Engineering Glucosamine-6-Phosphate Synthase to Achieve Efficient One-Step Biosynthesis of Glucosamine.

As an important functional monosaccharide, glucosamine (GlcN) is widely used in fields such as medicine, food nutrition, and health care. Here, we report a distinct GlcN biosynthesis method that utilizes engineered Bacillus subtilis glucosamine-6-phosphate synthase (BsGlmS) to convert D-fructose to directly generate GlcN. The best variant obtained by using a combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was a quadruple mutant S596D/V597G/S347H/G299Q (BsGlmS-BK19), which has a catalytic activity 1736-fold that of the wild type toward D-fructose. Upon using mutant BK19 as a whole-cell catalyst, D-fructose was converted into GlcN with 65.32% conversion in 6 h, whereas the wild type only attained a conversion rate of 0.31% under the same conditions. Molecular docking and molecular dynamics simulations were implemented to provide insights into the mechanism underlying the enhanced activity of BK19. Importantly, the BsGlmS-BK19 variant specifically catalyzes D-fructose without the need for phosphorylated substrates, representing a significant advancement in GlcN biosynthesis.

Preparation of uniform lignin/titanium dioxide nanoparticles by confined assembly: A multifunctional nanofiller for a waterborne polyurethane wood coating.

We report a facile synthesis for lignin/titanium dioxide (TiO2) nanoparticles (LT NPs) at room temperature by confining assembly of lignin macromolecules. The LT NPs had a uniform nanosize distribution (average diameter âˆ¼ 68 nm) and were directly employed as multifunctional nanofillers to reinforce a waterborne polyurethane wood coating (WBC). X-ray diffraction, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy revealed the mechanism by which formed TiO2 confined lignin assembly. The LT NPs considerably increased the tensile strength of a WBC film from 16.3 MPa to 28.1 MPa. The WBC-LT NPs exhibited excellent ultraviolet (UV) A and UVB blocking performances of 87 % and 98 %, respectively, while maintaining 94 % transmittance in the visible region. Incorporating LT NPs into the WBC enhanced the coating performance (the hardness, adhesion, and abrasion resistance) on wood substrates. A quantitative color and texture analysis revealed that the LT NPs increased the decorativeness of actual wooden products. After nearly 1800 h of UV irradiation, wood coated with the WBC-LT NPs exhibited good color stability, where the original color remained unchanged or even became brighter. In this study, value-added valorization of lignin is enabled by using organic-inorganic nanofillers and insights are gained into developing multifunctional WBCs.

Efficient extraction of nanocellulose from lignocellulose using aqueous butanediol fractionation to improve the performance of waterborne wood coating.

The highly efficient extraction of cellulose from lignocellulose with an excellent yield of 95.2 % and purity of 96.7 % was demonstrated using acid-catalyzed fractionation with aqueous butanediol. This cellulose was subsequently transformed into cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs) with specific dimensions and surface functional groups through various chemomechanical treatments. The average diameters of CNFs and CNCs produced by sulfuric acid hydrolysis-ultrasonication and deep eutectic solvent treatment-ultrasonication (DES-CNCs) were 29.7, 21.9 and 17.3 nm, respectively. The DES-CNCs were obtained in a good yield of 71 ± 1.27 wt% and exhibited a high zeta potential of -33.5 ± 2.51 mV following posthydrolysis and esterification during the DES treatment. These CNFs and CNCs were used as nanofillers in a waterborne wood coating (WWC), which significantly improved its dynamic viscosity and storage modulus. The addition of these materials also enhanced the mechanical strength of the WWC but had little effect on transmittance. Glossiness, hardness, abrasion resistance and adhesion strength were evaluated, and the DES-CNCs provided the greatest improvements at a low concentration. A plausible reinforcement mechanism was presented. This work provided an efficient cellulose extraction method and detailed structure elucidation of the nanocellulose together with suggestions for value-added applications of cellulosic nanofillers for reinforcing WWC.

Composites based on electrospun fibers modified with cellulose nanocrystals and SiO2 for selective oil/water separation.

