RESUMO
The Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) ectoenzyme regulates vascular intimal proliferation and mineralization of bone and soft tissues. ENPP1 variants cause Generalized Arterial Calcification of Infancy (GACI), a rare genetic disorder characterized by ectopic calcification, intimal proliferation, and stenosis of large- and medium-sized arteries. ENPP1 hydrolyzes extracellular ATP to pyrophosphate (PPi) and AMP. AMP is the precursor of adenosine, which has been implicated in the control of neointimal formation. Herein, we demonstrate that an ENPP1-Fc recombinant therapeutic inhibits proliferation of vascular smooth muscle cells (VSMCs) in vitro and in vivo. Addition of ENPP1 and ATP to cultured VSMCs generated AMP, which was metabolized to adenosine. It also significantly decreased cell proliferation. AMP or adenosine alone inhibited VSMC growth. Inhibition of ecto-5'-nucleotidase CD73 decreased adenosine accumulation and suppressed the anti-proliferative effects of ENPP1/ATP. Addition of AMP increased cAMP synthesis and phosphorylation of VASP at Ser157. This AMP-mediated cAMP increase was abrogated by CD73 inhibitors or by A2aR and A2bR antagonists. Ligation of the carotid artery promoted neointimal hyperplasia in wild-type mice, which was exacerbated in ENPP1-deficient ttw/ttw mice. Prophylactic or therapeutic treatments with ENPP1 significantly reduced intimal hyperplasia not only in ttw/ttw but also in wild-type mice. These findings provide the first insight into the mechanism of the anti-proliferative effect of ENPP1 and broaden its potential therapeutic applications beyond enzyme replacement therapy.
Assuntos
5'-Nucleotidase , Adenosina , Proliferação de Células , Músculo Liso Vascular , Miócitos de Músculo Liso , Diester Fosfórico Hidrolases , Pirofosfatases , Transdução de Sinais , Diester Fosfórico Hidrolases/metabolismo , Diester Fosfórico Hidrolases/genética , Pirofosfatases/metabolismo , Pirofosfatases/genética , 5'-Nucleotidase/metabolismo , 5'-Nucleotidase/genética , Animais , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Adenosina/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Camundongos , Humanos , Monofosfato de Adenosina/metabolismo , Camundongos Endogâmicos C57BL , AMP Cíclico/metabolismo , Masculino , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , Calcificação Vascular/genéticaRESUMO
Currently, the surface structure modification of photocatalysts is one of the effective means of enhancing their photocatalytic efficiency. Therefore, it is critically important to gain a deeper understanding of how the surface of α-Fe2O3 photocatalysts influences catalytic activity at the nanoscale. In this work, α-Fe2O3 catalysts were prepared using the solvothermal method, and four distinct morphologies were investigated: hexagonal bipyramid (THB), cube (CB), hexagonal plate (HS), and spherical (RC). The results indicate that the hexagonal bipyramid (THB) exhibits the highest degradation activity towards tetracycline (TC), with a reaction rate constant of k = 0.0969 min-1. The apparent reaction rate constants for the cube (CB), hexagonal plate (HS), and spherical (RC) morphologies are 0.0824, 0.0726, and 0.0585 min-1, respectively. In addition, it has been observed that the enhancement of photocatalytic activity is closely related to the increase in surface area, which provides more opportunities for interactions between Fe2+ and holes. The quenching experiments and electron paramagnetic resonance (EPR) results indicate that the ËO2, ËOH and h+ contribute mainly to the degradation of TC in the system. This research contributes to a more comprehensive understanding of catalyst surface alterations and their impact on catalytic performance.
RESUMO
As one of the most common fluid patterns in the fluid flow process of chemical production, a vortex has been successfully demonstrated to be a structure that promotes interphase mixing and enhances heat and mass transfer. Therefore, it is essential to reveal the vortex evolution laws in order to realize more efficient and less energy-consuming chemical production. In this Mini-Review, the vortex identification criteria are introduced in detail and categorized according to their development history. The application of vortex identification technology and its application in the chemical industry are explored with a large number of examples. This review enhances our understanding of vortex structures and provides plenty of innovative ideas for the study of chemical industry production.
