Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 253
Filtrar
1.
iScience ; 27(5): 109659, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38706841

RESUMO

Abnormal mTORC1 activation by the lysosomal Ragulator complex has been implicated in cancer and glycolytic metabolism associated with drug resistance. Fasting upregulates RNF152 and mediates the metabolic status of cells. We report that RNF152 regulates mTORC1 signaling by targeting a Ragulator subunit, p18, and attenuates gemcitabine resistance in gallbladder cancer (GBC). We detected levels of RNF152 and p18 in tissues and undertook mechanistic studies using activators, inhibitors, and lentivirus transfections. RNF152 levels were significantly lower in GBC than in adjacent non-cancer tissues. Fasting impairs glycolysis, induces gemcitabine sensitivity, and upregulates RNF152 expression. RNF152 overexpression increases the sensitivity of GBC cells to gemcitabine, whereas silencing RNF152 has the opposite effect. Fasting-induced RNF152 ubiquitinates p18, resulting in proteasomal degradation. RNF152 deficiency increases the lysosomal localization of p18 and increases mTORC1 activity, to promote glycolysis and decrease gemcitabine sensitivity. RNF152 suppresses mTORC1 activity to inhibit glycolysis and enhance gemcitabine sensitivity in GBC.

2.
Molecules ; 29(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38792214

RESUMO

BACKGROUND: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. RESULTS: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 µM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 µg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. CONCLUSIONS: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.


Assuntos
Flavonoides , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Flavonoides/farmacologia , Flavonoides/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Antibacterianos/farmacologia , Antibacterianos/química , NADH Desidrogenase/antagonistas & inibidores , NADH Desidrogenase/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Animais , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Humanos , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/metabolismo
3.
medRxiv ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38633799

RESUMO

Breast cancer screening is necessary to reduce mortality due to undetected breast cancer. Current methods have limitations, and as a result many women forego regular screening. Magnetic resonance imaging (MRI) can overcome most of these limitations, but access to conventional MRI is not widely available for routine annual screening. Here, we used an MRI scanner operating at ultra-low field (ULF) to image the left breasts of 11 women (mean age, 35 years ±13 years) in the prone position. Three breast radiologists reviewed the imaging and were able to discern the breast outline and distinguish fibroglandular tissue (FGT) from intramammary adipose tissue. Additionally, the expert readers agreed on their assessment of the breast tissue pattern including fatty, scattered FGT, heterogeneous FGT, and extreme FGT. This preliminary work demonstrates that ULF breast MRI is feasible and may be a potential option for comfortable, widely deployable, and low-cost breast cancer diagnosis and screening.

4.
Acta Biomater ; 180: 183-196, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604465

RESUMO

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.


Assuntos
Implantes Absorvíveis , Materiais Revestidos Biocompatíveis , Magnésio , Nanocompostos , Stents , Animais , Coelhos , Magnésio/química , Magnésio/farmacologia , Nanocompostos/química , Corrosão , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Incrustação Biológica/prevenção & controle , Dioxanos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Polímeros/química , Polímeros/farmacologia , Ligas/química , Ligas/farmacologia
5.
Proc Natl Acad Sci U S A ; 121(14): e2312700121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38498725

RESUMO

In nature, leafhoppers cover their body surfaces with brochosomes as a protective coating. These leafhopper-produced brochosomes are hollow, buckyball-shaped, nanoscopic spheroids with through-holes distributed across their surfaces, representing a class of deployable optical materials that are rare in nature. Despite their discovery in the 1950s, it remains unknown why the sizes of brochosomes and their through-holes consistently fall within the range of hundreds of nanometers across different leafhopper species. Here, we demonstrate that the hierarchical geometries of brochosomes are engineered within a narrow size range with through-hole architecture to significantly reduce light reflection. By utilizing two-photon polymerization three-dimensional printing to fabricate high-fidelity synthetic brochosomes, we investigated the optical form-to-function relationship of brochosomes. Our results show that the diameters of brochosomes are engineered within a specific size range to maximize broadband light scattering, while the secondary through-holes are designed to function as short-wavelength, low-pass filters, further reducing light reflection. These synergistic effects enable brochosomes to achieve a substantial reduction in specular reflection, by up to approximately 80 to 94%, across a broadband wavelength range. Importantly, brochosomes represent a biological example demonstrating short-wavelength, low-pass filter functionality. Furthermore, our results indicate that the geometries of natural brochosomes may have evolved to effectively reduce reflection from ultraviolet to visible light, thereby enabling leafhoppers to evade predators whose vision spectrum encompasses both ultraviolet and visible light. Our findings offer key design insights into a class of deployable bioinspired optical materials with potential applications in omnidirectional antireflection coatings, optical encryption, and multispectral camouflage.

