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1.
J Phys Condens Matter ; 32(1): 015401, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31519010

RESUMO

Low plasticity has been a major issue for the application of Mg alloys. Here, based on the generalized stacking fault energy curves and Arrhenius equation, we systematically study alloying effects on the stacking fault energies and the activation probability of basal and non-basal 〈a〉, and pyramidal 〈c + a〉 slip systems in twenty-one Mg alloys. Our results reveal that activation of 〈c + a〉 slip systems on pyramidal II plane can significantly improve the plasticity. For example, Ca is found to promote the activation probability of this slip system by one order of magnitude and dramatically improve the plasticity of Mg.

2.
Food Chem ; 303: 125363, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472383

RESUMO

Present in many plant foods, biogenic phenolic compounds are important bioactive phytonutrients with high anti-oxidant activity and thereby are praised for their health-promoting properties. However, current food nutrient improvement by high phenolic content in staples is limited by the shortage of genetic resources rich in phenolic compounds. To resolve this obstacle, we developed a non-destructive massive analytical approach to screen wheat phenolic mutants. In grains, multiple mutant lines showed significantly higher contents of flavonoids or cell wall-bound phenolic esters. Moreover, five mutants showed higher anti-oxidant potentials in wall-bound phenolic compounds ranging from 15% to 20%, with the maximal close to natural black wheat. In contrast to black wheat, two mutants accumulated higher phenolic compounds in the endosperm. lrf4 was mapped by BSR to a concentrated genomic region in the short arm of chromosome 1A. The present work represents an efficient high-throughput strategy to increase wheat anti-oxidant potential through traditional mutagenesis.


Assuntos
Antioxidantes/metabolismo , Mutação , Fenóis/metabolismo , Triticum/genética , Triticum/metabolismo , Flavonoides/metabolismo
3.
Biomed Microdevices ; 21(4): 96, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712916

RESUMO

Isothermal titration calorimetry (ITC) can benefit from operating in miniaturized devices as they enable quantitative, low-cost measurements with reduced analysis time and reagents consumption. However, most of the existing devices that offer ITC capabilities either do not yet allow proper control of reaction conditions or are limited by issues such as evaporation or surface adsorption caused inaccurate solution concentration information and unintended changes in biomolecular properties because of aggregation. In this paper, we present a microdevice that combines 3D-printed microfluidic structures with a polymer-based MEMS thermoelectric sensor to enable quantitative ITC measurements of biomolecular interactions. Benefitting from the geometric flexibility of 3D-printing, the microfluidic design features calorimetric chambers in a differential cantilever configuration that improves the thermal insulation and reduces the thermal mass of the implementing device. Also, 3D-printing microfluidic structures use non-permeable materials to avoid potential adsorption. Finally, the robustness of the polymeric MEMS sensor chip allows the device to be assembled reversibly and leak-free, and hence reusable. We demonstrate the utility of the device by quantitative ITC characterization of a biomolecular binding system, ribonuclease A (RNase A) bind with cytidine 2'-monophosphate (2'CMP) down to a practically useful sample concentration of 0.2 mM. The thermodynamic parameters of the binding system, including the stoichiometry, equilibrium binding constant, and enthalpy change are obtained and found to agree with values previously reported in the literature.

4.
Plant Cell Environ ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724184

RESUMO

Silicon (Si) accumulation in shoots differs greatly with plant species, but the molecular mechanisms for this interspecific difference are unknown. Here, we isolated homologous genes of rice Si influx (SlLsi1) and efflux (SlLsi2) transporter genes in tomato (Solanum lycopersicum L.) and functionally characterized these genes. SlLsi1 showed transport activity for Si when expressed in both rice lsi1 mutant and Xenopus laevis oocytes. SlLsi1 was constitutively expressed in the roots. Immunostaining showed that SlLsi1 was localized at the plasma membrane of both root tip and basal region without polarity. Furthermore, overexpression of SlLsi1 in tomato increased Si concentration in the roots and root cell sap, but did not alter the Si concentration in the shoots. By contrast, two Lsi2-like proteins did not show efflux transport activity for Si in Xenopus oocytes. However, when functional CsLsi2 from cucumber was expressed in tomato, the Si uptake was significantly increased, resulting in higher Si accumulation in leaves and enhanced tolerance of leaves to water deficit and high temperature. Our results suggest that the low Si accumulation in tomato is attributed to the lack of functional Si efflux transporter Lsi2 required for active Si uptake although SlLsi1 is functional.