Membranes for water remediation require structural stability, efficient operation, and durability. In this work, we used cellulose nanocrystals (CNC) to reinforce hierarchical nanofibrous membranes based on polyacrylonitrile (PAN). Hydrolysis of the electrospun nanofibers (H-PAN) enabled hydrogen bonding with CNC and provided reactive sites for grafting cationic polyethyleneimine (PEI). In a further modification, anionic silica particles (SiO2) were adsorbed on the fiber surfaces, obtaining CNC/H-PAN/PEI/SiO2 hybrid membranes, which developed swelling resistance (swelling ratio of 6.7 compared to 25.4 measured for a CNC/PAN membrane). Hence, the introduced hydrophilic membranes contain highly interconnected channels, they are non-swellable and exhibit mechanical and structural integrity. By contrast with untreated PAN membranes, those obtained after modification displayed high structural integrity and allowed regeneration and cyclic operation. Finally, wettability and oil-in-water emulsion separation tests demonstrated remarkable oil rejection and separation efficiency in aqueous media.

Multiple Receptors Contribute to the Attractive Response of Caenorhabditis elegans to Pathogenic Bacteria.

Nematodes feed mainly on bacteria and sense volatile signals through their chemosensory system to distinguish food from pathogens. Although nematodes recognizing bacteria by volatile metabolites are ubiquitous, little is known of the associated molecular mechanism. Here, we show that the antinematode bacterium Paenibacillus polymyxa KM2501-1 exhibits an attractive effect on Caenorhabditis elegans via volatile metabolites, of which furfural acetone (FAc) acts as a broad-spectrum nematode attractant. We show that the attractive response toward FAc requires both the G-protein-coupled receptors STR-2 in AWC neurons and SRA-13 in AWA and AWC neurons. In the downstream olfactory signaling cascades, both the transient receptor potential vanilloid channel and the cyclic nucleotide-gated channel are necessary for FAc sensation. These results indicate that multiple receptors and subsequent signaling cascades contribute to the attractive response of C. elegans to FAc, and FAc is the first reported ligand of SRA-13. Our current work discovers that P. polymyxa KM2501-1 exhibits an attractive effect on nematodes by secreting volatile metabolites, especially FAc and 2-heptanone, broadening our understanding of the interactions between bacterial pathogens and nematodes. IMPORTANCE Nematodes feed on nontoxic bacteria as a food resource and avoid toxic bacteria; they distinguish them through their volatile metabolites. However, the mechanism of how nematodes recognize bacteria by volatile metabolites is not fully understood. Here, the antinematode bacterium Paenibacillus polymyxa KM2501-1 is found to exhibit an attractive effect on Caenorhabditis elegans via volatile metabolites, including FAc. We further reveal that the attractive response of C. elegans toward FAc requires multiple G-protein-coupled receptors and downstream olfactory signaling cascades in AWA and AWC neurons. This study highlights the important role of volatile metabolites in the interaction between nematodes and bacteria and confirms that multiple G-protein-coupled receptors on different olfactory neurons of C. elegans can jointly sense bacterial volatile signals.

Efficient downstream valorization of lignocellulose after organosolv fractionation: Synergistic enhancement of waterborne coatings by co-assembled lignin@cellulose nanocrystals.

The simultaneous downstream valorization of cellulose and lignin is an important aspect of efficiently extracting value from lignocellulose. The present work, we demonstrated the preparation of a novel bio-based filler by the co-assembly of cellulose and lignin obtained from a one-pot ethanosolv lignocellulose fractionation process. The cellulose was valorized by forming cellulose nanocrystals (CNCs) through simple bleaching and ultrasonication processes. The lignin fractions demonstrated greater solubility (19.2 mg/mL) and lower molecular weight (6980 g/mol) than conventional industrial lignins. Various lignin@CNCs specimens were prepared via a facile co-assembly of the lignin and CNCs. These entirely bio-based materials could be used as a multifunctional filler to enhance the properties of a waterborne coating (WBC). Specifically, the mechanical properties, coating performance and ultraviolet resistance of a WBC were all significantly improved, demonstrating a synergistic enhancement effect obtained from the CNCs and lignin. In this manner, both cellulose and lignin components were efficiently transformed to value-added fillers for WBC, demonstrating a highly efficient pathway for lignocellulose utilization and downstream value-added applications.

