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1.
Nat Commun ; 15(1): 4230, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762475

RESUMO

Type 2 diabetes (T2D) presents a formidable global health challenge, highlighted by its escalating prevalence, underscoring the critical need for precision health strategies and early detection initiatives. Leveraging artificial intelligence, particularly eXtreme Gradient Boosting (XGBoost), we devise robust risk assessment models for T2D. Drawing upon comprehensive genetic and medical imaging datasets from 68,911 individuals in the Taiwan Biobank, our models integrate Polygenic Risk Scores (PRS), Multi-image Risk Scores (MRS), and demographic variables, such as age, sex, and T2D family history. Here, we show that our model achieves an Area Under the Receiver Operating Curve (AUC) of 0.94, effectively identifying high-risk T2D subgroups. A streamlined model featuring eight key variables also maintains a high AUC of 0.939. This high accuracy for T2D risk assessment promises to catalyze early detection and preventive strategies. Moreover, we introduce an accessible online risk assessment tool for T2D, facilitating broader applicability and dissemination of our findings.


Assuntos
Inteligência Artificial , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/genética , Humanos , Medição de Risco/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Predisposição Genética para Doença , Adulto , Diagnóstico por Imagem/métodos , Idoso , Fatores de Risco , Curva ROC , Herança Multifatorial/genética
2.
Exp Eye Res ; 244: 109939, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38789021

RESUMO

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.


Assuntos
Movimento Celular , Proliferação de Células , Janus Quinase 2 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Transdução de Sinais , Silibina , Malha Trabecular , Fator de Crescimento Transformador beta2 , Humanos , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo , Malha Trabecular/patologia , Fator de Crescimento Transformador beta2/farmacologia , Fator de Crescimento Transformador beta2/metabolismo , Fator de Transcrição STAT3/metabolismo , Janus Quinase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Cultivadas , Silibina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Western Blotting , Fibrose , Silimarina/farmacologia , Antioxidantes/farmacologia , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/patologia
3.
Front Bioeng Biotechnol ; 12: 1372155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572362

RESUMO

Solid acid catalysts are widely used in the field of biomass catalytic conversion owing to their advantages of low environmental pollution, easy separation and reusability. Nevertheless, there are relatively few studies on the mechanism of solid acid liquefaction for biomass. In this study, the effect of acid strength and acid amount of various solid acids on the liquefaction efficiency has been investigated using waste bamboo sawdust generated from the pulp and paper industry as the raw material. In addition, the physicochemical changes of cellulose, hemicellulose and lignin during the reaction process of bamboo sawdust have been studied, and the liquefaction mechanism of bamboo sawdust under the action of various solid acids has been concluded. As a result, the liquefaction efficiency of bamboo sawdust under the polyol system of PEG400/propanetriol is mainly related to the acid strength of the solid acid, and the greater the acid strength of the solid acid, the better the catalytic effect on the bamboo sawdust, in which the residual amount of bamboo sawdust liquefaction catalyzed by the SPA catalyst is only 17.72%. Noteworthy, the most difficult component to liquefy is the crystallization of natural cellulose I into cellulose II during the reaction process, which is the primary obstacle to the complete liquefaction of bamboo sawdust by solid acid. Overall, these findings are valuable for the high value utilization of waste bamboo sawdust in the pulp and paper industry, as well as the application of solid acid catalytic technology for biomass.

