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1.
Nucleic Acids Res ; 51(D1): D1150-D1159, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36305818

RESUMO

It is a challenge to efficiently integrate and present the tremendous amounts of single-cell data generated from multiple tissues of various species. Here, we create a new database named SPEED for single-cell pan-species atlas in the light of ecology and evolution for development and diseases (freely accessible at http://8.142.154.29 or http://speedatlas.net). SPEED is an online platform with 4 data modules, 7 function modules and 2 display modules. The 'Pan' module is applied for the interactive analysis of single cell sequencing datasets from 127 species, and the 'Evo', 'Devo', and 'Diz' modules provide comprehensive analysis of single-cell atlases on 18 evolution datasets, 28 development datasets, and 85 disease datasets. The 'C2C', 'G2G' and 'S2S' modules explore intercellular communications, genetic regulatory networks, and cross-species molecular evolution. The 'sSearch', 'sMarker', 'sUp', and 'sDown' modules allow users to retrieve specific data information, obtain common marker genes for cell types, freely upload, and download single-cell datasets, respectively. Two display modules ('HOME' and 'HELP') offer easier access to the SPEED database with informative statistics and detailed guidelines. All in all, SPEED is an integrated platform for single-cell RNA sequencing (scRNA-seq) and single-cell whole-genome sequencing (scWGS) datasets to assist the deep-mining and understanding of heterogeneity among cells, tissues, and species at multi-levels, angles, and orientations, as well as provide new insights into molecular mechanisms of biological development and pathogenesis.


Assuntos
Bases de Dados Factuais , Análise de Célula Única , Humanos , Animais , Evolução Biológica , Plantas/genética , Ecologia
2.
Magn Reson Med ; 92(3): 1095-1103, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38576077

RESUMO

PURPOSE: To develop a method that achieves simultaneous brain and neck time-of-flight (ToF) magnetic resonance angiography (MRA) within feasible scan timeframes. METHODS: Localized quadratic (LQ) encoding is efficient for both signal-to-noise ratio (SNR) and in-flow enhancement. We proposed a spiral multiband LQ method to enable simultaneous intracranial and carotid ToF-MRA within a single scan. To address the venous signal contamination that becomes a challenge with multiband (MB) ToF, tilt-optimized non-saturated excitation (TONE) and partial-Fourier slice selection (PFSS) were further introduced in the LQ framework to mitigate the venous signal and improve artery contrast. A sequential spiral MB and LQ reconstruction pipeline was employed to obtain the brain-and-neck image volumes. RESULTS: The proposed MB method was able to achieve simultaneous brain and neck ToF-MRA within a 2:50-min scan. The complementarily boosted SNR-efficiency by MB and LQ acquisitions allows for the increased spatial coverage without increase in scan time or noticeable compromise in SNR. The incorporation of both TONE and PFSS effectively alleviated the venous contamination with improved small vessel sensitivity. Selection of scan parameters such as the LQ factor and flip angle reflected the trade-off among SNR, blood contrast, and venous suppression. CONCLUSIONS: A novel MB spiral LQ approach was proposed to enable fast intracranial and carotid ToF-MRA with minimized venous corruption. The method has shown promise in MRA applications where large spatial coverage is necessary.


Assuntos
Encéfalo , Angiografia por Ressonância Magnética , Pescoço , Razão Sinal-Ruído , Humanos , Angiografia por Ressonância Magnética/métodos , Pescoço/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Artérias Carótidas/diagnóstico por imagem , Adulto , Masculino
3.
Opt Express ; 32(5): 7484-7494, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439427

RESUMO

This paper investigates the evolutionary dynamics of self-accelerating second-order Hermite complex-variable-function Gaussian (SSHCG) wave packets in a harmonic potential. The periodic variation of the wave packets is discussed via theoretical analysis and numerical simulation. The control variables method is applied to manipulate the distribution factor, cross-phase factor, potential depth, and chirp parameter, enabling the realization of unique propagation dynamics. In three-dimensional models, the SSHCG wave packets exhibit rotational states, featuring butterfly shape, three peaks shape, two polarity shape, elliptical shape, and ring-shaped double-vortex structures. Furthermore, the energy flow and the angular momentum of the wave packets are investigated. Additionally, the performance of the radiation force on a Rayleigh dielectric particle is studied. This investigation results in the emergence of distinct SSHCG wave packet propagation dynamics, and potential applications in optical communications and optical trapping are presented.

