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1.
Food Chem ; 316: 126262, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32058191

RESUMO

The composition and structure of starch are important indicators to evaluate the quality of rice, but the effect of protein on structural properties of rice has always been controversial. In the present study, the rheological properties and thermal properties were combined to investigate the effects of protein on mechanical and inner structure changes of rice kernel during cooking. The morphologic changes in overall form and inner structure of the kernel showed the limited and uneven gelatinization of starch, and reflected the good heating stability of protein. The comparison of molecular mobility in H2O/D2O reflected the special gelatinization behavior of starch and the hydrophobicity of protein during cooking. The similar proton distributions between starch, starch-protein mixture and rice flour indicated the weak interactions between starch and protein. The results of Fourier transform infrared spectra, thermogravimetric analysis and transmission electron microscope confirmed the wrapping effect of starch and surface interactions with protein.

2.
Fitoterapia ; 142: 104490, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017968

RESUMO

Privileged structures are widely used in the process of drug design, and provide an effective template in medicinal chemistry. Diarylheptanoids are a class of structurally distinctive compounds with a wide variety of bioactivity, raising keenly interest in the past decades. Turmeric is a golden spice from the rhizome of the plant Curcuma longa, used for food preparations and giving color since ancient times. Curcumin, obtained from turmeric, has showed widely biological abilities with low toxicity in recent studied. Thus, a spice originally common in the kitchen has recently broadened its application to the clinic. This review aims to highlight diarylheptanoid as a privileged scaffold in drug discovery. In this review, we summarized diverse biological and pharmacological effects of diarylheptanoids and explored the therapeutic application and development of diet based on their structure.

3.
Nanotechnology ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32018233

RESUMO

Two dimensional (2D) magnetic layered materials have got considerable attention in memory storage devices due to their exciting magnetic ordering. Herein, the electronic and magnetic properties of high-quality single crystals zirconium diselenide and copper (Cu) doped zirconium diselenide grown through chemical vapor transport technique combined with first principle density functional theory calculation were investigated. A semimetallic state is recognized for Cu0.052Zr0.93Se2 as measured through resistance vs temperature measurements and angle resolved photoemission spectroscopy (ARPES). The magnetic measurement shows diamagnetic semiconductor behaviour for ZrSe2, whereas Cu0.052Zr0.93Se2 exhibits the ferromagnetic semimetal character using perpendicular magnetic field. Cu0.052Zr0.93Se2 reveals the room temperature magnetic moment ~0.0125 emu/g, while their Curie temperature is ~363.49K. Furthermore, first principle density functional theory (DFT) calculations shows energetically long range ferromagnetic ordering in half-metallic Cu-doped ZrSe2, while a diamagnetic state in case of ZrSe2 agrees well with experiment results. These results suggest that due to strong interaction at octahedral site of zirconium atoms when replaced by copper atoms, which can change the spin ordering of electrons and make zirconium vacancy, their magnetic moment is increased. Very importantly the half-metallic character of Cu0.052Zr0.93Se2 promote much spin polarized electron around the Fermi level, suggest significant potential in future memory devices and spintronic applications.

4.
FASEB J ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043676

RESUMO

The development of the neuromuscular junction depends on signaling processes that involve protein phosphorylation. Motor neuron releases agrin to activate muscle protein Dok-7, a key tyrosine kinase essential for the formation of a mature and functional neuromuscular junction. However, the signaling cascade downstream of Dok-7 remains poorly understood. In this study, we combined the clustered regularly interspaced short palindromic repeats/Cas9 technique and quantitative phosphoproteomics analysis to study the tyrosine phosphorylation events triggered by agrin/Dok-7. We found tyrosine phosphorylation level of 36 proteins increased specifically by agrin stimulation. In Dok-7 mutant myotubes, however, 13 of the 36 proteins failed to be enhanced by agrin stimulation, suggesting that these 13 proteins are Dok-7-dependent tyrosine-phosphorylated proteins, could work as downstream molecules of agrin/Dok-7 signaling. We validated one of the proteins, Anxa3, by in vitro and in vivo assays. Knocking down of Anxa3 in the cultured myotubes inhibited agrin-induced AChR clustering, whereas reduction of Anxa3 in mouse muscles induced abnormal postsynaptic development. Collectively, our phosphoproteomics analysis provides novel insights into the complicated signaling network downstream of agrin/Dok-7.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32035861

