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1.
J Rehabil Med ; 55: jrm00367, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633287

RESUMO

BACKGROUND: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear. OBJECTIVE: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children. METHODS: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested. RESULTS: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I-III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differences were found in blood indicators among normal, undernourished and overnourished groups. CONCLUSION: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP.


Assuntos
Paralisia Cerebral , Transtornos de Deglutição , Desnutrição , Criança , Humanos , Estado Nutricional , Paralisia Cerebral/complicações , Estudos Transversais , Índice de Gravidade de Doença
2.
Insects ; 14(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36662013

RESUMO

Clarifying phylogenetic position and reconstructing robust phylogeny of groups using various evidences are an eternal theme for taxonomy and systematics. In this study, the complete mitogenomes of Longzhouacris mirabilis, Ranacris albicornis, and Conophyma zhaosuensis were sequenced using next-generation sequencing (NGS), and the characteristics of the mitogenomes are presented briefly. The mitogenomes of the three species are all circular molecules with total lengths of 16,164 bp, 15,720 bp, and 16,190 bp, respectively. The gene structures and orders, as well as the characteristics of the mitogenomes, are similar to those of other published mitogenomes in Caelifera. The phylogeny of the main subfamilies of Acrididae with prosternal process was reconstructed using a selected dataset of mitogenome sequences under maximum likelihood (ML) and Bayesian inference (BI) frameworks. The results showed that the genus Emeiacris consistently fell into the subfamily Melanoplinae rather than Oxyinae, and the genus Choroedocus had the closest relationship with Shirackiacris of the subfamily Eyprepocnemidinae in both phylogenetic trees deduced from mitogenome protein coding genes (PCGs). This finding is entirely consistent with the morphological characters, which indicate that Emeiacris belongs to Melanoplinae and Choroedocus belongs to Eyprepocnemidinae. In addition, the genera Conophymacris and Xiangelilacris, as well as Ranacris and Menglacris, are two pairs of the closest relatives, but their phylogenetic positions need further study to clarify.

3.
J Am Coll Cardiol ; 81(4): 336-354, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36697134

RESUMO

BACKGROUND: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. OBJECTIVES: We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. METHODS: In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-ßAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. RESULTS: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. CONCLUSIONS: SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).


Assuntos
Aterosclerose , Arterite de Células Gigantes , Infarto do Miocárdio , Arterite de Takayasu , Humanos , Receptores de Somatostatina , Estudos Prospectivos , Fluordesoxiglucose F18 , Inflamação/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética , Vasos Coronários/patologia , Aterosclerose/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacologia
4.
Mitochondrial DNA B Resour ; 8(1): 4-6, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36605185

RESUMO

Primula calliantha subsp. bryophila (Balf. f. et Farrer) W.W. Smith and Forrest (1928) is a perennial alpine species with ornamental value. It is distributed in northwestern Yunnan and adjacent eastern Tibet of China, and northern Myanmar. Here, we sequenced and assembled complete plastid genome of P. calliantha subsp. bryophila, which is a circular molecule of 152,045 bp in length, including a large single-copy region (83,966 bp), a small single-copy region (17,663 bp), and a pair of inverted repeats (25,208 bp). The chloroplast genome contained 113 genes, including 79 protein-coding genes, four rRNA genes, and 30 tRNA genes. The phylogenetic tree based on chloroplast genomes showed the relative relationship of P. calliantha subsp. bryophila and P. calliantha, which further supports P. calliantha subsp. bryophila as a subspecies of P. calliantha in taxonomy. The complete chloroplast (cp) genome of P. calliantha subsp. bryophila provides valuable data for further phylogenetic studies of Primulaceae.

5.
ACS Nano ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36661840

RESUMO

Layered charge-density-wave (CDW) materials have gained increasing interest due to their CDW stacking-dependent electronic properties for practical applications. Among the large family of CDW materials, those with star of David (SOD) patterns are very important due to the potentials for quantum spin liquid and related device applications. However, the spatial extension and the spin coupling information down to the nanoscale remain elusive. Here, we report the study of heterochiral CDW stackings in bilayer (BL) NbSe2 with high spatial resolution. We reveal that there exist well-defined heterochiral stackings, which have inhomogeneous electronic states among neighboring CDW units (star of David, SOD), significantly different from the homogeneous electronic states in the homochiral stackings. Intriguingly, the different electronic behaviors are spatially localized within each SOD with a unit size of 1.25 nm, and the gap sizes are determined by the different types of SOD stackings. Density functional theory (DFT) calculations match the experimental measurements well and reveal the SOD-stacking-dependent correlated electronic states and antiferromagnetic/ferromagnetic couplings. Our findings give a deep understanding of the spatial distribution of interlayer stacking and the delicate modulation of the spintronic states, which is very helpful for CDW-based nanoelectronic devices.

