Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.456
Filtrar
1.
Nanomaterials (Basel) ; 14(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38334547

RESUMO

Defect engineering constitutes a widely-employed method of adjusting the electronic structure and properties of oxide materials. However, controlling defects at room temperature remains a significant challenge due to the considerable thermal stability of oxide materials. In this work, a facile room-temperature lithium reduction strategy is utilized to implant oxide defects into perovskite BaTiO3 (BTO) nanoparticles to enhance piezocatalytic properties. As a potential application, the piezocatalytic performance of defective BTO is examined. The reaction rate constant increases up to 0.1721 min-1, representing an approximate fourfold enhancement over pristine BTO. The effect of oxygen vacancies on piezocatalytic performance is discussed in detail. This work gives us a deeper understanding of vibration catalysis and provides a promising strategy for designing efficient multi-field catalytic systems in the future.

2.
Genomics ; 116(2): 110806, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38325533

RESUMO

BACKGROUND: Cell differentiation agent II (CDA-II) exhibits potent anti-proliferative and apoptosis-inducing properties against a variety of cancer cells. However, its mechanism of action in chronic myeloid leukemia (CML) remains unclear. METHODS: Cell counting Kit 8 (CCK-8) and flow cytometry were used to investigate the effects of CDA-II on the biological characteristics of K562 cells. Gene (mRNA and lncRNA) expression profiles were analyzed by bioinformatics to screen differentially expressed genes and to perform enrichment analysis. The Pearson correlation coefficients of lncRNAs and mRNAs were calculated using gene expression values, and a lncRNA/mRNA co-expression network was constructed. The MCODE and cytoHubba plugins were used to analyze the co-expression network. RESULTS: The Results, derived from CCK-8 and flow cytometry, indicated that CDA-II exerts dual effects on K562 cells: it inhibits their proliferation and induces apoptosis. From bioinformatics analysis, we identified 316 mRNAs and 32 lncRNAs. These mRNAs were predominantly related to the meiotic cell cycle, DNA methylation, transporter complex and peptidase regulator activity, complement and coagulation cascades, protein digestion and absorption, and cell adhesion molecule signaling pathways. The co-expression network comprised of 163 lncRNA/mRNA interaction pairs. Notably, our analysis results implicated clustered histone gene families and five lncRNAs in the biological effects of CDA-II on K562 cells. CONCLUSION: This study highlights the hub gene and lncRNA/mRNA co-expression network as crucial elements in the context of CDA-II treatment of CML. This insight not only enriches our understanding of CDA-II's mechanism of action but also might provide valuable clues for subsequent experimental studies of CDA-II, and potentially contribute to the discovery of new therapeutic targets for CML.

3.
J Dent Sci ; 19(1): 70-78, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303830

RESUMO

Background/purpose: The serpin peptidase inhibitor, clade E, member 2 (SERPINE2), is upregulated in breast cancer, prostate cancer, and urothelial carcinoma; however, limited information exists regarding its expression in oral cancer. Therefore, this study aimed to analyze the association between SERPINE2 expression and oral squamous cell carcinoma (OSCC) outcomes. Materials and methods: SERPINE2 mRNA and protein expression in patients with head and neck squamous cell carcinoma and OSCC were investigated using online databases and tissue-array analysis. Its relationship with clinicopathological characteristics, OSCC prognosis and its biological function in OSCC cells were explored. Results: Analysis using online databases revealed higher SERPINE2 expression in tumor tissues and its role as a prognostic factor. High SERPINE2 protein levels were significantly correlated with adverse pathological parameters, including advanced clinical stage and tumor status (P < 0.001), lymph nodes (P = 0.014), and distant metastases (P = 0.013). High SERPINE2 expression was associated with worse overall survival (P < 0.001) and was identified as an independent prognostic factor for OSCC. In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines. Conclusion: This study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer.

