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1.
Mol Cells ; 46(1): 57-64, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36697238

RESUMO

In eukaryotic cells, a key RNA processing step to generate mature mRNA is the coupled reaction for cleavage and polyadenylation (CPA) at the 3' end of individual transcripts. Many transcripts are alternatively polyadenylated (APA) to produce mRNAs with different 3' ends that may either alter protein coding sequence (CDS-APA) or create different lengths of 3'UTR (tandem-APA). As the CPA reaction is intimately associated with transcriptional termination, it has been widely assumed that APA is regulated cotranscriptionally. Isoforms terminated at different regions may have distinct RNA stability under different conditions, thus altering the ratio of APA isoforms. Such differential impacts on different isoforms have been considered as post-transcriptional APA, but strictly speaking, this can only be considered "apparent" APA, as the choice is not made during the CPA reaction. Interestingly, a recent study reveals sequential APA as a new mechanism for post-transcriptional APA. This minireview will focus on this new mechanism to provide insights into various documented regulatory paradigms.


Assuntos
Poliadenilação , Transcrição Genética , Isoformas de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regiões 3' não Traduzidas/genética
2.
Mater Today Bio ; 19: 100557, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36714199

RESUMO

Regulatory T cells (Tregs) display great promise in rheumatoid arthritis (RA) therapy. However, their low number and differentiation rate limit their further application in the clinics. In the present study, we first optimized a combination of IL-2, TGF-ß and cyclin dependent kinase inhibitor AS2863619 (IL-2/TGF-ß/AS), which could induce Tregs with high efficiency in vitro. After the induced Tregs (iTregs) were confirmed to suppress lymphocyte proliferation and pro-inflammatory T help cells (Th1 and Th17) activation, a chitosan-stabilized nanoparticle drug delivery system (NDDS) was developed according to the optimized formula of IL-2/TGF-ß/AS. In vivo study, the NDDS was injected into the knees of mice with collagen-induced arthritis (CIA). As a result, the NDDS remarkably reduced the pathological score of the CIA, alleviated the inflammatory cell infiltration and synovial hyperplasia, and minimized cartilage tissue damage in the knee joint of the CIA mice. Mechanically, the NDDS administration promoted Treg differentiation and decreased Th17 production, consequently reversing the ratio of Treg/Th17, and reducing the secretion of TNF-α in the sera, which facilitated to relieve the severity and progression of arthritis. In sum, NDDS capable of efficiently inducing Tregs were constructed successfully and provided a potential platform for treating RA by restoring the equilibrium of Treg/Th17 destroyed in RA.

3.
Int J Nanomedicine ; 18: 437-453, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718193

RESUMO

Background: Ocular vascular diseases are the major causes of visual impairment, which are characterized by retinal vascular dysfunction and robust inflammatory responses. Traditional anti-angiogenic or anti-inflammatory drugs still have limitations due to the short-acting effects. To improve the anti-angiogenic or anti-inflammatory efficiency, a dual-drug nanocomposite formulation was proposed for combined anti-angiogenic and anti-inflammatory treatment of ocular vascular diseases. Methods : CBC-MCC@hMSN(SM) complex nanoformulation was prepared by integrating conbercept (CBC, an anti-angiogenic drug) and MCC950 (MCC, an inhibitor of inflammation) into the surface-modified hollow mesoporous silica nanoparticles (hMSN(SM)). CBC-MCC@hMSN(SM) complex nanoformulation was then characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, zeta potentials, and nitrogen adsorption-desorption measurement. CBC and MCC release profile, cytotoxicity, tissue toxicity, anti-angiogenic effects, and anti-inflammatory effects of CBC-MCC@hMSN(SM) were estimated using the in vitro and in vivo experiments. Results:  CBC-MCC@hMSN(SM) complex had no obvious cytotoxicity and tissue toxicity and did not cause a detectable ocular inflammatory responses. CBC-MCC@hMSN(SM) complex was more effective than free CBC or MCC in suppressing endothelial angiogenic effects and inflammatory responses in vitro. A single intraocular injection of CBC-MCC@hMSN(SM) complex potently suppressed diabetes-induced retinal vascular dysfunction, choroidal neovascularization, and inflammatory responses for up to 6 months. Conclusion : Combined CBC and MCC nanoformulation provides a promising strategy for sustained suppression of pathological angiogenesis and inflammatory responses to improve the treatment outcomes of ocular vascular diseases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36719427