6.
Horm Metab Res ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36638810

RESUMO

Oxaliplatin is a member of the platinum group that is often used to treat glioma, a common type of malignant brain tumor, though it does not come with desirable and notable effects. This study attempted to investigate how ELK3 impacts the oxaliplatin resistance of glioma cells and its molecular mechanism. Bioinformatics analysis was employed to screen mRNAs with differential expression in glioma cells and predict the possible regulator downstream. We used qRT-PCR to detect the expression of ELK3 and RNASEH2A. Dual-luciferase and ChIP assays were adopted to reassure the regulatory relationship between the two. We also evaluated cell viability and sphere formation efficiency through CCK-8 and sphere formation assay and calculated the IC50 value by using CCK-8 assay. The expression of stemness-related proteins (ALDH1 and Nanog) was assessed through western blot. Glioma cells and tissues presented a significantly high expression of ELK3, the knock-down of which would reduce the cell viability, stemness and oxaliplatin resistance dramatically. Bioinformatics analysis predicted RNASEH2A to be the downstream regulator of ELK3. RNASEH2A was remarkably upregulated in glioma tissue and cells. The results from dual luciferase assay and ChIP experiment verified the binding relationship between RNASEH2A promoter region and ELK3. Then through rescue experiments, we confirmed that overexpression of RNASEH2A could compensate for the inhibition of glioma cell progression resulting from the knock-down of ELK3. ELK3 could promote stemness and oxaliplatin resistance of glioma cells by upregulating RNASEH2A, indicating that targeting ELK3/RNASEH2A axis may be a possible solution to overcome oxaliplatin resistance of glioma cells.

7.
Int J Biol Sci ; 19(2): 412-425, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632453

RESUMO

Osteosarcoma is a highly mortal bone tumor, with a high metastatic potential, promoted in part by the enzyme procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2). Increasing level of PLOD2 in osteosarcoma tissue correlates with lymphatic and distant metastasis. The adipokine apelin (APLN) is also found in different cancers and APLN upregulation promotes angiogenesis and metastasis, but its effects on osteosarcoma metastasis are uncertain. We explored APLN functioning in metastatic osteosarcoma. An analysis of records from the Gene Expression Omnibus (GEO) database showed higher levels of APLN expression in osteosarcoma tissue than in normal tissue. Similarly, levels of APLN and PLOD2 mRNA synthesis were upregulated in osteosarcoma tissue. Levels of APLN and PLOD2 protein correlated positively with osteosarcoma clinical stages. APLN increased PLOD2 expression in human osteosarcoma cell lines and cell migration via the mammalian Sterile 20-like kinase 1 (MST1), monopolar spindle-one-binder protein (MOB)1, and YAP cascades, and through hsa_circ_0000004 functioning as a sponge of miR-1303. We also found that knockdown of APLN antagonized lung metastasis in mice with osteosarcoma. APLN may be a therapeutic target in osteosarcoma metastasis.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , Animais , Camundongos , Via de Sinalização Hippo , Apelina/genética , Apelina/metabolismo , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/genética , Mamíferos/metabolismo
8.
J Hazard Mater ; 446: 130643, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36586333

