Genome-wide analysis of the peanut CaM/CML gene family reveals that the AhCML69 gene is associated with resistance to Ralstonia solanacearum.

BACKGROUND: Calmodulins (CaMs)/CaM-like proteins (CMLs) are crucial Ca2+-binding sensors that can decode and transduce Ca2+ signals during plant development and in response to various stimuli. The CaM/CML gene family has been characterized in many plant species, but this family has not yet been characterized and analyzed in peanut, especially for its functions in response to Ralstonia solanacearum. In this study, we performed a genome-wide analysis to analyze the CaM/CML genes and their functions in resistance to R. solanacearum. RESULTS: Here, 67, 72, and 214 CaM/CML genes were identified from Arachis duranensis, Arachis ipaensis, and Arachis hypogaea, respectively. The genes were divided into nine subgroups (Groups I-IX) with relatively conserved exon‒intron structures and motif compositions. Gene duplication, which included whole-genome duplication, tandem repeats, scattered repeats, and unconnected repeats, produced approximately 81 pairs of homologous genes in the AhCaM/CML gene family. Allopolyploidization was the main reason for the greater number of AhCaM/CML members. The nonsynonymous (Ka) versus synonymous (Ks) substitution rates (less than 1.0) suggested that all homologous pairs underwent intensive purifying selection pressure during evolution. AhCML69 was constitutively expressed in different tissues of peanut plants and was involved in the response to R. solanacearum infection. The AhCML69 protein was localized in the cytoplasm and nucleus. Transient overexpression of AhCML69 in tobacco leaves increased resistance to R. solanacearum infection and induced the expression of defense-related genes, suggesting that AhCML69 is a positive regulator of disease resistance. CONCLUSIONS: This study provides the first comprehensive analysis of the AhCaM/CML gene family and potential genetic resources for the molecular design and breeding of peanut bacterial wilt resistance.

Intramolecular generation of endogenous Cu(III) for selectively self-catalytic degradation of Cu(II)-EDTA from wastewater by UV/peroxymonosulfate.

HO•/SO4•--based advanced oxidation processes for the decomplexation of heavy metal-organic complexes usually encounter poor efficiency in real scenarios. Herein, we reported an interesting self-catalyzed degradation of Cu(II)-EDTA with high selectivity in UV/peroxymonosulfate (PMS). Chemical probing experiments and competitive kinetic analysis quantitatively revealed the crucial role of in situ formed Cu(III). The Cu(III) species not only oxidized Cu(II)-EDTA rapidly at ∼3 × 107 M-1 s-1, but also exhibited 2-3 orders of magnitude higher steady-state concentration than HO•/SO4•-, leading to highly efficient and selective degradation of Cu(II)-EDTA even in complex matrices. The ternary Cu(II)-OOSO3- complexes derived from Cu(II)-EDTA decomposition could generate Cu(III) in situ via the Cu(II)-Cu(I)-Cu(III)-Cu(II) cycle involving intramolecular electron transfer. This method was also applicable to various Cu(II) complexes in real electroplating wastewater, demonstrating higher energy efficiency than commonly studied UV-based AOPs. This study provids a proof of concept for efficient decomplexation through activating complexed heavy metals into endogenous reactive species.

A modified group contribution method for estimating thermodynamic parameters of methanol-to-olefins over a SAPO-34 catalyst.

Group contribution (GC) methods, a semi-empirical approach based on the additivity of guest molecular properties, are widely applied to obtain the thermodynamic properties of complex reaction networks. In molecular sieve catalyzed processes, however, the interaction between guest molecules and host active sites also affects thermodynamic properties. In this study, therefore, we propose a modified group contribution (mGC) method by considering the interaction between the groups of guest molecules and independent active site functional groups (IASFGs) in molecular sieves. The mGC method has been used to estimate the thermodynamic properties of guest molecules as well as elementary reactions for the initial stage of methanol to olefins (MTO) reaction over SAPO-34 molecular sieves. It shows that mGC is more accurate than the conventional GC (cGC) methods when compared with the reference data calculated by density functional theory (DFT), indicating that mGC provides an effective way for batch calculation of thermodynamic properties in molecular sieve catalyzed processes.

