Search

Bioretentions can remarkably improve the rainwater quality. Though iron and aluminum as fillers in bioretentions can remove nitrate nitrogen, its adsorption mechanism is not clear yet and was rarely studied. This paper takes sand, iron powder, and aluminum powder as the research objects to study the adsorption characteristics of nitrate nitrogen in the bioretention with different pH values and different ionic strength. The results show that aluminum powder has the highest the adsorption capacity. Langmuir adsorption isotherm equation and the quasi-secondary kinetic model are adopted to analyze the experimental data.

Ammonia nitrogen is one of the important pollutants in urban rainfall. Though iron ions and aluminum ions as a filler for plant retention system have a good effect on the removal of ammonia nitrogen, their adsorption characteristics was rarely studied. This paper uses different media (sand, iron powder, aluminum powder) with different pH values and ionic strengths in the bioretention system to study the adsorption mechanism of ammonia nitrogen in an artificial rainwater. The result shows that Langmuir isothermal adsorption model is more in line with the ammonia nitrogen adsorption process, and the sand has the best adsorption capacity among three samples. Effect of pH values on adsorption kinetics is also studied.

Vascularizing printed tissues is a critical challenge in bioprinting. While protein-based hydrogel bioinks have been successfully used to bioprint microvasculature, their compositions are ill-defined and subject to batch variation. Few studies have focused on engineering proangiogenic bioinks with defined properties to direct endogenous microvascular network formation after printing. Here, a peptide-functionalized alginate hydrogel bioink with defined mechanical, rheological, and biochemical properties is developed for direct bioprinting of microvascularized tissues. An integrin-binding peptide (RGD) and a vascular endothelial growth factor (VEGF)-mimetic peptide with a protease-sensitive linker (MMPQK) are conjugated onto biodegradable alginate to synergistically promote vascular morphogenesis and capillary-scale endothelial tube formation. Partial ionic crosslinking before printing converts the otherwise unprintable hydrogel into a viscoelastic bioink with excellent printability and cytocompatibility. We use the bioink to fabricate a compartmentalized vascularized tissue construct, wherein we observe pericyte-endothelial cell colocalization and angiogenic sprouting across a tissue interface, accompanied by deposition of fibronectin and collagen in vascular and tissue components, respectively. This study provides a tunable and translational “off-the-shelf” hydrogel bioink with defined composition for vascularized bioprinting.

Microvasculature functions at the tissue and cell level, regulating local mass exchange of oxygen and nutrient-rich blood. While there has been considerable success in the biofabrication of large- and small-vessel replacements, functional microvasculature has been particularly challenging to engineer due to its size and complexity. Recently, three-dimensional bioprinting has expanded the possibilities of fabricating sophisticated microvascular systems by enabling precise spatiotemporal placement of cells and biomaterials based on computer-aided design. However, there are still significant challenges facing the development of printable biomaterials that promote robust formation and controlled 3D organization of microvascular networks. This review provides a thorough examination and critical evaluation of contemporary biomaterials and their specific roles in bioprinting microvasculature. We first provide an overview of bioprinting methods and techniques that enable the fabrication of microvessels. We then offer an in-depth critical analysis on the use of hydrogel bioinks for printing microvascularized constructs within the framework of current bioprinting modalities. We end with a review of recent applications of bioprinted microvasculature for disease modeling, drug testing, and tissue engineering, and conclude with an outlook on the challenges facing the evolution of biomaterials design for bioprinting microvasculature with physiological complexity.

Cardiomyocyte dysfunction is attributed to excess oxidative damage, but the molecular pathways involved in this process have not been completely elucidated. Evidence indicates that isosteviol sodium (STVNa) has cardioprotective effects. We therefore aimed to identify the effect of STVNa on cardiomyocytes, as well as the potential mechanisms involved in this process. We established two myocardial hypertrophy models by treating H9c2 cells with high glucose (HG) and isoprenaline (ISO). Our results showed that STVNa reduced H9c2 mitochondrial damage by attenuating oxidative damage and altering the morphology of mitochondria. The results also indicated that STVNa had a positive effect on HG‐ and ISO‐induced damages via mitochondrial biogenesis. The protective effects of STVNa on cardiomyocytes were associated with the regulation of the SIRT1/PGC‐1α signalling pathway. Importantly, the effects of STVNa involved different methods of regulation in the two models, which was confirmed by experiments using an inhibitor and activator of SIRT1. Together, the results provide the basis for using STVNa as a therapy for the prevention of cardiomyocyte dysfunctions.

The sodium salt of isosteviol (STVNa) is a beyerane diterpene synthesized through acid hydrolysis of stevioside. STVNa improves multiple types of tissue injuries. However, it is not known how isosteviol sodium affects high-fat and high cholesterol diet (HFD)-induced kidney. Therefore, in this study we examined the potential molecular mechanism underlying STVNa mediated protective effect against high fat/high cholesterol-induced kidney dysfunction in HFD-induced kidney injury. Sprague-Dawley (SD) rats were allocated into six groups: the normal group, HFD group and HFD treated with three doses of STVNa, fenofibrate treatment group. The results indicated that HFD induced kidney injury evident by a 60% increase in serum creatinine (CRE) leves. In addition, there was a significant accumulation of triglycerides (approx. 60%), fatty acids (approx. 50%) and total cholesterol (approx. 2.5 fold) in the kidneys. STVNa inhibited HFD-induced kidney injury evident by reducing the increased levels of serum CRE. Specifically, STVNa attenuated HFD-induced kidney injury by inhibiting inflammation, oxidative stress, and apoptosis. These findings indicate that STVNa has a therapeutic potential for HFD-induced kidney dysfunction. The mechanisms of this pharmacological effect are through the inhibition of inflammation, oxidative stress and apoptosis.

