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Background: miRNA therapeutics have gained attention during the past decade. These oligonucleotide treatments can modulate the expression of miRNAs in vivo and could be used to correct the imbalance of gene expression found in human diseases such as obesity, metabolic syndrome, and atherosclerosis. The in vivo efficacy of current anti-miRNA technologies hindered by physiological and cellular barriers to delivery into targeted cells and the nature of miRNAs that allows one to target an entire pathway that may lead to deleterious off-target effects. For these reasons, novel targeted delivery systems to inhibit miRNAs in specific tissues will be important for developing effective therapeutic strategies for numerous diseases including atherosclerosis. Methods: We used pH low-insertion peptide (pHLIP) constructs as vehicles to deliver microRNA-33-5p (miR-33) antisense oligonucleotides to atherosclerotic plaques. Immunohistochemistry and histology analysis was performed to assess the efficacy of miR-33 silencing in atherosclerotic lesions. We also assessed how miR-33 inhibition affects gene expression in monocytes/macrophages by single-cell RNA transcriptomics. Results: The anti-miR-33 conjugated pHLIP constructs are preferentially delivered to atherosclerotic plaque macrophages. The inhibition of miR-33 using pHLIP-directed macrophage targeting improves atherosclerosis regression by increasing collagen content and decreased lipid accumulation within vascular lesions. Single-cell RNA sequencing analysis revealed higher expression of fibrotic genes ( Col2a1, Col3a1, Col1a2, Fn1 , etc) and tissue inhibitor of metalloproteinase 3 ( Timp3 ) and downregulation of Mmp12 in macrophages from atherosclerotic lesions targeted by pHLIP-anti-miR-33. Conclusions: This study provides proof of principle for the application of pHLIP for treating advanced atherosclerosis via pharmacological inhibition of miR-33 in macrophages that avoid the deleterious effects in other metabolic tissues. This may open new therapeutic opportunities for atherosclerosis-associated cardiovascular diseases via selective delivery of other protective miRNAs.

Three-dimensional (3D) bioprinting technology, allowing rapid prototyping and personalized customization, has received much attention in recent years, while regenerated silk fibroin (RSF) has also been widely investigated for its excellent biocompatibility, processibility, and comprehensive mechanical properties. However, due to the difficulty in curing RSF aqueous solution and the tendency of conformational transition of RSF chains under shearing, it is rather complicated to fabricate RSF-based materials with high mechanical strength through extrusion bioprinting. To solve this problem, a printable hydrogel with thixotropy was prepared from regenerated silk fibroin with high-molecular-weight (HMWRSF) combined with a small amount of hydroxypropyl methylcellulose (HPMC) in urea containing aqueous solution. It was found that the introduction of urea could not only vary the solid content of the hydrogel to benefit the mechanical properties of the 3D-bioprinted pre-cured hydrogels or 3D-bioprinted sponges, but also expand the "printable window" of this system. Indeed, the printability and rheological properties could be modulated by varying the solid content, the heating time, the urea/HMWRSF weight ratio

Record-high power and energy density are achieved in gelatin/GTA-KCl-FeCN4−/3− i-TE cells by extending the working temperature range.

The desired preloading effect of a hydraulic press frame parts (upper/lower semi-circular beams and columns) with Pre-Tightening Stress (PTS) by means of Winding Steel Wires (WSW), which is directly related to the reliability and normal safe operation of the hydraulic press. The deformation of the Hydraulic Press Column (HPC) is an important indicator of the optimal preloading effect of the hydraulic press. As a technical bottleneck, the continuous cumulative deformation of a HPC under seven time-varying steps is critical issues especially in theoretically calculated for a 20 MN double-frame hydraulic press with PTS using WAW. A solid model with a PTS frame is pre-designed by 3D software, and two simulation methods, equivalent pressure loading and equivalent temperature loading, are used to simulate and analyze the continuous cumulative deformation of the HPC under each step in Ansys Workbench software. By comparing the deformation and error analysis in the three cases above, the feasibility of the two simulation methods is verified, which leads to the advantages and disadvantages of each method in order to guide the subsequent design.