4.
FASEB J ; 37(1): e22699, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36520055

RESUMO

Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1-/- MS-Exos reversed it. Furthermore, miRNA microarray and qPCR analysis showed that miR-494-3p was increased in WT MS-Exos while being down regulated in Peli1-/- MS-Exos. Mechanistically, Peli1 promoted miR-494-3p expression via NF-κB/AP-1 in CMs, and then miR-494-3p induced CFs activation by inhibiting PTEN and amplifying the phosphorylation of AKT, SMAD2/3, and ERK. Collectively, our study suggests that CMs Peli1 contributes to myocardial fibrosis via CMs-derived miR-494-3p-enriched exosomes under PO, and provides a potential exosomal miRNA-based therapy for cardiac fibrosis.


Assuntos
Comunicação Celular , Exossomos , Insuficiência Cardíaca , Miócitos Cardíacos , Humanos , Exossomos/genética , Exossomos/metabolismo , Fibrose/etiologia , Fibrose/genética , Fibrose/metabolismo , Fibrose/patologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator de Transcrição AP-1/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Cardiopatias/etiologia , Cardiopatias/genética , Cardiopatias/metabolismo , Cardiopatias/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Comunicação Celular/genética , Comunicação Celular/fisiologia
5.
Mol Psychiatry ; 28(10): 4353-4362, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37479784

RESUMO

The DPYSL2/CRMP2 gene encodes a microtubule-stabilizing protein crucial for neurogenesis and is associated with numerous psychiatric and neurodegenerative disorders including schizophrenia, bipolar disorder, and Alzheimer's disease. DPYSL2 generates multiple RNA and protein isoforms, but few studies have differentiated between them. We previously reported an association of a functional variant in the DPYSL2-B isoform with schizophrenia (SCZ) and demonstrated in HEK293 cells that this variant reduced the length of cellular projections and created transcriptomic changes that captured schizophrenia etiology by disrupting mTOR signaling-mediated regulation. In the present study, we follow up on these results by creating, to our knowledge, the first models of endogenous DPYSL2-B knockout in human induced pluripotent stem cells (iPSCs) and neurons. CRISPR/Cas9-faciliated knockout of DPYSL2-B in iPSCs followed by Ngn2-induced differentiation to glutamatergic neurons showed a reduction in DPYSL2-B/CRMP2-B RNA and protein with no observable impact on DPYSL2-A/CRMP2-A. The average length of dendrites in knockout neurons was reduced up to 58% compared to controls. Transcriptome analysis revealed disruptions in pathways highly relevant to psychiatric disease including mTOR signaling, cytoskeletal dynamics, immune function, calcium signaling, and cholesterol biosynthesis. We also observed a significant enrichment of the differentially expressed genes in SCZ-associated loci from genome-wide association studies (GWAS). Our findings expand our previous results to neuronal cells, clarify the functions of the human DPYSL2-B isoform and confirm its involvement in molecular pathologies shared between many psychiatric diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas , Transtornos do Neurodesenvolvimento , Humanos , Estudo de Associação Genômica Ampla , Células HEK293 , Neurônios , Serina-Treonina Quinases TOR , Isoformas de Proteínas , RNA
6.
PLoS Biol ; 19(9): e3001386, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499638

RESUMO

Plasmodium falciparum, the deadliest causal agent of malaria, caused more than half of the 229 million malaria cases worldwide in 2019. The emergence and spreading of frontline drug-resistant Plasmodium strains are challenging to overcome in the battle against malaria and raise urgent demands for novel antimalarial agents. The P. falciparum formate-nitrite transporter (PfFNT) is a potential drug target due to its housekeeping role in lactate efflux during the intraerythrocytic stage. Targeting PfFNT, MMV007839 was identified as a lead compound that kills parasites at submicromolar concentrations. Here, we present 2 cryogenic-electron microscopy (cryo-EM) structures of PfFNT, one with the protein in its apo form and one with it in complex with MMV007839, both at 2.3 Å resolution. Benefiting from the high-resolution structures, our study provides the molecular basis for both the lactate transport of PfFNT and the inhibition mechanism of MMV007839, which facilitates further antimalarial drug design.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Microscopia Crioeletrônica , Formiatos , Ácido Láctico/metabolismo , Malária Falciparum , Transportadores de Ácidos Monocarboxílicos/química , Nitritos , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Relação Estrutura-Atividade
7.
Infection ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679664