5.
Acta Neurochir (Wien) ; 161(12): 2505-2511, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31696300

RESUMO

BACKGROUND: Morphological and microstructural changes of the trigeminal nerve due to neurovascular compression (NVC) have been reported in primary trigeminal neuralgia (PTN) patients. This investigation was to examine the relationship between the trigeminal-pontine angle and nerve microstructural changes. METHODS: Twenty-five patients underwent microvascular decompression (MVD) for trigeminal neuralgia, and 25 age- and sex-matched controls were studied. The two groups underwent high-resolution three-dimensional MRI and diffusion tensor imaging (DTI). Bilateral trigeminal-pontine angle, cross-sectional area of cerebellopontine angle (CPA) cistern, and the length of trigeminal nerve were evaluated. The mean values of fractional anisotropy and apparent diffusion coefficient at the site of NVC were also measured. Correlation analyses were performed for the trigeminal-pontine angle and the diffusion metrics (FA and ADC) in PTN patients. RESULTS: The mean trigeminal-pontine angle and FA value on the affected side was significantly smaller than the unaffected side and the control group (p < 0.001), while the mean ADC value was significantly increased (p < 0.01). When taking the conflicting vessel types into consideration, the angle affected by the superior cerebellar artery (SCA) was statistically sharper than when affected by other vessels (p < 0.01). However, there were no significant changes in the area of the CPA cistern or the length of the trigeminal nerve between the groups. Correlation analyses showed that the trigeminal-pontine angle was positively correlated with FA and negatively correlated with ADC. CONCLUSIONS: A sharp trigeminal-pontine angle may increase the chance of NVC and exacerbate nerve degeneration, which may be one of the supplementary factors that contribute to the pathogenesis of trigeminal neuralgia.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31707128

RESUMO

BACKGROUND: Integrin α4ß7 mediates lymphocyte trafficking to the gut and gut-associated lymphoid tissues (GALT), a process critical for recruitment of effector lymphocytes from the circulation to the gut mucosa in inflammatory bowel disease (IBD) and murine models of intestinal inflammation. Antibody blockade of ß7 integrins is generally efficacious in IBD; however, some patients fail to respond, and a few can experience exacerbations. AIMS: To examine the effects of loss of ß7 integrin function in murine models of IBD. METHODS AND RESULTS: In a mouse IBD model caused by lack of IL-10, a cytokine important in CD25hiFoxP3+ regulatory T cells (Tregs) function, genetic deletion of ß7 integrin or antibody blockade of α4ß7-MAdCAM-1 interaction paradoxically exacerbated colitis. Loss of ß7 impaired the capacity of Tregs to home to and therefore suppress intestinal inflammation in an adoptive T cell transfer model; however, the intrinsic suppressive function of ß7-deficient Tregs remained intact, indicating that the ß7-deficiency selectively impacts gut homing. Deletion of ß7 integrin did not worsen colitis in an acute dextran sodium sulfate (DSS) model in which Tregs number and functions are normal. CONCLUSION: In Itgb7-/-Il10-/- mice loss ß7-dependent Treg homing to GALT combined with loss of intrinsic Treg function exacerbate intestinal inflammation. These results suggest that IBD patients with reduced CD25hiFoxP3+ Tregs numbers or function or lack of IL-10 could be at risk for failure of α4ß7 blocking therapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31743581