Lithium-air (Li-air) batteries stand out among the post-Li-ion batteries due to their high energy density, which has rapidly progressed in the past years. Regarding the fundamental mechanism of Li-air batteries that discharge products produced and decomposed during charging and recharging progress, the reversibility of products closely affects the battery performance. Along with the upsurge of the mainstream discharge products lithium peroxide, with devoted efforts to screening electrolytes, constructing high-efficiency cathodes, and optimizing anodes, much progress has been made in the fundamental understanding and performance. However, the limited advancement is insufficient. In this case, the investigations of other discharge products, including lithium hydroxide, lithium superoxide, lithium oxide, and lithium carbonate, emerge and bring breakthroughs for the Li-air battery technologies. To deepen the understanding of the electrochemical reactions and conversions of discharge products in the battery, we systematically review recent advances in the various discharge products, mainly focusing on the growth and decomposition mechanisms and the determining factors. We also provide perspectives for Li-air batteries on the fundamental development of discharge products and future applications. This article is protected by copyright. All rights reserved.

Background: Cross-talk between sterol metabolism and inflammatory pathways has been demonstrated to significantly affect the development of atherosclerosis. Cholesterol biosynthetic intermediates and derivatives are increasingly recognized as key immune regulators of macrophages in response to innate immune activation and lipid overloading. 25-Hydroxycholesterol (25-HC) is produced as an oxidation product of cholesterol by the enzyme cholesterol 25-hydroxylase (CH25H) and belongs to a family of bioactive cholesterol derivatives produced by cells in response to fluctuating cholesterol levels and immune activation. Despite the major role of 25-HC as a mediator of innate and adaptive immune responses, its contribution during the progression of atherosclerosis remains unclear. Methods: The levels of 25-HC were analyzed by liquid chromatography-mass spectrometry, and the expression of CH25H in different macrophage populations of human or mouse atherosclerotic plaques, respectively. The effect of CH25H on atherosclerosis progression was analyzed by bone marrow adoptive transfer of cells from wild-type or Ch25h –/– mice to lethally irradiated Ldlr –/– mice, followed by a Western diet feeding for 12 weeks. Lipidomic, transcriptomic analysis and effects on macrophage function and signaling were analyzed in vitro from lipid-loaded macrophage isolated from Ldlr –/– or Ch25h–/–;Ldlr–/– mice . The contribution of secreted 25-HC to fibrous cap formation was analyzed using a smooth muscle cell lineage–tracing mouse model, Myh11 ERT2CRE mT/mG;Ldlr –/– , adoptively transferred with wild-type or Ch25h –/– mice bone marrow followed by 12 weeks of Western diet feeding. Results: We found that 25-HC accumulated in human coronary atherosclerotic lesions and that macrophage-derived 25-HC accelerated atherosclerosis progression, promoting plaque instability through autocrine and paracrine actions. 25-HC amplified the inflammatory response of lipid-loaded macrophages and inhibited the migration of smooth muscle cells within the plaque. 25-HC intensified inflammatory responses of lipid-laden macrophages by modifying the pool of accessible cholesterol in the plasma membrane, which altered Toll-like receptor 4 signaling, promoted nuclear factor-κB–mediated proinflammatory gene expression, and increased apoptosis susceptibility. These effects were independent of 25-HC–mediated modulation of liver X receptor or SREBP (sterol regulatory element–binding protein) transcriptional activity. Conclusions: Production of 25-HC by activated macrophages amplifies their inflammatory phenotype, thus promoting atherogenesis.

