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1.
J Biol Chem ; : 107801, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307307

RESUMO

A dynamic proteome is required for cellular adaption to changing environments including levels of O2, and the SKP1/CULLIN-1/F-box protein/RBX1 (SCF) family of E3 ubiquitin ligases contributes importantly to proteasome-mediated degradation. We examine, in the apicomplexan parasite Toxoplasma gondii, the influence on the interactome of SKP1 by its novel glycan attached to a hydroxyproline generated by PHYa, the likely ortholog of the HIFα PHD2 oxygen-sensor of human host cells. Strikingly, the representation of several putative F-box proteins (FBPs) is substantially reduced in PHYaΔ parasites grown in fibroblasts. One, FBXO13, is a predicted lysyl hydroxylase related to the human JmjD6 oncogene except for its F-box domain. The abundance of FBXO13, epitope-tagged at its genetic locus, was reduced in PHYaΔ parasites thus explaining its diminished presence in the SKP1 interactome. A similar effect was observed for FBXO14, a cytoplasmic protein of unknown function that may have co-evolved with PHYa in apicomplexans. Similar findings in glycosylation-mutant cells, rescue by proteasomal inhibitors, and unchanged transcript levels, suggested the involvement of the SCF in their degradation. The effect was selective, because FBXO1 was not affected by loss of PHYa. These findings are physiologically significant because the effects were phenocopied in parasites reared at 0.5% O2. Modest impact on steady-state SKP1 modification levels suggests that effects are mediated during a lag phase in hydroxylation of nascent SKP1. The dependence of FBP abundance on O2-dependent SKP1 modification likely contributes to the reduced virulence of PHYaΔ parasites owing to impaired ability to sense O2 as an environmental signal.

2.
Toxicol Appl Pharmacol ; 484: 116872, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428465

RESUMO

Previous studies have demonstrated that tetramethylpyrazine (TMP) can enhance the recovery of motor function in spinal cord injury (SCI) rats. However, the underlying mechanism involved in this therapeutic effect remains to be elucidated. We conducted RNA sequencing with a network pharmacology strategy to predict the targets and mechanism of TMP for SCI. The modified Allen's weight-drop method was used to construct an SCI rat model. The results indicated that the nuclear transfer factor-κB (NF-κB) pathway was identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and an inflammatory response was identified through the Gene Ontology (GO) enrichment analysis. Tumor necrosis factor (TNF) was identified as a crucial target. Western blotting revealed that TMP decreased the protein expression of TNF superfamily receptor 1 (TNFR1), inhibitor κB-α (IκB-α), and NF-κB p65 in spinal cord tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) demonstrated that TMP inhibited TNF-α, interleukin-1ß (IL-1ß), reactive oxygen species (ROS), and malondialdehyde (MDA) expression and enhanced superoxide dismutase (SOD) expression. Histopathological observation and behavior assessments showed that TMP improved morphology and motor function. In conclusion, TMP inhibits inflammatory response and oxidative stress, thereby exerting a neuroprotective effect that may be related to the regulation of the TNFR1/IκB-α/NF-κB p65 signaling pathway.


Assuntos
NF-kappa B , Pirazinas , Traumatismos da Medula Espinal , Animais , Ratos , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa , Pirazinas/farmacologia , Ratos Sprague-Dawley , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/farmacologia , Receptores Tipo I de Fatores de Necrose Tumoral/uso terapêutico , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa/metabolismo
3.
Chemistry ; : e202402119, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007706

RESUMO

The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2 lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis. While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid multifunctional material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco=N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction (HER) due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the density functional theory (DFT) calculations revealed that the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based multifunctional hybrid materials.