RESUMO

Triphenyl phosphate (TPHP) is a widely used aryl organophosphate flame retardant (OPFR) that has attracted attention due to its frequent detection in the environment and living organisms. To date, the reproductive toxicity of TPHP has been investigated in organisms, but its molecular mechanisms are not fully understood. Caenorhabditis elegans (C. elegans) is the ideal animal for the study of reproductive toxicity following environmental pollutants, with short generation times, intact reproductive structures, and hermaphroditic fertilization. This study aimed to explore the reproductive dysfunction and molecular mechanisms induced by TPHP exposure in C. elegans. Specifically, exposure to TPHP resulted in a reduction in the number of eggs laid and developing embryos in utero, an increase in the number of apoptotic gonadal cells, and germ cell cycle arrest. The JNK signaling pathway is a potential pathway inducing reproductive toxicity following TPHP exposure based on transcriptome sequencing (RNA-seq). Moreover, TPHP exposure induced down-regulation of vhp-1 and kgb-2 gene transcription levels, and the knockout of vhp-1 and kgb-2 in the mutant strains exhibited more severe toxicity in apoptotic gonad cells, embryos, and eggs developing in utero, suggesting that vhp-1 and kgb-2 genes play a crucial role in TPHP-induced reproductive toxicity. Our data provide convergent evidence showing that TPHP exposure results in reproductive dysfunction through the JNK signaling pathway and improve our understanding of the ecotoxicity and toxicological mechanisms of aryl-OPFRs.


Assuntos
Caenorhabditis elegans , Retardadores de Chama , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Sistema de Sinalização das MAP Quinases , Organofosfatos/toxicidade , Retardadores de Chama/toxicidade , Retardadores de Chama/metabolismo
9.
BMC Bioinformatics ; 23(Suppl 7): 518, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457083

RESUMO

BACKGROUND: Self-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information. RESULTS: In this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins. CONCLUSIONS: Extensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.


Assuntos
Evolução Biológica , Biologia Computacional , Humanos , Sequência de Aminoácidos , Matrizes de Pontuação de Posição Específica , Leucócitos , Saccharomyces cerevisiae/genética
10.
Front Oncol ; 12: 1051148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465358

RESUMO

Background: Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-ß and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism. Methods: Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-ß1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-ß1 on breast cancer progression. Results: In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-ß1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-ß1 induced EndMT by activation of TGF-ß and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-ß and Notch signaling pathways. Conclusion: Our findings elucidated the mechanism of TGF-ß1 in the promotion of angiogenesis and progression by EndMT in breast cancer.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36454524

RESUMO

Configuration of street canyon and the wind environment have a great influence on the self-ventilation capacity of the canyon, but the couple-effect of these two factors could not be considered in the previous study. The purpose of this study is to clarify the couple effect of street canyon configuration and wind environment on the ventilation and pollutant dispersion inside the street canyon. For this purpose, five wind directions of α = 90°, 60°, 45°, 30°, and 0° (α is the angle between the approaching wind and street canyon) and three canyon configurations (flat, step-up, and step-down canyons) were considered with numerical simulation and wind-tunnel experiment. Meanwhile, ACH (air exchange rate) and NEV (net escape velocity) were used to evaluate the ventilation capacity of the canyon. The results reveal that the wind direction has a vital influence on the ventilation in the different canyon configurations. Under the parallel wind direction (α = 0°), the airflow and ventilation capacity inside the three canyons are similar. Relative difference of ACH, named as RDA ((ACHasymmetric-ACHsymmetric)/ACHsymmetric [Formula: see text] 100%), is 1.82%. However, under the oblique (α = 30°, 45°, and 60°) and perpendicular wind direction (α = 90°), the airflow of the step-down canyon is very different from the step-up and flat canyons. In step-down canyons, reverse flow occurs under the oblique and perpendicular wind direction, and the strength of the reverse flow increases as α increases. Due to this reverse flow, the ventilation capacity of the step-down canyon is lower than that of the step-up and flat canyons. As for the ventilation capacity in the pedestrian respiration domain, the ventilation capacity of the leeward pedestrian domain (leeward NEV) is higher in the step-down canyon than in the step-up canyon and the flat canyon (when α = 90°, leeward NEV of step-down canyon is 2.47 times the flat canyon). Conversely, the ventilation capacity of the windward pedestrian domain is lower in step-down canyons than in step-up or flat canyon (when α = 90°, windward NEV of step-down canyon is 0.1 times that of step-up canyon). The aforementioned findings are helpful to understand the effects of canyon configurations together with wind directions on the airflow as well as pollutant concentration inside the canyon. Although further researches are still required to provide practical guidelines, this study present effective methodologies to quantify the influences of street configurations and wind directions on street canyon ventilation for urban design purpose.

