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1.
J Neurovirol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570476

RESUMO

Apart from the typical respiratory symptoms, coronavirus disease 2019 (COVID-19) also affects the central nervous system, leading to central disorders such as encephalopathy and encephalitis. However, knowledge of pediatric COVID-19-associated encephalopathy is limited, particularly regarding specific subtypes of encephalopathy. This study aimed to assess the features of COVID-19-associated encephalopathy/encephalitis in children. We retrospectively analyzed a single cohort of 13 hospitalized children with COVID-19-associated encephalopathy. The primary outcome was the descriptive analysis of the clinical characteristics, magnetic resonance imaging and electroencephalography findings, treatment progression, and outcomes. Thirteen children among a total of 275 (5%) children with confirmed COVID-19 developed associated encephalopathy/encephalitis (median age, 35 months; range, 3-138 months). Autoimmune encephalitis was present in six patients, acute necrotizing encephalopathy in three, epilepsy in three, and central nervous system small-vessel vasculitis in one patient. Eight (62%) children presented with seizures. Six (46%) children exhibited elevated blood inflammatory indicators, cerebrospinal fluid inflammatory indicators, or both. Two (15%) critically ill children presented with multi-organ damage. The magnetic resonance imaging findings varied according to the type of encephalopathy/encephalitis. Electroencephalography revealed a slow background rhythm in all 13 children, often accompanied by epileptic discharges. Three (23%) children with acute necrotizing encephalopathy had poor prognoses despite immunotherapy and other treatments. Ten (77%) children demonstrated good functional recovery without relapse. This study highlights COVID-19 as a new trigger of encephalopathy/encephalitis in children. Autoimmune encephalitis is common, while acute necrotizing encephalopathy can induce poor outcomes. These findings provide valuable insights into the impact of COVID-19 on children's brains.

2.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615243

RESUMO

OBJECTIVE: To investigate the alterations in cortical-cerebellar circuits and assess their diagnostic potential in preschool children with autism spectrum disorder using multimodal magnetic resonance imaging. METHODS: We utilized diffusion basis spectrum imaging approaches, namely DBSI_20 and DBSI_combine, alongside 3D structural imaging to examine 31 autism spectrum disorder diagnosed patients and 30 healthy controls. The participants' brains were segmented into 120 anatomical regions for this analysis, and a multimodal strategy was adopted to assess the brain networks using a multi-kernel support vector machine for classification. RESULTS: The results revealed consensus connections in the cortical-cerebellar and subcortical-cerebellar circuits, notably in the thalamus and basal ganglia. These connections were predominantly positive in the frontoparietal and subcortical pathways, whereas negative consensus connections were mainly observed in frontotemporal and subcortical pathways. Among the models tested, DBSI_20 showed the highest accuracy rate of 86.88%. In addition, further analysis indicated that combining the 3 models resulted in the most effective performance. CONCLUSION: The connectivity network analysis of the multimodal brain data identified significant abnormalities in the cortical-cerebellar circuits in autism spectrum disorder patients. The DBSI_20 model not only provided the highest accuracy but also demonstrated efficiency, suggesting its potential for clinical application in autism spectrum disorder diagnosis.


Assuntos
Transtorno do Espectro Autista , Humanos , Pré-Escolar , Transtorno do Espectro Autista/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Cerebelo/diagnóstico por imagem , Encéfalo
3.
Org Biomol Chem ; 22(16): 3204-3208, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563260

RESUMO

An efficient palladium-catalyzed [2 + 2 + 1] annulation of 3-iodochromones, bridged olefins, and iodomethane is described, affording a range of chromone-containing polycyclic compounds. Additionally, the corresponding deuterated products were smoothly obtained with iodomethane-d3 instead of iodomethane. Moreover, the synthetic utility of this method is further substantiated by gram scale preparation and application to late-stage modification of estrone.

