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1.
Water Res ; 256: 121646, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38657309

ABSTRACT

Sewage treatment processes are a critical anthropogenic source of bioaerosols and may present significant health risks to plant workers. Compared with the specialization and scale of urban sewage treatment, many decentralized treatment models are flexible and extensive. These treatment facilities are usually close to residential areas owing to the pipe network layout and other restrictions. Bioaerosols generated by these facilities may present a serious and widespread occupational and non-occupational exposure risk to nearby residents, particularly the elderly and children. An understanding of the characteristics and exposure risks of bioaerosols produced during decentralized sewage treatment is lacking. We compared bioaerosol emission characteristics and potential exposure risks under four decentralized sewage discharge methods and treatment models: small container collection (SCC), open-channel discharge (OCD), single household/combined treatment (SHCT), and centralized treatment (CT) in northwest China. The OCD mode had the highest bioaerosol production, whereas the CT mode had the lowest. The OCD model contained the most pathogenic bacterial species, up to 43 species, including Sphingomonas, Pseudomonas, Cladosporium, and Alternaria. Risk assessments indicated bioaerosol exposure was lower in the models with sewage treatment (SHCT and CT) than in those without (SCC and OCD). Different populations exhibited large variations in potential risks owing to differences in time spent indoors and outdoors. The highest risk was observed in males exposed to the SCC model. This study provides a theoretical basis and theories for the future joint prevention and control of the bioaerosol exposure risk from decentralized sewage treatment.


Subject(s)
Aerosols , Air Microbiology , Sewage , Sewage/microbiology , Waste Disposal, Fluid , China , Humans , Risk Assessment , Bacteria
2.
Proc Natl Acad Sci U S A ; 121(13): e2315407121, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38502699

ABSTRACT

Organic electrodes mainly consisting of C, O, H, and N are promising candidates for advanced batteries. However, the sluggish ionic and electronic conductivity limit the full play of their high theoretical capacities. Here, we integrate the idea of metal-support interaction in single-atom catalysts with π-d hybridization into the design of organic electrode materials for the applications of lithium (LIBs) and potassium-ion batteries (PIBs). Several types of transition metal single atoms (e.g., Co, Ni, Fe) with π-d hybridization are incorporated into the semiconducting covalent organic framework (COF) composite. Single atoms favorably modify the energy band structure and improve the electronic conductivity of COF. More importantly, the electronic interaction between single atoms and COF adjusts the binding affinity and modifies ion traffic between Li/K ions and the active organic units of COFs as evidenced by extensive in situ and ex situ characterizations and theoretical calculations. The corresponding LIB achieves a high reversible capacity of 1,023.0 mA h g-1 after 100 cycles at 100 mA g-1 and 501.1 mA h g-1 after 500 cycles at 1,000 mA g-1. The corresponding PIB delivers a high reversible capacity of 449.0 mA h g-1 at 100 mA g-1 after 150 cycles and stably cycled over 500 cycles at 1,000 mA g-1. This work provides a promising route to engineering organic electrodes.

3.
Angew Chem Int Ed Engl ; 63(15): e202320259, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38332561

ABSTRACT

Fatal issues in lithium metal anodes (LMA), such as detrimental lithium dendrites growth and fragile solid-electrolyte interphase (SEI) during the Li plating/stripping process, often hinder the practical application of Li metal batteries (LMBs). Herein, cobalt-coordinated sp-carbon-conjugated organic polymer (Co-spc-COP) is constructed as the protective layer for regulating the interface stability of LMA. The unique synergistic beneficial effect of organic functional groups (C≡C linkage, C=N units and aromatic rings) and Co sites not only regulate the Li+ coordination environment and rearrange Li+ concentration to facilitate its transport by optimizing the electronic density, enhancing the compatibility with electrolyte interface and supplying "external magnetic driving strategy", but also strengthens the interfacial stiffness with high Young's modulus to better withstand the mechanical stress. These beneficial effects and relative underlying working mode and mechanism of uniform Li plating and rapid Li+ migration on the Co-spc-COP are also revealed by various in situ/ex situ experimental technologies and theory calculation. The Co-spc-COP-based cell delivers an extraordinary lifespan of 6600 h and ultrahigh capacity retention of 78.3 % (111.9 mAh g-1) after 1000 cycles at 1 C. This demonstrated synergistic strategy in Co-coordinated organic polymer may gain new insights to regulate the uniform and non-dendritic deposition/dissolution behaviors for highly stable LMBs.