RESUMO
In this study, ozone catalysts (hydrogenation-modified red mud, HM-RM) successfully prepared by hydrogenation-modification of industrial hazardous solid waste red mud (RM) as a raw material in accordance with the viewpoint of treating waste with waste and using waste. Meanwhile, as for the common phenomenon of membrane fouling, uneven distribution of multiphase solid catalysts and ozone in liquids, the addition of ultrasound can not only disperse materials, but also play a role in online cleaning of ceramic membranes and catalysts. The optimum treatment conditions for Rhodamine B (RhB) solution with volume of 2 L and concentration of 40 mg/L were catalyst concentration of 0.4 mg/L, reaction temperature of 45 °C, ultrasonic time of 1 h, ultrasonic intensity of 600 W, removal rate of RhB was up to 90 %. In addition, the computational fluid dynamics (CFD) simulation method was used to investigate the fluid flow between the two gas-liquid phases and the effect of the negative pressure of the membrane pump on the fluid by the analysis of flow, pressure and ozone flux of the ceramic membrane(CM) reaction apparatus. The CFD simulation results showed that at the inlet gas-liquid flow rate of 3 m/s and the negative pressure of 20,000 Pa, the maximum flow rates of CM-1 were 3 m/s, 0.752 m/s for CM-2, and 0.228 m/s for CM-3, respectively. Vortices, which are beneficial to solid-liquid mixing and gas-liquid mass transfer, formed between the suction port CM-1 of CM-1 and the inlets of CM-2 and CM-3. This discovery is consistent with relevant experimental research results. Significantly higher concentrations of both â¢OH and dissolved ozone were observed in the US/HM-RM/O3 system compared to other systems, indicating the significant improvement in ozone utilization rate through the application of ultrasound. The superiority of the US/HM-RM/O3 device was demonstrated. The real dye effluent was tested under optimum operating conditions and the results showed that COD and TOC were reduced by 81.34 % and 60.23 % respectively after 180 min of treatment. The above research can provide technical support for the treatment of dye wastewater using Ultrasound-enhanced ozone oxidation ceramic membranes.
RESUMO
A low band gap and visible light-responsive heterogeneous Photo-Fenton catalyst of γ-Fe2O3/CQDs micron composite was prepared under the one-pot hydrothermal method. The Photo-Fenton degradation of γ-Fe2O3/CQDs towards dye solution of rhodamine B(RhB), methyl blue (MB), and methyl orange (MO) was studied comparatively with α-Fe2O3. The γ-Fe2O3/CQDs exhibited remarkable catalytic performance for various dyes and with a first-order rate (k) of 14 times higher than that of initial α-Fe2O3 with a low concentration of H2O2 of 0.049 mmol. L-1 and a wider pH range of 3.1-7.1. The microstructure of the compounds was observed by XRD, SEM, TEM, FT-IR, and XPS characterization results suggested that the γ-Fe2O3/CQDs nanocomposite was formed through the stable Fe-O-C bonds, thus, the band gap decreased, and it is more favorable for the distance of holes and electrons. The free radical trapping experiment and EPR analysis indicated that â¢OH and 1O2 were the major active species during the typical photo-Fenton reaction. What's more, the γ-Fe2O3/CQDs also exhibited good stability and magnetic properties. DFT conclusion shows that the mechanism of the potential determination step (PDS) on α-Fe2O3(220) is the cleavage of H2O2 with an energy barrier of only 0.08 eV, which is 0.54 eV lower than that of OH* on γ-Fe2O3(220). Thus it can be deemed that γ-Fe2O3/CQDs perform much higher catalytic activity for the dissociation of H2O2 than α-Fe2O3. This work gives a feasible and economical countermeasure of visible light Photo-Fenton dispose of dye wastewater with a recyclable magnetic γ-Fe2O3/CQDs micron catalyst.
