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1.
Nat Aging ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143319

RESUMEN

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aß42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.

2.
Nano Lett ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140872

RESUMEN

Antiplatelet agents, particularly P2Y12 receptor inhibitors, are critical medicines in the prevention and treatment of thrombotic diseases in the clinic. However, their long-term use introduces a significant risk of bleeding in patients with cardiovascular diseases. Whether the bleeding is caused by the drug itself or due to surgical procedures or trauma, the need to rapidly reverse the effects of antiplatelet agents in the circulation is essential; however, no such agents are currently available. To address this need, here we describe a strategy that uses cell-membrane-wrapped nanoparticles (CM-NPs) for the rapid reversal of P2Y12 inhibitors. CM-NPs are fabricated with membranes derived from 293T cells genetically engineered to overexpress the P2Y12 receptor. Our findings support the potential of CM-NPs as a strategy for managing bleeding complications associated with P2Y12 receptor inhibitors, offering an approach to improve the safety in the use of these drugs in clinical settings.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39120580

RESUMEN

Spinal cord injury poses considerable challenges, particularly in diaphragm paralysis. To address limitations in existing diaphragm pacing technologies, we report an implantable, self-driven diaphragm pacing system based on a microvibration triboelectric nanogenerator (MV-TENG). Leveraging the efficient MV-TENG, the system harvests micromechanical energy and converts this energy into pulses for phrenic nerve stimulation. In vitro tests confirm a stable MV-TENG output, while subcutaneous implantation of the device in rats results in a constant amplitude over 4 weeks with remarkable energy-harvesting efficacy. The system effectively induces diaphragmatic motor-evoked potentials, triggering contractions of the diaphragm. This proof-of-concept system has potential clinical applications in implantable phrenic nerve stimulation, presenting a novel strategy for advancing next-generation diaphragm pacing devices.

4.
PeerJ Comput Sci ; 10: e2009, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39145230

RESUMEN

With the popularity of Internet applications, a large amount of Internet behavior log data is generated. Abnormal behaviors of corporate employees may lead to internet security issues and data leakage incidents. To ensure the safety of information systems, it is important to research on anomaly prediction of Internet behaviors. Due to the high cost of labeling big data manually, an unsupervised generative model-Anomaly Prediction of Internet behavior based on Generative Adversarial Networks (APIBGAN), which works only with a small amount of labeled data, is proposed to predict anomalies of Internet behaviors. After the input Internet behavior data is preprocessed by the proposed method, the data-generating generative adversarial network (DGGAN) in APIBGAN learns the distribution of real Internet behavior data by leveraging neural networks' powerful feature extraction from the data to generate Internet behavior data with random noise. The APIBGAN utilizes these labeled generated data as a benchmark to complete the distance-based anomaly prediction. Three categories of Internet behavior sampling data from corporate employees are employed to train APIBGAN: (1) Online behavior data of an individual in a department. (2) Online behavior data of multiple employees in the same department. (3) Online behavior data of multiple employees in different departments. The prediction scores of the three categories of Internet behavior data are 87.23%, 85.13%, and 83.47%, respectively, and are above the highest score of 81.35% which is obtained by the comparison method based on Isolation Forests in the CCF Big Data & Computing Intelligence Contest (CCF-BDCI). The experimental results validate that APIBGAN predicts the outlier of Internet behaviors effectively through the GAN, which is composed of a simple three-layer fully connected neural networks (FNNs). We can use APIBGAN not only for anomaly prediction of Internet behaviors but also for anomaly prediction in many other applications, which have big data infeasible to label manually. Above all, APIBGAN has broad application prospects for anomaly prediction, and our work also provides valuable input for anomaly prediction-based GAN.

