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1.
J Neuroinflammation ; 17(1): 45, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007102

RESUMO

BACKGROUND: G-protein-coupled estrogen receptor (GPER/GPR30) is a novel membrane-associated estrogen receptor that can induce rapid kinase signaling in various cells. Activation of GPER can prevent hippocampal neuronal cell death following transient global cerebral ischemia (GCI), although the mechanisms remain unclear. In the current study, we sought to address whether GPER activation exerts potent anti-inflammatory effects in the rat hippocampus after GCI as a potential mechanism to limit neuronal cell death. METHODS: GCI was induced by four-vessel occlusion in ovariectomized female SD rats. Specific agonist G1 or antagonist G36 of GPER was administrated using minipump, and antisense oligonucleotide (AS) of interleukin-1ß receptor antagonist (IL1RA) was administrated using brain infusion kit. Protein expression of IL1RA, NF-κB-P65, phosphorylation of CREB (p-CREB), Bcl2, cleaved caspase 3, and microglial markers Iba1, CD11b, as well as inflammasome components NLRP3, ASC, cleaved caspase 1, and Cle-IL1ß in the hippocampal CA1 region were investigated by immunofluorescent staining and Western blot analysis. The Duolink II in situ proximity ligation assay (PLA) was performed to detect the interaction between NLRP3 and ASC. Immunofluorescent staining for NeuN and TUNEL analysis were used to analyze neuronal survival and apoptosis, respectively. We performed Barnes maze and Novel object tests to compare the cognitive function of the rats. RESULTS: The results showed that G1 attenuated GCI-induced elevation of Iba1 and CD11b in the hippocampal CA1 region at 14 days of reperfusion, and this effect was blocked by G36. G1 treatment also markedly decreased expression of the NLRP3-ASC-caspase 1 inflammasome and IL1ß activation, as well as downstream NF-κB signaling, the effects reversed by G36 administration. Intriguingly, G1 caused a robust elevation in neurons of a well-known endogenous anti-inflammatory factor IL1RA, which was reversed by G36 treatment. G1 also enhanced p-CREB level in the hippocampus, a transcription factor known to enhance expression of IL1RA. Finally, in vivo IL1RA-AS abolished the anti-inflammatory, neuroprotective, and anti-apoptotic effects of G1 after GCI and reversed the cognitive-enhancing effects of G1 at 14 days after GCI. CONCLUSIONS: Taken together, the current results suggest that GPER preserves cognitive function following GCI in part by exerting anti-inflammatory effects and enhancing the defense mechanism of neurons by upregulating IL1RA.

2.
Environ Pollut ; 260: 113995, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32004962

RESUMO

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers.

3.
Theranostics ; 10(4): 1923-1947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042345

RESUMO

The continuous or real-time tracking of biological processes using biocompatible contrast agents over a certain period of time is vital for precise diagnosis and treatment, such as monitoring tissue regeneration after stem cell transplantation, understanding the genesis, development, invasion and metastasis of cancer and so on. The rationally designed nanoparticles, including aggregation-induced emission (AIE) dots, inorganic quantum dots (QDs), nanodiamonds, superparamagnetic iron oxide nanoparticles (SPIONs), and semiconducting polymer nanoparticles (SPNs), have been explored to meet this urgent need. In this review, the development and application of these nanoparticle-based cell trackers for a variety of imaging technologies, including fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, magnetic particle imaging, positron emission tomography and single photon emission computing tomography are discussed in detail. Moreover, the further therapeutic treatments using multi-functional trackers endowed with photodynamic and photothermal modalities are also introduced to provide a comprehensive perspective in this promising research field.