Assuntos
Peróxido de Hidrogênio , Ferro , Ferro/química , Peróxido de Hidrogênio/química , Corantes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Luz , CatáliseRESUMO
A long-term use of chemical drugs cannot cure type II diabetes mellitus (T2DM) and their numerous toxic side effects can be harmful to human health. In recent years, probiotics have emerged as a natural resource to replace chemical drugs in alleviating many human ailments. Healthy children's intestines have a lot of colonized Lactobacilli and Bifidobacterium, and these beneficial bacteria can help promote overall health. The objective of this study was to isolate potential antidiabetic probiotic strains from healthy children and evaluate their application prospects. Firstly, Lactobacillus and Bifidobacterium strains were isolated from healthy children's feces and identified by the pheS or clpC genes with their respective 16S rRNA genes. Then, hydrophobicity, artificial gastrointestinal fluid tolerance, α-Glucosidase and Dipeptidyl peptidase IV (DPP-IV) inhibitory activities of isolated strains were determined, and antioxidant activities and promoting secretion of GLP-1 in STC-1 cells of candidate strains were tested. Results showed that 6 strains of Lactobacillus and Bifidobacterium were obtained from the feces of healthy children aged 3 years, respectively, including Lacticaseibacillus paracasei L-21 and L-25, Levilactobacillus brevis L-16, Lentilactobacillus buchneri L-9, Lactiplantibacillus plantarum L-8 and L-3, Bifidobacterium bifidum 11-1 and B-84, Bifidobacterium longum subsp. longum 6-1, 6-2, B42 and B53. The hydrophobicity and auto-aggregation levels of all these strains were higher than 30% and 50%, respectively, and the decrease in the number of colonies of all strains in the artificial gastrointestinal fluid was less than 2 log CFU/mL. Strains L-3, L-8, L-9, L-21, 6-1, 11-1, B53 and B84 were selected based on their high α-glucosidase inhibitory activity and DPP-IV inhibitory activity, and results of the antioxidant capacity assay showed that the remaining strains all had intense comprehensive antioxidant activity. Additionally, Lacticaseibacillus paracasei L-21 and Bifidobacterium longum subsp. longum B-53 had the most substantial prompting effect on GLP-1 secretion in the STC-1 cell line. These results indicated that Lacticaseibacillus paracasei L-21 and Bifidobacterium longum subsp. longum B-53 could be used as a potential antidiabetic strain; thus, its application as a food supplement and drug ingredient could be recommended after in vivo mitigation of type II diabetes test.
RESUMO
Direct air capture (DAC) can be used to decrease the CO2 concentration in the atmosphere, but this requires substantial energy consumption. If residual waste carbon (in the form of bicarbonate solution) from DAC can be directly reused, it might present a novel method for overcoming the aforementioned challenges. Electrochemical CN coupling methods for synthesizing urea have garnered considerable attention for waste carbon utilization, but the carbon source is high-purity CO2. No research has been conducted regarding the application of bicarbonate solution as the carbon source. This study proposes a proof-of-concept electrochemical CN coupling process for synthesizing urea using bicarbonate solution from DAC as the carbon source and nitrate from wastewater as the nitrogen source. These results confirmed the feasibility of synthesizing urea using a three-electrode system employing TF and CuInS2/TF as the working electrodes via potentiostatic electrolysis. Under the optimal conditions (initial pH 5.0 and applied potential of -1.3 V vs. Ag/AgCl), the urea yield after 2 h of electrolysis reached 3017.2 µg h-1 mgcat.-1 and an average Faradaic efficiency of 19.6 %. The in-situ attenuated total reflection surface-enhanced infrared absorption spectroscopy indicated a gradual increase in the intensity of the -CONH bond signal on the surface of the CuInS2/TF electrode as the reaction progressed. This implied that this bond may be a key chemical group in this process. The density functional theory calculations demonstrated that *CONH was a pivotal intermediate during CN coupling, and a two-step CN coupling reaction path was proposed. *NH + *CO primarily transformed into *CONH, followed by the conversion reaction of *CONH + *NO to *NOCONH2. This study offers a groundbreaking approach for waste carbon utilization from DAC and holds the potential to furnish technical underpinnings for advancing electrochemical CN coupling methods.
