37775761

RESUMO

Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.


Assuntos
Protetores Solares , Raios Ultravioleta , Humanos , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversos , Antioxidantes/farmacologia , Melaninas/farmacologia , Pele , Anti-Inflamatórios/farmacologia
11.
Int J Numer Method Biomed Eng ; 39(12): e3775, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37740645

RESUMO

Arterial pulse waveforms contain a wealth of information about the cardiovascular system. There is a lack of physical meaning in the mathematical model of arterial pulse waves, while the physical model fails to offer individuality as too many assumptions are involved. In this article, we focus on promoting the interpretability of the arterial pulse mathematical model. The proposed method is based on newly developed 3-term fitting functions individualized by the physiological parameter assignment, which are the peak times of the reflected and dicrotic waves in a pulse. In this manner, the model allows decomposition of the pulse into sub-signals with clear physiological significance. With nearly 10,000 pulse fitting experiments, it is demonstrated that the proposed method outperforms the standard methods in fitting accuracy while providing parameters linked to hemodynamic characteristics and common clinical indices such as the peripheral augmentation index (pAI). The proposed method innovatively maintains the individuality and accuracy of mathematical models while improving the interpretability of their parameters. The applications of this newly developed method, which explicitly incorporates hemodynamic characteristics, are expected to be particularly valuable in future pulse wave decomposition studies.


Assuntos
Hemodinâmica , Análise de Onda de Pulso , Análise de Onda de Pulso/métodos , Frequência Cardíaca , Modelos Teóricos , Pressão Sanguínea
12.
Nanoscale ; 15(33): 13750-13759, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37577964

RESUMO

The construction of heterostructures is an effective strategy to enhance electrocatalysis for hydrogen evolution reactions (HERs) and biomass oxidative upgrading. In this work, a Ni/TiO2 heterostructure prepared by a phase-separation strategy was adopted as a bifunctional electrocatalyst for HERs and biomass oxidation in alkaline media. Due to the optimized hydrogen adsorption energetics as well as the interfacial water structure and hydrogen bond connectivity in the electrical double layer, Ni/TiO2 exhibited high activity for HERs with an overpotential of 28 mV at 10 mA cm-2 and good durability at 1000 mA cm-2 for over 100 h in an anion exchange membrane (AEM) electrolyzer. In addition, Ni/TiO2 showed high catalytic performance for the oxidation of biomass-based platform compound 5-hydroxymethylfurfural (HMF) to high-value added compound 2,5-furandicarboxylic acid (FDCA). Continuous production of FDCA with a yield >95% was achieved in the AEM electrolyzer for over 50 h. The superior HMF oxidation performance on the Ni/TiO2 heterostructure compared to Ni resulted from stronger HMF adsorption, lower Ni3+-O formation potential, longer Ni3+-O bond and smaller Ni crystal size.

13.
Cell Mol Biol (Noisy-le-grand) ; 69(6): 181-185, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37605571

RESUMO

To elucidate the role of LINC01094 in accelerating the metastatic potential of hepatocellular carcinoma (HCC) via the miR-26b-3p/MDM4 axis. Differential levels of LINC01094 in clinical samples of HCC and their influence on pathological indicators of recruited HCC patients were detected. Hep3B and SK-HEP-1 cell lines with stable knockdown of LINC01094 were generated by shRNA transfection, followed by detection of migration and invasion by Transwell and wound healing assay. Bioinformatic analysis, dual-luciferase reporter assay and rescue experiments were conducted to assess the interaction between LINC01094 and the miR-26b-3p/MDM4 axis. LINC01094 was upregulated in clinical samples of HCC and its level was linked to the incidences of lymphatic and distant metastasis of HCC patients. Knockdown of LINC01094 weakened migratory and invasive abilities in Hep3B and SK-HEP-1 cells. MiR-26b-3p was the downstream target of LINC01094, which was lowly expressed in HCC tissues and negatively correlated to the LINC01094 level. Moreover, MDM4 was the target gene of miR-26b-3p, which was highly expressed in HCC tissues and negatively correlated to the miR-26b-3p level. Rescue experiments showed that the knockdown of miR-26b-3p could reverse the inhibited metastasis in Hep3B and SK-HEP-1 cells with a stable knockdown of LINC01094. LINC01094 accelerates the metastasis of HCC via the miR-26b-3p/MDM4 axis, which is a potential biomarker and therapeutic target to be utilized in clinical practice.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Bioensaio , Linhagem Celular , MicroRNAs/genética , Proteínas Proto-Oncogênicas , Proteínas de Ciclo Celular
14.
Lab Chip ; 23(19): 4232-4244, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37650583