5.
J Virol ; : e0112923, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305155

RESUMO

The global circulation of clade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) in poultry and wild birds, increasing mammal infections, continues to pose a public health threat and may even form a pandemic. An efficacious vaccine against H5Ny HPAIVs is crucial for emergency use and pandemic preparedness. In this study, we developed a parainfluenza virus 5 (PIV5)-based vaccine candidate expressing hemagglutinin (HA) protein of clade 2.3.4.4b H5 HPAIV, termed rPIV5-H5, and evaluated its safety and efficacy in mice and ferrets. Our results demonstrated that intranasal immunization with a single dose of rPIV5-H5 could stimulate H5-specific antibody responses, moreover, a prime-boost regimen using rPIV5-H5 stimulated robust humoral, cellular, and mucosal immune responses in mice. Challenge study showed that rPIV5-H5 prime-boost regimen provided sterile immunity against lethal clade 2.3.4.4b H5N1 virus infection in mice and ferrets. Notably, rPIV5-H5 prime-boost regimen provided protection in mice against challenge with lethal doses of heterologous clades 2.2, 2.3.2, and 2.3.4 H5N1, and clade 2.3.4.4h H5N6 viruses. These results revealed that rPIV5-H5 can elicit protective immunity against a diverse clade of highly pathogenic H5Ny virus infection in mammals, highlighting the potential of rPIV5-H5 as a pan-H5 influenza vaccine candidate for emergency use.IMPORTANCEClade 2.3.4.4b H5Ny highly pathogenic avian influenza viruses (HPAIVs) have been widely circulating in wild birds and domestic poultry all over the world, leading to infections in mammals, including humans. Here, we developed a recombinant PIV5-vectored vaccine candidate expressing the HA protein of clade 2.3.4.4b H5 virus. Intranasal immunization with rPIV5-H5 in mice induced airway mucosal IgA responses, high levels of antibodies, and robust T-cell responses. Importantly, rPIV5-H5 conferred complete protection in mice and ferrets against clade 2.3.4.4b H5N1 virus challenge, the protective immunity was extended against heterologous H5Ny viruses. Taken together, our data demonstrate that rPIV5-H5 is a promising vaccine candidate against diverse H5Ny influenza viruses in mammals.

6.
Opt Express ; 32(2): 2554-2560, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297781

RESUMO

We investigate the robustness of a modified multi-trench fiber (MTF) design with two gaps numerically. The excellent suppression of high-order modes is demonstrated over a wide range of the gap misalignment and the fundamental mode loss is barely affected even with the 5 dB/m scattering loss in gaps at the modified two-gap MTF for the first time. Therefore, the required fabrication accuracy decreases.

7.
Biosci Trends ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38325823

RESUMO

Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti-PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC.

8.
PLoS One ; 19(2): e0298607, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394114

RESUMO

Real time parameter measurement cannot be carried out to dynamic ring parts during automation ring rolling processes so that rolling process parameters cannot be adjusted in time. Considering effects of shaping of ring rolling parts, a visual measurement platform was set up and a machine vision-based non-contact real -time measurement method was put forward. This article improves the subpixel level edge extraction algorithm to extract edge data information of circular rolling pieces. Based on the characteristics of circular rolling pieces, an RG-Hough transform method is proposed to fit the detected edge data information. The conversion relationship between pixel and actual sizes were determined in combination with the camera calibration to gain parameters of ring rolling parts. Measurements of ring parts (OD: 462.12mm; and ID: 315.53mm) were applied to verify the effectiveness of our method. Our measurement error is ±0.25mm and our average speed can be up to 104ms/frame. Our study can provide powerful technical supports for intelligent control of ring rolling pieces.

9.
Sci Total Environ ; 921: 171078, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38382615

RESUMO

Decreased snow depth resulting from global warming has the potential to significantly impact biogeochemical cycles in cold forests. However, the specific mechanisms of how snow reduction affects litter decomposition and the underlying microbial processes remain unclear, this knowledge gap limits our ability to precisely predict ecological processes within cold forest ecosystems under climate change. Hence, a field experiment was conducted in a subalpine forest in southwestern China, involving a gradient of snow reduction levels (control, 50 %, 100 %) to investigate the effects of decreased snow on litter decomposition, as well as microbial biomass and activity, specifically focused on two common species: red birch (Betula albosinensis) and masters larch (Larix mastersiana). After one year of incubation, the decomposition rate (k-value) of the two types of litter ranged from 0.12 to 0.24 across three snow treatments. A significant lower litter mass loss, microbial biomass and enzyme activity were observed under decreased snow depth in winter. Furthermore, a hysteresis inhibitory effect of snow reduction on hydrolase activity was observed in the following growing season. Additionally, the high initial quality (lower C/N ratio) of red birch litter facilitated the colonization by a greater quantity of microorganisms, making it more susceptible to snow reduction compared to the low-quality masters larch litter. Structural equation models indicated that decreased snow depth hindered litter decomposition by altering the biological characterization of litter (e.g., microbial biomass and enzyme activity) and environmental variables (e.g., mean temperature and moisture content). The findings suggest that the potential decline in snow depth could inhibit litter decomposition by reducing microbial biomass and activity, implying that the future climate change may alter the material cycling processes in subalpine forest ecosystems.

