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1.
Nature ; 620(7973): 310-315, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37558849

RESUMO

In everyday life, rolling motion is typically associated with cylindrical (for example, car wheels) or spherical (for example, billiard balls) bodies tracing linear paths. However, mathematicians have, for decades, been interested in more exotically shaped solids such as the famous oloids1, sphericons2, polycons3, platonicons4 and two-circle rollers5 that roll downhill in curvilinear paths (in contrast to cylinders or spheres) yet indefinitely (in contrast to cones, Supplementary Video 1). The trajectories traced by such bodies have been studied in detail6-9, and can be useful in the context of efficient mixing10,11 and robotics, for example, in magnetically actuated, millimetre-sized sphericon-shaped robots12,13, or larger sphericon- and oloid-shaped robots translocating by shifting their centre of mass14,15. However, the rolling paths of these shapes are all sinusoid-like and their diversity ends there. Accordingly, we were intrigued whether a more general problem is solvable: given an infinite periodic trajectory, find the shape that would trace this trajectory when rolling down a slope. Here, we develop an algorithm to design such bodies-which we call 'trajectoids'-and then validate these designs experimentally by three-dimensionally printing the computed shapes and tracking their rolling paths, including those that close onto themselves such that the body's centre of mass moves intermittently uphill (Supplementary Video 2). Our study is motivated largely by fundamental curiosity, but the existence of trajectoids for most paths has unexpected implications for quantum and classical optics, as the dynamics of qubits, spins and light polarization can be exactly mapped to trajectoids and their paths16.

2.
Cytokine ; 181: 156685, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38945040

RESUMO

The close link between immune and pathogenesis of venous thromboembolism (VTE) has been recognized, but not fully elucidated. The current study was designed to identify immune microenvironment related signature and subtypes using explainable machine learning in VTE. We first observed an alteration of immune microenvironment in VTE patients and identified eight key immune cells involved in VTE. Then PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 were determined as key immune microenvironment-related genes, which could divide VTE patients into two subtypes with different immune and metabolic characteristics. Also, we found that prunetin and torin-2 may be most promising to treat VTE patients in Cluster 1 and 2, respectively. By comparing six machine learning models in both training and external validation sets, XGboost was identified as the best one to predict the risk of VTE, followed by the interpretation of each immune microenvironment-related gene contributing to the model. Moreover, CR2 and FPR2 had high accuracy in distinguishing VTE and control, which may act as diagnostic biomarkers of VTE, and their expressions were validated by qPCR. Collectively, immune microenvironment related PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 are key genes involved in the pathogenesis of VTE. The VTE risk prediction model and immune microenvironment subtypes based on those genes might benefit prevention, diagnosis, and the individualized treatment strategy in clinical practice of VTE.


Assuntos
Tromboembolia Venosa , Humanos , Tromboembolia Venosa/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Aprendizado de Máquina , Microambiente Celular/imunologia
3.
Langmuir ; 40(27): 14110-14117, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38937926

RESUMO

The complex diffusion behaviors of rod-shaped nanoparticles near the solid-liquid interface are closely related to various biological processes and technological applications. Despite recent advancements in understanding the diffusion dynamics of nanoparticles near some specific solid-liquid interfaces, systematical studies to tune the interfacial interaction or fabricating nonuniform wall to see their effects on the nanorod (NR) diffusion are still lacking. This work utilized molecular dynamics simulations to investigate the rotational and translational diffusion dynamics of a single NR near the solid-liquid interface. We constructed a patterned wall featuring adjustable nonuniformity, which was accomplished by modifying the interaction between NR and the wall, noting that the resulting nonuniformity limits both the translational and rotational diffusion of NR, evident from decreases in diffusion coefficients and exponents. By trajectory analysis, we categorized the diffusion modes of NRs near the patterned wall with varied nonuniformities into three types: Fickian diffusion, desorption-mediated flight, and in-plane diffusion. Furthermore, energy analysis based on the adsorption-desorption mechanism has demonstrated that the three diffusion states are driven by interactions between the NR and the wall, which are primarily influenced by rotational diffusion. These results could significantly deepen the understanding of anisotropic nanoparticle interfacial diffusion and would provide new insights into the transport mechanisms of nanoparticles within confined environments.

4.
BMC Cardiovasc Disord ; 24(1): 289, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822281

RESUMO

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response.


