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1.
Artículo en Inglés | MEDLINE | ID: mdl-38861440

RESUMEN

Negative emotional states, such as anxiety and depression, pose significant challenges in contemporary society, often stemming from the stress encountered in daily activities. Stress (state or level) recognition is a crucial prerequisite for effective stress management and intervention. Presently, wearable devices have been employed to capture physiological signals and analyze stress states. However, their constant skin contact can lead to discomfort and disturbance during prolonged monitoring. In this paper, a peak attention-based multitasking framework is presented for non-contact stress recognition. The framework extracts rPPG signals from RGB facial videos, utilizing them as inputs for a novel multi-task attentional convolutional neural network for stress recognition (MTASR). It incorporates peak detection and HR estimation as auxiliary tasks to facilitate stress recognition. By leveraging multi-task learning, MTASR can utilize information related to stress physiological responses, thereby enhancing feature extraction efficiency. For stress recognition, two binary classification tasks are applied: stress state recognition and stress level recognition. The model is validated on the UBFC-Phys public dataset and demonstrates an accuracy of 94.33% for stress state recognition and 83.83% for stress level recognition. The proposed method outperforms the dataset's baseline methods and other competing approaches.

2.
Int Immunopharmacol ; 137: 112427, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38889506

RESUMEN

The hematopoietic homeostasis in the bone marrow is inextricably intertwined with the immune milieu in peripheral circulation. Researches investigating the pathogenesis of systemic lupus erythematosus (SLE) have defined considerable secretion of inflammatory mediators and activation of pro-inflammatory cells. However, the impacts of "extrinsic" factors on hematopoietic stem and progenitor cells (HSPCs) remain unclear, and it is uncertain whether treatments can help coordinate the biased differentiation. In this study, we showed differences in the proportions of common myeloid progenitors (CMP) and myeloid output in the bone marrow of premorbid and morbid MRL/lpr mice using flow cytometry. RNA-seq analysis of lineage-affiliated transcriptional factors and dysregulated genes within lin- HSPCs revealed inflammation potentiation during disease progression. Further, intra-bone marrow mesenchymal stem cells transplantation (IBM-MSCT) partially coordinated myeloid generation and counteracted lupus-associated inflammation gene alterations, compared to intravenous injection. Additionally, co-culturing with umbilical cord mesenchymal stem cells (UC-MSCs) intervened in myeloid lineage tendency, as detected by RT-qPCR of myeloid-related genes. Our research demonstrated enhanced tendency toward myeloid differentiation and highlighted the feasibility of IBM-MSCT for lineage-biased HSPCs in MRL/lpr lupus model, providing novel insight into hematopoiesis and MSC-related treatments for SLE.

3.
J Environ Manage ; 363: 121387, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38850914

RESUMEN

The persistence of dissolved organic matter (DOM) plays a crucial role in the cycling and distribution of carbon and nutrients. Nonetheless, our understanding of how environmental alterations affect the persistence of sedimentary DOM remains incomplete. Excitation Emission Fluorescence Matrix-Parallel Factor Analysis (EEM-PARAFAC) was used to examine the fluorescence and compositional characteristics of hydrophilic and hydrophobic DOM (separated using XAD-8 resin) within sediments from twelve lakes and reservoirs. Fluorescence analysis indicated that DOM persistence is dependent on the proportions of the three components derived from PARAFAC. The Mantel test showed that climatic factors had the most significant impact on DOM persistence (Mantel's r = 0.46-0.54, Mantel's p = 0.001-0.007), while anthropogenic (Mantel's r = 0.24-0.32, Mantel's p = 0.03-0.05) and hydrological factors (Mantel's r = 0.03-0.22, Mantel's p = 0.06-0.40) had a somewhat lesser influence. Environmental changes resulted in a consistent decline in DOM persistence from Northeast to Southwest China, accompanied by an increase in gross primary productivity (GPP). Reduced DOM persistence due to climate, hydrological, and anthropogenic factors may lead to elevated concentrations of total phosphorus (TP), contributing to deteriorating water quality and events such as algal blooms. The decline in water quality due to reduced DOM persistence in lakes with high GPP can exacerbate the transition from carbon sinks to carbon sources. Consequently, the persistence of sedimentary DOM significantly influences nutrient and carbon cycling in lakes. Investigating DOM persistence in lakes across diverse geographic locations offers a new perspective on lake eutrophication and carbon emissions. Furthermore, it is crucial to develop targeted recommendations for lake restoration and management.