4.
Acta Pharmacol Sin ; 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38351317

ABSTRACT

Transforming growth factor-ß (TGF-ß) signaling is initiated by activation of transmembrane TGF-ß receptors (TGFBR), which deploys Smad2/3 transcription factors to control cellular responses. Failure or dysregulation in the TGF-ß signaling pathways leads to pathological conditions. TGF-ß signaling is regulated at different levels along the pathways and begins with the liberation of TGF-ß ligand from its latent form. The mechanisms of TGFBR activation display selectivity to cell types, agonists, and TGF-ß isoforms, enabling precise control of TGF-ß signals. In addition, the cell surface compartments used to release active TGF-ß are surprisingly vibrant, using thrombospondins, integrins, matrix metalloproteinases and reactive oxygen species. The scope of TGFBR activation is further unfolded with the discovery of TGFBR activation initiated by other signaling pathways. The unique combination of mechanisms works in series to trigger TGFBR activation, which can be explored as therapeutic targets. This comprehensive review provides valuable insights into the diverse mechanisms underpinning TGFBR activation, shedding light on potential avenues for therapeutic exploration.

5.
Angew Chem Int Ed Engl ; 63(1): e202316208, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-37990065

ABSTRACT

Green organic materials composed of C, H, O, and N elements are receiving more and more attention worldwide. However, the high solubility, poor electrical conductivity, and long activation time limit the development of organic materials in practice. Herein, two stable covalent organic materials with alkynyl linkage between benzene rings and benzothiadiazole groups with different amounts of fluorine atoms modification (defined as BOP-0F and BOP-2F), are designed for lithium-ion batteries. Both BOP-0F and BOP-2F can achieve superior reversible capacities of ≈719.8 and 713.5 mAh g-1 over 100 cycles on account of the redox activity of alkynyl (two-electron involved) and benzothiadiazole units (five-electron involved) in these organic materials. While BOP-2F electrodes exhibit much more stable cycling performance than BOP-0F electrodes, especially without pronounced capacity ascending during initial cycling. It can be assigned to the synergy effect of alkynyl linkage and fluorine atom modification in BOP-2F. The lithium storage and activation mechanism of alkynyl, benzothiadiazole, and fluorine groups have also been deeply probed by a series of material characterizations and theoretical simulations. This work could be noteworthy in providing novel tactics for the molecular design and investigation of high-efficiency organic electrodes for energy storage.

6.
iScience ; 26(12): 108378, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38025774

ABSTRACT

In most economically underdeveloped areas, scattered farming and human‒livestock cohabitation are common. However, production of bioaerosols and their potential harm in these areas have not been previously researched. In this study, bioaerosol characteristics were analyzed in scattered farming areas in rural Northwest China. The highest bacteria, fungi, and Enterobacteria concentrations were 125609 ± 467 CFU/m³, 25175 ± 10305 CFU/m³, and 4167 ± 592 CFU/m³, respectively. Most bioaerosols had particle sizes >3.3 µm. A total of 71 bacterial genera and 16 fungal genera of potential pathogens were identified, including zoonotic potential pathogenic genera. Moreover, our findings showed that the scattered farming pattern of human‒animal cohabitation can affect the indoor air environment in the surrounding area, leading to chronic respiratory diseases in the occupants. Therefore, relevant government departments and farmers should enhance their awareness of bioaerosol risks and consider measures that may be taken to reduce them.

7.
Waste Manag Res ; : 734242X231190811, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37555586

ABSTRACT

Soil microplastic pollution is currently a worldwide concern. Microplastics are organic pollutants that are abundant in the natural environment, are persistent and difficult to degrade and may endanger human health while harming the environment. This article offers a bibliometric analysis of the environmental behaviour of microplastics in soils, as well as a thorough statistical analysis of research goals and trends in this field. We conducted a thorough search of all relevant literature from 2012 to 2022 in the Web of Science core database. The data analysis shows that, starting in 2012, there has been an upward trend in the number of articles about soil microplastic pollution. It can also be seen that China is relatively ahead of the curve in this area of research, followed by the United Kingdom and the United States. This article also systematically describes the research hotspots in this field. The results show that the current research on soil microplastics is mainly focused on their identification, enrichment and toxicity, whereas studies on the migration and transformation of soil microplastics and the mechanism of interaction with other pollutants are still lacking. Our results provide ideas and prospects for future research in this field.