Assuntos
Aterosclerose , Estresse do Retículo Endoplasmático , Hidroximetilglutaril-CoA Redutases , Lipoproteínas LDL , Macrófagos , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 2 , Regulação para Cima , Humanos , Lipoproteínas LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Hidroximetilglutaril-CoA Redutases/metabolismo , Hidroximetilglutaril-CoA Redutases/genética , Placa Aterosclerótica , Células THP-1 , Masculino , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Colesterol/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-38940805

RESUMO

Objective: This study evaluated the effectiveness of nalbuphine combined with propofol in reducing visceral pain and preserving cognitive function during laparoscopic ovarian tumor resection. Methods: A total of 100 patients undergoing laparoscopic ovarian tumor resection from January 2019 to January 2022 were randomly assigned to either the control group or the research group (50 patients each). The control group received fentanyl combined with propofol for anesthesia, while the research group received nalbuphine combined with propofol. Various anesthetic parameters, hemodynamics, visceral pain(Visual analog scale was used to evaluate the degree of pain at rest and during movement at 2h, 6h, and 12h after the operation), cognitive function (Mini-Mental State Examination (MMSE) scale was used to assess the cognitive function before the operation and 1 day, 3 days, and 5 days after the operation, including time and place, language, orientation, calculation, delayed memory and useability), and incidence of adverse reactions were assessed and compared between the two groups. Results: The research group exhibited significantly lower propofol dosage and anesthesia recovery time compared to the control group (P < .05). Hemodynamic stability, as indicated by SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), and SpO2 (Peripheral Capillary Oxygen Saturation)levels, was better maintained in the research group, especially at the beginning of the operation (P < .05). VAS (Visual Analog Scale) scores for pain at rest and during exercise were significantly lower in the research group at 2h and 6h post-operation (P < .05). MMSE (Mini-Mental State Examination) scores were higher in the research group compared to the control group at 1and3 days post-operation (P < .05). Additionally, the incidence of adverse reactions was significantly lower in the research group (8.00%) compared to the control group (20.00%, P < .05).The above results were subjected to t test and χ2 test. Conclusions: Nalbuphine combined with propofol effectively alleviates visceral pain during laparoscopic ovarian tumor resection, stabilizes hemodynamics, and preserves cognitive function. This combination demonstrates promising analgesic and sedative effects with high safety, suggesting its potential for widespread clinical use.

6.
Molecules ; 28(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36985394

RESUMO

Photocatalytic technology is considered an ideal approach for clean energy conversion and environmental pollution applications. In this work, a bifunctional BiOBr/ZIF-8/ZnO photocatalyst was proposed for removing phenols in wastewater and generating hydrogen peroxide. Insights from scanning electron microscopy measurements revealed the well-dispersion of ZIF-8/ZnO was on the BiOBr layer, which could effectively prevent agglomeration of ZIF-8 and facilitate the separation of carriers. In addition, the optimal H2O2 yield of the BiOBr/ZIF-8/ZnO sample could reach 116 mmol·L-1·g-1 within 2 h, much higher than that of pure BiOBr (with the value of 82 mmol·L-1·g-1). The optimal BiOBr/ZIF-8/ZnO sample could also remove 90% of the phenol or bisphenol A in 2 h, and its kinetic constants were 3.8 times and 2.3 times that of pure BiOBr, respectively. Based on the analysis of the various experimental characterizations, the photocatalytic mechanism of the S-scheme BiOBr/ZIF-8/ZnO composite for the degradation of phenolic pollutants and generation of H2O2 was proposed. The formation of the heterojunction and the oxygen vacancy work together to significantly improve its photocatalytic efficiency. In addition, the BiOBr/ZIF-8/ZnO catalyst has a certain impact on the degradation of phenol in actual wastewater, providing a way to effectively remove refractory pollutants and generate H2O2 in actual water.