12.
Insect Sci ; 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36519267

RESUMO

Insect olfactory receptors (iORs) with atypical 7-transmembrane domains, unlike Chordata olfactory receptors, are not in the GPCR protein family. iORs selectively bind to volatile ligands in the environment and affect essential insect behaviors. In this study, we constructed a new platform (iORbase, https://www.iorbase.com) for the structural and functional analysis of iORs based on a combined algorithm for gene annotation and protein structure prediction. Moreover, it provides the option to calculate the binding affinities and binding residues between iORs and pheromone molecules by virtual screening of docking. Furthermore, iORbase supports the automatic structural and functional prediction of user-submitted iORs or pheromones. iORbase contains the well-analyzed results of approximately 6 000 iORs and their 3D protein structures identified from 59 insect species and 2 077 insect pheromones from the literature, as well as approximately 12 million pairs of simulated interactions between functional iORs and pheromones. We also built 4 online modules, iORPDB, iInteraction, iModelTM, and iOdorTool to easily retrieve and visualize the 3D structures and interactions. iORbase can help greatly improve the experimental efficiency and success rate, identify new insecticide targets, or develop electronic nose technology. This study will shed light on the olfactory recognition mechanism and evolutionary characteristics from the perspectives of omics and macroevolution.

13.
Plants (Basel) ; 11(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36501381

RESUMO

In this paper, a novel point cloud segmentation and completion framework is proposed to achieve high-quality leaf area measurement of melon seedlings. In particular, the input of our algorithm is the point cloud data collected by an Azure Kinect camera from the top view of the seedlings, and our method can enhance measurement accuracy from two aspects based on the acquired data. On the one hand, we propose a neighborhood space-constrained method to effectively filter out the hover points and outlier noise of the point cloud, which can enhance the quality of the point cloud data significantly. On the other hand, by leveraging the purely linear mixer mechanism, a new network named MIX-Net is developed to achieve segmentation and completion of the point cloud simultaneously. Different from previous methods that separate these two tasks, the proposed network can better balance these two tasks in a more definite and effective way, leading to satisfactory performance on these two tasks. The experimental results prove that our methods can outperform other competitors and provide more accurate measurement results. Specifically, for the seedling segmentation task, our method can obtain a 3.1% and 1.7% performance gain compared with PointNet++ and DGCNN, respectively. Meanwhile, the R2 of leaf area measurement improved from 0.87 to 0.93 and MSE decreased from 2.64 to 2.26 after leaf shading completion.

14.
Microbiome ; 10(1): 245, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36581858

RESUMO

BACKGROUND: The early life gut microbiome is crucial in maintaining host metabolic and immune homeostasis. Though neonates with critical congenital heart disease (CCHD) are at substantial risks of malnutrition and immune imbalance, the microbial links to CCHD pathophysiology remain poorly understood. In this study, we aimed to investigate the gut microbiome in neonates with CCHD in association with metabolomic traits. Moreover, we explored the clinical implications of the host-microbe interactions in CCHD. METHODS: Deep metagenomic sequencing and metabolomic profiling of paired fecal samples from 45 neonates with CCHD and 50 healthy controls were performed. The characteristics of gut microbiome were investigated in three dimensions (microbial abundance, functionality, and genetic variation). An in-depth analysis of gut virome was conducted to elucidate the ecological interaction between gut viral and bacterial communities. Correlations between multilevel microbial features and fecal metabolites were determined using integrated association analysis. Finally, we conducted a subgroup analysis to examine whether the interactions between gut microbiota and metabolites could mediate inflammatory responses and poor surgical prognosis. RESULTS: Gut microbiota dysbiosis was observed in neonates with CCHD, characterized by the depletion of Bifidobacterium and overgrowth of Enterococcus, which was highly correlated with metabolomic perturbations. Genetic variations of Bifidobacterium and Enterococcus orchestrate the metabolomic perturbations in CCHD. A temperate core virome represented by Siphoviridae was identified to be implicated in shaping the gut bacterial composition by modifying microbial adaptation. The overgrowth of Enterococcus was correlated with systemic inflammation and poor surgical prognosis in subgroup analysis. Mediation analysis indicated that the overgrowth of Enterococcus could mediate gut barrier impairment and inflammatory responses in CCHD. CONCLUSIONS: We demonstrate for the first time that an aberrant gut microbiome associated with metabolomic perturbations is implicated in immune imbalance and adverse clinical outcomes in neonates with CCHD. Our data support the importance of reconstituting optimal gut microbiome in maintaining host metabolic and immunological homeostasis in CCHD. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Cardiopatias Congênitas , Recém-Nascido , Humanos , Microbioma Gastrointestinal/genética , Inflamação , Bactérias , Disbiose/microbiologia
15.
Mol Metab ; 66: 101647, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36503893

