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1.
Artigo em Inglês | MEDLINE | ID: mdl-38626424

RESUMO

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1ß-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38568073

RESUMO

A novel bacterial strain, designated WL0086T, was isolated from a marine sediment sample collected in Lianyungang city, Jiangsu province, PR China. This strain showed the highest 16S rRNA gene sequence similarity to Geminisphaera colitermitum TAV2T (92.7 %) of the family Opitutaceae, and all the unclassified cultured and uncultured isolates with similarities >95 % were from marine environments. Cells were Gram-stain-negative, aerobic, non-motile cocci with a size of 0.6-0.8 µm in diameter. Strain WL0086T was positive for both oxidase and catalase, and grew at 20-37 °C (optimum, 28 °C), with 1.5-11.0 % NaCl (w/v; optimum, 2.5-4.0 %) and at pH 5.0-9.0 (optimum, pH 7.0). The major polar lipid profile of strain WL0086T consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and phosphatidylcholine. The major isoprenoid quinone was menaquinone-7 and the predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0 and C16 : 1 ω9c. The complete genome consisted of a chromosome with 6 109 182 bp. The G+C content of genomic DNA was 64.0%. Results of phylogenomic analysis based on the 16S rRNA gene sequence and the whole genome suggested that strain WL0086T formed a distinct clade closely neighbouring the members of the family Opitutaceae. On the basis of phylogenetic, phenotypic, and chemotaxonomic evidences, strain WL0086T should represent a novel genus of the family Opitutaceae, for which the name Actomonas aquatica gen. nov., sp. nov. is proposed. The type strain is WL0086T (=MCCC 1K05844T=JCM 34677T=GDMCC 1.2411T).


Assuntos
Carbono , Fixação de Nitrogênio , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
3.
Ying Yong Sheng Tai Xue Bao ; 35(3): 577-586, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646744

RESUMO

The analytical equation based on Monin-Obukhov (M-O) similarity theory (i.e., wind profile equation) has been adopted since 1970s for using in the prediction of wind vertical profile over flat terrains, which is mature and accurate. However, its applicability over complex terrains remains unknown. This applicability signifies the accuracy of the estimations of aerodynamic parameters for the boundary layer of non-flat terrain, such as zero-displacement height (d) and aerodynamic roughness length (z0), which will determine the accuracy of frequency correction and source area analysis in calculating carbon, water, and trace gas fluxes based on vorticity covariance method. Therefore, the validation of wind profile model in non-flat terrain is the first step to test whether the flux model needs improvement. We measured three-dimensional wind speed data by using the Ker Towers (three towers in a watershed) at Qingyuan Forest CERN in the Mountainous Region of east Liaoning Province, and compared them with data from Panjin Agricultural Station in the Liaohe Plain, to evaluate the applicability of a generalized wind profile model based on the Monin-Obukhov similarity theory on non-flat terrain. The results showed that the generalized wind profile model could not predict wind speeds accurately of three flux towers separately located in different sites, indicating that wind profile model was not suitable for predicting wind speeds in complex terrains. In the leaf-off and leaf-on periods, the coefficient of determination (R2) between observed and predicted wind speeds ranged from 0.12 to 0.30. Compared to measured values, the standard error of the predicted wind speeds was high up to 2 m·s-1. The predicted wind speeds were high as twice as field-measured wind speed, indicating substantial overestimation. Nevertheless, this model correctly predicted wind speeds in flat agricultural landscape in Panjin Agricultural Station. The R2 between observed wind speeds and predicted wind speed ranged from 0.90 to 0.93. The standard error between observed and predicted values was only 0.5 m·s-1. Results of the F-test showed that the root-mean-square error of the observed and predicted wind speeds in each secondary forest complex terrain was much greater than that in flat agricultural landscape. Terrain was the primary factor affecting the applicability of wind profile model, followed by seasonality (leaf or leafless canopy). The wind profile model was not applicable to the boundary-layer flows over forest canopies in complex terrains, because the d was underestimated or both the d and z0 were underestimated, resulting in inaccurate estimation of aerodynamic height.


Assuntos
Florestas , Modelos Teóricos , Vento , China , Árvores/crescimento & desenvolvimento , Monitoramento Ambiental/métodos , Ecossistema , Altitude
4.
Cell Rep Med ; : 101513, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38608697

RESUMO

Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39. Through promoter engineering and ribosome binding site screening, we achieved ultrasound (US)-induced protein expression and secretion in engineered bacteria with minimal noise and high induction efficiency. Specifically, delivered either intratumorally or intravenously, engineered bacteria colonizing tumors suppressed tumor growth through US-irradiation-induced release of the apoptotic protein azurin and an immune checkpoint inhibitor, a nanobody targeting programmed death-ligand 1, in different tumor mouse models. Beyond developing safe and high-performance designer bacteria for tumor therapy, our study illustrates a sonogenetics-controlled therapeutic platform that can be harnessed for bacteria-based precision medicine.