RESUMO

Rechargeable aqueous zinc ion batteries are attractive for high safety, low cost and high energy density. However, the viable cathode materials, e.g., vanadium oxides, suffer from strong Coulombic ion-lattice interactions with divalent Zn2+, leading to very limited stability when cycled at high charge/discharge depth with high capacity. Here we report a synthetic strategy to make oxygen-deficient vanadium oxide cathode, in which the facilitated Zn2+ reaction kinetic enhances capacity and Zn2+ pathways for high reversibility. Benefited from the robust cathode, the aqueous Zinc ion battery shows an unprecedented stability over 200 cycles with high specific capacity of ~400 mAh g-1, achieving 95% utilization of its theoretical capacity, and long cycle life up to 2000 cycles at high utilization of 67%. This work opens up a new avenue to synthesize novel cathode materials for advanced batteries by designing oxygen-deficient structure.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31675288

RESUMO

A Gram-stain-negative, strictly aerobic, rod-shaped bacterium, without flagellum and designated ZYF765T, was isolated from seawater sampled at a depth of 4000 m in the Mariana Trench. Strain ZYF765T grew with 1-15 % (w/v) NaCl (optimum, 4 %), at 16-37 °C (28 °C) and at pH 6.0-10.0 (pH 7.0-8.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain ZYF765T formed a lineage within the family Hyphomonadaceae, and was distinct from the most closely related species Glycocaulis abyssi, Glycocaulis albus and Glycocaulis alkaliphilus with 16S rRNA gene sequences similarities ranging from 98.42 to 98.63 %. The major respiratory quinone was ubiquinone-10 (Q-10). The polar lipids comprised three unidentified glycolipids, one unidentified aminophospholipid, one unidentified phospholipid and one unidentified aminolipid. The predominant fatty acids (more than 10 % of total fatty acids) were C18  :  1ω7c (46.2 %) and C18  :  0 (14.1 %). The DNA G+C content was 67.7 mol%. On the basis of the results of polyphasic taxonomic analysis, strain ZYF765T is considered to represent a novel species within the genus Glycocaulis, for which the name Glycocaulis profundi sp. nov. is proposed. The type strain is ZYF765T (=JCM 33028T=MCCC 1K03554T).

9.
Gene ; : 144169, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669642

RESUMO

BACKGROUND (OBJECTIVE): In the development of tumor therapy, the role of long non-coding RNA actin filagenin 1 antisense RNA 1 (1ncRNA AFAP1-AS1) is quite significant, but the actual role of AFAP1-AS1 in the treatment of prostate cancer has not been determined. In view of this, the author took AFAP1-AS1 as the research object to design an experimental study, and conducted an in-depth exploration of the pathogenesis of prostate cancer. METHODS: RT-qPCR was used to detect the expression of AFAP1-AS1 and miR-512-3p in prostate cancer tissues and cell lines. Perforation, flow cytometry and CCK-8 were used to detect the effects of cell proliferation, migration and invasion of mir-512-3p and a AFAP1-AS1. And the luciferase reporter gene was used to detect the downstream target gene of AFAP1-AS1, and the expression of CDK4, CDK6 and CCND1 protein was detected by Western blot. RESULTS: AFAP1-AS1 is highly expressed in prostate cancer tissues and cell lines. The expression level of AFAP1-AS1 is correlated with histological grade and distant metastasis. The overall level of patients with high expression of AFAP1-AS1 is low, and their survival rate is relatively low. Silencing AFAP1-AS1 can significantly increase the proliferation and migration of prostate cancer cells. AFAP1-AS1 silencing induces cell cycle arrest at G0/G1 phase. The downstream target of AFAP1-AS1 was mir-512-3p. The role of AFAP1-AS1 in the progression of prostate cancer cells was mediated by mir-512-3p. CONCLUSION: AFAP1-AS1 regulates miR-512-3p, so as to realize the regulation effect on the proliferation, invasion and migration of prostate cancer cells, and thereby promote the occurrence and development of prostate cancer, so as to provide the corresponding program for the treatment of prostate cancer. Abberivation: ADPC, androgen-dependent prostate cancer; CRPC, castrated prostate cancer; RNA1 AFAP1-Asl, Actin fiber-associated protein 1-anti-RNA1; miRNAs, MicroRNAs.