4.
Front Biosci (Landmark Ed) ; 29(3): 91, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38538254

RESUMO

OBJECTIVE: The morphology and functions of the human trabecular meshwork (HTM) are dysregulated in glaucoma, and the molecular mechanisms of this dysregulation remain unknown. According to an established in vitro model, whose function was to study the regulatory networks sustaining the response of HTM cells to the increased substrate stiffness, we systematically analyzed the expression pattern of long noncoding RNAs (lncRNAs), the important regulatory RNAs in cells. METHODS: Bioinformatics analysis was performed to identify the dysregulated lncRNAs in response to increased substrate stiffness using transcriptome sequencing data (RNA-seq). Then we interfered with the expression of several dysregulated lncRNAs in HTM cells to explore their molecular targets. The cross-linking immunoprecipitation and sequencing method (CLIP-seq) was used to identify enhancer of zeste homolog 2 (EZH2)-targeted RNAs in HTM cells. The chromatin IP and sequencing method (ChIP-seq) was used to identify the targets of EZH2 and histone H3 at lysine 27 (H3K27me3). RESULTS: The response of thousands of dysregulated lncRNAs to increased substrate stiffness was identified through RNA-seq. Functional prediction of these lncRNAs revealed that they potentially regulated key biological processes, including extracellular matrix (ECM) organization. By interfering with the expression of lncRNA SHNG8, ZFHX4-AS1, and RP11-552M11.4, the results demonstrated that those lncRNAs extensively regulated the expression levels of ECM-associated genes. Moreover, we found that EZH2 expression was significantly decreased at high substrate stiffness. Using CLIP-seq to identify EZH2-targeted RNAs in HTM cells, we found that SNHG8 was bound by EZH2. According to the CLIP-seq data of EZH2, we found that EZH2 binding sites were observed in the transcripts of SNHG8-regulated genes, but not in the ChIP-seq results of EZH2 and H3K27me3. CONCLUSION: Our results suggest that SNHG8 and EZH2 may cooperate to regulate the expression of a subset of genes by influencing their RNA abundance, explaining how they support HTM cell morphology and high density. This study contributes to the understanding of the alteration of HTM during the progression of glaucoma by identifying functional lncRNAs, especially SNHG8, and suggests novel therapeutic targets to treat glaucoma.


Assuntos
Glaucoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Histonas/metabolismo , Transcriptoma , Malha Trabecular/metabolismo , Cromatina/metabolismo , Biologia Computacional/métodos , Glaucoma/genética , Glaucoma/metabolismo
5.
BMC Oral Health ; 24(1): 365, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515110

RESUMO

BACKGROUND: Treating white spot lesions (WSLs) with resin infiltration alone may not be sufficient, raising questions about its compatibility with other treatments amid controversial or incomplete data. Therefore, this study aimed to assess the aesthetic feasibility of resin infiltration combined with bleaching, as well as its potential mechanical effect on ceramic bonding to WSLs. METHODS: One hundred and fifty flat enamel surfaces of bovine incisors were prepared. Ninety specimens were deminerailized and randomly assigned to three groups(n = 30): post-bleaching resin infiltration (Bl-R), pre-bleaching resin infiltration (R-Bl), and only resin infiltration (R). Color, surface roughness and microhardness were assessed in immediate, thermocycling and pigmentation tests. The remaining sixty samples were randomly assigned to three groups (n = 20): control (Ctrl), bonding (Bo), pre-bonding resin infiltration (R-Bo). Shear bonding strength, failure mode, micro-leakage depth and interface morphology were evaluated after ceramic bonding. The Tukey test and analysis of variance (ANOVA) were used for statistical analysis. RESULTS: For the effect of resin infiltration and bleaching on WSLs, the R-Bl group showed the worst chromic masking ability, with the highest |ΔL|, |Δa|, |Δb|, and ΔE values after treatment. Compared with those in the Bl-R group, the R-Bl and R groups showed significant time-dependent staining, which is possibly attributed to their surface roughness. For the effect of resin infiltration on the adhesive properties of WSLs, resin infiltration reduced the staining penetration depth of WSLs from 2393.54 ± 1118.86 µm to 188.46 ± 89.96 µm (P < 0.05) while reducing WSLs porosity in SEM observation. CONCLUSIONS: Post-bleaching resin infiltration proved to be advantageous in the aesthetic treatment of WSLs. Resin infiltration did not compromise bonding strength but it did reduce microleakage and enhance marginal sealing. Overall, resin infiltration can effectively enhance the chromatic results of treated WSLs and prevent long-term bonding failure between ceramics and enamel. Based on these findings, the use of post-bleaching resin infiltration is recommended, and resin infiltration before ceramic bonding is deemed viable in clinical practice.