8.
J Am Chem Soc ; 145(36): 19945-19952, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37641545

ABSTRACT

Thermophoretic micro/nanomotors (MNMs) generate self-propulsion without a chemical reaction. Intrinsically, this promises excellent biocompatibility and is thus suitable for biomedical applications. However, their propulsion efficiency is severely limited due to the poor understanding of the thermophoretic process, which dominates the conversion from thermal energy into mechanical movement. We here developed a series of self-thermophoresis light-powered MNMs with variable surface coatings and discovered obvious self-thermophoresis propulsion enhancement of the polymeric layer. An intrinsically negative self-thermophoretic movement is also observed for the first time in the MNM system. We propose that enthalpic contributions from polymer-solvent interactions should play a fundamental role in the self-thermophoretic MNMs. Quantitative microcalorimetry and molecular dynamics simulations are performed to support our hypothesis. The polymer solvation enthalpy and coating thickness influences on self-thermophoresis are investigated, further highlighting the essential enthalpy contributions to thermophoresis. Our work indicates that surface grafting would be important in designing high-efficiency thermally driven nanorobotic systems for biomedical applications.

9.
Angew Chem Int Ed Engl ; 62(30): e202302143, 2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37269463

ABSTRACT

The poor conductivity of the pristine bulk covalent organic material is the main challenge for its application in energy storage. The mechanism of symmetric alkynyl bonds (C≡C) in covalent organic materials for lithium storage is still rarely reported. Herein, a nanosized (≈80 nm) alkynyl-linked covalent phenanthroline framework (Alkynyl-CPF) is synthesized for the first time to improve the intrinsic charge conductivity and the insolubility of the covalent organic material in lithium-ion batteries. Because of the high degree of electron conjugation along alkynyl units and N atoms from phenanthroline groups, the Alkynyl-CPF electrodes with the lowest HOMO-LUMO energy gap (ΔE=2.629 eV) show improved intrinsic conductivity by density functional theory (DFT) calculations. As a result, the pristine Alkynyl-CPF electrode delivers superior cycling performance with a large reversible capacity and outstanding rate properties (1068.0 mAh g-1 after 300 cycles at 100 mA g-1 and 410.5 mAh g-1 after 700 cycles at 1000 mA g-1 ). Moreover, by Raman, FT-IR, XPS, EIS, and theoretical simulations, the energy-storage mechanism of C≡C units and phenanthroline groups in the Alkynyl-CPF electrode has been investigated. This work provides new strategies and insights for the design and mechanism investigation of covalent organic materials in electrochemical energy storage.

10.
Environ Pollut ; 324: 121338, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36842620

ABSTRACT

In rural China, the release of bioaerosols containing pathogens from solid waste dumps poses a potential health risk to the local population. Here, we sampled bioaerosols from rural solid waste-treatment in four provinces of northwest China to investigate their emission and dispersion characteristics in order to provide a scientific basis for control and risk reduction of bioaerosols released from rural sanitation facilities. The airborne bioaerosol concentrations and particle size distributions were calculated using an Anderson six-stage airborne microbial sampler and counting with its internal Petri dish culture. High-throughput sequencing was used to characterize the microbial composition at different sampling sites and to explore possible influencing factors, while the health risk associated with exposure was estimated based on average daily dose-rate. The highest concentration point values of bacteria and fungi in bioaerosols near the solid waste were 63,617 ± 15,007 and 8044 ± 893 CFU/m³, respectively. Furthermore, the highest concentration point values of Enterobacteriaceae was 502 ± 35 CFU/m³. Most bioaerosols were coarse particles larger than 3.3 µm. Potentially pathogenic genera of winter-indicator species detected in the air were primarily Delftia, Rhodococcus and Aspergillus. The composition of solid waste and environmental conditions are important factors in determining the characteristics of bioaerosols. Local residents are exposed to bioaerosols mainly through inhalation. Children are at a particularly high risk of exposure through both inhalation and skin contact. The results of this study show that bioaerosols in the vicinity of rural solid waste dumps pose a health risk to the surrounding population. More suitable risk assessment criteria for rural areas should be established, and corresponding control and protection measures should be taken from three aspects: generation source and transmission pathway, as well as the recipient.