4.
Int J Mol Sci ; 25(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38542442

RESUMO

The Shanlan landrace rice in Hainan Province, China, is a unique upland rice germplasm that holds significant value as a genetic resource for rice breeding. However, its genetic diversity and its usefulness in rice breeding have not been fully explored. In this study, a total of eighty-four Shanlan rice, three typical japonica rice cultivars, and three typical indica rice cultivars were subjected to resequencing of their genomes. As a result, 11.2 million high-quality single nucleotide polymorphisms (SNPs) and 1.6 million insertion/deletions (InDels) were detected. Population structure analysis showed all the rice accessions could be divided into three main groups, i.e., Geng/japonica 1 (GJ1), GJ2, and Xian/indica (XI). However, the GJ1 group only had seven accessions including three typical japonica cultivars, indicating that most Shanlan landrace rice are different from the modern japonica rice. Principal component analysis (PCA) showed that the first three principal components explained 60.7% of the genetic variation. Wide genetic diversity in starch physicochemical parameters, such as apparent amylose content (AAC), pasting viscosity, texture properties, thermal properties, and retrogradation representing the cooking and eating quality was also revealed among all accessions. The genome-wide association study (GWAS) for these traits was conducted and identified 32 marker trait associations in the entire population. Notably, the well-known gene Waxy (Wx) was identified for AAC, breakdown viscosity, and gumminess of the gel texture, and SSIIa was identified for percentage of retrogradation and peak gelatinization temperature. Upon further analysis of nucleotide diversity in Wx, six different alleles, wx, Wxa, Wxb, Wxin, Wxla/mw, and Wxlv in Shanlan landrace rice were identified, indicating rich gene resources in Shanlan rice for quality rice breeding. These findings are expected to contribute to the development of new rice with premium quality.


Assuntos
Estudo de Associação Genômica Ampla , Oryza , Oryza/metabolismo , Melhoramento Vegetal , Amilose/genética , Polimorfismo de Nucleotídeo Único , Culinária
5.
Inflammopharmacology ; 32(2): 1039-1058, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38153536

RESUMO

BACKGROUND: This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain. METHODS: Randomized controlled trials retrieved from nine databases included anti-inflammatory drugs (NSAIDs or steroids) versus non-anti-inflammatory drugs in patients with acute pain and reported the incidence of chronic pain. No specified date, age, sex, or language restrictions. Subgroup analyses were performed according to pain classification, follow-up time, and medication. The GRADE method was used to evaluate quality of evidence. RESULTS: A total of 29 trials (5220 patients) were included. Steroids or NSAIDs did not reduce the incidence of chronic nociceptive pain. Steroid use in acute phase significantly reduced the incidence of chronic neuropathic pain. In subgroup analysis, benefits were observed for methylprednisolone and dexamethasone, with some adverse effects. Steroids or NSAIDs were statistically significant in reducing pain intensity over 1 year, but the effect size was too small, and whether the long-term effect is clinically relevant needs to be further studied. CONCLUSION: Quality of the evidence was low to moderate. No drug can be recommended to prevent chronic nociceptive pain. Injections of steroids (methylprednisolone or dexamethasone) during the acute phase reduce the incidence of chronic neuropathic pain, but most included studies also used local anesthetics. The results are indirect and need to be interpreted with caution. The pooled data effect sizes for pain intensity were small, so the clinical relevance was unclear. Study registration PROSPERO (CRD42022367030).


Assuntos
Dor Aguda , Anti-Inflamatórios não Esteroides , Dor Crônica , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Dor Crônica/tratamento farmacológico , Dor Crônica/epidemiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Aguda/tratamento farmacológico , Dor Aguda/epidemiologia , Incidência , Esteroides/administração & dosagem , Esteroides/efeitos adversos , Neuralgia/tratamento farmacológico , Neuralgia/epidemiologia , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico
6.
Angew Chem Int Ed Engl ; 63(26): e202404025, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38659286

RESUMO

Reactive metals hydrolysis offers significant advantages for hydrogen storage and production. However, the regeneration of common reactive metals (e.g., Mg, Al, etc.) is energy-intensive and produces unwanted byproducts such as CO2 and Cl2. Herein, we employ Zn as a reactive mediator that can be easily regenerated by electrolysis of ZnO in an alkaline solution with a Faradaic efficiency of >99.9 %. H2 is produced in the same electrolyte by constructing a Zn-H2O hydrolysis battery consisting of a Zn anode and a Raney-Ni cathode to unlock the Zn-H2O reaction. The entire two-step water splitting reaction with a net energy efficiency of 70.4 % at 80 °C and 50 mA cm-2. Additionally, the Zn-H2O system can be charged using renewable energy to produce H2 on demand and runs for 600 cycles only sacrificing 3.76 % energy efficiency. DFT calculations reveal that the desorption of H* on Raney-Ni (-0.30 eV) is closer to zero compared with that on Zn (-0.87 eV), indicating a faster desorption of H* at low overpotential. Further, a 24 Ah electrolyzer is demonstrated to produce H2 with a net energy efficiency of 65.5 %, which holds promise for its real application.

