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1.
Int Arch Allergy Immunol ; : 1-13, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36657406

RESUMO

INTRODUCTION: Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children. METHODS: The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry. RESULTS: Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury. CONCLUSION: Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells.

2.
Molecules ; 28(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36677818

RESUMO

In recent years, metal-organic framework (MOF)-based nanofibrous membranes (NFMs) have received extensive attention in the application of water treatment. Hence, it is of great significance to realize a simple and efficient preparation strategy of MOF-based porous NFMs. Herein, we developed a direct in situ formation of MOF/polymer NFMs using an electrospinning method. The porous MOF/polymer NFMs were constructed by interconnecting mesopores in electrospun composite nanofibers using poly(vinylpolypyrrolidone) (PVP) as the sacrificial pore-forming agent. MOF (MIL-88A) particles were formed inside the polyacrylonitrile (PAN)/PVP nanofibers in situ during electrospinning, and the porous MIL-88A/PAN (pMIL-88A/PAN) NFM was obtained after removing PVP by ethanol and water washing. The MOF particles were uniformly distributed throughout the pMIL-88A/PAN NFM, showing a good porous micro-nano morphological structure of the NFM with a surface area of 143.21 m2 g-1, which is conducive to its efficient application in dye adsorption and removal. Specifically, the dye removal efficiencies of the pMIL-88A/PAN NFM for amaranth red, rhodamine B, and acid blue were as high as 99.2, 94.4, and 99.8%, respectively. In addition, the NFM still showed over 80% dye removal efficiencies after five adsorption cycles. The pMIL-88A/PAN NFM also presented high adsorption capacities, fast adsorption kinetics, and high cycling stabilities during the processes of dye adsorption and removal. Overall, this work demonstrates that the in situ electrospun porous MOF/polymer NFMs present promising application potential in water treatment for organic dyestuff removal.

3.
iScience ; 26(1): 105890, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36691611

RESUMO

Searching for an efficient, durable, and low cost catalyst toward oxygen reduction reaction (ORR) is of paramount importance for the application of fuel cell technology. Herein, PtFeCoNiCu high-entropy alloy nanoparticles (PFCNC-HEA) is reported as electrocatalyst toward ORR. It shows remarkable ORR catalytic mass activity of 1.738 A mg-1 Pt at 0.90 V, which is 15.8 times higher than that of the state-of-art commercial Pt/C catalyst. It also exhibits outstanding stability with negligible voltage decay (3 mV) after 10k cycles accelerated durability test. High ORR activity is ascribed to the ligand effect caused by polymetallic elements, the optimization of the surface electronic structure, and the formation of multiple active sites on the surface. In the proton exchange membrane fuel cell setup, this cell delivers a power density of up to 1.380 W cm-2 with a cathodic Pt loading of 0.03 mgPt cm-2, demonstrating a promising catalyst design direction for highly efficient ORR.

4.
ACS Appl Mater Interfaces ; 15(3): 4643-4651, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36630692

RESUMO

High-entropy transition-metal oxides are potentially interesting cathode materials for lithium-ion batteries, among which high-entropy layered oxides are considered highly promising because there exist two-dimensional ion transport channels that may, in principle, enable fast ion transport. However, high-entropy layered oxides reported to date exhibit fast capacity fading in initial cycles and thus are hardly of any practical value. Here, we investigate the structural and property changes of a five-element layered oxide, LiNi0.2Co0.2Mn0.2Fe0.2Al0.2O2, using electrochemical and physical characterization techniques. It is revealed that the M3O4 phase formed at the surface of LiNi0.2Co0.2Mn0.2Fe0.2Al0.2O2 due to the migration of metal ions from octahedral sites of the transition-metal layer to tetrahedral 8a and octahedral sites of the lithium layer hinders the intercalation of lithium ion, which leads to the low initial Coulombic efficiency and fast decay of reversible capacity. This mechanism could be generally applicable to other high-entropy layered oxides with different elemental compositions.