RESUMO

PURPOSE: The aim of this study was to evaluate the impact of the spatial heterogeneity of prostate-specific membrane antigen (PSMA) uptake on circulating tumor DNA (ctDNA) characteristics and the response rate to new hormonal agent (NHA) treatment. METHODS: This retrospective study included 153 patients with metastatic castration-resistant prostate cancer (mCRPC) who underwent gallium-68 [68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and ctDNA sequencing with a less than 2-week interval. SUVhetero was defined as the variance of SUVmean for each PSMA-positive lesion. SUVmax-mean was obtained by subtracting the SUVmax by the SUVmean. Patients receiving abiraterone treatment after [68 Ga]Ga-PSMA-11 PET/CT and ctDNA sequencing and with complete follow-up record were included into prostate-specific antigen (PSA) response rate analysis. PSA response was defined as a reduction of greater than 50% from baseline. RESULTS: The ctDNA detection rate was 65% (100/153). Higher SUVhetero value contributed to higher ctDNA% (Spearman's rho = 0.278, p < 0.002). A total of 60 patients were included in PSA response rate analysis. The median follow-up was 19.3 (IQR 16.2-23.2) months. Compare to patients with higher SUVhetero value, patients with NA SUVhetero had a higher PSA response rate (52% vs. 90%, p = 0.036). A higher SUVmax-mean value was strongly correlated with higher SUVhetero (Spearman's rho = 0.833, p < 0.0001). Patients with higher SUVmax-mean value also had a higher PSA response rate compared to patients with lower SUVmax-mean value (83.3% vs. 53.3%, p = 0.024). An external cohort confirmed baseline SUVmax-mean value was associated with enzalutamide treatment response rate. Patients with alterations in AR, DNA damage repair pathway, TP53, AR-associated pathway, cell cycle pathway, or WNT pathway had higher SUVmax-mean value compared to those without (p < 0.05). CONCLUSION: Spatial heterogeneity of the PSMA uptake was associated with ctDNA characteristics and response rate to NHA treatment.

5.
Adv Mater ; : e2211579, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637436

RESUMO

Induction of immunogenic cell death (ICD) plays crucial roles in cancer immunotherapy, whereas its efficacy is severely compromised by redundant antioxidant defenses in cancer cells and aberrant lipid metabolism in immunosuppressive cell populations. Herein, we find that hollow mesoporous CuS nanoparticles (NPs) possess an intrinsic capacity of inhibiting the glutathione peroxidase 4 (GPX4). When loaded with an inhibitor of the ferroptosis suppressor protein 1 (FSP1), these NPs block two parallel redox systems and cooperate with near-infrared irradiation to reinforce ICD. We further fabricate a hydrogel co-delivering cancer cell-targeting CuS NPs and immunosuppressive cell-targeting sulfo-N-succinimidyl oleate (SSO) for spatiotemporal lipid intervention. While the CuS NPs augment ICD via synergistic lipid peroxidation, SSO reinstates immune perception via lipid metabolic reprogramming, thereby coordinately triggering robust innate and adaptive immunity to restrain tumor growth, relapse and metastasis. Our study provides an immunometabolic therapy via orchestrated lipid modulation in the tumor milieu. This article is protected by copyright. All rights reserved.

6.
BMC Plant Biol ; 23(1): 9, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604614

RESUMO

BACKGROUND: The Ferula genus encompasses 180-185 species and is one of the largest genera in Apiaceae, with many of Ferula species possessing important medical value. The previous studies provided more information for Ferula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within the Ferula genus, few studies have been conducted using chloroplast genomes, especially for endemic species in China. RESULTS: Comprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification in Ferula and related genera. Phylogenomic analyses with high supports and resolutions showed that Talassia transiliensis and Soranthus meyeri were nested in the Ferula genus, and thus they should be transferred into the Ferula genus. Our phylogenies also indicated the monophyly of subgenera Sinoferula and subgenera Narthex in Ferula genus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to help Ferula species adapt to high-temperatures, strong-light, and drought habitats. CONCLUSION: Plastome data is powerful and efficient to improve the support and resolution of the complicated Ferula phylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful for Ferula to adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution of Ferula.


