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Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin‐1 (MaR1), one of metabolites from Omega‐3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)‐infused mouse model. In addition, MaR1‐treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin‐dependent protein kinase II/nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension. [ABSTRACT FROM AUTHOR]

Transient receptor potential ankyrin 1 (TRPA1) plays an important role in different cardiovascular diseases. However, the role of TRPA1 in dilated cardiomyopathy (DCM) remains unclear. Here, we aimed to investigate the role of TRPA1 in DCM induced by doxorubicin (DOX) and explore its possible mechanisms. GEO data were used to explore the expression of TRPA1 in DCM patients. DOX (2.5 mg/kg/week, 6 weeks, i.p.) was used to induce DCM. Bone marrow‐derived macrophages (BMDMs) and neonatal rat cardiomyocytes (NRCMs) were isolated to explore the role of TRPA1 in macrophage polarization, cardiomyocyte apoptosis, and pyroptosis. In addition, DCM rats were treated with the TRPA1 activator, cinnamaldehyde to explore the possibility of clinical translation. TRPA1 expression was increased in left ventricular (LV) tissue in DCM patients and rats. TRPA1 deficiency aggravated the cardiac dysfunction, cardiac injury, and LV remodeling in DCM rats. In addition, TRPA1 deficiency promoted the M1 macrophage polarization, oxidative stress, cardiac apoptosis, and pyroptosis induced by DOX. RNA‐seq results showed that TRPA1 knockout promoted the expression of S100A8, an inflammatory molecule that belongs to the family of Ca2+‐binding S100 proteins, in DCM rats. Furthermore, S100A8 inhibition attenuated M1 macrophage polarization in BMDMs isolated from TRPA1 deficiency rats. Recombinant S100A8 promoted the apoptosis, pyroptosis, and oxidative stress in primary cardiomyocytes stimulated with DOX. Finally, TRPA1 activation via cinnamaldehyde alleviated the cardiac dysfunction and reduced S100A8 expression in DCM rats. Taken together, these results suggested that TRPA1 deficiency aggravates DCM by promoting S100A8 expression to induce M1 macrophage polarization and cardiac apoptosis. [ABSTRACT FROM AUTHOR]

Efferocytosis is defined as the clearance of apoptotic cells (ACs) in physiological and pathological states and is performed by efferocytes, such as macrophages. Efferocytosis can lead to the resolution of inflammation and restore tissue homoeostasis; however, the mechanisms of efferocytosis in determining inflammation resolution are still not completely understood, and the effects of efferocytosis on other proresolving properties need to be explored and explained. In this review, the process of efferocytosis will be summarized briefly, and then these mechanisms and effects will be thoroughly discussed. In addition, the association between mechanisms of efferocytosis in determining resolution of inflammation and cardiovascular diseases will also be reviewed, as an understanding of this association may provide information on novel treatment targets. [ABSTRACT FROM AUTHOR]

Single‐atom nickel catalysts hold great promise for photocatalytic water splitting due to their plentiful active sites and cost‐effectiveness. Herein, we adopt a reactive‐group guided strategy to prepare atomically dispersed nickel catalysts on red phosphorus. The hydrothermal treatment of red phosphorus leads to the formation of P−H and P−OH groups, which behave as the reactive functionalities to generate the dual structure of single‐atom P−Ni and P−O−Ni catalytic sites. The produced single‐atom sites provide two different functions: P−Ni for water reduction and P−O−Ni for water oxidation. Benefitting from this specific Janus structure, Ni‐red phosphorus shows an elevated hydrogen evolution rate compared to Ni nanoparticle‐modified red phosphorus under visible‐light irradiation. The hydrogen evolution rate was additionally enhanced with increased reaction temperature, reaching 91.51 μmol h−1 at 70 °C, corresponding to an apparent quantum efficiency of 8.9 % at 420 nm excitation wavelength. [ABSTRACT FROM AUTHOR]

Among different kinds of modified release profiles, sustained drug release (SDR) has received the most attention due to its capability to provide a "safe, efficacious, and convenient" drug delivery effect. Electrospun nanofibers have shown their popularity in this interdisciplinary field, as demonstrated by the first reports about SDRs on drug delivery applications of blended nanofibers and core–shell nanofibers. Along with the evolution of electrospinning from a single‐fluid blending process to coaxial, tri‐axial, side‐by‐side, and other multi‐fluid processes, more multi‐chamber nanostructures can be created through a single‐step straight forward manner. These multi‐chamber nanostructures can act as a powerful platform to support a wide variety of new strategies for the development of novel SDR nanomaterials. Thus, this review describes a combination history of electrospinning and SDR and its further development trend. After a summary of the presently popular multi‐chamber core–shell nanostructures, 15 strategies for furnishing SDR profiles are categorized and exemplified. The perspectives of electrospun multi‐chamber nanostructures for further promoting SDR are narrated. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

