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1.
Theranostics ; 10(10): 4359-4373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292500

RESUMO

Lateral flow assay (LFA) has become one of the most widely used point-of-care diagnostic methods due to its simplicity and low cost. While easy to use, LFA suffers from its low sensitivity and poor quantification, which largely limits its applications for early disease diagnosis and requires further testing to eliminate false-negative results. Over the past decade, signal enhancement strategies that took advantage of the laser excitation of plasmonic nanomaterials have pushed down the detection limit and enabled quantification of analytes. Significantly, these methods amplify the signal based on the current LFA design without modification. This review highlights these strategies of signal enhancement for LFA including surface enhanced Raman scattering (SERS), photothermal and photoacoustic methods. Perspectives on the rational design of the reader systems are provided. Future translation of the research toward clinical applications is also discussed.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32300856

RESUMO

ClpX and ClpP are involved in many important functions, including stress responses and energy metabolism, in microorganisms. However, the ClpX and ClpP of microbes used in industrial scale have rarely been studied. Industrial bacterial fermentation experiences a variety of stresses, and energy metabolism is extremely important for industrial bacteria. Thus, the role played by the ClpX and ClpP of industrial bacteria in fermentation should be investigated. Most microorganisms have a single clpP gene, while Corynebacterium crenatum AS 1.542 possesses two clpPs. Herein, the clpX, clpP1, and clpP2 of C. crenatum were cloned, and its fusion protein was expressed and characterized. We also constructed clpX deletion mutant and complementation strain. Results indicate that ClpX serves an important function in thermal, pH, and ethanol stresses. It is also involved in NADPH synthesis and glucose consumption during fermentation.

3.
EClinicalMedicine ; : 100331, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32292899

RESUMO

Background: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes. Methods: We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020. Findings: Of the 34 operative patients, the median age was 55 years (IQR, 43-63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91·2%]), fatigue (25 [73·5%]) and dry cough (18 [52·9%]). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. Interpretation: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%. Funding: National Natural Science Foundation of China.

4.
Oxid Med Cell Longev ; 2020: 6837982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318240

RESUMO

As a pair of differential isomers, Kaji-ichigoside F1 and Rosamultin are both pentacyclic triterpenoids isolated from the subterranean root of Potentilla anserina L., a plant used in folk medicine in western China as antihypoxia and anti-inflammatory treatments. We demonstrated that Kaji-ichigoside F1 and Rosamultin effectively prevented hypoxia-induced apoptosis in vascular endothelial cells. We established a hypoxia model, using EA.hy926 cells, to further explore the mechanisms. Hypoxia promoted the phosphorylation of AKT, ERK1/2, and NF-κB. In hypoxic cells treated with Kaji-ichigoside F1, p-ERK1/2 and p-NF-κB levels were increased, while the level of p-AKT was decreased. Treatment with Rosamultin promoted phosphorylation of ERK1/2, NF-κB, and AKT in hypoxic cells. Following the addition of LY294002, the levels of p-AKT, p-ERK1/2, and p-NF-κB decreased significantly. Addition of PD98059 resulted in reduced levels of p-ERK1/2 and p-NF-κB, while p-AKT levels were increased. Pharmacodynamic analysis demonstrated that both LY294002 and PD98059 significantly inhibited the positive effects of Kaji-ichigoside F1 on cell viability during hypoxia, consistent with the results of hematoxylin-eosin (H&E) staining, DAPI staining, and flow cytometry. The antihypoxia effects of Rosamultin were remarkably inhibited by LY294002 but promoted by PD98059. In Kaji-ichigoside F1- and Rosamultin-treated cells, Bcl2 expression was significantly upregulated, while expression of Bax and cytochrome C and levels of cleaved caspase-9 and cleaved caspase-3 were reduced. Corresponding to pharmacodynamic analysis, LY294002 inhibited the regulatory effects of Kaji-ichigoside F1 and Rosamultin on the above molecules, while PD98059 inhibited the regulatory effects of Kaji-ichigoside F1 but enhanced the regulatory effects of Rosamultin. In conclusion, Kaji-ichigoside F1 protected vascular endothelial cells against hypoxia-induced apoptosis by activating the ERK1/2 signaling pathway, which positively regulated the NF-κB signaling pathway and negatively regulated the PI3K/AKT signaling pathway. Rosamultin protected vascular endothelial cells against hypoxia-induced apoptosis by activating the PI3K/AKT signaling pathway and positively regulating ERK1/2 and NF-κB signaling pathways.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32322944