RESUMO

BACKGROUND: The stress hyperglycemia ratio (SHR), adjusted for average glycemic status, is suggested for assessing actual blood glucose levels. Its link with adverse outcomes is known in certain populations, yet its impact on sepsis patients' prognosis is unclear. This study explores the association between SHR and mortality in sepsis. METHODS: We included 13,199 sepsis patients in this study and categorized SHR into distinct groups. Additionally, we utilized restricted cubic spline analysis to evaluate the correlation between SHR as a continuous variable and mortality. The primary outcome was 1-year all-cause mortality. Logistic regression and Cox proportional hazards models were employed to assess the associations between the SHR and both in-hospital mortality and 1-year mortality, respectively. RESULTS: Among the study participants, 4,690 (35.5%) patients died during the 1-year follow-up. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and 1-year mortality. Using an SHR of 0.99 as the reference point, the hazard ratio for predicted 1-year mortality increased by 1.17 (95% CI 1.08 to 1.27) per standard deviation above 0.99, whereas each standard deviation increase predicted the hazard ratio of 0.52 (95% CI 0.39 to 0.69) below 0.99. Furthermore, we found that SHR could enhance the predictive performance of conventional severity scores. CONCLUSION: There exists a U shaped association between SHR and mortality in sepsis patients, where both low and high SHR values are associated with an increased risk of poor outcomes.

8.
Genomics ; 115(6): 110739, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37918455

RESUMO

To study the mitochondrial and cellular responses to physiological and pathological hypoxia, corneal epithelial cells were preconditioned under 21% O2, 8% O2 or 1% O2. The cell survival rate, mitochondrial fluorescence and mitophagy flux were quantified using flow cytometry. After RNA sequencing, gene set enrichment analysis (GSEA) was performed. When the oxygen level decreased from 21% to 8%, mitochondrial fluorescence decreased by 45% (p < 0.001), accompanied by an 80% increase in mitophagy flux (p < 0.001). When the oxygen level dropped to 1%, the cell survival rate and mitochondrial fluorescence decreased, while mitophagy flux further increased (each p < 0.001). Comparison of 1% O2 vs. 21% O2 revealed enrichment of the HYPOXIA hallmark. Most of the significantly enriched mitochondrion-related gene sets were involved in apoptosis. The corresponding foremost leading edge genes belonged to the BCL-2 family. Corneal epithelial cell fate decisions under hypoxia may involve noncanonical pathways of mitophagy.


Assuntos
Epitélio Corneano , Mitofagia , Humanos , Mitofagia/genética , Epitélio Corneano/metabolismo , Hipóxia Celular/genética , Hipóxia/metabolismo , Oxigênio/metabolismo , Mitocôndrias/genética
9.
Nano Lett ; 23(18): 8399-8405, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37339058

RESUMO

Stem cells possess exceptional proliferation and differentiation abilities, making them highly promising for targeted recruitment research in tissue engineering and other clinical applications. DNA is a naturally water-soluble, biocompatible, and highly editable material that is widely used in cell recruitment research. However, DNA nanomaterials face challenges, such as poor stability, complex synthesis processes, and demanding storage conditions, which limit their potential applications. In this study, we designed a highly stable DNA nanomaterial that embeds nucleic acid aptamers in the single strand region. This material has the ability to specifically bind, recruit, and capture human mesenchymal stem cells. The synthesis process involves rolling circle amplification and topological isomerization, and it can be stored for extended periods under varying temperatures and humidity conditions. This DNA material offers high specificity, ease of fabrication, simple preservation, and low cost, providing a novel approach to stem cell recruitment strategies.