6.
Nature ; 629(8010): 114-120, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38538797

RESUMO

Mountain ranges contain high concentrations of endemic species and are indispensable refugia for lowland species that are facing anthropogenic climate change1,2. Forecasting biodiversity redistribution hinges on assessing whether species can track shifting isotherms as the climate warms3,4. However, a global analysis of the velocities of isotherm shifts along elevation gradients is hindered by the scarcity of weather stations in mountainous regions5. Here we address this issue by mapping the lapse rate of temperature (LRT) across mountain regions globally, both by using satellite data (SLRT) and by using the laws of thermodynamics to account for water vapour6 (that is, the moist adiabatic lapse rate (MALRT)). By dividing the rate of surface warming from 1971 to 2020 by either the SLRT or the MALRT, we provide maps of vertical isotherm shift velocities. We identify 17 mountain regions with exceptionally high vertical isotherm shift velocities (greater than 11.67 m per year for the SLRT; greater than 8.25 m per year for the MALRT), predominantly in dry areas but also in wet regions with shallow lapse rates; for example, northern Sumatra, the Brazilian highlands and southern Africa. By linking these velocities to the velocities of species range shifts, we report instances of close tracking in mountains with lower climate velocities. However, many species lag behind, suggesting that range shift dynamics would persist even if we managed to curb climate-change trajectories. Our findings are key for devising global conservation strategies, particularly in the 17 high-velocity mountain regions that we have identified.


Assuntos
Altitude , Migração Animal , Biodiversidade , Mapeamento Geográfico , Aquecimento Global , Animais , África Austral , Brasil , Conservação dos Recursos Naturais , Aquecimento Global/estatística & dados numéricos , Umidade , Indonésia , Chuva , Refúgio de Vida Selvagem , Imagens de Satélites , Especificidade da Espécie , Temperatura , Fatores de Tempo
7.
Sci Adv ; 10(9): eadl4027, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427742

RESUMO

Microscale thermal signature control using incoherent heat sources remains challenging, despite recent advancements in plasmonic materials and phase-change materials. Inspired by leafhopper-generated brochosomes, we design binary metastructures functioning as pixel twins to achieve pixelated thermal signature control at the microscale. In the infrared range, the pixel twins exhibit distinct emissivities, creating thermal counterparts of "0-1" binary states for storing and displaying information. In the visible range, the engineered surface morphology of the pixel twins ensures similar scattering behaviors. This renders them visually indistinguishable, thereby concealing the stored information. The brochosome-like pixel twins are self-emitting when thermally excited. Their structure-enabled functions do not rely on the permittivities of specific materials, which distinguishes them from the conventional laser-illuminated plasmonic holographic metasurfaces. The unique combination of visible camouflage and infrared display offers a systemic solution to microscale spatial control of thermal signatures and has substantial implications for optical security, anticounterfeiting, and data encryption.

8.
Nano Lett ; 24(5): 1502-1509, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38277641

RESUMO

With the continuous advancement of nanotechnology, nanodevices have become crucial components in computing, sensing, and energy conversion applications. The structures of nanodevices typically possess subwavelength dimensions and separations, which pose significant challenges for understanding energy transport phenomena in nanodevices. Here, on the basis of a judiciously designed thermal photonic nanodevice, we report the first measurement of near-field energy transport between two coplanar subwavelength structures over temperature bias up to ∼190 K. Our experimental results demonstrate a 20-fold enhancement in energy transfer beyond blackbody radiation. In contrast with the well-established near-field interactions between two semi-infinite bodies, the subwavelength confinements in nanodevices lead to increased polariton scattering and reduction of supporting photonic modes and, therefore, a lower energy flow at a given separation. Our work unveils exciting opportunities for the rational design of nanodevices, particularly for coplanar near-field energy transport, with important implications for the development of efficient nanodevices for energy harvesting and thermal management.