Asunto(s)
Ciclo del Carbono , Sedimentos Geológicos , Lagos , Sedimentos Geológicos/química , Sedimentos Geológicos/análisis , Lagos/química , Carbono/análisis , Fósforo/análisis , China , Monitoreo del Ambiente
4.
Small ; : e2403879, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38881274

RESUMEN

Ocean energy harvesting based on a triboelectric nanogenerator (TENG) has great application potential, while the encapsulation of triboelectric devices in water poses a critical issue. Herein, a triboelectric-electromagnetic hybrid nanogenerator (TE-HNG) consisting of TENGs and electromagnetic generators (EMGs) is proposed to harvest water flow energy. A magnetic coupling transmission component is applied to replace traditional bearing structures, which can realize the fully enclosed packaging of the TENG devices and achieve long-lasting energy harvesting from water flow. Under the intense water impact, magnetic coupling reduces the possibility of internal gear damage due to excessive torque, indicating superior stability and robustness compared to conventional TENG. At the waterwheel rotates speed of 75 rpm, the TE-HNG can generate an output peak power of 114.83 mW, corresponding to a peak power density of 37.105 W m-3. After 5 h of continuous operation, the electrical output attenuation of TENG is less than 3%, demonstrating excellent device durability. Moreover, a self-powered temperature sensing system and a self-powered cathodic protection system based on the TE-HNG are developed and illustrated. This work provides a prospective strategy for improving the output stability of TENGs, which benefits the practical applications of the TENGs in large-scale blue energy harvesting.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38668842

RESUMEN

The ammonia fiber expansion (AFEX) pretreatment of lignocellulosic biomass offers a significant advantage in terms of obtaining high glucan conversion, with the added benefit of ammonia being fully recyclable. However, despite the high efficiency of AFEX in pretreating lignocellulose, relatively high enzyme loading is still required for effective cellulose conversions. In this study, we have updated the AFEX pretreatment method; ammonia and sodium sulfite (ASS) can be used to produce a more digestible substrate. The results demonstrate that ASS-pretreated corn stover (CS) yields a higher fermentable sugar yield compared with AFEX pretreatment, even at lower enzyme loadings. Specifically, at an enzyme loading of 12 mg protein/g glucan, ASS-CS achieved 88.8% glucose and 80.6% xylose yield. Characterization analysis reveals that lignin underwent sulfonation during ASS pretreatment. This modification results in a more negative zeta potential for ASS-CS, indicating a reduction in nonproductive adsorption between lignin and cellulase through increased electrostatic repulsion.

6.
Anal Chem ; 96(17): 6523-6527, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38634570

RESUMEN

Complete sample digestion is a prerequisite for acquiring high-quality analytical results for geological samples. Closed-vessel acid digestion (bomb) has typically been used for the total digestion of refractory geological samples. However, the long digestion time (4-5 days) and insoluble fluoride complexes still pose challenges for digesting refractory geological samples using this approach. In this study, an efficient and simplified digestion technique combining ultrafine powders from planetary ball milling with bomb digestion was developed for trace element analysis of refractory geological samples: peridotite and granitoid. The method shows two significant improvements compared with previous approaches. (1) By performing dry planetary ultrafine milling, the initial 200 mesh peridotite (<74 µm) could be reduced to 800 mesh (<20 µm) in 6 min at a ball-to-powder mass ratio of approximately 15 using 3 mm tungsten carbide milling balls. (2) Complete peridotite and granitoid dissolution were achieved in approximately 2 h, 60 times faster than what is achievable using previous methods (2 h vs 120 h). Moreover, ultrafine powders effectively suppressed insoluble fluoride formation during bomb digestion. A suite of peridotite and granitoid reference materials were measured to evaluate the stability of this method. This efficient, simple, and reliable sample digestion method could benefit geological, food, environmental, and other fields requiring solid sample decomposition via wet acid, fusion, combustion, or dry ashing.

