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1.
Nat Commun ; 14(1): 1290, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894562

RESUMO

Acquired chemoresistance to proteasome inhibitors is a major obstacle in managing multiple myeloma but key regulators and underlying mechanisms still remain to be explored. We find that high level of HP1γ is associated with low acetylation modification in the bortezomib-resistant myeloma cells using SILAC-based acetyl-proteomics assay, and higher HP1γ level is positively correlated with poorer outcomes in the clinic. Mechanistically, elevated HDAC1 in the bortezomib-resistant myeloma cells deacetylates HP1γ at lysine 5 and consequently alleviates the ubiquitin-mediated protein degradation, as well as the aberrant DNA repair capacity. HP1γ interacts with the MDC1 to induce DNA repair, and simultaneously the deacetylation modification and the interaction with MDC1 enhance the nuclear condensation of HP1γ protein and the chromatin accessibility of its target genes governing sensitivity to proteasome inhibitors, such as CD40, FOS and JUN. Thus, targeting HP1γ stability by using HDAC1 inhibitor re-sensitizes bortezomib-resistant myeloma cells to proteasome inhibitors treatment in vitro and in vivo. Our findings elucidate a previously unrecognized role of HP1γ in inducing drug resistance to proteasome inhibitors of myeloma cells and suggest that targeting HP1γ may be efficacious for overcoming drug resistance in refractory or relapsed multiple myeloma patients.


Assuntos
Antineoplásicos , Mieloma Múltiplo , Humanos , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Inibidores de Proteassoma/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Fatores de Transcrição/farmacologia , Antineoplásicos/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo
2.
J Biotechnol ; 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36948403

RESUMO

d-(-)-Pantolactone (DPL) is a key intermediate for the production of d-(+)-pantothenate (vitamin B5). Deracemization of d,l-pantolactone (D,L-PL) through oxidizing l-(+)-pantolactone (LPL) to ketopantoyl lactone (KPL) and subsequently reducing KPL to DPL is a promising route for synthesizing DPL. Herein, a newly mined l-pantolactone dehydrogenase from Rhodococcus hoagie (RhoLPLDH) was used for the oxidative dehydrogenation of LPL. To alleviate inclusion bodies formed by membrane-bound RhoLPLDH intracellular expression in E. coli, strategies involving chaperone assistance and decreasing induction temperature were used to achieve RhoLPLDH soluble expression. To enhance its activity, directed evolution and hydrophilicity-based engineering yielded increased catalytic activity and thermostability. 1M LPL was efficiently converted to KPL by engineering strain CM5 co-expressing RhoLPLDHL254I/V241I/I156L/F224Q/N164K and chaperone. A "two stages in one-pot" method was employed in deracemization of 1M D,L-PL with 91.2% yield. These results demonstrated that CM5 catalyst exhibits great potential in enzyme cascade deracemization for the production of DPL.

3.
Plant Cell ; 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36881857

RESUMO

Inflorescence branch number is a yield-related trait controlled by cell fate determination in meristems. Two MADS-box transcription factors (TFs)-SISTER OF TM3 (STM3) and JOINTLESS 2 (J2)-have opposing regulatory roles in inflorescence branching. However, the mechanisms underlying their regulatory functions in inflorescence determinacy remain unclear. Here, we characterized the functions of these TFs in tomato (Solanum lycopersicum) floral and inflorescence meristems through chromatin immunoprecipitation and sequencing (ChIP-seq) analysis of their genome-wide occupancy. STM3 and J2 activate or repress the transcription of a set of common putative target genes, respectively, through recognition and binding to CArG box motifs. FRUITFULL1 (FUL1) is a shared putative target of STM3 and J2 and these transcription factors antagonistically regulate FUL1 in inflorescence branching. Moreover, STM3 physically interacts with J2 to mediate its cytosolic redistribution and restricts J2 repressor activity by reducing its binding to target genes. Conversely, J2 limits STM3 regulation of target genes by transcriptional repression of the STM3 promoter and reducing STM3 binding activity. Our study thus reveals an antagonistic regulatory relationship in which STM3 and J2 control tomato inflorescence meristem determinacy and branch number.

