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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.
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Parásitos , Avispas , Animales , Drosophila/genética , Drosophila melanogaster , Interacciones Huésped-Parásitos/genética , Avispas/genéticaRESUMEN
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.
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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.
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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.
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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/metabolismoRESUMEN
OBJECTIVE: Pregnancy complicated with type B aortic dissection is a rare but devastating condition. Guidelines for managing this condition are lacking. We present our observation and experiences in managing five pregnant women with complicated type B aortic dissection in the second or third trimesters, aiming to gain insights that can aid in proposing an appropriate management strategy. DESIGN: A retrospective study. SETTING: Zhongnan Hospital of Wuhan University. POPULATION: Pregnant women with complicated type B aortic dissection. METHODS: Clinical data of five pregnant women with complicated type B aortic dissection admitted to Zhongnan Hospital of Wuhan University from January 2022 to June 2023 were collected. The clinical characteristics, treatment strategies, and corresponding maternal and infant outcomes were retrospectively analysed. MAIN OUTCOME MEASURES: Survival of mothers and foetuses. RESULTS: All five study participants were diagnosed with complicated type B aortic dissection by computed tomography angiography (CTA). The range of gestational weeks at admission was 27 weeks + 3 days to 36 weeks + 6 days. The first patient, planning a caesarean section (C-section) followed by thoracic endovascular aortic repair (TEVAR), died of aortic dissection rupture during C-section. Her neonate was successfully rescued. In contrast, the remaining four patients who underwent TEVAR first survived. Among them, three patients underwent single-stage aortic repair and delivery, while one patient received C-section 31 days after TEVAR. Three preterm live births were recorded among these surviving mothers. Neonatal death occurred in one case with a gestational age of 29 weeks + 5 days, who had foetal distress before surgery. During the follow-up period of up to 3 months, no maternal or infant death occurred. No device-related or systemic complications were observed in the surviving mothers after discharge. Routine physical examinations of the four live births showed no abnormalities. CONCLUSIONS: For pregnant women with thoracic back pain and high suspicion of aortic dissection, CTA should be conducted promptly to prevent missed or delayed diagnosis. Maternal survival should be prioritised over foetal outcome once diagnosed. TEVAR was demonstrated to be safe and feasible for such patients. For women with complicated type B aortic dissection in late pregnancy, TEVAR followed by C-section may be a promising treatment strategy.
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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.
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Ciclo del Carbono , Sedimentos Geológicos , Lagos , Sedimentos Geológicos/química , Sedimentos Geológicos/análisis , Lagos/química , Carbono/análisis , Fósforo/análisis , China , Monitoreo del AmbienteRESUMEN
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.
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A bio-based flame retardant nickel phytate (PA-Ni) was synthesized and combined with soybean oil-based polyol (SO) to create a green rigid polyurethane foam (RPUF) with enhanced compressive strength, good thermal stability and flame retardant. The results showed that the RPUF-SO2/Ni3 with 3 wt% PA-Ni had the highest initial and termination temperature, maximum thermal decomposition rate temperature and carbon residue, and better thermal stability. Its limiting oxygen index was increased by 2.6% compared with RPUF-SO2 without PA-Ni added, and the peak heat release rate (PHRR) and total heat release rate (THR) were reduced by 14.92% and 19.92%, respectively. In addition, RPUF-SO2/Ni3 had the lowest Ds under the conditions of flame (18.90) and flameless (22.41), and had the best smoke suppression effect. And the compressive strength of RPUF-SO/Ni3 was significantly enhanced by the addition of PA-Ni. The results show that the improvement of flame retardancy of RPUF is mainly the result of the combined effect of gas-phase and condensed-phase flame retardancy, among which the flame retardancy of RPUF-SO/Ni3 was the best. The current findings offer a practical way to produce green and low-carbon RPUF as well as promising prospects for the material's safe application.
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In this paper, an event-triggered adaptive neural prescribed performance admittance control (ETANPPAC) scheme is proposed to control the constrained robotic systems without velocity sensors. To ensure compliance during human-robot interaction, the reference trajectory is obtained by reshaping the desired trajectory for the robotic systems based on the admittance relationship, where a saturation function is used to constrain the reference trajectory, avoiding excessive contact forces that could render the trajectory inexecutable. Moreover, a barrier Lyapunov function is used to constrain the tracking errors for prescribed performance, where a velocity observer and a radial basis function neural network are designed to estimate the velocity and the uncertainty of the robotic systems, respectively, to enhance control performance. To reduce the communication burden, an event-triggered mechanism is introduced and the Zeno behavior is avoided with the event-triggered condition. The stability of the whole control scheme is analyzed by the Lyapunov function. Simulation and experimental tests demonstrate that the proposed ETANPPAC scheme can track the desired trajectory well under constraints and reduce the communication burden, thereby achieving better efficiency for controlling the robotic systems compared with similar control schemes.