7.
World J Stem Cells ; 16(3): 267-286, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38577236

RESUMEN

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

8.
Cell Prolif ; : e13640, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38556840

RESUMEN

Macrophages play a pivotal role in the immunological cascade activated in response to biomedical implants, which predetermine acceptance or rejection of implants by the host via pro- and anti-inflammatory polarisation states. The role of chemical signals in macrophage polarisation is well-established, but how physical cues regulate macrophage function that may play a fundamental role in implant-bone interface, remains poorly understood. Here we find that bone marrow-derived macrophages (BMDM) cultured on polyacrylamide gels of varying stiffness exhibit different polarisation states. BMDM are 'primed' to a pro-inflammatory M1 phenotype on stiff substrates, while to an anti-inflammatory M2 phenotype on soft and medium stiffness substrates. It is further observed that matrix stiffening increases Piezo1 expression, as well as leads to subsequent activation of the mechanotransduction signalling effector YAP, thus favouring M1 polarisation whilst suppressing M2 polarisation. Moreover, upon treatment with YAP inhibitor, we successfully induce macrophage re-polarisation to the M2 state within the implant site microenvironment, which in turn promotes implant osseointegration. Collectively, our present study thus characterises the critical role of the Piezo1-YAP signalling axis in macrophage mechanosensing and stiffness-mediated macrophage polarisation and provides cues for the design of immuno-modulatory biomaterials that can regulate the macrophage phenotype.

9.
Brain Behav Immun ; 119: 56-83, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38555992

RESUMEN

Decreased hippocampal tropomyosin receptor kinase B (TrkB) level is implicated in the pathophysiology of stress-induced mood disorder and cognitive decline. However, how TrkB is modified and mediates behavioral responses to chronic stress remains largely unknown. Here the effects and mechanisms of TrkB cleavage by asparagine endopeptidase (AEP) were examined on a preclinical murine model of chronic restraint stress (CRS)-induced depression. CRS activated IL-1ß-C/EBPß-AEP pathway in mice hippocampus, accompanied by elevated TrkB 1-486 fragment generated by AEP. Specifi.c overexpression or suppression of AEP-TrkB axis in hippocampal CaMKIIα-positive cells aggravated or relieved depressive-like behaviors, respectively. Mechanistically, in addition to facilitating AMPARs internalization, TrkB 1-486 interacted with peroxisome proliferator-activated receptor-δ (PPAR-δ) and sequestered it in cytoplasm, repressing PPAR-δ-mediated transactivation and mitochondrial function. Moreover, co-administration of 7,8-dihydroxyflavone and a peptide disrupting the binding of TrkB 1-486 with PPAR-δ attenuated depression-like symptoms not only in CRS animals, but also in Alzheimer's disease and aged mice. These findings reveal a novel role for TrkB cleavage in promoting depressive-like phenotype.