Subject(s)
Air Microbiology , Solid Waste , Child , Humans , Aerosols/analysis , Bacteria , Fungi , China , Environmental Monitoring
11.
Angew Chem Int Ed Engl ; 61(48): e202213276, 2022 Nov 25.
Article in English | MEDLINE | ID: mdl-36196009

ABSTRACT

The rechargeable lithium/sodium-iodine battery (Li/Na-I2 ) is a promising candidate for meeting the growing energy demand. Herein, a flexible hydrogen-bonded organic framework (HOF) linked to the Ti3 C2 Tx MXene complex (HOF@Ti3 C2 Tx ) has been presented for iodine loading. HOF is self-assembled by organic monomers through hydrogen bonding interactions between each monomer. It leads to numerous cavities in HOF structure, which can encapsulate iodine through various adsorptive sites and intermolecular interactions. The unique structure of complex can accelerate the nucleation of iodine, achieve fast reaction kinetics, stabilize iodide and retard the shuttle effect, thus improving the cycling stability of I2 -based batteries. The I2 /HOF@Ti3 C2 Tx exhibits large reversible capacities of 260.2 and 207.6 mAh g-1 at 0.2 C after repeated cycling for Li-I2 and Na-I2 batteries, respectively. This work can gain insights into the HOF-related energy storage application with reversible iodine encapsulation and its related redox reaction mechanisms with Li and Na metal ions.

12.
ACS Nano ; 16(6): 9830-9842, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35658409

ABSTRACT

Covalent organic polymers are attracting more and more attention for energy storage devices due to their lightweight, molecular viable design, stable structure, and environmental benignity. However, low charge-carrier mobility of pristine covalent organic materials is the main drawback for their application in lithium-ion batteries. Herein, a yolk-shell bimetal-modified quinonyl-rich covalent organic material, Co@2AQ-MnO2, has been designed and synthesized by in situ loading of petal-like nanosized MnO2 and coordinating with Co centers, with the aim to improve the charge conductivity of the covalent organic polymer and activate its Li-storage sites. As investigated by in situ FT-IR, ex situ XPS, and electrochemical probing, the quinonyl-rich structure provides abundant redox sites (carbonyl groups and π electrons from the benzene ring) for lithium reaction, and the introduction of two types of metallic species promotes the charge transfer and facilitates more efficient usage of active energy-storage sites in Co@2AQ-MnO2. Thus, the Co@2AQ-MnO2 electrode exhibits good cycling performance with large reversible capacity and excellent rate performance (1534.4 mA h g-1 after 200 cycles at 100 mA g-1 and 596.0 mA h g-1 after 1000 cycles at 1000 mA g-1).

13.
ACS Appl Mater Interfaces ; 14(26): 29974-29985, 2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35758292

ABSTRACT

The high solubility of the small organic molecule materials in organic electrolytes hinders their development in rechargeable batteries. Hence, this work designs an ultrarobust hydrogen-bonded organic-inorganic hybrid material: the small organic unit of the 1,3,6,8-tetrakis (p-benzoic acid) pyrene (TBAP) molecule connected with the hydroxylated Ti3C2Tx MXene through hydrogen bonds between the terminal groups of -COOH and -OH. The robust and elastic hydrogen bonds can empower the TBAP, despite being a low-molecule organic chemical, with unusually low solubility in organic electrolytes and thermal stability. The alkali-treated Ti3C2Tx MXene provides a hydroxyl-rich conductive network, and the small organic molecule of TBAP reduces the restacking of MXene layers. Therefore, the combination of these two materials complements each other well, and this organic-inorganic TBAP@D-Ti3C2Tx electrode delivers large reversible capacities and long cyclic life. Notably, with the assistance of the in situ FT-IR characterization of the electrode within the fully lithiated (0.005 V) and the delithiated (3.0 V) states, it is revealed that a powerful π-Li cation effect mainly governs the lithium-storage mechanism with the highly activated benzene ring and each C6 aromatic ring, which can reversibly accept six Li-ions to form a 1:1 Li/C complex.