10.
Cureus ; 16(1): e52745, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38384599

RESUMO

Acute lung injury following fentanyl overdose is an unusual presentation. Pulmonary edema has been associated with opioid and naloxone use. However, to our knowledge, there have been no previous reports of inhaled fentanyl-associated acute lung injury presenting with acute hypoxic respiratory failure secondary to severe acute respiratory distress syndrome. We report a case of inhaled fentanyl-related severe acute respiratory distress syndrome which presented immediately after snorting fentanyl. This patient developed hypoxia requiring 100% oxygen on non-rebreather mask, and acute respiratory distress syndrome was confirmed on chest X-ray and computed tomography on admission. He was successfully treated with steroids with recovery in 48 hours. Naloxone was used in this patient, which has been associated with pulmonary edema in case reports and series, but clinical findings were more consistent with acute respiratory distress syndrome rather than pulmonary edema. The mechanism for this clinical presentation is not well known. Proposed mechanisms include lung injury from inhalation against an obstruction in a manner similar to post-obstructive pulmonary edema. Although our patient rapidly responded to symptomatic treatment and steroid course, our case also highlights the need for further study to elucidate the various clinical presentations associated with fentanyl use-related lung toxicity including acute respiratory distress syndrome.

11.
Sleep Med ; 115: 155-161, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38367357

RESUMO

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

12.
Sleep Med ; 115: 193-201, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38367362

RESUMO

OBJECTIVE: To investigate the effects of mid-pregnancy sleep deprivation (SD) in C57BL/6 J mice on the motor coordination of the offspring and to explore the potential mechanism of microglia activation in the cerebellar vermis of the offspring involved in the induction of impaired motor coordination development. METHODS: C57BL/6 J pregnant mice were randomly divided into the SD and control groups. SD was implemented by the multi-platform method from first day of the middle pregnancy (gestation day 8, GD8). At postnatal day 21 (PND21), we measured the development of motor behavior and collected cerebellar vermis tissues to observe the activation of microglia by H&E staining, the expression of microglia-specific markers ionized calcium-binding adaptor molecule-1 (Iba-1) and cluster of differentiation 68 (CD68) by immunohistochemical, and interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor -α (TNF-α) by real-time quantitative PCR (RT-qPCR). RESULTS: In the offspring of SD group, comparing to the control group, the total time of passage and the reverse crawl distance in the balance beam test, and the frequency of falls from the suspension cord was increased; with lower max rotational speed and shorter duration in the rotarod experiment. Further, we found that the microglia of cerebellar vermis tissues emerged an amoeba-like activation. The mean gray value of Iba-1 was lower, the density of positive cells of CD68 and the expression levels of IL-6 and TNF-α were increased. CONCLUSIONS: The motor coordination of offspring is impaired, accompanying a SD from mid-pregnancy, and the cerebellar vermis showed microglia activation and pro-inflammatory response. It suggested the adverse effects of SD from mid-gestation on the development of motor coordination through the inflammatory response in the cerebellar vermis of the offspring.

13.
Brief Funct Genomics ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38376798

RESUMO

Gut microbes is a crucial factor in the pathogenesis of type 1 diabetes (T1D). However, it is still unclear which gut microbiota are the key factors affecting T1D and their influence on the development and progression of the disease. To fill these knowledge gaps, we constructed a model to find biomarker from gut microbiota in patients with T1D. We first identified microbial markers using Linear discriminant analysis Effect Size (LEfSe) and random forest (RF) methods. Furthermore, by constructing co-occurrence networks for gut microbes in T1D, we aimed to reveal all gut microbial interactions as well as major beneficial and pathogenic bacteria in healthy populations and type 1 diabetic patients. Finally, PICRUST2 was used to predict Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways and KO gene levels of microbial markers to investigate the biological role. Our study revealed that 21 identified microbial genera are important biomarker for T1D. Their AUC values are 0.962 and 0.745 on discovery set and validation set. Functional analysis showed that 10 microbial genera were significantly positively associated with D-arginine and D-ornithine metabolism, spliceosome in transcription, steroid hormone biosynthesis and glycosaminoglycan degradation. These genera were significantly negatively correlated with steroid biosynthesis, cyanoamino acid metabolism and drug metabolism. The other 11 genera displayed an inverse correlation. In summary, our research identified a comprehensive set of T1D gut biomarkers with universal applicability and have revealed the biological consequences of alterations in gut microbiota and their interplay. These findings offer significant prospects for individualized management and treatment of T1D.