4.
Plant J ; 2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36932869

RESUMO

Fruit size and shape are controlled by genes expressed during the early developmental stages of the fruit. Although the function of ASYMMETRIC LEAVES 2 (AS2) in promoting leaf adaxial cell fates has been well characterized in Arabidopsis thaliana, the molecular mechanisms conferring freshy fruit development as a spatial-temporal expression gene in tomato pericarp remain unclear. In the present study, we verified the transcription of SlAS2 and SlAS2L, two homologs of AS2, in the pericarp during early fruit development. Disruption of SlAS2 or SlAS2L caused a significant decrease in pericarp thickness owing to a reduction in the number of pericarp cell layers and cell area, leading to smaller tomato fruit size, which revealed their critical roles in tomato fruit development. In addition, leaves and stamens exhibited severe morphological defects in slas2 and slas2l single mutants, as well as in the double mutants. These results demonstrated the redundant and pleiotropic functions of SlAS2 and SlAS2L in tomato fruit development. Yeast two-hybrid and split-luciferase complementation assays showed that both SlAS2 and SlAS2L physically interact with SlAS1. Molecular analyses further indicated that SlAS2 and SlAS2L regulate various downstream genes in leaf and fruit development, and that some genes participating in the regulation of cell division and cell differentiation in the tomato pericarp are affected by these genes. Our findings demonstrate that SlAS2 and SlAS2L are vital transcription factors required for tomato fruit development.

5.
Cardiovasc Diabetol ; 22(1): 45, 2023 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870978

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) accumulation is associated with multiple cardiometabolic risk factors and prognosis of heart failure with preserved ejection fraction (HFpEF). The correlation between EAT density and cardiometabolic risk and the effect of EAT density on clinical outcome in HFpEF remain unclear. We evaluated the relationship between EAT density and cardiometabolic risk factors, also the prognostic value of EAT density in patients with HFpEF. METHODS: We included 154 HFpEF patients who underwent noncontrast cardiac computed tomography (CT) and all patients received follow-up. EAT density and volume were quantified semi-automatically. The associations of EAT density and volume with cardiometabolic risk factors, metabolic syndrome and the prognostic impact of EAT density were analyzed. RESULTS: Lower EAT density was associated with adverse changes in cardiometabolic risk factors. Each 1 HU increase in fat density, BMI was 0.14 kg/m2 lower (95% CI 0.08-0.21), waist circumference was 0.34 cm lower (95% CI 0.12-0.55), non-HDL-cholesterol was 0.02 mmol/L lower (95% CI 0-0.04), triglyceride was 0.03 mmol/L lower (95% CI 0.01-0.04), fasting plasma glucose was 0.05 mmol/L lower (95% CI 0.02-0.08), TyG index was 0.03 lower (95% CI 0.02-0.04), Log2(TG/HDL-C) was 0.03 lower (95% CI 0.02-0.05), METS-IR was 0.36 lower (95% CI 0.23-0.49), MetS Z-score was 0.04 lower (95% CI 0.02-0.06), and Log2(CACS + 1) was 0.09 lower (95% CI 0.02-0.15). After adjusting for BMI and EAT volume, the associations of non-HDL-cholesterol, triglyceride, fasting plasma glucose, insulin resistance indexes, MetS Z-score, and CACS with fat density remained significant. The area under the curve (AUC) for the presence and severity of metabolic syndrome was greater in EAT density than volume (AUC: 0.731 vs 0.694, 0.735 vs 0.662, respectively). Over a median follow-up of 16 months, the cumulative incidence of heart failure readmission and composite endpoint increased with lower level of EAT density (both p < 0.05). CONCLUSIONS: EAT density was an independent impact factor of cardiometabolic risk in HFpEF. EAT density might have better predictive value than EAT volume for metabolic syndrome and it might have prognostic value in patients with HFpEF.