5.
Nat Med ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147830

RESUMEN

Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during aging. Large, diverse population studies enable identifying comprehensive and representative brain change patterns resulting from distinct but overlapping pathological and biological factors, revealing intersections and heterogeneity in affected brain regions and clinical phenotypes. Herein, we leverage a state-of-the-art deep-representation learning method, Surreal-GAN, and present methodological advances and extensive experimental results elucidating brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies. Five dominant patterns of brain atrophy were identified and quantified for each individual by respective measures, R-indices. Their associations with biomedical, lifestyle and genetic factors provide insights into the etiology of observed variances, suggesting their potential as brain endophenotypes for genetic and lifestyle risks. Furthermore, baseline R-indices predict disease progression and mortality, capturing early changes as supplementary prognostic markers. These R-indices establish a dimensional approach to measuring aging trajectories and related brain changes. They hold promise for precise diagnostics, especially at preclinical stages, facilitating personalized patient management and targeted clinical trial recruitment based on specific brain endophenotypic expression and prognosis.

6.
Nat Commun ; 15(1): 5577, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38956082

RESUMEN

Recent advances in single-cell immune profiling have enabled the simultaneous measurement of transcriptome and T cell receptor (TCR) sequences, offering great potential for studying immune responses at the cellular level. However, integrating these diverse modalities across datasets is challenging due to their unique data characteristics and technical variations. Here, to address this, we develop the multimodal generative model mvTCR to fuse modality-specific information across transcriptome and TCR into a shared representation. Our analysis demonstrates the added value of multimodal over unimodal approaches to capture antigen specificity. Notably, we use mvTCR to distinguish T cell subpopulations binding to SARS-CoV-2 antigens from bystander cells. Furthermore, when combined with reference mapping approaches, mvTCR can map newly generated datasets to extensive T cell references, facilitating knowledge transfer. In summary, we envision mvTCR to enable a scalable analysis of multimodal immune profiling data and advance our understanding of immune responses.


Asunto(s)
COVID-19 , Receptores de Antígenos de Linfocitos T , SARS-CoV-2 , Análisis de la Célula Individual , Transcriptoma , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Análisis de la Célula Individual/métodos , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/inmunología , COVID-19/virología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Perfilación de la Expresión Génica/métodos , Antígenos Virales/inmunología , Antígenos Virales/genética
7.
Sleep Adv ; 5(1): zpae045, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076610

RESUMEN

Study Objectives: Few studies of middle-aged and older adults have examined the association between age and sleep using objective sleep measures. We examined these associations in adults aged ≥40 years using wrist actigraphy, and investigated whether these associations differed by sex and race. Methods: Participants were 468 cognitively normal adults aged ≥40 years enrolled in the Baltimore Longitudinal Study of Aging who completed wrist actigraphy. We used Generalized Least Squares Models to examine the associations of age with actigraphic sleep parameters, including total sleep time (TST), sleep efficiency, sleep onset latency, and wake after sleep onset (WASO). We conducted interaction and stratification analyses to test whether cross-sectional age-sleep associations were modified by sex and race. Results: In analyses adjusting for sex, body mass index, and individual medical conditions, older age was associated with longer TST from ages 40-70 that plateaued after age 70. Older age also was associated with lower sleep efficiency, longer sleep onset latency, and greater WASO. In men only, after age 70, older age was associated with shorter TST, lower sleep efficiency, longer onset latency, and greater WASO. However, we did not observe any significant interactions of race with age. Conclusions: Older age was associated with longer TST from ages 40 to 70 and with poorer sleep quality after age 40, and these relationships might vary by sex. Future studies with larger sample sizes are needed to investigate mechanisms that may account for sex differences in the observed age-sleep associations.