Developing efficient metal sulfides for pure water splitting is a challenging topic in the field of photocatalysis. Herein, inspired by natural photosynthesis, an all‐solid‐state Z‐scheme photocatalyst was constructed with Cd0.9Zn0.1S (CZS) for water reduction, red phosphorus (RP) for water oxidation, and metallic CoP as the electron mediator. RP@CoP core‐shell nanostructures were uniformly attached on the CZS nanorods, which gave rise to multiple monodispersed nanojunctions. The integrated Z‐scheme nanosystem exhibited an apparent quantum efficiency of 6.4 % at 420 nm for pure water splitting. Theoretical analysis and femtosecond transient absorption results revealed that the impressive performance was mainly due to efficient hole transfer of CZS, resulting from the intimate atomic contacts between CoP mediator and photocatalysts, together with favorable band alignment. Meanwhile, the multiple monodispersed Z‐scheme nanojunctions could provide abundant reaction sites, which was also important for the boosted activity. [ABSTRACT FROM AUTHOR]

Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development. [ABSTRACT FROM AUTHOR]

Increased inflammation is the key mechanism that mediates sepsis induced cardiac injury. Resolvin D1 (RvD1), a bioactive lipid mediator synthesized from docosahexaenoic acid, can attenuate the severity of many inflammation‐related diseases through anti‐inflammatory and pro‐resolving properties. However, the protective role of RvD1 in sepsis induced cardiac injury remains unclear. Mice were randomly divided into three groups: the control group, LPS group and RvD1 + LPS group. LPS (10 mg/kg, i.p.) was used to establish a sepsis‐induced cardiac injury model. RvD1 (5 ug/kg, i.p.) was injected 30 min before LPS injection. RvD1 treatment significantly attenuated the deteriorated cardiac function and cardiac injury induced by LPS, as evidenced by the improved left ventricular ejection fraction, serum levels of cardiac injury markers and severity of cardiomyocyte apoptosis. In addition, RvD1 treatment significantly attenuated the infiltration of pro‐inflammatory M1 macrophages and expression of inflammatory cytokines in the heart. Mechanistically, the attenuated activation of NK‐κB and MAPK signaling mediated the anti‐inflammatory and antiapoptotic effects of RvD1. In addition, LPS‐induced infiltration of neutrophils and M1 macrophages in the spleen was significantly attenuated by the RvD1 treatment. Results of the present study suggest that RvD1 protects the heart against LPS‐induced injuries by attenuating the local and systemic inflammatory response, highlighting the therapeutic effects of RvD1 in sepsis‐induced cardiac injury. [ABSTRACT FROM AUTHOR]

Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane‐localized legume‐lectin receptor kinase that we named OsLecRK‐S.7. OsLecRK‐S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK‐S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376, Ser378, Thr386, Thr403, and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk‐s.7 mutant plant overexpressing OsLecRK‐S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK‐S.7 was a key regulator of pollen development. [ABSTRACT FROM AUTHOR]

Large‐scale production of male sterile seeds can be achieved by introducing a fertility‐restoration gene linked with a pollen‐killer gene into a recessive male sterile mutant. We attempted to construct this system in rice by using a late‐stage pollen‐specific (LSP) promoter driving the expression of maize α‐amylase gene ZM‐AA1. To obtain such promoters in rice, we conducted comparative RNA‐seq analysis of mature pollen with meiosis anther, and compared this with the transcriptomic data of various tissues in the Rice Expression Database, resulting in 269 candidate LSP genes. Initial test of nine LSP genes showed that only the most active OsLSP3 promoter could drive ZM‐AA1 to disrupt pollen. We then analyzed an additional 22 LSP genes and found 12 genes stronger than OsLSP3 in late‐stage anthers. The promoters of OsLSP5 and OsLSP6 showing higher expression than OsLSP3 at stages 11 and 12 could drive ZM‐AA1 to inactivate pollen, while the promoter of OsLSP4 showing higher expression at stage 12 only could not drive ZM‐AA1 to disrupt pollen, suggesting that strong promoter activity at stage 11 was critical for pollen inactivation. The strong pollen‐specific promoters identified in this study provided valuable tools for genetic engineering of rice male sterile system for hybrid rice production. [ABSTRACT FROM AUTHOR]