Effect of macrophage migration inhibitory factor on pulmonary vein arrhythmogenesis through late sodium current.

AIMS: Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF. METHODS AND RESULTS: A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, ΔF/F0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, ΔF/F0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 µM], ranolazine (an INa-Late inhibitor, 10 µM), and N-(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue. CONCLUSION: Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment.

Melatonin Inhibits NF-κB/CREB/Runx2 Signaling and Alleviates Aortic Valve Calcification.

Calcific aortic valve disease (CAVD) is linked to high mortality. Melatonin inhibits nuclear factor-kappa B (NF-κB)/cyclic AMP response element-binding protein (CREB), contributing to CAVD progression. This study determined the role of melatonin/MT1/MT2 signaling in valvular interstitial cell (VIC) calcification. Western blotting and Alizarin red staining were used to analyze NF-κB/CREB/runt-related transcription factor 2 (Runx2) signaling in porcine VICs treated with an osteogenic (OST) medium without (control) or with melatonin for 5 days. Chromatin immunoprecipitation (ChIP) assay was used to analyze NF-κB's transcription regulation of NF-κB on the Runx2 promoter. OST medium-treated VICs exhibited a greater expression of NF-κB, CREB, and Runx2 than control VICs. Melatonin treatment downregulated the effects of the OST medium and reduced VIC calcification. The MT1/MT2 antagonist (Luzindole) and MT1 receptor neutralized antibody blocked the anticalcification effect of melatonin, but an MT2-specific inhibitor (4-P-PDOT) did not. Besides, the NF-κB inhibitor (SC75741) reduced OST medium-induced VIC calcification to a similar extent to melatonin at 10 nmol/L. The ChIP assay demonstrated that melatonin attenuated OST media increased NF-κB binding activity to the promoter region of Runx2. Activation of the melatonin/MT1-axis significantly reduced VIC calcification by targeting the NF-κB/CREB/Runx2 pathway. Targeting melatonin/MT1 signaling may be a potential therapeutic strategy for CAVD.

Identification and Validation of Long Non-Coding RNA LCIIAR as a Biomarker in LUAD.

Lung cancer is the leading cause of cancer-related death worldwide. Therapies for lung cancer have relatively poor outcomes and need to be improved. Lung cancer immune cell infiltration associated RNA (LCIIAR) is a long noncoding RNA (lncRNA), which is overexpressed in human cancers. However, the clinical significance and functional role of LCIIAR in Lung Adenocarcinoma remain unclear. Here, we identified a novel long non-coding RNA (ENSG00000256802), termed LCIIAR (lung cancer immune cell infiltration associated lncRNA), up-regulated in lung cancer tissue and cell lines. We show that increase LCIIAR expression correlated with poor clinical stage and adverse clinical outcomes and that could also serve as an independent unfavorable prognostic factor in patients with Lung Adenocarcinima. GSEA analysis demonstrated that LCIIAR is mainly involved in the regulation of the immune response. We uncovered that elevate LCIIAR expression positively correlated with immune infiltration and immune modulator in Lung Adenocarcinoma. More importantly, we confirmed that silencing of LCIIAR expression significantly inhibits the proliferation, and migration abilities of these tumour cells. We also demonstrated that the LCIIAR/hsa-miR184/SLC16A3/CDCP1 network regulates SLC16A3/CDCP1 overexpression in and is associated with poor prognosis in this tumour. Therefore our findings revealed the critical role of LCIIAR in Lung Adenocarcinoma progression, which may also serve as a prognostic biomarker and novel therapeutic target.