Assuntos
Cárie Dentária , Resinas Sintéticas , Humanos , Animais , Bovinos , Resinas Sintéticas/uso terapêutico , Cárie Dentária/terapia , Estética Dentária , Esmalte Dentário , Cerâmica
6.
Phys Chem Chem Phys ; 25(29): 20026-20031, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37461911

RESUMO

All-dielectric sensors featuring low-loss resonances have been proposed instead of plasmonic-based sensors. However, reported dielectric-based sensors generally work in the visible and near-infrared regions and detect the intensity variation of resonant modes because the electromagnetic energy is mainly confined inside dielectric nanoparticles. It is a challenge to adjust the hotspots from the inside to the surface of the all-dielectric metasurface. In this study, highly uniform Si3N4 all-dielectric metasurfaces have been successfully fabricated as sensing platforms by utilizing nanosphere self-assembly and plasma enhanced chemical vapor deposition techniques. Experimental and simulated results demonstrate that proposed Si3N4 all-dielectric metasurfaces exhibit multiple optical resonant modes in the ultraviolet and visible wavelength and present distinct field-confinement in the gaps of nanoparticles. The hotspots have been successfully adjusted to the surface of Si3N4 nanoparticles. Delightedly, Si3N4 all-dielectric metasurfaces show characteristic wavelength shifts with variation of the refractive index, and the sensitivity can reach 707 nm per RIU for trace detection as sensing substrates. Proposed Si3N4 all-dielectric metasurfaces are promising to act as high-sensitive sensing substrates in the ultraviolet and visible wavelength with the ease of high-throughput fabrication.

7.
Ageing Res Rev ; 91: 102023, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37507092

RESUMO

The objective of this systematic review and meta-analysis was to determine if there are sex-based differences in adaptations to resistance exercise training in healthy older adults. Following the screening process, data from 36 studies comparing older males and females (602 males; 703 females; ≥60 years of age) for changes in skeletal muscle size, muscle strength, and/or physical performance following the same resistance exercise training intervention were extracted. Mean study quality was 16/29 (modified Downs and Black checklist), considered moderate quality. Changes in absolute upper-body (Effect Size [ES] = 0.81 [95% CI 0.54, 1.09], P < 0.001), and lower-body (ES = 0.40 [95% CI 0.24, 0.56], P < 0.001) strength were greater in older males than females. Alternatively, changes in relative upper-body (ES = -0.46 [95% CI -0.77, -0.14], P < 0.01), and lower-body (ES = -0.24 [95% CI -0.42, -0.06], P < 0.01) strength were greater in older females than males. Changes in absolute, but not relative, whole-body fat-free mass (ES = 0.18 [95% CI 0.04, 0.33], P < 0.05) were greater in older males than females. There were no sex-based differences for absolute or relative changes in limb muscle size, muscle fiber size, or physical performance.


Assuntos
Treinamento Resistido , Masculino , Feminino , Humanos , Idoso , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Força Muscular/fisiologia , Desempenho Físico Funcional
8.
STAR Protoc ; 4(1): 102065, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36853688

RESUMO

Kupffer cells (KCs) are the major sentinels to guard the bloodstream by recognizing diverse microbial ligands of blood-borne pathogens. Here, we establish a protocol for identifying the KC receptors recognizing the capsular polysaccharides (CPSs) of low-virulence Streptococcus pneumoniae in a mouse model. This protocol includes preparation of CPS-coated microspheres and KC membrane proteins, affinity pulldown of CPS-binding proteins, and functional validation of the CPS receptors. This protocol provides a platform to investigate the receptor-ligand interactions between KCs and encapsulated bacteria. For complete details on the use and execution of this protocol, please refer to An et al. (2022).1.


Assuntos
Streptococcus pneumoniae , Animais , Camundongos , Streptococcus pneumoniae/metabolismo
9.
J Opt Soc Am A Opt Image Sci Vis ; 39(5): 793-799, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215439

RESUMO

In order to meet the demand for broadband absorbers in the infrared transparent window of the atmosphere, we designed an ultrabroadband metamaterial absorber (MA), which is composed of a germanium-zinc sulfide-chromium-zinc sulfide (Ge-ZnS-Cr-ZnS) disk periodic array and a chromium (Cr) bottom layer. In the infrared transparent window of the atmosphere, the average absorption of the MA is as high as 99.1%, and ultrabroadband near-perfect absorption is realized. Moreover, the absorber is polarization independent and insensitive to the angle of incidence. The ultrabroadband and high-absorption metamaterial absorber has broad application prospects in solar cells, photodetectors, thermophotovoltaics, and thermal emitters.