5.
NAR Cancer ; 5(1): zcad004, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36694725

RESUMO

Alternative polyadenylation (APA) is a widespread posttranscriptional regulation process. APA generates diverse mRNA isoforms with different 3' UTR lengths, affecting mRNA expression, miRNA binding regulation and alternative splicing events. Previous studies have demonstrated the important roles of APA in tumorigenesis and cancer progression through diverse aspects. Thus, a comprehensive functional landscape of diverse APA events would aid in a better understanding of the underlying mechanisms related to APA in human cancers. Here, we built CAFuncAPA (https://relab.xidian.edu.cn/CAFuncAPA/) to systematically annotate the functions of 15478 APA events in human pan-cancers. Specifically, we first identified APA events associated with cancer survival and tumor progression. We annotated the potential downstream effects of APA on genes/isoforms expression, regulation of miRNAs, RNA binding proteins (RBPs) and alternative splicing events. Moreover, we also identified up-regulators of APA events, including the effects of genetic variants on poly(A) sites and RBPs, as well as the effect of methylation phenotypes on APA events. These findings suggested that CAFuncAPA can be a helpful resource for a better understanding of APA regulators and potential functions in cancer biology.

6.
J Nanobiotechnology ; 21(1): 2, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36593514

RESUMO

BACKGROUND: Silica nanoparticles (SiNPs) have been demonstrated to have beneficial effects on plant growth and development, especially under biotic and abiotic stresses. However, the mechanisms of SiNPs-mediated plant growth strengthening are still unclear, especially under field condition. In this study, we evaluated the effect of SiNPs on the growth and sugar and hormone metabolisms of wheat in the field. RESULTS: SiNPs increased tillers and elongated internodes by 66.7% and 27.4%, respectively, resulting in a larger biomass. SiNPs can increase the net photosynthetic rate by increasing total chlorophyll contents. We speculated that SiNPs can regulate the growth of leaves and stems, partly by regulating the metabolisms of plant hormones and soluble sugar. Specifically, SiNPs can increase auxin (IAA) and fructose contents, which can promote wheat growth directly or indirectly. Furthermore, SiNPs increased the expression levels of key pathway genes related to soluble sugars (SPS, SUS, and α-glucosidase), chlorophyll (CHLH, CAO, and POR), IAA (TIR1), and abscisic acid (ABA) (PYR/PYL, PP2C, SnRK2, and ABF), whereas the expression levels of genes related to CTKs (IPT) was decreased after SiNPs treatment. CONCLUSIONS: This study shows that SiNPs can promote wheat growth and provides a theoretical foundation for the application of SiNPs in field conditions.


Assuntos
Nanopartículas , Triticum , Triticum/metabolismo , Dióxido de Silício , Clorofila , Açúcares , Hormônios
7.
Nanoscale ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606731

RESUMO

Dry eye disease (DED), a complex ocular surface disease with a high prevalence rate, is associated with corneal injury, excess oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to address all the deleterious factors or to achieve a clinical cure due to their temporary or side effects. Here, we prepared a multiple-functional eyedrop based on the deposition of gold nanoparticles (AuNPs) reduced by ascorbic acid (AA) onto the exosomal phospholipid membrane of mesenchymal stem cell (mExo)-derived exosomes in situ (mExo@AA). The therapeutic value of mExo@AA for DED was demonstrated in a mouse DED model. Combining the benefits of mExo and AA, mExo@AA effectively improves corneal epithelium recovery and anti-inflammation capacity, decreases corneal reactive oxygen species, and restores tear secretion without adverse effects. Thus, this study suggests that mExo@AA is effective and safe as a therapeutic agent for the treatment of DED.

8.
Biochim Biophys Acta Proteins Proteom ; 1871(3): 140897, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36642204

RESUMO

Natural and artificial nucleases have extensive applications in biotechnology and biomedicine. The exploration of protein with potential DNA cleavage activity also inspires the design of artificial nuclease and helps to understand the physiological process of DNA damage. In this study, we engineered four human cytochrome c (Cyt c) mutants (N52S, N52A, I81N, and I81D Cyt c), which showed enhanced DNA cleavage activity and degradation in comparison with WT Cyt c, especially under acidic conditions. The mechanism assays revealed that the superoxide (O2•-) plays an important role in the nuclease reaction. The kinetic assays showed that the peroxidase activity of the I81D Cyt c mutant enhanced up to 9-fold at pH 5. This study suggests that the mutations of Ile81 and Asn52 in Ω-loop C/D are critical for the nuclease activity of Cyt c, which may have physiological significance in DNA damage and potential applications in biomedicine.