RESUMO

Baicalin is reported as an effective drug for ulcerative colitis (UC). However, its effect on gut microbiota and short-chain fatty acids (SCFAs) remains unknown. In this study, we investigated the role of baicalin on Th17/Treg balance, gut microbiota community, and SCFAs levels in trinitrobenzene sulphonic acid (TNBS)-induced UC rat model. We found the DAI scores were significantly increased in the TNBS-treated rats, while reduced in the baicalin-treated group in a dose-dependent manner, accompanied with the alleviation of mucosal injury, the reduction of ZO-1, Occludin, and MUC2 expression. At the meanwhile, baicalin repressed the increased levels of reactive oxygen species (ROS) and MDA, while deceased the GSH and SOD levels in colon tissue of rats treated with TNBS. On the other hand, administration of baicalin attenuated the TNBS-induced upregulations of Th17/Treg ratio, indicating a strong amelioration in the colorectal inflammation. More importantly, pyrosequencing of the V4 regions of 16S rRNA genes in rat feces revealed a deviation of the gut microbiota in response to baicalin treatment. In particular, the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels indicated that baicalin reversed TNBS-induced gut dysbiosis OTUs. In addition, we further investigated the fecal levels of major SCFAs in rats and found that baicalin significantly resorted the fecal butyrate levels in rats treated with TNBS. The increased butyrate levels were in consistent with the higher abundance of butyrate-producing species such as Butyricimonas spp., Roseburia spp., Subdoligranulum spp., and Eubacteriu spp. in baicalin-treated group. In conclusion, our findings suggest that baicalin possibly protected rats against ulcerative colitis by regulation of Th17/Treg balance, and modulation of both gut microbiota and SCFAs. Baicalin may be used as a prebiotic agent to treat ulcerative colitis-associated inflammation and gut dysbiosis.

6.
Acta Pharmacol Sin ; 41(5): 629-637, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31911638

RESUMO

Geissoschizine methyl ether (GM) is an indole alkaloid isolated from Uncaria rhynchophyll (UR) that has been used for the treatment of epilepsy in traditional Chinese medicine. An early study in a glutamate-induced mouse seizure model demonstrated that GM was one of the active ingredients of UR. In this study, electrophysiological technique was used to explore the mechanism underlying the antiepileptic activity of GM. We first showed that GM (1-30 µmol/L) dose-dependently suppressed the spontaneous firing and prolonged the action potential duration in cultured mouse and rat hippocampal neurons. Given the pivotal roles of ion channels in regulating neuronal excitability, we then examined the effects of GM on both voltage-gated and ligand-gated channels in rat hippocampal neurons. We found that GM is an inhibitor of multiple neuronal channels: GM potently inhibited the voltage-gated sodium (NaV), calcium (CaV), and delayed rectifier potassium (IK) currents, and the ligand-gated nicotinic acetylcholine (nACh) currents with IC50 values in the range of 1.3-13.3 µmol/L. In contrast, GM had little effect on the voltage-gated transient outward potassium currents (IA) and four types of ligand-gated channels (γ-amino butyric acid (GABA), N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainite (AMPA/KA receptors)). The in vivo antiepileptic activity of GM was validated in two electricity-induced seizure models. In the maximal electroshock (MES)-induced mouse seizure model, oral administration of GM (50-100 mg/kg) dose-dependently suppressed generalized tonic-clonic seizures. In 6-Hz-induced mouse seizure model, oral administration of GM (100 mg/kg) reduced treatment-resistant seizures. Thus, we conclude that GM is a promising antiepileptic candidate that inhibits multiple neuronal channels.