7.
Soft Matter ; 18(19): 3748-3755, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35506704

RESUMO

Self-wrinkling hydrogels enable various engineering and biomedical applications. The major challenge is to couple the self-wrinkling technologies and enhancement strategies, so as to get rid of the poor mechanical properties of existing self-wrinkling gels. Herein we present a facile diffusion-complexation strategy for constructing strong and ultratough self-wrinkling polyelectrolyte hydrogels with programmable wrinkled structures and customizable 3D configurations. Driven by the diffusion of low-molecular-weight chitosan polycations into the polyanion hydrogels, the high-modulus polyelectrolyte complexation shells can form directly on the hydrogel surface. Meanwhile, the polyanion hydrogels deswell/shrink due to the low osmotic pressure, which applies an isotropous surface compressive stress for inducing the formation of polygonal wrinkled structures. When the diffusion-complexation reaction occurs on a pre-stretched hydrogel sheet, the long-range ordered wrinkled structures can form during the springback/recovery of the hydrogel matrix. Moreover, through controlling the regions of diffusion-complexation reaction on the pre-stretched hydrogels, they can be spontaneously transformed into various 3D configurations with ordered wrinkled structures. Notably, because of the introduction of plenty of electrostatic binding (i.e., sacrificial bonds), the as-prepared self-wrinkling gels possess outstanding mechanical properties, far superior to the reported ones. This diffusion-complexation strategy paves the way for the on-demand design of high-performance self-wrinkling hydrogels.


Assuntos
Quitosana , Envelhecimento da Pele , Hidrogéis/química , Polieletrólitos
8.
Ann Vasc Surg ; 77: 352.e1-352.e5, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34461240

RESUMO

Renovascular hypertension is a common cause of secondary hypertension. According to the epidemiological survey, the prevalence of renovascular hypertension accounts for 1-5% of the population with hypertension. Most of the cases are associated with atherosclerosis and Fibromuscular Dysplasia (FMD). Owing to the lack of standard treatment, they will eventually develop into chronic kidney disease, which significantly affects the patient's quality of life. Hypertension is considered a prerequisite for renal artery surgery; renal function research is used to guide the treatment of unilateral lesions because endovascular intervention can only slightly improve hypertension and renal function. We advocate open surgery for patients with congenital dysplasia of renal vascular hypertension, in which the most common surgical operations are aortorenal artery bypass, renal artery endarterectomy, and renal artery replantation. This paper reports a rare case of renovascular hypertension. The patient was a 13-year-old female, and the operation was risky and complicated. He was diagnosed with a congenital absence of the right renal artery. The right renal function was recovered, and the blood pressure was well controlled after the Aorta-Right Renal Artery Bypass.


Assuntos
Pressão Sanguínea , Hipertensão Renovascular/cirurgia , Artéria Renal/cirurgia , Enxerto Vascular , Malformações Vasculares/cirurgia , Adolescente , Anastomose Cirúrgica , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Artéria Renal/anormalidades , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiopatologia , Resultado do Tratamento , Malformações Vasculares/complicações , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/fisiopatologia
9.
Langmuir ; 36(26): 7701-7705, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571028

RESUMO

Micromotors enjoy burgeoning interest but a limitation of their design is to require continuous supply of new fuel. The preponderance of extant micromotors depend, for their motion, on irradiation by light or exposure to acid in their environment. Here we demonstrate a motor that carries its own fuel internally, in this sense representing an analogue, in micron-sized objects, of the internal combustion engine. The fuel is DPCP (diphenylcyclopropenone) microcrystal, a solid-state chemical that after ignition by UV light requires no further irradiation to sustain a chemical reaction that emits carbon monoxide gas that can be used to propel the particle on which this chemical resides. It is loaded asymmetrically onto inexpensive microparticles to produce internally fueled propulsion with speed up to ∼20 µm/s over distances up to 15 times the capsule length in water. Once ignited, the motors maintain their direction of motion and move without need for light to follow their path. Possible strategies to extend the idea beyond the current proof of concept are discussed.

10.
Nanotechnology ; 31(46): 465403, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-32857731

RESUMO

Active thermal management is essential for the operation of modern technologies like electronic circuits and spacecraft systems to deal with the complex control and conversion of thermal energy. One basic requirement for the materials is its tunable and reversible thermal properties. Here, we try to provide a systematic investigation of the thermal smart materials composed of low-dimensional solid particles suspended in liquid media, whose structures and properties can be tuned by external field. A two-step theoretical model, which takes into account the effects from particle aggregation and orientational variation, was proposed and obtained reasonable agreement with both literature and our own experimental results. Graphene nanosheets/Mg-Al layered double hydroxides (GNS/LDH) were fabricated and their silicone oil suspension shows reversible thermal conductivity switching under DC electric field due to the formation/break-up of chain-like structures with a maximum switching ratio around 1.35×. This study reveals the underlying mechanism of thermal conductivity enhancement in nanoparticle suspensions, and provides a preliminary example to design and fabricate responsive thermal materials for the next generation technologies.