Assuntos
Ferula , Genoma de Cloroplastos , Genomas de Plastídeos , Filogenia , Evolução Molecular , Genoma de Cloroplastos/genética , Códon/genética
7.
Plant Physiol ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36659854

RESUMO

Bud dormancy is an important trait in geophytes that largely affects their flowering process and vegetative growth after dormancy release. Compared with seed dormancy, the regulation of bud dormancy is still largely unclear. Abscisic acid (ABA) acts as the predominant hormone that regulates the whole dormancy process. In Gladiolus (Gladiolus hybridus), cold storage promotes corm dormancy release (CDR) by repressing ABA biosynthesis and signaling. However, the mechanisms governing ABA-related processes during CDR via epigenetics are poorly understood. Here, we show that class I BASIC PENTACYSTEINE2, (GhBPC2) directly binds to 9-CIS-EPOXYCAROTENOID DIOXYGENASE (GhNCED) and ABA INSENSITIVE5 (GhABI5) loci and down-regulates their expression to accelerate CDR. During CDR, histone modifications change dramatically at the GhBPC2-binding loci of GhABI5 with an increase in H3K27me3 and a decrease in H3K4me3. GhBPC2 is involved in both H3K27me3 and H3K4me3 and fine-tunes GhABI5 expression by recruiting Polycomb Repressive Complex 2 (PRC2) and the chromatin remodeling factor EARLY BOLTING IN SHORT DAYS (GhEBS). These results show GhBPC2 epigenetically regulates corm dormancy release in Gladiolus by mediating GhABI5 expression with PRC2 and GhEBS.

8.
J Colloid Interface Sci ; 636: 588-601, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36669452

RESUMO

Bimetal oxide is a popular defluorinating material. Hexadecyl trimethyl ammonium bromide (CTAB) as a surfactant successfully synthesizes a novel lanthanum-zirconium phosphate to remove fluorine from groundwater. Lanthanum-zirconium phosphate at a Zr/La molar ratio of 2 exhibited a specific surface area of 455.14 m2/g with a wide pore size, which was achieved by incorporating lanthanum into materials and removing CTAB through calcination. The maximum fluoride adsorption capacity is 109.17 mg/g, which is tenfold that of mesostructured zirconium phosphate. Specifically, analysis revealed that mZrP and LamZrP2-1 were amorphous, which is consistent with HAADF-STEM. The fluoride adsorption fitted well with the pseudo-second-order equation model and Langmuir isotherm mode. LamZrP2-1 had potent anti-interference ability without PO43-. Moreover, LamZrP2-1 was reusable for at least six cycles of adsorption-desorption with little influence. The adsorption mechanism of fluoride was discussed by X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance spectroscopy (NMR) analysis, and Fourier transform infrared (FTIR) spectroscopy. Fluoride was captured by LamZrP2-1 via charge attraction, ligand exchange of different bond strengths, and ion exchange. Lanthanum-zirconium phosphate is important not only in the research and development of bimetal oxides but also in the treatment of groundwater for fluoride removal.

10.
Med Image Anal ; 85: 102750, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682153

RESUMO

Accurate and automatic segmentation of individual tooth and root canal from cone-beam computed tomography (CBCT) images is an essential but challenging step for dental surgical planning. In this paper, we propose a novel framework, which consists of two neural networks, DentalNet and PulpNet, for efficient, precise, and fully automatic tooth instance segmentation and root canal segmentation from CBCT images. We first use the proposed DentalNet to achieve tooth instance segmentation and identification. Then, the region of interest (ROI) of the affected tooth is extracted and fed into the PulpNet to obtain precise segmentation of the pulp chamber and the root canal space. These two networks are trained by multi-task feature learning and evaluated on two clinical datasets respectively and achieve superior performances to several comparing methods. In addition, we incorporate our method into an efficient clinical workflow to improve the surgical planning process. In two clinical case studies, our workflow took only 2 min instead of 6 h to obtain the 3D model of tooth and root canal effectively for the surgical planning, resulting in satisfying outcomes in difficult root canal treatments.