New nanostructure means new nanotechnology and nanoscience. The need of complex nanostructure‐based advanced functional nanomaterials has promoted the appearance of several kinds of multifluid electrospinning processes, such as tri‐axial electrospinning, quad‐fluid coaxial electrospinning, tri‐fluid side‐by‐side electrospinning, and coaxial electrospinning with a side‐by‐side core. These multifluid processes can greatly expand the capability of electrospinning in generating new types of nanostructures with different organization manner of the inner parts, and from both spinnable and unspinnable working fluids. The key elements for conducting a multifluid electrospinning lie in a well‐designed spinneret, compatibility of the working fluids, and special operational parameters. The complex nanostructures can be created through direct electrospinning of multiple fluids, through after‐treatment of the electrospun products, and through ingenious design of the components, compositions and their spatial distributions as well. This article provides a simple review on the most recent publications about the multifluid electrospinning processes and the corresponding complex nanostructures. This article is characterized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesImplantable Materials and Surgical Technologies > Nanomaterials and Implants [ABSTRACT FROM AUTHOR]

In Arabidopsis, both the membrane-anchored receptor-like kinase (RLK) BAK1 and the receptor-like cytoplasmic kinase (RLCK) BIK1 are important mediators of transmembrane signal transduction that regulate plant development and immunity. However, little attention has been paid to their genetic association. This study found the bak1 bik1 double mutant of Arabidopsis displayed a severe dwarfism phenotype due to constitutive immunity and cell death in developing plants. These data suggest that BIK1 cooperates with BAK1 to regulate constitutive immunity and cell death. [ABSTRACT FROM AUTHOR]

Microbe-associated molecular pattern ( MAMP)-triggered immunity plays critical roles in the basal resistance defense response in plants. Chitin and peptidoglycan ( PGN) are major molecular patterns for fungi and bacteria, respectively. Two rice ( Oryza sativa) lysin motif-containing proteins, Os LYP4 and Os LYP6, function as receptors that sense bacterial PGN and fungal chitin. These membrane receptors, which lack intracellular kinase domains, likely contain another component for transmembrane immune signal transduction. Here, we demonstrate that the rice LysM receptor-like kinase Os CERK1, a key component of the chitin elicitor signaling pathway, also plays an important role in PGN-triggered immunity in rice. Silencing of Os CERK1 suppressed PGN-induced (and chitin-induced) immunity responses, including reactive oxygen species generation, defense gene expression, and callose deposition, indicating that Os CERK1 is essential for both PGN and chitin signaling initiated by Os LYP4 and Os LYP6. Os LYP4 associated with Os LYP6 and the rice chitin receptor chitin oligosaccharide elicitor-binding protein ( CEBiP) in the absence of PGN or chitin, and treatment with PGN or chitin led to their disassociation in vivo. Os CERK1 associated with Os LYP4 or Os LYP6 when induced by PGN but it associated with Os LYP4, Os LYP6, or CEBiP under chitin treatment, suggesting the presence of different patterns of ligand-induced heterooligomeric receptor complexes. Furthermore, the receptor-like cytoplasmic kinase Os RLCK176 functions downstream of Os CERK1 in the PGN and chitin signaling pathways, suggesting that these MAMPs share overlapping intracellular signaling components. Therefore, Os CERK1 plays dual roles in PGN and chitin signaling in rice innate immunity and as an adaptor involved in signal transduction at the plasma membrane in conjunction with Os LYP4 and Os LYP6. [ABSTRACT FROM AUTHOR]

Regulated cell death (RCD) is a complex process that involves several cell types and plays a crucial role in vascular diseases. Vascular smooth muscle cells (VSMCs) are the predominant elements of the medial layer of blood vessels, and their regulated death contributes to the pathogenesis of vascular diseases. The types of regulated VSMC death include apoptosis, necroptosis, pyroptosis, ferroptosis, parthanatos, and autophagy‐dependent cell death (ADCD). In this review, we summarize the current evidence of regulated VSMC death pathways in major vascular diseases, such as atherosclerosis, vascular calcification, aortic aneurysm and dissection, hypertension, pulmonary arterial hypertension, neointimal hyperplasia, and inherited vascular diseases. All forms of RCD constitute a single, coordinated cell death system in which one pathway can compensate for another during disease progression. Pharmacologically targeting RCD pathways has potential for slowing and reversing disease progression, but challenges remain. A better understanding of the role of regulated VSMC death in vascular diseases and the underlying mechanisms may lead to novel pharmacological developments and help clinicians address the residual cardiovascular risk in patients with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor-like repeats and discoidin I-like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear., Methods and Results: A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL-1β (interleukin 1β) and TGF-β (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin-induced EndMT by promoting Smad4 deubiquitination in HUVECs., Conclusions: Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.