14.
J Food Biochem ; 46(3): e13882, 2022 03.
Article in English | MEDLINE | ID: mdl-34312884

ABSTRACT

Atherosclerosis, the major underlying pathology of cardiovascular disease, commences with the binding and trapping of lipids on modified proteoglycans, with hyperelongated glycosaminoglycan chains. Transforming growth factor (TGF)-ß stimulates glycosaminoglycan elongation in vascular smooth muscle cells. We have recently shown that this TGF-ß signaling pathway involves reactive oxygen species (ROS). YY-11 is a dodecapeptide derived from camel milk and it has antioxidant activity. We have investigated the role of YY-11 in blocking ROS signaling and downstream atherogenic responses. YY-11 inhibited TGF-ß stimulated ROS production and inhibited the expression of genes for glycosaminoglycan chain elongation as a component of an in vitro model of atherosclerosis. This study provides a biochemical mechanism for the role of camel milk as a potential nutritional product to contribute to the worldwide amelioration of cardiovascular disease. PRACTICAL APPLICATIONS: The identification of readily accessible foods with antioxidant properties would provide a convenient and cost-effective approach community wide reducing oxidative stress induced pathologies such as atherosclerosis. We demonstrate that camel milk-derived peptide is an antioxidant that can inhibit growth factor-mediated proteoglycan modification in vitro. As proteoglycan modification is being recognized as one of the earliest atherogenic responses, these data support the notion of camel milk as a suitable nutritional product to contribute to the prevention of early stage of atherosclerosis development.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Atherosclerosis/drug therapy , Camelus/metabolism , Cardiovascular Diseases/metabolism , Glycosaminoglycans/chemistry , Glycosaminoglycans/metabolism , Humans , Milk/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Phosphorylation , Proteoglycans/chemistry , Proteoglycans/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Smad2 Protein/chemistry , Smad2 Protein/metabolism , Transforming Growth Factor beta/metabolism
15.
Macromol Rapid Commun ; 42(23): e2100551, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34610177

ABSTRACT

This work has prepared polymeric self-assembled monolayer (SAM) sensors for the detection of trace volatile nitroaromatic compound (NAC) explosives by fluorescence quenching. A typical aggregation-induced emission (AIE) luminogen 1,1,2,2-tetraphenylethene (TPE) polymerizes into PTPE to increase the fluorescence intensity in the SAMs, and the phosphoric acid acts as the anchor group to form stable covalent bonds with the Al2 O3 substrate. This design takes advantage of the high sensitivity and good stability of SAMs, and high fluorescence intensity, and "wire effect" of the conjugated polymers. The polymeric SAM sensors are prepared on the Al2 O3 silicon wafer and testing paper. Both of them show good response speed, reversibility, selectivity, and sensitivity. The detection limits down to 0.07, 0.35, and 4.11 ppm for TNT, DNB, and NB, respectively, are achieved on the inorganic testing paper. Furthermore, due to the higher fluorescence intensity by interlacing and overlapping of fibers, the detection of the paper can be distinguished by naked eyes even with a low-power handheld UV lamp, which provides an experimental basis for the development of cheap and easy trace NAC explosive sensors.


Subject(s)
Explosive Agents , Fluorescence , Polymers
16.
Langmuir ; 37(19): 5916-5922, 2021 May 18.
Article in English | MEDLINE | ID: mdl-33909431

ABSTRACT

High-performance formaldehyde sensors play an important role in air quality assessment. Herein, a self-assembled monolayer (SAM) sensor for trace formaldehyde (FA) is fabricated based on the fluorescence enhancement of oxidized thiophene derivatives. In the primary SAM molecules, the functional backbone trithiophene (3T) links to the anchor through an n-propyl group. The anchor with an active Si-Cl bond can form a covalent bond with the SiO2 substrate by solution incubation, which ensures good stability against organic solvents and high sensitivity via monolayer structures. With the alkyl chain's leading, a dense 3T SAM can be obtained on SiO2. Upon exposure to UV light in the presence of oxygen, 3T can be oxidized into a nonfluorescent but coordination-active product with abundant carbonyl groups, which can be doped with FA and induce a blueshifted fluorescence. With this mechanism, we proposed an SAM-based FA sensor by detecting the enhancement of the blueshifted fluorescence. Reliable reversibility, selectivity, stability, and detection limit lower than 1 ppm are achieved in this system. The work provides an experimental basis for developing a cheap, efficient, and flexible sensor for trace FA detection.

