Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/ CX3C chemokine receptor 1 (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages in ...the central nervous system (CNS). Although CX3CR1 deficiency is associated with an improved outcome following ischemic brain injury, the mechanism of this observation is largely unknown. The aim of this study was to investigate how CX3CR1 deficiency influences microglia/macrophage functions in the context of its protection following brain ischemia.
Wild-type (WT) and CX3CR1-deficient (CX3CR1⁻/⁻) mice were subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion. The ischemic brain damage was monitored by rodent high-field magnetic resonance imaging. Neurological deficit was assessed daily. Neuronal apoptotic death and reactive oxygen species (ROS) production were analyzed by immunostaining and live imaging. Activation/inflammatory response of microglia/macrophage were assessed using immunohistochemistry, flow cytometry, 5-bromo-2-deoxyuridine labeling, cytokine ELISA, and real-time PCR.
CX3CR1⁻/⁻ mice displayed significantly smaller infarcts and less severe neurological deficits compared to WT controls, following MCAO. In addition, CX3CR1⁻/⁻ MCAO mice displayed fewer apoptotic neurons and reduced ROS levels. Impaired CX3CR1 signaling abrogated the recruitment of monocyte-derived macrophages from the periphery, suppressed the proliferation of CNS microglia and infiltrated macrophage, facilitated the alternative activation (M2 state) of microglia/macrophages, and attenuated their ability to synthesize and release inflammatory cytokines.
Our results suggest that inhibition of CX3CR1 signaling could function as a therapeutic modality in ischemic brain injury, by reducing recruitment of peripheral macrophages and expansion/activation of CNS microglia and macrophages, resulting in protection of neurological function.
Brain ischemia and reperfusion activate the immune system. The abrupt development of brain ischemic lesions suggests that innate immune cells may shape the outcome of stroke. Natural killer (NK) ...cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses, but their role during stroke remains unknown. Herein, we found that NK cells infiltrated the ischemic lesions of the human brain. In a mouse model of cerebral ischemia, ischemic neuron-derived fractalkine recruited NK cells, which subsequently determined the size of brain lesions in a T and B cell-independent manner. NK cell-mediated exacerbation of brain infarction occurred rapidly after ischemia via the disruption of NK cell tolerance, augmenting local inflammation and neuronal hyperactivity. Therefore, NK cells catalyzed neuronal death in the ischemic brain.
Global warming threatens many aspects of human life, for example, by reducing crop yields. Breeding heat-tolerant crops using genes conferring thermotolerance is a fundamental way to help deal with ...this challenge. Here we identify a major quantitative trait locus (QTL) for thermotolerance in African rice (Oryza glaberrima), Thermo-tolerance 1 (TT1), which encodes an α2 subunit of the 26S proteasome involved in the degradation of ubiquitinated proteins. Ubiquitylome analysis indicated that OgTT1 protects cells from heat stress through more efficient elimination of cytotoxic denatured proteins and more effective maintenance of heat-response processes than achieved with OsTT1. Variation in TT1 has been selected for on the basis of climatic temperature and has had an important role in local adaptation during rice evolution. In addition, we found that overexpression of OgTT1 was associated with markedly enhanced thermotolerance in rice, Arabidopsis and Festuca elata. This discovery may lead to an increase in crop security in the face of the ongoing threat of global warming.
Herbivore‐induced terpenes have been reported to function as ecological signals in plant–insect interactions. Here, we showed that insect‐induced cotton volatile blends contained 16 terpenoid ...compounds with a relatively high level of linalool. The high diversity of terpene production is derived from a large terpene synthase (TPS) gene family. The TPS gene family of Gossypium hirsutum and Gossypium raimondii consist of 46 and 41 members, respectively. Twelve TPS genes (GhTPS4–15) could be isolated, and protein expression in Escherichia coli revealed catalytic activity for eight GhTPS. The upregulation of the majority of these eight genes additionally supports the function of these genes in herbivore‐induced volatile biosynthesis. Furthermore, transgenic Nicotiana tabacum plants overexpressing GhTPS12 were generated, which produced relatively large amounts of (3S)‐linalool. In choice tests, female adults of Helicoverpa armigera laid fewer eggs on transgenic plants compared with non‐transformed controls. Meanwhile, Myzus persicae preferred feeding on wild‐type leaves over leaves of transgenic plants. Our findings demonstrate that transcript accumulation of multiple TPS genes is mainly responsible for the production and diversity of herbivore‐induced volatile terpenes in cotton. Also, these genes might play roles in plant defence, in particular, direct defence responses against herbivores.
We systematically analysed insect‐induced cotton volatile blends and characterized 12 terpene synthases (GhTPS4–15) from upland cotton plants. Furthermore, GhTPS12 was transformed into Nicotiana tabacum plants to produce (3S)‐linalool and thus enhanced the repellency of two insect pests belong to different feeding guilds, Helicoverpa armigera and Myzus persicae. Our data indicate that these TPS genes might play roles in plant defence and could be used as tools for the metabolic engineering of terpene biosynthesis in cotton or other plant species.
Parkinson's disease (PD) is a prevalent disease that leads to motor and cognitive disabilities, and oxidative stress (OS) injury was found to be related to the etiology of PD. Increasing evidence has ...shown that SHC3 is aberrantly expressed in neurons. The current study examines the involvement of SHC3 silencing in OS injury in the nigral dopamine neurons in rats with PD via the PI3K-AKT-FoxO signaling pathway.