Assuntos
Aptâmeros de Nucleotídeos , Nanoestruturas , Humanos , DNA , Engenharia Tecidual
10.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542295

RESUMO

Hedgehog (Hh) signaling is crucial in cardiovascular development and maintenance. However, the biological role of Patched1 (Ptch1), an inhibitory receptor of the Hh signaling pathway, remains elusive. In this study, a Ptch1 ortholog was characterized in Nile tilapia (Oreochromis niloticus), and its function was investigated through CRISPR/Cas9 gene knockout. When one-cell embryos were injected with CRISPR/Cas9 targeting ptch1, the mutation efficiency exceeded 70%. During 0-3 days post fertilization (dpf), no significant differences were observed between the ptch1 mutant group and the control group; at 4 dpf (0 day after hatching), about 10% of the larvae showed an angiogenesis defect and absence of blood flow; from 5 dpf, most larvae exhibited an elongated heart, large pericardial cavity, and blood leakage and coagulation, ultimately dying during the 6-8 dpf period due to the lack of blood circulation. Consistently, multiple differentially expressed genes related to angiogenesis, blood coagulation, and heart development were enriched in the ptch1 mutants. Furthermore, Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.


Assuntos
Ciclídeos , Animais , Ciclídeos/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Transdução de Sinais , Técnicas de Inativação de Genes , Mutação , Receptor Smoothened/genética
11.
J Sci Food Agric ; 104(2): 746-758, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37670420

RESUMO

BACKGROUND: Aconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in traditional Chinese medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non-toxic polysaccharides in this plant have attracted less attention than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were isolated systematically from different plant parts of A. carmichaelii, and their structural features and bioactivity were studied and compared. RESULTS: The neutral fraction isolated from the rootlets differed from those isolated from the lateral and mother roots. It consisted of less starch and more possible mannans, galactans, and/or xyloglucans, being similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type-I rhamnogalacturonan (RG-I) were present in all plant parts of A. carmichaelii. However, more arabinogalactan (AG)-II side chains in the RG-I backbone were present in the aerial parts of the plants, while more amounts of arabinans were found in the roots. Various immunomodulatory effects were observed, determined by complement fixation activity and anti-inflammatory effects on the intestinal epithelial cells of all polysaccharide fractions. CONCLUSION: This study highlighted the diversity of polysaccharides present in A. carmichaelii, especially in the unutilized plant parts, and showed their potential medicinal value. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Aconitum , Alcaloides , Plantas Medicinais , Aconitum/química , Alcaloides/análise , Polissacarídeos/química , China , Raízes de Plantas/química
12.
Curr Issues Mol Biol ; 45(3): 1889-1901, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36975492

RESUMO

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

13.
Magn Reson Med ; 90(5): 2190-2197, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37379476

RESUMO

PURPOSE: The combination of SENSE and spiral imaging with fat/water separation enables high temporal efficiency. However, the corresponding computation increases due to the blurring/deblurring operation across the multi-channel data. This study presents two alternative models to simplify computational complexity in the original full model (model 1). The performances of the models are evaluated in terms of the computation time and reconstruction error. METHODS: Two approximated spiral MRI reconstruction models were proposed: the comprehensive blurring before coil operation (model 2) and the regional blurring before coil operation (model 3), respectively, by altering the order of coil-sensitivity encoding process to distribute signals among the multi-channel coils. Four subjects were recruited for scanning both fully sampled T1 - and T2 -weighted brain image data with simulated undersampling for testing the computational efficiency and accuracy on the approximation models. RESULTS: Based on the examples, the computation time can be reduced to 31%-47% using model 2, and to 39%-56% using model 3. The quality of the water image remains unchanged among the three models, whereas the primary difference in image quality is in the fat channel. The fat images from model 3 are consistent with those from model 1, but those from model 2 have higher normalized error, differing by up to 4.8%. CONCLUSION: Model 2 provides the fastest computation but exhibits higher error in the fat channel, particularly in the high field and with long acquisition window. Model 3, an abridged alternative, is also faster than the full model and can maintain high accuracy in reconstruction.