Using anaerobic membrane bioreactors (AnMBRs) to treat swine wastewater is an effective method to recover bioenergy. However, due to the inhibitory effect of high concentrations of organic matter and ammonia nitrogen on microbial activities in swine wastewater, some problems are evident such as low recovery efficiency and serious membrane fouling. In this study, biochar prepared from spent coffee grounds (SCG-BC) was added to AnMBR to investigate its effect on the operation process. Results reported that methane yield rose from 0.227 LCH4/g-CODremoved to 0.267 LCH4/g-CODremoved along with a reduction in CO2 being produced at 35.25 % after adding SCG-BC. It confirmed that in-situ biogas upgrading was achieved. As well, the total volatile fatty acids declined to a low concentration of 194.87 ± 51.82 mg/L while pH remained steadily at 7.70 ± 0.31. Adding SCG-BC reduced irreversible membrane fouling by 34.69 %. Microbial community analysis showed that SCG-BC increased the relative abundance of methanogenic archaea, especially Methanosarcina (from 1.47 % to 8.03 %). Also, Anaerolinea and Methanosaeta participating in direct interspecies electron transfer were enriched onto biochar. They acted together to enhance the biogas production. It can be concluded that AnMBR with SCG-BC addition has good application prospects in recovering bioenergy from wastewater.

Background and Aims COVID-19 is associated with liver injury and elevated interleukin-6 (IL-6). We hypothesized that IL-6 trans-signaling in liver sinusoidal endothelial cells (LSECs) leads to endotheliopathy (a proinflammatory and procoagulant state) and liver injury in COVID-19. Methods Coagulopathy, endotheliopathy, and alanine aminotransferase (ALT) were retrospectively analyzed in a subset (n = 68), followed by a larger cohort (n = 3,780) of patients with COVID-19. Liver histology from 43 patients with COVID-19 was analyzed for endotheliopathy and its relationship to liver injury. Primary human LSECs were used to establish the IL-6 trans-signaling mechanism. Results Factor VIII, fibrinogen, D-dimer, von Willebrand factor (vWF) activity/antigen (biomarkers of coagulopathy/endotheliopathy) were significantly elevated in patients with COVID-19 and liver injury (elevated ALT). IL-6 positively correlated with vWF antigen (p = 0.02), factor VIII activity (p = 0.02), and D-dimer (p, Graphical abstract

Objectives Platycarya strobilacea Sieb. et Zucc. is the dry infructescence of P. strobilacea, a Juglandaceae plant and is a traditional Chinese medicine with great development potential and utilization value. This study summarizes the research progress on the traditional uses, botany, phytochemistry, extraction methods, pharmacology and toxicology of Platycarya strobilacea Sieb. et Zucc., and provides potential therapeutic uses and drug development prospects for this plant. Key findings Phytochemical studies showed that this plant mainly contains volatile constituents, phenols, terpenoids and a carbohydrate. The pharmacological activity of Platycarya strobilacea Sieb. et Zucc. includes antibacterial and anti-inflammatory effects, anti-tumour effects and antioxidant effects. This plant is especially effective in the treatment of allergic rhinitis and chronic sinusitis. Summary In this review, the phytochemistry and pharmacological effects of Platycarya strobilacea Sieb. et Zucc. are described in detail, which will have guiding significance for the future development of this drug.

Nitrogen (N) is an essential nutrient element required for plant growth, and the development of wheat varieties with high nitrogen use efficiency (NUE) is an urgent need for sustainable crop production. However, the molecular mechanism of NUE between diverse wheat varieties in response to N application remains unclear. To reveal the possible molecular mechanisms underlying this complex phenomenon, we investigated the transcriptional and metabolic changes of flag leaves of two wheat near-isogenic lines (NILs) differing in NUE under two N fertilizer treatments. Comparative transcriptome analysis indicated that the expression levels of the genes responsible for carbon and nitrogen metabolism were significantly higher in high-NUE wheat. The metabolome comparison revealed that the activity of the tricarboxylic acid (TCA) cycle was enhanced in high-NUE wheat, while reduced in low-NUE wheat after the N fertilizer application. Additionally, amino acid metabolism increased in both wheat NILs but more increased in high-NUE wheat. In summary, more upregulated transcripts and metabolites were identified in high-NUE wheat, and this study provides valuable new insights for improving NUE in wheat.