4.
ACS Nano ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32023035

RESUMO

Photodynamic therapy (PDT) has been a well-accepted clinical treatment for malignant tumors owing to its noninvasiveness and high spatiotemporal selectivity. However, the efficiency of PDT is still severely hindered by an inherent aggregation-caused quenching (ACQ) effect of traditional photosensitizers (PSs), the presence of B-cell lymphoma 2 (Bcl-2), an antiapoptosis protein in cells, and hypoxia in the tumor microenvironment. To address these issues, hybrid nanospheres containing Fe3+, aggregation-induced emission (AIE) PS, and Bcl-2 inhibitor of sabutoclax were constructed via coordination-driven self-assembly in aqueous media. Once the hybrid nanospheres are taken up by tumor cells, intracellular O2 concentration is observed to increase via Fenton reaction driven by Fe3+, whereas intracellular PDT resistance of the AIE PS was mitigated by sabutoclax. The design of the multifunctional hybrid nanospheres demonstrates a prospective nanoplatform for image-guided enhanced PDT of tumors.

5.
BMC Pregnancy Childbirth ; 20(1): 81, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033602

RESUMO

BACKGROUND: The prevalence of both placenta previa and cesarean are on the rise. Multiple adverse outcomes are critically increased when placenta previa is subsequent to prior cesarean. The purpose of the present study is to develop a pre-surgical method for predicting adverse outcomes in pregnancy complicated with both placenta previa and prior cesarean. METHODS: Clinical data was obtained from the medical history system at the First Affiliated Hospital of Sun Yat-sen University from February 2003 to December 2016. All cases with a final diagnosis of "placenta previa/low lying placenta (ICD:O44.001-105)" and "scarred uterus complicated with pregnancy (ICD: O34.200-202)" were collected and reviewed. Hysterectomy was taken as the primary outcome; and blood loss was taken as the secondary outcome. RESULTS: Of 219 pregnant women in the final analysis, 25 received a hysterectomy following delivery, and 48 had blood loss exceeding 1000 ml. Pre-surgical risk factors for hysterectomy are ultrasonic signs of vascular lacunae, central placenta previa, and loss of normal hypoechoic retroplacental zone. A pre-surgical predictive equation referred to as "Hysterectomy Index in Placenta Previa with Prior cesarean (HIPs)" was generated and each risk factor was weighted to create an 8-point scale. This index yielded an area under the curve of 0.972 for the prediction of hysterectomy. CONCLUSIONS: Application of the HIPs score may provide an effective pre-surgical prediction of cesarean hysterectomy in pregnant women complicated with both placenta previa and prior cesarean.

6.
Mol Plant ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017998

RESUMO

Improved soybean cultivars have been adapted to grow at a wide range of latitudes, enabling expansion of cultivation worldwide. However, the genetic basis for this broad adaptation is still not clear. Here we report the identification of GmPRR3b as a major flowering time regulatory gene that has been selected during domestication and genetic improvement for geographic expansion. Through genome-wide association study (GWAS) of a diverse landrace panel of soybean (comprised of 279 accessions), we identified 16 candidate quantitative loci associated with flowering time and maturity time. The strongest signal resides on the known flowering gene E2, verify the effectiveness of our approach. We detected strong association signals of a genomic region containing GmPRR3b with both flowering and maturity time. Haplotype analysis revealed that GmPRR3bH6 is the major form that has been utilized during recent breeding of modern cultivars. mRNA profiling analysis showed that GmPRR3bH6 displays a rhythmic and photoperiod-dependent expression that is preferentially induced under long day conditions. Overexpression of GmPRR3bH6 conferred increased main stem node number and high yield phenotypes, while knockout of GmPRR3bH6 by CRISPR-Cas9 technology retarded growth and delayed floral transition. GmPRR3bH6 appears to act as a transcriptional repressor of multiple predicted circadian clock genes, including GmCCA1a which directly upregulates J/GmELF3a to modulate flowering time. Taken together, the causal SNP (Chr12:5520945) likely endows GmPRR3bH6 a moderate but appropriate activity, which is associated with early flowering and vigorous growth traits preferentially selected for broad adaption in landraces and improved cultivars.

