Preparation of ultra-light, highly compressible, and biodegradable chitosan porous materials for heavy metal adsorption, dye adsorption and oil-water separation.

Chitosan materials are much important in adsorption, separation and water treatment due to their hydrophilicity, biodegradability and easy functionalization. However, they were difficult to form structural materials, which limited its application in engineering. In this paper, a new type of chitosan porous materials was prepared with two-step strategy involving the freezing crosslinking of chitosan with glutaraldehyde to form cryogels, and their subsequent reduction with NaBH to transform CN bonds into CN bonds, resulting in remarkable improvement of mechanical property.

Podocyte-specific silencing of acid sphingomyelinase gene to abrogate hyperhomocysteinemia-induced NLRP3 inflammasome activation and glomerular inflammation.

Acid sphingomyelinase (ASM) has been reported to increase tissue ceramide and thereby mediate hyperhomocysteinemia (hHcy)-induced glomerular nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation, inflammation, and sclerosis. In the present study, we tested whether somatic podocyte-specific silencing of gene (mouse ASM gene code) attenuates hHcy-induced NLRP3 inflammasome activation and associated extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. In vivo, somatic podocyte-specific Smpd1 gene silencing almost blocked hHcy-induced glomerular NLRP3 inflammasome activation in Podo (podocyte-specific expression of cre recombinase) mice compared with control littermates.

Elucidating polyethylene microplastic degradation mechanisms and metabolic pathways via iron-enhanced microbiota dynamics in marine sediments.

The extensive use of plastics has given rise to microplastics, a novel environmental contaminant that has sparked considerable ecological and environmental concerns. Biodegradation offers a more environmentally friendly approach to eliminating microplastics, but their degradation by marine microbial communities has received little attention. In this study, we used iron-enhanced marine sediment to augment the natural bacterial community and facilitate the decomposition of polyethylene (PE) microplastics.

Regulation of NLRP3 Inflammasome Activation and Inflammatory Exosome Release in Podocytes by Acid Sphingomyelinase During Obesity.

The activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been reported to importantly contribute to glomerular inflammation and injury under different pathological conditions such as obesity. However, the mechanism mediating NLRP3 inflammasome activation in podocytes and subsequent glomerular injury remains poorly understood. Given that the ceramide signaling pathway has been reported to be implicated in obesity-related glomerulopathy (ORG), the present study was designed to test whether the ceramide-producing enzyme, acid sphingomyelinase (ASM), determines NLRP3 inflammasome activation and inflammatory exosome release in podocytes leading to glomerular inflammation and injury during ORG.

Regulation of exosome release by lysosomal acid ceramidase in coronary arterial endothelial cells: Role of TRPML1 channel.

Lysosomal acid ceramidase (AC) has been reported to determine multivesicular body (MVB) fate and exosome secretion in different mammalian cells including coronary arterial endothelial cells (CAECs). However, this AC-mediated regulation of exosome release from CAECs and associated underlying mechanism remain poorly understood. In the present study, we hypothesized that AC controls lysosomal Ca release through TRPML1 channel to regulate exosome release in murine CAECs.

Impaired autophagic flux and dedifferentiation in podocytes lacking Asah1 gene: Role of lysosomal TRPML1 channel.

Podocytopathy and associated nephrotic syndrome have been reported in a mouse strain (Asah1/Podo) with a podocyte-specific deletion of α subunit (the main catalytic subunit) of acid ceramidase (Ac). However, the pathogenesis of podocytopathy in these mice remains unclear. The present study tested whether Ac deficiency impairs autophagic flux in podocytes through blockade of transient receptor potential mucolipin 1 (TRPML1) channel as a potential pathogenic mechanism of podocytopathy in Asah1/Podo mice.

Renomedullary exosomes produce antihypertensive effects in reversible two-kidney one-clip renovascular hypertensive mice.

The rapid fall in blood pressure following unclipping of the stenotic renal artery in the Goldblatt two-kidney one-clip (2K1C) model of renovascular hypertension is proposed to be due to release of renomedullary vasodepressor lipids, but the mechanism has remained unclear. In this study, we hypothesized that the hypotensive response to unclipping is mediated by exosomes released from the renal medulla. In male C57BL6/J mice made hypertensive by the 2K1C surgery, unclipping of the renal artery after 10 days decreased mean arterial pressure (MAP) by 23 mmHg one hr after unclipping.

Impairment of Ceramide-Mediated Endothelial Instant Membrane Resealing During Diabetes Mellitus.

