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1.
IEEE Trans Image Process ; 33: 2880-2894, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38607703

RESUMO

Color transfer aims to change the color information of the target image according to the reference one. Many studies propose color transfer methods by analysis of color distribution and semantic relevance, which do not take the perceptual characteristics for visual quality into consideration. In this study, we propose a novel color transfer method based on the saliency information with brightness optimization. First, a saliency detection module is designed to separate the foreground regions from the background regions for images. Then a dual-branch module is introduced to implement color transfer for images. Finally, a brightness optimization operation is designed during the fusion of foreground and background regions for color transfer. Experimental results show that the proposed method can implement the color transfer for images while keeping the color consistency well. Compared with other existing studies, the proposed method can obtain significant performance improvement. The source code and pre-trained models are available at https://github.com/PlanktonQAQ/SCTNet.

2.
Opt Express ; 32(7): 11193-11201, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570973

RESUMO

Bound states in the continuum (BICs) allow to obtain an ultrahigh-quality-factor optical cavity. Nevertheless, BICs must be extended in one or more directions, substantially increasing the device footprint. Although super-cavity mode quasi-BICs supported by single nanopillars have been demonstrated recently, their low-quality factor and localized electromagnetic field inside the dielectric nanopillar are insufficient for high-sensitivity refractive index sensing applications. We propose a ring structure rotated by a dielectric sectorial nanostructure, which can achieve a high quality factor by breaking the rotational symmetry of the ring structure with a footprint as small as 3 µm2. As a straightforward application, we demonstrate high performance local refractive index and nanoscale film thickness sensing based on rotational symmetry breaking induced BICs. These BICs reach quality factor and sensitivity of one order of magnitude better than those of conventional super-cavity mode BICs. The proposed method provides insights into the design of compact high quality factor photonic devices, opening up new possibilities for applications in refractive index and nanoscale film thickness sensing.

3.
4.
Invest Ophthalmol Vis Sci ; 65(3): 6, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38466285

RESUMO

Purpose: Isolating extracellular vesicles (EVs) with high yield, replicable purity, and characterization remains a bottleneck in the development of EV therapeutics. To address these challenges, the current study aims to establish the necessary framework for preclinical and clinical studies in the development of stem cell-derived intraocular EV therapeutics. Methods: Small EVs (sEVs) were separated from the conditioned cell culture medium (CCM) of the human embryogenic stem cell-derived fully polarized retinal pigment epithelium (hESC-RPE-sEV) by a commercially available microfluidic tangential flow filtration (TFF) device ExoDisc (ED) or differential ultracentrifugation (dUC). The scaling and concentration capabilities and purity of recovered sEVs were assessed. Size, number, and surface markers of sEVs were determined by orthogonal approaches using multiple devices. Results: ED yielded higher numbers of sEVs, ranging from three to eight times higher depending on the measurement device, compared to dUC using the same 5 mL of CCM input. Within the same setting, the purity of ED-recovered hESC-RPE-sEVs was higher than that for dUC-recovered sEVs. ED yielded a higher concentration of particles, which is strongly correlated with the input volume, up to 10 mL (r = 0.98, P = 0.016). Meanwhile, comprehensive characterization profiles of EV surface markers between ED- and dUC-recovered hESC-RPE-sEVs were compatible. Conclusions: Our study supports TFF as a valuable strategy for separating sEVs for the development of intraocular EV therapeutics. However, there is a growing need for diverse devices to optimize TFF for use in EV preparation. Using orthogonal approaches in EV characterization remains ideal for reliably characterizing heterogeneous EV.


Assuntos
Vesículas Extracelulares , Células-Tronco Embrionárias Humanas , Humanos , Meios de Cultivo Condicionados , Filtração , Epitélio Pigmentado da Retina
5.
Angew Chem Int Ed Engl ; 63(17): e202316907, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38436539