10.
Mucosal Immunol ; 15(5): 867-881, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35680973

RESUMO

Timely initiation and termination of inflammatory response after corneal epithelial abrasion is critical for the recovery of vision. The cornea is innervated with rich sensory nerves with highly dense TRPV1 nociceptors. However, the roles of TRPV1+ sensory neurons in corneal inflammation after epithelial abrasion are not completely understood. Here, we found that depletion of TRPV1+ sensory nerves using resiniferatoxin (RTX) and blockade of TRPV1 using AMG-517 delayed corneal wound closure and enhanced the infiltration of neutrophils and γδ T cells to the wounded cornea after epithelial abrasion. Furthermore, depletion of TRPV1+ sensory nerves increased the number and TNF-α production of corneal CCR2+ macrophages and decreased the number of corneal CCR2- macrophages and IL-10 production. In addition, the TRPV1+ sensory nerves inhibited the recruitment of neutrophils and γδ T cells to the cornea via RAMP1 and SSTR5 signaling, decreased the responses of CCR2+ macrophages via RAMP1 signaling, and increased the responses of CCR2- macrophages via SSTR5 signaling. Collectively, our results suggest that the TRPV1+ sensory nerves suppress inflammation to support corneal wound healing via RAMP1 and SSTR5 signaling, revealing potential approaches for improving defective corneal wound healing in patients with sensory neuropathy.


Assuntos
Lesões da Córnea , Proteína 1 Modificadora da Atividade de Receptores , Receptores de Somatostatina , Canais de Cátion TRPV , Animais , Córnea , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Receptores de Somatostatina/metabolismo , Canais de Cátion TRPV/metabolismo , Cicatrização
11.
Exp Eye Res ; 220: 109111, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35569517

RESUMO

PURPOSE: Thyroid hormones have a critical role in maintaining metabolic and physiological homeostasis. However, understanding of the possible effects of thyroid dysfunction on corneal homeostasis and the wound healing process is quite limited. To explore the influence of hypothyroidism on corneal homeostasis and the post-wound repair processes of the murine cornea. METHODS: A hypothyroidism model was established by total thyroidectomy (TThy) in C57BL/6J mice. On day 10 after TThy, hypothyroidism was confirmed via thyronine (T3 and T4) and thyroid-stimulating hormone serum levels. We further assessed changes in corneal thickness, corneal sensitivity, sub-basal nerve density, and the corneal expression of thyroid hormone receptors. A corneal epithelial abrasion model was established via mechanical removal of a central epithelium 2 mm in diameter. Wound closure and recruitment of inflammatory cells (neutrophils and γδ T-cells) were evaluated. RNA-sequencing and gene set enrichment analysis were performed in injured corneas after abrasion. The effect of local T3 administration on corneal wound healing in thyroidectomized mice was also observed. RESULTS: Compared with sham-operated control mice, the TThy-treated mice showed the following: (1) a significant decrease in corneal epithelial thickness, sensitivity to external stimuli, and sub-basal nerve density, as well as an alteration in thyroid hormone receptor expression in the steady state; (2) delayed corneal wound repair and enhanced inflammatory response after corneal abrasion; (3) down-regulation of actin-skeleton and DNA replication pathways and up-regulation of inflammation-associated pathways in abraded corneas; and (4) significant restoration of delayed corneal wound repair and inhibition of excessive inflammation following topical T3 administration. CONCLUSIONS: We conclude that deficient thyroid hormone secretion significantly affects corneal homeostasis and post-wound repair processes. Topical T3 administration might have a potential reversal effect on delayed corneal wound repair among hypothyroid individuals.