Ag/AgBr/AgVO3 Photocatalyst-Embedded Polyacrylonitrile/Polyamide/Chitosan Nanofiltration Membrane for Integrated Filtration and Degradation of RhB.

A nanofiltration (NF) membrane containing a NaOH-treated electrospun polyacrylonitrile (HPAN) substrate, an interfacial polymerization (IP) polyamide (PA) layer, a chitosan (CS) coating layer, and an Ag/AgBr/AgVO3 photocatalyst loading layer was prepared. The structural evolution of the membranes was investigated, and their performance was estimated in accordance with the water flux and rejection rate. A probable mechanism for the photocatalytic activity of Ag/AgBr/AgVO3 was proposed. The loading of the Ag/AgBr/AgVO3 heterojunction on the HPAN/PA/CS NF membrane endowed the membrane with excellent self-cleaning properties owing to the photolytic degradation of the dye. The filtration and degradation processes of the Ag/AgBr/AgVO3-loaded membrane constantly promoted each other, and the treatment efficiency achieved with the integrated (filtration + degradation) process was superior to those obtained with the filtration and degradation processes alone. The Ag/AgBr/AgVO3-NF membrane exhibited excellent recyclability and stability when subjected to five integrated filtration-degradation processes. In addition, the Ag/AgBr/AgVO3-NF membrane exhibited an elastic modulus of 65.75 MPa and a toughness of 38.9 kJ/m3 along with a good disinfection effect on Escherichia coli in visible light. The as-prepared photocatalyst-loaded NF membrane with excellent antifouling performance, antimicrobial activity, high strength, and recyclability showed potential for continuous water purification operation.

Occurrence of macroplastic debris in the long-term plastic film-mulched agricultural soil: A case study of Northwest China.

Widespread presence of plastic mulch has led to macroplastic (MaP) pollution. While this issue is widely explored in aquatic ecosystems, MaP pollution on land has been neglected. In 2019, we conducted a large-scale survey of MaPs in Northwest China in 0-30 cm soil with long-term mulching. Samples of MaP debris were collected from 67 sites across Gansu, east Qinghai, and north Shannxi Provinces. All visible MaP pieces for each site were separated and weighed. The mass of each MaP piece was calibrated by size measured in digital images. The MaP mass averaged 47.2 kg ha-1, and the number of MaPs averaged 266.2 pieces ha-1. The mass and number of MaPs varied from site to site. The mean size of MaPs was 19.5 cm2 piece-1 or 28.0 mg piece-1. More importantly, the number of small MaP pieces (<5 and 5-20 cm2 piece-1) accounted for 76.7% of the total number of MaPs detected, and small-sized plastic debris (<10 and 10-25 mg piece-1) were detected in 70.1% of the sampling sites. The percentage of small fragments increased before 15-year of mulching and then declined. However, the amount of medium-large debris (20-50 and >50 cm2 piece-1) showed a trend opposite to that of small fragments. The percentage of MaPs was greater in the small size group than in the medium-large size group. The arid to semi-arid area exhibited higher MaP contamination compared with the semi-arid to the semi-humid area. These observations indicate that plastic debris residing in soil tend to be fragmented, making plastic film recovery more challenging and causing severe soil pollution. Further studies are required to regulate plastic mulch methods and explore the degradation process.

Spider-web-inspired membrane reinforced with sulfhydryl-functionalized cellulose nanocrystals for oil/water separation.

The cellulose nanocrystals (CNC) has attracted widespread attention in reinforced materials. However, the application of CNC in electrospinning has been limited due to its self-polymerization. Herein, a cobweb-like nanofibrous membrane was fabricated by electrospinning the polyacrylonitrile (PAN) and sulfydryl-functionalized CNC (SC). The SC content could reach to 48 wt% after the thiolation modification. The membrane with ultrafine fibers and interlaced nets possessed outstanding porosity (91.7%) and underwater superoleophobicity. An ultrahigh permeation flux of 1244 L·m-2·h-1 with a separation efficiency of >99.9% was achieved driven by gravity. The mechanical properties also enhanced significantly with the increase of SC. When the addition amount of SC was 48 wt%, the maximum tensile stress was 2.9 MPa, which was 3.4 times than that of the PAN membrane. The antifouling performance and chemical stability endowed the SC(48)/PAN membrane with intriguing reusability, thus making it exhibit enormous potential in oil/water separation.