9.
J Med Virol ; 96(2): e29400, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38293843

RESUMO

Serum hepatitis B virus (HBV) spliced RNAs (spRNAs) are ubiquitous in HBV-infected patients; however, their clinical significance remains unknown. Therefore, we aimed to explore the relationship between HBV spRNAs and liver disease progression in chronic hepatitis B (CHB) patients; in vitro cell line assessment was also performed. The serum HBV wild-type RNA (wtRNA) and spRNA levels were individually quantified in a cohort of 279 treatment-naïve, hepatitis B e antigen positive CHB patients with or without cirrhosis. The spRNA proportion was determined as (spRNA × 100%)/(spRNAs + wtRNA). 20 patients' serum samples underwent spRNA species profiling using next-generation sequencing. Serum spRNA species 1, 2, 3, 4, and 5 were the most common variants. The spRNA proportion varied from 0.00% to 19.02%, with higher levels in HBV genotype C patients than in those with genotype B (1.76% vs. 0.84%, p < 0.001). The spRNA proportion was positively associated with the alanine aminotransferase levels (r = 0.144, p = 0.053) and significantly higher in cirrhotic than in non-cirrhotic patients (1.69% vs. 1.04%, p = 0.001). Multivariate analysis revealed a 2.566-fold higher risk of cirrhosis in patients with elevated spRNA proportion (p = 0.024). In vitro experiments confirmed that spRNAs contributed to hepatic stellate cell activation, which is critical in liver fibrosis development. Therefore, increased HBV spRNA expression poses a risk for liver disease progression. Quantifying serum HBV spRNAs can aid in monitoring liver disease progression. Furthermore, the therapeutic targeting of spRNAs may improve the prognosis of patients with CHB.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Humanos , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , RNA/uso terapêutico , Cirrose Hepática/complicações , Antígenos E da Hepatite B , Progressão da Doença , DNA Viral/genética
10.
Opt Express ; 31(18): 29664-29675, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710762

RESUMO

With the development of three-dimensional (3D) light-field display technology, 3D scenes with correct location information and depth information can be perceived without wearing any external device. Only 2D stylized portrait images can be generated with traditional portrait stylization methods and it is difficult to produce high-quality stylized portrait content for 3D light-field displays. 3D light-field displays require the generation of content with accurate depth and spatial information, which is not achievable with 2D images alone. New and innovative portrait stylization techniques methods should be presented to meet the requirements of 3D light-field displays. A portrait stylization method for 3D light-field displays is proposed, which maintain the consistency of dense views in light-field display when the 3D stylized portrait is generated. Example-based portrait stylization method is used to migrate the designated style image to the portrait image, which can prevent the loss of contour information in 3D light-field portraits. To minimize the diversity in color information and further constrain the contour details of portraits, the Laplacian loss function is introduced in the pre-trained deep learning model. The three-dimensional representation of the stylized portrait scene is reconstructed, and the stylized 3D light field image of the portrait is generated the mask guide based light-field coding method. Experimental results demonstrate the effectiveness of the proposed method, which can use the real portrait photos to generate high quality 3D light-field portrait content.

11.
J Virol ; 97(10): e0076023, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37754759

RESUMO

IMPORTANCE: The biogenesis and clinical application of serum HBV pgRNA have been a research hotspot in recent years. This study further characterized the heterogeneity of the 3' terminus of capsid RNA by utilizing a variety of experimental systems conditionally supporting HBV genome replication and secretion, and reveal that the 3' truncation of capsid pgRNA is catalyzed by cellular ribonuclease(s) and viral RNaseH at positions after and before 3' DR1, respectively, indicating the 3' DR1 as a boundary between the encapsidated portion of pgRNA for reverse transcription and the 3' unprotected terminus, which is independent of pgRNA length and the 3' terminal sequence. Thus, our study provides new insights into the mechanism of pgRNA encapsidation and reverse transcription, as well as the optimization of serum HBV RNA diagnostics.


