Grass Carp Reovirus Nonstructural Proteins Avoid Host Antiviral Immune Response by Targeting the RLR Signaling Pathway.

Grass carp reovirus (GCRV) is a highly virulent RNA virus that mainly infects grass carp and causes hemorrhagic disease. The roles of nonstructural proteins NS38 and NS80 of GCRV-873 in the viral replication cycle and viral inclusion bodies have been established. However, the strategies that NS38 and NS80 used to avoid host antiviral immune response are still unknown. In this study, we report the negative regulations of NS38 and NS80 on the RIG-I-like receptors (RLRs) antiviral signaling pathway and the production of IFNs and IFN-stimulated genes. First, both in the case of overexpression and GCRV infection, NS38 and NS80 inhibited the IFN promoter activation induced by RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7 and mRNA abundance of key antiviral genes involved in the RLR-mediated signaling. Second, both in the case of overexpression and GCRV infection, NS38 interacted with piscine TBK1 and IRF3, but not with piscine RIG-I, MDA5, MAVS, and TNF receptor-associated factor (TRAF) 3. Whereas NS80 interacted with piscine MAVS, TRAF3, and TBK1, but not with piscine RIG-I, MDA5, and IRF3. Finally, both in the case of overexpression and GCRV infection, NS38 inhibited the formation of the TBK1-IRF3 complex, but NS80 inhibited the formation of the TBK1-TRAF3 complex. Most importantly, NS38 and NS80 could hijack piscine TBK1 and IRF3 into the cytoplasmic viral inclusion bodies and inhibit the translocation of IRF3 into the nucleus. Collectively, all of these data demonstrate that GCRV nonstructural proteins can avoid host antiviral immune response by targeting the RLR signaling pathway, which prevents IFN-stimulated gene production and facilitates GCRV replication.

The Impact of Home Cardiac Rehabilitation on Quality of Life and Psychological Well-Being in Patients with Coronary Heart Disease: A Randomized Controlled Study.

BACKGROUND Percutaneous coronary intervention (PCI), a therapeutic approach to coronary heart disease, significantly alleviates symptoms of coronary heart disease (CHD) and substantially improves quality of life. This study aimed to investigate the effect of home cardiac rehabilitation (HCR) on patients after PCI. MATERIAL AND METHODS We randomly divided 106 patients after PCI into an Intervention group (n=52) and a Control group (n=53). Left ventricular ejection fraction (LVEF), blood pressure, blood glucose, and low-density lipoprotein were measured in both groups before hospital discharge and after 3 months of engaging in the intervention. Patients were assessed using the short-form health survey (SF-12) scale and Hospital Anxiety and Depression Scale (HADS) scale. RESULTS After 3 months of HCR intervention, SF-12 scores of patients in the Intervention group were significantly higher compared to patients in the Control group (physical component summary (PCS): 47.46±9.86 vs 43.28±8.21; and Mental Component Summary (MCS): 50.68±9.82 vs 48.26±9.69) (P.

Effects of beauvericin on the blood cells of Bombyx mori.

In this study, silkworms were treated by injection of the bioactive depsipeptide beauvericin (BEA) to explore its effect on the cellular immunity of larvae of the silkworm Bombyx mori. The results showed that: The LC50 of BEA for silkworms on the 3rd day of the 4th instar was 362.36 µM. The total count of circulating hemocytes in the silkworms decreased at 12 h after injection with 350 µM BEA, and reached the minimum value at 72 h post-treatment; at 48 h post-treatment, a large number of nodules formed by the aggregation of blood cells of the silkworms were observed under the light microscope. The survival rate of hemocytes in the larvae treated with BEA was significantly reduced in a dose-dependent manner in vivo and in vitro. The encapsulation of Q-Sepharose Fast Flow (QFF) gel particles by hemocytes in the treatment group was significantly higher than that in the control group at 1.5 h and 3 h post-treatment (P < 0.05). Moreover, the melanization ratio of QFF gel particles kept increasing with treatment time. The melanization rate at 24 h after treatment was significantly higher than that at other times (P < 0.05), reaching 55.33 %. Under the scanning electron microscope, BEA-treated larvae showed protrusions on the surface of their blood cells in vivo. Under the transmission electron microscope, it was observed that silkworm hemocytes were vacuolated. This study demonstrated that BEA had an effect on the blood cells of silkworms, and has thrown some light on the inhibitory effect and mechanism of BEA on insect cellular immunity.