Assuntos
Lesões da Córnea , Epitélio Corneano , Hipotireoidismo , Animais , Córnea/metabolismo , Lesões da Córnea/metabolismo , Epitélio Corneano/metabolismo , Homeostase , Hipotireoidismo/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização/fisiologia
12.
Exp Eye Res ; 219: 109065, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35421396

RESUMO

Mast cells (MCs) regulate wound healing and are influenced by the autonomic nervous system (ANS). However, the underlying mechanisms affecting wound healing outcomes remain elusive. Here, we explored the specific role of the ANS by regulating MC degranulation following corneal epithelium abrasion. A mouse model of corneal abrasion was established by mechanically removing a 2-mm central epithelium. Wound closure, neutrophil infiltration, and transcription of injured corneas were investigated using whole-mount immunostaining, flow cytometry, and RNA-sequencing analysis, respectively. Inhibition of MC degranulation by the MC stabilizers cromolyn sodium and lodoxamide tromethamine increased the infiltration of neutrophils and delayed healing of abraded corneas. Moreover, transcriptomic profiling analysis showed that purified MCs from the limbus expressed adrenergic and cholinergic receptors. Pharmacological manipulation and sympathectomy with 6-hydroxydopamine confirmed that sympathetic nervous system signaling inhibited MC degranulation after corneal abrasion, whereas parasympathetic nervous system signaling enhanced MC degranulation. We conclude that normal degranulation of MCs in the corneal limbus and crosstalk between the ANS and MCs are crucial for the appropriate control of inflammation and the repair progress of wounded corneas. This suggests a potential approach for improving defective corneal wound healing by the administration of clinically available autonomic activity-modulating agents.


Assuntos
Lesões da Córnea , Epitélio Corneano , Animais , Sistema Nervoso Autônomo , Degranulação Celular , Epitélio Corneano/fisiologia , Inflamação , Mastócitos , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização/fisiologia
13.
Huan Jing Ke Xue ; 43(4): 2030-2038, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393826

RESUMO

It has been verified that, as an emerging contaminant, microplastics are capable of adsorbing certain traditional contaminants like the heavy metal Cd. However, the majority of previous studies only focused on certain types of virgin microplastics, especially for PE and PS. In addition, this adsorption process might be affected by microplastics inevitably undergoing aging and consequent changes in the natural environment. Unfortunately, the relevant reports on aging effects were mainly about organic pollutants, rather than heavy metals. By far, there have been few comprehensive and mechanistic studies on the key aging effects on the Cd adsorption by various types of microplastics. In this study, five representative types of microplastics (i.e., PS, ABS, PP, PVC, and PET) were selected for aging by ultraviolet radiation, and the physicochemical properties of virgin and aged microplastics were thoroughly compared, including specific surface area, crystallinity, surface functional groups, and surface elements. Accordingly, the changes in adsorption isotherms of Cd by microplastics were discussed. The results showed that:① aging induced non-significant changes in specific surface area but a significant decrease in crystallinity. Surface functional groups also changed, including the emergence of a C=O functional group on PS and ABS, the decrease in C=C absorption peak intensity on ABS, and the increase in absorption peak intensities of C=O, C-O, and polar ester groups on PET. Regarding surface C content, C=C/C-C decreased, whereas C-O and O-C=O increased. The total O content and O/C significantly increased as well. ② The Langmuir model well-fitted the adsorption isotherms of Cd by virgin and aged microplastics. Aging significantly expanded the adsorption capacity of Cd by microplastics, as the order of saturated adsorption capacity before aging was ABS (0.2284 mg·g-1)>PVC (0.1360 mg·g-1)>PS (0.1286 mg·g-1)>PP (0.1005 mg·g-1)>PET (0.0462 mg·g-1) and then became PS (0.2768 mg·g-1)>ABS (0.2586 mg·g-1)>PVC (0.1776 mg·g-1)>PP (0.1721 mg·g-1)>PET (0.0951 mg·g-1) after aging. ③ Both crystallinity and surface functional groups played key roles in the adsorption of Cd by microplastics. As for virgin microplastics, crystallinity was negatively correlated with the saturated adsorption capacity of Cd, because the amorphous regions contributed most to Cd adsorption. Aging brought about the decrease in crystallinity and the increase in amorphous regions, which further promoted the oxidation reaction on microplastics. Consequently, oxygen-containing functional groups increased on the surface and eventually expanded the adsorption capacity of Cd by microplastics. Note that certain specific functional groups of various microplastics also had impacts on the adsorption process. These results provide valuable information about the environmental behaviors and interactions of microplastics and heavy metals in nature.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio , Microplásticos , Plásticos/química , Cloreto de Polivinila , Raios Ultravioleta , Poluentes Químicos da Água/análise
14.
J Exp Med ; 219(4)2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35258552

RESUMO

Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) "untouchable" for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.