7.
J Org Chem ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019308

RESUMO

One of the fundamental and highly valuable transformations in organic chemistry is the nucleophilic substitution of alcohols. Traditionally, these reactions require strategies that employ stoichiometric hazardous reagents and are associated with difficulty in purification of the biproducts. To overcome these challenges, here we report a simple route toward the diverse conversion of alcohols via an SN2 pathway, in which blue light promoted iodination is used to form alkyl iodide intermediates from simple unreactive alcohols. The scope of the process tolerates a range of nucleophiles to construct C-N, C-O, C-S, and C-C bonds. Furthermore, we also demonstrate that this method can be used for the preparation and late stage functionalization of pharmaceuticals, as highlighted by the synthesis of thiocarlide, butoxycaine, and pramoxine.

8.
Eur Radiol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020400

RESUMO

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

9.
J Am Chem Soc ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023041

RESUMO

The conditions that led to the formation of the first organisms and the ways that life originates from a lifeless chemical soup are poorly understood. The recent hypothesis of ''RNA-peptide coevolution'' suggests that the current close relationship between amino acids and nucleobases may well have extended to the origin of life. We now show how the interplay between these compound classes can give rise to new self-replicating molecules using a dynamic combinatorial approach. We report two strategies for the fabrication of chimeric amino acid/nucleobase self-replicating macrocycles capable of exponential growth. The first one relies on mixing nucleobase- and peptide-based building blocks, where the ligation of these two gives rise to highly specific chimeric ring structures. The second one starts from peptide nucleic acid (PNA) building blocks in which nucleobases are already linked to amino acids from the start. While previously reported nucleic acid-based self-replicating systems rely on pre-synthesis of (short) oligonucleotide sequences, self-replication in the present systems start from units containing only a single nucleobase. Self-replication is accompanied by self-assembly, spontaneously giving rise to an ordered one-dimensional arrangement of nucleobase nanostructures.

10.
Sensors (Basel) ; 20(3)2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32024314

RESUMO

Quantitative online detection of microcracks in long-distance oil and gas pipelines is an international problem, and the effective detection method is still lacking. In this paper, a mathematical model of non-uniform distribution of crack magnetic charges is established based on the stress distribution laws of pipeline cracks under internal pressure. The weak magnetic signal characteristics of pipeline cracks with different sizes are analyzed. The internal pressure increasing factor of weak magnetic signals are extracted to analyze the corresponding relationship between crack size and weak magnetic signals. The experimental study of the X70 pipeline is carried out. The results show that the axial component of the weak magnetic signal at the crack has a maximum value near the tip, and a minimum value appears in the middle of the crack. The internal pressure increasing factor is introduced to quantify the weak magnetic signal, the crack is in a safe state (not expanding) when the internal pressure increasing factor is positive, the weak magnetic signal has a linear relationship with the crack size. However, the crack is in a dangerous state when the internal pressure increasing factor is negative, and the pipeline crack will expand as the internal pressure increases.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32011852

RESUMO

Many arthropods have compound eyes, which are made up of numerous separate visual units (microlenses) or ommatidia. These natural compound eyes have exceptional optical properties such as wide field of view (FOV), low aberration, and fast motion tracking capability. In this paper, a large-scale artificial compound eye (ACE) is fabricated efficiently using a combination of inkjet printing and air-assisted deformation processes. Both size and geometry of the microlens are controlled via superposed drops on the substrate. The simulation results show that the light intensity of the ACE follows a systematic distribution for tilted incident light, which represents a significant improvement, compared to planar distributed microlenses. We then manufacture ACEs with different heights and diameters, and their FOVs are compared with the theoretically predicted results. The measured FOV was 50°-140°. The acceptance angles for the different ACEs are determined, and their relationship with the ratio of height to radius (H/r) of the microlens is investigated in more detail. Furthermore, the imaging properties of the microlenses with different angles of incidences are studied, which suggest a FOV up to 140° and an acceptance angle of about 50°. The microlens captures images even at an angle of incidence of about 60°. The corresponding distortion in both the x and y directions is also investigated. Our findings provide guidelines for the development and fabrication of ACEs with large FOVs and acceptance angles, which may find applications in military, robotics, medical imaging, and astronomy.