Asunto(s)
Depresión , Hipocampo , Estrés Psicológico , Animales , Hipocampo/metabolismo , Ratones , Depresión/metabolismo , Masculino , Estrés Psicológico/metabolismo , Receptor trkB/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Conducta Animal/fisiología , Transducción de Señal/fisiología , Enfermedad de Alzheimer/metabolismo , Glicoproteínas de Membrana/metabolismo
10.
Sci Total Environ ; 918: 170625, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38320705

RESUMEN

Intensive anthropogenic activities, such as excessive nitrogen input and dam construction, have altered the nitrogen cycle in the global river system. However, the focus on the source, transformation and fate of nitrogen in the Yellow River is still scarce. In this study, the multiple isotopes (δ15N-NO3-, δ18O-NO3-, δ15N-NH4+ and δ15N-PN) were deciphered to explore the nitrogen cycling processes and the driving factors in the thermally stratified cascade reservoirs (Sanmenxia Reservoir: SMXR and Xiaolangdi Reservoir: XLDR) and Lower Yellow River (LYR) during the drainage period of the XLDR. In the SMXR, algal bloom triggered the assimilation process in the upper layer before the SMX Dam, followed by remineralization and subsequent nitrification processes in the lower water layers. The nitrification reaction in the XLDR progressively increased along both longitudinal and vertical directions to the lower layer of the XLD Dam, which was linked to the variation in the water residence time of riverine, transition and lentic zones. The robust nitrification rates in the lower layer of the lentic zone coincided with the substantial depletion of nitrate isotopic composition and enrichment of both δ15N-PN and δ15N-NH4+, indicating the longer water residence time not only promoted the growth of the nitrifying population but also facilitated the remineralization to enhance NH4+ availability. In the LYR, the slight nitrate assimilation, as indicated by nitrate isotopic composition and fractionation models, was the predominant nitrogen transformation process. The Bayesian isotope mixing model results showed that manure and sewage was the dominant nitrate source (50 %) in the middle and lower Yellow River. Notably, the in-reservoir nitrification was a significant nitrate source (27 %) in the XLDR and LYR. Our study deepens the understanding of anthropogenic activities impacting the nitrogen cycle in the river-reservoir system, providing valuable insight into water quality management and nitrogen cycle mechanisms in the Yellow River.

11.
PLoS Pathog ; 20(1): e1011729, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38206983

RESUMEN

Both constitutive and inducible immune mechanisms are employed by hosts for defense against infection. Constitutive immunity allows for a faster response, but it comes with an associated cost that is always present. This trade-off between speed and fitness costs leads to the theoretical prediction that constitutive immunity will be favored where parasite exposure is frequent. We selected populations of Drosophila melanogaster under high parasite pressure from the parasitoid wasp Leptopilina boulardi. With RNA sequencing, we found the evolution of resistance in these populations was associated with them developing constitutively active humoral immunity, mediated by the larval fat body. Furthermore, these evolved populations were also able to induce gene expression in response to infection to a greater level, which indicates an overall more activated humoral immune response to parasitization. The anti-parasitoid immune response also relies on the JAK/STAT signaling pathway being activated in muscles following infection, and this induced response was only seen in populations that had evolved under high parasite pressure. We found that the cytokine Upd3, which induces this JAK/STAT response, is being expressed by immature lamellocytes. Furthermore, these immune cells became constitutively present when populations evolved resistance, potentially explaining why they gained the ability to activate JAK/STAT signaling. Thus, under intense parasitism, populations evolved resistance by increasing both constitutive and induced immune defenses, and there is likely an interplay between these two forms of immunity.


Asunto(s)
Parásitos , Avispas , Animales , Drosophila/genética , Drosophila melanogaster , Interacciones Huésped-Parásitos/genética , Avispas/genética
12.
Int J Biol Macromol ; 256(Pt 2): 128358, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37995785