Assuntos
Células de Kupffer , Infecções Pneumocócicas , Animais , Cápsulas Bacterianas , Cápsulas , Fígado , Camundongos , Streptococcus pneumoniae , Virulência
15.
Opt Express ; 30(2): 1337-1350, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209296

RESUMO

Efficient control of the phase and polarization of light is of significant importance in modern optics and photonics. However, traditional methods are often accompanied with cascaded and bulky designs that cannot fulfill the ongoing demand for further integrations. Here, a single-layered metasurface composed of nonvolatile phase-change material Ge2Sb2Se4Te1 (GSST) is proposed with tunable spin-orbit interactions in subwavelength scale. According to the spin-dependent destructive or constructive interference, asymmetric transmission for circularly polarized incidence (extinction ratio > 8:1) can be achieved when GSST is in an amorphous state. Moreover, when GSST changes to crystalline state, reversed chiral transmission (extinction ratio > 12:1) can be observed due to the existence of intrinsic chirality. In addition, as the average cross-polarized transmitted amplitude is larger than 85%, arbitrary wavefront manipulations can be achieved in both states simultaneously based on the theory of Pancharatnam-Berry phase. As a proof of concept, several functional metasurface devices are designed and characterized to further demonstrate the validation of our design methodology. It is believed that these multifunctional devices with ultrahigh compactness are promising for various applications including chiroptical spectroscopy, EM communication, chiral imaging, and information encryption.

16.
J Mol Cell Biol ; 13(12): 853-863, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-34562084

RESUMO

The biogenesis of autophagosomes provides the basis for macroautophagy to capture and degrade intracellular cargoes. Binding of the autophagy-related protein ATG8/LC3 to autophagic membranes is essential to autophagosome formation, which involves the specific and dynamic processing of ATG8/LC3 by cysteine protease ATG4. However, to date, the mechanism whereby ATG4 is recruited to the membranes, the interaction of ATG4 and ATG8/LC3 on the membranes, and its role in the growth of phagophore are not completely understood. Here, we used fluorescence recovery after photobleaching to monitor the turnover of GFP-tagged ATG4B and LC3B in living animal cells. The data show that ATG4B localizes to early autophagic membranes in an LC3B-dependent manner. During autophagy, ATG4B and LC3B undergo rapid cytosol/isolation membrane exchange but not at the cytosol/completed autophagosome. In addition, ATG4B activity controls the efficiency of autophagosome formation by impacting the membrane binding/dissociation of LC3B. These data suggest that ATG4 and LC3 play interdependent roles in the formation of autophagosomes.


Assuntos
Autofagossomos , Macroautofagia , Animais , Autofagossomos/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo
17.
ACS Appl Mater Interfaces ; 13(38): 45890-45897, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34520183

RESUMO

Compared with conventional mirrors that behave as isotropic electromagnetic (EM) reflectors, metamirrors composed of periodically aligned artificial meta-atoms exhibit increased degrees of freedom for EM manipulations. However, the functionality of most metamirrors is fixed by design, and how to achieve active EM control is still elusive. Here, we propose a multistate metamirror based on the nonvolatile phase change material Ge2Sb2Te5 (GST) with four distinct functionalities that can be realized in the infrared region by exploiting the temperature-activated phase transition. When varying the crystallinity of GST, the metamirror has the capability to perform as a right-handed circular polarization chiral mirror, a narrowband achiral mirror, a left-handed circular polarization chiral mirror, or a broadband achiral mirror, respectively. The inner physics is further explained by the construction or cancellation of extrinsic two-dimensional chirality. As a proof of concept, experimental verification is carried out and the measured results agree well with their simulated counterparts. Such a multifunctional tunable metamirror could address a wide range of applications from sensing and spectroscopy to analytical chemistry and imaging.