12.
BMC Plant Biol ; 20(1): 59, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019505

RESUMO

BACKGROUND: Basal leaf removal is widely practiced to increase grape cluster sunlight exposure that controls berry rot and improves quality. Studies on its influence on volatile compounds in grape berries have been performed mostly in Mediterranean or marine climate regions. It is uncertain whether similar efficiency can be achieved when grape berries are grown under continental climate. This study aimed to dissect the variation in volatile compound production and transcriptome in sunlight-exposed grape berries in a dry-hot climate region and to propose the key genes related to the variation. RESULTS: Four cluster sunlight exposure strategies, including basal leaf removal at pepper-corn size stage, leaf removal at véraison (LR-V), leaf moving at véraison (LM-V), and half-leaf removal at véraison, were implemented at the north foot of the Mt. Tianshan region of northwestern China. Various cluster exposure treatments resulted in a decline in the concentrations of norisoprenoids and monoterpenes in ripening grape berries. Both ß-carotene and lutein, the substrates of norisoprenoid biosynthesis, were reduced by cluster sunlight exposure. K-means cluster analysis showed that some genes involved in biosynthesis such as VviTPS55, VviTPS60, VviTPS66, VviCCD4a and VviCCD4b exhibited lower expression levels in exposed berries at least at one of the tested stages. Two C6-derived esters with fruity attributes, ethyl hexanoate and hexyl acetate, were reduced markedly. In contrast, main C6 alcohol compound levels were elevated in the LR-V- and LM-V-treated grape berries, which corresponded to the up-regulated expression of VviLOXA, VviLOXO and VviADH1 in the oxylipin pathway. Most of the differentially expressed genes in the exposed and control berries were enriched to the "stress response" processes, and this transcriptome difference was accumulated as the berries matured. Besides, LR-V treatment stimulated a significant up-regulation in photosynthesis-related genes in the grape berries, which did not happen with LM-V treatment. CONCLUSIONS: Cluster sunlight exposure in dry-hot climate viticulture resulted in different volatile-targeted transcriptomic and metabolic responses from those obtained in the temperate Mediterranean or marine climate region. Therefore, a modified canopy management should be adopted to improve the aroma of grape berries.

13.
Sci Rep ; 10(1): 2285, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042026

RESUMO

The Dy3+ doped (Lu,Gd)3Al5O12 garnet phosphors with spherical morphology were obtained via homogeneous precipitation method, followed by calcination at 1100 °C. The particle morphology does not change significantly, but can be controlled by adjusting the urea content. The synthesis, structure, luminescent properties of precursor and resultant particles were analyzed by the combined technologies of XRD, FE-SEM, PLE/PL decay behavior. The (Lu0.975Dy0.025)AG phosphors display strong blue and yellow emission at ~481 nm (4F9/2 → 6H15/2 transition of Dy3+) and ~582 nm 4F9/2 → 6H13/2 transition of Dy3+), respectively. The phosphors have similar color coordinate and temperature of (~0.33, ~0.34), ~5517 K, respectively, which are closed to the white emission. The particle size and luminescent intensity decreased while the lifetime increased with the urea concentration increasing. The Gd3+ addition does not alter the shape/position of emission peaks, but enhance the blue and yellow emission of Dy3+ owing to the efficient Gd3+ → Dy3+ energy transfer. The [(Lu1-xGdx)0.975Dy0.025]3Al5O12 phosphors are expected to be widely used in the lighting and display areas.