5.
Methods Mol Biol ; 2794: 341-351, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630243

RESUMO

Single-cell RNA sequencing (scRNA-seq) has been widely applied in neuroscience research, enabling the investigation of cellular heterogeneity at the transcriptional level, the characterization of rare cell types, and the detailed analysis of the stochastic nature of gene expression. Isolation of single nerve cells in good health, especially from the adult rodent brain, is the most difficult and critical process for scRNA-seq. Here, we describe methods to optimize protease digestion of brain slices, which enable yield of millions of cells in good health from the adult brain.


Assuntos
Astrócitos , Neurônios , Animais , Camundongos , RNA-Seq , Encéfalo , Endopeptidases , Suspensões
6.
Food Chem X ; 22: 101377, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38633741

RESUMO

In this study, the effects on the structures and emulsion gels of carrageenan (CA) and gum arabic (GA) with soybean protein isolate (SPI) were investigated. The results showed that CA and GA exposed hydrophobic groups to SPI, and formed complexes through non-covalent interactions to improve the stability of the complexes. Furthermore, the emulsion gels based on the emulsions exhibited that CA formed emulsion-filled gels with higher elasticity, stronger gel strength, and thermal reversibility, whereas GA formed emulsion-aggregated gels with higher viscosity, and a weak-gel network. The results of digestion showed that, CA was more helpful to slow down the release of free fatty acids and protect vitamin E during digestion. Compared with SPI-GA emulsion gel, SPI-CA emulsion gel had better physicochemical properties and stronger network structure. The results of this study may be useful in the development of anionic polysaccharides that interact with SPI, and they may provide new insights on the preparation of emulsion gels that slowly release fat-soluble nutrients.

7.
Sci Rep ; 14(1): 5147, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429352

RESUMO

Rice husk, an agricultural waste from the rice industry, can cause serious environmental pollution if not properly managed. However, rice husk ash (RHA) has been found to have many positive properties, making it a potential replacement for non-renewable peat in soilless planting. Thus, this study investigated the impact of a RHA composite substrate on the growth, photosynthetic parameters, and fruit quality of cucumber (Yuyi longxiang variety) and melon (Yutian yangjiaomi variety). The RHA, peat, vermiculite, and perlite were blended in varying proportions, with the conventional seedling substrate (peat:vermiculite:perlite = 1:1:1 volume ratio) serving as the control (CK). All plants were cultivated in barrels filled with 10L of the mixed substrates. The results from this study found that RHA 40 (RHA:peat:vermiculite:perlite = 4:4:1:1 volume ratio) significantly enhanced substrate ventilation and positively influenced the stem diameter, root activity, seedling index, chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of cucumber and melon plants. Additionally, plant planted using RHA 40, the individual fruit weight of cucumber and melon found to increase by 34.62% and 21.67%, respectively, as compared to the control. Aside from that, both cucumber and melon fruits had significantly higher sucrose, total soluble sugar, vitamin C, and soluble protein levels. This subsequently improved the activity of sucrose synthase and sucrose phosphate synthase in both cucumber and melon. In conclusion, the RHA 40 found to best promote cucumber and melon plant growth, increase plant leaf photosynthesis, and improve cucumber and melon fruit quality, making it a suitable substrate formula for cucumber and melon cultivation in place of peat.


Assuntos
Óxido de Alumínio , Silicatos de Alumínio , Cucumis sativus , Cucurbitaceae , Oryza , Dióxido de Silício , Carboidratos da Dieta , Solo
8.
Am J Cancer Res ; 14(2): 809-831, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455406