Assuntos
Insuficiência Cardíaca , Síndrome Metabólica , Humanos , Glicemia , Estudos Prospectivos , Volume Sistólico , Tecido Adiposo
6.
J Immunother Cancer ; 11(3)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36918219

RESUMO

BACKGROUND: Immunotherapies targeting CD38 have demonstrated salient efficacy in relapsed/refractory multiple myeloma (MM). However, loss of CD38 antigen and outgrowth of CD38 negative plasma cells have emerged as a major obstacle in clinics. All-trans retinoic acid (ATRA) has been reported to upregulate CD38 expression, but the mechanism and adaptive genetic background remain unexplored. METHODS: The efficacy of ATRA in upregulating CD38 expression in MM cells is evaluated by flow cytometry. The interaction between NSD2 and the RARα is analyzed by immunoprecipitation, and the nuclear condensation of RARα is evaluated under laser confocal microscope. A graft model of MM is established in NOD.Cg-PrkdcscidIl2rgtm1Wjl /SzJ mice, and the tumor burden is assessed by in vivo fluorescence imaging. RESULTS: We report that ATRA upregulates MM cells CD38 in a non-linear manner, which is t(4;14) translocation dependent, and t(4;14) translocation-induced NSD2 shows positive correlation with ATRA-induced level of, but not with basal level of CD38 expression. Mechanistically, NSD2 interacts with the ATRA receptor, RARα, and protects it from degradation. Meanwhile, NSD2 enhances the nuclear condensation of RARα and modifies the histone H3 dimethylation at lysine 36 on CD38 promoter. Knockdown of NSD2 attenuates the sensitization of MM against ATRA induced CD38 upregulation. Translationally, ATRA is prone to augment the efficacy of anti-CD38 CAR T cells in NSD2high MM cells in vitro and in vivo. CONCLUSION: This study elucidates a mechanism of ATRA in regulating CD38 expression and expands the clinical potential of ATRA in improving immunotherapies against CD38 in patients with MM.Cite Now.


Assuntos
Mieloma Múltiplo , Receptores do Ácido Retinoico , Camundongos , Animais , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Imunoterapia Adotiva , Camundongos Endogâmicos NOD , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Tretinoína/metabolismo , Receptor alfa de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/metabolismo
7.
Adv Mater ; : e2211075, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36897809

RESUMO

Beyond traditional heteroepitaxy, 2D-materials-assisted epitaxy opens opportunities to revolutionize future material integration methods. However, basic principles in 2D-material-assisted nitrides' epitaxy remain unclear, which impedes understanding the essence, thus hindering its progress. Here, the crystallographic information of nitrides/2D material interface is theoretically established, which is further confirmed experimentally. It is found that the atomic interaction at the nitrides/2D material interface is related to the nature of underlying substrates. For single-crystalline substrates, the heterointerface behaves like a covalent one and the epilayer inherits the substrate's lattice. Meanwhile, for amorphous substrates, the heterointerface tends to be a van der Waals one and strongly relies on the properties of 2D materials. Therefore, modulated by graphene, the nitrides' epilayer is polycrystalline. In contrast, single-crystalline GaN films are successfully achieved on WS2 . These results provide a suitable growth-front construction strategy for high-quality 2D-material-assisted nitrides' epitaxy. It also opens a pathway toward various semiconductors heterointegration.