RESUMO

OBJECTIVE: Primary pseudomyogenic hemangioendothelioma (PMH) of bone is an extremely rare vascular neoplasm. We present here a case of primary PMH occurring in the maxilla. STUDY DESIGN: A 34-year-old man was referred to our hospital for treatment because of possible recurrence after surgery and chemotherapy of a right maxillary malignant tumor. Morphologic features, immunophenotypes, and FOSB gene rearrangement status of the surgically sectioned sample were assessed by hematoxylin-eosin staining, immunohistochemistry, and fluorescence in situ hybridization, respectively. RESULTS: Morphologically, the tumor cells were arranged in a loose fascicular and sheet-like manner, with a large number of reactive woven bones forming. The most striking feature was the presence of epithelioid cells with abundant brightly eosinophilic cytoplasm, which resembled the rhabdomyoblast in appearance. The tumor was diffusely positive for AE1/AE3, CD31, erythroblast transformation-specific transcription factor, and Friend leukemia integration 1; negative for CD34, CAM5.2, epithelial membrane antigen, and desmin; and had retained expression of integrase interactor 1. The tumor harbored FOSB rearrangement. No distant metastasis was found during the follow-up period (18 months). CONCLUSIONS: To the best of our knowledge, this case represents the first report of PMH arising in the maxilla. The distinct morphologic features, immunophenotypes, and FOSB rearrangement could help achieve precise diagnosis and prevent misdiagnosis of mimics with overlapping features.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32013375

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder with a continuous pathophysiological process starting from the preclinical and mild cognitive impairment (MCI) phases to the dementia phase. Early diagnosis is prerequisite for the early intervention of AD but meanwhile challenging. Amyloid-beta 1-42 (Aß42) plays a crucial part in AD pathology. Positron-emission tomography (PET) imaging of Aß42 in the brain and the measurement of Aß42 in the cerebrospinal fluid (CSF) have been adopted for the auxiliary diagnosis of AD, but their widespread clinical application has been limited due to the radiation and the high-cost of PET and the invasive lumbar puncture for collecting CSF. Noninvasive and cost-effective blood-based assay is desirable for the early diagnosis of AD. Here, a label-free assay for the quantification of blood Aß42 was developed using the high-throughput surface plasmon resonance imaging method with the aid of an antibody-mimetic peptoid nanosheet equipping Aß42-recognizing loops. We demonstrated that this nanosheet-based sensor system could distinguish the plasma and sera from normal individuals and patients suffering AD and amnestic MCI with high sensitivity and specificity, preceding the diagnostic performance of the Aß42-recognizing molecule and the antibody specific to Aß42. This work provides a label-free, cost-effective, highly sensitive, and high-throughput blood-based assay for early detection of AD.