RESUMO
Background: Phthalocyanine (PC) and naphthalocyanine (NC) dyes have long garnered interest as theranostic agents for optical imaging and phototherapy due to their near-infrared absorbance, photostability, imaging contrast, and proven safety in clinical trials. Yet, only a small fraction of these dyes has been evaluated as photothermal therapy (PTT) agents for cancer treatment. Methods: Nearly 40 distinct NC and PC dyes were encapsulated within polymeric PEG-PCL micelles via oil-in-water emulsions. The optimal NC/PC-loaded micelle formulations for PTT and photoacoustic (PA) imaging were identified through in vivo and in vitro studies. Results: The most promising candidate, CuNC(Octa)-loaded micelles, demonstrated a strong PA signal with a peak absorbance at ~870 nm, high photothermal efficiency, and photostability. The CuNC(Octa)-loaded micelles exhibited heat generation as good or better than gold nanorods/nanoshells and >10-fold higher photoacoustic signals. Micelle preparation was reproducible/scalable, and the CuNC(Octa)-loaded micelles are highly stable under physiological conditions. The CuNC(Octa)-loaded micelles localize within tumors via enhanced permeability and retention and are readily detectable by PA imaging. In a syngeneic murine tumor model of triple-negative breast cancer, CuNC(Octa)-loaded micelles demonstrate efficient heat generation with PTT, leading to the complete eradication of tumors. Conclusions: CuNC(Octa)-loaded micelles represent a promising theranostic agent for PA imaging and PTT. The ability to utilize conventional ultrasound in combination with PA imaging enables the simultaneous acquisition of information about tumor morphology and micelle accumulation. PTT with CuNC(Octa)-loaded micelles can lead to the complete eradication of highly invasive tumors.
Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Animais , Camundongos , Micelas , Terapia Fototérmica , Medicina de Precisão , Técnicas Fotoacústicas/métodos , Nanopartículas/uso terapêutico , Indóis , Corantes/uso terapêutico , Neoplasias/terapia , Neoplasias/tratamento farmacológicoRESUMO
Iron-rich red mud (RM) is a potential catalyst. However, as industrial waste, is strongly alkaline, low effectiveness, and safety concerns are problems that cannot be ignored, it is urgent to mine out a reasonable disposal and utilization technology for the waste. In this study, an effective catalyst (H-RM) was obtained by facile hydrogenation heating modification of red mud. Then above-prepared H-RM was applied in the catalytic ozonation degradation of levofloxacin (LEV). The H-RM exhibited more remarkable catalytic activities than the RM in terms of LEV degradation, and the optimal efficiency can reach over 90% within 50 min. The mechanism experiment proved that the concentration of dissolved ozone and hydroxyl radical (â¢OH) significantly increased, which enhanced the oxidation effect. Hydroxyl radical played a dominant role in the degradation of LEV. In the safety test, it is concluded that the concentration of total hexavalent chromium (total Cr(â ¥)) in the H-RM catalyst decreases and the leaching concentration of water-soluble Cr(â ¥) in aqueous solution is low. The results indicated that the hydrogenation technique is an available Cr (â ¥) detoxification method for RM. Moreover, the H-RM has excellent catalytic stability, which is beneficial to recycling and maintains high activity. This research provides an effective means to fulfill the reuse of industrial waste as an alternative to standard raw materials, and comprehensive utilization of the waste to attain the purpose of treating pollution with wastes.
Assuntos
Ozônio , Poluentes Químicos da Água , Levofloxacino , Radical Hidroxila , Resíduos Industriais , Hidrogenação , CatáliseRESUMO
The current standard of care for colon cancer surveillance relies heavily on white light endoscopy (WLE). However, dysplastic lesions that are not visible to the naked eye are often missed when conventional WLE equipment is used. Although dye-based chromoendoscopy shows promise, current dyes cannot delineate tumor tissues from surrounding healthy tissues accurately. The goal of the present study was to screen various phthalocyanine (PC) dye-loaded micelles for their ability to improve the direct visualization of tumor tissues under white light following intravenous administration. Zinc PC (tetra-tert-butyl)-loaded micelles were identified as the optimal formulation. Their accumulation within syngeneic breast tumors led the tumors to turn dark blue in color, making them clearly visible to the naked eye. These micelles were similarly able to turn spontaneous colorectal adenomas in Apc+/Min mice a dark blue color for easy identification and could enable clinicians to more effectively detect and remove colonic polyps.