11.
Sci Total Environ ; : 161561, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682550

RESUMO

Ecological security has important influence on regional sustainable development. The ecological security of Nanyang, the water source area of the Middle Route of South-to-North Water Diversion Project, was threatened because of surface water pollution. The existing studies had not been able to comprehensively assess the ecological security and future trend of water source area. In order to promote the high-quality development of the follow-up projects of the South-to-North Water Diversion project, it is very important to probe into the current situation and predict the future trend of ecological security in the water source area. Therefore, this paper constructed an ecological security evaluation index system based on the Driving force, Pressure, State, Impact and Response (DPSIR) model, used the combination of Analytic Hierarchy Process and- entropy weighting method to evaluate the ecological security of each district and county in Nanyang from 2000 to 2020, and used the auto regressive integrated moving average (ARIMA) model to predict the ecological security of the water source area from 2021 to 2030. The results demonstrated that: (1) The ecological security of Nanyang had changed from a moderate warning to a general safety, and the ecological security index had improved. The ecological security level of Nanyang would improve continuously from 2021 to 2030. (2) The northwest area and the central area of Nanyang had better ecological security states, while the southeast area wasn't so. Based on the results, the countermeasures for improving ecological security were proposed.

12.
J Magn Reson Imaging ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688928

RESUMO

BACKGROUND: Differentiating hypertrophic cardiomyopathy (HCM) from hypertensive heart disease (HHD) is challenging. PURPOSE: To identify differences between HCM and HHD on a patient basis using MRI. STUDY TYPE: Retrospective. POPULATION: A total of 219 subjects, 148 in phase I (baseline data and algorithm development: 75 HCM, 33 HHD, and 40 controls) and 71 in phase II (algorithm validation: 56 HCM and 15 HHD). FIELD STRENGTH/SEQUENCE: Contrast-enhanced inversion-prepared gradient echo and cine-balanced steady-state free precession sequences at 3.0 T. ASSESSMENT: MRI parameters assessed included left ventricular (LV) ejection fraction (LVEF), LV end systolic and end diastolic volumes (LVESV and LVEDV), mean maximum LV wall thickness (MLVWT), LV global longitudinal and circumferential strain (GRS, GLS, and GCS), and native T1. Parameters, which were significantly different between HCM and HHD in univariable analysis, were entered into a principal component analysis (PCA). The selected components were then introduced into a multivariable regression analysis to model an integrated algorithm (IntA) for screening the two disorders. IntA performance was assessed for patients with and without LGE in phase I (development) and phase II (validation). STATISTICAL TESTS: Univariable regression, PCA, receiver operating curve (ROC) analysis. A P value <0.05 was considered statistically significant. RESULTS: Derived IntA formulation included LVEF, LVESV, LVEDV, MLVWT, and GCS. In LGE-positive subjects in phase l, the cutoff point of IntA ≥81 indicated HCM (83% sensitivity and 91% specificity), with the area under the ROC curve (AUC) of 0.900. In LGE-negative subjects, a higher possibility of HCM was indicated by a cutoff point of IntA ≥84 (100% sensitivity and 82% specificity), with an AUC of 0.947. Validation of IntA in phase II resulted in an AUC of 0.846 in LGE-negative subjects and 0.857 in LGE-positive subjects. DATA CONCLUSION: A per-patient-based IntA algorithm for differentiating HCM and HHD was generated from MRI data and incorporated FT, LGE and morphologic parameters. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

13.
Cell Rep ; 42(1): 112029, 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36689329

RESUMO

Transposons are mobile elements that are commonly silenced to protect eukaryotic genome integrity. In plants, transposable element (TE)-derived inverted repeats (IRs) are commonly found near genes, where they affect host gene expression. However, the molecular mechanisms of such regulation are unclear in most cases. Expression of these IRs is associated with production of 24-nt small RNAs, methylation of the IRs, and drastic changes in local 3D chromatin organization. Notably, many of these IRs differ between Arabidopsis thaliana accessions, causing variation in short-range chromatin interactions and gene expression. CRISPR-Cas9-mediated disruption of two IRs leads to a switch in genome topology and gene expression with phenotypic consequences. Our data show that insertion of an IR near a gene provides an anchor point for chromatin interactions that profoundly impact the activity of neighboring loci. This turns IRs into powerful evolutionary agents that can contribute to rapid adaptation.