7.
J Anim Sci ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999321

RESUMO

The composition of dietary macronutrients (proteins, carbohydrates and fibres) and micronutrients (vitamins, phytochemicals) can markedly influence the development of immune responses to enteric infection. This has important implications for livestock production, where a significant challenge exists to ensure healthy and productive animals in an era of increasing drug resistance and concerns about the sector's environmental footprint. Nutritional intervention may ultimately be a sustainable method to prevent disease and improve efficiency of livestock enterprises, and it is now well-established that certain phytonutrients can significantly improve animal performance during challenge with infectious pathogens. However, many questions remain unanswered concerning the complex interplay between diet, immunity and infection. In this review, we examine the role of phytonutrients in regulating immune and inflammatory responses during enteric bacterial and parasitic infections in livestock, with a specific focus on some increasingly well-studied phytochemical classes - polyphenols (especially proanthocyanidins), essential oil components (cinnamaldehyde, eugenol and carvacrol), and curcumin. Despite the contrasting chemical structures of these molecules, they appear to induce a number of similar immunological responses. These include promotion of mucosal antibody and anti-microbial peptide production, coupled with a strong suppression of inflammatory cytokines and reactive oxygen species. Whilst there have been some recent advances in our understanding of the mechanisms underlying their bioactivity, how these phytonutrients modulate immune responses in the intestine remains mostly unknown. We discuss the complex inter-relationships between metabolism of dietary phytonutrients, the gut microbiota and the mucosal immune system, and propose that an increased understanding of the basic immunological mechanisms involved will allow the rational development of novel dietary additives to promote intestinal health in farmed animals.

8.
Cell Res ; 30(2): 105-118, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31959917

RESUMO

Dominance hierarchy is a fundamental phenomenon in grouped animals and human beings, however, the underlying regulatory mechanisms remain elusive. Here, we report that an antisense long non-coding RNA (lncRNA) of synapsin II, named as AtLAS, plays a crucial role in the regulation of social hierarchy. AtLAS is decreased in the prefrontal cortical excitatory pyramidal neurons of dominant mice; consistently, silencing or overexpression of AtLAS increases or decreases the social rank, respectively. Mechanistically, we show that AtLAS regulates alternative polyadenylation of synapsin II gene and increases synapsin 2b (syn2b) expression. Syn2b reduces AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through a direct binding with AMPAR at the postsynaptic site via its unique C-terminal sequence. Moreover, a peptide disrupting the binding of syn2b with AMPARs enhances the synaptic strength and social ranks. These findings reveal a novel role for lncRNA AtLAS and its target syn2b in the regulation of social behaviors by controlling postsynaptic AMPAR trafficking.

9.
Int J Biol Macromol ; 149: 246-255, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31958556

RESUMO

The pasting behavior of rice starch and its relationship with cooking properties of rice have been extensively studied. However, the viscosity changes of rice starch and flour under conventional cooking mode and high temperature and high pressure (HTHP) mode remain unknown. In this study, three typical rice starches and seven rice flours of different types and varieties were used to evaluate the effect of cooking modes on their pasting behaviors. A detailed discussion about the relationships among chemical composition, thermal properties, and crystallinity were conducted to explain the different pasting behaviors of the rice samples. The pasting behavior of rice starch was found to be similar with rice flour under standard and conventional heating modes, while remarkably different when treated at different HTHP levels, especially for sticky rice flour. The morphological changes of rice samples at 95 °C and 120 °C confirmed that high temperature long time heating caused extending of molecules, which exhibited layered structure at 120 °C. The rice flour samples showed different morphologies after heating at different modes due to varied amylose content and crystallinity, which contributed to different pasting behavior. These results provide useful information for developing strategies to control rice cooking and improve eating quality.

10.
Transbound Emerg Dis ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31968152

RESUMO

Pseudorabies is a disease that seriously endangers the pig industry in China. Recently, we successfully isolated a pseudorabies virus from the brain tissue of piglets at a farm in Sichuan, China, and named it the FJ62 strain. In order to understand the molecular biological characteristics of the strain, primers were designed for glycoproteins gB, gC, gD and gE, which were amplified by a polymerase chain reaction (PCR) and sequenced. After comparing the sequence with the GenBank 22 pseudorabies virus reference strains and establishing the genetic evolutionary tree, it was found that the gB gene of pseudorabies virus was highly homologous (up to 100%) with the MY-1 strain which is isolated from a wild boar in Japan (AP018925) but that homology with other strains in China was low. The gC gene was in the same branch as most of the representative strains in China, with 99.5% homology. The gD gene is in the same branch as the domestic strain LA in China (KU552118), and the homology was 99.9%. The gE gene was in the same branch as the domestic BJ/YT strain in China (KC981239), with 99.9% homology. The results showed that the FJ62 strain of the pseudorabies virus isolated here may be a variant strain of FJ62 isolated from a domestic pig after natural recombination of pseudorabies virus genotype I from wild boar and genotype II from pigs in China. There have been no similar reports in Sichuan. The discovery of the recombinant virus strain provides a reference basis for the prevention and control of pseudorabies and a design strategy for a vaccine in Sichuan, China, in the future.