7.
Int J Biol Macromol ; 142: 592-599, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739036

RESUMO

Zein electrospun nanofibers have poor water resistance, which restricts its applications in food preservation. To improve the water resistance of nanofibers, zein/ethyl cellulose (EC) hybrid nanofibers were prepared at different ratios. Besides, we also encapsulated cinnamon essential oil (CEO) into electrospun fibers for Agaricus bisporus preservation. As the weight ratio of EC increased from 0% (ZE-10) to 100% (ZE-01), the viscosity of electrospinning solutions gradually increased from 80.33 ±â€¯19.23 mPa·s to 756.78 ±â€¯22.48 mPa·s, resulting in sufficient chain entanglement for the preparation of uniform fibers. The average diameters of ZE-01, ZE-12, ZE-11, ZE-21, and ZE-10 nanofibers were 326 ±â€¯53 nm, 267 ±â€¯31 nm, 237 ±â€¯51 nm, 292 ±â€¯45 nm, and 362 ±â€¯70 nm, respectively. The hydrogen bonds between the hydroxyl groups of ethyl cellulose and the amino groups of zein decreased the amount of free hydrophilic group, thus improving water resistance of nanofibers. Food packaging potential was evaluated using Agaricus bisporus. The zein/EC nanofibers loaded CEO significantly decreased weight loss and maintained the firmness of the Agaricus bisporus, and improved the quality of the Agaricus bisporus during storage.

8.
Curr Med Sci ; 39(6): 906-912, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845221

RESUMO

This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1 (Dectin-1), Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) influence the susceptibility to pulmonary invasive fungal disease (IFD) in patients with acute myeloid leukemia (AML) from a Chinese Han population. Eight single nucleotide polymorphisms (SNPs) of Dectin-1 (rs16910526, rs3901533, and rs7309123), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791) and MyD88 (rs4988453 and rs4988457) in the genomic DNA of 172 adult AML patients were genotyped. Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus guidelines. SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD. The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR (qRT-PCR), and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed. Two Dectin-1 intron SNPs (rs3901533 and rs7309123) were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population. Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model (G/T+G/G vs. T/T, OR: 2.158; 95% CI: 1.109-4.2, P=0.02), Dectin-1 rs3901533 G allele (OR: 2.201; 95% CI: 1.206-4.019, P=0.01), or Dectin-1 rs7309123 C allele (OR: 1.919; 95% CI: 1.047-3.518, P=0.03). There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs (rs16910526), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791) or MyD88 (rs4988453 and rs4988457). In conclusion, two Dectin-1 SNPs (rs3901533 and rs7309123) are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Infecções Fúngicas Invasivas/genética , Lectinas Tipo C/genética , Leucemia Mieloide Aguda/microbiologia , Pneumopatias Fúngicas/genética , Grupo com Ancestrais do Continente Asiático/genética , China/etnologia , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Infecções Fúngicas Invasivas/etnologia , Leucemia Mieloide Aguda/etnologia , Leucemia Mieloide Aguda/genética , Pneumopatias Fúngicas/etnologia , Masculino , Fator 88 de Diferenciação Mieloide/genética , Polimorfismo de Nucleotídeo Único , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
9.
Materials (Basel) ; 12(23)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766508

RESUMO

Silicon carbide particle-reinforced aluminum matrix composite (SiCp/Al) has been widely used in the military and aerospace industry due to its special performance; however, there remain many problems in the processing. The present paper introduces an ultrasonic vibration tensile apparatus and a composite tensile specimen and performs Abaqus finite element simulation on high-volume SiCp/Al. The results show that the stress-strain curve increases linearly during conventional tensile strength; the intermittent vibration tensile strength is similar to the full course vibration tensile strength: The magnitude of the stress reduction increases as the amplitude of the ultrasound increases and the vibration frequency increases. The tensile rate is inversely proportional to the magnitude of the stress reduction, and in the ultrasonic parameters, the amplitude has the greatest influence on the magnitude of the stress reduction, followed by the tensile rate; additionally, the frequency has the least influence on the magnitude of the stress reduction. The experimental results show that the simulation results are consistent with the experimental results.

10.
Opt Lett ; 44(20): 5097-5100, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613273

RESUMO

We report an enhanced scheme to achieve superluminal propagation at negative group velocity in optical fibers with a hybrid Brillouin lasing cavity. The hybrid cavity was constructed by introducing a pumped erbium-doped fiber to enhance the Brillouin lasing. Experimental results show that with the assistance of a hybrid cavity, the threshold power of the Brillouin lasing was reduced from 758.7 to 235.7 mW, and the time advancement was promoted to 444.4 ns after passing through 2 m highly nonlinear fiber at a modulation frequency of 1 MHz, corresponding to a group index of -44.6 and group velocity of -0.0224c. Moreover, a maximum negative group index of -21,029 was observed at the modulation frequency of 1 kHz, which, to the best of our knowledge, is the highest negative group index ever reported in optical fibers via stimulated Brillouin scattering.