High-fidelity and clean nanotransfer lithography using structure-embedded and electrostatic-adhesive carriers.

Metallic nanostructures are becoming increasingly important for both fundamental research and practical devices. Many emerging applications employing metallic nanostructures often involve unconventional substrates that are flexible or nonplanar, making direct lithographic fabrication very difficult. An alternative approach is to transfer prefabricated structures from a conventional substrate; however, it is still challenging to maintain high fidelity and a high yield in the transfer process. In this paper, we propose a high-fidelity, clean nanotransfer lithography method that addresses the above challenges by employing a polyvinyl acetate (PVA) film as the transferring carrier and promoting electrostatic adhesion through triboelectric charging. The PVA film embeds the transferred metallic nanostructures and maintains their spacing with a remarkably low variation of <1%. When separating the PVA film from the donor substrate, electrostatic charges are generated due to triboelectric charging and facilitate adhesion to the receiver substrate, resulting in a high large-area transfer yield of up to 99.93%. We successfully transferred the metallic structures of a variety of materials (Au, Cu, Pd, etc.) with different geometries with a <50-nm spacing, high aspect ratio (>2), and complex 3D structures. Moreover, the thin and flexible carrier film enables transfer on highly curved surfaces, such as a single-mode optical fiber with a curvature radius of 62.5 µm. With this strategy, we demonstrate the transfer of metallic nanostructures for a compact spectrometer with Cu nanogratings transferred on a convex lens and for surface-enhanced Raman spectroscopy (SERS) characterization on graphene with reliable responsiveness.

Shock lung is not "wet" but characterized as necroptotic inflammation in a mouse model of hypotension.

OBJECTIVES: Hypotension episodes before or after donor brain death are assumed to trigger hypoxia-reoxygenation, causing diffuse alveolar-capillary damage via necrosis. However, alveolar-capillary membranes have direct access to oxygen in alveoli. We hypothesized hypotension-induced lung injury is not diffuse alveolar-capillary damage but interstitial inflammation resulting from nonhypoxic lung ischemia and systemic responses to hypoxic extrapulmonary ischemia. METHODS: The 4-hour hypotension model was established by subjecting C57BL/6J mice to 4-hour hypotension at 15 ± 5 mm Hg of mean artery pressure and resuscitated with whole shed blood and norepinephrine. Nonhypoxic lung ischemia model was established by 4-hour left pulmonary artery ligation. At 24 hours postprocedure, an arterial blood gas analysis and a gastroduodenal occult blood test were conducted. Lung samples were assessed for histology, cytokine transcripts, regulated cell death, and alveolar-capillary permeability. RESULTS: The 4-hour hypotension model had an intraoperative mortality rate of 17.7% (41/231) and a stress-ulcer bleeding rate of 15.3% (29/190). No signs of alveolar flooding were observed in both models. Four-hour hypotension without stress ulcer showed normal oxygenation and permeability but increased interstitial infiltration, transcription of Tnf and Il1b, phosphorylation of MLKL and RIPK3, and cleaved caspase 3 compared with 4-hour pulmonary artery ligation and naïve control. Animals that developed stress ulcer presented with worse pulmonary infiltration, intracellular edema, and oxygenation but just slightly increased permeability. Immunoblotting showed significant upregulations of protein expression and phosphorylation of MLKL and RIPK3, cleaved Caspase-3, but not its prototype in 4-hour hypotension with stress ulcer. CONCLUSIONS: Hypotensive lung injury is essentially a nonhypoxic ischemia-reperfusion injury enhanced by systemic responses. It is predominated by necroptosis-induced inflammation rather than necrosis-induced diffuse alveolar-capillary damage.