11.
J Neurochem ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951013

RESUMO

MicroRNAs have been implicated in diverse physiological and pathological processes. We previously reported that aberrant microRNA-124 (miR-124)/non-receptor-type protein phosphatase 1 (PTPN1) signaling plays an important role in the synaptic disorders associated with Alzheimer's disease (AD). In this study, we further investigated the potential role of miR-124/PTPN1 in the tau pathology of AD. We first treated the mice with intra-hippocampal stereotactic injections. Then, we used quantitative real-time reverse transcription PCR (qRT-PCR) to detect the expression of microRNAs. Western blotting was used to measure the level of PTPN1, the level of tau protein, the phosphorylation of tau at AD-related sites, and alterations in the activity of glycogen synthase kinase 3ß (GSK-3ß) and protein phosphatase 2 (PP2A). Immunohistochemistry was also used to detect changes in tau phosphorylation levels at AD-related sites and somadendritic aggregation. Soluble and insoluble tau protein was separated by 70% formic acid (FA) extraction to examine tau solubility. Finally, behavioral experiments (including the Morris water maze, fear conditioning, and elevated plus maze) were performed to examine learning and memory ability and emotion-related behavior. We found that artificially replicating the abnormalities in miR-124/PTPN1 signaling induced AD-like tau pathology in the hippocampus of wild-type mice, including hyperphosphorylation at multiple sites, insolubility and somadendritic aggregation, as well as learning/memory deficits. We also found that disruption of miR-124/PTPN1 signaling was caused by the loss of RE1-silencing transcription factor protein, which can be initiated by Aß insults or oxidative stress, as observed in the brains of P301S mice. Correcting the deregulation of miR-124/PTPN1 signaling rescued the tau pathology and learning/memory impairments in the P301S mice. We also found that miR-124/PTPN1 abnormalities induced activation of glycogen synthase kinase 3 (GSK-3) and inactivation of protein phosphatase 2A (PP2A) by promoting tyrosine phosphorylation, implicating an imbalance in tau kinase/phosphatase. Thus, targeting the miR-124/PTPN1 signaling pathway is a promising therapeutic strategy for AD.

12.
Sci Total Environ ; 713: 136395, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31954249

RESUMO

In this study, the adsorption behaviors and mechanisms of Pb(II) and Zn(II) by animal-derived biochar (ADB) in single and binary metal systems were comparatively investigated. ADB contains considerable amounts of Ca/P components and is mainly composed of hydroxyapatite (HAP), which plays an important role in the adsorption of Pb(II) and Zn(II). The maximum adsorption capacities of Pb(II) and Zn(II) on ADB were in the order of Zn(II)-single (3.23 mmol g-1) > Pb(II)-single (2.74 mmol g-1) ≈ Pb(II)-binary (2.71 mmol g-1) > Zn(II)-binary (2.31 mmol g-1). In the single metal system, approximately 99.9% of the adsorbed Pb(II) existed as Pb5(PO4)3Cl, while the dominant adsorption mechanism of Zn(II) was cation exchange, followed by precipitation, accounting for 78.0%-80.6% and 19.4%-21.5% of the adsorption capacity, respectively. These findings were verified by X-ray diffraction refinement, X-ray photoelectron spectroscopy, metal speciation modeling, and Ca(II) exchange experiment. In the binary metal system, the proportion and form of Pb(II) precipitate remained unchanged. However, the binding of Zn(II) to ADB was completely dependent on the cation exchange with Ca(II), and no remarkable Zn(II) precipitation was observed. Phosphate released from HAP preferentially precipitated with Pb(II) than with Zn(II) when they coexisted. Consequently, Pb(II) competition may alter the Zn(II) adsorption mechanism on ADB. Nonetheless, ADB could serve as an efficient biochar for the simultaneous immobilization of Pb(II) and Zn(II) via different mechanisms.