Assuntos
Capsídeo , Genoma Viral , Vírus da Hepatite B , RNA Viral , Replicação Viral , Capsídeo/metabolismo , Genoma Viral/genética , Hepatite B/diagnóstico , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/crescimento & desenvolvimento , Vírus da Hepatite B/metabolismo , Transcrição Reversa , Ribonuclease H/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral/genética
12.
J Funct Biomater ; 14(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37754876

RESUMO

The human body comprises various tubular structures that have essential functions in different bodily systems. These structures are responsible for transporting food, liquids, waste, and other substances throughout the body. However, factors such as inflammation, tumors, stones, infections, or the accumulation of substances can lead to the narrowing or blockage of these tubular structures, which can impair the normal function of the corresponding organs or tissues. To address luminal obstructions, stenting is a commonly used treatment. However, to minimize complications associated with the long-term implantation of permanent stents, there is an increasing demand for biodegradable stents (BDS). Magnesium (Mg) metal is an exceptional choice for creating BDS due to its degradability, good mechanical properties, and biocompatibility. Currently, the Magmaris® coronary stents and UNITY-BTM biliary stent have obtained Conformité Européene (CE) certification. Moreover, there are several other types of stents undergoing research and development as well as clinical trials. In this review, we discuss the required degradation cycle and the specific properties (anti-inflammatory effect, antibacterial effect, etc.) of BDS in different lumen areas based on the biocompatibility and degradability of currently available magnesium-based scaffolds. We also offer potential insights into the future development of BDS.

13.
Nanomaterials (Basel) ; 13(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37446435

RESUMO

Converting and storing solar energy directly as chemical energy through photoelectrochemical devices are promising strategies to replace fossil fuels. Metal oxides are commonly used as photoanode materials, but they still encounter challenges such as limited light absorption, inefficient charge separation, sluggish surface reactions, and insufficient stability. The regulation of surface oxygen species on metal oxide photoanodes has emerged as a critical strategy to modulate molecular and charge dynamics at the reaction interface. However, the precise role of surface oxygen species in metal oxide photoanodes remains ambiguous. The review focuses on elucidating the formation and regulation mechanisms of various surface oxygen species in metal oxides, their advantages and disadvantages in photoelectrochemical reactions, and the characterization methods employed to investigate them. Additionally, the article discusses emerging opportunities and potential hurdles in the regulation of surface oxygen species. By shedding light on the significance of surface oxygen species, this review aims to advance our understanding of their impact on metal oxide photoanodes, paving the way for the design of more efficient and stable photoelectrochemical devices.

14.
Angew Chem Int Ed Engl ; 62(38): e202307246, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37488928

RESUMO

Core-shell photoanodes have shown great potential for photoelectrochemical (PEC) water oxidation. However, the construction of a high-quality interface between the core and shell, as well as a highly catalytic surface, remains a challenge. Herein, guided by computation, we present a BiVO4 photoanode coated with ZnCoFe polyphthalocyanine using pyrazine as a coordination agent. The bidirectional axial coordination of pyrazine plays a dual role by facilitating intimate interfacial contact between BiVO4 and ZnCoFe polyphthalocyanine, as well as regulating the electron density and spin configuration of metal sites in ZnCoFe phthalocyanine, thereby promoting the potential-limiting step of *OOH desorption. The resulting photoanode displayed a high photocurrent density of 5.7±0.1 mA cm-2 at 1.23 VRHE . This study introduces a new approach for constructing core-shell photoanodes, and uncovers the key role of pyrazine axial coordination in modulating the catalytic activity of metal phthalocyanine.