RESUMEN

Cr (VI) accumulates in an aqueous environment and exhibits huge harm to human health and the ecological system. Developed lignin biomass materials are complicated to prepare and have limited properties, and advances in lignin phenolic modification are lacking. Herein, an aminated poplar lignin-pyrogallol (PLP-PEI) with a simple design and adjustable phenolic hydroxyl content was developed using the acid hydrolysis-phase separation (AH-PS) method, and modified by the atom transfer radical polymerization (ATRP) strategy. Through diverse characterization analysis, the structural changes of PLP-PEI in the step-by-step synthesis process were monitored. An effective biomass capture system (Bio-Cap) was shown via systematically investigating the adsorption behaviors of Cr (VI) on PLP-PEI under various environmental conditions. Benefiting from introducing phenolic hydroxyl and amino groups, PLP-PEI demonstrated efficient adsorption capacity (598.80 mg/g for Cr (VI)). Additionally, the material also exhibited advantages, including monomeric chemisorption properties, strong reduction capability, and stable regeneration properties. Multiple driving forces were involved in the capture and removal process of Cr (VI), including complexation and electrostatic interaction. The low-cost natural biomass resources supported the industrial-scale synthesis and practical application of advanced aminated lignin polyphenol material, which showed outstanding advantages and enormous potential in the field of water environmental restoration.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Humanos , Lignina/química , Hidrólisis , Separación de Fases , Polimerizacion , Cromo/química , Agua , Adsorción , Radical Hidroxilo , Contaminantes Químicos del Agua/química , Cinética , Concentración de Iones de Hidrógeno
13.
Adv Mater ; 36(8): e2306292, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37723937

RESUMEN

Nanozymes, as one of the most efficient reactive oxygen species (ROS)-scavenging biomaterials, are receiving wide attention in promoting diabetic wound healing. Despite recent attempts at improving the catalytic efficiency of Pt-based nanozymes (e.g., PtCu, one of the best systems), they still display quite limited ROS scavenging capacity and ROS-dependent antibacterial effects on bacteria or immunocytes, which leads to uncontrolled and poor diabetic wound healing. Hence, a new class of multifunctional PtCuTe nanosheets with excellent catalytic, ROS-independent antibacterial, proangiogenic, anti-inflammatory, and immuno-modulatory properties for boosting the diabetic wound healing, is reported. The PtCuTe nanosheets show stronger ROS scavenging capacity and better antibacterial effects than PtCu. It is also revealed that the PtCuTe can enhance vascular tube formation, stimulate macrophage polarization toward the M2 phenotype and improve fibroblast mobility, outperforming conventional PtCu. Moreover, PtCuTe promotes crosstalk between different cell types to form a positive feedback loop. Consequently, PtCuTe stimulates a proregenerative environment with relevant cell populations to ensure normal tissue repair. Utilizing a diabetic mouse model, it is demonstrated that PtCuTe significantly facilitated the regeneration of highly vascularized skin, with the percentage of wound closure being over 90% on the 8th day, which is the best among the reported comparable multifunctional biomaterials.


Asunto(s)
Diabetes Mellitus , Cicatrización de Heridas , Animales , Ratones , Especies Reactivas de Oxígeno , Piel , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Materiales Biocompatibles/farmacología , Hidrogeles
14.
IEEE Trans Med Imaging ; 43(2): 807-819, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37788194

RESUMEN

Medical professionals rely on surgical video retrieval to discover relevant content within large numbers of videos for surgical education and knowledge transfer. However, the existing retrieval techniques often fail to obtain user-expected results since they ignore valuable semantics in surgical videos. The incorporation of rich semantics into video retrieval is challenging in terms of the hierarchical relationship modeling and coordination between coarse- and fine-grained semantics. To address these issues, this paper proposes a novel semantic-preserving surgical video retrieval (SPSVR) framework, which incorporates surgical phase and behavior semantics using a dual-level hashing module to capture their hierarchical relationship. This module preserves the semantics in binary hash codes by transforming the phase and behavior similarities into high- and low-level similarities in a shared Hamming space. The binary codes are optimized by performing a reconstruction task, a high-level similarity preservation task, and a low-level similarity preservation task, using a coordinated optimization strategy for efficient learning. A self-supervised learning scheme is adopted to capture behavior semantics from video clips so that the indexing of behaviors is unencumbered by fine-grained annotation and recognition. Experiments on four surgical video datasets for two different disciplines demonstrate the robust performance of the proposed framework. In addition, the results of the clinical validation experiments indicate the ability of the proposed method to retrieve the results expected by surgeons. The code can be found at https://github.com/trigger26/SPSVR.