CRISPR/Cas-based mRNA imaging has been developed to labeling of high-abundance mRNAs. A lack of non-genetically encoded mRNA-tagged imaging tools has limited our ability to explore the functional distributions of endogenous low-abundance mRNAs in cells. Here, we developed a CRISPR-Sunspot method based on the SunTag signal amplification system that allows efficient imaging of low-abundance mRNAs with CRISPR/Cas9. Methods: We created a stable TRE3G-dCas9-EGFP cell line and generated an Inducible dCas9-EGFP imaging system for assessment of two factors, sgRNA and dCas9, which influence imaging quality. Based on SunTag system, we established a CRISPR-Sunspot imaging system for amplifying signals from single-molecule mRNA in live cells. CRISPR-Sunspot was used to track co-localization of Camk2a mRNA with regulatory protein Xlr3b in neurons. CRISPR-Sunspot combined with CRISPRa was used to determine elevated mRNA molecules. Results: Our results showed that manipulating the expression of fluorescent proteins and sgRNA increased the efficiency of RNA imaging in cells. CRISPR-Sunspot could target endogenous mRNAs in the cytoplasm and amplified signals from single-molecule mRNA. Furthermore, CRISPR-Sunspot was also applied to visualize mRNA distributions with its regulating proteins in neurons. CRISPR-Sunspot detected the co-localization of Camk2a mRNA with overexpressed Xlr3b proteins in the neuronal dendrites. Moreover, we also manipulated CRISPR-Sunspot to detect transcriptional activation of target gene such as HBG1 in live cells. Conclusion: Our findings suggest that CRISPR-Sunspot is a novel applicable imaging tool for visualizing the distributions of low-abundance mRNAs in cells. This study provides a novel strategy to unravel the molecular mechanisms of diseases caused by aberrant mRNA molecules.

Rainfall runoff contains a huge number of pathogenic bacteria that seriously deteriorate water quality. Bioretention is an effective approach to removal of pathogenic bacteria from rainwater. This study uses sandy soil, fly ash, slag, sandy soil+5% fly ash, and sandy soil+5% slag as media to evaluate the adsorption of fecal Escherichia coli. The mechanisms of the five media conform to the Langmuir?s isotherm adsorption equation, and a pseudo-first-order kinetic model is adopted to reveal the absorption kinetics.

A bioretention medium has considerable influence on the removal of pollutants, especially phosphorus pollutants. In this paper, the phosphorus adsorption properties of three bioretention media (sand, iron powder, and aluminum powder) are studied, and the effects of pH and ionic strength on the phosphorus adsorption are analyzed. Results show that the phosphorus adsorption isotherm can be well modeled by the Langmuir equation. The experimental results show the monolayer adsorption capacity of sand is the highest, while the iron powder the lowest. The pH of the solution has a considerable influence on the phosphorus adsorption of sand and iron powder, but has a minimal effect on aluminum powder.

Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has become an attractive therapeutic strategy for lowering low-density lipoprotein cholesterol (LDL-C). In this study, a novel high affinity humanized IgG1 mAb (named h5E12-L230G) targeting the catalytic domain of human PCSK9 (hPCSK9) was generated by using CDR-grafting, alanine-scanning mutagenesis, and saturated site-directed mutagenesis. The heavy-chain constant region of h5E12-L230G was modified to eliminate the cytotoxic effector functions and mitigate the heterogeneity. The biolayer interferometry (BLI) binding assay and molecular docking study revealed that h5E12-L230G binds to the catalytic domain of hPCSK9 with nanomolar affinity (KD = 1.72 nM) and an extremely slow dissociation rate (koff, 4.84 × 10−5 s−1), which interprets its quite low binding energy (−54.97 kcal/mol) with hPCSK9. Additionally, h5E12-L230G elevated the levels of LDLR and enhanced the LDL-C uptake in HepG2 cells, as well as reducing the serum LDL-C and total cholesterol (TC) levels in hyperlipidemic mouse model with high potency comparable to the positive control alirocumab. Our data indicate that h5E12-L230G is a high-affinity anti-PCSK9 antibody candidate with an extremely slow dissociation rate for favorably treating hypercholesterolemia and relevant cardiovascular diseases.

Severe anorexia limits the clinical application of cisplatin, and even leads to the discontinuation of treatment. However, the mechanisms underlying cisplatin-induced anorexia are unknown. Herein, we demonstrated that cisplatin could affect neuronal gamma oscillations and induce abnormal neuronal theta-gamma phase-amplitude coupling in the arcuate nucleus (Arc) of the hypothalamus, and these findings were associated with significantly decreased food intake and weight loss in mice. Chemogenetic activation of AgRP neurons in the Arc reversed the cisplatin-induced food intake reduction in mice. We further demonstrated that endothelial peroxynitrite (ONOO−) formation in the Arc induced nitrosative stress following cisplatin treatment via a previously uncharacterized pathway involving neuronal caspase-1 activation. Strikingly, treatment with the ONOO− scavenger uric acid (UA) reversed the reduced action potential (AP) frequency of AgRP neurons and increased the AP frequency of POMC neurons induced by SIN1, a donor of ONOO−, in the Arc, as determined by whole-cell patch-clamp electrophysiological recording. Consistent with these findings, UA treatment effectively alleviated cisplatin-induced dysfunction of neuronal oscillations and neuronal theta-gamma phase-amplitude coupling in the Arc of mice. Taken together, these results suggest, for the first time, that targeting the overproduction of endothelial ONOO− can regulate cisplatin-induced neurotoxicity through neuronal caspase-1, and thereby serve as a potential therapeutic approach to alleviate chemotherapy-induced anorexia and weight loss., Highlights • Endothelial ONOO– induced the abnormal neuronal oscillations following cisplatin treatment through caspase-1 in the Arc. • ONOO– scavenger UA could attenuate cisplatin-induced neurotoxicity and caspase-1 activation in the Arc. • Targeting endothelial ONOO– provided a promising approach to alleviate chemotherapy-induced anorexia and weight loss.

Inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9) has become an attractive therapeutic strategy for lowering low-density lipoprotein cholesterol (LDL-C). In this study, a novel high affinity humanized IgG1 mAb (named h5E12-L230G) targeting the catalytic domain of human PCSK9 (hPCSK9) was generated by using CDR-grafting, alanine-scanning mutagenesis, and saturated site-directed mutagenesis. To eliminate the cytotoxic effector functions and mitigate the heterogeneity, the heavy-chain constant region of h5E12-L230G was modified with L234A/L235A/N297G mutations and C-terminal lysine deletion. The biolayer interferometry (BLI) binding assay and molecular docking study revealed that h5E12-L230G binds to the catalytic domain of hPCSK9 with nanomolar affinity (KD =1.72 nM) and an extremely slow dissociation rate (koff, 4.84 × 10−5 s−1), which interprets its quite low binding energy (-54.97 kcal/mol) with hPCSK9. Additionally, h5E12-L230G elevated the levels of LDLR and enhanced the LDL-C uptake in HepG2 cells, as well as reduced the serum LDL-C and total cholesterol (TC) levels in hyperlipidemic mouse model with high potency comparable to Alirocumab. Our data suggest that h5E12-L230G is a highly potent antibody binding to PCSK9 catalytic domain with slow dissociation rate which may be utilized as a therapeutic candidate for treating hypercholesterolemia and relevant cardiovascular diseases.

Background Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). Methods CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. Results CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.

Eriocitrin is a flavanone glycoside which exists in lemon or lime citrus fruits. It exhibits antioxidant, anti-cancer and anti-allergy activities. β-casein is important protein in bovine milk, under appropriate conditions, it can form stable micelle like structures in aqueous solution, which is beneficial to the nutritional ingredient transportation in body. In this work, the interaction mechanisms of eriocitrin with β-casein under physiological conditions (pH = 7.4) were investigated by utilizing multi-spectroscopic techniques and molecular docking methods. The endogenous fluorescence of β-casein was quenched by the interaction with eriocitrin and the quenching mode was static quenching. The interaction of eriocitrin with β-casein was a spontaneous reaction principally driven by hydrophobic interaction. At 310 K, the binding constant was equal to 6.68 × 105 L mol−1 and the number of binding sites was approximately equal to 1. The changes of β-casein conformation were confirmed by FTIR, circular dichroism spectroscopy and synchronous fluorescence spectroscopy. Moreover, molecular docking studies illustrated the most possible binding position of eriocitrin on β-casein.

A porphyrin dimer (BPD) was introduced for selective detection of aluminum ions (Al3+) in a fully aqueous system. BPD produces a ratiometric emission profile in the near-infrared (NIR) region upon Al3+ complexation. The sensing mechanism involves photoinduced electron transfer (PET) and intramolecular charge transfer (ICT). The binding mode of BPD/Al3+ was fully examined based on spectroscopic titration, time-resolved fluorescence decay, NMR spectroscopy, mass spectrometry, and IR analyses. In aqueous media, the strong interaction between Lewis acid Al3+ and nitrogen atoms allows BPD to conquer the high energy barriers of the solvent for only Al3+, resulting in the high selectivity and low detection limit (2.65 × 10–8 M) of the probe. Practical applications of BPD for Al3+ monitoring in real samples and fluorescent prints were further investigated with satisfactory results. With its organic solvent-free sensing medium, good biocompatibility, and NIR ratiometric emission properties, the designed BPD probe is appropriate for ratiometric visualization of Al3+ in living cells.

Nitrogen-doped carbon materials (NCMs) were prepared via hydrothermal treatment together with pyrolysis under nitrogen atmosphere by using melamine as nitrogen source and sucrose as carbon source. The NCMs were characterized by X-ray diffraction (XRD), laser Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). The results showed that nitrogen species were successfully doped into NCMs in the formation of pyridinic N, pyrrolic N, graphitic N, and oxidized N. With the temperature of pyrolysis increasing, the total amount of nitrogen species decreased, while the proportion of graphitic N increased. The catalytic performance was investigated by the reduction of p-nitrophenol with excessive KBH4 at 30 ℃. The reaction rate constant can reach 1.06 min-1 for NCM-800. The NCM-800 has good stability, which can be used for 8 cycles without obvious deactivation. Copyright © 2018 BCREC Group. All rights reservedReceived: 1st May 2018; Revised: 30th September 2018; Accepted: 2nd Oktober 2018; Available online: 25th January 2019; Published regularly: April 2019How to Cite: Wang, X., Yang, L., Cai, K.Y., Zhou, Y.M., Wang, P., Song, M. (2019). Preparation of Metal-Free Nitrogen-Doped Carbon Material and Its Catalytic Performance. Bulletin of Chemical Reaction Engineering & Catalysis, 14 (1): 105-111 (doi:10.9767/bcrec.14.1.2593.105-111)Permalink/DOI: https://doi.org/10.9767/bcrec.14.1.2593.105-111

N-doped carbon materials (NCMs) are generally used as electrode materials, and seldom used as catalysts in chemical reaction. In this work, NCMs were prepared by high-temperature pyrolysis using monosodium glutamate as sources of both carbon and nitrogen, magnesium acetate as a porogen, and nickel hydroxide as a graphitization catalyst. The catalytic performance of NCMs was investigated in the reduction of 4-nitrophenol (4-NP) with potassium borohydride at 30 ºC. As metal-free catalysts, all of the NCMs can catalyze the reaction. The graphitization degree and N-doped amount of NCM have a great influence on the catalytic activity. The NCM annealed at 800 ºC has higher activity and stability. The reaction rate constant can reach 0.57 min-1, and the activation energy was about 36.4 kJ/mol. Copyright © 2019 BCREC Group. All rights reservedReceived: 19th March 2018; Revised: 16th August 2018; Accepted: 20th August 2018; Available online: 25th January 2019; Published regularly: April 2019How to Cite: Zhou, Y.M., Wang, X.H., Cai, K.Y., Wu, J.M., Wang, P., Song, M. (2019). Preparation of Nitrogen-Doped Graphene from Monosodium Glutamate and Its Catalytic Performance. Bulletin of Chemical Reaction Engineering & Catalysis, 14 (1): 28-34 (doi:10.9767/bcrec.14.1.2237.28-34)Permalink/DOI: https://doi.org/10.9767/bcrec.14.1.2237.28-34