10.
J Environ Pathol Toxicol Oncol ; 38(2): 119-131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679275

RESUMO

BACKGROUND/AIMS: LncRNAs are significant regulators in multiple cancers including hepatocellular carcinoma (HCC). Recently, lncRNA ANRIL has been reported to be elevated during multiple cancer types, exhibiting oncogenic roles. However, the exact biological mechanism of ANRIL is still poorly understood in HCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were utilized to detect expressions of ANRIL, miR-384, and STAT3. CCK8 and EDU assays were employed to evaluate HCC cell proliferation. A flow cytometry assay was used to detect the HCC cell cycle and cell apoptosis. The scratch migration and Transwell invasion assays were performed to test cell migration and invasion, respectively. RIP and RNA pull-down assays were carried out to confirm the correlation between ANRIL and miR-384. The dual-luciferase reporter assay was used to prove the association between miR-384 and STAT3. Western blotting analysis was performed to examine protein levels of STAT3. IHC and HE staining were employed to detect Ki-67 and histopathology. RESULTS: ANRIL expression was upregulated in HCC cells, including SMCC7721, HepG2, MHCC-97H, SNU449 and HUH-7 cells, in comparison to the normal human liver cells LO2. Knockdown of ANRIL suppressed HCC cell proliferation and induced cell cycle arrest and apoptosis. HCC cell migration and invasion capacity were inhibited by inhibition of ANRIL. Bioinformatics analyses revealed that ANRIL could interact with miR-384. miR-384 was significantly decreased in HCC cells, and overexpression of miR-384 repressed HCC progression. STAT3 was predicted as a target of miR-384, and miR-384 can modulate STAT3 levels negatively in vitro. ANRIL can suppress HCC development through regulating miR-384 and STAT3 in vivo. CONCLUSION: ANRIL is involved in HCC progression by direct targeting of miR-384 and STAT3. Also, ANRIL could act as a potential candidate for HCC diagnosis, prognosis, and therapy.


Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/genética , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Células HEK293 , Células Hep G2 , Humanos , Neoplasias Hepáticas/fisiopatologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-31638312

RESUMO

Reversible oxygen conversion is important for various green energy technologies. Herein we synthesize a series of bimetallic coordination polymers by varying the Ni/Co ratio and using HITP (HITP=2,3,6,7,10,11-hexaiminotriphenylene) as the ligand, to interrogate the role of metal centres in modulating the activity of the oxygen reduction reaction (ORR). Co3 HITP2 and Ni3 HITP2 are compared. Unpaired 3d electrons in Co3 HITP2 result in less coplanarity but more radical character. Thus, despite of a reduced crystallinity and conductivity, the best ORR activity, comparable to 20 % Pt/C, is obtained for Co3 HITP2 , showing the 3d orbital configuration of the metal centre promotes ORR. Experimental and DFT studies show a transition of ORR pathway from four-electron for Co3 HITP2 to two-electron for Ni3 HITP2 . Rechargeable zinc-air batteries using Co3 HITP2 as the air cathode catalyst demonstrate excellent energy efficiency and stability.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31581102