Assuntos
Processamento de Imagem Assistida por Computador , Água , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Encéfalo/diagnóstico por imagem
14.
Magn Reson Med ; 89(4): 1531-1542, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36480000

RESUMO

PURPOSE: To improve calibrationless parallel imaging using pre-learned subspaces of coil sensitivity functions. THEORY AND METHODS: A subspace-based joint sensitivity estimation and image reconstruction method was developed for improved parallel imaging with no calibration data. Specifically, we proposed to use a probabilistic subspace model to capture prior information of the coil sensitivity functions from previous scans acquired using the same receiver system. Both the subspace basis and coefficient distributions were learned from a small set of training data. The learned subspace model was then incorporated into the regularized reconstruction formalism that includes a sparsity prior. The nonlinear optimization problem was solved using alternating minimization algorithm. Public fastMRI brain dataset was retrospectively undersampled by different schemes for performance evaluation of the proposed method. RESULTS: With no calibration data, the proposed method consistently produced the most accurate coil sensitivity estimation and highest quality image reconstructions at all acceleration factors tested in comparison with state-of-the-art methods including JSENSE, DeepSENSE, P-LORAKS, and Sparse BLIP. Our results are comparable to or even better than those from SparseSENSE, which used calibration data for sensitivity estimation. The work also demonstrated that the probabilistic subspace model learned from T2 w data can be generalized to aiding the reconstruction of FLAIR data acquired from the same receiver system. CONCLUSION: A subspace-based method named JSENSE-Pro has been proposed for accelerated parallel imaging without the acquisition of companion calibration data. The method is expected to further enhance the practical utility of parallel imaging, especially in applications where calibration data acquisition is not desirable or limited.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Aumento da Imagem/métodos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
15.
Clin Genet ; 103(6): 617-624, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36843357

RESUMO

The Popeye domain-containing protein 3 (POPDC3), a transmembrane protein with a unique cyclic adenosine monophosphate (cAMP) binding site, is widely expressed in mammalian tissues, with the highest levels of expression in skeletal muscle. POPDC3 plays a key role in many physiological and pathological processes and is considered a candidate biomarker and potential therapeutic target of cancer. In addition, POPDC3 gene variants have been associated with limb-girdle muscular dystrophy (LGMD) type 26. However, there are only a few studies on the biological role of POPDC3, interacting proteins, potential downstream targets, and regulated signaling pathways. Therefore, this review focuses on the structure of POPDC3 protein, interacting molecules, and the role and mechanism in cancer, and in cardiac and skeletal muscle, and to review the current research progress of POPDC3 and propose possible future study directions.


Assuntos
Músculo Estriado , Distrofia Muscular do Cíngulo dos Membros , Neoplasias , Animais , Humanos , Moléculas de Adesão Celular/genética , Homeostase , Mamíferos/metabolismo , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Músculo Estriado/metabolismo
16.
Opt Express ; 31(11): 17930-17942, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37381514

RESUMO

Described by the fractional Schrödinger equation (FSE) with the parabolic potential, the periodic evolution of the astigmatic chirped symmetric Pearcey Gaussian vortex beams (SPGVBs) is exhibited numerically and some interesting behaviors are found. The beams show stable oscillation and autofocus effect periodically during the propagation for a larger Lévy index (0 < α ≤ 2). With the augment of the α, the focal intensity is enhanced and the focal length becomes shorter when 0 < α ≤ 1. However, for a larger α, the autofocusing effect gets weaker, and the focal length monotonously reduces, when 1 < α ≤ 2. Moreover, the symmetry of the intensity distribution, the shape of the light spot and the focal length of the beams can be controlled by the second-order chirped factor, the potential depth, as well as the order of the topological charge. Finally, the Poynting vector and the angular momentum of the beams prove the autofocusing and diffraction behaviors. These unique properties open more opportunities of developing applications to optical switch and optical manipulation.

17.
J Cardiovasc Pharmacol ; 81(4): 300-316, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36701487

RESUMO

ABSTRACT: Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , RNA Longo não Codificante , Ratos , Animais , RNA Longo não Codificante/genética , RNA Circular , RNA Mensageiro/genética , Células Endoteliais , Sequenciamento do Exoma , Glucose
18.
Environ Res ; 223: 115470, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36775088