7.
Opt Lett ; 48(19): 5009-5012, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37773372

RESUMO

Terahertz (THz) absorbers are highly desired with the rapid development of THz technology. Although metasurface-based absorbers can realize perfect absorption, their fabrication often requires complicated micro-nano-processing with a high cost. In this paper, fast printable and low-cost metasurface absorbers based on a laser-induced graphene (LIG) technique are proposed. Experimental results demonstrate that these two metasurfaces can achieve maximum absorptions of 99.3% and 99.9% at their resonant frequencies in an incident angle range of ±55°. Fabrication of a metasurface with a size of 1 × 1 cm costs only 11 s. The absorbers may be applied in THz dichroism and communications.

8.
Inorg Chem ; 62(29): 11701-11707, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37427412

RESUMO

Switchable materials have attracted enormous interest due to their promising applications in important fields such as sensing, electronic components, and information storage. Nevertheless, obtaining multifunctional switching materials is still a problem worth investigating. Herein, by incorporating (Rac-, L-, D-2-amino-1-propanol) as the templating cation, we have obtained (Rac-, L-, D-HTMPA)CdCl3 (HTMPA = 1-hydroxy-N, N, N-trimethyl-2-propanaminium). We have adopted a chiral chemistry strategy that causes (Rac-HTMPA)CdCl3 in the central symmetric space to crystallize in the chiral space group. Based on the modulation of the homochiral strategy, (L-, D-HTMPA)CdCl3 shows a dual phasic transition at 269 and 326 K and a switchable second-harmonic generation response. In addition, (L-, D-HTMPA)CdCl3 is chiral switchable material to exhibit stable dual dielectric and second-harmonic generation (SHG) switches. This work provides an approach to exploring multifunctional chiral switchable materials.

9.
BMC Infect Dis ; 23(1): 232, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37059988

RESUMO

OBJECTIVE: This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections. METHODS: A search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs). RESULTS: A total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I2 = 29%). Omadacycline had a microbiological eradication rate similar to comparators in the treatment of acute bacterial infections (OR = 1.02, 95%CI = 0.81, 1.29, I2 = 42%). No statistical differences were observed between omadacycline and the comparators in terms of infection caused by Staphylococcus aureus (OR = 1.14, 95%CI = 0.80, 1.63, I2 = 0%), methicillin-resistant S. aureus (MRSA, OR = 1.28, 95%CI = 0.73, 2.24, I2 = 0%), methicillin-susceptible S. aureus (MSSA, OR = 1.12, 95%CI = 0.69, 1.81, I2 = 0%), and Enterococcus faecalis (OR = 2.47, 95%CI = 0.36, 16.97, I2 = 7%). A significant difference was found between omadacycline and the comparators for the risk of any AEs and treatment related AEs. The risk of discontinuation of the study drug due to an AEs was lower for omadacycline than for the comparators. CONCLUSION: Omadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.


Assuntos
Infecções Bacterianas , Infecções Estafilocócicas , Adulto , Humanos , Antibacterianos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Tetraciclinas/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto
10.
Exp Cell Res ; 412(2): 113026, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35026284

RESUMO

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are well-established as vital regulators of fracture healing, whereas angiogenesis is one of the critical processes during the course of bone healing. Accordingly, the current study sought to determine the functions of microRNA (miR)-29b-3p from BM-MSCs-derived extracellular vesicles (EVs) on the angiogenesis of fracture healing via the PTEN/PI3K/AKT axis. Firstly, BM-MSCs-EVs were extracted and identified. The lentiviral protocol was adopted to construct miR-29b-3pKD-BMSCs or miR-negative control-BMSCs, which were then co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro to determine the roles of EVs-encapsulated miR-29b-3p on the proliferation, migration, and angiogenesis of HUVECs in vitro with the help of a CCK-8 assay, scratch test, and tube formation assay. Subsequent database prediction, luciferase activity assay, RT-qPCR, and Western blot assay findings identified the downstream target gene of miR-29b-3p, PTEN, and a signaling pathway, PI3K/AKT. Furthermore, the application of si-PTEN attenuated the effects induced by miR-29b-3pKD-EVs. Finally, a mouse model of femoral fracture was established with a locally instilled injection of equal volumes of BM-MSCs-EVs and miR-29b-3pKD-BM-MSCs-EVs. Notably, the mice treated with BMSC-EVs presented with enhanced neovascularization at the fracture site, in addition to increased bone volume (BV), BV/tissue volume, and mean bone mineral density; whereas miR-29b-3pKD-BMSCs-EVs-treated mice exhibited decreased vessel density with poor fracture healing capacity. Collectively, our findings elicited that BM-MSCs-EVs carrying miR-29b-3p were endocytosed by HUVECs, which consequently suppressed the PTEN expression and activated the PI3K/AKT pathway, thereby promoting HUVEC proliferation, migration, and angiogenesis, and ultimately facilitating fracture healing.