4.
BMC Cancer ; 24(1): 465, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622522

RESUMO

BACKGROUND: Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. METHODS: A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. RESULTS: Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629-0.950 in the TCGA dataset and 0.736-0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. CONCLUSIONS: Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína do Fator Nuclear 45/genética
5.
Front Microbiol ; 15: 1394104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650888

RESUMO

Background: Tillage practices can substantially affect soil properties depending on crop stage. The interaction between tillage and crop growth on arbuscular mycorrhizal fungi (AMF) communities remains unclear. We investigated the interactions between four tillage treatments (CT: conventional tillage, RT: reduced tillage, NT: no tillage with mulch, and SS: subsoiling with mulch), maintained for 25 years, and two wheat growth stages (elongation stage and grain filling stage) on AMF diversity and community composition. Results: The AMF community composition strongly changed during wheat growth, mainly because of changes in the relative abundance of dominant genera Claroideoglomus, Funneliformi, Rhizophagu, Entrophospora, and Glomus. Co-occurrence network analysis revealed that the grain filling stage had a more complex network than the elongation stage. Redundancy analysis results showed that keystone genera respond mainly to changes in soil organic carbon during elongation stage, whereas the total nitrogen content affected the keystone genera during grain filling. Compared with CT, the treatments with mulch, i.e., NT and SS, significantly changed the AMF community composition. The change of AMF communities under different tillage practices depended on wheat biomass and soil nutrients. NT significantly increased the relative abundances of Glomus and Septoglomus, while RT significantly increased the relative abundance of Claroideoglomus. Conclusion: Our findings indicate that the relative abundance of dominant genera changed during wheat growth stages. Proper tillage practices (e.g., NT and SS) benefit the long-term sustainable development of the Loess Plateau cropping systems.

6.
Sci Total Environ ; 928: 172325, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604371

RESUMO

Cities, where human energy activities and greenhouse gas emissions are concentrated, contribute significantly to alleviating the impacts of global climate change. Utilizing the China Carbon Emissions Accounting Database (CEADs) to provide carbon dioxide emission inventories for urban areas in China at the prefecture level, this study closely examines the historical evolution trajectories of carbon emissions across 247 urban units from 2005 to 2019. The logarithmic cubic function model was employed to simulate these trajectories, evaluating urban emission peaks and classifying the different carbon emission trajectories. Further, the Geographical and Temporal Weighted Regression model was employed to explore spatiotemporal traits and essential variables that impact the variations in carbon emissions among four identified trajectory types. Our results showed that Chinese urban carbon emission trajectories can be classified into four categories: a) peaking emissions, b) fluctuating growth, c) continuous growth, and d) passive decline. Specifically, 43 cities, primarily in North China, proactively attained their emission peak post-2010, driven by the reduction in secondary industry and energy intensity. 90 cities, largely industrial hubs in the southeast coast and inland, reached an emission plateau around 2015, exhibiting fluctuating growth due to dependencies on secondary industries. 101 cities, predominantly located in western and central regions, demonstrated a clear upward trend in carbon emissions, propelled by rapid urbanization and heavy industry-oriented economic development. Lastly, 13 cities, typically in the northeastern and southwestern regions, experienced a passive decline in carbon emissions, attributable to resource depletion or economic downturns. It is evident that China's city-level carbon peaking has demonstrated some effectiveness, yet considerable progress is still required.

7.
Neuroreport ; 35(9): 590-600, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38652514

RESUMO

Intracerebral hemorrhage (ICH) is a fatal brain injury, but the current treatments for it are inadequate to reduce the severity of secondary brain injury. Our study aims to explore the molecular mechanism of Egr1 and Phlda1 in regulating hemin-induced neuronal pyroptosis, and hope to provide novel therapeutic targets for ICH treatment. Mouse hippocampal neuron cells treated with hemin were used to simulate an in-vitro ICH model. Using qRT-PCR and western blot to evaluate mRNA and protein concentrations. MTT assay was utilized to assess cell viability. LDH levels were determined by lactate Dehydrogenase Activity Assay Kit. IL-1ß and IL-18 levels were examined by ELISA. The interaction of Egr1 and Phlda1 promoter was evaluated using chromatin immunoprecipitation and dual-luciferase reporter assays. Egr1 and Phlda1 were both upregulated in HT22 cells following hemin treatment. Hemin treatment caused a significant reduction in HT22 cell viability, an increase in Nlrc4 and HT22 cell pyroptosis, and heightened inflammation. However, knocking down Egr1 neutralized hemin-induced effects on HT22 cells. Egr1 bound to the promoter of Phlda1 and transcriptionally activated Phlda1. Silencing Phlda1 significantly reduced Nlrc4-dependent neuronal pyroptosis. Conversely, overexpressing Phlda1 mitigated the inhibitory effects of Egr1 knockdown on Nlrc4 and neuronal pyroptosis during ICH. Egr1 enhanced neuronal pyroptosis mediated by Nlrc4 under ICH via transcriptionally activating Phlda1.