9.
Small ; : e2206462, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36642788

RESUMO

Developing efficient heterojunction electrocatalysts and uncovering their atomic-level interfacial mechanism in promoting sulfur-species adsorption-electrocatalysis are interesting yet challenging in lithium-sulfur batteries (LSBs). Here, multifunctional SnS2 -MXene Mott-Schottky heterojunctions with interfacial built-in electric field (BIEF) are developed, as a model to decipher their BIEF effect for accelerating synergistic adsorption-electrocatalysis of bidirectional sulfur conversion. Theoretical and experimental analysis confirm that because Ti atoms in MXene easily lost electrons, whereas S atoms in SnS2 easily gain electrons, and under Mott-Schottky influence, SnS2 -MXene heterojunction forms the spontaneous BIEF, leading to the electronic flow from MXene to SnS2 , so SnS2 surface easily bonds with more lithium polysulfides. Moreover, the hetero-interface quickly propels abundant Li+ /electron transfer, so greatly lowering Li2 S nucleation/decomposition barrier, promoting bidirectional sulfur conversion. Therefore, S/SnS2 -MXene cathode displays a high reversible capacity (1,188.5 mAh g-1 at 0.2 C) and a stable long-life span with 500 cycles (≈82.7% retention at 1.0 C). Importantly, the thick sulfur cathode (sulfur loading: 8.0 mg cm-2 ) presents a large areal capacity of 7.35 mAh cm-2 at lean electrolyte of 5.0 µL mgs -1 . This work verifies the substantive mechanism that how BIEF optimizes the catalytic performance of heterojunctions and provides an effective strategy for deigning efficient bidirectional Li-S catalysts in LSBs.

10.
Neurosci Bull ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622575

RESUMO

The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity (OIH) and analgesic tolerance. Among the different forms of OIH and tolerance, the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved. Here we demonstrated that the loss of peripheral µ-opioid receptors (MORs) or MOR-expressing neurons attenuated thermal tolerance, but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance. To confirm this result, we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aß-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons. Consistent with the behavioral results, peripheral MOR loss did not prevent the opening of Aß mechanical allodynia pathways in the spinal dorsal horn. Therefore, the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance. Future studies should focus more on central mechanisms.

11.
J Cereb Blood Flow Metab ; : 271678X221135419, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635875

RESUMO

Post-stroke depression exacerbates neurologic deficits and quality of life. Depression after ischemic stroke is known to some extent. However, depression after intracerebral hemorrhage (ICH) is relatively unknown. Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective effects in animal models, but its impact after ICH is unknown. In this study, we investigated the effect of EE on long-term functional outcomes in mice subjected to collagenase-induced striatal ICH. Mice were subjected to ICH with the standard environment (SE) or ICH with EE for 6 h/day (8:00 am-2:00 pm). Depressive, anxiety-like behaviors and cognitive tests were evaluated on day 28 with the sucrose preference test, tail suspension test, forced swim test, light-dark transition experiment, morris water maze, and novel object recognition test. Exposure to EE improved neurologic function, attenuated depressive and anxiety-like behaviors, and promoted spatial learning and memory. These changes were associated with increased expression of transcription factor Nrf2 and brain-derived neurotrophic factor (BDNF) and inhibited glutaminase activity in the perihematomal tissue. However, EE did not change the above behavioral outcomes in Nrf2-/- mice on day 28. Furthermore, exposure to EE did not increase BDNF expression compared to exposure to SE in Nrf2-/- mice on day 28 after ICH. These findings indicate that EE improves long-term outcomes in sensorimotor, emotional, and cognitive behavior after ICH and that the underlying mechanism involves the Nrf2/BDNF/glutaminase pathway.

12.
J Am Chem Soc ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700857

RESUMO

Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, NAD+, are closely associated with numerous diseases. While supplementing cells with precursors needed for NAD+ synthesis has shown poor efficacy in combatting NAD+ decline, an alternative strategy is the development of synthetic materials that catalyze the oxidation of NADH into NAD+, thereby taking over the natural role of the NADH oxidase (NOX) present in bacteria. Herein, we discovered that metal-nitrogen-doped graphene (MNGR) materials can catalyze the oxidation of NADH into NAD+. Among MNGR materials with different transition metals, Fe-, Co-, and Cu-NGR displayed strong catalytic activity combined with >80% conversion of NADH into NAD+, similar specificity to NOX for abstracting hydrogen from the pyridine ring of nicotinamide, and higher selectivity than 51 other nanomaterials. The NOX-like activity of FeNGR functioned well in diverse cell lines. As a proof of concept of the in vivo application, we showed that FeNGR could specifically target the liver and remedy the metabolic flux anomaly in obesity mice with NAD+-deficient cells. Overall, our study provides a distinct insight for exploration of drug candidates by design of synthetic materials to mimic the functions of unique enzymes (e.g., NOX) in bacteria.