11.
J Chem Phys ; 140(3): 034703, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25669403

RESUMO

Rotational diffusion processes are correlated with nanoparticle visualization and manipulation techniques, widely used in nanocomposites, nanofluids, bioscience, and so on. However, a systematical methodology of deriving this diffusivity is still lacking. In the current work, three molecular dynamics (MD) schemes, including equilibrium (Green-Kubo formula and Einstein relation) and nonequilibrium (Einstein-Smoluchowski relation) methods, are developed to calculate the rotational diffusion coefficient, taking a single rigid carbon nanotube in fluid argon as a case. We can conclude that the three methods produce same results on the basis of plenty of data with variation of the calculation parameters (tube length, diameter, fluid temperature, density, and viscosity), indicative of the validity and accuracy of the MD simulations. However, these results have a non-negligible deviation from the theoretical predictions of Tirado et al. [J. Chem. Phys. 81, 2047 (1984)], which may come from several unrevealed factors of the theory. The three MD methods proposed in this paper can also be applied to other situations of calculating rotational diffusion coefficient.


Assuntos
Nanotubos de Carbono/química , Argônio/química , Difusão , Simulação de Dinâmica Molecular
12.
Neuroimage Clin ; 43: 103636, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38950504

RESUMO

The long-term motor outcome of acute stroke patients may be correlated to the reorganization of brain motor network. Abundant neuroimaging studies contribute to understand the pathological changes and recovery of motor networks after stroke. In this review, we summarized how current neuroimaging studies have increased understanding of reorganization and plasticity in post stroke motor recovery. Firstly, we discussed the changes in the motor network over time during the motor-activation and resting states, as well as the overall functional integration trend of the motor network. These studies indicate that the motor network undergoes dynamic bilateral hemispheric functional reorganization, as well as a trend towards network randomization. In the second part, we summarized the current study progress in the application of neuroimaging technology to early predict the post-stroke motor outcome. In the third part, we discuss the neuroimaging techniques commonly used in the post-stroke recovery. These methods provide direct or indirect visualization patterns to understand the neural mechanisms of post-stroke motor recovery, opening up new avenues for studying spontaneous and treatment-induced recovery and plasticity after stroke.

13.
J Colloid Interface Sci ; 675: 848-856, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39002235

RESUMO

HYPOTHESIS: The scaling laws of drop pinch-off are known to be affected by drop compositions including dissolved polymers and non-Brownian particles. When the size of the particles is comparable to the characteristic length scale of the polymer network, these particles may interact strongly with the polymer environment, leading to new types of scaling behaviors not reported before. EXPERIMENTS: Using high-speed imaging, we experimentally studied the time evolution of the neck diameter hmin of drops composed of silica nanoparticles dispersed in PEO solution when extruded from a nozzle. FINDINGS: After initial Newtonian necking with hmin âˆ¼ t2/3, the subsequent stage may exhibit scaling variation, characterized by either exponential or power-law decay, depending on the nanoparticle volume fraction ϕ. The exponential decay hmin âˆ¼ e-t/τ signifies the coil-stretch transition in typical viscoelastic suspensions. We conducted an analysis of the power-law scenario hmin âˆ¼ tα at high ϕ, categorizing the entire process into three distinct regimes based on the exponents α. The dependences of critical thicknesses at transition points and exponents on polymer concentration offer initial insights into the potential transition from heterogeneous to homogeneous thinning in the mixture. This novel scaling variation bears implications for accurately predicting and controlling droplet fragmentation in industrial applications.

14.
Spectrochim Acta A Mol Biomol Spectrosc ; 310: 123958, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38281462

RESUMO

Regulation of the fluorescence through crystalizing from the matrix in the Carbon dots (CDs)-based solid-state materials has been verified to be one of the effective methods, yet there are not only challenges in preparing such materials efficiently, but also insufficient insight into their regulation mechanisms. Here, a one-pot solvothermal route to synthesize a series of CDs-based composites with crystalline matrix is reported. These crystals exhibited multicolor fluorescence with the feature of multi-peaks emissions with increasing temperatures from 140 ℃ to 220 ℃, in which the orange emitting O-CDs@PA and the yellow emitting Y-CDs@PA crystals obtained the FLQYs of 22% and 68% respectively due to relatively stable crystalline structures. After comparative analysis to both crystals in detail, the core and the groups associated with them on the interface between CDs and matrix were adjusted in size and species during structural transformation of the crystal matrix, which changes radically the energy band structures to influence fluorescent emitting of both crystals ultimately. In addition, the reasons resulting in higher FLQY for Y-CDs@PA were provided leveraging the schematic illustration presumed based on the PL properties of both crystals. Because of the optimal optical performances, these fluorescent materials promised to fabricate WLED devices and obtained a number of photometric parameters endowed these WLED devices with the feature of warm-white light.