RESUMO

The efficient ethanol electrosynthesis from CO2 is challenging with low selectivity at high CO2 electrolysis rates, due to the competition with H2 and other reduction products. Copper-based bimetallic electrocatalysts are potential candidates for the CO2-to-ethanol conversion, but the secondary metal has mainly been focused on active components (such as Ag, Sn) for CO2 electroreduction, which also promote selectivity of ethylene or other reduction products rather than ethanol. Limited attention has been given to alkali-earth metals due to their inherently active chemical property. Herein, we rationally synthesized a (111) facet-oriented nano Cu2Mg (designated as Cu2Mg(111)) intermetallic compound with high-density ordered Cu3-Mg sites. The in situ Raman spectroscopy and density function theory calculations revealed that the Cu3 - δ $_{^{\rm{{\rm \delta} }} }$ --Mg- δ $_{^{\rm{{\rm \delta} }} }$ + active sites allowed to increase *CO surface coverage, decrease reaction energy for *CO-CO coupling, and stabilize *CHCHOH intermediates, thus promoting the ethanol formation pathway. The Cu2Mg(111) catalyst exhibited a high FEC2H5OH of 76.2±4.8 % at 600 mA⋅cm-2, and a peak value of |jC2H5OH| of 720±34 mA⋅cm-2, almost 4 times of that using conventional Cu2Mg with (311) facets, comparable to the best reported values for the CO2-to-ethanol electroreduction.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38548952

RESUMO

Traditional medical imaging and biomechanical studies have challenges in analyzing the long-term evolution process of abdominal aortic aneurysm (AAA). The homogenized constrained mixture theory (HCMT) allows for quantitative analysis of the changes in the multidimensional morphology and composition of AAA. However, the accuracy of HCMT still requires further clinical verification. This study aims to establish a patient-specific AAA growth model based on HCMT, simulate the long-term growth and remodeling (G&R) process of AAA, and validate the feasibility and accuracy of the method using two additional AAA cases with five follow-up datasets. The media and adventitia layers of AAA were modeled as mixtures composed of elastin, collagen fibers, and smooth muscle cells (SMCs). The strain energy function was used to describe the continuous deposition and degradation effect of the mixture during the AAA evolution. Multiple sets of growth parameters were applied to finite element simulations, and the simulation results were compared with the follow-up data for gradually selecting the optimal growth parameters. Two additional AAA patients with different growth rates were used for validating this method, the optimal growth parameters were obtained using the first two follow-up imaging data, and the growth model was applied to simulate the subsequent four time points. The differences between the simulated diameters and the follow-up diameters of AAA were compared to validate the accuracy of the mechanistic model. The growth parameters, especially the stress-mediated substance deposition gain factor, are highly related to the AAA G&R process. When setting the optimal growth parameters to simulate AAA growth, the proportion of simulation results within the distance of less than 0.5 mm from the baseline models is above 80%. For the validating cases, the mean difference rates between the simulated diameter and the real-world diameter are within 2.5%, which basically meets the clinical demand for quantitatively predicting the AAA growth in maximum diameters. This study simulated the growth process of AAA, and validated the accuracy of this mechanistic model. This method was proved to be used to predict the G&R process of AAA caused by dynamic changes in the mixtures of the AAA vessel wall during long-term, assisting accurately and quantitatively predicting the multidimensional morphological development and mixtures evolution process of AAA in the clinic.

7.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38546324

RESUMO

Enrichment analysis contextualizes biological features in pathways to facilitate a systematic understanding of high-dimensional data and is widely used in biomedical research. The emerging reporter score-based analysis (RSA) method shows more promising sensitivity, as it relies on P-values instead of raw values of features. However, RSA cannot be directly applied to multi-group and longitudinal experimental designs and is often misused due to the lack of a proper tool. Here, we propose the Generalized Reporter Score-based Analysis (GRSA) method for multi-group and longitudinal omics data. A comparison with other popular enrichment analysis methods demonstrated that GRSA had increased sensitivity across multiple benchmark datasets. We applied GRSA to microbiome, transcriptome and metabolome data and discovered new biological insights in omics studies. Finally, we demonstrated the application of GRSA beyond functional enrichment using a taxonomy database. We implemented GRSA in an R package, ReporterScore, integrating with a powerful visualization module and updatable pathway databases, which is available on the Comprehensive R Archive Network (https://cran.r-project.org/web/packages/ReporterScore). We believe that the ReporterScore package will be a valuable asset for broad biomedical research fields.