RESUMO

Increasing evidence indicates that long noncoding RNAs (lncRNAs) are therapeutic targets and key regulators of tumors development and progression, including melanoma. Long intergenic non-protein-coding RNA 511 (LINC00511) has been demonstrated as an oncogenic molecule in breast, stomach, colorectal, and lung cancers. However, the precise role and functional mechanisms of LINC00511 in melanoma remain unknown. This study confirmed that LINC00511 was highly expressed in melanoma cells (A375 and SK-Mel-28 cells) and tissues, knockdown of LINC00511 could inhibit melanoma cell migration and invasion, as well as the growth of subcutaneous tumor xenografts in vivo. By using Chromatin immunoprecipitation (ChIP) assay, it was demonstrated that the transcription factor Yin Yang 1 (YY1) is capable of binding to the LINC00511 promoter and enhancing its expression in cis. Further mechanistic investigation showed that LINC00511 was mainly enriched in the cytoplasm of melanoma cells and interacted directly with microRNA-150-5p (miR-150-5p). Consistently, the knockdown of miR-150-5p could recover the effects of LINC00511 knockdown on melanoma cells. Furthermore, ADAM metallopeptidase domain expression 19 (ADAM19) was identified as a downstream target of miR-150-5p, and overexpression of ADAM19 could promote melanoma cell proliferation. Rescue assays indicated that LINC00511 acted as a competing endogenous RNA (ceRNA) to sponge miR-150-5p and increase the expression of ADAM19, thereby activating the PI3K/AKT pathway. In summary, we identified LINC00511 as an oncogenic lncRNA in melanoma and defined the LINC00511/miR-150-5p/ADAM19 axis, which might be considered a potential therapeutic target and novel molecular mechanism the treatment of patients with melanoma.

9.
Front Neurosci ; 18: 1364338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486967

RESUMO

In clinical practice and research, the classification and diagnosis of neurological diseases such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA) have long posed a significant challenge. Currently, deep learning, as a cutting-edge technology, has demonstrated immense potential in computer-aided diagnosis of PD and MSA. However, existing methods rely heavily on manually selecting key feature slices and segmenting regions of interest. This not only increases subjectivity and complexity in the classification process but also limits the model's comprehensive analysis of global data features. To address this issue, this paper proposes a novel 3D context-aware modeling framework, named 3D-CAM. It considers 3D contextual information based on an attention mechanism. The framework, utilizing a 2D slicing-based strategy, innovatively integrates a Contextual Information Module and a Location Filtering Module. The Contextual Information Module can be applied to feature maps at any layer, effectively combining features from adjacent slices and utilizing an attention mechanism to focus on crucial features. The Location Filtering Module, on the other hand, is employed in the post-processing phase to filter significant slice segments of classification features. By employing this method in the fully automated classification of PD and MSA, an accuracy of 85.71%, a recall rate of 86.36%, and a precision of 90.48% were achieved. These results not only demonstrates potential for clinical applications, but also provides a novel perspective for medical image diagnosis, thereby offering robust support for accurate diagnosis of neurological diseases.

10.
Front Oncol ; 14: 1336375, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500660

RESUMO

Background: Bladder cancer stands as the predominant malignant tumor in the urological system, presenting a significant challenge to public health and garnering extensive attention. Recently, with the deepening research into tumor molecular mechanisms, non-coding RNAs (ncRNAs) have emerged as potential biomarkers offering guidance for the diagnosis and prognosis of bladder cancer. However, the definitive role of ncRNAs in bladder cancer remains unclear. Hence, this study aims to elucidate the relevance and significance of ncRNAs through a Meta-analysis. Methods: A systematic meta-analysis was executed, including studies evaluating the diagnostic performance of ncRNAs and their associations with overall survival (OS) and disease-free survival (DFS). Key metrics such as hazard ratios, sensitivity, specificity, and diagnostic odds ratios were extracted and pooled from these studies. Potential publication bias was assessed using Deeks' funnel plot, and the robustness of the results was ascertained through a sensitivity analysis. Results: Elevated ncRNA expression showed a positive correlation with improved OS, evidenced by a hazard ratio (HR) of 0.82 (95% CI: 0.66-0.96, P<0.001). Similarly, a significant association was observed between heightened ncRNA expression and DFS, with an HR of 0.86 (95% CI: 0.73-0.99, P<0.001). Diagnostic performance analysis across 17 articles yielded a pooled sensitivity of 0.76 and a specificity of 0.83. The diagnostic odds ratio was recorded at 2.71, with the area under the ROC curve (AUC) standing at 0.85. Conclusion: Exosome ncRNAs appear to possess potential significance in the diagnostic and prognostic discussions of bladder cancer. Their relationship with survival outcomes and diagnostic measures suggests a possible clinical utility. Comprehensive investigations are needed to fully determine their role in the ever-evolving landscape of bladder cancer management, especially within the framework of personalized medicine.

11.
Front Pediatr ; 12: 1362657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419973

RESUMO

[This corrects the article DOI: 10.3389/fped.2022.966510.].