To study the mechanisms and functions of SHC3 silencing in PD at the tissue level, 170 rats were selected, and a lentivirus-based packaging system was designed to silence SHC3 expression in rats. Furthermore, PC12 cells were selected for in vitro experimentation. To evaluate the effect of SHC3 silencing in nigral dopamine neuronal growth, an MTT assay, propidium iodide (PI) single staining and Annexin V-PI double staining were performed to detect cell viability, cell cycle progression and cell apoptosis, respectively.
SHC3 shRNA led to decreased SOD and MDA levels and enhanced GSH activity, indicating that SHC3 silencing leads to motor retardation. SHC3 silencing repressed the extent of Akt and FoxO phosphorylation, thereby inhibiting the PI3K-AKT-FoxO signaling pathway. Furthermore, in cell experiments, SHC3 silencing suppressed PC12 cell proliferation and cell cycle progression, whereas it enhanced cell apoptosis.
The current study provides evidence suggesting that SHC3 silencing may aggravate OS injury in nigral dopamine neurons via downregulation of the PI3K-AKT-FoxO signaling pathway in PD rats.
A multifunctional design based on vanadium dioxide (VO
2
) metamaterial structure is proposed. Broadband absorption, linear-to-linear (LTL) polarization conversion, linear-to-circular (LTC) ...polarization conversion, and total reflection can be achieved based on the insulator-to-metal transition (IMT) of VO
2
. When the VO
2
is in the metallic state, the multifunctional structure can be used as a broadband absorber. The results show that the absorption rate exceeds 90% in the frequency band of 2.17 - 4.94 THz, and the bandwidth ratio is 77.8%. When VO
2
is in the insulator state, for the incident terahertz waves with a polarization angle of 45°, the structure works as a polarization converter. In this case, LTC polarization conversion can be obtained in the frequency band of 0.1 - 3.5 THz, and LTL polarization conversion also can be obtained in the frequency band of 3.5 - 6 THz, especially in the 3.755 - 4.856 THz band that the polarization conversion rate is over 90%. For the incident terahertz waves with a polarization angle of 0°, the metamaterial structure can be used as a total reflector. Additionally, impacts of geometrical parameters, incidence angle and polarization angle on the operating characteristics have also been investigated. The designed switchable multifunctional metasurfaces are promising for a wide range of applications in advanced terahertz research and smart applications.
Recently studies have demonstrated that the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) may participate in the development and progression of lung ...cancer. In this study, we hypothesized that genetic variant of this lncRNA may affect the prognosis of lung cancer patients.
We conducted a follow-up study for 538 patients with non-small cell lung carcinoma (NSCLC), including 140 early-staged (stage I and II) and 398 advanced staged (stage III and IV) patients. The genetic variant rs3200401 in MALAT1 was then genotyped among this population by using TaqMan assay. The association of this variant with overall survival of these patients was further analyzed.
It was shown that among the advanced lung adenoma patients, subjects carrying rs3200401 CT and CT + TT genotypes had significantly longer median survival time (MST = 29.9, 28.9 vs. 19.3 month, Long-rank P = 0.019 and 0.024, respectively) and decreased death risks crude HR (95% CI) = 0.65 (0.43-0.98) and 0.64 (0.44-0.95), P = 0.040 and 0.025, respectively, when compared to subjects wtih the MALAT1 rs3200401 CC genotype. However, the beneficial effect of rs3200401 was not seen among early NSCLC and advanced lung squamous cell carcinoma patients. We further tested the TCGA data, and found that a higher expression of MALAT1 was associated with metastatic of advanced lung adenocarcinoma but not with lung squamous cell carcinoma.
The rs3200401 T allele located on the lncRNA MALAT1 was associated with a better survival for advanced lung adenocarcinoma patients, which may offer a novel prognostic biomarker for this patient subgroup. However, these results need to be validated in larger populations of lung cancer and the biological function of this variant still warrants further investigation.
Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal ...network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.
To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA).
Design: a multicentre, open-label, randomised ...controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen.
207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24.
174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216).
TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA.
NCT01613079.
The initialization of a quantum system into a certain state is a crucial aspect of quantum information science. While a variety of measurement strategies have been developed to characterize how well ...the system is initialized, for a given one, there is in general a trade-off between its efficiency and the accessible information of the quantum state. Conventional quantum state tomography can characterize unknown states while requiring exponentially expensive time-consuming postprocessing. Alternatively, recent theoretical breakthroughs show that quantum state verification provides a technique to quantify the prepared state with significantly fewer samples, especially for multipartite entangled states. In this Letter, we modify the original proposal to be robust to practical imperfections, and experimentally implement a scalable quantum state verification on two-qubit and four-qubit entangled states with nonadaptive local measurements. For all the tested states, the estimated infidelity is inversely proportional to the number of samples, which illustrates the power to characterize a quantum state with a small number of samples. Compared to the globally optimal strategy which requires nonlocal measurements, the efficiency in our experiment is only worse by a small constant factor ( < 2.5 ). We compare the performance difference between quantum state verification and quantum state tomography in an experiment to characterize a four-photon Greenberger-Horne-Zeilinger state, and the results indicate the advantage of quantum state verification in both the achieved efficiency and precision.
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