Anxiety disorders are the most prevalent psychiatric disorders, but their pathogenic mechanism remains poorly understood. Here, we report that transmembrane protein 74 (TMEM74), which contains two putative transmembrane domains and exhibits high levels of mRNA in the brain, is closely associated with the pathogenesis of anxiety disorders. TMEM74 was decreased in the serum of patients with anxiety and the basolateral amygdaloid nucleus (BLA) in chronic stress mice. Furthermore, genetic deletion of Tmem74 or selective knockdown of Tmem74 in BLA pyramidal neurons resulted in anxiety-like behaviors in mice. Whole-cell recordings in BLA pyramidal neurons revealed lower hyperpolarization-activated cation current (Ih) and greater input resistance and excitability in Tmem74-/- neurons than in wild-type neurons. Accordingly, surface expression of hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels was also lower in the BLA of Tmem74-/- mice. The Ih current blocker ZD7288 mimicked these effects in BLA pyramidal neurons in wild-type mice but not in Tmem74-/- mice. Consistent with the improvement in anxiety-like behaviors, Tmem74 overexpression restored HCN1 channel trafficking and pyramidal neuron excitability in the BLA of Tmem74-/- and chronic stress mice. Mechanistically, we demonstrate that interactions between Tmem74 and HCN1 are physiologically relevant and that transmembrane domain 1 (TM1) is essential for the cellular membrane localization of Tmem74 to enhance Ih. Together, our findings suggest that Tmem74 coupling with HCN1 acts as a critical component in the pathophysiology of anxiety and is a potential target for new treatments of anxiety disorders.

Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by α-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in Fxr-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR.

Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. Methods: A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. Results: GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. Conclusion: Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.

Background Stevioside, isolated from the herb Stevia rebaudiana, has been widely used as a food sweetener all over the world. Isosteviol Sodium (STV-Na), an injectable formulation of isosteviol sodium salt, has been proved to possess much greater solubility and bioavailability and exhibit protective effects against cerebral ischemia injury in vivo by inhibiting neuron apoptosis. However, the underlying mechanisms of the neuroprotective effects STV-Na are still not completely known. In the present study, we investigated the effects of STV-Na on neuronal cell death caused by hypoxia in vitro and its underlying mechanisms. Methods We used cobalt chloride (CoCl2) to expose mouse neuroblastoma N2a cells to hypoxic conditions in vitro. Results Our results showed that pretreatment with STV-Na (20 μM) significantly attenuated the decrease of cell viability, lactate dehydrogenase release and cell apoptosis under conditions of CoCl2-induced hypoxia. Meanwhile, STV-Na pretreatment significantly attenuated the upregulation of intracellular Ca2+ concentration and reactive oxygen species production, and inhibited mitochondrial depolarization in N2a cells under conditions of CoCl2-induced hypoxia. Furthermore, STV-Na pretreatment significantly downregulated expressions of nitric oxide synthase, interleukin-1β, tumor necrosis factor-α, interleukin-6, nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signalings in N2a cells under conditions of CoCl2-induced hypoxia. Conclusions Taken together, STV-Na protects neural cells against hypoxia-induced apoptosis through inhibiting MAPK and NF-κB pathways.

A di-orthometallated triphenyl phosphite iridium complex Ir(dttpit)(phen)Cl (dttpitH2 = tris (2, 4-di-tert-butylphenyl) phosphite, phen = phenanthroline), has been synthesied and characterized. The crystal structure was determined by X-ray crystallography. The photoluminescence spectrum of Ir(dttpit)(phen)Cl in CH3CN shows emission maximum at 528 nm. In 0.01 wt% PMMA films, its quantum yields and lifetime are 0.16 and 1.78 μs, respectively. The emission of Ir(dttpit)(phen)Cl at 528 exhibits 1393% enhance upon addition of Ag+ in CH3CN/H20. The ratio of Ir(dttpit)(phen)Cl responding to Ag+ is 1:1, and the limit of detection is 0.13 μM. Ir(dttpit)(phen)Cl is a highly selective chemosensor for Ag+ over other metal ions. The interaction between the chlorine atom and Ag+ is responsible for the highly selective and sensitive phosphorescent senor for Ag+.

One-step introduction of metallic Bi, non-metallic C into Bi2WO6 was successfully prepared via a facile hydrothermal synthetic route. The obtained materials were characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope, X-ray photoelectron spectroscopy (XPS), nitrogen absorption–desorption isotherms, photoluminescence spectroscopy, photocurrent responses, electrochemical impedance spectroscopy (EIS), electron paramagnetic resonance (EPR), UV–vis diffuse reflectance spectra (DRS). As a result, C/Bi codecorated Bi2WO6 shows profoundly photocatalytic activity in comparison with undoped Bi2WO6 for decomposition of various industrial pollutants, including phenol, ciprofloxacin, bisphenol A, rhodamine B, and methyl orange under visible light (λ ≥ 420 nm). The enhanced photocatalytic properties may be ascribed to the fact that the synergistic effects of the SPR effect of Bi metal and the hybrid orbital constructed by C doping not only enhance the absorption of visible light but also accelerate the separation and migration of photo-generated carriers. Moreover, on the basis of the radical species trapping experiments, EPR analyses, DRS technique and Mott–Schottky plots, we proposed a simple photocatalytic mechanism.

Aims Autism spectrum disorder (ASD) is a wide range of neurodevelopmental disorders involving deficits in social interaction and communication. Unfortunately, autism remains a scientific and clinical challenge owing to the lack of understanding the cellular and molecular mechanisms underlying it. This study aimed to investigate the pathophysiological mechanism underlying leukocyte-endothelial adhesion in autism-related neurovascular inflammation. Methods Male BTBR T+tf/J mice were used as an autism model. The dynamic pattern of leukocyte-endothelial adhesion in mouse cerebral vessels was detected by two-photon laser scanning microscopy (TPLSM). Using FACS, RT-PCR, and Western blotting, we explored the expression of cell adhesion molecules, the mRNA expression of endothelial chemokine, the protein levels of cathepsin B, and inflammatory mediators. Results We found a significant increase in leukocyte-endothelial adhesion in BTBR mice, accompanied by elevated expression of the adhesion molecule neutrophils CD11b and endothelial ICAM-1. Our data further indicate that elevated neutrophil cathepsin B levels contribute to elevated endothelial chemokine CXCL7 levels in BTBR mice. The pharmacological inhibition of cathepsin B reverses the enhanced leukocyte-endothelial adhesion in the cerebral vessels of autistic mice. Conclusion Our results revealed the prominent role of cathepsin B in modulating leukocyte-endothelial adhesion during autism-related neurovascular inflammation and identified a promising novel approach for autism treatment.