RESUMO

Even in the vertical dimension, soil bacterial communities are spatially distributed in a distance-decay relationship (DDR). However, whether this pattern is universal among all soil microbial taxonomic groups, and how body size influences this distribution, remains elusive. Our study consisted of obtaining 140 soil samples from two adjacent ecosystems in the Yellow River Delta (YRD), both nontidal and tidal, and measuring the DDR between topsoil and subsoil for bacteria, archaea, fungi and protists (rhizaria). Our results showed that the entire community generally fitted the DDR patterns (P < 0.001), this was also true at the kingdom level (P < 0.001, with the exception of the fungal community), and for most individual phyla (47/75) in both ecosystems and with soil depth. Meanwhile, these results presented a general trend that the community turnover rate of nontidal soils was higher than tidal soils (P < 0.05), and that the rate of topsoil was also higher than that of subsoil (P < 0.05). Additionally, microbial spatial turnover rates displayed a negative relationship with body sizes in nontidal topsoil (R2 = 0.29, P = 0.009), suggesting that the smaller the body size of microorganisms, the stronger the spatial limitation was in this environment. However, in tidal soils, the body size effect was negligible, probably owing to the water's fluidity. Moreover, community assembly was judged to be deterministic, and heterogeneous selection played a dominant role in the different environments. Specifically, the spatial distance was much more influential, while the soil salinity in these ecosystems was the major environmental factor in selecting the distributions of microbial communities. Overall, this study revealed that microbial community compositions at different taxonomic levels followed relatively consistent distribution patterns and mechanisms in this coastal area.


Assuntos
Bactérias , Microbiota , Bactérias/genética , Solo , Microbiologia do Solo
19.
Int J Med Sci ; 20(12): 1644-1661, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859703

RESUMO

Numerous preclinical models have been developed to advance biomedical research in type 1 diabetes mellitus (T1DM). They are essential for improving our knowledge of T1DM development and progression, allowing researchers to identify potential therapeutic targets and evaluate the effectiveness of new medications. A deeper comprehension of these models themselves is critical not only to determine the optimal strategies for their utilization but also to fully unlock their potential applications in both basic and translational research. Here, we will comprehensively summarize and discuss the applications, advantages, and limitations of the commonly used animal models for human T1DM and also overview the up-to-date human tissue bioengineering models for the investigation of T1DM. By combining these models with a better understanding of the pathophysiology of T1DM, we can enhance our insights into disease initiation and development, ultimately leading to improved therapeutic responses and outcomes.


Assuntos
Pesquisa Biomédica , Diabetes Mellitus Tipo 1 , Animais , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Modelos Animais
20.
Neurol Sci ; 44(10): 3669-3673, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37243793

RESUMO

BACKGROUND: Valproic acid (VPA) is a prevalent antiseizure medication (ASM) used to treat epilepsy. Valproate-related hyperammonemic encephalopathy (VHE) is a type of encephalopathy that can occur during neurocritical situations. In VHE, the electroencephalogram (EEG) displays diffuse slow waves or periodic waves, and there is no generalized suppression pattern. CASE PRESENTATION: We present a case of a 29-year-old female with a history of epilepsy who was admitted for convulsive status epilepticus (CSE), which was controlled by intravenous VPA, as well as oral VPA and phenytoin. The patient did not experience further convulsions but instead developed impaired consciousness. Continuous EEG monitoring revealed a generalized suppression pattern, and the patient was unresponsive. The patient's blood ammonia level was significantly elevated at 386.8 µmol/L, indicating VHE. Additionally, the patient's serum VPA level was 58.37 µg/ml (normal range: 50-100 µg/ml). After stopping VPA and phenytoin and transitioning to oxcarbazepine for anti-seizure and symptomatic treatment, the patient's EEG gradually returned to normal, and her consciousness was fully restored. DISCUSSION: VHE can cause the EEG to display a generalized suppression pattern. It is crucial to recognize this specific situation and not to infer a poor prognosis based on this EEG pattern.


Assuntos
Encefalopatias , Epilepsia , Hiperamonemia , Síndromes Neurotóxicas , Humanos , Feminino , Adulto , Ácido Valproico/efeitos adversos , Anticonvulsivantes/efeitos adversos , Fenitoína/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia/complicações , Encefalopatias/complicações , Eletroencefalografia , Síndromes Neurotóxicas/tratamento farmacológico , Hiperamonemia/induzido quimicamente , Hiperamonemia/tratamento farmacológico
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