8.
Stem Cell Res Ther ; 15(1): 198, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971766

RESUMEN

BACKGROUND: Trans-sutural distraction osteogenesis (TSDO) involves the application of distraction force to facial sutures to stimulate osteogenesis. Gli1+ cells in the cranial sutures play an important role in bone growth. However, whether Gli1+ cells in facial sutures differentiate into bone under distraction force is unknown. METHODS: 4-week-old Gli1ER/Td and C57BL/6 mice were used to establish a TSDO model to explore osteogenesis of zygomaticomaxillary sutures. A Gli1+ cell lineage tracing model was used to observe the distribution of Gli1+ cells and explore the role of Gli1+ cells in facial bone remodeling. RESULTS: Distraction force promoted bone remodeling during TSDO. Fluorescence and two-photon scanning images revealed the distribution of Gli1+ cells. Under distraction force, Gli1-lineage cells proliferated significantly and co-localized with Runx2+ cells. Hedgehog signaling was upregulated in Gli1+ cells. Inhibition of Hedgehog signaling suppresses the proliferation and osteogenesis of Gli1+ cells induced by distraction force. Subsequently, the stem cell characteristics of Gli1+ cells were identified. Cell-stretching experiments verified that mechanical force promoted the osteogenic differentiation of Gli1+ cells through Hh signaling. Furthermore, immunofluorescence staining and RT-qPCR experiments demonstrated that the primary cilia in Gli1+ cells exhibit Hedgehog-independent mechanosensitivity, which was required for the osteogenic differentiation induced by mechanical force. CONCLUSIONS: Our study indicates that the primary cilia of Gli1+ cells sense mechanical stimuli, mediate Hedgehog signaling activation, and promote the osteogenic differentiation of Gli1+ cells in zygomaticomaxillary sutures.


Asunto(s)
Diferenciación Celular , Cilios , Suturas Craneales , Proteínas Hedgehog , Osteogénesis , Transducción de Señal , Proteína con Dedos de Zinc GLI1 , Animales , Ratones , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Osteogénesis/fisiología , Cilios/metabolismo , Suturas Craneales/metabolismo , Ratones Endogámicos C57BL , Osteogénesis por Distracción/métodos , Proliferación Celular
9.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063036

RESUMEN

BACKGROUND: As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. METHODS: By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. RESULTS: A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. CONCLUSION: A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Liposarcoma , Microambiente Tumoral , Humanos , Liposarcoma/genética , Liposarcoma/inmunología , Liposarcoma/patología , Liposarcoma/mortalidad , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Transcriptoma , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Nomogramas , Masculino , Femenino , Estimación de Kaplan-Meier , Curva ROC
10.
Curr Issues Mol Biol ; 46(7): 6633-6645, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39057037

RESUMEN

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway allergic disease may not be a high-risk factor, but may be a protective factor for COVID-19 infection, which is closely related to its low-level expression of the ACE2 receptor and the complex cytokines network as underlying molecular regulatory mechanisms. In addition, steroid hormones and age factors could not be ignored. In this review, we have summarized some current evidence on the relationship between COVID-19 and allergic rhinitis to highlight the underlying mechanisms of COVID-19 infection and provide novel insights for its prevention and treatment. The key findings show that allergic rhinitis and its related molecular mechanisms may have a protective effect against COVID-19 infection.

11.
J Plast Reconstr Aesthet Surg ; 95: 357-367, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38971123

RESUMEN

BACKGROUND: Autologous fat transplantation is limited by the uncertainty of graft retention, impeding its application. Among the current strategies for processing lipoaspirates, high-density fat (HDF) is recommended owing to the enrichment of stem cells and washing before cotton concentration for simplicity of operation. Poloxamer 188 (P188) washing has been shown to repair the membranes of damaged cells. This study aimed to investigate the effect of P188-washing on fat graft survival and identify the best technique for processing lipoaspirates. METHODS: Lipoaspirates were prepared using centrifugation to obtain HDF, which was then washed with saline or P188 followed by cotton concentration. Tissue integrity, adipocytic activity, and viability of stromal vascular fraction (SVF) in the samples from the 3 groups were assessed. Samples were sequenced in vitro using high-throughput RNA-seq, and differentially expressed genes were validated using qPCR and western blotting (WB). After transplantation under the dorsum of nude mice for 8 weeks, the grafts were extracted and examined for residual volume, histologic characteristics, and vascularization. RESULTS: The HDF and P188 groups showed a higher survival rate of SVF, more Ki67-positive cells, intact tissue structure, and lesser fibrosis than the saline group. There were no significant differences in the density of SVF and residual volume of grafts. HDF showed significantly improved vascularization during 8 weeks. Through RNA-seq and bioinformatic analysis, notable changes in several related genes after transplantation were observed. CONCLUSIONS: P188 treatment can prevent cells from apoptosis and preserve tissue viability, thereby improving graft quality. HDF contains large amounts of SVF and can be regarded as an excellent grafting material.