14.
Mol Ecol Resour ; 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587992

RESUMO

Chloroplast genomes have been widely used in studying plant phylogeny and evolution. Several chloroplast genome visualization tools have been developed to display the distribution of genes on the genome. However, these tools do not draw features, such as exons, introns, repetitive elements, and variable sites, disallowing in-depth examination of the genome structures. Here, we developed and validated a software package called Chloroplast Genome Viewers (CPGView). CPGView can draw three maps showing (i) the distributions of genes, variable sites, and repetitive sequences, including microsatellites, tandem and dispersed repeats; (ii) the structure of the cis-splicing genes after adjusting the exon-intron boundary positions using a coordinate scaling algorithm, and (iii) the structure of the trans-splicing gene rps12. To test the accuracy of CPGView, we sequenced, assembled, and annotated 31 chloroplast genomes from 31 genera of 22 families. CPGView drew maps correctly for all the 31 chloroplast genomes. Lastly, we used CPGView to examine 5998 publicly released chloroplast genomes from 2513 genera of 553 families. CPGView succeeded in plotting maps for 5882 but failed to plot maps for 116 chloroplast genomes. Further examination showed that the annotations of these 116 genomes had various errors needing manual correction. The test on newly generated data and publicly available data demonstrated the ability of CPGView to identify errors in the annotations of chloroplast genomes. CPGView will become a widely used tool to study the detailed structure of chloroplast genomes. The web version of CPGView can be accessed from http://www.1kmpg.cn/cpgview.

15.
Biosens Bioelectron ; 225: 115073, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36701948

RESUMO

Point-of-care testing (POCT) platforms for microRNA (miRNA) detection have attracted considerable attention in recent years, due to the increasingly important role of miRNA as biomarkers for the diagnosis of many diseases, such as cancers. However, several limitations such as the requirement of enzyme-related amplification system, expensive preservation cost, sophisticated analysis instruments and tedious operations of conventional miRNA biosensing devices severely hinder their widespread applications. In this work, a portable and smart colorimetric analysis platform was developed by employing the ultrathin DNA-gold nanoparticle (AuNP) hybrid hydrogel film as the signaling unit and the enzyme-free entropy-driven dynamic DNA network (EDN) as the signal converter and amplification unit. By programming the DNA sequences of the EDN, the EDN could respond to a specific miRNA, with miRNA-155 or miRNA-21 as the model target, and release a converter DNA with amplified concentration to further trigger the release of AuNPs from the hydrogel film as a colorimetric signal output. To avoid the use of sophisticated spectral instruments, digital analysis based on primary three-color channel (R/G/B) was further introduced by using user-friendly camera and image processing software, and a detection limit at pM level was achieved. Moreover, by introducing H2O2-mediated AuNPs enlargement procedure in the colorimetric analysis platform, the detection limit for miRNA target could further be enhanced to fM level. The POCT platform is also portable and storable with a good storage stability for at least 45 days, suggesting its great potential in practical diagnosis applications.

16.
J Phys Chem A ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703560

RESUMO

Carbon aggregates containing between 10 and 30 atoms preferentially arrange themselves as planar rings. To learn more about this exotic allotrope of carbon, electronic spectra are measured for even cyclo[n]carbon radical cations (C14+-C36+) using two-color photodissociation action spectroscopy. To eliminate spectral contributions from other isomers, the target cyclo[n]carbon radical cations are isomer-selected using a drift tube ion mobility spectrometer prior to spectroscopic interrogation. The electronic spectra exhibit sharp transitions spanning the visible and near-infrared spectral regions with the main absorption band shifting progressively to longer wavelength by ≈100 nm for every additional two carbon atoms. This behavior is rationalized with a Hückel theory model describing the energies of the in-plane and out-of-plane π orbitals. Photoexcitation of smaller carbon rings leads preferentially to neutral C3 and C5 loss, whereas rings larger than C24+ tend to also decompose into two smaller rings, which, when possible, have aromatic stability. Generally, the observed charged photofragments correspond to low energy fragment pairs, as predicted by density functional theory calculations (CAM-B3LYP-D3(BJ)/cc-pVDZ). Using action spectroscopy it is confirmed that C14+ and C18+ photofragments from C28+ rings have cyclic structures.