Effect of Ultrasonic Treatment on Structure, Antibacterial Activity of Sugarcane Leaf Polysaccharides.

This study investigated the impact of ultrasonic extraction (UE) on the structure and in vitro antibacterial activity of polysaccharides from sugarcane leaves (SLW). Native sugarcane leaf polysaccharides were treated with ultrasound (480 W) for 3 h to yield sugarcane leaf polysaccharides (SLU). Compared to SLW (33.59 kDa), the molecular weight of SLU (13.08 kDa) was significantly decreased, while the monosaccharide composition of SLU was unchanged. The results of SEM and XRD indicated that UE significantly changed the surface morphology of SLW and destroyed its inner crystalline structure. In vitro experiments showed that SLU had stronger antibacterial activity. These findings revealed that UE treatment could alter the tertiary structure of SLW but had no impact on its primary structure. Furthermore, the antibacterial activity of SLW could be greatly enhanced after UE treatment. As a bioactive additive, SLU has great application potential in functional foods, cosmetics, and pharmaceuticals.

NOD1 Promotes Antiviral Signaling by Binding Viral RNA and Regulating the Interaction of MDA5 and MAVS.

Nucleotide oligomerization domain-like receptors (NLRs) and RIG-I-like receptors (RLRs) detect diverse pathogen-associated molecular patterns to activate the innate immune response. The role of mammalian NLR NOD1 in sensing bacteria is well established. Although several studies suggest NOD1 also plays a role in sensing viruses, the mechanisms behind this are still largely unknown. In this study, we report on the synergism and antagonism between NOD1 and MDA5 isoforms in teleost. In zebrafish, the overexpression of NOD1 enhances the antiviral response and mRNA abundances of key antiviral genes involved in RLR-mediated signaling, whereas the loss of NOD1 has the opposite effect. Notably, spring viremia of carp virus-infected NOD1-/- zebrafish exhibit reduced survival compared with wild-type counterparts. Mechanistically, NOD1 targets MDA5 isoforms and TRAF3 to modulate the formation of MDA5-MAVS and TRAF3-MAVS complexes. The cumulative effects of NOD1 and MDA5a (MDA5 normal form) were observed for the binding with poly(I:C) and the formation of the MDA5a-MAVS complex, which led to increased transcription of type I IFNs and ISGs. However, the antagonism between NOD1 and MDA5b (MDA5 truncated form) was clearly observed during proteasomal degradation of NOD1 by MDA5b. In humans, the interactions between NOD1-MDA5 and NOD1-TRAF3 were confirmed. Furthermore, the roles that NOD1 plays in enhancing the binding of MDA5 to MAVS and poly(I:C) are also evolutionarily conserved across species. Taken together, our findings suggest that mutual regulation between NOD1 and MDA5 isoforms may play a crucial role in the innate immune response and that NOD1 acts as a positive regulator of MDA5/MAVS normal form-mediated immune signaling in vertebrates.

Phosphatase PPM1L Prevents Excessive Inflammatory Responses and Cardiac Dysfunction after Myocardial Infarction by Inhibiting IKKß Activation.

Although the inflammatory response triggered by damage-associated molecular patterns (DAMPs) in the infarcted cardiac tissues after acute myocardial infarction (MI) contributes to cardiac repair, the unrestrained inflammation induces excessive matrix degradation and myocardial fibrosis, leading to the development of adverse remodeling and cardiac dysfunction, although the molecular mechanisms that fine tune inflammation post-MI need to be fully elucidated. Protein phosphatase Mg2+/Mn2+-dependent 1L (PPM1L) is a member of the serine/threonine phosphatase family. It is originally identified as a negative regulator of stress-activated protein kinase signaling and involved in the regulation of ceramide trafficking from the endoplasmic reticulum to Golgi apparatus. However, the role of PPM1L in MI remains unknown. In this study, we found that PPM1L transgenic mice exhibited reduced infarct size, attenuated myocardial fibrosis, and improved cardiac function. PPM1L transgenic mice showed significantly lower levels of inflammatory cytokines, including IL-1ß, IL-6, TNF-α, and IL-12, in myocardial tissue. In response to DAMPs, such as HMGB1 or HSP60, released in myocardial tissue after MI, macrophages from PPM1L transgenic mice consistently produced fewer inflammatory cytokines. PPM1L-silenced macrophages showed higher levels of inflammatory cytokine production induced by DAMPs. Mechanically, PPM1L overexpression selectively inhibited the activation of NF-κB signaling in myocardial tissue post-MI and DAMP-triggered macrophages. PPM1L directly bound IKKß and then inhibited its phosphorylation and activation, leading to impaired NF-κB signaling activation and suppressed inflammatory cytokine production. Thus, our data demonstrate that PPM1L prevents excessive inflammation and cardiac dysfunction after MI, which sheds new light on the protective regulatory mechanism underlying MI.