15.
Lancet Diabetes Endocrinol ; 11(8): 567-577, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37414069

RESUMO

BACKGROUND: Impaired glucose regulation (defined as either impaired glucose tolerance or impaired fasting glucose) is an important risk factor for the development of diabetes. We aimed to evaluate the safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing diabetes in Chinese participants with impaired glucose regulation. METHODS: We did a multicentre, open-label, randomised controlled trial at 43 endocrinology departments in general hospitals across China. Eligible participants were individuals with impaired glucose regulation (ie, impaired glucose tolerance or impaired fasting glucose, or both), men or women aged 18-70 years with a BMI of 21-32 kg/m2. Eligible participants were randomly assigned (1:1) via a computer-generated randomisation to receive either standard lifestyle intervention alone or metformin (850 mg orally once per day for the first 2 weeks and titrated to 1700 mg orally per day [850 mg twice per day]) plus lifestyle intervention. Block randomisation was used with a block size of four, stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), hypertension, and use of any anti-hypertensive medication. Lifestyle intervention advice was given by investigators at all participating sites. The primary endpoint was the incidence of newly diagnosed diabetes at the end of the 2-year follow-up. Analysis was done using the full analysis set and per-protocol set. This study is registered with ClinicalTrials.gov, number NCT03441750, and is completed. FINDINGS: Between April, 2017, and June, 2019, 3881 individuals were assessed for eligibility, of which 1678 (43·2%) participants were randomly assigned to either the metformin plus lifestyle intervention group (n=831) or the lifestyle intervention alone group (n=847) and received the allocated intervention at least once. During a median follow-up of 2·03 years, the incidence rate of diabetes was 17·27 (95% CI 15·19-19·56) per 100 person-years in the metformin plus lifestyle intervention group and 19·83 (17·67-22·18) per 100 person-years in the lifestyle intervention alone group. The metformin plus lifestyle intervention group showed a 17% lower risk of developing diabetes than the lifestyle intervention alone group (HR 0·83 [95% CI 0·70-0·99]; log-rank p=0·043). A higher proportion of participants in the metformin plus lifestyle intervention group reported adverse events than in the lifestyle intervention alone group, primarily due to more gastrointestinal adverse events. The percentage of participants reporting a serious adverse event was similar in both groups. INTERPRETATION: Metformin plus lifestyle intervention further reduced the risk of developing diabetes than lifestyle intervention alone in Chinese people with impaired glucose regulation, showing additional benefits of combined intervention in preventing progression to diabetes without new safety concerns. FUNDING: Merck Serono China, an affiliate of Merck KGaA, Darmstadt, Germany. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Metformina , Estado Pré-Diabético , Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , População do Leste Asiático , Glucose , Intolerância à Glucose/tratamento farmacológico , Estilo de Vida , Metformina/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Resultado do Tratamento , Comportamentos Relacionados com a Saúde , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso
16.
Sci Transl Med ; 15(699): eadf3843, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37285400

RESUMO

The association between neutrophil extracellular traps (NETs) and response to inhaled corticosteroids (ICS) in asthma is unclear. To better understand this relationship, we analyzed the blood transcriptomes from children with controlled and uncontrolled asthma in the Taiwanese Consortium of Childhood Asthma Study using weighted gene coexpression network analysis and pathway enrichment methods. We identified 298 uncontrolled asthma-specific differentially expressed genes and one gene module associated with neutrophil-mediated immunity, highlighting a potential role for neutrophils in uncontrolled asthma. We also found that NET abundance was associated with nonresponse to ICS in patients. In a neutrophilic airway inflammation murine model, steroid treatment could not suppress neutrophilic inflammation and airway hyperreactivity. However, NET disruption with deoxyribonuclease I (DNase I) efficiently inhibited airway hyperreactivity and inflammation. Using neutrophil-specific transcriptomic profiles, we found that CCL4L2 was associated with ICS nonresponse in asthma, which was validated in human and murine lung tissue. CCL4L2 expression was also negatively correlated with pulmonary function change after ICS treatment. In summary, steroids fail to suppress neutrophilic airway inflammation, highlighting the potential need to use alternative therapies such as leukotriene receptor antagonists or DNase I that target the neutrophil-associated phenotype. Furthermore, these results highlight CCL4L2 as a potential therapeutic target for individuals with asthma refractory to ICS.


Assuntos
Asma , Armadilhas Extracelulares , Animais , Criança , Humanos , Camundongos , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Desoxirribonuclease I/metabolismo , Desoxirribonuclease I/uso terapêutico , Armadilhas Extracelulares/metabolismo , Inflamação/metabolismo , Neutrófilos/metabolismo , Quimiocina CCL4/metabolismo
17.
Ecol Lett ; 26(7): 1145-1156, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37127410

RESUMO

Although social species as diverse as humans and ants are among the most abundant organisms on Earth, animals cooperate and form groups for many reasons. How these different reasons for grouping affect a species' ecological dominance remains unknown. Here we use a theoretical model to demonstrate that the different fitness benefits that animals receive by forming groups depend on the quality of their environment, which in turn impacts their ecological dominance and resilience to global change. We then test the model's key predictions using phylogenetic comparative analysis of >6500 bird species. As predicted, we find that cooperative breeders occurring in harsh and fluctuating environments have larger ranges and greater abundances than non-cooperative breeders, but cooperative breeders occurring in benign and stable environments do not. Using our model, we further show that social species living in harsh and fluctuating environments will be less vulnerable to climate change than non-social species.