Assuntos
Pesquisa Biomédica , Microbiota , Benchmarking , Bases de Dados Factuais , Metaboloma
8.
Adv Healthc Mater ; : e2303395, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554036

RESUMO

In the last 30 years, there are ≈60 000 publications about electrospun nanofibers, but it is still unclear whether nanoscale fibers are really necessary for electrospun tissue engineering scaffolds. The present report puts forward this argument and reveals that compared with electrospun nanofibers, microfibers with diameter of ≈3 µm (named as "oligo-micro fiber") are more appropriate for tissue engineering scaffolds owing to their better cell infiltration ability caused by larger pores with available nuclear deformation. To further increase pore sizes, electrospun poly(ε-caprolactone) (PCL) scaffolds are fabricated using latticed collectors with meshes. Fiber orientation leads to sufficient mechanical strength albeit increases porosity. The latticed scaffolds exhibit good biocompatibility and improve cell infiltration. Under aortic conditions in vitro, the performances of latticed scaffolds are satisfactory in terms of the acute systolic hemodynamic functionality, except for the higher regurgitation fraction caused by the enlarged pores. This hierarchical electrospun scaffold with sparse fibers in macropores and oligo-micro fibers in filaments provides new insights into the design of tissue engineering scaffolds, and tissue engineering may provide living heart valves with regenerative capabilities for patients with severe valve disease in the future.

9.
NPJ Vaccines ; 9(1): 65, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514651

RESUMO

Lumpy skin disease virus (LSDV) is a poxvirus that mainly affects cattle and can lead to symptoms such as severe reduction in milk production as well as infertility and mortality, which has resulted in dramatic economic loss in affected countries in Africa, Europe, and Asia. In this study, we successfully isolated two strains of LSDV from different geographical regions in China. Comparative genomic analyses were performed by incorporating additional LSDV whole genome sequences reported in other areas of Asia. Our analyses revealed that LSDV exhibited an 'open' pan-genome. Phylogenetic analysis unveiled distinct branches of LSDV evolution, signifying the prevalence of multiple lineages of LSDV across various regions in Asia. In addition, a reporter LSDV expressing eGFP directed by a synthetic poxvirus promoter was generated and used to evaluate the cell tropism of LSDV in various mammalian and avian cell lines. Our results demonstrated that LSDV replicated efficiently in several mammalian cell lines, including human A549 cells. In conclusion, our results underscore the necessity for strengthening LSD outbreak control measures and continuous epidemiological surveillance.

10.
Environ Sci Technol ; 58(12): 5229-5243, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38466915

RESUMO

Silicone-based passive samplers, commonly paired with gas chromatography-mass spectrometry (GC-MS) analysis, are increasingly utilized for personal exposure assessments. However, its compatibility with the biotic exposome remains underexplored. In this study, we introduce the wearable silicone-based AirPie passive sampler, coupled with nontargeted liquid chromatography with high-resolution tandem mass spectrometry (LC-HRMS/MS), GC-HRMS, and metagenomic shotgun sequencing methods, offering a comprehensive view of personalized airborne biotic and abiotic exposomes. We applied the AirPie samplers to 19 participants in a unique deep underwater confined environment, annotating 4,390 chemical and 2,955 microbial exposures, integrated with corresponding transcriptomic data. We observed significant shifts in environmental exposure and gene expression upon entering this unique environment. We noted increased exposure to pollutants, such as benzenoids, polycyclic aromatic hydrocarbons (PAHs), opportunistic pathogens, and associated antibiotic-resistance genes (ARGs). Transcriptomic analyses revealed the activation of neurodegenerative disease-related pathways, mostly related to chemical exposure, and the repression of immune-related pathways, linked to both biological and chemical exposures. In summary, we provided a comprehensive, longitudinal exposome map of the unique environment and underscored the intricate linkages between external exposures and human health. We believe that the AirPie sampler and associated analytical methods will have broad applications in exposome and precision medicine.