8.
J Agric Food Chem ; 2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-36967580

RESUMO

Glycine-rich flexible peptide linkers have been widely adopted in fusion protein engineering; however, they can hardly be cleaved for the separation of fusion partners unless specific protease recognition sites are introduced. Herein, we report the use of the peptidoglycan-targeting staphylolytic enzyme lysostaphin to directly digest the glycine-rich flexible linkers of various lengths including oligoglycine linkers and (G4S)x linkers, without the incorporation of extra amino acids. Using His-MBP-linker-LbCpf1 as a model substrate, we show that both types of linkers could be digested by lysostaphin, and the digestion efficiency improved with increasing linker length. The enzyme LbCpf1 retained full activity after tag removal. We further demonstrated that the proteolytic activity of lysostaphin could be well maintained under different environmental conditions and in the presence of a series of chemical reagents at various concentrations that are frequently used in protein purification and stabilization. In addition, such a digestion strategy could also be applied to remove the SUMO domain linked to LwCas13a via an octaglycine linker. This study extends the applications of lysostaphin beyond an antimicrobial reagent and demonstrates its potential as a novel, efficient, and robust protease for protein engineering.

9.
Comput Intell Neurosci ; 2023: 4228610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936669

RESUMO

Object detection technology plays a crucial role in people's everyday lives, as well as enterprise production and modern national defense. Most current object detection networks, such as YOLOX, employ convolutional neural networks instead of a Transformer as a backbone. However, these techniques lack a global understanding of the images and may lose meaningful information, such as the precise location of the most active feature detector. Recently, a Transformer with larger receptive fields showed superior performance to corresponding convolutional neural networks in computer vision tasks. The Transformer splits the image into patches and subsequently feeds them to the Transformer in a sequence structure similar to word embeddings. This makes it capable of global modeling of entire images and implies global understanding of images. However, simply using a Transformer with a larger receptive field raises several concerns. For example, self-attention in the Swin Transformer backbone will limit its ability to model long range relations, resulting in poor feature extraction results and low convergence speed during training. To address the above problems, first, we propose an important region-based Reconstructed Deformable Self-Attention that shifts attention to important regions for efficient global modeling. Second, based on the Reconstructed Deformable Self-Attention, we propose the Swin Deformable Transformer backbone, which improves the feature extraction ability and convergence speed. Finally, based on the Swin Deformable Transformer backbone, we propose a novel object detection network, namely, Swin Deformable Transformer-BiPAFPN-YOLOX. experimental results on the COCO dataset show that the training period is reduced by 55.4%, average precision is increased by 2.4%, average precision of small objects is increased by 3.7%, and inference speed is increased by 35%.


Assuntos
Fontes de Energia Elétrica , Redes Neurais de Computação , Humanos , Tecnologia
10.
Front Endocrinol (Lausanne) ; 14: 1143458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950688

RESUMO

Background: Hyperuricemia and right ventricular dysfunction (RVD) are both widespread in heart failure with preserved ejection fraction (HFpEF) patients. RVD is associated with a poor prognosis in HFpEF. The correlation between serum uric acid (UA) levels and right ventricular function is unclear. The prognostic performance of UA in patients with HFpEF needs further validation. Methods and results: A total of 210 patients with HFpEF were included in the study and divided into two groups according to UA level: the normal UA group (≤7 mg/dl) and the high UA group (>7 mg/dl). The variables examined included clinical characteristics, echocardiography, and serum biochemical parameters. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TAPSV). Baseline characteristics were compared between the two groups, and the correlation between baseline UA and RVD was assessed using multifactorial binary logistic regression. Kaplan-Meier curves were used to describe all-cause mortality and heart failure readmission. Results showed that right ventricular function parameters were worse in the high UA group. After adjusting for UA, left ventricular posterior wall thickness (LVPWT), N-terminal B-type natriuretic peptide (NT-proBNP), atrial fibrillation (AF), and low-density lipoprotein cholesterol (LDL-C), UA (odds ratio = 2.028; p < 0.001) was independently associated with RVD, and UA >7 mg/dl (HR = 2.98; p < 0.001) was associated with heart failure readmission in patients with HFpEF. Conclusion: Elevated serum UA is closely associated with RVD and significantly associated with the heart failure readmission rate in patients with HFpEF.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Direita , Humanos , Insuficiência Cardíaca/complicações , Ácido Úrico , Volume Sistólico , Disfunção Ventricular Direita/complicações , Prognóstico , Fatores de Risco
12.
Proc Inst Mech Eng H ; : 9544119231157448, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927106