Polyimide Films Impregnated with Epoxy Resin Demonstrating Superior Self-Healing Properties for Thermally Stable Energy Storage Capacitors.

Metallized polymer films (MPFs) with superior self-healing properties are extremely attractive for application in energy storage capacitors. Self-healing behaviors allow MPFs to keep insulating between the local electrical breakdown region and the electrode, thereby reserving long-term operational viability of the capacitors. Polyimide (PI) is a type of well-developed polymer material with excellent mechanical and thermal stabilities, but it is deficient in intrinsic self-healing capabilities. This work reports a facile surface engineering strategy to endow metalized PI films with self-healing capabilities. By simple immersion of bare PI films in the solution of epoxy resin (ER) accompanied by curing of ER, PI films impregnated with ER (P-E films) not only show enhanced dielectric characteristics but also obtain excellent self-healing abilities upon multiple cycles of electrical breakdowns, even at a high temperature. For example, in comparison to bare PI films, PI films impregnated in ER solution with a solid content of 1 wt % (P-1%E) display improved initial Weibull breakdown strength (αb1 of 353.0 versus 310.9 kV/mm), maximum discharging energy density (Ud of 2.1836 versus 0.8254 J/cm3), and charging/discharging efficiency (η of 95.72 versus 55.19%) at 150 °C. After 5 breakdown cycles, P-1%E films could maintain a much higher breakdown strength (αb5 of 338.1 versus 21.3 kV/mm). When subjected to a constant electrical strength of 350 kV/mm at 150 °C, P-1%E films show merely <6% decline in both Ud and η values after 5 breakdown cycles. On the contrary, bare PI films would undergo dramatic performance decay after 1 or 2 breakdowns under similar conditions. In view of their outstanding self-healing properties at a high temperature, P-E films can serve as a promising candidate to fabricate thermally stable MPF capacitors for long-term operation.

Cancer-associated fibroblasts-derived lncRNA signature as a putative biomarker in breast cancer.

Long noncoding RNAs (lncRNAs) have been reported to play a key role in regulating tumor microenvironment and immunity. Cancer-associated fibroblasts (CAFs) are abundant in many tumors. However, the functional and clinical significance of lncRNAs specifically expressed in CAFs has not been fully elucidated. In this study, we identified a list of 95 CAF-specific lncRNAs (FibLnc), including HHLA3, TP53TG1, ST7-AS1, LINC00536, ZNF503-AS1, MIR22HG, and MAPT-AS1, based on immune cell transcriptome expression profiling data. Based on the Cancer Genome Atlas and Gene Expression Omnibus datasets, we found that the FibLnc score predicted differences in overall patient survival and performed well in multiple datasets. FibLnc score was associated with the clinical stage of patients with breast cancer but did not significantly correlate with the PAM50 classification. Functional analysis showed that FibLnc was positively correlated with signaling pathways associated with malignant tumor progression. In addition, FibLnc was positively correlated with tumor mutational load and could predict immunotherapy response in patients with breast cancer receiving anti-PD-1 or anti-CTLA4 therapy. Our proposed FibLnc score was able to reflect the status of the immune environment and immunotherapeutic response in breast cancer, which could help explore potential therapeutic decisions and regulatory mechanisms of CAF-specific lncRNAs.

LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.