Atherosclerotic cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in people with type 2 diabetes (T2D) and new therapies are urgently needed. We recently developed an orally available, liver-directed controlled-release mitochondrial protonophore (CRMP) and showed that this agent safely reverses hypertriglyceridemia, fatty liver, and T2D in rodent and nonhuman primate models of obesity by promoting a subtle sustained increase in hepatic mitochondrial inefficiency. To determine the effect of CRMP on atherogenesis, we performed intervention studies in which 12-week Western-diet fed Ldlr -/- mice with established atherosclerosis were treated with CRMP (30 mg/kg-day) or vehicle control for an additional 12 weeks. CRMP-treated mice displayed a significant reduction in fasting plasma and hepatic triglyceride content, independently of changes in body weight, fasting plasma glucose, insulin or cholesterol levels. Morphometric analysis of the aortic root and brachiocephalic artery revealed that CRMP treatment significantly reduced total plaque area and neutral lipid accumulation. CRMP treatment also decreased markers of plaque vulnerability, as evidenced by a reduction in necrotic core area and increase in fibrous cap area ( P Ldlr -/- mice fed a Western diet containing CRMP or vehicle control for 12 weeks. Similarly to the intervention studies, CRMP significantly reduced aortic root plaque area, neutral lipid accumulation and necrotic core area. These changes were associated with a reduction in plasma triglyceride content and improvement in whole-body insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamps (all P Ldlr -/- mice revealed that CRMP reduced the frequency of inflammatory macrophages compared to vehicle (~19% vs ~2%), consistent with an immune-dampening effect of CRMP. Taken together, these data support an anti-atherogenic role for CRMP and suggest the therapeutic potential of liver-directed mitochondrial uncouplers for the treatment of early and late-stage atherosclerosis.

The transformation of halogenated organics in advanced oxidation processes (AOPs) has been extensively investigated. However, we currently know little about the fate of halogenated pollutants in the presence of exogenic halides (Cl- or Br-). Herein, the degradability, mineralization rate, and accumulation capacity of adsorbable organic halogen (AOX) for chlorophenols (2-chlorophenol (2-CP), 3-chlorophenol (3-CP), 4-chlorophenol (4-CP), and 2,4,6-trichlorophenol (TCP)) were compared in the Fe2+/persulfate (PS) process with the addition of exogenic halides. Results indicate that exogenic X- can lead to a decrease in chlorophenols degradation and mineralization rate, undesirable accumulation of AOX, and generation of halogenated by-products which are more toxic than precursor chlorophenols. Results of kinetics modeling show that Cl2•- plays more important role than SO4•- with an addition of Cl-, while SO4•-, Br2•-, and Br2 are responsible for the effect of Br-. As well, the effect of endogenic chlorine atoms on chlorophenols reveals that the degradability and AOX formation potential of 3-CP are highest while that of TCP are the lowest. This study demonstrates the significant influence of endogenic chlorine atoms and exogenic X- on the fate of typical organic halogen compounds. Consequently, the X- level and position/number of halogen atoms should be considered simultaneously when treating organohalogen compounds.

The safety testing of ferromagnetic materials, which are the main materials for various machines and equipment, is particularly important. Stress concentration zones (stress defects) cause stress corrosion of ferromagnetic materials, and also have the potential to cause direct damage to ferromagnetic materials. Estimation of stress sources state using electromagnetic nondestructive measurement methods is a critical and difficult problem. In this paper, a visual and intelligent identification method of stress defects in ferromagnetic materials by low frequency AC magnetic flux leakage (ACMFL) technique is proposed. A new three-point compression experiment was designed in this paper. Time-difference vision is established to analyze the ACMFL signal caused by stress defects. A visual transformed convolutional neural network deep learning algorithm has been proposed to identify grayscale patterns pre-processed by the time-difference vision. The results show that the method proposed in this paper elucidates the relationship between the time-difference vision of a stress defect and the stress source state of the mechanical stress. Our proposed method allows to analyze the pressure indenter size of the pressure source of stress defects.