RESUMO

A temperature exceeding the safety threshold and excessive drilling force occurring during bone drilling may lead to irreversible damage to bone tissue and postoperative complications. Previous studies have shown that vibration-assisted drilling methods could have lower temperatures and drilling forces than those of the conventional drilling method; we hypothesized that the main reason for these reductions stems from the differences in the transient machining processes between conventional and vibration-assisted drilling methods. To investigate these differences, comparative experiments and two-dimensional finite element models were performed and developed. The differences in the transient machining processes were verified by experimentation and clearly exhibited by the finite element models. Compared with the steady cutting process that produced continuous-spiral chips in the conventional drilling method, transient machining in the low-frequency vibration-assisted drilling method was a periodically dynamic cutting-separation process that produced uniform petal chips with specific settings of drilling and vibration parameters. Moreover, the transient machining process in the ultrasonic vibration-assisted drilling method was transformed into a combined action with high-speed impact and negative rake angle cutting processes; this action produced a large proportion of powdery chips. Therefore, it could be concluded that the superposed axial vibration significantly changed the transient machining process and radically changed the mechanical state and thermal environment; these changes were the main reason for the apparent differences in the drilling performance levels.

13.
Front Physiol ; 14: 1062034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36866173

RESUMO

Background and Objective: Bone age detection plays an important role in medical care, sports, judicial expertise and other fields. Traditional bone age identification and detection is according to manual interpretation of X-ray images of hand bone by doctors. This method is subjective and requires experience, and has certain errors. Computer-aided detection can effectually enhance the validity of medical diagnosis, especially with the fast development of machine learning and neural network, the method of bone age recognition using machine learning has gradually become the focus of research, which has the advantages of simple data pretreatment, good robustness and high recognition accuracy. Methods: In this paper, the hand bone segmentation network based on Mask R-CNN was proposed to segment the hand bone area, and the segmented hand bone region was directly input into the regression network for bone age evaluation. The regression network is using an enhancd network Xception of InceptionV3. After the output of Xception, the convolutional block attention module is connected to refine the feature mapping from channel and space to obtain more effective features. Results: According to the experimental results, the hand bone segmentation network model based on Mask R-CNN can segment the hand bone region and eliminate the interference of redundant background information. The average Dice coefficient on the verification set is 0.976. The mean absolute error of predicting bone age on our data set was only 4.97 months, which exceeded the accuracy of most other bone age assessment methods. Conclusion: Experiments show that the accuracy of bone age assessment can be enhancd by using the Mask R-CNN-based hand bone segmentation network and the Xception bone age regression network to form a model, which can be well applied to actual clinical bone age assessment.

14.
Plant Physiol ; 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36747310

RESUMO

Inflorescence architecture directly impacts yield potential in most crops. As a model of sympodial plants, tomato (Solanum lycopersicum) inflorescence exhibits highly structural plasticity. However, the genetic regulatory network of inflorescence architecture in tomato remains unclear. Here, we investigated a modulator of inflorescence branching in tomato, TARGET OF EAT1 (SlTOE1), an APETALA2 (AP2) family member found to be predominantly expressed in the floral meristem (FM) of tomato. sltoe1 knockout mutants displayed highly branched inflorescences and defective floral organs. Transcriptome analysis revealed that SISTER of TM3 (STM3) and certain floral development-related genes were up-regulated in the flower meristem of sltoe1. SlTOE1 could directly bind the promoters of STM3 and TM3 (Tomato MADS-box gene 3) to repress their transcription. Simultaneous mutation of STM3 and TM3 partially restored the inflorescence branching of the sltoe1cr mutants, suggesting that SlTOE1 regulates inflorescence development, at least in part through an SlTOE1-STM3/TM3 module. Genetic analysis showed that SlTOE1 and ENHANCER OF JOINTLESS 2 (EJ2) additively regulate tomato inflorescence branching; their double mutants showed more extensive inflorescence branching. Our findings uncover a pathway controlling tomato inflorescence branching and offer deeper insight in the functions of AP2 subfamily members.