Assuntos
Hemorragia Cerebral , Proteína 1 de Resposta de Crescimento Precoce , Neurônios , Piroptose , Animais , Piroptose/fisiologia , Piroptose/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Hemorragia Cerebral/metabolismo , Camundongos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Hemina/farmacologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Linhagem Celular
8.
J Am Chem Soc ; 146(17): 11978-11990, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626322

RESUMO

Tethered nonplanar aromatics (TNAs) make up an important class of nonplanar aromatic compounds showing unique features. However, the knowledge on the synthesis, structures, and properties of TNAs remains insufficient. In this work, a new type of TNAs, the tethered aromatic lactams, is synthesized via Pd-catalyzed consecutive intramolecular direct arylations. These molecules possess a helical ladder-type conjugated system of up to 13 fused rings. The overall yields ranged from 3.4 to 4.3%. The largest of the tethered aromatic lactams, 6L-Bu-C14, demonstrates a guest-adaptive hosting capability of TNAs for the first time. When binding fullerene guests, the cavity of 6L-Bu-C14 became more circular to better accommodate spherical fullerene molecules. The host-guest interaction is thoroughly studied by X-ray crystallography, theoretical calculations, fluorescence titration, and nuclear magnetic resonance (NMR) titration experiments. 6L-Bu-C14 shows stronger binding with C70 than with C60 due to the better convex-concave π-π interaction. P and M enantiomers of all tethered aromatic lactams show distinct and persistent chiroptical properties and demonstrate the potential of chiral TNAs as circularly polarized luminescence (CPL) emitters.

9.
Sensors (Basel) ; 24(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38475243

RESUMO

High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody's back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.

10.
J Am Chem Soc ; 146(12): 8260-8268, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497725

RESUMO

We report the synthesis, crystal structure, and physical properties of a novel ternary compound, Th2Cu4As5. The material crystallizes in a tetragonal structure with lattice parameters a = 4.0639(3) Å and c = 24.8221(17) Å. Its structure can be described as an alternating stacking of fluorite-type Th2As2 layers with antifluorite-type double-layered Cu4As3 slabs. The measurement of electrical resistivity, magnetic susceptibility, and specific heat reveals that Th2Cu4As5 undergoes bulk superconducting transition at 4.2 K. Additionally, all these physical quantities exhibit anomalies at 48 K, accompanied by a sign change in the Hall coefficient, suggesting a charge-density-wave-like (CDW) phase transition. Drawing from both experimental data and band calculations, we propose that the superconducting and CDW-like phase transitions are, respectively, associated with the Cu4As3 slabs and the As plane in the Th2As2 layers.

11.
Adv Healthc Mater ; : e2304136, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551143

RESUMO

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

12.
Acta Biomater ; 179: 243-255, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38458511

RESUMO

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.


Assuntos
Adenoviridae , Neoplasias Colorretais , Cobre , Imunoterapia , Manganês , Terapia Viral Oncolítica , Vírus Oncolíticos , Cobre/química , Cobre/farmacologia , Manganês/química , Manganês/farmacologia , Imunoterapia/métodos , Animais , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Terapia Viral Oncolítica/métodos , Humanos , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Feminino
13.
J Environ Manage ; 356: 120668, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492419

RESUMO

Grazing causes great disturbances in grassland ecosystems and may change the abundance, diversity, and ecological function of soil biota. Because of their important role in nutrient cycling and as good environmental indicators, nematodes are very representative soil organisms. However, the mechanisms by which grazing intensity, livestock type, duration, and environmental factors (e.g., climate and edaphic factors) affect soil nematodes remain poorly understood. In this study, we collected 1964 paired observations all over the world from 53 studies to clarify the grazing response patterns of soil nematodes and their potential mechanisms. Overall, grazing significantly decreased the abundance of bacterial-feeding (BF) nematodes (-16.54%) and omnivorous-predatory (OP) nematodes (-36.81%), and decreased nematode community diversity indices (Shannon-Weiner index: -4.33%, evenness index: -9.22%, species richness: -5.35%), but had no effect on ecological indices under a global regional scale. The response of soil nematodes to grazing varied by grazing intensity, animals, and duration. Heavy grazing decreased OP nematode abundance, but had no effect on the abundance of other trophic groups, or on diversity or ecological indices. Grazing by small animals had stronger effects than that by large animals and mixed-size animals on BF, fungal-feeding (FF), plant-feeding (PF) and OP nematodes, the Shannon-Wiener index, and the species richness index. The abundance of FF and OP nematodes influenced significantly under short-term grazing. The evenness index decreased significantly under long-term grazing (>10 years). Climate and edaphic factors impacted the effects of grazing on nematode abundance, diversity, and ecological indices. When resources (i.e., rain, heat, and soil nutrients) were abundant, the negative effects of grazing on nematodes were reduced; under sufficiently abundant resources, grazing even had positive effects on soil nematode communities. Thus, the influence of grazing on soil nematode communities is resource-dependent. Our study provides decision makers with grazing strategies based on the resource abundance. Resource-poor areas should have less grazing, while resource-rich areas should have more grazing to conserve soil biodiversity and maintain soil health.