Recent studies have indicated that instant cell membrane resealing (ICMR) controls the activation of NOD-like receptor pyrin domain containing 3 (Nlrp3) inflammasomes in endothelial cells, thereby initiating and promoting vascular inflammation. It remains unknown whether this impaired ICMR occurs under diabetic condition or hyperglycemia contributing to endothelial dysfunction leading to vascular inflammation, a hallmark of diabetic vascular injury. The present study aims to examine whether ICMR occurs during in control and diabetic mice and to explore related molecular mechanisms associated with acid sphingomyelinase (ASM)-mediated ceramide production.

Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.

Lysosomal ion channels mediate ion flux from lysosomes and regulate membrane potential across the lysosomal membrane, which are essential for lysosome biogenesis, nutrient sensing, lysosome trafficking, lysosome enzyme activity, and cell membrane repair. As a cation channel, the transient receptor potential mucolipin 1 (TRPML1) channel is mainly expressed on lysosomes and late endosomes. Recently, the normal function of TRPML1 channels has been demonstrated to be important for the maintenance of cardiovascular and renal glomerular homeostasis and thereby involved in the pathogenesis of some cardiovascular and kidney diseases.

Exosome Biogenesis and Lysosome Function Determine Podocyte Exosome Release and Glomerular Inflammatory Response during Hyperhomocysteinemia.

Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation in podocytes is reportedly associated with enhanced release of exosomes containing NLRP3 inflammasome products from these cells during hyperhomocysteinemia (hHcy). This study examined the possible role of increased exosome secretion during podocyte NLRP3 inflammasome activation in the glomerular inflammatory response. Whether exosome biogenesis and lysosome function are involved in the regulation of exosome release from podocytes during hHcy in mice and upon stimulation of homocysteine (Hcy) in podocytes was tested.

Release and Actions of Inflammatory Exosomes in Pulmonary Emphysema: Potential Therapeutic Target of Acupuncture.

Background: Exosomes have been reported to mediate activation of the inflammatory response by secretion of inflammasome products such as IL-1β or IL-18 and that changes in exosomes production or secretion may be a therapeutic target for treatment of a variety of different chronic diseases. The present study tested the hypothesis that exosome-mediated release of NLRP3 inflammasome products instigates the inflammatory response in the lung during emphysema, a type of chronic obstructive pulmonary disease (COPD) and that electroacupuncture (EA) may attenuate emphysema by inhibition of NLRP3 inflammasome activation and consequent inflammation.

Methods: The COPD mice model was developed by injecting porcine pancreatic elastase (PPE) via puncture tracheotomy and instillation.

In situ growth zeolite imidazole framework materials on chitosan for greatly enhanced antibacterial effect.

Zeolite imidazole framework materials (ZIFs) are a new type of antibacterial material with high chemical and thermal stability, and good antibacterial effect. However, powder ZIFs materials have the disadvantages of difficult separation and easy aggregation, which limit their application. In this work, ZIFs and chitosan (CS) were compounded by in-situ growth method to prepare a new antibacterial agent.

Regulation of TRPML1 channel activity and inflammatory exosome release by endogenously produced reactive oxygen species in mouse podocytes.

The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in podocytes has been implicated in the initiation of glomerular inflammation during hyperhomocysteinemia (hHcy). However, the mechanism by which NLRP3 inflammasome products are released from podocytes remains unknown. The present study tested whether exosome secretion from podocytes is enhanced by NADPH oxidase-produced reactive oxygen species (ROS), which may serve as a pathogenic mechanism mediating the release of inflammatory cytokines produced by the NLRP3 inflammasome in podocytes after Hcy stimulation.

Contribution of podocyte inflammatory exosome release to glomerular inflammation and sclerosis during hyperhomocysteinemia.

The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and glomerular sclerosis in response to hyperhomocysteinemia (hHcy). However, it remains unknown how the products of NLRP3 inflammasome in cytoplasm are secreted out of podocytes. In the present study, we tested whether exosome release serves as a critical mechanism to mediate the action of NLRP3 inflammasome activation in hHcy-induced glomerular injury.

Podocyte Sphingolipid Signaling in Nephrotic Syndrome.

Podocytes play a vital role in the pathogenesis of nephrotic syndrome (NS), which is clinically characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and peripheral edema. The pathogenesis of NS has evolved through several hypotheses ranging from immune dysregulation theory and increased glomerular permeability theory to the current concept of podocytopathy. Podocytopathy is characterized by dysfunction or depletion of podocytes, which may be caused by unknown permeability factor, genetic disorders, drugs, infections, systemic disorders, and hyperfiltration.

Abnormal podocyte TRPML1 channel activity and exosome release in mice with podocyte-specific Asah1 gene deletion.