Asunto(s)
Tejido Adiposo , Supervivencia de Injerto , Lipectomía , Ratones Desnudos , Poloxámero , Animales , Poloxámero/farmacología , Ratones , Tejido Adiposo/trasplante , Lipectomía/métodos , Humanos , Femenino , Recolección de Tejidos y Órganos/métodos , Trasplante Autólogo
12.
Adv Sci (Weinh) ; : e2402178, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943253

RESUMEN

Gene-editing technology shows great potential in glioblastoma (GBM) therapy. Due to the complexity of GBM pathogenesis, a single gene-editing-based therapy is unlikely to be successful; therefore, a multi-gene knockout strategy is preferred for effective GBM inhibition. Here, a non-invasive, biodegradable brain-targeted CRISPR/Cas12a nanocapsule is used that simultaneously targeted dual oncogenes, EGFR and PLK1, for effective GBM therapy. This cargo nanoencapsulation technology enables the CRISPR/Cas12a system to achieve extended blood half-life, efficient blood-brain barrier (BBB) penetration, active tumor targeting, and selective release. In U87MG cells, the combinatorial gene editing system resulted in 61% and 33% knockout of EGFR and PLK1, respectively. Following systemic administration, the CRISPR/Cas12a system demonstrated promising brain tumor accumulation that led to extensive EGFR and PLK1 gene editing in both U87MG and patient-derived GSC xenograft mouse models with negligible off-target gene editing detected through NGS. Additionally, CRISPR/Cas12a nanocapsules that concurrently targeted the EGFR and PLK1 oncogenes showed superior tumor growth suppression and significantly improved the median survival time relative to nanocapsules containing single oncogene knockouts, signifying the potency of the multi-oncogene targeting strategy. The findings indicate that utilization of the CRISPR/Cas12a combinatorial gene editing technique presents a practical option for gene therapy in GBM.

13.
bioRxiv ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38915636

RESUMEN

INTRODUCTION: The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. METHODS: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. RESULTS: Sex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.

14.
Aesthetic Plast Surg ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839614

RESUMEN

BACKGROUND: Deviation and asymmetry relapse after secondary unilateral cleft rhinoplasty with septal extension graft is a common yet serious problem especially among Asian patients. Therefore, finding an effective approach to reduce deformity relapse remains a great challenge to plastic surgeons. METHODS: In this study, authors established finite element models to simulate different nasal cartilage-corrected options and different reinforcing strategies in secondary unilateral cleft rhinoplasty. A load of 0.01N was given to the nasal tip to simulate the soft tissue pressure, while two loads of 0.5N were separately given to the anterior and posterior part of the septal extension graft to simulate the rhinoplasty condition. Maximum deformations were evaluated to make stability judgments. RESULTS: The maximum deformation of different cartilage correction models in ascending order was: UCL deformity with septum correction, normal nasal cartilage, UCL nasal deformity, and UCL nasal deformity with lower lateral cartilage correction. When applied L-strut reinforcement graft was harvested from the perpendicular plate of the ethmoid bone, the maximum deformation of the models decreased significantly, and strong fixation of the septum could further enhance this decreasing effect. CONCLUSIONS: Correcting the septum and lower lateral cartilage together could improve the structural stability and symmetry in secondary unilateral cleft rhinoplasty. To keep the corrected septum stable and thus reduce deformity relapse, reinforcing the L-strut with perpendicular plate of ethmoid graft while strongly anchoring the septal cartilage to the anterior nasal spine was proved to be effective in both finite element analysis and clinical observation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