Luminescence materials have shown promise as display apparatus and lighting devices. The particularly interesting systems are photoluminescence materials that are capable of reversible colors emitting repeatedly on exposure to light. Here we report a series of color tunable flexible and transparent photoluminescence films consisting of multi-metals (Eu3+, Tb3+ and Zn2+) induced polymer aggregates (MIPAs) which are distributed uniformly in the polyacrylonitrile (PAN) films without agglomeration. MIPAs have a unique spherical structure due to the self-assembly of polystyrene-block-polyacrylic acid (PS-b-PAA) induced by metal ions. Notably, when applied in photoluminescence devices, these photoluminescence films exhibit not only red, green, blue colors (RGB) light, but also other tuned various color light covering the whole visible range upon excitation of 345 nm through adjusting the relative ratios of metal complexes. As the most important key point, non-conductive polymers can be used in photoluminescence devices as host medium, which is not realized in electroluminescent devices. Thus, the flexible photoluminescence films (FPFs) innovated herein exhibit the great potential to apply for flexible light-color and light-energy transformation devices.

The synergistic removal of multi-pollutants, including particles, SO2, and NO2, is a key concern in the process of flue gas purification, during which the supersaturated environment is an essential premise for the nucleation and deep reduction of particles. The condensation of desulfurized flue gas using heat exchangers can not only recover condensed water and latent heat but also create supersaturated environment to promote the flue gas purification. In this study, an experimental system for desulfurized flue gas condensation is established. The effect and associated mechanism of condensation process on the removal of multi-pollutions are clarified. The results show that particles with an aerodynamic diameter larger than 2.5 μm accounts for 50% in mass proportion. The flue gas temperature drop has positive influence to the increase of the ideal supersaturation degree, which is beneficial for the removal of particles (especially when the aerodynamic diameter is less than 1 μm), SO2, and NO2. The ideal supersaturation degree slightly reduces with the rise of inlet flue gas temperature, which can promote the removal efficiency of small particles, while weaken that of large particles, SO2, and NO2. Caused by the increase of flue gas flow rate, the nucleation process weakens, reducing the removal efficiency of all pollutants (particles, 45.2–28.3%; SO2, 27.5–14.5%; NO2, 21.5–15%). On the whole, the increase of the ideal supersaturation degree contributes to the synergistic removal of pollutants especially particles with smaller radius in the flue gas. The reduction of particles with aerodynamic diameter less than 1 μm is conductive to the synergistic removal of SO2 and NO2.

Objective: Mitogen-activated protein kinases (MAPKs), including JNK, ERK, and p38 MAPK, are critical in regulating the expression of various pro-inflammatory and anti-inflammatory cytokines and chemokines. Previous work has suggested that the absence of MAP Kinase Phosphatase-5 (MKP-5) inhibits oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation without influencing the MAKP activation. The current study is to determine the role of macrophage MKP-5 in the pathogenesis of atherosclerosis and underlying mechanisms. Approach and Results: Nine-week-old male congenic MKP-5 deficient (MKP-5 -/- ) and C57Bl/6J control (WT) mice on an LDL receptor knock-out (LDLR -/- ) background were fed with a high-fat diet containing 1.25% cholesterol (HFD) for 14 weeks. Global deficiency of MKP-5 attenuated atherosclerotic plaque formation without altering the lipid profile in vivo. To further elucidate the macrophage-specific effect of MKP-5 in atherogenesis, Lethally irradiated LDLR -/- mice were transplanted with WT or MKP-5 -/- bone marrow and subjected to high-fat feeding. Mice transplanted with MKP-5 -/- bone marrow developed smaller atherosclerotic lesions accompanied by decreased lipid deposition and macrophage content compared to WT. Lack of MKP-5 in macrophages reduced plasma levels of interleukin-1α (IL-1α) and IL-7, elevated anti-inflammatory cytokines IL-1 receptor antagonist (IL-1rn), and IL-4. Mechanistically, lack of MKP-5 in macrophages inhibited ox-LDL-induced foam cell formation through enhanced cholesterol efflux mediated by increased expression of ATP-binding cassette transporters ABCA1 and ABCG1. Conclusions: These data suggest that the myeloid MKP-5 deficiency reduces atherosclerosis progression and foam cell formation by ameliorating cholesterol efflux and inhibiting inflammation.