RESUMO

OBJECTIVE: Insulin is a principal metabolic hormone. It regulates a plethora of metabolic pathways in peripheral tissues. The highly homologous insulin-like growth factor 1 (IGF-1), on the other hand, is important for development and growth. Recent studies have shown that insulin and IGF-1 signaling plays fundamental roles in the brain. Loss of insulin or IGF-1 receptors in astrocytes leads to altered glucose handling, mitochondrial metabolism, neurovascular coupling, and behavioral abnormalities in mice. Here, we aim to investigate molecular mechanisms by which insulin and IGF-1 signaling regulates astrocyte functions. METHODS: IR-flox and IRKO primary astrocytes were treated with 100 nM insulin or IGF-1 for 6 h, and their transcriptomes were analyzed. Astrocytes with either IR deletion, IGF1R deletion or both were used to examine receptor-dependent transcriptional regulations using qPCR. Additional immunoblotting and confocal imaging studies were performed to functionally validate pathways involved in protein homeostasis. RESULTS: Using next-generation RNA sequencing, we show that insulin significantly regulates the expression of over 1,200 genes involved in multiple functional processes in primary astrocytes. Insulin-like growth factor 1 (IGF-1) triggers a similar robust transcriptional regulation in astrocytes. Thus, over 50% of the differentially expressed genes are regulated by both ligands. As expected, these commonly regulated genes are highly enriched in pathways involved in lipid and cholesterol biosynthesis. Additionally, insulin and IGF-1 induce the expression of genes involved in ribosomal biogenesis, while suppressing the expression of genes involved in autophagy, indicating a common role of insulin and IGF-1 on protein homeostasis in astrocytes. Insulin-dependent suppression of autophagy genes, including p62, Ulk1/2, and several Atg genes, is blunted only when both IR and IGF1R are deleted. CONCLUSIONS: In summary, insulin and IGF-1 potently suppress autophagy in astrocytes through transcriptional regulation. Both IR and IGF1R can elicit ligand-dependent transcriptional suppression of autophagy. These results demonstrate an important role of astrocytic insulin/IGF-1 signaling on proteostasis. Impairment of this regulation in insulin resistance and diabetes may contribute to neurological complications related to diabetes.


Assuntos
Fator de Crescimento Insulin-Like I , Insulina , Animais , Camundongos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , Astrócitos/metabolismo , Regulação da Expressão Gênica , Autofagia/genética
16.
Small ; : e2204747, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585358

RESUMO

As the foremost cause of cancer-related death, metastasis consists of three steps: invasion, circulation, and colonization. Only targeting one single phase of the metastasis cascade may be insufficient since there are many alternative routes for tumor cells to disseminate. Here, to target the whole cascade of metastasis, hybrid erythrocyte and tumor cell membrane-coated nanoparticle (Hyb-NP) is designed with dual functions of increasing circulation time and recognizing primary, circulating, and colonized tumors. After loading with monensin, a recently reported metastasis inhibitor, the delivery system profoundly reduces spontaneous metastasis in an orthotopic breast cancer model. Underlying mechanism studies reveal that Hyb-NP can deliver monensin to its action site in the Golgi apparatus, and in return, monensin can block the exocytosis of Hyb-NP from the Golgi apparatus, forming a reservoir-like subcellular structure. Notably, the Golgi apparatus reservoir displays three vital functions for suppressing metastasis initialization, including enhanced subcellular drug retention, metastasis-related cytokine release inhibition, and directional migration inhibition. Collectively, based on metastasis cascade targeting at the tissue level, further formation of the Golgi apparatus drug reservoir at the subcellular level provides a potential therapeutic strategy for cancer metastasis suppression.