13.
J Atheroscler Thromb ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31956237

RESUMO

AIM: To examine the association between carotid plaque and variants in genes involved in inflammation and endothelial function. METHODS: This was a multicenter, cross-sectional survey in southwestern China. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in eight communities. A total of 2,377 subjects with high stroke risk were enrolled. Carotid plaque and plaque phenotype were assessed by carotid ultrasound. Genotypes of 19 variants in 10 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). RESULTS: Carotid plaques were found in 852 (35.8%) subjects, and 454 (53.3%) had stable plaques, whereas 398 (46.7%) had vulnerable plaques. PPARA rs4253655, HABP2 rs7923349, and IL1A rs1609682 were associated with the presence of carotid plaque, and NOS2A rs2297518 and PPARA rs4253655 were associated with vulnerable plaque in univariate analysis. The GMDR analysis revealed that there was a significant gene-gene interaction among HABP2 rs7923349, ITGA2 rs1991013, IL1A rs1609682, and NOS2A rs8081248, and the high-risk interactive genotype among the four variants was independently associated with a higher risk of carotid vulnerable plaque after adjusting the covariates (OR, 2.86, 95% CI: 1.32-7.13, P=0.003). CONCLUSION: The prevalence of carotid plaque was very high in the high-risk stroke population in southwestern China. Variants in genes involved in the endothelial function and inflammation were associated with the carotid plaque. The high-risk interactive genotype among rs7923349, rs1991013, rs1609682, and rs8081248 was independently associated with a higher risk of vulnerable plaque.

14.
Eur J Med Genet ; : 103851, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31953237

RESUMO

Only eleven SPECC1L mutations have been reported worldwide which were associated with autosomal dominant oblique facial clefts, Opitz G/BBB Syndrome and Teebi hypertelorism syndrome. In this study, we reported the first Chinese patient with Teebi hypertelorism syndrome. Utilizing whole exome sequencing and Sanger sequencing, we identified a de novo missense mutation NM_015330.3: c.1249A > C, p.(Thr417Pro) in SPECC1L gene. With common manifestations in Teebi hypertelorism syndrome such as special facial appearance, umbilical malformations and congenital heart defects, the patient also had unusual symptoms including recurrent infections, febrile seizures and widely opened anterior fontanelle. Furthermore, all the recorded SPECC1L mutations were analyzed by in silico analysis. Coiled-coil domain 2 was the most frequently mutated domain and positions e and g might be more important than other positions. This paper expanded the phenotypic spectrum of Teebi hypertelorism syndrome and elaborated molecular characteristics of SPECC1L mutations.

15.
Adv Exp Med Biol ; 1232: 409-414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893438

RESUMO

Nakamura et al. examined the evidence, using a discovery and a validation database, that amyloid-ß precursor protein (APP)669-711/amyloid-ß (Aß)1-42 and Aß1-40/Aß1-42 ratios, and composites based on traditional statistics; they concluded that these may be useful as biomarkers of Alzheimer's Disease (AD). We reexamined the same datasets, each of which included cognitively normal individuals (CN), individuals with mild cognitive impairment (MCI) and individuals with AD. We used fractal self-similar analyses and reexamined their data from (1) the Japanese National Center for Geriatrics and Gerontology (NCGG) (discovery database) and (2) the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohort (validation database). Results: Using our methods, the three groups of individuals were found to be self-similar, i.e., they could not be differentiated quantitatively, in contrast to the findings of Nakamura et al. Conclusion: Appropriate biomarkers need further study. Our results suggest that APP669-711/Aß1-42 and Aß1-40/Aß1-42 ratios and their composites may not be valid biomarkers of AD, when reexamined using fractal methods for comparing biomarkers across populations.