RATIONALE: Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of long noncoding RNAs in VSMCs phenotype switching remain to be fully elucidated. OBJECTIVES: To illustrate the biological function and mechanism of a VSMC-enriched long noncoding RNA and its encoded peptide in VSMC phenotype switching and vascular remodeling. RESULTS: We identified a VSMC-enriched transcript encoded by a previously uncharacterized gene, which we called phenotype switching regulator (PSR), which was markedly upregulated during vascular remodeling. Although PSR was annotated as a long noncoding RNA, we demonstrated that the lncPSR (PSR transcript) also encoded a protein, which we named arteridin. In VSMCs, both arteridin and lncPSR were necessary and sufficient to induce phenotype switching. Mechanistically, arteridin and lncPSR regulate downstream genes by directly interacting with a transcription factor YBX1 (Y-box binding protein 1) and modulating its nuclear translocation and chromatin targeting. Intriguingly, the PSR transcription was also robustly induced by arteridin. More importantly, the loss of PSR gene or arteridin protein significantly attenuated the vascular remodeling induced by carotid arterial injury. In addition, VSMC-specific inhibition of lncPSR using adeno-associated virus attenuated Ang II (angiotensin II)-induced hypertensive vascular remodeling. CONCLUSIONS: PSR is a VSMC-enriched gene, and its transcript IncPSR and encoded protein (arteridin) coordinately regulate transcriptional reprogramming through a shared interacting partner, YBX1. This is a previously uncharacterized regulatory circuit in VSMC phenotype switching during vascular remodeling, with lncPSR/arteridin as potential therapeutic targets for the treatment of VSMC phenotype switching-related vascular remodeling.

Prenatal Lipopolysaccharides Exposure Induces Transgenerational Inheritance of Hypertension.

BACKGROUND: Adverse environmental exposure during the prenatal period can lead to diseases in the offspring, including hypertension. Whether or not the hypertensive phenotype can be transgenerationally transmitted is not known. METHODS: Pregnant Sprague Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) on gestation days 6, 8, 10, and 12 to generate the prenatal LPS exposure model. Blood pressure was monitored by both telemetry and tail-cuff method. RNA sequencing was performed to analyze transcriptome alteration in the kidney of the third generation. Tempol and spironolactone were used to test the potential preventative and therapeutic effect of targeting reactive oxygen species and mineralocorticoid receptor signaling, respectively. Molecular biological experiments were performed to illustrate the mechanism of epigenetic and transcription regulation. RESULTS: Prenatal LPS exposure can impair the ability to excrete a salt load and induce hypertension from the first to the third generations, with the fourth and fifth generations, inducing salt-sensitive hypertension. Compared with control pups, the transcriptome in the kidney of the hypertensive third-generation prenatal LPS-exposed offspring have upregulation of the Ras-related C3 botulinum toxin substrate 1 (Rac1) gene and activation of mineralocorticoid receptor signaling. Furthermore, we found that LPS exposure during pregnancy triggered oxidative stress that upregulated KDM3B (histone lysine demethylase 3B) in the oocytes of first-generation female rats, leading to an inheritable low level of H3K9me2 (histone H3 lysine 9 dimethylation), resulting in the transgenerational upregulation of Rac1. Based on these findings, we treated the LPS-exposed pregnant rats with the reactive oxygen species scavenger, tempol, which successfully prevented hypertension in the first-generation offspring and the transgenerational inheritance of hypertension. CONCLUSIONS: These findings show that adverse prenatal exposure induces transgenerational hypertension through an epigenetic-regulated mechanism and identify potentially preventive and therapeutic strategies for hypertension.

Non-stationary time-varying vehicular channel characteristics for different roadside scattering environments.

With the deep integration of wireless communication technology and automobile industry, vehicular communication has become one of the key technologies supporting the development of Internet-of-vehicle. Due to the high-speed mobility of vehicles and the rapid change of the propagation environments, vehicle-to-vehicle (V2V) wireless communication channels are generally non-stationary. Meanwhile, the variability of V2V channel characteristics is obvious in different scattering environments. Focusing on these research points, this paper presents the analysis and comparison of V2V channel characteristics for different scattering scenarios based on a series of 5.9 GHz channel measurements. The measurement data are collected from the iron bridge, the soundproof wall, and the road lamp scenarios. The stationary time and frequency are investigated on the basis of method of local scattering functions. The classical channel characteristics, including power delay profile, Ricean K-factor, root means square (RMS) delay spread and RMS Doppler spread are extracted following the propagation principle. Furthermore, considering the source and birth-death process of multi-path components (MPCs) in different scattering propagation environments, cluster identification and statistical results are presented and compared. The different values of the channel parameters and the different performance of the channel under different scattering environments can help us understand the V2V channel deeply. The research results can be used for the design and optimization of vehicular communication systems in different scattering environments.