Assuntos
Neoplasias , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Luz , Corantes/química , Micelas , Masculino , Animais , Camundongos , Humanos , Camundongos Endogâmicos BALB C , Linhagem Celular TumoralRESUMO
Posttraumatic osteoarthritis (PTOA) results in joint pain, loss of joint function, and impaired quality of daily life in patients with limited treatment options. We previously demonstrated that epidermal growth factor receptor (EGFR) signaling is essential for maintaining chondroprogenitors during articular cartilage development and homeostasis. Here, we used a nonsurgical, loading-induced PTOA mouse model to investigate the protective action of EGFR signaling. A single bout of cyclic tibial loading at a peak force of 6 N injured cartilage at the posterior aspect of lateral femoral condyle. Similar loading at a peak force of 9 N ruptured the anterior cruciate ligament, causing additional cartilage damage at the medial compartment and ectopic cartilage formation in meniscus and synovium. Constitutively overexpression of an EGFR ligand, heparin binding EGF-like growth factor (HBEGF), in chondrocytes significantly reduced cartilage injury length, synovitis, and pain after 6 N loading and mitigated medial side cartilage damage and ectopic cartilage formation after 9 N loading. Mechanistically, overactivation of EGFR signaling protected chondrocytes from loading-induced apoptosis and loss of proliferative ability and lubricant synthesis. Overexpressing HBEGF in adult cartilage starting right before 6 N loading had similar beneficial effects. In contrast, inactivating EGFR in adult cartilage led to accelerated PTOA progression with elevated cartilage Mankin score and synovitis score and increased ectopic cartilage formation. As a therapeutic approach, we constructed a nanoparticle conjugated with the EGFR ligand TGFα. Intra-articular injections of this nanoconstruct once every 3 weeks for 12 weeks partially mitigated PTOA symptoms in cartilage and synovium after 6 N loading. Our findings demonstrate the anabolic actions of EGFR signaling in maintaining articular cartilage during PTOA development and shed light on developing a novel nanomedicine for PTOA. © 2022 American Society for Bone and Mineral Research (ASBMR).
Assuntos
Receptores ErbB , Osteoartrite , Animais , Camundongos , Cartilagem Articular/metabolismo , Receptores ErbB/metabolismo , Ligantes , Osteoartrite/metabolismo , Sinovite/metabolismoRESUMO
The realization of high-efficient digestion in a microfluidic reactor is considered to be advantageous for pretreatment toward online pollutant detection. However, it is difficult to achieve satisfactory device performance due to the gap between the low digestion reaction efficiency and the demand for rapid pretreatment for online detection. Herein, we design and manufacture an optofluidic microreactor combined with a MnO2 nanofilm localizing the heat inside the reaction chamber under solar irradiation, which contributes a lot to the on-chip nutrient digestion efficiency enhancement. The overall temperature of the water sample in the reactor chamber can be dramatically increased in a fleeting time of less than 1 s and maintained at 78 °C. The digestion rate constant of the microreactor is improved by about 100 times compared with that obtained by the traditional method in the national standard, which is attributed to temperature enhancement and various oxidation reactions in the heated reaction chamber. Notably, when pretreating the actual total phosphorus water samples, the digestion efficiency is demonstrated to be higher than 95% within 12 s under solar light irradiation. The optofluidic platform brings many benefits to accelerate the various photochemically enhanced reactions using solar light and is extremely adapted for rapid pretreatment of biochemical samples to further develop their online analysis.
Assuntos
Poluentes Ambientais , Compostos de Manganês , Microfluídica , Óxidos , ÁguaRESUMO
Pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic calcification disorder, is predominantly caused by inactivating mutations in ABCC6. The encoded protein, ABCC6, is a hepatic efflux transporter and a key regulator of extracellular inorganic pyrophosphate (PPi). Recent studies demonstrated that deficiency of plasma PPi, a potent endogenous calcification inhibitor, is the underlying cause of PXE. This study examined whether restoring plasma PPi levels by INZ-701, a recombinant human ENPP1 protein, the principal PPi-generating enzyme, prevents ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 6 weeks of age, the time of earliest stages of ectopic calcification, were injected subcutaneously with INZ-701 at 2 or 10 mg/kg for 2 or 8 weeks. INZ-701 at both doses increased steady-state plasma ENPP1 activity and PPi levels. In the 8-week treatment study, histopathologic examination and quantification of the calcium content in INZ-701-treated Abcc6-/- mice revealed significantly reduced calcification in the muzzle skin containing vibrissae, a biomarker of the calcification process in these mice. The extent of calcification corresponds to the local expression of two calcification inhibitors, osteopontin and fetuin-A. These results suggest that INZ-701 might provide a therapeutic approach for PXE, a disease with high unmet needs and no approved treatment.