15.
J Am Soc Mass Spectrom ; 34(3): 366-373, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36735536

RESUMO

Flavonoids are polyphenolic secondary metabolites with extensive biological activities and pharmacological effects. Exploring the interactions of flavonoids with proteins may be helpful for understanding their biological processes. Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool to characterize the noncovalent protein-ligand (PL) complexes. However, some protein-flavonoid complexes are labile during electrospray ionization. Here, the labile lysozyme-flavonoid (rutin, icariin, and naringin) complexes were determined by direct ESI-MS without derivation. It has been found that low amounts of N-methylpyrrolidinone and dimethylformamide can protect labile lysozyme-flavonoid complexes away from dissociation during electrospray ionization process. The intact lysozyme-flavonoid complexes were specifically observed in mass spectra, and the measured binding affinities by ESI-MS were matched with the fluorescence data. The effects of additives on the analysis of lysozyme-flavonoid complexes were investigated by ESI-MS, combined with the molecular docking and fluorescence. This strategy was helpful to investigate the labile PL interactions by direct ESI-MS.


Assuntos
Muramidase , Espectrometria de Massas por Ionização por Electrospray , Muramidase/química , Simulação de Acoplamento Molecular , Espectrometria de Massas por Ionização por Electrospray/métodos , Ligantes , Flavonoides/química
16.
ACS Appl Mater Interfaces ; 15(6): 7793-7803, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36745737

RESUMO

Nanomaterials are often used as immunomodulators because they can be tailored by a controllable process. In this work, a complex based on a tetrahedral framework nucleic acid delivery system and MicroRNA-155, known as T-155, is synthesized for the modulation of immunosuppression. In vivo, T-155 ameliorated spleen and thymus damage and hematopoiesis suppression in cyclophosphamide-induced immunosuppressed mice by promoting T-cell proliferation to resist oxidative stress. In vitro, T-155 induced immature dendritic cells (DCs) to differentiate into mature DCs by the ERK1/2 pathway and converted M0 macrophages (Mφ) into the M1 type by the NF-κB pathway to enhance the surveillance capabilities of antigen-presenting cells. The experimental results suggest that T-155 has therapeutic potential as an immunomodulator for immunosuppression.


Assuntos
Macrófagos , MicroRNAs , Camundongos , Animais , Ciclofosfamida/farmacologia , Fatores Imunológicos , Adjuvantes Imunológicos , Células Dendríticas , MicroRNAs/genética , Imunocompetência
17.
Micromachines (Basel) ; 14(2)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36837949

RESUMO

A single-layer multimode metasurface antenna is proposed with a coplanar waveguide (CPW)-fed aperture. The ultra-wideband (UWB) performance is implemented based on a three-step evolution process with the aid of characteristic mode analysis (CMA). Considering the efficient excitation with a fixed feeding structure, the metasurface modal current variation at different frequencies is analyzed and optimized, in addition to that at the resonant frequency. Correspondingly, the metasurface is firstly designed utilizing an array of 4 × 4 patches. Then, the 1 × 3 and the 1 × 1 parasitic patch arrays are located near the edge patches. Finally, every patch is split into two by a center slot along the current distribution of the required polarization. Four resonant modes of the metasurface become more desirable step by step and can be efficiently excited over the entire band. To enhance the impedance matching level, a pair of 5-stage gradient transitions are added to the CPW-fed slot. The slot mode combined with the four modes further improves the bandwidth. The experimental results demonstrate that the proposed antenna exhibits a 3 dB gain bandwidth of over 74% (4.0-8.7 GHz) with a peak gain of 8.2 dBi. The overall dimensions of the prototype are 1.40λ0 × 1.40λ0 × 0.075λ0 (λ0 is the free-space wavelength at 6 GHz).