From 1990 until 2017, global air-pollution related mortality increased by 40%. Few studies addressed the renal responses to ultrafine particulate [3.5/>2.5 mg per mmol creatinine in women/men) were correlated in individual participants via their residential address with PM2.5 [median 13.1 (range 0.3-2.9) mu g/m(3)] and BC [1.1 (0.3-18) mu g/m(3)], using mixed models accounting for address clusters. Cross-sectional and longitudinally, no renal outcome was associated with PM2.5 or BC in models adjusted for sex and baseline or time varying covariables, including age, blood pressure, heart rate, body mass index, plasma glucose, the total-to-HDL serum cholesterol ratio, alcohol intake, smoking, physical activity, socioeconomic class, and antihypertensive treatment. The subject-level geocorrelations of eGFR change with to BC and PM2.5 were 0.13 and 0.02, respectively (P >= 0.68). In conclusion, in a population with moderate exposure, renal function was unrelated to ultrafine particulate. FLEMENGHO was supported by the European Union (Grants IC15-CT98-0329-EPOGH, LSHM CT 037093-InGenious HyperCare, HEALTH-201550-HyperGenes, HEALTH-278249-EU-MASCARA, HEALTH-305507 HOMAGE), the European Research Council (Advanced Researcher Grant-2011–294713-EPLORE and Proof-of-Concept Grant-713601 uPROPHET), the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT), and the Research Foundation Flanders, Ministry of the Flemish Community, Brussels, Belgium. APPREMED (URL: http://www.appremed.org) received a non-binding grant from OMRON Healthcare Co., Ltd., Kyoto, Japan. Te National Science Fund in China (Grant Numbers: 81470566 and 81670765) supported collaboration between Youan Hospital, Beijing, China and the Research Unit Hypertension and Cardiovascular Epidemiology, Leuven, Belgium. Bram Janssen is a postdoctoral fellow supported by the Research Foundation Flanders (Grant Number: 12W3218). Te authors gratefully acknowledge the expert clerical assistance of Vera De Leebeeck and Renilde Wolfs, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.

Breast cancer is one of the most common cancer with high morbidity and mortality in women. This study aimed to explore the potential mechanism of costunolide inducing MCF-7 cells apoptosis by multi-spectroscopy, molecular docking, and cell experiments. The results manifested that costunolide interacted with calf thymus DNA (ct-DNA) in a spontaneous manner, and the minor groove as the preferential binding mode. Furthermore, costunolide inhibited cell proliferation and colony formation. Hoechst 33258 staining showed that cell apoptosis induced by costunolide might be related to DNA damage. The apoptosis mechanism relied on regulating the protein expression of Bax, Bcl-2, p53, Caspase-3 and the activation of p38MAPK and nuclear factor κB (NF-κB) pathways. This study will provide some experimental basis and potential therapeutic strategy for breast cancer treatment.

Tim-3, which is expressed on a variety of innate immune cells including NK cells, plays a key role in many autoimmune diseases. However, the immunomodulatory actions of Tim-3 on NK cells in primary biliary cholangitis (PBC) remain uncertain. Using a murine model of PBC we evaluated the expression of Tim-3 and its ligand Gal-9 in peripheral blood, liver, and spleen. Additionally, we studied Tim-3 regulation of chemokine receptors (CXCR1 and CXCR3) in vitro. Flow cytometric analysis indicated large numbers of infiltrating NK cells in the liver which exhibited high expression of Tim-3 and CXCR3. Moreover, we found overexpression of CXCR1 in liver tissue and liver-derived NK cells in PBC mice. We also observed lower levels of soluble Tim-3 in the serum of PBC mice. In vitro experiments with liver-derived NK cells from PBC mice indicated that CXCR3 was up-regulated by treatment with recombinant mouse TIM-3 Fc (rmTim-3 Fc) to activate the Tim-3 pathway. Furthermore, stimulating normal mouse spleen NK cells with poly I:C resulted in elevated expression of CXCR1 and interferon-γ release. Nonetheless, adding rmTim-3 Fc or rmGal-9 significantly down-regulated CXCR1 expression and IFN-γ release in NK cells activated by poly I:C, proposing a means to exploit the Tim-3 pathway to reverse responses in NK cells. In conclusion, our data demonstrate that dysregulation of Tim-3/Gal-9 is involved in modulating the local immune microenvironment in PBC mice. Our findings highlight the potential of Tim-3 pathway to modulate chemokine responses in NK cells during autoimmunity.

Background: Hyaluronan (HA) metabolism by chondrocytes is essential for cartilage development and homeostasis. However, the function of circular RNAs (circRNAs)in HA metabolism is limited. In this study, we profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis.Methods: The function of circHYBID in HA metabolism in chondrocytes was investigated using gain-of-function experiments. The mechanism of HA-binding protein involved in hyaluronan depolymerization (HYBID) was confirmed through bioinformatics analysis and luciferase assays. The expression correlation of the circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by qRT-PCR and western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using immunohistochemistry. ELISA assay was used to assess HA accumulation in chondrocyte supernatant.Results: CircHYBID expression was significantly downregulated in damaged cartilage samples comparing with that in the corresponding intact cartilage samples. CircHYBID expression was inversely correlated with the Mankin score and positively correlated with HA expression. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis illustrated that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions: Our results describe a novel HA-related circRNA that could promote the synthesis and accumulation of HA. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and Osteoarthritis (OA) progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.

Spreading depolarization (SD) represents a neurological process characterized by a massive, self-sustaining wave of brain cell depolarization. Understanding its mechanism is important for treating ischemic or hemorrhagic stroke and migraine with aura. Many believed that ion fluxes through NMDA receptors (NMDARs) are responsible for neuronal transmembrane currents of SD. However, the explicit role of NMDARs remains ambiguous. This is in part due to the limitation of traditional pharmacological approaches in resolving the contribution of NMDARs in different intercellular and intracellular processes of SD. Here, we applied single-cell blockade and genetic deletion methods to remove functional NMDARs from individual hippocampal CA1 neurons in order to examine the role of NMDARs in the depolarization mechanism without affecting the propagation of SD. We analyzed neuronal membrane potential changes to demonstrate that NMDARs are not required for initiating the depolarization. Consistently, neuronal input resistance (RN) revealed a sharp decline at the start of SD, which was unaffected by blocking NMDARs. Instead, the recovery of both membrane potential and RN during the late phase of SD was facilitated by inhibition of NMDARs, indicating that NMDARs are responsible for sustaining the depolarization. Our results strongly indicate that NMDAR activation is not a determinant of the initiation of depolarization but is important for sustaining transmembrane ion fluxes during SD.