Assuntos
Calcinose , Diester Fosfórico Hidrolases , Pseudoxantoma Elástico , Pirofosfatases , Animais , Calcinose/tratamento farmacológico , Calcinose/prevenção & controle , Modelos Animais de Doenças , Humanos , Fígado , Camundongos , Camundongos Knockout , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Diester Fosfórico Hidrolases/uso terapêutico , Pseudoxantoma Elástico/genética , Pseudoxantoma Elástico/terapia , Pirofosfatases/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Pele/metabolismoRESUMO
Oxidative stress and the reactive oxygen species (ROS) have important roles in osteoarthritis (OA) development and progression. Scavenging ROS by exogenous antioxidant enzymes could be a promising approach for OA treatment. However, the direct use of antioxidant enzymes, such as superoxide dismutase (SOD), is challenging due to a lack of effective drug delivery system to knee joints. This study utilized a highly efficient antioxidative nanoparticle based on SOD-loaded porous polymersome nanoparticles (SOD-NPs) for delivery of SOD to mouse knee joints. The resultant SOD-NPs had prolonged mouse joint retention time with predominant accumulation in synovium but not in articular cartilage. Examining human synovial explants revealed that SOD-NPs minimize oxidative damages induced by OA-like insults. Intra-articular injections of SOD-NPs in mice receiving OA surgery were effective in attenuating OA initiation and preventing its further progression. Mechanistically, SOD-NPs reduced ROS production and the synthesis of catabolic proteases in both articular cartilage and synovium. Hence, our work demonstrates the therapeutic potential of SOD-NPs and indicate that targeting synovium holds a great promise for OA therapy.
Assuntos
Cartilagem Articular , Nanopartículas , Osteoartrite , Animais , Antioxidantes/metabolismo , Cartilagem Articular/metabolismo , Camundongos , Nanopartículas/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Porosidade , Superóxido Dismutase/metabolismo , Membrana Sinovial/metabolismoRESUMO
Optofluidic devices are of high interest for online monitoring and analyzing biochemical targets in water by integrating the complex on-chip pretreatment of target analytes and spectral analysis. Compared with the traditional bulk equipment, versatile optical detection and biochemical analysis are more easily integrated on an optofluidic chip, which promotes the development of on-chip real-time rapid detection and monitoring. Here, we report an optofluidic platform for online monitoring total phosphorous in water by absorption spectrometry, which naturally combines the merits of both the photo-Fenton effect and microfluidics to realize the rapid on-chip digestion of phosphate at room temperature and normal pressure. The functional cells for chromogenic reaction and optical absorption detection are, respectively, fabricated on the platform to analyze the content of total phosphorus in surface water. In the experiment, the on-chip digestion time of phosphate is dramatically declined to 8.6 sec, and thus, the detection time is greatly shortened to a few minutes. The detection range of total phosphorus is demonstrated as 0.005-1.00 mg L-1, which satisfies the detection requirements of most environmental water samples. Its availability for measuring the total phosphorous in real water samples is also verified. Predictably, this platform is adapted to on-chip analysis of many other biochemical targets in water.
Assuntos
Fósforo , Água , Microfluídica , Fosfatos , Análise EspectralRESUMO
Electrochemical oxidation (EO) is often used in the advanced treatment of refractory wastewater. However, in a conventional EO process of direct-current (DC) power supply, oxide layers often form on the anodes, which not only hinder the oxidation reaction on them but also cause higher energy consumption. In this paper, a biologically treated leachate (BTL) of municipal solid waste (MSW) was comparably treated by EO with DC (DC-EO), monopulse (MP-EO), and double pulse (DP-EO) power source models in a home-made multi-channel flow reactor. The effects of process parameters of current density (I A), superficial liquid velocity (U L), pulse frequency (f P), duty ratio (R D), and so forth on the removal efficiency of chemical oxygen demand (COD) (RECOD), total organic carbon (TOC) (RETOC), and total nitrogen (TN) (RETN) were investigated simultaneously. Average energy consumption () and organic composition of the treated effluent of DC-EO and MP-EO were also compared comprehensively, and a new mechanism of MP-EO has been proposed accordingly. Under optimal conditions, 2 L of BTL was treated by MP-EO for 180 min, and the RECOD, RETOC, and RETN could reach as high as 80, 30, and 80%, respectively. Compared with DC-EO, the of MP-EO is reduced by 69.27%. Besides, the kinds of organic matter in the treated effluent of MP-EO are reduced from 53 in the BTL to 11, which is much less than in the DC-EO process of 29 kinds. Therefore, the MP-EO process exhibits excellent removal performance of organics and TN and economic prospects in the treatment of refractory organic wastewater.