Reproductive Toxicity of Furfural Acetone in Meloidogyne incognita and Caenorhabditis elegans.

Furfural acetone (FAc) is a promising alternative to currently available nematicides, and it exhibits equivalent control efficiency on root-knot nematodes with avermectin in fields. However, its effect on the reproduction of root-knot nematode is poorly understood. In this study, the natural metabolite FAc was found to exhibit reproductive toxicity on Meloidogyne incognita and Caenorhabditis elegans. The number of germ cells of C. elegans was observed to decrease after exposure to FAc, with a reduction of 59.9% at a dose of 200 mg/L. FAc in various concentrations induced the germ-cell apoptosis of C. elegans, with an increase over six-fold in the number of apoptotic germ cells at 200 mg/L. These findings suggested that FAc decreased the brood size of nematode by inducing germ-cell apoptosis. Moreover, FAc-induced germ-cell apoptosis was suppressed by the mutation of gene hus-1, clk-2, cep-1, egl-1, ced-3, ced-4, or ced-9. The expression of genes spo-11, cep-1, and egl-1 in C. elegans was increased significantly after FAc treatment. Taken together, these results indicate that nematode exposure to FAc might inflict DNA damage through protein SPO-11, activate CEP-1 and EGL-1, and induce the core apoptosis pathway to cause germ-cell apoptosis, resulting in decreased brood size of C. elegans.

Galectin-3 enhances atrial remodelling and arrhythmogenesis through CD98 signalling.

AIM: Galectin-3 (Gal-3) is a biomarker of atrial fibrillation (AF) that mediates atrial inflammation. CD98 is the membrane surface receptor for Gal-3. Nevertheless, the role of the Gal-3/CD98 axis in atrial arrhythmogenesis is unclear. In this study, we investigated the effects of Gal-3/CD98 signalling on atrial pathogenesis. METHODS: Whole cell patch clamp and western blotting were used to analyse calcium/potassium homeostasis and calcium-related signalling in Gal-3-administrated HL-1 atrial cardiomyocytes with/without CD98 neutralized antibodies. Telemetry electrocardiographic recording, Masson's trichrome staining and immunohistochemistry staining of atrium were obtained from mice having received tail-vein injections with Gal-3. RESULTS: Gal-3-treated HL-1 myocytes had a shorter action potential duration, smaller L-type calcium current, increased sarcoplasmic reticulum (SR) calcium content, Na+ /Ca2+ exchanger (NCX) current, transient outward potassium current, and ultrarapid delayed rectifier potassium current than control cells had. Gal-3-treated HL-1 myocytes had greater levels of SR Ca2+ ATPase, NCX, Nav1.5, and NLR family pyrin domain containing 3 (NLRP3) expression and increased calcium/calmodulin-dependent protein kinase II (CaMKII), ryanodine receptor 2 (RyR2), and nuclear factor kappa B (NF-κB) phosphorylation than control cells had. Gal-3-mediated activation of CaMKII/RyR2 pathway was diminished in the cotreatment of anti-CD98 antibodies. Mice that were injected with Gal-3 had more atrial ectopic beats, increased atrial fibrosis, and activated NF-κB/NLRP3 signalling than did control mice (nonspecific immunoglobulin) or mice treated with Gal-3 and anti-CD98 antibodies. CONCLUSION: Gal-3 recombinant protein administration increases atrial fibrosis and arrhythmogenesis through CD98 signalling. Targeting Gal-3/CD98 axis might be a novel therapeutic strategy for patients with AF and high Gal-3 levels.

RYR2 mutation in non-small cell lung cancer prolongs survival via down-regulation of DKK1 and up-regulation of GS1-115G20.1: A weighted gene Co-expression network analysis and risk prognostic models.