Iliosacral screw fixation of pelvic ring disruption with tridimensional patient-specific template guidance.

INTRODUCTION: Posterior pelvic ring disruption includes sacral fractures, sacroiliac joint fracture dislocations and ilium fractures. Percutaneous iliosacral screw fixation of sacral fractures and sacraoiliac joint fracture dislocations have been prevailing, it has the advantages of minimal invasiveness, less blood loss and low wound infection rate. HYPOTHESIS: This study was to evaluate the application of three-dimensional (3D) printed patient-specific guide template in closed reduction and iliosacral screw fixation of posterior pelvic ring disruption. MATERIAL AND METHODS: The data of patients, who were treated with closed reduction and iliosacral screw fixation of posterior pelvic ring disruption with the assistance of 3D printed guide template from December 2014 to September 2018, were collected. The screw placement time, fluoroscopy time, intraoperative blood loss, fracture reduction, screw position, and functional assessment were recorded. RESULTS: There were 17 cases of unstable pelvic fractures,and 20 screws were inserted for fixation of sacral fractures or sacroiliac joint dislocations, with bilateral screw placement in 3 cases. The average time for each screw placement was 45.9±8.6min (30-60min). The average fluoroscopy time for each screw insertion was 50.3±19.7s (24-96 s). The mean blood loss for each screw placement was 32.0±11.1ml (20-50ml). According to Matta scale, the fracture reduction was graded as excellent in all the 17 cases. According to the modified Gras classification, the 3D CT reconstruction of the pelvis demonstrated Grade 1 for 18 screws and Grade 2 for 2 screw. Functional outcome 1 year postoperatively was rated as 15 excellent and 2 good, according to the Majeed functional scale. DISCUSSION: It is feasible and safe to stabilize the posterior pelvic ring disruption using iliosacral screw fixation under assistance of the 3D printed guide template. It could reduce fluoroscopy time, screw placement time and intraoperative blood loss and achieve good postoperative recovery. LEVEL OF PROOF: IV; Retrospective study.

Screening and prioritizing substances in groundwater in the Beijing-Tianjin-Hebei region of the North China Plain based on exposure and hazard assessments.

Screening and prioritizing hazardous substances in groundwater is crucial to monitor and control groundwater quality. Total of 283 substances were determined in 213 groundwater samples from the Beijing-Tianjin-Hebei region during 2019-2020. 184 substances were screened as candidates. 22 prioritizing indicators were evaluated and scored for the candidates to reflect their occurrence, mobility, persistence, bioaccumulation, acute and chronic ecotoxicities with different trophic levels, and long-term human health effects. Multi-attribute decision-making technologies were applied to prioritize these candidates, including analytic hierarchy process (AHP), TOPSIS and VIKOR. Greater weightings in AHP were assigned to attributes of occurrence and acute toxicity by experts' judgment. Hierarchical cluster analysis and principal component analysis were used to transform initial matrix with the 22 indicators into an orthogonalized matrix with 6 principal components, which represented general toxicity to aquatic organism and mammal, bioaccumulation, carcinogenicity & mutagenicity, persistence, and teratogenicity & endocrine, respectively. VIKOR and TOPSIS results were similar, but different from the AHP ranking. Two filter criteria harmonized their difference. Twenty-three substances were proposed as the priority substance with high hazard and potential exposure, and nitrate-nitrogen and ammonia-nitrogen were selected as additional priority substance frequently and extensively exceeding official groundwater quality standard on the regional scale.

Rapid postmortem ventilation improves donor lung viability by extending the tolerable warm ischemic time after cardiac death in mice.