18.
ACS Appl Mater Interfaces ; 13(36): 42917-42926, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34478622

RESUMO

The LiCoO2 cathode undergoes undesirable electrochemical performance when cycled with a high cut-off voltage (≥4.5 V versus Li/Li+). The unstable interface with poor kinetics is one of the main contributors to the performance failure. Hence, a hybrid Li-ion conductor (Li1.5Al0.5Ge1.5P3O12) and electron conductor (Al-doped ZnO) coating layer was built on the LiCoO2 surface. Characterization studies prove that a thick and conductive layer is homogeneously covered on LiCoO2 particles. The coating layer can not only enhance the interfacial ionic and electronic transport kinetics but also act as a protective layer to suppress the side reactions between the cathode and electrolyte. The modified LiCoO2 (HC-LCO) achieves an excellent cycling stability (77.1% capacity retention after 350 cycles at 1C) and rate capability (139.8 mAh g-1 at 10C) at 3.0-4.6 V. Investigations show that the protective layer can inhibit the particle cracks and Co dissolution and stabilize the cathode electrolyte interface (CEI). Furthermore, the irreversible phase transformation is still observed on the HC-LCO surface, indicating the phase transformation of the LiCoO2 surface may not be the main factor for fast performance failure. This work provides new insight of interfacial design for cathodes operating with a high cut-off voltage.

19.
Invest Ophthalmol Vis Sci ; 62(10): 22, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34415987

RESUMO

Purpose: Endogenous and exogenous stressors, including nutritional challenges, may alter circadian rhythms in the cornea. This study aimed to determine the effects of high fructose intake (HFI) on circadian homeostasis in murine cornea. Methods: Corneas of male C57BL/6J mice subjected to 10 days of HFI (15% fructose in drinking water) were collected at 3-hour intervals over a 24-hour circadian cycle. Total extracted RNA was subjected to high-throughput RNA sequencing. Rhythmic transcriptional data were analyzed to determine the phase, rhythmicity, unique signature, metabolic pathways, and cell signaling pathways of transcripts with temporally coordinated expression. Corneas of HFI mice were collected for whole-mounted techniques after immunofluorescent staining to quantify mitotic cell number in the epithelium and trafficking of neutrophils and γδ-T cells to the limbal region over a circadian cycle. Results: HFI significantly reprogrammed the circadian transcriptomic profiles of the normal cornea and reorganized unique temporal and clustering enrichment pathways, but did not affect core-clock machinery. HFI altered the distribution pattern and number of corneal epithelial mitotic cells and enhanced recruitment of neutrophils and γδ-T cell immune cells to the limbus across a circadian cycle. Cell cycle, immune function, metabolic processes, and neuronal-related transcription and associated pathways were altered in the corneas of HFI mice. Conclusions: HFI significantly reprograms diurnal oscillations in the cornea based on temporal and spatial distributions of epithelial mitosis, immune cell trafficking, and cell signaling pathways. Our findings reveal novel molecular targets for treating pathologic alterations in the cornea after HFI.


Assuntos
Ritmo Circadiano/genética , Epitélio Corneano/efeitos dos fármacos , Proteínas do Olho/genética , Frutose/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , RNA/genética , Administração Oral , Animais , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epitélio Corneano/citologia , Proteínas do Olho/biossíntese , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , RNA/metabolismo , Edulcorantes/administração & dosagem , Transcriptoma
20.
Materials (Basel) ; 14(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925768

RESUMO

As promising building blocks for functional materials and devices, metasurfaces have gained widespread attention in recent years due to their unique electromagnetic (EM) properties, as well as subwavelength footprints. However, current designs based on discrete unit cells often suffer from low working efficiencies, narrow operation bandwidths, and fixed EM functionalities. Here, by employing the superior performance of a continuous metasurface, combined with the reconfigurable properties of a phase change material (PCM), a dual-functional meta-grating is proposed in the infrared region, which can achieve a broadband polarization conversion of over 90% when the PCM is in an amorphous state, and a perfect EM absorption larger than 91% when the PCM changes to a crystalline state. Moreover, by arranging the meta-grating to form a quasi-continuous metasurface, subsequent simulations indicated that the designed device exhibited an ultralow specular reflectivity below 10% and a tunable thermal emissivity from 14.5% to 91%. It is believed that the proposed devices with reconfigurable EM responses have great potential in the field of emissivity control and infrared camouflage.

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