Assuntos
Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Humanos
16.
Eur J Med Chem ; 186: 111852, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759729

RESUMO

Heart failure is a disease with high mortality and the risk of heart failure increases in magnitude with age. The patients of heart failure is increasing year by year. Hence, Pharmaceutical researchers have to develop new drugs with better pharmacological effects to coping with this phenomenon. In this article, we reviewed the small molecule compounds for heart failure that have been marketed in recent years or are promising to enter clinical research. We also reviewed the SAR (structure activity relationship) of these molecules, such as renin inhibitors, ROMK inhibitors, a kind of new diuretics, and some dual-targets inhibitors. These small molecules proven to be beneficial effect on heart failure patients. Which may provide ideas for the design of novel anti-heart failure therapeutic drugs.

17.
Hepatol Int ; 14(1): 80-95, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31802389

RESUMO

BACKGROUND: Sorafenib is the most widely used first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but such treatment provides only limited survival benefits that might be related to the immune status of distinct tumor microenvironments. A fundamental understanding of the distribution and phenotypes of T lymphocytes in tumors will undoubtedly lead to the development of novel immunotherapeutic strategies that could possibly enhance the efficacy of sorafenib treatments. METHODS: Flow cytometry, immunohistochemistry and immunofluorescence analyses were performed to detect the infiltration and distribution of various leukocyte populations, and the expression of different immune checkpoint molecules in fresh HCC tumor tissues. Correlations among indicating genes were calculated in 365 patients with HCC from The Cancer Genome Atlas (TCGA) data set, and the cumulative overall survival time was calculated using the Kaplan-Meier method. Moreover, role of adenosinergic pathway on sorafenib anti-tumor efficacy was investigated using both subcutaneous and orthotopic transplantation tumor model in immune competent C57BL/6 mice. RESULTS: We revealed that levels of CD3+ and CD8+ T cells were significantly downregulated in HCC tumor tissue, so were the infiltration of CD169+ cells (a Mφ subpopulation with T cell activation capacities) and their contact with CD8+ cells in tumor milieus. Moreover, levels of PD-1 and CD39 expression were significantly upregulated in human HCC-infiltrating CD4+ and CD8+ T cells, and CD39+CD8+ T cells exhibited a CD69+PD-1+perforinlowIFNγlow "exhausted" phenotype. Levels of both CD39+ T cells infiltration and adenosine receptor ADORA2B expression in tumor tissues were negatively correlated with overall survival of patients with HCC. Accordingly, mice treated with sorafenib in combination with adenosine A2B receptor blockage reagents exhibited significantly reduced tumor progression compared with control groups. CONCLUSIONS: These results suggest that adenosinergic pathway might represent an applicable target for sorafenib-combined-therapies in human HCC.

18.
J Neurosci ; 40(1): 237-254, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31704787

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disability that demonstrates impaired social interactions, communication deficits, and restrictive and repetitive behaviors. ASD has a strong genetic basis and many ASD-associated genes have been discovered thus far. Our previous work has shown that loss of expression of the X-linked gene NEXMIF/KIDLIA is implicated in patients with autistic features and intellectual disability (ID). To further determine the causal role of the gene in the disorder, and to understand the cellular and molecular mechanisms underlying the pathology, we have generated a NEXMIF knock-out (KO) mouse. We find that male NEXMIF KO mice demonstrate reduced sociability and communication, elevated repetitive grooming behavior, and deficits in learning and memory. Loss of NEXMIF/KIDLIA expression results in a significant decrease in synapse density and synaptic protein expression. Consistently, male KO animals show aberrant synaptic function as measured by excitatory miniatures and postsynaptic currents in the hippocampus. These findings indicate that NEXMIF KO mice recapitulate the phenotypes of the human disorder. The NEXMIF KO mouse model will be a valuable tool for studying the complex mechanisms involved in ASD and for the development of novel therapeutics for this disorder.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by behavioral phenotypes. Based on our previous work, which indicated the loss of NEXMIF/KIDLIA was associated with ASD, we generated NEXMIF knock-out (KO) mice. The NEXMIF KO mice demonstrate autism-like behaviors including deficits in social interaction, increased repetitive self-grooming, and impairments in communication and in learning and memory. The KO neurons show reduced synapse density and a suppression in synaptic transmission, indicating a role for NEXMIF in regulating synapse development and function. The NEXMIF KO mouse faithfully recapitulates the human disorder, and thus serves as an animal model for future investigation of the NEXMIF-dependent neurodevelopmental disorders.