14.
Nanomedicine (Lond) ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043430

RESUMO

Aim: Development of a new drug-delivery system using a compound derived from Pronephrium penangianum (J5) for the treatment of cervical cancer. Materials & methods: The delivery system was developed using Prussian blue nanoparticles, camouflaged by red blood cell membrane and with folic acid surface modifications. Results: Our results showed the successful development of a nanodrug-delivery system, which increases the half-life and immune evasion ability of the drug. The mechanism of this system was through suppressing B-cell lymphoma 2 and increasing B-cell lymphoma 2-associated X protein and the cleaved caspase level. An in vivo study also confirmed good antitumor activity without any side effects to normal tissue. Conclusion: This drug-delivery system provides a good alternative for the treatment of cervical cancer using J5.

15.
Clin Chest Med ; 41(1): 25-38, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32008627

RESUMO

Lung cancer is a heterogeneous disease with abundant genomic alterations. Chronic dysregulated airway inflammation facilitates lung tumorigenesis. In contrast, antitumor host immune responses apply continuous selective pressure on the tumor cells during the evolutionary course of the disease. Unprecedented advances in integrative genomic, epigenomic, and cellular profiling of lung cancer and the tumor microenvironment are enhancing the understanding of pulmonary tumorigenesis. This understanding in turn has led to advancements in lung cancer prevention and early detection strategies, and the development of effective targeted therapies and immunotherapies with survival benefit in selected patients.

16.
World J Biol Psychiatry ; : 1-16, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009492

RESUMO

Objectives: Lateral habenula (LHb) is a key brain structure for mediating behavioral responses to aversive stimuli. It receives presynaptic inputs from ventral pallidum (VP) which relates to reward, motivation and hedonics. This study investigated the role of glutamatergic VP-LH projection in negative emotions and depression-like behavior.Methods: The glutamatergic VP-LHb circuits in Vglut2-Cre mice were activated or inhibited using optogenetic manipulation. Real time place aversion test was performed to access aversive behavior. Mice underwent chronic social defeat stress or subthreshold social defeat stress paradigm. Then social interaction test and tail suspension test were carried out to evaluate the stress-induced depression-like behaviors.Results: Activation of VP-LHb glutamatergic projections induced aversive behavior in the real time place aversion test. Activation of this circuit induced depressive-like phenotype after social stress, while optogenetic inhibition of this circuit exerted an antidepressant effect in social stress susceptible mice. Local LHb ketamine administration rescued the depression-like phenotype caused by activation of this circuit.Conclusions: Data from our study demonstrated an involvement of the glutamatergic VP-LHb circuit in the stress-induced depression-related behaviors.

17.
Life Sci Alliance ; 3(3)2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32029571

RESUMO

The gammaherpesviruses (γHVs), human Kaposi sarcoma-associated herpesvirus (KSHV), EBV, and murine γHV68 are prevalent infections associated with lymphocyte pathologies. After primary infection, EBV and γHV68 undergo latent expansion in germinal center (GC) B cells and persists in memory cells. The GC reaction evolves and selects antigen-specific B cells for memory development but whether γHV passively transients or manipulates this process in vivo is unknown. Using the γHV68 infection model, we analyzed the Ig repertoire of infected and uninfected GC cells from individual mice. We found that infected cells displayed the hallmarks of affinity maturation, hypermutation, and isotype switching but underwent clonal expansion. Strikingly, infected cells displayed distinct repertoire, not found in uninfected cells, with recurrent utilization of certain Ig heavy V segments including Ighv10-1 In a manner observed with KSHV, γHV68 infected cells also displayed lambda light chain bias. Thus, γHV68 subverts GC selection to expand in a specific B cell subset during the process that develops long-lived immunologic memory.

18.
Cell Death Dis ; 11(2): 97, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029701

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

19.
Chem Asian J ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034862

RESUMO

We have demonstrated B 2 pin 2 as superior deoxidizing agent for the reductive deoxygenation of quinol derivatives under basic conditions. A wide range of highly functionalized phenols were obtained in good yields including complex drug molecule which revealed the high functional group tolerance of this protocol.

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