17.
Science ; : eabj9090, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705538

RESUMO

N6-methyladenosine (m6A) is the most abundant mRNA modification and plays crucial roles in diverse physiological processes. Utilizing a Massively Parallel Assay for m6A (MPm6A), we discover that m6A specificity is globally regulated by "suppressors" that prevent m6A deposition in unmethylated transcriptome regions. We identify Exon Junction Complexes (EJCs) as m6A suppressors that protect exon junction-proximal RNA within coding sequences from methylation and regulate mRNA stability through m6A suppression. EJC suppression of m6A underlies multiple global characteristics of mRNA m6A specificity, with the local range of EJC protection sufficient to suppress m6A deposition in average-length internal exons, but not in long internal and terminal exons. EJC-suppressed methylation sites co-localize with EJC-suppressed splice sites, suggesting that exon architecture broadly determines local mRNA accessibility to regulatory complexes.

18.
Exp Eye Res ; 227: 109385, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36638858

RESUMO

Choroidal neovascularization (CNV) is a typical pathological feature of neovascular age-related macular degeneration and has become a major cause of vision loss in the elderly. Current therapies require repeated intraocular injections of anti-VEGF drugs by inhibiting endothelial angiogenic effects, which is painful and may cause adverse effects on normal vascular and neuronal functions. Herein, we designed a novel retinoid drug, EYE-101, determined its therapeutic effects on CNV, and clarified the anti-angiogenic mechanism. The results show that administration of EYE-101 did not cause obvious cytotoxicity and ocular tissue toxicity at the concentrations less than 5 µM. Topical administration of EYE-101 could reduce choroidal sprouting, suppress laser-induced CNV formation, and decrease pericyte coverages on ocular vessels. Administration of EYE-101 also suppressed endothelial cell proliferation, migration, and tube formation and reduced pericyte proliferation, migration, recruitment towards endothelial cells. EYE-101 exerted its anti-angiogenic effects by targeting endothelial cells and pericytes via antagonizing Wnt/ß-catenin signaling and PDGF signaling. Thus, EYE-101 administration may offer an"one stone and two birds" strategy for the prevention and treatment of ocular neovascular disorders.

19.
Bioact Mater ; 24: 463-476, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36685806

RESUMO

Diabetes mellitus, an epidemic with a rapidly increasing number of patients, always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization, decreased angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Herein, a poly (lactic-co-glycolic acid) (PLGA)-based microneedle patch loaded with magnesium hydride (MgH2) (MN-MgH2) is manufactured for defeating diabetic wounds. The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH2 that can generate hydrogen (H2) and magnesium ions (Mg2+) after reaction with body fluids. The released H2 reduces the production of ROS, transforming the pathological microenvironment induced by diabetes mellitus. Meanwhile, the released Mg2+ promotes the polarization of pro-healing M2 macrophages. Consequently, cell proliferation and migration are improved, and angiogenesis and tissue regeneration are enhanced. Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H2 and Mg2+ locally and sustainably.

20.
ACS Omega ; 8(2): 2398-2405, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36687052

RESUMO

Bubbling carbonation is the most widely used method for production of CaCO3. A structure-controllable preparation of calcium carbonate with homogeneous crystallinity and narrow particle size distribution is generally required. In this work, a gas distributor is designed and fabricated by light-curing three-dimensional (3D) printing technology to optimize the pore size and distribution of the distributor. The printed gas distributor is combined with a home-made glass vessel to form a simple carbonation reactor without the need for stirring. With the optimized gas flow rate and concentration of Ca(OH)2, this reactor produces small-sized bubbles continuously and uniformly. A homogeneous bubble flow regime can be thus easily formed with the printed distributor, which leads to an enhanced production of calcium carbonate at room temperature with a uniform morphology and narrow particle size distribution. The time required for carbonization is significantly reduced as well. The present study extends the 3D printing to the construction of bubbling reactors with broad applications beyond production of CaCO3.

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