14.
Anal Chim Acta ; 1296: 342346, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401935

RESUMO

"MS/MS spectrum to structure" analysis is the most challenging task for MS/MS-relied qualitative characterization. The conventional database- and computation-assisted strategies cannot reach confirmative identification, notably for isomers. Hence, an advanced strategy was proposed here through tackling the two determinant obstacles such as the transformation from elemental compositions to fragment ion structures and the linkage style amongst substructures. As typical conjugated structures, esters were measured for strategy illustration, and metabolite identification of a famous natural antioxidant namely rosmarinic acid (RosA) in rat was undertaken for applicability justification. Through programming online energy-resolved (ER)-MS for the first collision cell of Qtrap-MS device, full collision energy ramp (FCER)-MS2 spectrum was configured for [M-H]- ion of each ester to provide optimal collision energies (OCEs) for all concerned diagnostic fragment ions (DFIs), i.e. a-, b-, c-, y-, and z-type ions. The linear correlations between masses and OCEs were built for each ion type to facilitate DFIs recognition from chaotic MS2 spectrum. To identify 1st-generation fragment ions, full exciting energy ramp (FEER)-MS3 spectra were configured for key DFIs via programming the second ER-MS in the latter collision chamber. FEER-MS3 spectrum of 1st-generation fragment ion for ester was demonstrated to be identical with FEER-MS2 spectrum of certain hydrolysis product when sharing the same structure. After applying the advanced strategy to recognize DFIs and identify 1st-generation fragment ions, a total of forty metabolites (M1-M40), resulted from hydrolysis, methylation, sulfation, and glucuronidation, were unambiguously identified for RosA after oral administration. Together, the advanced bottom-up strategy hyphenating FCER-MS2 and FEER-MS3 spectra, is meaningful to strengthen "MS/MS spectrum to structure" analysis through recognizing and identifying fragment ions.

15.
Adv Mater ; : e2311272, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377229

RESUMO

The rational construction of highly active and durable oxygen-reactive electrocatalysts for oxygen reduction/evolution reaction (ORR/OER) plays a critical role in rechargeable metal-air batteries. It is pivotal to achieve optimal utilization of electrocatalytically active sites and valid control of the high specific internal surface area. Inspiration for designing electrocatalysts can come from nature, as it is full of precisely manipulated and highly efficient structures. Herein, inspired by earthworms fertilizing soil, a three-dimensional (3D) carbon nanofibrous electrocatalyst with multiple interconnected nanoconfined channels, cobalt-based heterojunction active particles and enriched N, S heteroatoms (Co/Co3 O4 /CoF2 @NSC with confined channels) is rationally designed, showing superior bifunctional electrocatalytic activity in alkaline electrolyte, even outperforming that of benchmark Pt/C-RuO2 catalyst. This work demonstrates a new method for porous structural regulation, in which the internal confined channels within the nanofibers are controllably formed by the spontaneous migration of cobalt-based nanoparticles under a CO2 atmosphere. Theoretical analysis reveals that constructing Co/Co3 O4 /CoF2 @NSC electrocatalyst with confined channels can greatly adjust the electron distribution, effectively lower the reaction barrier of inter-mediate and reduce the OER/ORR overpotential. This work introduces a novel and nature-inspired strategy for designing efficient bifunctional electrocatalysts with well-designed architectures. This article is protected by copyright. All rights reserved.