RESUMO

Uterine cancer (also known as endometrial cancer) can seriously affect the female reproductive system, and histopathological image analysis is the gold standard for diagnosing endometrial cancer. Due to the limited ability to model the complicated relationships between histopathological images and their interpretations, existing computer-aided diagnosis (CADx) approaches using traditional machine learning algorithms often failed to achieve satisfying results. In this study, we develop a CADx approach based on a convolutional neural network (CNN) and attention mechanisms, called HIENet. In the ten-fold cross-validation on ~3,300 hematoxylin and eosin (H&E) image patches from ~500 endometrial specimens, HIENet achieved a 76.91 ± 1.17% (mean ± s. d.) accuracy for four classes of endometrial tissue, i.e., normal endometrium, endometrial polyp, endometrial hyperplasia, and endometrial adenocarcinoma. Also, HIENet obtained an area-under-the-curve (AUC) of 0.9579 ± 0.0103 with an 81.04 ± 3.87% sensitivity and 94.78 ± 0.87% specificity in a binary classification task that detected endometrioid adenocarcinoma. Besides, in the external validation on 200 H&E image patches from 50 randomly-selected female patients, HIENet achieved an 84.50% accuracy in the four-class classification task, as well as an AUC of 0.9829 with a 77.97% (95% confidence interval, CI, 65.27%~87.71%) sensitivity and 100% (95% CI, 97.42%~100.00%) specificity. The proposed CADx method outperformed three human experts and five CNN-based classifiers regarding overall classification performance. It was also able to provide pathologists better interpretability of diagnoses by highlighting the histopathological correlations of local pixel-level image features to morphological characteristics of endometrial tissue.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31646346

RESUMO

RATIONALE: A role of group I metabotropic glutamate receptor 5 (mGlu5) in regulating spontaneous locomotion and psychostimulant-induced hyperactivity has been proposed. OBJECTIVES: This study aims to determine if mGlu5 in GABAergic neurons regulates spontaneous or psychostimulant-induced locomotion. METHODS: We generated mice specifically lacking mGlu5 in forebrain GABAergic neuron by crossing DLX-Cre mice with mGlu5flox/flox mice to generate DLX-mGlu5 KO mice. The locomotion of adult mice was examined in the open-field assay (OFA) and home cage setting. The effects of the mGlu5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP), cocaine, and methylphenidate on acute motor behaviors in DLX-mGlu5 KO and littermate control mice were assessed in OFA. Striatal synaptic plasticity of these mice was examined with field potential electrophysiological recordings. RESULTS: Deleting mGlu5 from forebrain GABAergic neurons results in failure to induce long-term depression (LTD) in the dorsal striatum and absence of habituated locomotion in both novel and familiar settings. In a familiar environment (home cage), DLX-mGlu5 KO mice were hyperactive. In the OFA, DLX-mGlu5 KO mice exhibited initial hypo-activity, and then gradually increased their locomotion with time, resulting in no habituation response. DLX-mGlu5 KO mice exhibited almost no locomotor response to MPEP (40 mg/kg), while the same dose elicited hyperlocomotion in control mice. The DLX-mGlu5 KO mice also showed reduced hyperactivity response to cocaine, while they retained normal hyperactivity response to methylphenidate, albeit with delayed onset. CONCLUSION: mGlu5 in forebrain GABAergic neurons is critical to trigger habituation upon the initiation of locomotion as well as to mediate MPEP-induced hyperlocomotion and modulate psychostimulant-induced hyperactivity.

14.
Angew Chem Int Ed Engl ; 58(48): 17359-17364, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31595626

RESUMO

Harnessing metal-free photoinduced reversible-deactivation radical polymerization (photo-RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme-responsive and pro-apoptotic peptide brush polymers. Thermolysin-responsive peptide-based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm-like micelles upon enzyme-triggered cleavage of coronal peptide sidechains. Moreover, pro-apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro-apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo-RDRP, make it possible to access well-defined peptide-based polymer bioconjugate structures with tunable bioactivity.