17.
ACS Nano ; 15(4): 6517-6529, 2021 04 27.
Article in English | MEDLINE | ID: mdl-33749240

ABSTRACT

The combination of photothermal therapy (PTT) and gene therapy (GT) shows great potential to achieve synergistic anti-tumor activity. However, the lack of a controlled release of genes from carriers remains a severe hindrance. Herein, peptide lipid (PL) and sucrose laurate (SL) were used to coat single-walled carbon nanotubes (SCNTs) and multi-walled carbon nanotubes (MCNTs) to form bifunctional delivery systems (denoted SCNT-PS and MCNT-PS, respectively) with excellent temperature-sensitivity and photothermal performance. CNT/siRNA suppressed tumor growth by silencing survivin expression while exhibiting photothermal effects under near-infrared (NIR) light. SCNT-PS/siRNA showed very high anti-tumor activity, resulting in the complete inhibition of some tumors. It was highly efficient for systemic delivery to tumor sites and to facilitate siRNA release owing to the phase transition of the temperature-sensitive lipids, due to PL and SL coating. Thus, SCNT-PS/siRNA is a promising anti-tumor nanocarrier for combined PTT and GT.


Subject(s)
Nanotubes, Carbon , Cell Line, Tumor , Genetic Therapy , Lipids , Phototherapy , Photothermal Therapy , Temperature
18.
J Nanobiotechnology ; 18(1): 144, 2020 Oct 17.
Article in English | MEDLINE | ID: mdl-33069258

ABSTRACT

BACKGROUND: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. RESULTS: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (- 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the "proton sponge effect" of the lipid. CONCLUSIONS: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.


Subject(s)
Genetic Therapy/methods , Lipids/chemistry , Liposomes/chemistry , Peptides/chemistry , Cations/chemistry , Cell Membrane , DNA/chemistry , Endosomes , Gene Transfer Techniques , HeLa Cells , Humans , Kinetics , Liposomes/metabolism , Transfection
19.
Biochim Biophys Acta Mol Cell Res ; 1867(12): 118848, 2020 12.
Article in English | MEDLINE | ID: mdl-32920014

ABSTRACT

Lysophosphatidic acid (LPA) via transactivation dependent signalling pathways contributes to a plethora of physiological and pathophysiological responses. In the vasculature, hyperelongation of glycosaminoglycan (GAG) chains on proteoglycans leads to lipid retention in the intima resulting in the early pathogenesis of atherosclerosis. Therefore, we investigated and defined the contribution of transactivation dependent signalling in LPA mediated GAG chain hyperelongation in human vascular smooth muscle cells (VSMCs). LPA acting via the LPA receptor 5 (LPAR5) transactivates the TGFBR1 to stimulate the mRNA expression of GAG initiation and elongation genes xylosyltransferase-1 (XYLT1) and chondroitin 6-sulfotransferase-1 (CHST3), respectively. We found that LPA stimulates ROS and Akt signalling in VSMCs, however they are not associated in LPAR5 transactivation of the TGFBR1. We observed that LPA via ROCK dependent pathways transactivates the TGFBR1 to stimulate genes associated with GAG chain elongation. We demonstrate that GPCR transactivation of the TGFBR1 occurs via a universal biochemical mechanism and the identified effectors represent potential therapeutic targets to inhibit pathophysiological effects of GPCR transactivation of the TGFBR1.


Subject(s)
Lysophospholipids/metabolism , Pentosyltransferases/genetics , Receptor, Transforming Growth Factor-beta Type I/genetics , Receptors, Lysophosphatidic Acid/genetics , Sulfotransferases/genetics , Gene Expression Regulation, Developmental/genetics , Glycosaminoglycans/biosynthesis , Humans , Lysophospholipids/genetics , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Protein Biosynthesis/genetics , Proteoglycans/biosynthesis , RNA, Messenger/genetics , rho-Associated Kinases/genetics , UDP Xylose-Protein Xylosyltransferase , Carbohydrate Sulfotransferases
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