12.
Brain Res Bull ; 208: 110894, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325758

RESUMO

Neutrophil infiltration has been linked to worse clinical outcomes after ischemic stroke. Microglia, a key type of immune-competent cell, engage in cross-talk with the infiltrating immune cells in the inflamed brain area, yet the molecular mechanisms involved remain largely unexplored. In this study, we investigated the mechanisms of how canonical transient receptor potential 1 (TRPC1) modulated neutrophil infiltration in male mouse cerebral ischemia and reperfusion injury (CIRI) models. Our findings revealed a notable upregulation of TRPC1 in microglia within both middle cerebral artery occlusion reperfusion (MCAO/R) and in vitro oxygen-glucose deprivation/regeneration (OGD/R) model. Conditional Trpc1 knockdown in microglia markedly reduced infarct volumes and alleviated neurological deficits. Microglia conditional Trpc1 knockdown mice displayed less neutrophil infiltration in peri-infarct area. Trpc1 knockdown microglia exhibited a reduced primed proinflammatory phenotype with less secretion of CC-Chemokines ligand (CCL) 5 and CCL2 after MCAO/R. Blocking CCL5/2 significantly mitigated neutrophil infiltration in microglia/neutrophil transwell co-culture system upon OGD/R condition. Trpc1 knockdown markedly reduced store-operated calcium entry and nuclear factor of activated T-cells c1 (NFATc1) level in OGD/R treated microglia. Overexpression of Nfatc1 reversed the CCL5/2 reducing effect of Trpc1 knockdown, which is mediated by small interfering RNA in BV2 cells upon OGD/R. Our data indicate that upregulation of TRPC1 in microglia stimulates the production of CCL5/2 through the Ca2+/NFATc1 pathway. Upregulated CCL5/2 leads to an increase in neutrophil infiltration into the brain, thereby aggravating reperfusion injury. Our results demonstrate the importance of TRPC1 in microglia-mediated neuroinflammation and suggest a potential means for reducing CIRI induced neurological injury.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Masculino , Camundongos , Animais , Regulação para Cima , AVC Isquêmico/metabolismo , Microglia/metabolismo , Infiltração de Neutrófilos , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/metabolismo
13.
Phytomedicine ; 126: 155470, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417242

RESUMO

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.


Assuntos
Asma , 60556 , Humanos , Imunidade Inata , RNA Ribossômico 16S/genética , Lipopolissacarídeos , Serotonina , Linfócitos , Asma/tratamento farmacológico , Asma/metabolismo , Pulmão/metabolismo , Ácidos Graxos Voláteis/metabolismo
14.
RSC Adv ; 14(8): 5627-5637, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38352672

RESUMO

To fabricate a two-electrode flexible pH sensor based on polypropylene spunbonded nonwoven fabric (PP SF), oily polyurethane (OPU) was first coated on the surface of PP SF to obtain OPU/PP SF. Then, silver/silver chloride (Ag/AgCl) paste, used as the reference electrode and conductive carbon (C) paste were transferred to the OPU/PP SF surface through screen printing. Polyaniline (PANI) was deposited on the surface of the C paste to form a sensing working electrode via the electro-chemical deposition method. The results showed that the surface of the obtained PANI@OPU/PP SF flexible pH sensor (3D PANI pH sensor) presented a three-dimensional (3D) porous network structure. The 3D PANI pH sensor had good mechanical properties, an excellent Nernst response (-67.67 mV pH-1) and linearity (R2 = 0.99) in the pH range from 2.00 to 8.00 in the normal state. In the bent state, the 3D PANI pH sensor retained similar sensitivity (-68.87 mV pH-1) and linearity (R2 = 0.99). Moreover, the 3D PANI pH sensor exhibited a short response time (8 s), excellent reversibility (1.20 mV), low temperature drift (-0.0872 mV pH-1 °C-1) and long-term stability (0.83 mV h-1) in the normal state. Furthermore, the 3D PANI pH sensor can be effectively applied for pH monitoring of liquids and fruits with irregular curved surfaces. The error margin is no more than 0.16 compared to a commercial pH meter.

15.
Database (Oxford) ; 20242024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345567

RESUMO

Detecting changes in the dynamics of secreted proteins in serum has been a challenge for proteomics. Enter secreted protein database (SEPDB), an integrated secretory proteomics database offering human, mouse and rat secretory proteomics datasets collected from serum, exosomes and cell culture media. SEPDB compiles secreted protein information from secreted protein database, UniProt and Human Protein Atlas databases to annotate secreted proteomics data based on protein subcellular localization and disease markers. SEPDB integrates the latest predictive modeling techniques to measure deviations in the distribution of signal peptide structures of secreted proteins, extends signal peptide sequence prediction by excluding transmembrane structural domain proteins and updates the validation analysis pipeline for secreted proteins. To establish tissue-specific profiles, we have also created secreted proteomics datasets associated with different human tissues. In addition, we provide information on heterogeneous receptor network organizational relationships, reflective of the complex functional information inherent in the molecular structures of secreted proteins that serve as ligands. Users can take advantage of the Refreshed Search, Analyze, Browse and Download functions of SEPDB, which is available online at https://sysomics.com/SEPDB/. Database URL:  https://sysomics.com/SEPDB/.