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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.
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Fósforo , Suelo , Fósforo/análisis , Suelo/química , Agua/química , Inundaciones , Coloides/químicaRESUMEN
Ammonium polyphosphate (APP) and self-made nickel phytate (PANi) were used as modified materials to prepare green biomass rigid polyurethane foam (RPUF). The flame retardancy, thermal stability, smoke toxicity and mechanical properties of the modified RPUF were investigated by limiting oxygen index (LOI), a cone calorimetry (CONE) test, thermogravimetric analysis and a compression test. The results showed that the RPUF with 10 wt% APP (PANi/APP10) had the highest LOI of 26.5%. Its peak heat release rate (PHRR) and total heat release (THR) were reduced by 29.64% and 24.05% compared with PANi/APP0 without APP. And its smoke production rate (SPR) and total smoke release (TSR) decreased by 33.14% and 19.88%, respectively. Compared with pure RPUF, the compressive strength of PANi/APP10 was increased by 50%, mainly because APP itself was an ultra-fine powder, which was better compatible with the matrix and improved the hardness of the material. The results showed that the synergistic effect of the gas phase and the condensed phase mechanism could effectively improve the flame-retardant effect. The current research results provided a new strategy for the preparation of green and low-toxicity RPUF.
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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.
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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.
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The construction of ultrathin porous membranes with stable structures is critical for achieving efficient gas separation. Inspired by the binary-cooperative structural features of bones and teeth-composed of rigid hydroxyapatite and flexible collagen, which confer excellent mechanical strength-a binary-cooperative porous membrane constructed with gel-state zeolitic imidazolate frameworks (g-ZIFs), synthesized using a metal-gel-induced strategy, is proposed. The enlarged cavity size and flexible frameworks of the g-ZIF nanoparticles significantly improve gas adsorption and diffusion, respectively. After thermal treatment, the coordination structures forming rigid segments in the g-ZIF membranes appear at the stacked g-ZIF boundaries, exhibiting a higher Young's modulus than the g-ZIF nanoparticles, denoted as the flexible segments. The g-ZIF membranes demonstrate excellent tensile and compression resistances, attributed to the effective translation of binary-cooperative effects of rigidity and flexibility into the membranes. The resulting dual-aperture structure, composed of g-ZIF nanoparticles surrounded by nanoscale apertures at the boundaries, yields a membrane with a stable CO2 permeance of 4834 GPU and CO2/CH4 selectivity of 90 within 3.0 MPa.
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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.
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Células Madre Hematopoyéticas , Lupus Eritematoso Sistémico , Trasplante de Células Madre Mesenquimatosas , Ratones Endogámicos MRL lpr , Animales , Lupus Eritematoso Sistémico/terapia , Ratones , Células Madre Hematopoyéticas/metabolismo , Femenino , Células Madre Mesenquimatosas , Modelos Animales de Enfermedad , Diferenciación Celular , Células Mieloides/inmunología , Células Cultivadas , HumanosRESUMEN
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.
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OBJECTIVE: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. METHODS: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. CONCLUSION: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.
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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.
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Canales Iónicos , Macrófagos , Mecanotransducción Celular , Transducción de Señal , Proteínas Señalizadoras YAP , Macrófagos/metabolismo , Animales , Ratones , Canales Iónicos/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Ratones Endogámicos C57BL , Polaridad Celular/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Cultivadas , Matriz Extracelular/metabolismo , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Proteínas de Ciclo Celular/metabolismo , Oseointegración/efectos de los fármacosRESUMEN
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.
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Disposable medical protective clothing for 2019-nCoV mainly consists of stacked layers with nanopore films, polymer coated nonwoven fabrics and melt-blown nonwoven fabrics against anti-microbial and anti-liquid penetration. However, such structures lack moisture permeability and breathability leading to an uncomfortable, stuffy wearing experience. Here, we propose a novel medical protective clothing material with a superabsorbent layer to enhance moisture absorption. Poly(acrylic acid-co-acrylamide)/polyvinyl alcohol superabsorbent fibers (PAAAM/PVA fibers) were prepared via wet spinning. And the superabsorbent composite layer was stacked from PAAAM/PVA fibers, bamboo pulp fibers (BPF) and ethylene-propylene side by side fibers (ESF). The novel disposable medical protective composite fabric was obtained through gluing the superabsorbent layer to the inner surface of strong antistatic polypropylene nonwoven fabric. The resultant composite fabric possesses excellent absorption and retention capacity for sweat, up to 12.3 g/g and 63.8%, and a maximum hygroscopic rate of 1.04 g/h, higher than that of the conventional material (only 0.53 g/h). The moisture permeability of the novel material reached 12,638.5 g/(m2 d), which was 307.6% of the conventional material. The novel material can effectively reduce the humidity inside the protective clothing and significantly improve the comfort of medical staff.