13.
Plant Sci ; : 111546, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464025

RESUMO

N6-methyladenosine (m6A) is the most widely distributed and most abundant type of mRNA modification in eukaryotic. It provides a posttranscriptional level regulation of gene expression by regulating pre-mRNA splicing, mRNA degradation, or mRNA translational efficiency etc. The function of m6A modification is decoded by binding proteins that can specially bind to m6A. YT521-B homology (YTH) family proteins are the most important m6A-binding proteins in mammals and Arabidopsis. However, their roles in growth and development remain unknown. Here, we demonstrated that the YTH family proteins YTH03, YTH05 and YTH10 specifically bind to m6A-containing RNAs. Knockout of YTH03, YTH05 or YTH10 causes reduced plant height. Further research showed that simultaneously knockout of YTH03, YTH05 and YTH10 shows severe dwarf phenotype, suggesting these three genes regulate rice plant height in a functionally redundant manner. Additional transcriptome study showed that the reduced plant height of the yth03/05/10 triple mutant may be due to the blocked of diterpenoid and brassinolide synthesis pathway. Overall, we demonstrate that YTH03, YTH05 and YTH10 are all the m6A readers in rice and redundantly regulate rice plant height through the hormonal related pathway.

14.
Orthop Surg ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36458444

RESUMO

OBJECTIVE: The percutaneous IS screws and the minimally invasive percutaneous plate are the most popular internal methods for Zone II unstable sacral fractures. However, the choice of fixation remains controversial for orthopaedic surgeons. The purpose of study was to evaluate and compare the clinical results of percutaneous iliosacral (IS) screw fixation under three-dimensional (3D) navigation and minimally invasive percutaneous plate fixation in the treatment of Zone II unstable sacral fractures. METHODS: A retrospective study was performed, including 64 patients with Zone II unstable sacral fractures who underwent percutaneous IS screw fixation under 3D navigation (navigation group) and minimally invasive percutaneous plate fixation (plate group) from January 2011 and March 2021 in our department. The age, gender, fracture type, mechanism of injury, injury severity score (ISS), time from admission to operation, operative time, intraoperative blood loss, hospital stay, incision length, follow-up time, time to clinical healing, and complications were recorded and analyzed. Matta standard was used to assess fracture reduction outcomes. The Majeed function system assessed functional outcomes at the last follow-up. RESULTS: The average follow-up time was (14.42 ± 1.57) months in the navigation group and (14.79 ± 1.37) months in the plate group. No statistical difference between the two groups in age, gender, fracture type, mechanism of injury, ISS, time from admission to operation, and time to clinical healing. However, significant differences were detected in operative time, intraoperative blood loss, hospital stay, and incision length (p < 0.001). According to Matta standard at 2 days postoperatively, the excellent and good rate was 91.42% in the navigation group, and it was 93.10% in the plate group. There was no significant difference between the two groups (p = 0.961). According to Majeed function system at the follow-up, the excellent and good rate was 97.14% in the navigation group, and 93.10% in the plate group. The difference between the two groups was not statistically significant (p = 0.748). There were no neurovascular injuries associated with this procedure. The incidence of complications was 44.82% (13/29) in the plate group, while 14.28% (5/35) in the navigation group (p = 0.007). CONCLUSION: This study found that compared with minimally invasive percutaneous plate fixation, percutaneous IS screw fixation under 3D navigation is a suitable option for the treatment of Zone II unstable sacral fractures. This approach is characterized by its shorter operation time, less surgical trauma, less bleeding, less hospital time, and fewer complications.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36459266

RESUMO

BACKGROUND: Left bundle branch area pacing (LBBAP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We aimed to compare the morbidity and mortality associated with LBBAP versus BVP in patients undergoing CRT implantation. METHODS: Consecutive patients who received CRT from two high-volume implantation centers were retrospectively recruited. The primary endpoint was a composite of all-cause death and heart failure hospitalization, and the secondary endpoint was all-cause death. RESULTS: A total of 491 patients receiving CRT (154 via LBBAP and 337 via BVP) were included, with a median follow-up of 31 months. The primary endpoint was reached by 21 (13.6%) patients in the LBBAP group, as compared with 74 (22.0%) patients in the BVP group [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.43-1.14, P = 0.15]. There were 10 (6.5%) deaths in the LBBAP group, as compared with 31 (9.2%) in the BVP group (HR 0.91, 95% CI 0.44-1.86, P = 0.79). No significant difference was observed in the risk of either the primary or secondary endpoint between LBBAP and BVP after multivariate Cox regression (HR 0.74, 95% CI 0.45-1.23, P = 0.24, and HR 0.77, 95% CI 0.36-1.67, P = 0.51, respectively) or propensity score matching (HR 0.72, 95% CI 0.41-1.29, P = 0.28, and HR 0.69, 95% CI 0.29-1.65, P = 0.40, respectively). CONCLUSION: LBBAP was associated with a comparable effect on morbidity and mortality relative to BVP in patients with indications for CRT.