Assuntos
Ecossistema , Nematoides , Animais , Pradaria , Solo , Nematoides/fisiologia , Biodiversidade , Bactérias
14.
J Hepatocell Carcinoma ; 11: 317-325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348099

RESUMO

Purpose: The differential diagnosis of atypical hepatocellular carcinoma (aHCC) and atypical benign focal hepatic lesions (aBFHL) usually depends on pathology. This study aimed to develop non-invasive approaches based on conventional blood indicators for the differential diagnosis of aHCC and aBFHL. Patients and Methods: Hospitalized patients with pathologically confirmed focal hepatic lesions and their clinical data were retrospectively collected, in which patients with HCC with serum alpha-fetoprotein (AFP) levels of ≤200 ng/mL and atypical imaging features were designated as the aHCC group (n = 224), and patients with benign focal hepatic lesions without typical imaging features were designated as the aBFHL group (n = 178). The performance of indexes (both previously reported and newly constructed) derived from conventional blood indicators by four mathematical operations in distinguishing aHCC and aBFHL was evaluated using the receiver operating characteristic (ROC) curve and diagnostic validity metrics. Results: Among ten previously reported derived indexes related to HCC, the index GPR, the ratio of γ-glutamyltransferase (GGT) to platelet (PLT), showed the best performance in distinguishing aHCC from aBFHL with the area under ROC curve (AUROC) of 0.853 (95% CI 0.814-0.892), but the other indexes were of little value (AUROCs from 0.531 to 0.700). A new derived index, sAGP [(standardized AFP + standardized GGT)/standardized PLT], was developed and exhibited AUROCs of 0.905, 0.894, 0.891, 0.925, and 0.862 in differentiating overall, BCLC stage 0/A, TNM stage I, small, and AFP-negative aHCC from aBFHL, respectively. Conclusion: The sAGP index is an efficient, simple, and practical metric for the non-invasive differentiation of aHCC from aBFHL.

15.
Sci Total Environ ; 917: 170505, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38301778

RESUMO

Although soil microbial biomass responses to experimental warming have been extensively studied, the mechanisms through which elevated temperatures influence soil microbial biomass remain unclear. In this study, we performed a global meta-analysis to quantify the global pattern of soil microbial biomass in response to warming. Our findings suggest that global warming effect is not apparent when all the data are pooled together, while warming does increase microbial biomass under specific conditions (Δ°C ≥ 2 °C). This constructive influence is particularly accentuated under certain circumstances, including high precipitation levels (>800 mm), short treatment durations (<1 year), and within agricultural ecosystems. More importantly, our findings suggest that the impact of global warming on soil microbial biomass is largely mediated by changes in soil nitrogen availability. These findings underscore the pivotal role of nitrogen availability in modulating the response of soil microbial biomass to warming, while also emphasizing the intricate influence between multiple factors such as temperature, duration, and precipitation in shaping the patterns of warming effects.


Assuntos
Ecossistema , Solo , Biomassa , Nitrogênio/análise , Microbiologia do Solo , Carbono
16.
J Biol Chem ; 300(3): 105704, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309506