15.
PeerJ ; 11: e15341, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151293

RESUMO

Background: Immune cell infiltration (ICI) has a close relationship with the progression of atherosclerosis (AS). Therefore, the current study was aimed to explore the role of genes related to ICI and to investigate potential mechanisms in AS. Methods: Single-sample gene set enrichment analysis (ssGSEA) was applied to explore immune infiltration in AS and controls. Genes related to immune infitration were mined by weighted gene co-expression network analysis (WGCNA). The function of those genes were analyzed by enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The interactions among those genes were visualized in the protein-protein interaction (PPI) network, followed by identification of hub genes through Cytoscape software. A receiver operating characteristic (ROC) plot was generated to assess the performance of hub genes in AS diagnosis. The expressions of hub genes were measured by reverse transcription quantitative real-time PCR (RT-qPCR) in human leukemia monocyticcell line (THP-1) derived foam cells and macrophages, which mimic AS and control, respectively. Results: We observed that the proportions of 27 immune cells were significantly elevated in AS. Subsequent integrative analyses of differential expression and WGCNA identified 99 immune cell-related differentially expressed genes (DEGs) between AS and control. Those DEGs were associated with tryptophan metabolism and extracellular matrix (ECM)-related functions. Moreover, by constructing the PPI network, we found 11 hub immune cell-related genes in AS. The expression pattern and receiver ROC analyses in two independent datasets showed that calsequestrin 2 (CASQ2), nexilin F-Actin binding protein (NEXN), matrix metallopeptidase 12 (MMP12), C-X-C motif chemokine ligand 10 (CXCL10), phospholamban (PLN), heme oxygenase 1 (HMOX1), ryanodine receptor 2 (RYR2), chitinase 3 like 1 (CHI3L1), matrix metallopeptidase 9 (MMP9), actin alpha cardiac muscle 1 (ACTC1) had good performance in distinguishing AS from control samples. Furthermore, those biomarkers were shown to be correlated with angiogenesis and immune checkpoints. In addition, we found 239 miRNAs and 47 transcription factor s (TFs), which may target those biomarkers and regulate their expressions. Finally, we found that RT-qPCR results were consistent with sequencing results.


Assuntos
Aterosclerose , Humanos , Biomarcadores , Aterosclerose/diagnóstico , Endopeptidases , Matriz Extracelular , Metaloproteases
16.
J Phys Condens Matter ; 36(13)2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38096577

RESUMO

Single-molecule junctions (SMJs) may bring exotic physical effects. In this work, a significant thermal rectification effect is observed in a cross-dimensional system, comprising a diamond, a single-molecule junction, and a carbon nanotube (CNT). The molecular dynamics simulations indicate that the interfacial thermal resistance varies with the direction of heat flow, the orientation of the crystal planes of the diamond, and the length of the CNT. We find that the thermal rectification ratio escalates with the length of the CNT, achieving a peak value of 730% with the CNT length of 200 nm. A detailed analysis of phonon vibrations suggests that the primary cause of thermal rectification is the mismatched vibrations between the biphenyl and carbonyl groups. This discovery may offer theoretical insights for both the experimental exploration and practical application of SMJs in efficient thermal management strategy for high power and highly integrated chips.

17.
Nat Commun ; 14(1): 8491, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123592

RESUMO

Chimeric antigen receptor (CAR)-T therapy requires autologous T lymphocytes from cancer patients, a process that is both costly and complex. Universal CAR-T cell treatment from allogeneic sources can overcome this limitation but is impeded by graft-versus-host disease (GvHD) and host versus-graft rejection (HvGR). Here, we introduce a mutated calcineurin subunit A (CNA) and a CD19-specific CAR into the T cell receptor α constant (TRAC) locus to generate cells that are resistant to the widely used immunosuppressant, cyclosporine A (CsA). These immunosuppressant-resistant universal (IRU) CAR-T cells display improved effector function in vitro and anti-tumour efficacy in a leukemia xenograft mouse model in the presence of CsA, compared with CAR-T cells carrying wild-type CNA. Moreover, IRU CAR-T cells retain effector function in vitro and in vivo in the presence of both allogeneic T cells and CsA. Lastly, CsA withdrawal restores HvGR, acting as a safety switch that can eliminate IRU CAR-T cells. These findings demonstrate the efficacy of CsA-resistant CAR-T cells as a universal, 'off-the-shelf' treatment option.