Assuntos
Expossoma , Doenças Neurodegenerativas , Hidrocarbonetos Policíclicos Aromáticos , Dispositivos Eletrônicos Vestíveis , Humanos , Espaços Confinados , Transcriptoma , Monitoramento Ambiental/métodos , Silicones
11.
J Vis Exp ; (203)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38314785

RESUMO

Spinal cord injury (SCI) due to traumatic injuries such as car accidents and falls is associated with permanent spinal cord dysfunction. Creation of contusion models of spinal cord injury by impacting the spinal cord results in similar pathologies to most spinal cord injuries in clinical practice. Accurate, reproducible, and convenient animal models of spinal cord injury are essential for studying spinal cord injury. We present a novel automated spinal cord injury contusion device for mice, the Guangzhou Jinan University smart spinal cord injury system, that can produce spinal cord injury contusion models with accuracy, reproducibility, and convenience. The system accurately produces models of varying degrees of spinal cord injury via laser distance sensors combined with an automated mobile platform and advanced software. We used this system to create three levels of spinal cord injury mice models, determined their Basso mouse scale (BMS) scores, and performed behavioral as well as staining assays to demonstrate its accuracy and reproducibility. We show each step of the development of the injury models using this device, forming a standardized procedure. This method produces reproducible spinal cord injury contusion mice models and reduces human manipulation factors via convenient handling procedures. The developed animal model is reliable for studying spinal cord injury mechanisms and associated treatment approaches.


Assuntos
Contusões , Traumatismos da Medula Espinal , Camundongos , Humanos , Animais , Reprodutibilidade dos Testes , Medula Espinal/patologia , Modelos Animais , Contusões/patologia , Modelos Animais de Doenças
12.
Front Immunol ; 15: 1323174, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415255

RESUMO

Background: The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are both novel biomarkers and predictors of inflammation. Psoriasis is a skin disease characterized by chronic inflammation. This study aimed to investigate the potential association between SII, SIRI, and adult psoriasis. Methods: Data of adults aged 20 to 80 years from the National Health and Nutrition Examination Survey (NHANES) (2003-2006, 2009-2014) were utilized. The K-means method was used to group SII and SIRI into low, medium, and high-level clusters. Additionally, SII or SIRI levels were categorized into three groups: low (1st-3rd quintiles), medium (4th quintile), and high (5th quintile). The association between SII-SIRI pattern, SII or SIRI individually, and psoriasis was assessed using multivariate logistic regression models. The results were presented as odds ratios (ORs) and confidence intervals (CIs). Restricted cubic spline (RCS) regression, subgroup, and interaction analyses were also conducted to explore the potential non-linear and independent relationships between natural log-transformed SII (lnSII) levels or SIRI levels and psoriasis, respectively. Results: Of the 18208 adults included in the study, 511 (2.81%) were diagnosed with psoriasis. Compared to the low-level group of the SII-SIRI pattern, participants in the medium-level group had a significantly higher risk for psoriasis (OR = 1.40, 95% CI: 1.09, 1.81, p-trend = 0.0031). In the analysis of SII or SIRI individually, both SII and SIRI were found to be positively associated with the risk of psoriasis (high vs. low group OR = 1.52, 95% CI: 1.18, 1.95, p-trend = 0.0014; OR = 1.48, 95% CI: 1.12, 1.95, p-trend = 0.007, respectively). Non-linear relationships were observed between lnSII/SIRI and psoriasis (both p-values for overall < 0.05, p-values for nonlinearity < 0.05). The association between SII levels and psoriasis was stronger in females, obese individuals, people with type 2 diabetes, and those without hypercholesterolemia. Conclusion: We observed positive associations between SII-SIRI pattern, SII, SIRI, and psoriasis among U.S. adults. Further well-designed studies are needed to gain a better understanding of these findings.


Assuntos
Diabetes Mellitus Tipo 2 , Psoríase , Adulto , Feminino , Humanos , Inquéritos Nutricionais , Interpretação Estatística de Dados , Inflamação
13.
ISA Trans ; 147: 350-359, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38311497

RESUMO

Energy efficiency optimization for the ultra supercritical (USC) boiler-turbine unit is a major concern in the field of power generation. In order to deal with the nonlinearity and slow dynamic response problems, a new nonlinear control method is proposed which integrates internal model control (IMC) and generalized predictive control (GPC) into a unified framework. Specifically, through a long short-term memory (LSTM) neural network based IMC, the system achieves rapid convergence to the vicinity of the desired setpoint, significantly enhancing the response speed. Then, by a composite weighted human learning optimization network based nonlinear generalized predictive control (CWHLO-GPC), high-accuracy tracking performance is achieved. Finally, an example on a 1000MW USC power plant demonstrates the proposed method can achieve fast and stable dynamic response under large load variation.