Assuntos
Formigas , Comportamento Social , Animais , Humanos , Filogenia , Reprodução , Aves , Comportamento Cooperativo
18.
J Med Virol ; 95(4): e28749, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37185850

RESUMO

Hepatitis B Virus (HBV) replication has been reported to be restricted by the intrahepatic host restriction factors and antiviral signaling pathways. The intracellular mechanisms underlying the significant viremia difference among different phases of the natural history chronic HBV infection remain elusive. We herein report that the hypoxia-induced gene domain protein-1a (HIGD1A) was highly expressed in the liver of inactive HBV carriers with low viremia. Ectopic expression of HIGD1A in hepatocyte-derived cells significantly inhibited HBV transcription and replication in a dose-dependent manner, while silence of HIGD1A promoted HBV gene expression and replication. Similar results were also observed in both de novo HBV-infected cell culture model and HBV persistence mouse model. Mechanistically, HIGD1A is located on the mitochondrial inner membrane and activates nuclear factor kappa B (NF-κB) signaling pathway through binding to paroxysmal nonkinesigenic dyskinesia (PNKD), which further enhances the expression of a transcription factor NR2F1 to inhibit HBV transcription and replication. Consistently, knockdown of PNKD or NR2F1 and blockage of NF-κB signaling pathway abrogated the inhibitory effect of HIGD1A on HBV replication. Mitochondrial HIGD1A exploits the PNKD-NF-κB-NR2F1 nexus to act as a host restriction factor of HBV infection. Our study thus shed new lights on the regulation of HBV by hypoxia-related genes and related antiviral strategies.


Assuntos
Vírus da Hepatite B , Hepatite B , Animais , Camundongos , Antivirais/farmacologia , Vírus da Hepatite B/fisiologia , NF-kappa B/genética , NF-kappa B/metabolismo , Transcrição Viral , Viremia , Replicação Viral , Humanos
19.
Proc Biol Sci ; 290(1999): 20230529, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37221845

RESUMO

Deforestation is a major contributor to biodiversity loss, yet the impact of forest loss on daily microclimate variability and its implications for species with different daily activity patterns remain poorly understood. Using a recently developed microclimate model, we investigated the effects of deforestation on the daily temperature range (DTR) in low-elevation tropical regions and high-elevation temperate regions. Our results show that deforestation substantially increases DTR in these areas, suggesting a potential impact on species interactions. To test this hypothesis, we studied the competitive interactions between nocturnal burying beetles and all-day-active blowfly maggots in forested and deforested habitats in Taiwan. We show that deforestation leads to increased DTR at higher elevations, which enhances the competitiveness of blowfly maggots during the day and leads to a higher failure rate of carcass burial by the beetles at night. Thus, deforestation-induced temperature variability not only modulates exploitative competition between species with different daily activity patterns, but also likely exacerbates the negative impacts of climate change on nocturnal organisms. In order to limit potential adverse effects on species interactions and their ecological functions, our study highlights the need to protect forests, especially in areas where deforestation can greatly alter temperature variability.


Assuntos
Biodiversidade , Besouros , Animais , Temperatura , Mudança Climática , Febre , Larva
20.
Sensors (Basel) ; 23(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36991634

RESUMO

Few-shot semantic segmentation has attracted much attention because it requires only a few labeled samples to achieve good segmentation performance. However, existing methods still suffer from insufficient contextual information and unsatisfactory edge segmentation results. To overcome these two issues, this paper proposes a multi-scale context enhancement and edge-assisted network (called MCEENet) for few-shot semantic segmentation. First, rich support and query image features were extracted, respectively, using two weight-shared feature extraction networks, each consisting of a ResNet and a Vision Transformer. Subsequently, a multi-scale context enhancement (MCE) module was proposed to fuse the features of ResNet and Vision Transformer, and further mine the contextual information of the image by using cross-scale feature fusion and multi-scale dilated convolutions. Furthermore, we designed an Edge-Assisted Segmentation (EAS) module, which fuses the shallow ResNet features of the query image and the edge features computed by the Sobel operator to assist in the final segmentation task. We experimented on the PASCAL-5i dataset to demonstrate the effectiveness of MCEENet; the results of the 1-shot setting and 5-shot setting on the PASCAL-5i dataset are 63.5% and 64.7%, which surpasses the state-of-the-art results by 1.4% and 0.6%, respectively.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...