Assuntos
Neoplasias , Linfócitos T , Humanos , Animais , Camundongos , Ciclosporina/farmacologia , Células Alógenas , Imunossupressores/farmacologia
18.
BMC Med Genomics ; 15(1): 245, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36437453

RESUMO

BACKGROUND: More and more evidence has established the crucial roles of the innate and adaptive immune systems in driving atherosclerosis-associated chronic inflammation in arterial blood vessels. Thus, the goal of this research was to determine immune-related biomarkers in atherosclerosis. METHODS: In this study, we conducted analysis on the mRNA expression profile of atherosclerosis obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) between atherosclerosis and control samples and immune-related genes (IRGs) were intersected to obtain differentially expressed immune-related genes (DEIRGs). The protein-protein interaction (PPI) network was created by STRING database and hub genes were identified by the MCODE plug-in. Furthermore, the receiver operating characteristic (ROC) curve was executed to verify the diagnostic value of the hub genes, and microRNA (miRNA)-gene-transcription factor (TF) regulatory networks were used to explain the regulatory mechanism of hub genes in atherosclerosis. Finally, qRT-PCR was performed to identify the mRNA levels of the target genes. RESULTS: A total of 199 overlapping genes were screened out as DEIRGs by intersecting the DEGs and IRGs. Then, 6 hub genes with high diagnostic value (IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3) were identified via PPI network and ROC curve. Finally, miRNA-gene-TF networks revealed the regulatory mechanism of diagnostic genes.We used the carotid artery of AS patients and normal human carotid artery plaque samples for qRT-PCR verification, and the results showed that the hub gene had the same trend. CONCLUSION: Our study identified IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3 as immune-related hub genes of atherosclerosis. These genes may serve as potential therapeutic targets for atherosclerosis patients.


Assuntos
Aterosclerose , MicroRNAs , Humanos , Helicase IFIH1 Induzida por Interferon , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Aterosclerose/genética
19.
Front Immunol ; 13: 889051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603176

RESUMO

Adoptive cell therapy (ACT) with engineered T cells has emerged as a promising strategy for the treatment of malignant tumors. Among them, there is great interest in engineered γδ T cells for ACT. With both adaptive and innate immune characteristics, γδ T cells can be activated by γδ TCRs to recognize antigens in a MHC-independent manner, or by NK receptors to recognize stress-induced molecules. The dual recognition system enables γδ T cells with unique activation and cytotoxicity profiles, which should be considered for the design of engineered γδ T cells. However, the current designs of engineered γδ T cells mostly follow the strategies that used in αß T cells, but not making good use of the specific characteristics of γδ T cells. Therefore, it is no surprising that current engineered γδ T cells in preclinical or clinical trials have limited efficacy. In this review, we summarized the patterns of antigen recognition of γδ T cells and the features of signaling pathways for the functions of γδ T cells. This review will additionally discuss current progress in engineered γδ T cells and provide insights in the design of engineered γδ T cells based on their specific characteristics.


Assuntos
Neoplasias , Receptores de Antígenos de Linfócitos T gama-delta , Antígenos , Humanos , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T
20.
Nanomaterials (Basel) ; 12(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36432343

RESUMO

Thermal management is a critical task for highly integrated or high-power semiconductor devices. Low dimensional materials including graphene and single-layer hexagonal boron nitride (BN) are attractive candidates for this task because of their high thermal conductivity, semi-conductivity and other excellent physical properties. The similarities in crystal structure and chemistry between graphene and boron nitride provide the possibility of constructing graphene/BN heterostructures bearing unique functions. In this paper, we investigated the interfacial thermal transport properties of graphene/BN nanosheets via non-equilibrium molecular dynamics (NEMD) simulations. We observed a significant thermal rectification behavior of these graphene/BN nanosheets, and the rectification ratio increased with the system length increases up to 117%. This phenomenon is attributed to the mismatch of out-of-plane phonon vibration modes in two directions at the interface. In addition, we explored the underlying mechanism of the length dependence of the thermal transport properties. The results show promise for the thermal management of this two-dimensional heterostructure in an actively tunable manner.

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