Assuntos
Vesículas Extracelulares/metabolismo , Consolidação da Fratura/fisiologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Densidade Óssea/fisiologia , Medula Óssea/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologia
11.
Nano Lett ; 22(1): 97-104, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34958590

RESUMO

The reported mechanical strength of carbon nanocoils (CNCs) obtained from traditional preparation of catalytic acetylene pyrolysis is far below its theoretical value. Herein, we report a molten salt electrolysis method that employs CO32- as feedstock to grow CNCs without using metal catalyst. We meticulously mediate the alkalinity of molten carbonate to tune the electrochemical reduction of CO32- on graphite electrode to selectively grow CNCs in Li2CO3-Na2CO3-K2CO3-0.001 wt %Li2O. Graphite substrate, current density, and alkalinity of molten salt dictate the growth of CNCs. In addition, the electrolytic CNCs shows a spring constant of 1.92-39.41 N/m and a shear modulus of 21-547 GPa, which are 10-200 times that of CNCs obtained from catalyst-assisted gas-to-solid conversions. Overall, this paper opens up an electrochemical way to prepare CNCs through liquid-to-solid conversion without using catalysts and acetylene, providing new perspectives on green synthesis of 1D carbon nanomaterials with high mechanical strength.


Assuntos
Carbono , Grafite , Carbonatos , Catálise , Eletrodos
12.
Int J Mol Sci ; 24(3)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36768457

RESUMO

In the last few decades, the prevalence of diabetes mellitus (DM) has increased rapidly. Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD) globally, attributed to hemodynamic changes and chronic hyperglycemia. Recent findings have emphasized the role of cell-cycle dysregulation in renal fibrosis and ESRD. Under normal physiological conditions, most mature renal cells are arrested in the G0 phase of the cell cycle, with a rather low rate of renewal. However, renal cells can bypass restriction points and re-enter the cell cycle under stimulation of injuries induced via metabolic disorders. Mild injuries activate proliferation of renal cells to compensate for cell loss and reinstate renal function, while severe or repeated injuries will lead to DNA damage and maladaptive repair which ultimately results in cell-cycle arrest or overproliferation, and eventually promote renal fibrosis and ESRD. In this review, we focus on the role of cell-cycle dysregulation in DKD and discuss new, emerging pathways that are implicated in the process.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Falência Renal Crônica , Humanos , Nefropatias Diabéticas/metabolismo , Rim/metabolismo , Falência Renal Crônica/complicações , Fibrose , Divisão Celular , Diabetes Mellitus/patologia
13.
Molecules ; 27(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36296549

RESUMO

The present study is to explore the anticancer effect of loonamycin (LM) in vitro and in vivo, and investigate the underlying mechanism with combined multi-omics. LM exhibited anticancer activity in human triple negative breast cancer cells by promoting cell apoptosis. LM administration inhibited the growth of MDA-MB-468 tumors in a murine xenograft model of breast cancer. Mechanistic studies suggested that LM could inhibit the topoisomerase I in a dose-dependent manner in vitro experiments. Combined with the transcriptomics and proteomic analysis, LM has a significant effect on O-glycan, p53-related signal pathway and EGFR/PI3K/AKT/mTOR signal pathway in enrichment of the KEGG pathway. The GSEA data also suggests that the TNBC cells treated with LM may be regulated by p53, O-glycan and EGFR/PI3K/AKT/mTOR signaling pathway. Taken together, our findings predicted that LM may target p53 and EGFR/PI3K/AKT/mTOR signaling pathway, inhibiting topoisomerase to exhibit its anticancer effect.