14.
Int Immunopharmacol ; 129: 111578, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38330795

RESUMO

BACKGROUND: Maintenance therapy (MT) for recurrent or metastatic cervical cancer remains non-standardized. This study assessed MT effectiveness using a comprehensive approach and identifies prognosis factors inpatients with recurrent or metastatic cervical cancer. METHODS: From January 2019 and December 2021, over 6000 patients from six Chinese institutions were retrospectively examined. Patients had recurrent/metastatic cervical cancer and underwent first-line chemotherapy with or without MT. We calculated overall and progression-free survival using Kaplan-Meier analysis, comparing via log-rank test, and conducted Cox regression for prognostic factors. RESULTS: Overall, 274 patients were stratified into an MT group (n = 77) and a non-MT group (n = 197). The 3-year OS rates were 52.5 % and 28.0 % for the MT and non-MT groups, respectively. The MT group had significantly enhanced median OS (37 vs. 21 months; HR, 0.43; 95 % CI, 0.30-0.61; P < 0.001) and PFS (21 vs. 14 months; HR, 0.65; 95 % CI, 0.47-0.90; P = 0.014) compared with the non-MT group. No significant differences in efficacy were observed among the various MT regimens, whether PD-1 monoclonal antibody, targeted therapeutic agents, or a combination of both. Extended PFS and OS were observed in patients receiving > 8 MT cycles. Multivariate analyses revealed that oligometastasis, MT, exclusive prior surgery (as opposed to combined surgery and radiotherapy), and extended interval before recurrence were independent OS predictors (P = 0.045, P < 0.001, P = 0.010, and P = 0.005, respectively); oligometastasis, concurrent radiotherapy, MT, and extended interval before recurrence were independent PFS predictors (P = 0.004, P = 0.007, P = 0.009, and P = 0.003). CONCLUSIONS: The MT integration markedly extended PFS and OS in patients diagnosed with recurrent or metastatic cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão
15.
Int J Surg ; 110(4): 1913-1918, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38265436

RESUMO

BACKGROUND: Contraction-type lymphatic vessels (LV) are considered suboptimal for lymphaticovenous anastomosis (LVA). However, despite these pathological changes, their functionality and link to outcomes have not been fully elucidated. The aim of this study was to determine the impact on outcomes when contraction-type LVs were used for LVA compared to the noncontraction-type (normal + ectatic) counterpart for treating lower limb lymphedema. STUDY DESIGN: Eighty-three patients with gynecologic cancer-related unilateral lower-limb lymphedema who underwent LVA as their primary treatment were enrolled in this study. The study group included 20 patients who used only contraction-type LVs. An additional 63 patients (control group) received noncontraction-type LVs only. Patients with a history of LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-LVA and post-LVA volume changes were recorded and matched using propensity scores. The primary endpoint was the volume change at 6/12 months after LVA. RESULTS: After matching, 20 patients were included in each group. All parameters were matched, except that the study group still had a significantly inferior indocyanine green (ICG)-positive ratio, lymph flow-positive ratio, and washout-positive ratios ( P <0.001, P =0.003, and P <0.001, respectively) when compared to the control group after matching. However, at 1-year follow-up, the postoperative percentage volume reduction was comparable between the groups ( P= 0.619). CONCLUSION: The use of contraction-type LVs for LVA is encouraged when no other LVs are available.