15.
Artículo en Inglés | MEDLINE | ID: mdl-38836734

RESUMEN

Objective: To investigate the effectiveness of strengthen psychological intervention in 85 clients who had pneumonia caused by a novel coronavirus. Methods: As the study's subjects, 162 new coronavirus pneumonia clients admitted to our hospital between January 2020 and September 2020 had their clinical records retrospectively examined. According to different nursing methods, 162 patients with new coronavirus pneumonia were separated into a control team (n=77) and an experimental team (n=85). The test group received the intense psychological intervention, whereas the controlling team only received standard nursing care. The two groups' treatment compliance and nursing satisfaction were observed, the self-rating symptom scale (SCL-90) scores and coping style (MCMQ) grades of the two teams prior to and after the interference was contrasted, and the nursing quality of the two teams was contrasted. Results: In terms of compliance, the overall treatment compliance rate of patients in the experimental group increased significantly. In terms of the psychological state of the experimental group, significant improvements were observed in all psychological dimensions of the patients in the experimental group, including a reduction in negative emotions and an increase in nursing satisfaction. In terms of self-coping, patients in the experimental group showed significant improvement in various dimensions. And the quality of nursing care in the experimental group has been significantly improved. Conclusion: This study highlights the importance of intensive psychological intervention in the overall care of COVID-19 patients and its role in improving patient treatment compliance, negative emotions, self-coping styles and patient health.

16.
Biotechnol Bioeng ; 121(9): 2752-2766, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38877732

RESUMEN

Natural hydrogels are widely employed in tissue engineering and have excellent biodegradability and biocompatibility. Unfortunately, the utilization of such hydrogels in the field of three-dimensional (3D) printing nasal cartilage is constrained by their subpar mechanical characteristics. In this study, we provide a multicrosslinked network hybrid ink made of photocurable gelatin, hyaluronic acid, and acrylamide (AM). The ink may be processed into intricate 3D hydrogel structures with good biocompatibility and high stiffness properties using 3D printing technology based on digital light processing (DLP), including intricate shapes resembling noses. By varying the AM content, the mechanical behavior and biocompatibility of the hydrogels can be adjusted. In comparison to the gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hydrogel, adding AM considerably enhances the hydrogel's mechanical properties while also enhancing printing quality. Meanwhile, the biocompatibility of the multicrosslinked network hydrogels and the development of cartilage were assessed using neonatal Sprague-Dawley (SD) rat chondrocytes (CChons). Cells sown on the hydrogels considerably multiplied after 7 days of culture and kept up the expression of particular proteins. Together, our findings point to GelMA/HAMA/polyacrylamide (PAM) hydrogel as a potential material for nasal cartilage restoration. The photocuring multicrosslinked network ink composed of appropriate proportions of GelMA/HAMA/PAM is very suitable for DLP 3D printing and will play an important role in the construction of nasal cartilage, ear cartilage, articular cartilage, and other tissues and organs in the future. Notably, previous studies have not explored the application of 3D-printed GelMA/HAMA/PAM hydrogels for nasal cartilage regeneration.