Motif analysis on evolutionarily conserved regions in laminin enabled the discovery of novel ligands for hydrogel development., Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix–protein–derived ligands for translational applications. Through motif analysis of evolutionarily conserved RGD-containing regions in laminin (LM) and peptide-functionalized hydrogel microarray screening, we identified a peptide (a1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of a1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in a1-functionalized hydrogels showed ~60% similarities with Matrigel in “vasculature development” gene ontology terms. Vasculogenesis assays revealed the capacity of a1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with a1 and MMPQK (a vascular endothelial growth factor–mimetic peptide with a matrix metalloproteinase–degradable linker) increased blood perfusion and functional recovery over decellularized extracellular matrix and (RGDS + MMPQK)–functionalized hydrogels in an ischemic hindlimb model, illustrating the power of this approach.

To identify potential application of GLP1-RAs (glucagon-like peptide-1 receptor agonists) and SGLT2-Is (sodium-dependent glucose cotrasnsporter-2 inhibitors) in cardiovascular medicine, we performed PubMed search until March 31, 2020 and selected placebo-controlled randomized trials (RCTs) in patients with type 2 diabetes mellitus. Twenty-four hour ambulatory and office blood pressure (BP), major adverse cardiovascular events (MACE), progression of chronic kidney disease (CKD), and changes in glycated hemoglobin and body weight were aggregated across RCTs using random-effect models. In 2238 patients (7 RCTs), SGLT2-Is lowered 24-hour systolic/diastolic BP by 4.4/1.9 mm Hg (95% CI, 3.4–5.5/1.2–2.6 mm Hg), whereas 2 GLP1-RAs RCTs produced contradictory BP results. Over 1.3 to 5.4 years of follow-up of 56 004 patients (7 RCTs), aggregate hazard ratios associated with GLP1-RA treatment were 0.88 (0.84–0.93) for MACE, 0.84 (0.74–0.89) for CKD, and ranged from 0.84 to 0.90 for individual MACE end points ( P ≤0.01). Across 5 SGLT2-Is RCTs, including 43 467 patients with 1.5 to 4.2 years follow-up, hazard ratios were 0.87 (0.82–0.93) for MACE, 0.68 (0.62–0.75) for HF, 0.82 (0.72–0.93) for cardiovascular death, 0.87 (0.79–0.96) for myocardial infarction, and 0.61 (0.56–0.67) for worsening CKD. The risk of HF and CKD, but not MACE, decreased with more BP lowering. Stricter glycemic control was associated with higher HF risk, but unrelated to MACE or CKD. The aggregate effect sizes on systolic BP, body weight, and glycated hemoglobin were −1.61 mm Hg, −2.40 kg, and −0.69% for GLP1-RAs, and −2.53 mm Hg, −1.15 kg and −0.24%, for SGLT2-Is ( P

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

Objective In recent decades, the role of microRNAs (miRNAs) in human diseases has been widely studied. This research is designed to explore the effect of miR-218-5p on knee osteoarthritis (KOA) progression in a rat model with the involvement of sclerostin (SOST). Methods The KOA rat models were constructed by Hulth method, and then were classified into the KOA, miR-218-5p inhibitor, inhibitor negative control (NC), overexpressed (OE)-SOST, OE-NC, miR-218-5p inhibitor + si-SOST, or miR-218-5p inhibitor + si-NC group. The pathological changes of rats' synovial tissues were observed; the apoptosis in rat synovial tissues was assessed; levels of IL-1β, TNF-α, PGE2 and COX-2 in serum and synovial tissues, along with SOD and MDA contents in synovial tissues were determined. The morphological changes in cartilage tissues were observed. MMP-13 and Col II expression in cartilage tissues was assessed; expression of β-catenin and Col2A1 in cartilage tissues was assessed. miR-218-5p and SOST expression in rat knee joint tissues was assessed. Results KOA rats had increased miR-218-5p expression and decreased SOST expression. MiR-218-5p targeted SOST. Rats injected with miR-218-5p inhibitor and OE-SOST had alleviated pathological changes, reduced TUNEL positive cell rate, decreased serum contents of IL-1β, TNF-α, PGE2, COX-2 and MDA, and increased SOD activity in synovial tissues, alleviated pathological changes, enhanced Col II positive rate and reduced MMP-13 positive rate, decreased β-catenin expression and increased Col2A1 expression in cartilage tissues. Conclusion The miR-218-5p inhibition could attenuate synovial inflammation and cartilage injury in KOA rats by promoting SOST, which may be helpful for KOA treatment.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) levels by facilitating the degradation of the LDL receptor (LDLR) and is an attractive therapeutic target for hypercholesterolemia intervention. Herein, we generated a novel fully human antibody with favorable druggability by utilizing phage display-based strategy. Methods: A potent single-chain variable fragment (scFv) named AP2M21 was obtained by screening a fully human phage display library with hPCSK9, and performing twoin vitro affinity maturation processes including CDR-targeted tailored mutagenesis and cross-cloning. Thereafter, it was transformed to a full-length Fc-silenced anti-PCSK9 antibody FAP2M21 by fusing to a modified human IgG1 Fc fragment with L234A/L235A/N297G mutations and C-terminal lysine deletion, thus eliminating its immune effector functions and mitigating mAb heterogeneity. Findings: Our data showed that the generated full-length anti-PCSK9 antibody FAP2M21 binds to hPCSK9 with a KD as low as 1.42 nM, and a dramatically slow dissociation rate (koff, 4.68 × 10−6s-1), which could be attributed to its lower binding energy (-47.51 kcal/mol) than its parent counterpart FAP2 (-30.39 kcal/mol). We verified that FAP2M21 potently inhibited PCSK9-induced reduction of LDL-C uptake in HepG2 cells, with an EC50 of 43.56 nM. Further, in hPCSK9 overexpressed C57BL/6 mice, a single tail i.v. injection of FAP2M21 at 1, 3 and 10 mg/kg, dose-dependently up-regulated hepatic LDLR levels, and concomitantly reduced serum LDL-C by 3.3% (P=0.658), 30.2% (P=0.002) and 37.2% (P=0.002), respectively. Interpretation: FAP2M21 with potent inhibitory effect on PCSK9 may serve as a promising therapeutic agent for treating hypercholesterolemia and associated cardiovascular diseases. Funding Statement: This work was funded by National Fund for Major Projects of China (2009ZX09103-653; 2013ZX09301303-006; 2018ZX09301035), The Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), National Fund for Fostering Talents of Basic Science (NFFTBS, 3050040016), China Pharmaceutical University “Double First-Class” project (CPU2018GY15). Declaration of Interests: The authors declare no conflict of interest concerning this article. Ethics Approval Statement: The experimental procedures for the in vivo studies were approved by the Animal Ethics Committees of China Pharmaceutical University (No. 201601179, 19 October 2016) and conformed to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.