Background Sympathetic hyperactivity contributes to pathological remodeling after myocardial infarction (MI). However, the mechanisms underlying the increase in sympathetic activity remain unknown. Microglia are the predominant immune cells in the central nervous system and can regulate sympathetic neuron activity through neuroimmune response in the hypothalamic paraventricular nucleus. The present study aimed to investigate whether microglia-mediated neuroimmune response can regulate sympathetic activity and cardiac remodeling after MI. Methods and Results PLX3397 (pexidartinib) was used to deplete central microglia via intragastric injection or intracerebroventricular injection. After that, MI was induced by ligation of the left anterior descending coronary artery. Our study showed that MI resulted in the activation of microglia in the paraventricular nucleus. Microglia depletion, which was induced by PLX3397 treatment via intragastric injection or intracerebroventricular injection, improved cardiac function, reduced infarction size, and attenuated cardiomyocyte apoptosis, fibrosis, pathological electrical remodeling, and myocardial inflammation after MI. Mechanistically, these protective effects were associated with an attenuated neuroimmune response in the paraventricular nucleus, which contributed to the decrease of sympathetic activity and attenuation of sympathetic remodeling in the heart. However, intragastric injection with PLX3397 obviously depleted macrophages and induced neutrophil and T-lymphocyte disorders in the heart, blood, and spleen. Conclusions Microglia depletion in the central nervous system attenuates pathological cardiac remodeling after MI by inhibiting neuroimmune response and sympathetic activity. Intragastric administration of PLX3397 leads to serious deleterious effects in peripheral immune cells, especially macrophages, which should be a cause for concern in animal experiments and clinical practice.

Scavenger receptors (SRs) are a structurally heterogeneous superfamily of evolutionarily conserved receptors that are divided into classes A to J. SRs can recognize multiple ligands, such as modified lipoproteins, damage-associated molecular patterns, and pathogen-associated molecular patterns, and regulate lipid metabolism, immunity, and homeostasis. According to the literature, SRs may play a critical role in myocardial infarction and ischemia/reperfusion injury, and the soluble types of SRs may be a series of promising biomarkers for the diagnosis and prognosis of patients with acute coronary syndrome or acute myocardial infarction. In this review, we briefly summarize the structure and function of SRs and discuss the association between each SR and ischemic cardiac injury in patients and animal models in detail. A better understanding of the effect of SRs on ischemic cardiac injury will inspire novel ideas for therapeutic drug discovery and disease evaluation in patients with myocardial infarction.

Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods and Results BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), a small-molecule inhibitor of branched-chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle-treated mice, whereas the BT2-treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity. Conclusions Our data provide the first proof-of-concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure.

Background: The mechanisms of atrial fibrillation (AF) induced by obstructive sleep apnea (OSA) are not completely understood. This study investigated the roles of the intrinsic and extrinsic cardiac autonomic nervous system in OSA-induced AF and provided noninvasive autonomic nervous modulation for the suppression of OSA-induced AF by using low-level transcutaneous electrical stimulation (LL-TS) of the auricular branch of the vagus nerve at the tragus., Methods and Results: Eighteen dogs received tracheostomy under general anesthesia and were randomly divided into 3 groups: the OSA group (OSA was simulated via clamping of the endotracheal tube at end expiration for 1.5 minutes every 10 minutes, n=6), the LL-TS + OSA group (simulated OSA plus LL-TS, at 80% of the slowing sinus rate, n=6), and the control group (sham surgery without stimulation, n=6). The effective refractory period was significantly shortened after 1 hour of simulated OSA, and the window of vulnerability and plasma norepinephrine levels were both markedly increased in the OSA group. OSA dramatically increased the neural function and activity of the intrinsic and extrinsic cardiac autonomic nervous system, including the superior left ganglionated plexus, the left stellate ganglion, and the left renal sympathetic nerve. OSA also significantly upregulated the expression levels of c-fos and nerve growth factor in the superior left ganglionated plexus and the left stellate ganglion. However, LL-TS markedly improved these parameters., Conclusions: These findings suggest that the intrinsic and extrinsic cardiac autonomic nervous system plays crucial roles in the acute stage of OSA-induced AF. Noninvasive LL-TS suppressed shortening of atrial refractoriness and autonomic remodeling, which prevented OSA-induced AF., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)