High-dynamic-range blood flow rate measurement in a large-diameter vessel.

We propose a new, to the best of our knowledge, compound technique to measure high-dynamic-range blood flow rate in a large-diameter vessel, which combines the dynamic scattering light (DLS) and the laser speckle contrast imaging (LSCI) methods, possessing the advantages of the high temporal resolution of DLS and the robust property of LSCI. By controlling the second-order spatial correlations of the laser speckle through two imaging systems, the speckle temporal intensity autocorrelation function g2(t) and the decorrelation time τc are directly measured using a high-speed camera. It turns out the enhanced spatial second-order correlation helps to measure the blood flow with higher dynamic range and that the measured parameter ß and the blood flow dynamics n were accurately determined. For further improvement the dynamic range, the modified LSCI method was adopted, and the decorrelation time as a function of blood flow rate was constructed. It reveals the feasibility of measuring the high flow rate in large-diameter vessels and provides significant guidance for the future biomedical study of the myocardial perfusion in coronary artery bypass grafting, ghost imaging, and ghost cytometry.

Malignancy is a risk factor for higher COVID-19 severity:A meta-analysis.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has been an almost global pandemic with significant public health impacts. The increasing prevalence of malignancy has become a leading cause of human mortality. However, conflicting findings have been published on the association between malignancy and COVID-19 severity. This study aims to assess the pooled proportion of malignancy amongst 2019-nCov patients and to investigate the association between malignancy and COVID-19 severity. METHODS: Correlative studies were identi?ed by systematically searching electronic databases (PubMed, Web of Sciences and Embase) up to September 2, 2020. All data analyses were carried out using Stata 15.0. RESULTS: Twenty-nine studies consisting of 9475 confirmed COVID-19 patients (median age 54.4 years [IQR 49-62], 54.0% men) were included. The overall proportion of malignancy was 2.5% (95% CI 1.6%-3.4%). The proportion of malignancy was higher in patients with severe/critical 2019-nCoV than those in non-severe/non-critical group (3.9% [95% CI 2.0-6.3] vs 1.4% [95% CI 0.8-2.2]). Furthermore, pre-existing malignancy was associated with more than twofold higher risk of severe/critical patients with COVID-19 (OR 2.25, 95% CI 1.65-3.06 I2 = 0.0%). CONCLUSION: Malignancy was associated with up to 2.3-fold higher risk of severe/critical COVID-19 and may serve as a clinical predictor for adverse outcomes.

Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology.

Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.

Acceleration and expansion of a photorealistic computer-generated hologram using backward ray tracing and multiple off-axis wavefront recording plane methods.

Holograms can reconstruct the light wave field of three-dimensional objects. However, the computer-generated hologram (CGH) requires much calculating time. Here we proposed a CGH generation algorithm based on backward ray tracing and multiple off-axis wavefront recording planes (MO-WRP) to generate photorealistic CGH with a large reconstruction image. In this method, multiple WRPs were placed parallelly between the virtual object and the hologram plane. Virtual rays were emitted from the pixel of WRPs and intersect with the object. The complex amplitude of WRPs is then determined by illumination module, such as Phong reflection module. The CGH was generated by the shifted Angular Spectrum Propagation (ASP) from WRPs to the hologram plane. Experimental results demonstrate the effectiveness of this method, and the CGH generation rate is 37.3 frames per second (1 WRP) and 9.8 frames per second (2×2 WRPs).

Calibration method of three-dimensional plane array laser radar based on space-time transformation.