Assuntos
Anastomose Cirúrgica , Extremidade Inferior , Vasos Linfáticos , Linfedema , Pontuação de Propensão , Humanos , Feminino , Pessoa de Meia-Idade , Linfedema/cirurgia , Linfedema/etiologia , Vasos Linfáticos/cirurgia , Estudos Retrospectivos , Extremidade Inferior/cirurgia , Idoso , Adulto , Resultado do Tratamento , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/complicações
16.
Basic Res Cardiol ; 119(1): 75-91, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38172251

RESUMO

Mast cells (MCs) are important intermediates between the nervous and immune systems. The cardiac autonomic nervous system (CANS) crucially modulates cardiac electrophysiology and arrhythmogenesis, but whether and how MC-CANS neuroimmune interaction influences arrhythmia remain unclear. Our clinical data showed a close relationship between serum levels of MC markers and CANS activity, and then we use mast cell stabilizers (MCSs) to alter this MC-CANS communication. MCSs, which are well-known anti-allergic agents, could reduce the risk of ventricular arrhythmia (VA) after myocardial infarction (MI). RNA-sequencing (RNA-seq) analysis to investigate the underlying mechanism by which MCSs could affect the left stellate ganglion (LSG), a key therapeutic target for modulating CANS, showed that the IL-6 and γ-aminobutyric acid (GABA)-ergic system may be involved in this process. Our findings demonstrated that MCSs reduce VA risk along with revealing the potential underlying antiarrhythmic mechanisms.


Assuntos
Antialérgicos , Estabilizadores de Mastócitos , Humanos , Neuroimunomodulação , Arritmias Cardíacas/prevenção & controle , Coração
17.
Proc Natl Acad Sci U S A ; 121(6): e2311847121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38294942

RESUMO

Taking stock of individuals' perceived family ideals is particularly important in the current moment given unprecedented fertility declines and the diversification of households in advanced industrial societies. Study participants in urban China, Japan, South Korea, Singapore, the United States, Italy, Spain, and Norway were asked to evaluate vignettes describing families whose characteristics vary on ten dimensions. In contrast to previous studies that focused on a single dimension, such as fertility ideals or gender roles, this holistic vignette approach identifies the relative importance of each dimension. Multilevel regression analysis reveals both expected and unexpected findings. Parenthood remains a positive ideal, but the number of children does not matter once other family dimensions are considered, a potentially important finding in light of conventional wisdom regarding the two-children ideal. When evaluating families with at least one child, respondents tend to positively evaluate more traditional arrangements, including valuing marriage relative to cohabitation and, particularly, divorce. Also, in addition to financial resources, good communication between immediate and extended family members, as well as maintaining respect in the larger community, are highly salient attributes of an ideal family. Notwithstanding some important cross-national differences, egalitarian gender roles and avoiding work-family conflict are also valued positively. Overall, even as the study reveals some notable variations between societies, respondents across countries identify similar components of an ideal family.


Assuntos
Características da Família , Fertilidade , Estados Unidos , Humanos , Casamento , Divórcio , China , Dinâmica Populacional , Países em Desenvolvimento
18.
EMBO Rep ; 25(2): 770-795, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182816

RESUMO

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.


Assuntos
Adenina , Infecções Bacterianas , Receptor 2 Toll-Like , Animais , Camundongos , Adenina/análogos & derivados , Inflamação/genética , Metiltransferases/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
19.
IEEE Trans Cybern ; PP2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38271176

RESUMO

This article aims to analyze H∞ stability of a class of networked control systems (NCSs) under random denial of service (DoS) attacks and design a sampled-data-based state feedback security controller to mitigate the influence of attacks. Different from the existing random attacks, the information about the maximum duration time of DoS attacks can be captured by introducing a predesigned logical processor. Then, based on the periodic sampling technique, the probability of attack occurrence and the resultant number of maximum allowable consecutive packet dropouts can be calculated, which is quite significant to investigating the security problem of NCSs. A DoS-dependent security controller which makes full use of the attack probability information and the number of attack-induced packet dropouts is designed. A novel networked sampled-data system model is first established that enables us to deal with the random DoS attacks phenomena and the time-varying delay induced by attacks under a uniform framework. By structuring a suitable Lyapunov-Krasovskii functional, the relationship between mean square asymptotic stability and attack characteristics is obtained. Finally, the reliability and applicability of the presented control strategy in eliminating the influence of DoS attacks are validated by two practical engineering applications.

20.
Oncoimmunology ; 13(1): 2303195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38235318

RESUMO

Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-ß signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias Gástricas , Humanos , Antígeno B7-H1/genética , Cromatina , Imunoterapia , Neoplasias Gástricas/patologia , Oncogenes/genética
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