19.
Anal Chem ; 92(1): 1470-1476, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31762255

RESUMO

This work reports a ZIF-8 (ZIF: Zeolitic Imidazolate Framework)-assisted NaYF4:Yb,Tm@ZnO upconverter for the photoelectrochemical (PEC) biosensing of carcinoembryonic antigen (CEA) under near-infrared (NIR) irradiation on a homemade 3D-printed device with DNA walker-based amplification strategy. The composite photosensitive material NaYF4:Yb,Tm@ZnO, as converter to transfer NIR import to photocurrent output, was driven from annealed NaYF4:Yb,Tm@ZIF-8. Yb3+ and Tm3+-codoped NaYF4 (NaYF4:Yb,Tm) converted NIR excitation into UV emission, matching with the absorption of ZnO for in situ excitation to generate the photocurrent. Upon target CEA introduction, the swing arm of DNA walker including the sequence of CEA aptamer carried out the sandwiched bioassembly with CEA capture aptamer on the G-rich anchorage DNA tracks-functionalized magnetic beads. Thereafter, DNA walker was triggered, and the swing arm DNA was captured by the G-rich anchorage DNA according to partly complementary pairing and Exonuclease III (Exo III) consumed anchorage DNA by a burnt-bridge mechanism to go into the next cycle. The released guanine (G) bases from DNA walker enhanced the photocurrent response on a miniature homemade 3D-printed device consisting of the detection cell, dark box, and light platform. Under optimal conditions, NaYF4:Yb,Tm@ZnO-based NIR light-driven PEC biosensor presented high sensitivity and selectivity for CEA sensing with a detection limit of 0.032 ng mL-1. Importantly, our strategy provides a new horizon for the development of NIR-based PEC biosensors in the aspect of developing MOF-derived photoelectric materials, flexible design of a 3D-printed device, and effective signal amplification mode.

20.
J Cell Mol Med ; 24(2): 2052-2063, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31883300

RESUMO

Studies have demonstrated that nuclear factor of activated T cells 5 (NFAT5) is not only a tonicity-responsive transcription factor but also activated by other stimuli, so we aim to investigate whether NFAT5 participates in collateral arteries formation in rats. We performed femoral artery ligature (FAL) in rats for hindlimb ischaemia model and found that NFAT5 was up-regulated in rat adductors with FAL compared with sham group. Knockdown of NFAT5 with locally injection of adenovirus-mediated NFAT5-shRNA in rats significantly inhibited hindlimb blood perfusion recovery and arteriogenesis. Moreover, NFAT5 knockdown decreased macrophages infiltration and monocyte chemotactic protein-1 (MCP-1) expression in rats adductors. In vitro, with interleukin-1ß (IL-1ß) stimulation and loss-of-function studies, we demonstrated that NFAT5 knockdown inhibits MCP-1 expression in endothelial cells and chemotaxis of THP-1 cells regulated by ERK1/2 pathway. More importantly, exogenous MCP-1 delivery could recover hindlimb blood perfusion, promote arteriogenesis and macrophages infiltration in rats after FAL, which were depressed by NFAT5 knockdown. Besides, NFAT5 knockdown also inhibited angiogenesis in gastrocnemius muscles in rats. Our results indicate that NFAT5 is a critical regulator of arteriogenesis and angiogenesis via MCP-1-dependent monocyte recruitment, suggesting that NFAT5 may represent an alternative therapeutic target for ischaemic diseases.

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