16.
Macromol Rapid Commun ; : e2200814, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36459585

RESUMO

Excessive exudate secreted from diabetic wounds often results in skin overhydration, severe infections and secondary damage upon dressing changes. However, conventional wound dressings are difficult to synchronously realize the non-maceration of wound sites and rapid exudate transport due to their random porous structure. Herein, a self-pumping Janus hydrogel with aligned channels (JHA) composed of hydrophilic poly (ethylene glycol) diacrylate (PEGDA) hydrogel layer and hydrophobic polyurethane (PU)/graphene oxide (GO)/ polytetrafluoroethylene (PTFE) layer is designed to rapidly export exudate and accelerate diabetic wound healing. In the design, the ice-templating process endows the hydrophilic hydrogel layer with superior liquid transport ability and mechanical strength due to the formation of aligned channel structure. The hydrophobic layer with controlled thickness functions as an effective barrier to prevent exudate from wetting the skin surface. Experiments in diabetic rat model show that JHA can significantly promote re-epithelialization and collagen deposition, shorten the inflammation phase and accelerate wound healing. This unique JHA dressing may have great potential for real-life usage in clinical patients. This article is protected by copyright. All rights reserved.

17.
Int J Stroke ; : 17474930221145259, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36461792

RESUMO

Objective To identify risk factors for early neurological deterioration (END) in acute lacunar stroke patients, and its influence on functional outcome.Methods Consecutive acute lacunar stroke patients defined by MRI between January 2018 and June 2020 were included in the study. END was defined as any persisting increase in National Institutes of Health Stroke Scale (NIHSS) score of ≥2 points post admission, and favorable outcome was defined as a modified Rankin Scale (mRS) of 0-2 at discharge. Univariable and multivariable logistic regression were performed to identify risk factors related to END, as well as the influence of END on functional outcome.Results Among a total of 638 lacunar stroke patients (420 males (65.8%), median age 66 years (IQR:56-74)), 108 (16.9%) developed END, and 94.4% (102/108) of the END occurred within 72 h post admission. Admission NIHSS score (aOR 1.132, 95%CI 1.046-1.225, p=0.002), female (aOR 2.752, 95%CI 1.277-5.933, p=0.010), admission systolic blood pressure (SBP) (160-179mmHg) (aOR 9.395, 95%CI 4.310-20.479, p<0.001) and admission SBP (≥180mmHg) (aOR 16.030, 95%CI 5.991-42.891, p<0.001) were significantly associated with END. Delay time from onset to admission (aOR 0.995, 95%CI 0.990-1.000, p=0.031) , SBP dropping (≥20mmHg) within 3 days or when END occurred (aOR 0.037, 95%CI 0.016-0.086, p<0.001) and thalamic lacunar infarction (aOR 0.098, 95%CI 0.012-0.827, p=0.033) were inversely associated with END. END (aOR 12.374, 95%CI 6.881-22.254, p<0.001) and higher admission NIHSS score (aOR 1.488, 95%CI 1.359-1.629, p<0.001) predicted unfavorable outcome at discharge.Conclusion END in lacunar stroke patients is common and is associated with unfavorable outcome. Admission high SBP is a potentially modifiable risk factor for prevention of END, but this needs further investigation.