RESUMO

Artificial intelligence (AI) has become a focal point across a multitude of societal sectors, with science not being an exception. Particularly in the life sciences, imaging flow cytometry has increasingly integrated AI for automated management and categorization of extensive cell image data. However, the necessity of AI over traditional classification methods when extending imaging flow cytometry to include cell sorting remains uncertain, primarily due to the time constraints between image acquisition and sorting actuation. AI-enabled image-activated cell sorting (IACS) methods remain substantially limited, even as recent advancements in IACS have found success while largely relying on traditional feature gating strategies. Here we assess the necessity of AI for image classification in IACS by contrasting the performance of feature gating, classical machine learning (ML), and deep learning (DL) with convolutional neural networks (CNNs) in the differentiation of Saccharomyces cerevisiae mutant images. We show that classical ML could only yield a 2.8-fold enhancement in target enrichment capability, albeit at the cost of a 13.7-fold increase in processing time. Conversely, a CNN could offer an 11.0-fold improvement in enrichment capability at an 11.5-fold increase in processing time. We further executed IACS on mixed mutant populations and quantified target strain enrichment via downstream DNA sequencing to substantiate the applicability of DL for the proposed study. Our findings validate the feasibility and value of employing DL in IACS for morphology-based genetic screening of S. cerevisiae, encouraging its incorporation in future advancements of similar technologies.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Saccharomyces cerevisiae , Redes Neurais de Computação , Aprendizado de Máquina
15.
Front Microbiol ; 14: 1215837, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37485517

RESUMO

The psychrotroph Pseudomonas fragi D12, which grew strongly under low temperatures, was screened from tundra soil collected from the permanent alpine zone on Changbai Mountain. To mine the genes critical for cold tolerance and to investigate the cold-adaptation mechanism, whole-genome sequencing, comparative genomic analysis, and transcriptome analysis were performed with P. fragi. A total of 124 potential cold adaptation genes were identified, including nineteen unique cold-adaptive genes were detected in the genome of P. fragi D12. Three unique genes associated with pili protein were significantly upregulated at different degrees of low temperature, which may be the key to the strong low-temperature adaptability of P. fragi D12. Meanwhile, we were pleasantly surprised to find that Pseudomonas fragi D12 exhibited different cold-adaptation mechanisms under different temperature changes. When the temperature declined from 30°C to 15°C, the response included maintenance of the fluidity of cell membranes, increased production of extracellular polymers, elevation in the content of compatibility solutes, and reduction in the content of reactive oxygen species, thereby providing a stable metabolic environment. When the temperature decreased from 15°C to 4°C, the response mainly included increases in the expression of molecular chaperones and transcription factors, enabling the bacteria to restore normal transcription and translation. The response mechanism of P. fragi D12 to low-temperature exposure is discussed. The results provide new ideas for the cold-adaptation mechanism of cold-tolerant microorganisms.

16.
Acta Biomater ; 168: 159-173, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37467837

RESUMO

Matrix mechanics regulate essential cell behaviors through mechanotransduction, and as one of its most important elements, substrate stiffness was reported to regulate cell functions such as viability, communication, migration, and differentiation. Neutrophils (Neus) predominate the early inflammatory response and initiate regeneration. The activation of Neus can be regulated by physical cues; however, the functional alterations of Neus by substrate stiffness remain unknown, which is critical in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional (3D) culture system made of hydrogels was developed to explore the effects of varying stiffnesses (1.5, 2.6, and 5.7 kPa) on the states of Neus. Neus showed better cell integrity and viability in the 3D system. Moreover, it was shown that the stiffer matrix tended to induce Neus toward an anti-inflammatory phenotype (N2) with less adhesion molecule expression, less reactive oxygen species (ROS) production, and more anti-inflammatory cytokine secretion. Additionally, the aortic ring assay indicated that Neus cultured in a stiffer matrix significantly increased vascular sprouting. RNA sequencing showed that a stiffer matrix could significantly activate JAK1/STAT3 signaling in Neus and the inhibition of JAK1 ablated the stiffness-dependent increase in the expression of CD182 (an N2 marker). Taken together, these results demonstrate that a stiffer matrix promotes Neus to shift to the N2 phenotype, which was regulated by JAK1/STAT3 pathway. This study lays the groundwork for further research on fabricating engineered tissue mimics, which may provide more treatment options for ischemic diseases and bone defects. STATEMENT OF SIGNIFICANCE.


Assuntos
Medula Óssea , Neutrófilos , Mecanotransdução Celular , Hidrogéis/farmacologia , Hidrogéis/química , Diferenciação Celular
17.
ACS Omega ; 8(28): 25066-25080, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37483184