15.
ACS Appl Mater Interfaces ; 11(43): 40006-40013, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31592629

RESUMO

Na-ion batteries (SIBs) and K-ion batteries (PIBs) are considered as promising alternatives to Li-ion batteries (LIBs) for large-scale electrical-energy-storage applications. Thus, developing an advanced anodic material with appropriate structure for both SIBs and PIBs is urgently desirable but remains an eager challenge because of the relatively large ionic radius of Na+ or K+. Herein, we rationally design a sulfur-mediated three-dimensional graphene aerogel (SMGA) with plant cell wall structure as a binder-free anodic material for SIBs and PIBs as well as LIBs, exhibiting high capacity and excellent rate capability along with long cycling stability. For instance, at 0.1 A g-1, the SMGA anodes can deliver a high capacity of 320 mAh g-1 in PIBs after 500 cycles and 304 mAh g-1 in SIBs and 690 mAh g-1 in LIBs after 200 cycles. Furthermore, a detailed electrochemical kinetic calculation manifests that the Li/Na/K-ion storage capability is mainly ascribed to the introduction of sulfur in graphene aerogel (GA) to enlarge the interlayer distance, the three-dimensional interconnected network with porous structure providing sufficient space to accommodate volumetric expansion, and a short transport pathway for electrons/alkali-ions. Our results demonstrate the advanced performance of alkali-ion batteries, thus making it possible to develop a universal electrode for applications of cost-effective next-generation rechargeable batteries.

16.
Environ Pollut ; : 113364, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31662245

RESUMO

While Cox17 functions importantly in copper metalation of cytochrome c oxidase and integral mitochondrial architecture in vertebrates, rare studies have been performed regarding the developmental and physiological characters of vertebrate cox17 mutants. In this study, normal-like developmental phenotype was observed in both cox17Δ6-/- and cox17Δ4-/- homozygous zebrafish mutants, while gene ontology term and pathway analysis of the differentially expressed genes in both mutants showed enrichment in oxidoreductase activity, ion transport, histone methylation, MICOS complex, Wnt signaling, etc. This implied the occurrence of damage to the integral function of Cox17 and change of transcriptomes in the two mutants. Further qRT-PCR and WISH assays revealed the down-regulated expression of Wnt signaling and reduced expression of swim bladder marker genes in the two mutants. Moreover, copper stimulation induced no obvious increase in reactive oxygen species (ROS) or in the expression of hemoglobin marker genes, but further reduced the expression of swim bladder marker genes in the mutants. The integral data in this study suggest that: (1) cox17 mutants cannot activate the response of oxidoreductase to copper stimulation; (2) copper depends on the integral function of Cox17 to induce developmental defects in hemoglobin rather than swim bladder and (3) Wnt signaling but not ROS might mediate copper-induced swim bladder developmental defects in fish.

17.
Bioorg Chem ; 92: 103268, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541800

RESUMO

Diabetes is one of the metabolic disorders in the world. It is the prime reason of mortality and morbidity owing to hyperglycemia which is link with numerus obstacles. Artemisia argyi is commonly used as an ingredient in healthy foods as well as an herbal medicine in Asian countries. The present research aims to evaluate the hypoglycemic effects of A. argyi and reveal its the potentially active constituents. The chemical composition was identified by HPLC-DAD-Q-TOF-MS, and fractionation was performed by extraction. The fractions were assessed by the blood glucose level, oral glucose tolerance and small intestinal α-glucosidase inhibitory tests, and an analysis of the total phenolic content (TPC), antioxidant and α-glucosidase inhibitory activities. In our efforts to characterize the compounds responsible for hypoglycemic effect, bioactivity-guided fraction of the MeOH extract and chemical investigation of its active EtOAc fraction led to the successful identification of caffeoylquinic acids, which were elucidated by molecular docking, using the crystal structure of S. cerevisiae isomaltase (PD code: 3AXI). In summary, this bio-guided search revealed that caffeoylquinic acids from A. argyi as potential active constituents displayed with hypoglycemic activity, which provided a basis for further study of pharmacological activity.