Asunto(s)
Hidrogeles , Cartílagos Nasales , Impresión Tridimensional , Ratas Sprague-Dawley , Andamios del Tejido , Animales , Ratas , Hidrogeles/química , Andamios del Tejido/química , Condrocitos/citología , Ingeniería de Tejidos , Ácido Hialurónico/química , Gelatina/química , Bioimpresión/métodos
18.
J Leukoc Biol ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753658

RESUMEN

Extracellular vesicles (EVs) are the nano-sized membrane particles secreted by various cell types, which are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells (CAR-T) and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we report the EVs released by cytokine-activated CD8 + T cells (caCD8) and its cytotoxicity against cancer cells. CaCD8 cells can release EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokines cocktail ex vivo. The isolated vesicles have typical EV characteristics, such as an oval shape and a size distribution between 30-200 nm, as well as CD81 expression. Notably, caCD8-EVs displayed cytotoxicity against various cancer cells in vitro. Furthermore, mechanism analysis demonstrates that caCD8-EVs not only contain typical cytotoxic proteins (i.e., granzyme B and perforin), but also significantly enrich IFNγ compared to caCD8 cells. The EVs-derived IFNγ participates in EVs-induced apoptosis in cancer cells. Therefore, our data reveal an antitumor effects of EVs secreted from caCD8 cells and the potential role of the EVs-derived IFNγ.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38742659

RESUMEN

BACKGROUND: Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (ß-amyloid [Aß] or apolipoprotein E-ε4 [APOE-ε4]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear. METHODS: Wrist accelerometry, brain Aß (+/-), and APOE-ε4 genotype were collected in 106 (Aß) and 472 (APOE-ε4) participants (mean age 76 [standard deviation{SD}: 8.5) or 75 [SD: 9.2] years, 60% or 58% women) in the Baltimore Longitudinal Study of Aging. Adjusted linear and function-on-scalar regression models examined whether Aß or APOE-ε4 status was cross-sectionally associated with activity patterns (amount, variability, or fragmentation) overall and by time of day, respectively. Differences in activity patterns by combinations of Aß and APOE-ε4 status were descriptively examined (n = 105). RESULTS: There were no differences in any activity pattern by Aß or APOE-ε4 status overall. Aß+ was associated with lower total amount and lower within-day variability of physical activity overnight and early evening, and APOE-ε4 carriers had higher total amount of activity in the evening and lower within-day variability of activity in the morning. Diurnal curves of activity were blunted among those with Aß+ regardless of APOE-ε4 status, but only when including older adults with mild cognitive impairment/dementia. CONCLUSIONS: Aß+ in cognitively unimpaired older adults might manifest as lower amount and variability of daily physical activity, particularly during overnight/evening hours. Future research is needed to examine changes in activity patterns in larger samples and by other AD biomarkers.


Asunto(s)
Acelerometría , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Apolipoproteína E4 , Biomarcadores , Humanos , Femenino , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Masculino , Anciano , Apolipoproteína E4/genética , Péptidos beta-Amiloides/metabolismo , Estudios Longitudinales , Factores de Riesgo , Anciano de 80 o más Años , Genotipo , Estudios Transversales , Ejercicio Físico/fisiología , Baltimore
20.
Nature ; 630(8015): 77-83, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38750367

RESUMEN

Intensity, polarization and wavelength are intrinsic characteristics of light. Characterizing light with arbitrarily mixed information on polarization and spectrum is in high demand1-4. Despite the extensive efforts in the design of polarimeters5-18 and spectrometers19-27, concurrently yielding high-dimensional signatures of intensity, polarization and spectrum of the light fields is challenging and typically requires complicated integration of polarization- and/or wavelength-sensitive elements in the space or time domains. Here we demonstrate that simple thin-film interfaces with spatial and frequency dispersion can project and tailor polarization and spectrum responses in the wavevector domain. By this means, high-dimensional light information can be encoded into single-shot imaging and deciphered with the assistance of a deep residual network. To the best of our knowledge, our work not only enables full characterization of light with arbitrarily mixed full-Stokes polarization states across a broadband spectrum with a single device and a single measurement but also presents comparable, if not better, performance than state-of-the-art single-purpose miniaturized polarimeters or spectrometers. Our approach can be readily used as an alignment-free retrofit for the existing imaging platforms, opening up new paths to ultra-compact and high-dimensional photodetection and imaging.

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