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease, severely reducing the cognitive level and life quality of patients. Byu dMar 25 (BM25) has been proved to have a therapeutic effect on AD. However, the pharmacological mechanism is still unclear. Therefore, this study aims to reveal the potential mechanism of BM25 affecting AD from the perspective of network pharmacology and experimental validation. METHODS: The potential active ingredients of BM25 were obtained from the TCMSP database and literature. Possible targets were predicted using SwissTargetPrediction tools. AD-related genes were identified by using GeneCards, OMIM, DisGeNET, and Drugbank databases. The candidate genes were obtained by extraction of the intersection network. Additionally, the "drug-target-disease" network was constructed by Cytoscape 3.7.2 for visualization. The PPI network was constructed by the STRING database, and the core network modules were filtered by Cytoscape 3.7.2. Enrichment analysis of GO and KEGG was carried out in the Metascape platform. Ledock software was used to dock the critical components with the core target. Furthermore, protein levels were evaluated by immunohistochemistry. RESULTS: In this study, 112 active components, 1112 disease candidate genes, 3084 GO functions, and 277 KEGG pathways were obtained. Molecular docking showed that the effective components of BM25 in treating AD were ß-asarone and hydroxysafflor yellow A. The most important targets were APP, PIK3R1, and PIK3CA. Enrichment analysis indicated that the Golgi genetic regulation, peroxidase activity regulation, phosphatidylinositol 3-kinase complex IA, 5-hydroxytryptamine receptor complexes, cancer pathways, and neuroactive ligand-receptor interactions played vital roles against AD. The rat experiment verified that BM25 affected PI3K-Akt pathway activation in AD. CONCLUSIONS: This study reveals the mechanism of BM25 in treating AD with network pharmacology, which provides a foundation for further study on the molecular mechanism of AD treatment.

19.
Obesity (Silver Spring) ; 31(8): 2076-2089, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37475688

RESUMO

OBJECTIVE: Obesity hypoventilation syndrome is associated with diaphragmatic dysfunction. This study aimed to explore the role of endoplasmic reticulum (ER) stress in mediating obesity-induced diaphragmatic dysfunction. METHODS: A pulmonary function test and ultrasound were applied to evaluate diaphragmatic function and magnetic resonance imaging was applied to measure diaphragmatic lipid deposition in human patients. For the mechanistic study, obese mice were introduced to a high-fat diet for 24 weeks, followed by diaphragmatic ultrasound measurement, transcriptomic sequencing, and respective biochemical analysis. Automatic force mapping was applied to measure the mechanical properties of C2C12 myotubes. RESULTS: People with obesity showed significant diaphragm weakness and lipid accumulation, which was further confirmed in obese mice. Consistently, diaphragms from obese mice showed altered gene expression profile in lipid metabolism and activation of ER stress response, indicated by elevated protein kinase R-like ER kinase (PERK) and c-Jun NH2 -terminal kinase (JNK) activation. In C2C12 myotubes, inhibition of PERK or JNK signaling abrogated lipotoxicity-induced intracellular lipid deposition and insulin resistance. Inhibition of JNK signaling reversed lipotoxicity-induced impairment of elasticity in C2C12 myotubes. CONCLUSIONS: These data suggest that ectopic lipid deposition impairs the diaphragmatic function of people with obesity. Activation of PERK/JNK signaling is involved in the pathogenesis of lipotoxicity-induced diaphragm weakness in obesity hypoventilation syndrome.


Assuntos
Síndrome de Hipoventilação por Obesidade , Transdução de Sinais , Camundongos , Animais , Humanos , Transdução de Sinais/fisiologia , Diafragma/metabolismo , Síndrome de Hipoventilação por Obesidade/complicações , Camundongos Obesos , Estresse do Retículo Endoplasmático/fisiologia , Obesidade/genética , Lipídeos
20.
J Environ Manage ; 342: 118244, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37269730

RESUMO

In order to explore the role of thermal-alkaline pretreatment temperatures (TAPT) in sludge fermentation and the microbial characteristics, five groups (100, 120, 140, 160 °C and control group) were set up and the results showed that the increasing TAPT promoted the dissolution of soluble chemical oxygen demand (SCOD) and VFAs, but had slight influence on the release of NH4+-N and PO43--P. What's more, when it was 120 °C, the SCOD dissolution was comparable to that at 160 °C. Overall, 120 °C was the optimal condition, corresponding to the fact that the maximum release of SCOD was 8788.74 mg/L (2.63 times of the control group), the maximum dissolution of VFAs was 4596 mg/L (about 1.28 times of the control group). The trend of C/N was not significant. High-throughput sequencing showed that Firmicutes and Actinobacteriota were enriched with the temperature increasing, while Proteobacteria and Chloroflexi did not change significantly. Firmicutes was in a stable dominant position. Temperature conditions brought about significant changes in microbial interspecific interaction. Carbohydrate and amino acids had the highest metabolic abundance, especially at 120 °C group. The change rule of amino acid metabolism was similar to that of lipid metabolism, and the abundance of energy metabolism gradually increased with temperature. The protein metabolism was greatly affected by temperature. This study revealed the effect of microbial mechanism of TAPT on the sludge acid production efficiency.


Assuntos
Microbiota , Esgotos , Esgotos/química , Temperatura , Fermentação , Ácidos Graxos Voláteis/metabolismo , Concentração de Íons de Hidrogênio , Reatores Biológicos
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