Recent data show that cardiac hypertrophy contributes substantially to the overall heart failure burden. Mitochondrial dysfunction is a common feature of cardiac hypertrophy. Recent studies have reported that isosteviol inhibits myocardial ischemia-reperfusion injury in guinea pigs and H9c2 cells. This work investigated the protective mechanisms of isosteviol sodium (STVNa) against isoproterenol (Iso)-induced cardiac hypertrophy. We found that STVNa significantly inhibited H9c2 cell and rat primary cardiomyocyte cell surface, restored mitochondrial membrane potential (MMP) and morphological integrity, and decreased the expression of mitochondrial function-related proteins Fis1 and Drp1. Furthermore, STVNa decreased reactive oxygen species (ROS) levels and upregulated the expression of antioxidant factors, Thioredoxin 1 (Trx1) and Peroxiredoxin 2 (Prdx2). Moreover, STVNa restored the activity of histone deacetylase 4 (HDAC4) in the nucleus. Together, our data show that STVNa confers protection against Iso-induced myocardial hypertrophy primarily through the Prdx2/ROS/Trx1 signaling pathway. Thus, STVNA is a potentially effective treatment for cardiac hypertrophy in humans.

Background/Aims: Peptidyl-prolyl cis-trans isomerase FKBP25 is a member of the FK506-binding proteins family which has peptidyl-prolyl cis/trans isomerase domain. The biological function and pathophysiologic role of FKBP25 remain elusive. Methods: The spatio-temporal changes in expression of endothelial FKBP25 upon oxygen-glucose deprivation (OGD) treatment were examined by Western blot and immunofluorescence. The immunoprecipitation and fluorescence resonance energy transfer (FRET) were used to address the interacting proteins with FKBP25. Results: In the present study, nuclear translocation of FKBP25 was observed following OGD in cultured endothelial cells. Intriguingly, FKBP25 nuclear translocation was further validated in peroxynitrite (ONOO-)-treated endothelial cells. Coimmunoprecipitation and FRET data indicated that FKBP25 translocated into the nucleus, in which it interacted with 60S ribosomal protein L7a, while overexpression FKBP25 protect endothelial cells against OGD injury. Conclusion: Our findings reveal that the nuclear import of FKBP25 and binding with 60S ribosomal protein L7a are protective stress responses to ischemia/nitrosaive stress injury.

Cortical spreading depolarization (CSD) reflects neuronal depolarization slowly propagating in the cortex and is accompanied with vascular response. Dynamic ultrafast Doppler has potential to access the hemodynamic response to CSD, specifically to the penetrating vessels in the cortex. In this study, the CSD was experimentally triggered by topical application of potassium chloride (KCl) on the surface of the brain. The vascular response caused by KCl induced CSD was successfully detected during the dynamic ultrafast Doppler. The propagation of vascular responses from the center of right cortex (stimulated side) to the medial and lateral side was observed. The perfusion change (ΔCBV) decreased over 30 % from the baseline at the beginning, and the CBV response subsequently elevated dramatically to over 30% very likely due to vasodilation. At the end of episode, CBV decreased slowly along the time. In this study, we firstly detect the vascular responses caused by KCl induced CSD with the dynamic ultrafast Doppler.

NF-κB signaling pathway plays a critical role in cerebral ischemic stroke. MicroRNA-181b (miR-181b) induces the expression of NF-κB signaling pathways indirectly, and isosteviol sodium (STVNa) protects against ischemic injury via the inhibition of NF-κB–mediated inflammatory and apoptotic responses. However, the function of miR-181b and the actual relationship between STVNa and miR-181b in the ischemia-induced activation of NF-κB signaling pathways remains unclear. In this study, we found that miR-181b expression was significantly decreased in N2A neuroblastoma cells after CoCl2-induced hypoxic injury in vitro. We further found, via western blot analysis and quantitative polymerase chain reaction assay, that altering miR-181b expression could induce changes in one of its target proteins, cylindromatosis (CYLD). Specifically, upregulation and downregulation of miR-181b (through transfection of either pre- or small interfering miR-181b, respectively) could negatively regulate CYLD protein levels as well as N2A cell survival rate and apoptosis following CoCl2-induced injury. Furthermore, STVNa treatment following ischemic injury significantly downregulated the expression of miR-181b to alter apoptotic proteins downstream of the NF-κB signaling pathway through increasing CYLD protein levels in vivo and in vitro. STVNa also had a protective effect on CoCl2-injured N2A cells, increasing cell survival rate, inhibiting apoptosis, reducing the damage of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Together, these results suggest that STVNa may downregulate miRNA-181b to protect mouse brain with ischemia stroke and against hypoxic injury in N2A cells by repressing NF-κB signaling pathways through the activation of CYLD, providing a novel therapy for ischemic stroke.