Assuntos
Fosfatidilinositol 3-Quinases , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Transcriptoma , Proteômica , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Apoptose , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proliferação de Células
14.
PLoS Pathog ; 15(7): e1007946, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31348812

RESUMO

By binding to the adaptor protein SKP1 and serving as substrate receptors for the SKP1 Cullin, F-box E3 ubiquitin ligase complex, F-box proteins regulate critical cellular processes including cell cycle progression and membrane trafficking. While F-box proteins are conserved throughout eukaryotes and are well studied in yeast, plants, and animals, studies in parasitic protozoa are lagging. We have identified eighteen putative F-box proteins in the Toxoplasma genome of which four have predicted homologs in Plasmodium. Two of the conserved F-box proteins were demonstrated to be important for Toxoplasma fitness and here we focus on an F-box protein, named TgFBXO1, because it is the most highly expressed by replicative tachyzoites and was also identified in an interactome screen as a Toxoplasma SKP1 binding protein. TgFBXO1 interacts with Toxoplasma SKP1 confirming it as a bona fide F-box protein. In interphase parasites, TgFBXO1 is a component of the Inner Membrane Complex (IMC), which is an organelle that underlies the plasma membrane. Early during replication, TgFBXO1 localizes to the developing daughter cell scaffold, which is the site where the daughter cell IMC and microtubules form and extend from. TgFBXO1 localization to the daughter cell scaffold required centrosome duplication but before kinetochore separation was completed. Daughter cell scaffold localization required TgFBXO1 N-myristoylation and was dependent on the small molecular weight GTPase, TgRab11b. Finally, we demonstrate that TgFBXO1 is required for parasite growth due to its function as a daughter cell scaffold effector. TgFBXO1 is the first F-box protein to be studied in apicomplexan parasites and represents the first protein demonstrated to be important for daughter cell scaffold function.


Assuntos
Proteínas F-Box/fisiologia , Proteínas de Protozoários/fisiologia , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/patogenicidade , Animais , Proteínas F-Box/antagonistas & inibidores , Proteínas F-Box/genética , Técnicas de Silenciamento de Genes , Genes de Protozoários , Humanos , Domínios e Motivos de Interação entre Proteínas , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/genética , Proteínas Quinases Associadas a Fase S/fisiologia , Toxoplasma/genética
15.
J Biol Chem ; 294(4): 1104-1125, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30463938

RESUMO

Infection with the protozoan parasite Toxoplasma gondii is a major health risk owing to birth defects, its chronic nature, ability to reactivate to cause blindness and encephalitis, and high prevalence in human populations. Unlike most eukaryotes, Toxoplasma propagates in intracellular parasitophorous vacuoles, but like nearly all other eukaryotes, Toxoplasma glycosylates many cellular proteins and lipids and assembles polysaccharides. Toxoplasma glycans resemble those of other eukaryotes, but species-specific variations have prohibited deeper investigations into their roles in parasite biology and virulence. The Toxoplasma genome encodes a suite of likely glycogenes expected to assemble N-glycans, O-glycans, a C-glycan, GPI-anchors, and polysaccharides, along with their precursors and membrane transporters. To investigate the roles of specific glycans in Toxoplasma, here we coupled genetic and glycomics approaches to map the connections between 67 glycogenes, their enzyme products, the glycans to which they contribute, and cellular functions. We applied a double-CRISPR/Cas9 strategy, in which two guide RNAs promote replacement of a candidate gene with a resistance gene; adapted MS-based glycomics workflows to test for effects on glycan formation; and infected fibroblast monolayers to assess cellular effects. By editing 17 glycogenes, we discovered novel Glc0-2-Man6-GlcNAc2-type N-glycans, a novel HexNAc-GalNAc-mucin-type O-glycan, and Tn-antigen; identified the glycosyltransferases for assembling novel nuclear O-Fuc-type and cell surface Glc-Fuc-type O-glycans; and showed that they are important for in vitro growth. The guide sequences, editing constructs, and mutant strains are freely available to researchers to investigate the roles of glycans in their favorite biological processes.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Edição de Genes , Glicômica , Polissacarídeos/genética , Polissacarídeos/metabolismo , Toxoplasma/genética , Toxoplasma/metabolismo , Técnicas de Inativação de Genes , Biblioteca Gênica
16.
Development ; 143(19): 3449-3458, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27510973