RESUMO

Selective gene expression in cells in physiological or pathological conditions is important for the growth and development of organisms. Acetylation of histone H4 at K16 (H4K16ac) catalyzed by histone acetyltransferase 8 (KAT8) is known to promote gene transcription; however, the regulation of KAT8 transcription and the mechanism by which KAT8 acetylates H4K16ac to promote specific gene expression are unclear. Using the lepidopteran insect Helicoverpa armigera as a model, we reveal that the transcription factor FOXO promotes KAT8 expression and recruits KAT8 to the promoter region of autophagy-related gene 8 (Atg8) to increase H4 acetylation at that location, enabling Atg8 transcription under the steroid hormone 20-hydroxyecdysone (20E) regulation. H4K16ac levels are increased in the midgut during metamorphosis, which is consistent with the expression profiles of KAT8 and ATG8. Knockdown of Kat8 using RNA interference results in delayed pupation and repression of midgut autophagy and decreases H4K16ac levels. Overexpression of KAT8-GFP promotes autophagy and increases H4K16ac levels. FOXO, KAT8, and H4K16ac colocalized at the FOXO-binding region to promote Atg8 transcription under 20E regulation. Acetylated FOXO at K180 and K183 catalyzed by KAT8 promotes gene transcription for autophagy. 20E via FOXO promotes Kat8 transcription. Knockdown or overexpression of FOXO appeared to give similar results as knockdown or overexpression of KAT8. Therefore, FOXO upregulates KAT8 expression and recruits KAT8 to the promoter region of Atg8, where the KAT8 induces H4 acetylation to promote Atg8 transcription for autophagy under 20E regulation. This study reveals the mechanism that KAT8 promotes transcription of a specific gene.


Assuntos
Autofagia , Ecdisterona , Helicoverpa armigera , Histona Acetiltransferases , Histonas , Processamento de Proteína Pós-Traducional , Acetilação , Autofagia/genética , Ecdisterona/metabolismo , Regiões Promotoras Genéticas , Helicoverpa armigera/genética , Helicoverpa armigera/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histonas/metabolismo
17.
Microsyst Nanoeng ; 10: 23, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38317693

RESUMO

Extracellular vesicles (EVs) have been identified as promising biomarkers for the noninvasive diagnosis of various diseases. However, challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low purities. Here, we report a high-yield ( > 90%) and rapid ( < 10 min) EV isolation method called FLocculation via Orbital Acoustic Trapping (FLOAT). The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid droplets. By adding a thermoresponsive polymer flocculant, nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the droplet. We demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein, addressing a significant obstacle in the development of EV-based liquid biopsies. Due to its high-yield nature, FLOAT reduces biofluid starting volume requirements by a factor of 100 (from 20 mL to 200 µL), demonstrating its promising potential in point-of-care diagnostics.

18.
Acta Neurochir (Wien) ; 166(1): 61, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305984

RESUMO

BACKGROUND: Microsurgery alone often proves to be challenging in treating paraclinoid internal carotid artery (ICA) aneurysms, which are known for their complex anatomy. METHOD: A 53-year-old female with a large right ICA-superior hypophyseal artery (SHA) aneurysm underwent clipping repair. Mixed reality technology was utilized in the preoperative planning and anatomical study. During the surgery, the anterior clinoid process was removed intradurally to improve access to the aneurysm neck. The aneurysm was then secured with a long curved clip. The patient's recovery was successful without any complications. CONCLUSION: This report aims to shed light on the intricacies involved in clipping ICA-SHA aneurysms.


Assuntos
Doenças das Artérias Carótidas , Aneurisma Intracraniano , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/complicações , Procedimentos Neurocirúrgicos , Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Hipófise/irrigação sanguínea , Microcirurgia , Instrumentos Cirúrgicos , Doenças das Artérias Carótidas/cirurgia
19.
Sci Adv ; 10(1): eadi5894, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38170776

RESUMO

Randomly distributed topological defects created during the spontaneous symmetry breaking are the fingerprints to trace the evolution of symmetry, range of interaction, and order parameters in condensed matter systems. However, the effective mean to manipulate topological defects into ordered form is elusive due to the topological protection. Here, we establish a strategy to effectively align the topological domain networks in hexagonal manganites through a mechanical approach. It is found that the nanoindentation strain gives rise to a threefold Magnus-type force distribution, leading to a sixfold symmetric domain pattern by driving the vortex and antivortex in opposite directions. On the basis of this rationale, sizeable mono-chirality topological stripe is readily achieved by expanding the nanoindentation to scratch, directly transferring the randomly distributed topological defects into an ordered form. This discovery provides a mechanical strategy to manipulate topological protected domains not only on ferroelectrics but also on ferromagnets/antiferromagnets and ferroelastics.

20.
Chin J Traumatol ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38262890

RESUMO

PURPOSE: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis. METHODS: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conforms to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q1, Q3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. RESULTS: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4 % (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) was lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, OR = 3.114) and 3rd space water > 0.95% (p = 0.045, OR = 2.342) were independent risk factors for lower extremity muscle injuries. CONCLUSION: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

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