11.
BMC Mol Cell Biol ; 20(1): 46, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660855

RESUMO

BACKGROUND: It was reported that microRNA-21(miR-21) was differentially expressed in the keratinocytes of psoriasis patients, and it may influence the apoptosis and proliferation of cells. The role of lncRNA maternally expressed gene3 (MEG3), a competing endogenous RNAs of miR-21, in the progression of psoriasis remains unclear. We aimed to unfold the influence of MEG3 and miR-21 on the proliferation and apoptosis of psoriasis epidermal cells. METHODS: 50µg/L TNF-α was used to treat HaCaTs and NHEKs cells for 24 h, and then different experiments were conducted. qRT-PCR were applied for measuring the mRNA level of MEG3, miR-2, and caspase-8, and the protein expression of caspase-8 was measured with western blotting. Flow cytometry was used for assessing apoptosis. Cell proliferation was detected using MTT and colony formation assays. Dual luciferase reporter assay was applied for confirming the binding site between MEG3 and miR-21, miR-21 and Caspase-8. RESULTS: A cell model for in vitro studying the role of MEG3 in psoriasis pathophysiology was established using HaCaT and HHEKs. MEG3 was significantly down-regulated in HaCaT, HHEKs, and psoriatic skin samples. MEG3 inhibits proliferation and promotes apoptosis of Activated-HaCaT (Act-HaCaT) and Activated-HHEKs (Act- HHEK) by regulating miR-21, and the binding site between MEG3 and miR-21 was identified. We also found that miR-21 could inhibit the level of caspase-8 and identified the binding site between caspase-8 and miR-21. Some down-stream proteins of caspase-8, Cleaved caspase-8, cytc, and apaf-1 were regulated by miR-21 and MEG3. CONCLUSION: MEG3/miR-21 axis may regulate the expression of caspase-8, and further influence the proliferation and apoptosis of psoriasis keratinocyte, Act-HaCaT and Act- HHEK. Therefore, our findings may provide a new thought for the study of pathogenesis and treatment of psoriasis.

12.
Hepatology ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509261

RESUMO

BACKGROUND AND AIMS: DNA damage-induced NF-κB activation is a major obstacle to effective antitumour chemotherapy. Long noncoding RNAs (lncRNAs) that regulate chemoresistance of cancer cells remain largely unknown. This study aimed to characterize the lncRNAs that may affect chemotherapy sensitivity. APPROACH AND RESULTS: We found that lncRNA PDIA3P1 (protein disulfide isomerase family A member 3 pseudogene 1) was up-regulated in multiple cancer types and following treatment with DNA-damaging chemotherapeutic agents, like doxorubicin (Dox). Higher PDIA3P1 level was associated with poorer recurrence-free survival of human hepatocellular carcinoma (HCC). Both gain-of-function and loss-of-function studies revealed that PDIA3P1 protected cancer cells from Dox-induced apoptosis and allowed tumor xenografts to grow faster and to be more resistant to Dox treatment. Mechanistically, miR-125a/b and miR-124 suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), but PDIA3P1 bound to miR-125a/b/miR-124 and relieved their repression on TRAF6, leading to activation of the nuclear factor kappa B (NF-κB) pathway. Consistently, the effect of PDIA3P1 inhibition in promoting Dox-triggered apoptosis was antagonized by silencing the inhibitor of κBα (IκBα) or overexpressing TRAF6. Administration of BAY 11-7085, an NF-κB inhibitor attenuated PDIA3P1-induced resistance to Dox treatment in mouse xenografts. Moreover, up-regulation of PDIA3P1 was significantly correlated with elevation of TRAF6, phosphorylated p65, or NF-κB downstream anti-apoptosis genes in human HCC tissues. These data indicate that enhanced PDIA3P1 expression may confer chemoresistance by acting as a microRNA sponge to increase TRAF6 expression and augment NF-κB signaling. Subsequent investigations into the mechanisms of PDIA3P1 up-regulation revealed that human homologue of mRNA transport mutant 4 (hMTR4), which promotes RNA degradation, could bind to PDIA3P1, and this interaction was disrupted by Dox treatment. Overexpression of hMTR4 attenuated Dox-induced elevation of PDIA3P1, whereas silencing hMTR4 increased PDIA3P1 level, suggesting that Dox may up-regulate PDIA3P1 by abrogating the hMTR4-mediated PDIA3P1 degradation. CONCLUSION: There exists a hMTR4-PDIA3P1-miR-125/124-TRAF6 regulatory axis that regulates NF-κB signaling and chemoresistance, which may be exploited for anticancer therapy.