As a measurement system that can realize target detection and optical imaging, the accuracy of three-dimensional laser radar is a main performance index, which makes calibration an extremely important work. Traditional calibration methods have many disadvantages, such as harsh environment requirements, complex and tedious calibration processes, and inaccurate calibration results. To solve these problems, we propose a calibration method so that the relative position of the cooperative target and the detection sensor is fixed. The principle of space-time transform is used to simulate distance, and the synchronous control of distance is realized by controlling the delay module. In addition, a simple and practical calibration device is designed. In the actual measurement, the average absolute error is 0.0019 m, and the relative error is 0.0678% in the range of 0.5-25 m. The experimental results show that this method is stable and accurate, and it can calibrate the plane array laser radar quickly and accurately.

Method of improving the measurement accuracy of plane array imaging laser radar by pixel cascade.

The plane array imaging laser radar is the product of the combination of the area array imaging optical system and the range laser radar. With extended illumination and area array detection, the target can be measured in three dimensions without mechanical scanning. In this paper, a CMOS-type built-in optical mixer is used, which is a kind of matrix depth sensor. The size of a single pixel of the sensor chip determines its maximum resolution accuracy in two-dimensional distribution measurement, which also restricts the improvement of measurement accuracy to a certain extent. In this paper, a post-processing measurement method is proposed, which expands the processed data object from a single pixel to a regional pixel, transforms the measurement of displacement into the measurement of amplitude distribution changes, and effectively utilizes the cascaded characteristics between a single pixel and pixel area. The purpose is to break through the limitation of the size of a single pixel and thus improve the measurement accuracy. The validity of the method is verified by theoretical calculation and experimental measurements, and the measurement accuracy is improved by 6 times in practical test. This method can improve the measurement accuracy and performance of existing system equipment without breaking through the limitation of pixel physical size and will be highly interesting for practical applications.

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress.

Excessive plasma triglyceride (TG) and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism and is involved in the regulation of oxidative stress. Although inflammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE-/- ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE-/- mice. ApoE/Plin5 double knockout (ApoE-/- Plin5-/- ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated TG, total cholesterol, and low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol contents. ApoE-/- Plin5-/- exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IκBα/nuclear factor kappa B pathway was strongly activated in ApoE-/- Plin5-/- . Notably, apoptosis was dramatically induced by ApoE-/- Plin5-/- , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2. In addition, ApoE-/- Plin5-/- contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinases pathways. In vitro, oxidized low-density lipoprotein (ox-LDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress, and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions.

Overexpression of ANAC046 Promotes Suberin Biosynthesis in Roots of Arabidopsis thaliana.

NAC (NAM (no apical meristem), ATAF1/2, and CUC2 (cup-shaped cotyledon)) proteins are one of the largest families of plant-specific transcription factors, and this family is present in a wide range of land plants. Here, we have investigated the role of ANAC046 in the regulation of suberin biosynthesis and deposition in Arabidopsis. Subcellular localization and transcriptional activity assays showed that ANAC046 localizes in the nucleus, where it functions as a transcription activator. Analysis of the PANAC046:GUS lines revealed that ANAC046 is mainly expressed in the root endodermis and periderm, and is also induced in leaves by wounding. The transgenic lines overexpressing ANAC046 exhibited defective surfaces on the aerial plant parts compared to the wild-type (WT) as characterized by increased permeability for Toluidine blue stain and greater chlorophyll leaching. Quantitative RT-PCR analysis showed that the expression of suberin biosynthesis genes was significantly higher in the roots and leaves of overexpression lines compared to the WT. The biochemical analysis of leaf cuticular waxes showed that the overexpression lines accumulated 30% more waxes than the WT. Concurrently, overexpression lines also deposited almost twice the amount of suberin content in their roots compared with the WT. Taken together, these results showed that ANAC046 is an important transcription factor that promotes suberin biosynthesis in Arabidopsis thaliana roots.

Long noncoding RNA FAM83H-AS1 exerts an oncogenic role in glioma through epigenetically silencing CDKN1A (p21).

Gliomas are the commonest and most aggressive primary malignant tumor in the central nervous system. Long noncoding RNAs (lncRNAs) have been identified to act as crucial regulators in multiple biological processes, including tumorigenesis. FAM83H antisense RNA1 (FAM83H-AS1) has been uncovered to be dysregulated in several cancers. However, the biological role of FAM83H-AS1 in glioma still needs to be investigated. Currently, our findings indicated that FAM83H-AS1 was upregulated in glioma tissues and cell lines and high level of FAM83H-AS1 was associated with poor prognosis of glioma. Loss-of-function assays demonstrated that silenced FAM83H-AS1 obviously suppressed cell proliferation via regulating the cell-cycle distribution and cell apoptosis rate, and mechanistic experiments revealed that FAM83H-AS1 could epidemically silence CDKN1A expression through recruiting EZH2 to the promoter of CDKN1A, thereby influencing the cell cycle and proliferation. Collectively, our findings suggested that FAM83H-AS1 participated in the progression of glioma and might act as a potential therapeutic target and prognosis biomarker for human glioma.