18.
Plant Physiol ; 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36461944

RESUMO

Fructokinase (FRK) activates fructose through phosphorylation, which sends the activated fructose into primary metabolism and regulates fructose signaling capabilities in plants. The apple (Malus × domestica) FRK gene MdFRK2 shows especially high affinity to fructose, and its overexpression decreases fructose levels in the leaves of young plants. However, in the current study of mature plants, fruits of transgenic apple trees overexpressing MdFRK2 accumulated a higher level of fructose than wild-type (WT) fruits (at both young and mature stages). Transgenic apple trees with high mRNA MdFRK2 expression showed no significant differences in MdFRK2 protein abundance or FRK enzyme activity compared to WT in mature leaves, young fruits, and mature fruits. Immunoprecipitation-mass spectrometry analysis identified an skp1, cullin, F-box (SCF) E3 ubiquitin ligase, calcyclin-binding protein (CacyBP), that interacted with MdFRK2. RNA-sequencing analysis provided evidence for ubiquitin-mediated post-transcriptional regulation of MdFRK2 protein for the maintenance of fructose homeostasis in mature leaves and fruits. Further analyses suggested an MdCacyBP-MdFRK2 regulatory module in which MdCacyBP interacts with and ubiquitinates MdFRK2 to facilitate its degradation by the 26S proteasome, thus decreasing the FRK enzyme activity to elevate fructose concentration in transgenic apple trees. This result uncovered an important mechanism underlying plant fructose homeostasis in different organs through regulating MdFRK2 protein level via ubiquitination and degradation. Our study provides usable data for the future improvement of apple flavor and expands our understanding of the molecular mechanisms underlying plant fructose content and signaling regulation.

19.
Artif Intell Med ; 134: 102424, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36462894

RESUMO

Radiological images have shown promising effects in patient prognostication. Deep learning provides a powerful approach for in-depth analysis of imaging data and integration of multi-modal data for modeling. In this work, we propose SurvivalCNN, a deep learning structure for cancer patient survival prediction using CT imaging data and non-imaging clinical data. In SurvivalCNN, a supervised convolutional neural network is designed to extract volumetric image features, and radiomics features are also integrated to provide potentially different imaging information. Within SurvivalCNN, a novel multi-thread multi-layer perceptron module, namely, SurvivalMLP, is proposed to perform survival prediction from censored survival data. We evaluate the proposed SurvivalCNN framework on a large clinical dataset of 1061 gastric cancer patients for both overall survival (OS) and progression-free survival (PFS) prediction. We compare SurvivalCNN to three different modeling methods and examine the effects of various sets of data/features when used individually or in combination. With five-fold cross validation, our experimental results show that SurvivalCNN achieves averaged concordance index 0.849 and 0.783 for predicting OS and PFS, respectively, outperforming the compared state-of-the-art methods and the clinical model. After future validation, the proposed SurvivalCNN model may serve as a clinical tool to improve gastric cancer patient survival estimation and prognosis analysis.


Assuntos
Aprendizado Profundo , Radiologia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Pesquisa , Redes Neurais de Computação
20.
Front Vet Sci ; 9: 1032945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467633

RESUMO

Clostridium difficile infection (CDI) in human and animals belonged usually to antibiotic-associated diarrhea, ranging in severity from mild to life-threatening intestinal tract illnesses. This study aimed to isolation and characterization, toxin genes test, molecular typing, and drug sensitivity of Clostridium difficile (C. difficile) which were isolated from clinical diseased dogs and cats. A total of 247 clinical samples were collected from five animal hospitals in Lanzhou City of Northwest China, of which dogs and cats accounted for 74.9% (185/247) and 25.1% (62/247), respectively. We successfully identified 24 C. difficile strains by 16S rRNA and Matrix-Assisted Laser Desorption/Ionization Time of Fight Mass Spectroscopy (MALDI-TOF-MS). 10.3% (19/185) of dogs and 8.1% (5/62) of cats were positive for C. difficile. Among them, 16 strains were toxic and 8 were non-toxic, with a toxic rate of 57.9% (11/19) in dogs and 100% (5/5) in cats. A total of 10 STs and 10 RTs were identified in this study. The percentages of ST42 (RT106) and ST2 (RT014/LW01) among 16 toxic strains were 41.7 and 12.5%, respectively. However, ST3 (RT001), ST1 (RT027), ST133 (LW04), and ST-UN (LW04) had only one strain. ST42 (RT106) was the most common genotype and RT027 strain was first isolated in China from pets. Antimicrobial susceptibility test showed that isolates were extremely sensitive to vancomycin and metronidazole but were resistant to erythromycin and ciprofloxacin. The drug resistant rates to clindamycin, levofloxacin, moxifloxacin and meropenem were 62.5, 20.8, 16.7, and 8.3%, respectively. In conclusion, C. difficile was quietly prevalent in dogs and cats in Lanzhou city with RT106 and RT014 as the main ribotypes. The CDI in pets should be paying more attention and further studies are needed.

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