17.
BMC Med ; 20(1): 497, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575511

RESUMO

BACKGROUND: The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren's syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases. METHODS: Untargeted liquid chromatography-tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD (n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis. RESULTS: The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, D-glutamic acid, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine, and hydroxyproline were useful in distinguishing between IgG4-RD, PC, SS, and HC [area under the curve (AUC) = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8). CONCLUSIONS: Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Neoplasias Pancreáticas , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/metabolismo , Doença Relacionada a Imunoglobulina G4/diagnóstico , Prognóstico , Biomarcadores , Neoplasias Pancreáticas/diagnóstico
18.
Artigo em Inglês | MEDLINE | ID: mdl-36554963

RESUMO

The rapidly changing global conditions of the environment and climate have resulted in higher requirements for urban design. Significant annual temperature variations and large day/night temperature differences in cold-region cities leads to high energy consumption. Therefore, it is challenging to achieve low energy consumption in cold-region cities. Urban morphology focuses on the physical elements of urban areas, reflecting the relationship between the city and its environment and the city's response to natural climatic conditions. Building clusters are common in cold regions due to the extreme climate. Thus, it is crucial to study the energy performance of cities by considering urban morphology. This study focuses on four morphological patterns of building clusters: point, linear, courtyard, and mixed patterns. A case study is conducted in Harbin, a cold-region city in China. Samples of the four morphological patterns are extracted, and GIS analysis and manual labeling are used to analyze the dominant morphological patterns of building clusters in cold regions. Average nearest-neighbor analysis is used to obtain quantitative results and determine the prevalence of different morphological patterns of building clusters in cold regions. This process can be used to determine the dominant patterns of urban building clusters and provide a scientific basis for selecting the morphological patterns of new building clusters in cold regions.


Assuntos
Temperatura Baixa , Temperatura , Cidades , China/epidemiologia
19.
Food Chem X ; 16: 100512, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36519110

RESUMO

Non-enzymatic browning induced by polyphenol oxidation is an essential problem during the processing and storage of fruit and vegetable products. Here, the non-enzymatic browning mechanism between catechin (CAT), chlorogenic acid (CQA) and their corresponding quinones was investigated in model systems during the 32-d long-term storage. The results showed that CAT and catechin quinone (CATQ), which contains both A ring with a resorcinol structure and an o-diphenol B ring, are important precursors for browning, while chlorogenic acid (CQA) has a minor effect on browning. Chlorogenic acid quinone (CQAQ)-mediated CAT oxidation (kCAT-degradation = 0.0458 mol·L-1·d-1) was faster than CAT autoxidation (kCAT-degradation = 0.0006 mol·L-1·d-1), and there was no significant difference between CQAQ-mediated CAT oxidation and CATQ-mediated CQA oxidation. These indicate that CQAQ oxidizes CAT to CATQ quickly, and CATQ reacts with CAT subsequently through complex reactions to produce brown pigments in model systems during long-term storage.

20.
Nat Commun ; 13(1): 7646, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36496444

RESUMO

Natural superlattice structures MnBi2Te4(Bi2Te3)n (n = 1, 2, ...), in which magnetic MnBi2Te4 layers are separated by nonmagnetic Bi2Te3 layers, hold band topology, magnetism and reduced interlayer coupling, providing a promising platform for the realization of exotic topological quantum states. However, their magnetism in the two-dimensional limit, which is crucial for further exploration of quantum phenomena, remains elusive. Here, complex ferromagnetic-antiferromagnetic coexisting ground states that persist down to the 2-septuple layers limit are observed and comprehensively investigated in MnBi4Te7 (n = 1) and MnBi6Te10 (n = 2). The ubiquitous Mn-Bi site mixing modifies or even changes the sign of the subtle interlayer magnetic interactions, yielding a spatially inhomogeneous interlayer coupling. Further, a tunable exchange bias effect, arising from the coupling between the ferromagnetic and antiferromagnetic components in the ground state, is observed in MnBi2Te4(Bi2Te3)n (n = 1, 2), which provides design principles and material platforms for future spintronic devices. Our work highlights a new approach toward the fine-tuning of magnetism and paves the way for further study of quantum phenomena in MnBi2Te4(Bi2Te3)n (n = 1, 2) as well as their magnetic applications.


Assuntos
Imãs , Viés
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