Asunto(s)
Semántica , Cirujanos , Humanos
15.
Environ Pollut ; 343: 123204, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38142807

RESUMEN

Colloid-facilitated phosphorus (P) migration plays an important role in P loss from farmland to adjacent water bodies. However, the dynamics of colloidal P (Pcoll) release as influenced by irrigation in alkaline calcareous soil remains a knowledge gap. The present study, monitored the dynamic change of Pcoll under different water management strategies: 1) control, 2) flooding, and 3) alternating flooding and drying cycles. Soil water-dispersible colloids (0.6 nm-1 µm) were extracted by combining filtration and ultrafiltration methods. The contents of P, cation and organic carbon in the water-dispersible colloids were determined and the stability and mineral composition of colloidal fractions were characterized. The results showed that Pcoll ranged from 16.5 to 25.5 mg kg-1 and represented 42.8%-64.9% of the water-extracted P in the control. Flooding significantly decreased the Pcoll content by 16.0%-62.1% (mean 32.7%) and it may be attributed to the dissolution of colloidal iron (Fe) bound P. The alternating flooding and drying treatment significantly reduced the Pcoll content by 11.6%-88.0% (mean 67.6%). The Pcoll content of the flooding event was always greater than the Pcoll content of the drying event during flooding and drying cycles. Redundancy analysis and random forest modeling showed that the colloidal calcium (Ca) and ionic strength in soil solutions had negative correlations with the Pcoll content, and pH, ionic strength and truly dissolved P were the critical factors affecting Pcoll. Drying of the flooded soil led to the decrease of pH and the increase of ionic strength, colloidal Ca content and positive charges of colloid surfaces, which promoted colloid aggregation and enhanced soil P sorption capacity. This restricted the loss potential of Pcoll. In summary, controlled flooding and drainage when managed correctly have a role to play in mitigating Pcoll loss from P-enriched calcareous soils.


Asunto(s)
Fósforo , Suelo , Fósforo/análisis , Suelo/química , Agua/química , Inundaciones , Coloides/química
16.
Front Aging Neurosci ; 15: 1293164, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38131009

RESUMEN

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-ß peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear. Methods: Depressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS. Results: We found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ-mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice. Conclusion: These results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer's disease.

17.
J Immunol Res ; 2023: 6696967, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37928434

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies and tissue inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising candidate therapy for SLE owing to the immunomodulatory and regenerative properties. Circulating miRNAs are small, single-stranded noncoding RNAs in a variety of body fluids that regulate numerous immunologic and inflammatory pathways. Recent studies have revealed many differentially expressed circulating miRNAs in autoimmune diseases including SLE. However, the role of circulating miRNAs in SLE has not been extensively studied. Here, we performed small RNA sequencing analysis to compare the circulating miRNA profiles of SLE patients before and after MSC transplantation (MSCT), and identified a significant decrease of circulating miR-320b level during MSCT. Importantly, we found that the expression of circulating miR-320b and its target gene MAP3K1 was closely associated with SLE disease activity. The in vitro experiments showed that decreased MAP3K1 level in SLE peripheral blood mononuclear cells (PBMCs) was involved in CD4+ T-cell proliferation. In MRL/lpr mice, miR-320b overexpression aggravated symptoms of SLE, while miR-320b inhibition could promote disease remission. Besides, MSCs regulate miR-320b/MAP3K1 expression both in vitro and in vivo. Our results suggested that circulating miR-320b and MAP3K1 may be involved in CD4+ T-cell proliferation in SLE. This trial is registered with NCT01741857.