RESUMO
Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia-reperfusion (I/R) injury. Here, nanoparticle-encapsulated SOD (NP-SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome-c assay. In an in vitro I/R model, free and NP-SOD reduce active ROS, preserve mitochondrial integrity and improve cell viability compared to controls. In a rat in vivo I/R injury model, NP-encapsulation of fluorescent-tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP-SOD administration in vivo improves left ventricular contractility at 3-hours post-reperfusion by echocardiography and 4-weeks by echocardiography and invasive pressure-volume catheter analysis. These findings suggest that NP-SOD mitigates ROS damage in cardiac I/R injury in vitro and maximizes retention in vivo. NP-SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP-SOD as a therapy to mitigate myocardial I/R injury.
RESUMO
Reverse osmosis (RO) concentrate produced in the municipal solid waste (MSW) leachate treatment process is extremely hard to be treated because of its high color, high salt content, and high concentration of recalcitrant organic compounds. A new multichannel flow reactor with electrode gaps of 5 mm was designed to desalinate and remove organics simultaneously from the RO leachate concentrate (ROLC) by electrochemical oxidation process using the RuO2/IrO2-coated titanium plate (RuO2/IrO2-Ti) as the anodes. The effects of the process parameters of current density (I A), superficial circulating velocity (U L), etc. on the removal efficiency (RE) of the chemical oxygen demand (COD) and average energy consumption () were investigated. The results illustrated that after 3 h of treatment, the RE of COD, Cl-, and color could reach as high as 96.5, 96.7, and 99.6%, respectively. Besides, the of the electrochemical oxidation treatment process is as low as 40.98 kWh/(kg COD), and a new mechanism of the simultaneous removal of COD and desalination has been proposed. This work provides an alternative technology for the treatment of MSW leachate RO concentrate.
RESUMO
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the major enzyme that cleaves extracellular adenosine triphosphate (ATP) to generate pyrophosphate (PPi), an inorganic metabolite with potent anticalcification activity. Loss-of-function mutations cause hypopyrophosphatemia and lead to a state of ENPP1 deficiency, which has an acute infantile phase known as generalized arterial calcification of infancy (GACI) and a pediatric to adult phase known as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). ENPP1 deficiency manifests as ectopic calcification of multiple tissues, neointimal proliferation, premature mortality, impaired growth, and bone deformities. INZ-701, a human ENPP1-Fc protein, is in clinical development as an enzyme replacement therapy for the treatment of ENPP1 deficiency. The pharmacokinetic and pharmacodynamic profile and therapeutic effect of INZ-701 were investigated in Enpp1asj/asj mice, a murine model of ENPP1 deficiency. Enpp1asj/asj mice have undetectable plasma PPi, lower plasma phosphate, and higher FGF23 levels compared with wild-type (WT) mice. Enpp1asj/asj mice on the acceleration diet, containing high phosphate and low magnesium, quickly develop clinical signs, including dehydration, rough hair coat, pinned ears, stiffed legs, and hunched back. Enpp1asj/asj mice treated with vehicle had aforementioned clinical signs plus severe ectopic calcification in multiple tissues and bone defects, characteristics of the clinical phenotype observed in GACI and ARHR2 patients. Our results showed a durable PPi response for more than 3 days after a single dose of INZ-701. Treatment of ENPP1-deficient mice every other day with INZ-701 for 8 weeks restored circulating levels of PPi, prevented pathological calcification in all the tested organs, restored growth parameters, corrected bone defects, improved clinical signs, and decreased mortality in Enpp1asj/asj mice, demonstrating the potential of INZ-701 to treat ENPP1 deficiency. © 2021 American Society for Bone and Mineral Research (ASBMR).
Assuntos
Coristoma , Raquitismo Hipofosfatêmico Familiar , Calcificação Vascular , Adulto , Animais , Criança , Fator de Crescimento de Fibroblastos 23 , Humanos , Camundongos , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/genéticaRESUMO
Treating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any notable clinical success, in part, due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in the articular cartilage in human and mouse OA cartilage tissues. We hypothesize that the inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop an sPLA2-responsive and nanoparticle (NP)-based interventional platform for OA management, we incorporated an sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar NPs (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.