RESUMO

Polycomb and Trithorax group (PcG and TrxG) genes function to regulate gene transcription by maintaining a repressive or active chromatin state, respectively. This antagonistic activity is important for body patterning during embryonic development, but whether this function module has a role in adult tissues is unclear. Here, we report that in the Drosophila ovary, disruption of the Polycomb repressive complex 1 (PRC1), specifically in the supporting escort cells, causes blockage of cystoblast differentiation and germline stem cell-like tumor formation. Tumors are caused by derepression of decapentaplegic (dpp), which prevents cystoblast differentiation. Interestingly, activation of dpp in escort cells requires the function of the TrxG gene brahma (brm), suggesting that loss of PRC1 in escort cells causes Brm-dependent dpp expression. Our study suggests a requirement for balanced activity between PcG and TrxG in an adult stem cell niche, and disruption of this balance could lead to the loss of tissue homeostasis and tumorigenesis.


Assuntos
Proteínas de Drosophila/metabolismo , Células Germinativas/citologia , Complexo Repressor Polycomb 1/metabolismo , Células-Tronco/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster , Complexo Repressor Polycomb 1/genética , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Proteínas Smad/genética , Proteínas Smad/metabolismo , Células-Tronco/citologia
17.
Faraday Discuss ; 190: 241-58, 2016 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-27193751

RESUMO

Electrochemical transformation of CO2 into functional materials or fuels (i.e., carbon, CO) in high temperature molten salts has been demonstrated as a promising way of carbon capture, utilisation and storage (CCUS) in recent years. In a view of continuous operation, the electrolysis process should match very well with the CO2 absorption kinetics. At the same time, in consideration of the energy efficiency, a molten salt electrochemical cell running at lower temperature is more beneficial to a process powered by the fluctuating renewable electricity from solar/wind farms. Ternary carbonates (Li : Na : K = 43.5 : 31.5 : 25.0) and binary chlorides (Li : K = 58.5 : 41.5), two typical kinds of eutectic melt with low melting points and a wide electrochemical potential window, could be the ideal supporting electrolyte for the molten salt CO2 capture and electro-transformation (MSCC-ET) process. In this work, the CO2 absorption behaviour in Li2O/CaO containing carbonates and chlorides were investigated on a home-made gas absorption testing system. The electrode processes as well as the morphology and properties of carbon obtained in different salts are compared to each other. It was found that the composition of molten salts significantly affects the absorption of CO2, electrode processes and performance of the product. Furthermore, the relationship between the absorption and electro-transformation kinetics are discussed based on the findings.

18.
Environ Sci Technol ; 50(19): 10588-10595, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27602783

RESUMO

Efficient and high-flux capture of CO2 is the prerequisite of its utilization. Static absorption of CO2 with solid Li2O and molten salts (Li2O-free and Li2O-containing Li-Na-K carbonates) was investigated using a reactor with in situ pressure monitoring. The absorption capacity of dissolved Li2O was 0.835 molCO2/molLi2O at 723 K, larger than that of solid Li2O. For the solid Li2O absorbents, formation of solid Li2CO3 on the surface can retard the further reactions between Li2O and CO2, whereas the dissociation/dissolution effect of molten carbonate on Li2O improved the mass-specific absorption capacity of liquid Li2O. In Li2O-containing Li-Na-K molten carbonate, CO2 was mostly absorbed by alkaline oxide ions (O2-). The chemical interactions between CO2 and CO32- contributed to CO2 uptake via formation of multiple carbonate ions. The mass transfer of these absorbing ions was found as the dominating factor governing the rate of static absorption. Higher temperatures reduced the thermodynamic tendency of CO2 absorption, but a lower viscosity at elevated temperature was conducive to absorption kinetics. Compared with the commonly used CaO absorbent, Li2O was much more dissolvable in molten carbonate. The Li2O-containing molten carbonate is potentially a promising medium for industrial carbon capture and electrochemical transformation process.