Asunto(s)
Lupus Eritematoso Sistémico , Quinasa 1 de Quinasa de Quinasa MAP , MicroARNs , Animales , Humanos , Ratones , Linfocitos T CD4-Positivos/metabolismo , Proliferación Celular , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/terapia , Quinasa 1 de Quinasa de Quinasa MAP/metabolismo , Ratones Endogámicos MRL lpr , MicroARNs/genética , MicroARNs/metabolismo
18.
Int J Mol Sci ; 24(22)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38003514

RESUMEN

The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, an RNA-based adaptive immune system found in bacteria and archaea, has catalyzed the development and application of a new generation of gene editing tools. Numerous studies have shown that this system can precisely target a wide range of human genes, including those associated with diseases such as cancer. In cancer research, the intricate genetic mutations in tumors have promoted extensive utilization of the CRISPR/Cas9 system due to its efficient and accurate gene editing capabilities. This includes improvements in Chimeric Antigen Receptor (CAR)-T-cell therapy, the establishment of tumor models, and gene and drug target screening. Such progress has propelled the investigation of cancer molecular mechanisms and the advancement of precision medicine. However, the therapeutic potential of genome editing remains underexplored, and lingering challenges could elevate the risk of additional genetic mutations. Here, we elucidate the fundamental principles of CRISPR/Cas9 gene editing and its practical applications in tumor research. We also briefly discuss the primary challenges faced by CRISPR technology and existing solutions, intending to enhance the efficacy of this gene editing therapy and shed light on the underlying mechanisms of tumors.


Asunto(s)
Edición Génica , Neoplasias , Humanos , Sistemas CRISPR-Cas/genética , Proteína 9 Asociada a CRISPR/genética , ARN , Neoplasias/genética , Neoplasias/terapia
19.
Light Sci Appl ; 12(1): 227, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37699904

RESUMEN

EDITORIAL: He is an explorer in micro-nano manufacturing, an adventurer in interdisciplinary studies, an impassioned educator; an ever-curious reader, a lover of sports, and a coffee connoisseur. In this episode of Light People Interview, we are honored to have Prof. Huigao Duan from Hunan University share his insights on micro-nano manufacturing, planar optics, teaching, nurturing, reading, growing up, and hobbies. "A man with a great smile", "a good teacher," and "an interesting soul" are just some of the descriptions that came through my mind during my conversation with him. Today, let's get to know this outstanding scholar who pursues "interesting and useful, extreme and ultimate" in micro-nano manufacturing and optics.

20.
Rheumatol Ther ; 10(6): 1535-1554, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37742321

RESUMEN

INTRODUCTION: The association between mycophenolate mofetil (MMF) and infection in patients with systemic lupus erythematosus (SLE) has not been clarified. This study evaluated the degree and factors in effect of MMF use on infection in patients with SLE. METHODS: A hospitalized-based observational study was conducted to collect medical records on patients with SLE during 2010-2021. A nested case-control study was performed among 3339 patients with SLE, including 1577 cases and 1762 controls by whether they developed any type of infection. The exposure of MMF use was determined within 1 year before diagnosed infection or the end of follow-up. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for association between MMF and subsequent infection. RESULTS: MMF was significantly associated with the risk of overall infection (adjusted OR 1.90, 95% CI 1.48-2.44) and different types of infections, including bacterial infection (adjusted OR 2.07, 95% CI 1.55-2.75), viral infection (adjusted OR 1.92, 95% CI 1.23-3.01), and opportunistic infection (adjusted OR 2.13, 95% CI 1.31-3.46). The top three risks of specific types of infections were bacteremia/septicemia, urinary tract infection/pyelonephritis, and herpes zoster. Stratification analysis showed risk of overall infection increased especially in MMF users with age over 55 years, diabetes, central nervous system involvement, and thrombocytopenia. Moreover, the risk of infection increased with increasing dosage and duration of MMF use. Additionally, the combination of MMF with CYC and other immunosuppressants significantly increases the risk of infections compared to using a single one. CONCLUSIONS: MMF use is associated with various type of infections in patients with SLE, particularly in those with longer use, older age, complications with comorbidities, and concomitant use of CYC or other immunosuppressants.

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