13.
Opt Express ; 27(18): 25485-25492, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31510420

RESUMO

We proposed and experimentally demonstrated a new scheme for enhancing the sensitivity of a fiber laser sensor using Brillouin slow light. The Brillouin laser was exposed to environmental vibrations, producing fluctuations at 408 kHz frequency, which were then interrogated using a Mach-Zehnder interferometer. By introducing Brillouin slow light into one arm of the interferometer, the sensitivity increased by 1.57 times that of a device without slow light. We believe this scheme may provide a new way of using Brillouin slow light and that it has some important implications regarding the use of fiber sensors for measuring the vibration, temperature, strain and so on.

14.
Front Microbiol ; 10: 1710, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402906

RESUMO

Listeria monocytogenes is an important foodborne pathogen causing public concern. A total of 3354 retail foods in bulk were sampled and screened for L. monocytogenes. Seventy-three (2.2%) samples including 21 ready-to-eat (RTE) foods and 52 raw foods were confirmed positive for L. monocytogenes. Sushi and salmon sashimi occupied the top two slots in RTE foods with relatively high presence rate of 12.9 and 6.9%, respectively. Meanwhile, L. monocytogenes was found to be distributed unequally in raw foods; the presence rates in raw meat (3.5%) and poultry (3.8%) were significantly higher than that in raw seafood (1.3%). Notably, L. monocytogenes was not detected in raw freshwater food. The L. monocytogenes isolates belonged to four serotypes, 1/2a, 1/2b, 1/2c, and 4b, with the most prevalent serotype being 1/2a (47.9%). Eighteen sequence types (STs) and eighteen virulence types (VTs) containing four newly assigned VTs (VT180, VT181, VT182, and VT183) were determined via multilocus sequence typing (MLST) and multi-virulence-locus sequence typing (MVLST). Among the 73 L. monocytogenes isolates, 23 (31.5%) belonged to epidemic clones (ECs) including ECI, ECIV, ECV, ECVI, ECVIII and ECXI among which ECV was predominant. Antibiotic susceptibility tests revealed a high resistance rate (11.0%) to tetracycline. Moreover, we identified the distribution patterns of virulence genes of four Listeria pathogenicity islands (LIPI) in L. monocytogenes isolates. prfA, hly, plcA, plcB, mpl, actA genes in LIPI-1 and inlA, inlB, inlC, inlJ genes in LIPI-2 were detected in approximately all L. monocytogenes isolates. The distribution of both LIPI-3 genes and LIPI-4 genes exhibited association with lineage and ST. LIPI-4 genes were present exclusively in ST87 isolates. Relatedness analysis revealed the absence of distinct association between STs, ECs, LIPI-3 and LIPI-4 distribution and specific food groups. This study provided fundamental data for Chinese food safety authorities to grasp the contamination status of L. monocytogenes in foods, assess the potential risk of this pathogen and further address the safety issue of retail foods in bulk in China.

15.
Opt Lett ; 44(16): 4008-4011, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415534

RESUMO

Bidirectional mode-locked lasers are very useful in laser sensing and optical communications. Here we report a bidirectional domain wall soliton (DWS) fiber laser with an anomalous dispersion cavity. Two mode-locked dark pulse trains propagating in the opposite directions have been generated. Moreover, the specific application as a gyroscopic effect has been demonstrated by mounting this DWS laser on a rotating platform. The beat frequency of the two dark pulse DWS beams is measured as a linear function of the rotation velocity. The rotation sensitivity reaches 3.31 kHz/(deg/s), which are comparable with the one in a bright pulse laser gyroscope. Without the limit of using tunable delay lines, the DWS laser gyroscope has the advantages of simple structure, high sensitivity, and low cost, while possessing the entire superiority of a mode-locked laser gyroscope. It is more promising for the applications in modern inertia navigation systems.

16.
Neurosci Bull ; 35(5): 781-790, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31168753

RESUMO

The laterodorsal tegmentum (LDT) is a brain structure involved in distinct behaviors including arousal, reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear. Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex (VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive (PV+) GABAergic cells received preferential projections from local LDT neurons. With regard to the different subtypes of GABAergic cells, a considerable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatin-positive cells than to PV+ cells. Diverse inputs to the LDT on a system-wide level were revealed.