Smad4, a common-mediator of Smads, plays a central role in forming complexes with receptor-phosphorylated Smads, and then transduces transforming growth factor (TGF)-β signals into the nuclei. Although many cellular factors are involved in TGF-β induced epithelial-to-mesenchymal transition (EMT) and cell migration, very little is known with the mechanism of Smad4 regulation on pro-oncogenes response by TGF-β. Herein, we demonstrate the interaction of Sentrin-specific protease 2 (SENP2) with Smad4 through SENP2 residue 363~400. The same segment is also important for desumoylation of Smad4, and able to relieve sumoylation-mediated TGF-β repression. The SENP2363~400 segment is critical for TGF-β-induced cell migration, which is correlated with SENP2363~400 deletion mutant failed to increase matrix metalloproteinase (MMP)-9 and EMT marker gene expression. Moreover, our results suggest that the interaction and desumoylation between SENP2 and Smad4 promote cell migration in triple-negative breast cancer cells. Altogether, our data show how SENP2 regulates its substrate for desumoylation, and also the role of SENP2 in TGF-β induced cancer cell migration.

The structures, semiconductor and photocurrent response properties of three 1,4-diazabicyclo[2.2.2]octane derivative-templated iodobismuthates, (Et2DABCO)3(BiI6)2 (1), (i-Pr2DABCO)2(Bi2I10) (2), [(Me2DABCO)2(Bi2I10)2] n (3) (Et2DABCO2+ = N,N′-diethyl-1,4-diazabicyclo[2.2.2] octane, i-Pr2DABCO2+ = N,N′-diisoproyl-1,4-diazabicyclo[2.2.2] octane, Me2DABCO2+ = N,N′-dimethyl-1,4-diazabicyclo[2.2.2] octane), are reported. Based on the templates with different substitutents on 1,4-diazabicyclo[2.2.2]octane, mono-nuclear ((BiI6) 3 − for 1), dimer ((Bi2I10) 4 − for 2) and 1-D chain ((BiI5) 2n− for 3) can be obtained. C-H···I hydrogen bonds contribute to the structural extension to 2-D layer (for 2) and 3-D network (for 3). Their absorption spectra were investigated, and energy band gaps of 2.24/1.73/1.44 eV indicate their narrow-gap semiconductor natures. Their photocurrent response properties were also discussed. Finally, theoretical calculation was executed to give structure-properties correlation.

A simple and effective fluorescence “turn on” chemosensor (ZPA) has been synthesized for rapid, sensitive and selective detection of copper ions (Cu 2+ ) in fully aqueous buffer. The binding interaction between ZPA and Cu 2+ was investigated through UV–vis absorption, fluorescence measurement, mass spectroscopy, and IR spectrum analysis. Cu 2+ could specifically bind with the hydroxyl-O and imine-N atom in ZPA with high affinity ( K a = 6.08 × 10 7 M −1 ). Coordination of Cu 2+ to ZPA restricting the photoinduced electron transfer (PET) process in free ZPA and generating a more rigid ZPA/Cu 2+ complex with an extended π-electron conjugation system, sequentially leading to the fluorescence enhancement of ZPA. The detection limit (calculated to be 1.49 × 10 −8 M) was far below the limit in the World Health Organization (WHO) guidelines for drinking water (30 μM) and the sensing process was fully reversible. Practical applications of ZPA for Cu 2+ detection in real water samples were investigated with satisfactory results. Endowed with attributes like high binding affinity, specificity, relatively long excitation/emission properties and excellent bio-compatibility, ZPA demonstrated outstanding fluorescent imaging of intracellular Cu 2+ in living cells.

We performed chlorination experiments to understand the impact of hypochlorite exposure on both cation exchange membranes (CEMs) and anion exchange membranes (AEMs) regarding their properties and performance in a reverse electrodialysis (RED) stack. Changes in membrane morphology, surface elemental composition and chemical bounding suggested the chlorine incorporation in the form of C-Cl bonds and side-chain cleavage of –SO3- or –NR3+ containing molecular fractions. These observations were further supported by observed increases in hydrophobicity and decreases in fixed charged groups of the membranes, respectively. Compared to CEMs, AEMs were less chlorine resistant such that the development of more extensive cracks in the membrane structure further increased water content and dramatically decreased membrane conductivity. The performance of both chlorinated CEMs and AEMs were tested in an RED stack and the results showed the reduced RED power density was largely attributed to the deteriorated electrical properties of AEMs.

The aim of this study is to assess the physical damage of cavitation effects induced by low frequency ultrasound and microbubbles (MBs) to an in vitro vessel. A rabbit carotid artery filled with SonoVue MBs and methylene blue was irradiated with 20-kHz ultrasound, and the results were recorded by high-speed photography at 3000 frames per second. The carotid artery filled with MBs experienced a slight tremor during ultrasonication. Six intermittent blue flow events occurred in two places on the artery wall during the 5-s process. The duration of each leakage event was 90–360 ms with an average of 200 ms. Hematoxylin-eosin (H-E) staining demonstrated the separation of the carotid artery elastic membrane, local blood vessel wall defects and hole formation, and the surface of the ruptured area was rough and irregular. Another carotid artery was filled with a 0.9% NaCl solution and methylene blue as a control and irradiated with 20-kHz ultrasound. No blue liquid flow was seen, and no holes in the vessel were observed. H-E staining revealed intact vascular endothelial cells and smooth muscles with no vascular wall defects. Low-frequency ultrasound combined with MBs can cause a vessel to rupture and holes to form in a short time. High-speed photography is useful for observing transient changes caused by the effects of ultrasound cavitation on an in vitro vessel.

In this paper, we investigated the synergistic effects of co-locating reverse electrodialysis (RED) with other water and power infrastructures. The potential benefit of greater salinity (e.g., using brine from seawater desalination plants) and higher feed water temperature (e.g., through the co-location with power plants) were studied. Maximum RED power was obtained when the low salinity stream (LS) had moderate salinity (0.01–0.02 M NaCl), which can be explained by the competing effects of reduced internal resistance and decreased electrochemical potential upon increasing the LS concentration. At the same time, greater salinity of the high salinity stream (HS) and higher feed water temperature both significantly improved the power performance. Compared to the HS temperature, the LS temperature played a more important role due to the dominance of electrical resistance of the LS compartment. When RED was applied as a pre- or post-treatment to RO, it can efficiently remove salt from the HS stream (e.g., nearly 50% reduction in the HS concentration demonstrated in our bench scale evaluation). We further show that, during the RED salt removal process, the ionic efficiency (~ 76% in the current study) was closely related to the permselectivity of the ion exchange membranes.