Uncontrolled donation after cardiac death (uDCD) contributes little to ameliorating donor lung shortage due to rapidly progressive warm ischemia after circulatory arrest. Here, we demonstrated that nonhypoxia improves donor lung viability in a novel uDCD lung transplant model undergoing rapid ventilation after cardiac death and compared the evolution of ischemia-reperfusion injury to mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37°C was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared with those that underwent rapid ventilation or no ventilation at 37°C before transplantation. Twenty-four hours following reperfusion, lung histology, [Formula: see text]/[Formula: see text] ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on [Formula: see text]/[Formula: see text] ratio and acute lung injury score in contrast to significant injury induced by 5 h of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared with naïve lungs and substantially injured 5 h PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in [Formula: see text]/[Formula: see text] ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37°C can be extended by maintaining alveolar ventilation for up to 4 h. Nonhypoxic lung undergoing warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis before blood-gas barrier dysfunction and significant tissue damage.

Novel Design of the Chimeric Deep Inferior Epigastric Artery Perforator Flap that Provides for Three-Dimensional Reconstruction of Composite Tissue Defects of the Heel in Children.

OBJECTIVE: The aim of the present study was to report a novel design of the chimeric deep inferior epigastric artery perforator flap (DIEP) to achieve dead space filling, Achilles tendon bridging, and skin resurfacing simultaneously with minimal donor-site morbidity. METHODS: From September 2012 to May 2016, a retrospective study was carried out on six pediatric patients with composite soft tissue defects of the heel that were repaired with the chimeric DIEP flap. The chimeric flap design included a flap of the anterior sheath of the rectus, a block of rectus muscle, and a large skin paddle. All the parts were supplied by a common artery. After harvesting the flap, all element parts were inserted at the corresponding sites in a tension-free manner. With one set of vessel anastomoses at the recipient site, accurate repair with tendon reconstruction, dead space elimination, and wound covering were accomplished. The donor site incisions were closed initially. Data on patient age, medical history, injury severity, defect size, flap dimensions, recipient vessels, donor site closure, complications, and follow-up were collected and reviewed. RESULTS: Five of the six chimeric DIEP flaps survived without complications. The remaining one case experienced partial necrosis of the skin paddle caused by venous congestion, which healed after routine dressing changes. Primary donor site closure was accomplished in all cases. The mean follow-up was 18.6 months (range, 10-36 months). Five patients had satisfactory aesthetic and functional outcomes; one patient needed a secondary debulking procedure. Compared to the unaffected side, the affected side showed no obvious difference for ankle movement, tiptoe function, and patient gait during the follow-up period. Good ankle function was observed in all patients. There was no donor site breakdown, with only a slightly noticeable linear scar. CONCLUSION: The chimeric DIEP flap reduced the operative time, solved the problem of deficiency of recipient vessels, and attained satisfactory functional and aesthetic outcomes with low donor site morbidity. Therefore, it is a promising option for three-dimensional reconstruction of composite defects with dead space and Achilles tendon defects as well as skin loss in children.

Long Noncoding RNA Ahit Protects Against Cardiac Hypertrophy Through SUZ12 (Suppressor of Zeste 12 Protein Homolog)-Mediated Downregulation of MEF2A (Myocyte Enhancer Factor 2A).