RYR2 mutation is clinically frequent in non-small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into RYR2 mutant group (n = 337) and RYR2 wild group (n = 634), and established Kaplan-Meier curves. The results showed that RYR2 mutant group lived longer than the wild group (p = 0.027). Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis-related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of DKK1 and GS1-115G20.1 expression levels were 0.607 and 0.560, respectively, which predicted the 3-year survival rate of NSCLC sufferers. GSEA identified an association of high DKK1 expression with TP53, MTOR, and VEGF expression. Several target miRNAs interacting with GS1-115G20.1 were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with RYR2 mutation may obtain better prognosis by down-regulating DKK1 and up-regulating GS1-115G20.1.

The Role of EREG/EGFR Pathway in Tumor Progression.

Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung cancer and colorectal cancer (CRC). Epiregulin (EREG) is one of the EGFR ligands and is low expressed in most normal tissues. Elevated EREG in various cancers mainly activates EGFR signaling pathways and promotes cancer progression. Notably, a higher EREG expression level in CRC with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) is related to better efficacy of therapeutic treatment. By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations. Additionally, EREG overexpression in non-small cell lung cancer (NSCLC) is anticipated to be a therapeutic target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that EREG derived from macrophages promotes NSCLC cell resistance to EGFR-TKI treatment. The emerging events of EREG-mediated tumor promotion signals are generated by autocrine and paracrine loops that arise from tumor epithelial cells, fibroblasts, and macrophages in the tumor microenvironment (TME). The TME is a crucial element for the development of various cancer types and drug resistance. The regulation of EREG/EGFR pathways depends on distinct oncogenic driver mutations and cell contexts that allows specific pharmacological targeting alone or combinational treatment for tailored therapy. Novel strategies targeting EREG/EGFR, tumor-associated macrophages, and alternative activation oncoproteins are under development or undergoing clinical trials. In this review, we summarize the clinical outcomes of EREG expression and the interaction of this ligand in the TME. The EREG/EGFR pathway may be a potential target and may be combined with other driver mutation targets to combat specific cancers.

Regional Diversities in Fibrogenesis Weighed as a Key Determinant for Atrial Arrhythmogenesis.

Atrial fibrosis plays a key role in atrial myopathy, resulting in the genesis of atrial fibrillation (AF). The abnormal distribution of fibrotic tissue, electrical coupling, paracrine interactions, and biomechanical-electrical interactions have all been suggested as causes of fibrosis-related arrhythmogenesis. Moreover, the regional difference in fibrogenesis, specifically the left atrium (LA) exhibiting a higher arrhythmogenesis and level of fibrosis than the right atrium (RA) in AF, is a key contributor to atrial arrhythmogenesis. LA fibroblasts have greater profibrotic cellular activities than RA fibroblasts, but knowledge about the regional diversity of atrial regional fibrogenesis remains limited. This article provides a comprehensive review of research findings on the association between fibrogenesis and arrhythmogenesis from laboratory to clinical evidence and updates the current understanding of the potential mechanism underlying the difference in fibrogenesis between the LA and RA.

Sugar Fructose Triggers Gut Dysbiosis and Metabolic Inflammation with Cardiac Arrhythmogenesis.

Fructose is a main dietary sugar involved in the excess sugar intake-mediated progression of cardiovascular diseases and cardiac arrhythmias. Chronic intake of fructose has been the focus on the possible contributor to the metabolic diseases and cardiac inflammation. Recently, the small intestine was identified to be a major organ in fructose metabolism. The overconsumption of fructose induces dysbiosis of the gut microbiota, which, in turn, increases intestinal permeability and activates host inflammation. Endotoxins and metabolites of the gut microbiota, such as lipopolysaccharide, trimethylamine N-oxide, and short-chain fatty acids, also influence the host inflammation and cardiac biofunctions. Thus, high-fructose diets cause heart-gut axis disorders that promote cardiac arrhythmia. Understanding how gut microbiota dysbiosis-mediated inflammation influences the pathogenesis of cardiac arrhythmia may provide mechanisms for cardiac arrhythmogenesis. This narrative review updates our current understanding of the roles of excessive intake of fructose on the heart-gut axis and proposes potential strategies for inflammation-associated cardiac vascular diseases.