18.
Brain Behav Immun ; 82: 354-371, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513876

RESUMO

Stroke is a leading cause of long-term disability worldwide; survivors often show sensorimotor and cognitive deficits. Therapeutic exercise is the most common treatment strategy for rehabilitating patients with stroke via augmentation of neurogenesis, angiogenesis, neurotrophic factors expression, and synaptogenesis. Neurogenesis plays important roles in sensorimotor and cognitive functional recovery, and can be promoted by exercise; however, the mechanism underlying this phenomenon remains unclear. In this study, we explored the effects of treadmill exercise on sensorimotor and cognitive functional recovery, as well as the potential molecular mechanisms underlying the promotion of neurogenesis in a rat model of transient middle cerebral artery occlusion (tMCAO). We found that treadmill exercise facilitated sensorimotor and cognitive functional recovery after tMCAO, and that neural stem/progenitor cell proliferation, differentiation, and migration were enhanced in the ipsilateral subventricular and subgranular zones after tMCAO. Meanwhile, the newborn neurons induced by treadmill exercise after tMCAO had the similar function with pre-existing neurons. Treadmill exercise significantly increased CD200 and CD200 receptor (CD200R) levels in the ipsilateral hippocampus and cortex. Further study revealed that treadmill exercise-induced neurogenesis and functional recovery were clearly inhibited, while Il-ß and Tnf-α expression were upregulated, following lentivirus (LV)-induced suppression of post-stroke CD200R expression. Consistent with the effect of treadmill exercise, CD200Fc (a CD200R agonist) markedly promoted neurogenesis and functional recovery after stroke. In addition, CD200Fc could further enhance the functional recovery induced by treadmill exercise after stroke. Our results demonstrate the beneficial role of treadmill exercise in promoting neurogenesis and functional recovery via activating the CD200/CD200R signaling pathway and improving the inflammatory environment after stroke. Thus, the CD200/CD200R signaling pathway is a potential therapeutic target for functional recovery after stroke.

19.
J Bone Miner Res ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498925

RESUMO

Phosphorus is a necessary component of all living organisms. This nutrient is mainly transported from the maternal blood to the fetus via the placenta, and insufficient phosphorus availability via the placenta disturbs the normal development of the fetus, especially fetal bone formation in late gestation. Key proteins (phosphate transporters and exporters) that are responsible for the maintenance of placental-fetal phosphorus homeostasis have been identified. A deficiency in the phosphate transporter Pit2 has been shown to result in placental calcification and the retardation of fetal development in mice. What roles does XPR1 (the only known phosphate exporter) play in maintaining placental-fetal phosphorus homeostasis? In this study, we found that Xpr1 expression is strong in the murine placenta and increases with age during gestation. We generated a global Xpr1 knockout mouse and found that heterozygous (Xpr1+/- ) and homozygous (Xpr1-/- ) fetuses have lower inorganic phosphate (Pi) levels in amniotic fluid and serum and a decreased skeletal mineral content. Xpr1-deficient placentas show abnormal Pi exchange during gestation. Therefore, Xpr1 deficiency in the placenta disrupts placental-fetal Pi homeostasis. We also discovered that the placentas of the Xpr1+/- and Xpr1-/- embryos are severely calcified. Mendelian inheritance statistics for offspring outcomes indicated that Xpr1-deficient embryos are significantly reduced in late gestation. In addition, Xpr1-/- mice die perinatally and a small proportion of Xpr1+/- mice die neonatally. RNA sequence (RNA-Seq) analysis of placental mRNA revealed that many of the transcripts are significantly differentially expressed due to Xpr1 deficiency and are linked to dysfunction of the placenta. This study is the first to reveal that XPR1 plays an important role in maintaining placental-fetal Pi homeostasis, disruption of which causes severe placental calcification, delays normal placental function, and restricts fetal growth. © 2019 American Society for Bone and Mineral Research.

20.
Sci Rep ; 9(1): 13404, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527697

RESUMO

Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.

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