Assuntos
Dióxido de Carbono/química , Lítio/química , Carbonatos/química , Sais/química , Termodinâmica
19.
PLoS One ; 19(9): e0307905, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39269943

RESUMO

BACKGROUND: Although blood glucose changes have been suggested to be a potential better target for clinical control than baseline blood glucose levels, the association of blood glucose changes with the prognosis in acute myocardial infarction (AMI) patients with diabetes mellitus (DM) is unclear. Herein, this study aimed to investigate association of short-term longitudinal trajectory of blood glucose with 30-day mortality in this population. METHODS: Data of AMI patients with DM were extracted from the Medical Information Mart for Intensive Care (MIMIC) database in 2003-2019 in this retrospective cohort study. The latent growth mixture modeling (LGMM) model was utilized to classify the 24-hour longitudinal trajectory of blood glucose of the patients. Kaplan-Meier (KM) curve was drawn to show 30-day mortality risk in patients with different trajectory classes. Univariate and multivariate Cox regression analyses were employed to explore the association of longitudinal trajectory of blood glucose within 24 hours after the ICU admission with 30-day mortality. Also, subgroups analysis of age, gender, and AMI types was performed. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 1,523 eligible patients, 227 (14.9%) died within 30 days. We identified 4 longitudinal trajectories of blood glucose, including class 1 (a low initial average blood glucose level with steady trend within 24 hours), class 2 (a high initial average blood glucose with gently decreased trend), class 3 (the highest initial average blood glucose with rapidly decreased trend) and class 4 (a high initial average blood glucose level with the trend that increased at first and then decreased). After adjusting for covariates, an average blood glucose level of ≥200 mg/dL was linked to higher risk of 30-day mortality, comparing to that of <140 mg/dL (HR = 1.80, 95%CI: 1.23-2.63). Comparing to patients whose longitudinal trajectory of blood glucose conformed to class 1, those with class 2 (HR = 2.52, 95%CI: 1.79-3.53) or class 4 (HR = 3.53, 95%CI: 2.07-6.03) seemed to have higher risk of 30-day mortality. Additionally, these associations were also significant in aged ≥60 years old, female, male, NSTEMI, and STEMI subgroups (all P<0.05). CONCLUSION: A low level of average blood glucose at the ICU admission or reducing blood glucose to a normal level quickly with adequate measures in 24 hours after ICU admission may be beneficial for AMI patients with DM to reduce the risk of 30-day mortality. These findings may provide some information for further exploration on appropriate range of blood glucose changes in clinical practice.


Assuntos
Glicemia , Diabetes Mellitus , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Glicemia/análise , Glicemia/metabolismo , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Diabetes Mellitus/mortalidade , Diabetes Mellitus/sangue , Bases de Dados Factuais , Estudos Longitudinais , Prognóstico , Estimativa de Kaplan-Meier , Fatores de Risco , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou mais
20.
Food Chem ; 457: 140192, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38941906

RESUMO

This study introduced an innovative magnetic effervescence-assisted microextraction method, streamlining the preparation of effervescent tablets through a one-pot method that blends a CO2 donor (Na2CO3) and an H+ donor (NaH2PO4) with bare magnetic particles (Fe3O4) and an adsorbent (hydroxylated multi-walled carbon nanotubes), followed by pressing. During the extraction process, the bare magnetic particles and adsorbent undergo in-situ self-assembly to create a magnetic adsorbent. The effervescence generates bubbles that enhance effective extraction and magnetism facilitates the easy separation of the magnetic adsorbent from the sample solution, completing the process within 4 min. Applied to organochlorine pesticide analysis in fruit juices and herbal extracts, the method exhibits excellent linearity (R2 > 0.993), sensitivity (detection limits: 0.010-0.125 ng/mL), accuracy (recoveries: 85.8-99.9%), and precision (RSDs < 9.7%) with GC-ECD. Overall, this approach stands out for its simplicity, cost-effectiveness, and suitability for on-site analysis, owing to its operational ease and independence from specialized equipment.


Assuntos
Hidrocarbonetos Clorados , Praguicidas , Microextração em Fase Sólida , Hidrocarbonetos Clorados/isolamento & purificação , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/química , Adsorção , Praguicidas/isolamento & purificação , Praguicidas/análise , Praguicidas/química , Microextração em Fase Sólida/métodos , Microextração em Fase Sólida/instrumentação , Contaminação de Alimentos/análise , Sucos de Frutas e Vegetais/análise , Microextração em Fase Líquida/métodos , Microextração em Fase Líquida/instrumentação , Análise Custo-Benefício , Limite de Detecção
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