Effects of plastic particles on germination and growth of soybean (Glycine max): A pot experiment under field condition.

Plastic residues have become a serious environmental problem in areas where agricultural plastic film are used intensively. Although numerous of studies have been done to assess its impacts on soil quality and crop yields, the understanding of meso-plastic particles effects on plant is still limited. In this study, low density polyethylene (PE) and biodegradable plastic (Bio) mulch film were selected to study the effects of meso-plastic debris on soybean germination and plant growth with the accumulation levels of 0%, 0.1%, 0.5% and 1% in soil (w: w, size ranging 0.5-2 cm) by a pot experiment under field condition. Results showed that the germination viability of soybean seeds was reduced to 82.39%, 39.44% and 26.06% in the treatments with 0.1%, 0.5% and 1% added plastic debris compared to the control (CK), respectively, suggesting that plastic residues in soil inhibit the viability of soybean seed germination. The plastic debris had a significant negative effect on plant height and culm diameter during the entire growth stage of soybean. Similarly, the leaf area at harvest was reduced by 1.97%, 6.86% and 11.53% compared to the CK in the treatments with 0.1%, 0.5% and 1% plastic debris addition, respectively. In addition, the total plant biomass under plastic addition was reduced in both the flowering and harvesting stages, compared to the CK. For the different type of plastic residues, plant height, leaf area and root/shoot ratio at group PE were significantly lower than those of groups treated by Bio. In conclusion, PE debris had a greater negative effects on plant height, culm diameter, leaf area and root/shoot ratio while Bio debris mainly showed the adverse effects on germination viability and root biomass especially at the flowering stage. Therefore, further research is required to elaborate plastic particles' effects on different stages of crops and soil quality.

Empagliflozin and Liraglutide Differentially Modulate Cardiac Metabolism in Diabetic Cardiomyopathy in Rats.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are antihyperglycemic agents with cardioprotective properties against diabetic cardiomyopathy (DCM). However, the distinctive mechanisms underlying GLP-1RAs and SGLT2is in DCM are not fully elucidated. The purpose of this study was to investigate the impacts of GLP1RAs and/or SGLT2is on myocardial energy metabolism, cardiac function, and apoptosis signaling in DCM. Biochemistry and echocardiograms were studied before and after treatment with empagliflozin (10 mg/kg/day, oral gavage), and/or liraglutide (200 µg/kg every 12 h, subcutaneously) for 4 weeks in male Wistar rats with streptozotocin (65 mg/kg intraperitoneally)-induced diabetes. Cardiac fibrosis, apoptosis, and protein expression of metabolic and inflammatory signaling molecules were evaluated by histopathology and Western blotting in ventricular cardiomyocytes of different groups. Empagliflozin and liraglutide normalized myocardial dysfunction in diabetic rats. Upregulation of phosphorylated-acetyl coenzyme A carboxylase, carnitine palmitoyltransferase 1ß, cluster of differentiation 36, and peroxisome proliferator-activated receptor-gamma coactivator, and downregulation of glucose transporter 4, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α2 to adenosine monophosphate-activated protein kinase α2, and the ratio of phosphorylated protein kinase B to protein kinase B in diabetic cardiomyocytes were restored by treatment with empagliflozin or liraglutide. Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3, interleukin-1ß, tumor necrosis factor-α, and cleaved caspase-1 were significantly downregulated in empagliflozin-treated and liraglutide-treated diabetic rats. Both empagliflozin-treated and liraglutide-treated diabetic rats exhibited attenuated myocardial fibrosis and apoptosis. Empagliflozin modulated fatty acid and glucose metabolism, while liraglutide regulated inflammation and apoptosis in DCM. The better effects of combined treatment with GLP-1RAs and SGLT2is may lead to a potential strategy targeting DCM.