BACKGROUND: Long noncoding RNA (lncRNA) can regulate various physiological and pathological processes through multiple molecular mechanisms in cis and in trans. However, the role of lncRNAs in cardiac hypertrophy is yet to be fully elucidated. METHODS: A mouse lncRNA microarray was used to identify differentially expressed lncRNAs in the mouse hearts following transverse aortic constriction-induced pressure overload comparing to the sham-operated samples. The direct impact of one lncRNA, Ahit, on cardiomyocyte hypertrophy was characterized in neonatal rat cardiomyocytes in response to phenylephrine by targeted knockdown and overexpression. The in vivo function of Ahit was analyzed in mouse hearts by using cardiac-specific adeno-associated virus, serotype 9-short hairpin RNA to knockdown Ahit in combination with transverse aortic constriction. Using catRAPID program, an interaction between Ahit and SUZ12 (suppressor of zeste 12 protein homolog) was predicted and validated by RNA immunoprecipitation and immunoblotting following RNA pull-down. Chromatin immunoprecipitation was performed to determine SUZ12 or H3K27me3 occupancy on the MEF2A (myocyte enhancer factor 2A) promoter. Finally, the expression of human Ahit (leukemia-associated noncoding IGF1R activator RNA 1 [LUNAR1]) in the serum samples from patients of hypertrophic cardiomyopathy was tested by quantitative real-time polymerase chain reaction. RESULTS: A previously unannotated lncRNA, antihypertrophic interrelated transcript (Ahit), was identified to be upregulated in the mouse hearts after transverse aortic constriction. Inhibition of Ahit induced cardiac hypertrophy, both in vitro and in vivo, associated with increased expression of MEF2A, a critical transcriptional factor involved in cardiac hypertrophy. In contrast, overexpression of Ahit significantly attenuated stress-induced cardiac hypertrophy in vitro. Furthermore, Ahit was significantly upregulated in serum samples of patients diagnosed with hypertensive heart disease versus nonhypertrophic hearts (1.46±0.17 fold, P=0.0325). Mechanistically, Ahit directly bound and recruited SUZ12, a core PRC2 (polycomb repressive complex 2) protein, to the promoter of MEF2A, triggering its trimethylation on H3 lysine 27 (H3K27me3) residues and mediating the downregulation of MEF2A, thereby preventing cardiac hypertrophy. CONCLUSIONS: Ahit is a lncRNA with a significant role in cardiac hypertrophy regulation through epigenomic modulation. Ahit is a potential therapeutic target of cardiac hypertrophy.

SODs involved in the hormone mediated regulation of H2O2 content in Kandelia obovata root tissues under cadmium stress.

Cadmium (Cd) pollution in mangrove wetlands has received increasing attention as urbanization expands rapidly. As a dominant mangrove species, Kandelia obovata is highly tolerant to Cd toxicity. Plant hormones and superoxide dismutase (SODs) play critical roles in the response to heavy metal stress in K. obovata roots. Although theirs important influence have been reported, the regulation mechanism between SODs and plant hormones in Cd detoxification by K. obovata roots remains limited. Here, we investigated relationships among SOD, plant hormones, and Cd tolerance in K. obovata roots exposed to Cd. We found that Cd was retained in the epidermis and exodermis of roots, and the epidermis and exodermis had highest hydrogen peroxide (H2O2) content and SOD activity. Similarly, SOD isozymes also exhibited distinct activity in the different parts of root. Overexpressed KoCSD3 and KoFSD2 individually in Nicotiana benthamiana revealed that different SOD members contributed to H2O2 content regulation by promote the activity of downstream antioxidant enzymes under Cd treatment. In addition, assays on the effects of hormones showed that increased endogenous indole-3-acetic acid (IAA) was observed in the cortex and stele, whereas the abscisic acid (ABA) content was enhanced in the epidermis and exodermis in roots during Cd treatment. The results of exogenous hormones treatment indicated that KoFSD2 upregulated under ABA and IAA treatment, but KoCSD3 only induced by ABA stimulation. Taken together, our results reveal the relationship between SODs and plant hormones, which expands the knowledge base regarding KoSODs response to plant hormones and mediating H2O2 concentration under Cd stress.

Analysis of anatomical changes and cadmium distribution in Aegiceras corniculatum (L.) Blanco roots under cadmium stress.

Heavy metal stress changes the morphological and anatomical structure of plant organs. In this study, we determined the anatomical changes and Cd distribution in the roots of Aegiceras corniculatum (L.) Blanco (Black mangrove) under Cd stress. The results showed that Cd levels in A. corniculatum root tissues decreased in the following order: endodermis > pith > xylem > epidermis and exodermis > phloem > cortex. The endodermis secondary casparian strip replaces exodermis casparian strip and plays a role in the "retardation mechanism", which sort of compensates for the missing exodermis retardation effect. The xylem and pith both show high affinity for Cd and contain enriched Cd. This creates a low-Cd environment for phloem and protects the nutrient transport function of the vasculature against Cd toxicity. The present study provides new evidences suggesting that Cd regional enrichment and anatomical structure changes are an adaptive strategy of mangrove plants to HM tolerance.