Assuntos
Proteínas , Proteômica , Animais , Camundongos , Ratos , Humanos , Bases de Dados de Proteínas , Proteínas/química , Proteômica/métodos , Sinais Direcionadores de Proteínas
16.
Nat Commun ; 15(1): 1122, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321056

RESUMO

Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAVMUSE-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.


Assuntos
Alprostadil , Cicloparafinas , Camundongos , Humanos , Animais , Alprostadil/metabolismo , Transgenes , Cicloparafinas/metabolismo , Odorantes , Receptores Acoplados a Proteínas G/metabolismo , Dependovirus/genética , Vetores Genéticos
18.
Exp Brain Res ; 242(3): 769-780, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310175

RESUMO

Using event-related potentials (ERPs), this study examined the impact of reward expectations on working memory of emotional faces under different levels of cognitive load in a task combining the N-back paradigm and the reward expectation paradigm. The experiment involved presenting high- or low-reward cues followed by an N-back task for emotional faces with different loads. The accuracy results showed that under a high task load, both reward and emotion effects were significantly observed. However, these effects disappeared under a low task load. Analysis of the ERP data revealed that the early P2 and VPP components exhibited greater responses to fearful faces than to neutral faces. In the later stages, the P3 and LPP components showed greater reactions to high rewards than to low rewards. Additionally, the P2 component was found to be modulated by task load in relation to rewards, the EPN component demonstrated task load modulation with respect to emotions, and the N170 component showed an interaction effect between rewards and emotions. These findings imply that load regulates the reward effect and the emotional superiority effect in the process of working memory for emotional faces. In the cognitive processing of working memory, motivation and emotion jointly influence processing. Emotional factors have a greater impact in the early stage of processing, while motivation factors have a greater impact in the late stage of processing.


Assuntos
Eletroencefalografia , Motivação , Humanos , Memória de Curto Prazo , Emoções/fisiologia , Potenciais Evocados/fisiologia , Cognição , Recompensa , Expressão Facial
19.
Langmuir ; 40(5): 2729-2744, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38277675

RESUMO

We synthesized Sr-doped spinel CoCr2O4 using the solution combustion method and characterized the structure, morphology, chemical state, and photocatalytic properties through different techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and electrochemical impedance spectroscopy (EIS). 30-50 nm cuboid CoCr2O4 nanocrystals with Sr doping levels ranging from 0 to 0.6% were obtained; the increasing Sr doping deformed the coordination number of Co and Cr, transitioning to octahedral and tetrahedral units, inducing the phase transition from spinel to inverse spinel at 0.6% Sr content. This modification enhanced optical absorption, reduced the energy band gap, increased photoluminescence intensity, and maintained a high-spin state with oxygen vacancies. 0.6% Sr-doped CoCr2O4 demonstrated the highest photocatalytic efficiency at 93%. The XRD structure and photocatalytic activity remained at 87% over 7 cycles after 14 h. Employing degradation pathways and Mott-Schottky curves elucidated the enhancement mechanism.

20.
Sci Rep ; 14(1): 237, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167897

RESUMO

This study aimed to examine the role played by the physical literacy and mindfulness in the health-related quality of life (QoL) of college students. In early 2022, 24,236 college students from three universities in southern China were recruited in the study. R software and the lavvan package was utilized to build the structural equation model. The measurement model was composed of three latent factors (physical literacy, mindfulness, and quality of life) and 16 observed variables in total. The results of the measurement model indicated goodness fit with p > .05 in Chi-square result, and GFI = .92. In addition, the comparative fit index (.92), Tucker-Lewis index (.91), root-mean-square error of approximation (.07), and root of mean square residual (.11) were in accord with the cutoff model-fit criteria. The results confirm that physical literacy and mindfulness can play a significant and positive role in the structural equation model of quality of life. In addition, this study provides initial evidence that mindfulness and physical literacy could potentially buffer declines in student QoL during the COVID-19 pandemic. Moreover, this study is the first to develop a structural equation model of QoL with multiple indicators, making it a strong addition to existing research on QoL during a pandemic.


Assuntos
COVID-19 , Atenção Plena , Humanos , Qualidade de Vida , Pandemias , Alfabetização , Inquéritos e Questionários , COVID-19/epidemiologia , Estudantes
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