Podocytopathy and associated nephrotic syndrome (NS) have been reported in a knockout mouse strain (Asah1/Podo) with a podocyte-specific deletion of α subunit (the main catalytic subunit) of acid ceramidase (Ac). However, the pathogenesis of podocytopathy of these mice remains unknown. The present study tested whether exosome release from podocytes is enhanced due to Asah1 gene knockout, which may serve as a pathogenic mechanism switching on podocytopathy and associated NS in Asah1/Podo mice.

Podocytopathy and Nephrotic Syndrome in Mice with Podocyte-Specific Deletion of the Asah1 Gene: Role of Ceramide Accumulation in Glomeruli.

Lysosomal acid ceramidase (Ac) has been shown to be critical for ceramide hydrolysis and regulation of lysosome function and cellular homeostasis. In the present study, we generated a knockout mouse strain (Asah1/Podo) with a podocyte-specific deletion of the α subunit (main catalytic subunit) of Ac. Although no significant morphologic changes in glomeruli were observed in these mice under light microscope, severe proteinuria and albuminuria were found in these podocyte-specific knockout mice compared with control genotype littermates.

Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases.

Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney.

Arterial Medial Calcification through Enhanced small Extracellular Vesicle Release in Smooth Muscle-Specific Asah1 Gene Knockout Mice.

Arterial medial calcification (AMC) involves an increased small extracellular vesicle (sEV) secretion and apatite calcium precipitation in the arterial wall. The mechanisms mediating AMC remain poorly understood. In the present study, smooth muscle-specific acid ceramidase (Ac) gene knockout mice (Asah1/SM) were used to demonstrate the role of lysosomal ceramide signaling pathway in AMC.

D-Ribose Induces Podocyte NLRP3 Inflammasome Activation and Glomerular Injury via AGEs/RAGE Pathway.

D-ribose levels are demonstrated to be increased in type II diabetes mellitus and increased blood D-ribose is involved in the development of diabetic complications such as diabetic encephalopathy and nephropathy. However, the mechanism mediating the pathogenic role of D-ribose in nephropathy remains poorly understood. Given that D-ribose was reported to induce advanced glycation end products (AGEs) formation, the present study tested whether D-ribose induces NLRP3 activation and associated glomerular injury via AGEs/receptor of AGEs (RAGE) signaling pathway.

Preparation of thermally stable and surface-functionalized cellulose nanocrystals via mixed HSO/Oxalic acid hydrolysis.

A mild and efficient approach for the preparation of cellulose nanocrystals (CNCs) was developed by using mixed HSO/Oxalic acid hydrolysis. In this process, the mixed acid of sulfuric acid, oxalic acid and HO in an optimal mass ratio of 1:5:4 was used to produce CNCs from bleached eucalyptus kraft pulp (BEKP) at 80 °C for 2-5 h. The CNCs with a diameter range of 5-20 nm and a length range of 150-400 nm were obtained at a high yield (>70%) and showed excellent dispersion stability in water and good thermal stability.

Control of lysosomal TRPML1 channel activity and exosome release by acid ceramidase in mouse podocytes.

The transient receptor potential mucolipin 1 (TRPML1) channel has been reported to mediate lysosomal Ca release that is involved in Ca-dependent lysosome trafficking and autophagic flux. However, this regulatory mechanism of lysosomal TRPML1 channel activity in podocytes remains poorly understood. In the present study, we tested whether the TRPML1 channel in podocytes mediates lysosome trafficking, which is essential for multivesicular body (MVB) degradation by lysosomes.

Rac1 GTPase Inhibition Blocked Podocyte Injury and Glomerular Sclerosis during Hyperhomocysteinemia via Suppression of Nucleotide-Binding Oligomerization Domain-Like Receptor Containing Pyrin Domain 3 Inflammasome Activation.

Elevated homocysteine (Hcy) levels have been shown to activate nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome leading to podocyte dysfunction and glomerular injury. However, it remains unclear how this inflammasome activation in podocytes is a therapeutic target for reversal of glomerular injury and ultimate sclerosis. The present study tested whether inhibition of Rac1 GTPase activity suppresses NLRP3 inflammation activation and thereby blocks podocyte injury induced by elevated Hcy.

Lysosomal regulation of extracellular vesicle excretion during d-ribose-induced NLRP3 inflammasome activation in podocytes.

The NLRP3 inflammasome is activated in the cytoplasm of cells and its products such as IL-1β are exported through a non-classical ER-Golgi pathway. Several mechanistically distinct models including exocytosis of secretory lysosomes, microvesicles (MVs) and extracellular vehicles (EVs) have been proposed for their release. In this study, we hypothesized that the NLRP3 inflammasome product, IL-1β in response to exogenously administrated and endogenously produced d-ribose stimulation is released via extracellular vesicles including EVs via a sphingolipid-mediated molecular mechanisms controlling lysosome and multivesicular body (MVB) interaction.