To investigate hedging effectiveness of multinational companies in respect of using currency derivatives, the author adapts an innovative and multi layers GJR-GARCH-based model. This model broke down the currency risk faced by MNCs in each business area and added six control variables other than foreign sales ratio, all these variables have been proved to be related to MNCs’ currency risk exposure but was not included into previous models. Moreover, this model absorbs advantages of several models built in previous studies and combines them into a whole, intact model. This paper also employed a wide research scope, using a sample of 48 non-financial and 28 financial firms headquartered in USA. Also, comparison between financial and non-financial firms is an innovation of our research. According to the result, hedging of non-financial companies in respect of currency risk is ineffective, and financial companies are more likely using currency derivatives to speculate.

The overall purpose of this research was to investigate the typical types of chemically enhanced backwash by-products (CEBBPs) produced in the chemically enhanced backwash (CEB) process and the influence of variability of CEB factors on typical CEBBPs in the adsorption-ultrafiltration process. Moreover, health risk assessment was utilized to assess the potential adverse health effects from exposure to effluent after the optimal online CEB. The results of the study found the NaClO backwash reagent could react with organic matter to produce CEBBPs, including 9 kinds of volatile halogenated organic compounds (VHOCs) and 9 kinds of haloacetic acids (HAAs) during the CEB process. After a comprehensive consideration of the influence of a single factor on the CEBBPs formation and membrane cleaning effect, the optimal CEB parameters were 6 min of BD, 120 min of BI, 30 L/(m2·h) of BF and 50 mg/L of RC. Under the optimum CEB cleaning parameters, the effluent does not pose a non-carcinogenic risk and posed potential carcinogenic risk to local residents. The lifetime carcinogenic risk (LCR) value for HAAs (6.68E-06) is very close to the LCR value of CEBBPs (6.78E-06), indicating that the HAAs are the main substances in the effluent after CEB.

Supplemental Digital Content is available in the text., Objective: Endothelial Cav-1 (caveolin-1) expression plays a relevant role during atherogenesis by controlling NO production, vascular inflammation, LDL (low-density lipoprotein) transcytosis, and extracellular matrix remodeling. Additional studies have identified cholesterol-rich membrane domains as important regulators of autophagy by recruiting ATGs (autophagy-related proteins) to the plasma membrane. Here, we investigate how the expression of Cav-1 in the aortic endothelium influences autophagy and whether enhanced autophagy contributes to the atheroprotective phenotype observed in Cav-1–deficient mice. Approach and Results: To analyze the impact of Cav-1 deficiency on regulation of autophagy in the aortic endothelium during the progression of atherosclerosis, we fed Ldlr−/− and Cav-1−/−Ldlr−/− mice a Western diet and assessed autophagy in the vasculature. We observe that the absence of Cav-1 promotes autophagy activation in athero-prone areas of the aortic endothelium by enhancing autophagic flux. Mechanistically, we found that Cav-1 interacts with the ATG5-ATG12 complex and influences the cellular localization of autophagosome components in lipid rafts, which controls the autophagosome formation and autophagic flux. Pharmacological inhibition of autophagy attenuates the atheroprotection observed in Cav-1−/− mice by increasing endothelial inflammation and macrophage recruitment, identifying a novel molecular mechanism by which Cav-1 deficiency protects against the progression of atherosclerosis. Conclusions: These results identify Cav-1 as a relevant regulator of autophagy in the aortic endothelium and demonstrate that pharmacological suppression of autophagic flux in Cav-1–deficient mice attenuates the atheroprotection observed in Cav-1−/− mice. Additionally, these findings suggest that activation of endothelial autophagy by blocking Cav-1 might provide a potential therapeutic strategy for cardiovascular diseases including atherosclerosis.