Overexpression of miR169o, an Overlapping MicroRNA in Response to Both Nitrogen Limitation and Bacterial Infection, Promotes Nitrogen Use Efficiency and Susceptibility to Bacterial Blight in Rice.

Limiting nitrogen (N) supply contributes to improved resistance to bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) in susceptible rice (Oryza sativa). To understand the regulatory roles of microRNAs (miRNAs) in this phenomenon, 63 differentially expressed overlapping miRNAs in response to Xoo infection and N limitation stress in rice were identified through deep RNA sequencing and stem-loop quantitative real-time PCR. Among these, miR169o was further assessed as a typical overlapping miRNA through the overexpression of the miR169o primary gene. Osa-miR169o-OX plants were taller, and had more biomass accumulation with significantly increased nitrate and total amino acid contents in roots than the wild type (WT). Transcript level assays showed that under different N supply conditions, miR169o oppositely regulated NRT2, and this is reduced under normal N supply conditions but remarkably induced under N-limiting stress. On the other hand, osa-miR169o-OX plants also displayed increased disease lesion lengths and reduced transcriptional levels of defense gene (PR1b, PR10a, PR10b and PAL) compared with the WT after inoculation with Xoo. In addition, miR169o impeded Xoo-mediated NRT transcription. Therefore, the overlapping miR169o contributes to increase N use efficiency and negatively regulates the resistance to BB in rice. Consistently, transient expression of NF-YA genes in rice protoplasts promoted the transcripts of PR genes and NRT2 genes, while it reduced the transcripts of NRT1 genes. Our results provide novel and additional insights into the co ordinated regulatory mechanisms of cross-talk between Xoo infection and N deficiency responses in rice.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Plin5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis and oxidative stress.

Excessive plasma triglyceride and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism, and is involved in the regulation of oxidative stress. Although, in?ammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE-/- ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE-/- mice. ApoE/Plin5 double knockout (ApoE-/- Plin5-/- ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and reduced high-density lipoprotein cholesterol (HDLC) contents. ApoE-/- Plin5-/- exhibited higher number of inflammatory monocytes and neutrophils, as well as over-expression of cytokines and chemokines linked with inflammatory response. Consistently, IκBα/nuclear factor kappa B (NF-κB) pathway was strongly activated in ApoE-/- Plin5-/- . Notably, apoptosis was dramatically induced by ApoE-/- Plin5-/- , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2 (PARP-2). In addition, ApoE-/- Plin5-/- contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) pathways. In vitro, oxidized low-density lipoprotein (oxLDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions. This article is protected by copyright. All rights reserved.

Overexpression of OsGATA12 regulates chlorophyll content, delays plant senescence and improves rice yield under high density planting.

Agronomic traits controlling the formation, architecture and physiology of source and sink organs are main determinants of rice productivity. Semi-dwarf rice varieties with low tiller formation but high seed production per panicle and dark green and thick leaves with prolonged source activity are among the desirable traits to further increase the yield potential of rice. Here, we report the functional characterization of a zinc finger transcription factor, OsGATA12, whose overexpression causes increased leaf greenness, reduction of leaf and tiller number, and affects yield parameters. Reduced tillering allowed testing the transgenic plants under high density which resulted in significantly increased yield per area and higher harvest index compared to wild-type. We show that delayed senescence of transgenic plants and the corresponding longer stay-green phenotype is mainly due to increased chlorophyll and chloroplast number. Further, our work postulates that the increased greenness observed in the transgenic plants is due to more chlorophyll synthesis but most significantly to decreased chlorophyll degradation, which is supported by the reduced expression of genes involved in the chlorophyll degradation pathway. In particular we show evidence for the down-regulation of the STAY GREEN RICE gene and in vivo repression of its promoter by OsGATA12, which suggests a transcriptional repression function for a GATA transcription factor for prolonging the onset of senescence in cereals.