18.
Biomacromolecules ; 24(2): 1052-1060, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36723425

RESUMO

Antibiotic multiresistance (AMR) has emerged as a major threat to human health as millions of people die from AMR-related problems every year. As has been witnessed during the global COVID-19 pandemic, the significantly increased demand for antibiotics has aggravated the issue of AMR. Therefore, there is an urgent need to find ways to alleviate it. Tetrahedral framework nucleic acids (tFNAs) are novel nanomaterials that are often used as drug delivery platforms because of their structural diversity. This study formed a tFNAs-antibiotic compound (TAC) which has a strong growth inhibitory effect on Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro owing to the increased absorption of antibiotics by bacteria and improved drug movement across cell membranes. We established a mouse model of systemic peritonitis and local wound infections. The TAC exhibited good biosafety and improved the survival rate of severely infected mice, promoting the healing of local infections. In addition to the better transport of antibiotics to the target, the TAC may also enhance immunity by regulating the differentiation of M1 and M2 macrophages, providing a new option for the treatment of infections.


Assuntos
COVID-19 , Staphylococcus aureus Resistente à Meticilina , Ácidos Nucleicos , Infecções Estafilocócicas , Humanos , Camundongos , Animais , Preparações Farmacêuticas , Ácidos Nucleicos/uso terapêutico , Pandemias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
19.
Front Immunol ; 14: 1062590, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36793719

RESUMO

Background: It is well known that periodontitis has an important impact on systemic diseases. The aim of this study was to investigate potential crosstalk genes, pathways and immune cells between periodontitis and IgA nephropathy (IgAN). Methods: We downloaded periodontitis and IgAN data from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify shared genes. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the shared genes. Hub genes were further screened using least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was drawn according to the screening results. Finally, single-sample GSEA (ssGSEA) was used to analyze the infiltration level of 28 immune cells in the expression profile and its relationship with shared hub genes. Results: By taking the intersection of WGCNA important module genes and DEGs, we found that the SPAG4, CCDC69, KRT10, CXCL12, HPGD, CLDN20 and CCL187 genes were the most important cross-talk genes between periodontitis and IgAN. GO analysis showed that the shard genes were most significantly enriched in kinase regulator activity. The LASSO analysis results showed that two overlapping genes (CCDC69 and CXCL12) were the optimal shared diagnostic biomarkers for periodontitis and IgAN. The immune infiltration results revealed that T cells and B cells play an important role in the pathogenesis of periodontitis and IgAN. Conclusion: This study is the first to use bioinformatics tools to explore the close genetic relationship between periodontitis and IgAN. The SPAG4, CCDC69, KRT10, CXCL12, HPGD, CLDN20 and CCL187 genes were the most important cross-talk genes between periodontitis and IgAN. T-cell and B-cell-driven immune responses may play an important role in the association between periodontitis and IgAN.


Assuntos
Glomerulonefrite por IGA , Periodontite , Humanos , Glomerulonefrite por IGA/genética , Transcriptoma , Homologia de Genes , Periodontite/genética , Linfócitos B
20.
Org Lett ; 25(9): 1573-1577, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36825803

RESUMO

Three zigzag BNBNB-embedded anthracene-fused fluoranthenes are synthesized from 1,3,2-benzodiazaboroles through an indole-type N-directed C-H borylation reaction. Single-crystal X-ray diffraction analyses confirm the double bond character of all four alternating B-N bonds and reveal the five-center four-π-electron nature of the BNBNB group. Experimental spectra and density functional theory calculations indicate that borylation remarkably enhances the planarity, extends π-conjugation, and leads to a bathochromic shift in the absorption and emission bands, with remarkable fluorescence quantum yields in solution (92%).

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