17.
Appl Opt ; 58(10): 2624-2629, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045062

RESUMO

We introduce a fast compensation scheme to realize arbitrary focusing after propagation through a scattering sample. Theoretical analysis of the effect of cross terms on multi-point focusing is conducted based on the transmission matrix theory. The results show that the cross-term influence is very significant, which needs to be considered. The Multi-Population Genetic Algorithm is adopted to retrieve the input mode for the suppression of the cross-term effect. In order to realize fast compensation and reduce measurement noise, the off-axis holographic method is used to measure the large transmission matrix, which reduces the number of measurements compared with the traditional method. In the experiment, after retrieving the input phase, we obtain a high-quality focal output, and the signal-to-noise ratio is increased by 13.6 dB.

18.
J Diabetes Res ; 2019: 8520856, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906786

RESUMO

Background: A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. Methods: Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. Results: HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. Conclusions: These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Inibidores de Histona Desacetilases/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Inibidores de Histona Desacetilases/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
19.
Nature ; 567(7749): 516-520, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30818324

RESUMO

The nitrogen cycle has been radically changed by human activities1. China consumes nearly one third of the world's nitrogen fertilizers. The excessive application of fertilizers2,3 and increased nitrogen discharge from livestock, domestic and industrial sources have resulted in pervasive water pollution. Quantifying a nitrogen 'boundary'4 in heterogeneous environments is important for the effective management of local water quality. Here we use a combination of water-quality observations and simulated nitrogen discharge from agricultural and other sources to estimate spatial patterns of nitrogen discharge into water bodies across China from 1955 to 2014. We find that the critical surface-water quality standard (1.0 milligrams of nitrogen per litre) was being exceeded in most provinces by the mid-1980s, and that current rates of anthropogenic nitrogen discharge (14.5 ± 3.1 megatonnes of nitrogen per year) to fresh water are about 2.7 times the estimated 'safe' nitrogen discharge threshold (5.2 ± 0.7 megatonnes of nitrogen per year). Current efforts to reduce pollution through wastewater treatment and by improving cropland nitrogen management can partially remedy this situation. Domestic wastewater treatment has helped to reduce net discharge by 0.7 ± 0.1 megatonnes in 2014, but at high monetary and energy costs. Improved cropland nitrogen management could remove another 2.3 ± 0.3 megatonnes of nitrogen per year-about 25 per cent of the excess discharge to fresh water. Successfully restoring a clean water environment in China will further require transformational changes to boost the national nutrient recycling rate from its current average of 36 per cent to about 87 per cent, which is a level typical of traditional Chinese agriculture. Although ambitious, such a high level of nitrogen recycling is technologically achievable at an estimated capital cost of approximately 100 billion US dollars and operating costs of 18-29 billion US dollars per year, and could provide co-benefits such as recycled wastewater for crop irrigation and improved environmental quality and ecosystem services.


Assuntos
Agricultura/métodos , Fertilizantes/análise , Fertilizantes/provisão & distribução , Ciclo do Nitrogênio , Nitrogênio/análise , Nitrogênio/provisão & distribução , Qualidade da Água/normas , Agricultura/estatística & dados numéricos , Animais , China , Ecossistema , Monitoramento Ambiental , Abastecimento de Alimentos/métodos , Abastecimento de Alimentos/estatística & dados numéricos , Humanos , Poluentes Químicos da Água/análise , Poluição da Água/análise
20.
Hepatology ; 70(1): 259-275, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30865310

RESUMO

Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc-UCID (lncRNA up-regulating CDK6 by interacting with DHX9). Lnc-UCID was up-regulated in hepatocellular carcinoma (HCC), and a higher lnc-UCID level was correlated with shorter recurrence-free survival of HCC patients. Both gain-of-function and loss-of function studies revealed that lnc-UCID enhanced cyclin-dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc-UCID-silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc-UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850-1030-nt domain of lnc-UCID interacted physically with DEAH (Asp-Glu-Ala-His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post-transcriptionally suppressed CDK6 expression by binding to the 3'-untranslated region (3'UTR) of CDK6 mRNA. Further investigation disclosed that lnc-UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6-3'UTR. In an attempt to explore the mechanisms responsible for lnc-UCID up-regulation in HCC, we found that the lnc-UCID gene was frequently amplified in HCC. Furthermore, miR-148a, whose down-regulation was associated with an increase of lnc-UCID in HCC, could bind lnc-UCID and inhibit its expression. Conclusion: Up-regulation of lnc-UCID, which may result from amplification of its gene locus and down-regulation of miR-148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy.

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