Glucagon Receptor Antagonism Ameliorates Progression of Heart Failure.

Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at 4 weeks after myocardial infarction. In addition, REMD2.59 treatment at the onset of pressure overload significantly suppressed cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. Initiation of REMD2.59 treatment 2 weeks after pressure overload significantly blunted the progression of cardiac pathology. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to ameliorate both onset and progression of heart failure.

Regulation of Cholesterol Homeostasis by a Novel Long Non-coding RNA LASER.

Genome-wide association studies (GWAS) have identified many genetic variants in genes related to lipid metabolism. However, how these variations affect lipid levels remains elusive. Long non-coding RNAs (lncRNAs) have been implicated in a variety of biological processes. We hypothesize lncRNAs are likely to be located within disease or trait-associated DNA regions to regulate lipid metabolism. The aim of this study was to investigate whether and how lncRNAs in lipid- associated DNA regions regulate cholesterol homeostasis in hepatocytes. In this study, we identified a novel long non-coding RNA in Lipid Associated Single nucleotide polymorphism gEne Region (LASER) by bioinformatic analysis. We report that LASER is highly expressed in both hepatocytes and peripheral mononuclear cells (PBMCs). Clinical studies showed that LASER expression is positively related with that of cholesterol containing apolipoprotein levels. In particular, we found that LASER is positively correlated with plasma PCSK9 levels in statin free patients. siRNAs mediated knock down of LASER dramatically reduces intracellular cholesterol levels and affects the expression of genes involved in cholesterol metabolism. Transcriptome analyses show that knockdown of LASER affects the expression of genes involved in metabolism pathways. We found that HNF-1α and PCSK9 were reduced after LASER knock-down. Interestingly, the reduction of PCSK9 can be blocked by the treatment of berberine, a natural cholesterol-lowering compound which functions as a HNF-1α antagonist. Mechanistically, we found that LASER binds to LSD1 (lysine-specific demethylase 1), a member of CoREST/REST complex, in nucleus. LASER knock-down enhance LSD1 targeting to genomic loci, resulting in decreased histone H3 lysine 4 mono-methylation at the promoter regions of HNF-1α gene. Conversely, LSD1 knock-down abolished the effect of LASER on HNF-1α and PCSK9 expressions. Finally, we found that statin treatment increased LASER expression, accompanied with increased PCSK9 expression, suggesting a feedback regulation of cholesterol on LASER expression. This observation may partly explain the statin escape during anti-cholesterol treatment. These findings identified a novel lncRNA in cholesterol homeostasis. Therapeutic targeting LASER might be an effective approach to augment the effect of statins on cholesterol levels in clinics.

Epigenetics in dilated cardiomyopathy.

PURPOSE OF REVIEW: Characterized by enlarged ventricle and loss of systolic function, dilated cardiomyopathy (DCM) has the highest morbidity among all the cardiomyopathies. Although it is well established that DCM is typically caused by mutations in a large number of genes, there is an emerging appreciation for the contribution of epigenetic alteration in the development of DCM. RECENT FINDINGS: We present some of the recent progress in the field of epigenetics in DCM by focusing on the four major epigenetic modifications, that is, DNA methylation, histone modification, chromatin remodeling as well as the noncoding RNAs. The major players involved in these DCM-related epigenetic reprogramming will be highlighted. Finally, the diagnostic and the therapeutic implications for DCM based on new knowledge of epigenetic regulation will also be discussed. SUMMARY: As a rapidly expanding field, epigenetic studies in DCM have the promise to yield both novel mechanistic insights as well as potential new avenues for more effective treatment of the disease.