16.
Small ; : e2311056, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377262

RESUMO

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER -Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER -Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

17.
J Comput Biol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38377572

RESUMO

More and more studies have shown that microRNAs (miRNAs) play an indispensable role in the study of complex diseases in humans. Traditional biological experiments to detect miRNA-disease associations are expensive and time-consuming. Therefore, it is necessary to propose efficient and meaningful computational models to predict miRNA-disease associations. In this study, we aim to propose a miRNA-disease association prediction model based on sparse learning and multilayer random walks (SLMRWMDA). The miRNA-disease association matrix is decomposed and reconstructed by the sparse learning method to obtain richer association information, and at the same time, the initial probability matrix for the random walk with restart algorithm is obtained. The disease similarity network, miRNA similarity network, and miRNA-disease association network are used to construct heterogeneous networks, and the stable probability is obtained based on the topological structure features of diseases and miRNAs through a multilayer random walk algorithm to predict miRNA-disease potential association. The experimental results show that the prediction accuracy of this model is significantly improved compared with the previous related models. We evaluated the model using global leave-one-out cross-validation (global LOOCV) and fivefold cross-validation (5-fold CV). The area under the curve (AUC) value for the LOOCV is 0.9368. The mean AUC value for 5-fold CV is 0.9335 and the variance is 0.0004. In the case study, the results show that SLMRWMDA is effective in inferring the potential association of miRNA-disease.

18.
Mol Oncol ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381121

RESUMO

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT-driven LIF/LIFR signaling induces brain-derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration-resistant PCa (CRPC) and a positive correlation with programmed death-ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.

19.
Nat Commun ; 15(1): 1249, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341419

RESUMO

Lateral hypothalamic (LH) hypocretin/orexin neurons (HONs) control brain-wide electrical excitation. Abnormally high excitation produces epileptic seizures, which affect millions of people and need better treatments. HON population activity spikes from minute to minute, but the role of this in seizures is unknown. Here, we describe correlative and causal links between HON activity spikes and seizures. Applying temporally-targeted HON recordings and optogenetic silencing to a male mouse model of acute epilepsy, we found that pre-seizure HON activity predicts and controls the electrophysiology and behavioral pathology of subsequent seizures. No such links were detected for HON activity during seizures. Having thus defined the time window where HONs influence seizures, we targeted it with LH deep brain stimulation (DBS), which inhibited HON population activity, and produced seizure protection. Collectively, these results uncover a feature of brain activity linked to seizures, and demonstrate a proof-of-concept treatment that controls this feature and alleviates epilepsy.


Assuntos
Epilepsia , Convulsões , Camundongos , Animais , Masculino , Humanos , Orexinas/genética , Convulsões/prevenção & controle , Epilepsia/genética , Epilepsia/terapia , Neurônios/fisiologia , Hipotálamo
20.
Sci Total Environ ; 919: 170900, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38354804

RESUMO

The sensitivity of grassland above- (AGB, gC m-2) and below-ground biomass (BGB, gC m-2) to climate has been shown to be significant on the Tibetan Plateau, however, the spatial patterns and sensitivity of biomass with altitudinal change needs to be quantitated. In this study, large data sets of AGB and BGB during the peak growth season, and the corresponding geographical and climate conditions in the grasslands of the Tibetan Plateau between 2001 and 2020 were analyzed, and modelled using a Cubist regression trees algorithm. The mean values for AGB and BGB were 61.3 and 1304.3 gC m-2, respectively, for the whole region over the two decades. There was a significant change in spatial AGB of 64.8 % on the Plateau (P < 0.05, with areas where AGB increased being twice as large as areas where AGB decreased), while BGB did not change significantly in majority the of the region (≥ 90.1 %, P > 0.05). In general, the areas where AGB showed positive partial correlations with precipitation were larger than the areas where AGB had positive correlations with temperature (P < 0.05). However, these trends varied depending on the climatic conditions: in the wetter regions, temperature had a greater effect on the size of the areas with positive AGB responses than precipitation (P < 0.05), while precipitation had a greater effect on the size of areas with positive BGB changes than temperature (P < 0.05). In the drier areas, however, precipitation affected the AGB response significantly compared to temperature (P < 0.05), while temperature influenced the BGB response greater than precipitation (P < 0.05). The response and sensitivity of grassland biomass to temperature and precipitation varied according to the altitude of the Plateau: the response and sensitivity were stronger and more sensitive at medium altitudes, and weak at the higher or lower altitudes. Likely, this phenomenon was resulted from the natural selection of plants to maintain the efficient use of resources during un-favourable and stressed conditions for maximum plant development and growth. These findings will help assess the ecological consequences of global climate change for the grasslands of the Tibetan Plateau, particularly in those regions with highly variable altitudes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...