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1.
Sci Rep ; 14(1): 12895, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839812

ABSTRACT

Aiming at the practical teaching of intelligent manufacturing majors faced with lack of equipment, tense teachers and other problems such as high equipment investment, high material loss, high teaching risk, difficult to implement internship, difficult to observe production, difficult to reproduce the results, and so on, we take the electrical automation technology, mechatronics technology and industrial robotics technology majors of intelligent manufacturing majors as an example, and design and establish a virtual simulation teaching platform for intelligent manufacturing majors by using the cloud computing platform, edge computing technology, and terminal equipment synergy. The platform includes six major virtual simulation modules, including virtual simulation of electrician electronics and PLC control, virtual and real combination of typical production lines of intelligent manufacturing, dual-axis collaborative robotics workstation, digital twin simulation, virtual disassembly of industrial robots, virtual simulation of magnetic yoke axis flexible production line. The platform covers the virtual simulation teaching content of basic principle experiments, advanced application experiments, and advanced integration experiments in intelligent manufacturing majors. In order to test the effectiveness of this virtual simulation platform for practical teaching in engineering, this paper organizes a teaching practice activity involving 246 students from two parallel classes of three different majors. Through a one-year teaching application, we analyzed the data on the grades of 7 core courses involved in three majors in one academic year, the proportion of participation in competitions and innovative activities, the number of awards and certificates of professional qualifications, and the subjective questionnaires of the testers. The analysis shows that the learners who adopt the virtual simulation teaching platform proposed in this paper for practical teaching are better than the learners under the traditional teaching method in terms of academic performance, proportion of participation in competitions and innovative activities, and proportion of awards and certificates by more than 13%, 37%, 36%, 27% and 22%, respectively. Therefore, the virtual simulation teaching platform of intelligent manufacturing established in this paper has obvious superiority in solving the problem of "three highs and three difficulties" existing in the practical teaching of engineering, and according to the questionnaire feedback from the testers, the platform can effectively alleviate the shortage of practical training equipment, stimulate the interest in learning, and help to broaden and improve the knowledge system of the learners.

2.
Anticancer Drugs ; 35(5): 466-480, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38507233

ABSTRACT

Anoikis is a programmed cell death process triggered when cells are dislodged from the extracellular matrix. Numerous long noncoding RNAs (lncRNAs) have been identified as significant factors associated with anoikis resistance in various tumor types, including glioma, breast cancer, and bladder cancer. However, the relationship between lncRNAs and the prognosis of hepatocellular carcinoma (HCC) has received limited research attention. Further research is needed to investigate this potential link and understand the role of lncRNAs in the progression of HCC. We developed a prognostic signature based on the differential expression of lncRNAs implicated in anoikis in HCC. A co-expression network of anoikis-related mRNAs and lncRNAs was established using data obtained from The Cancer Genome Atlas (TCGA) for HCC. Cox regression analyses were conducted to formulate an anoikis-related lncRNA signature (ARlncSig) in a training cohort, which was subsequently validated in both a testing cohort and a combined dataset comprising the two cohorts. Receiver operating characteristic curves, nomograms, and decision curve analyses based on the ARlncSig score and clinical characteristics demonstrated robust predictive ability. Moreover, gene set enrichment analysis revealed significant enrichment of several immune processes in the high-risk group compared to the low-risk group. Furthermore, significant differences were observed in immune cell subpopulations, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy between the high- and low-risk groups. Lastly, we validated the expression levels of the five lncRNAs included in the signature using quantitative real-time PCR. In conclusion, our ARlncSig model holds substantial predictive value regarding the prognosis of HCC patients and has the potential to provide clinical guidance for individualized immunotherapy. In this study, we obtained 36 genes associated with anoikis from the Gene Ontology and Gene Set Enrichment Analysis databases. We also identified 22 differentially expressed lncRNAs that were correlated with these genes using data from TCGA. Using Cox regression analyses, we developed an ARlncSig in a training cohort, which was then validated in both a testing cohort and a combined cohort comprising data from both cohorts. Additionally, we collected eight pairs of liver cancer tissues and adjacent tissues from the Affiliated Tumor Hospital of Nantong University for further analysis. The aim of this study was to investigate the potential of ARlncSig as a biomarker for liver cancer prognosis. The study developed a risk stratification system called ARlncSig, which uses five lncRNAs to categorize liver cancer patients into low- and high-risk groups. Patients in the high-risk group exhibited significantly lower overall survival rates compared to those in the low-risk group. The model's predictive performance was supported by various analyses including the receiver operating characteristic curve, nomogram calibration, clinical correlation analysis, and clinical decision curve. Additionally, differential analysis of immune function, immune checkpoint, response to chemotherapy, and immune cell subpopulations revealed significant differences between the high- and low-risk groups. Finally, quantitative real-time PCR validated the expression levels of the five lncRNAs. In conclusion, the ARlncSig model demonstrates critical predictive value in the prognosis of HCC patients and may provide clinical guidance for personalized immunotherapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/genetics , RNA, Long Noncoding/genetics , Anoikis/genetics , Liver Neoplasms/genetics , Prognosis
3.
Small ; 20(25): e2308724, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38229571

ABSTRACT

In future information storage and processing, magnonics is one of the most promising candidates to replace traditional microelectronics. Yttrium iron garnet (YIG) films with perpendicular magnetic anisotropy (PMA) have aroused widespread interest in magnonics. Obtaining strong PMA in a thick YIG film with a small lattice mismatch (η) has been fascinating but challenging. Here, a novel strategy is proposed to reduce the required minimum strain value for producing PMA and increase the maximum thickness for maintaining PMA in YIG films by slight oxygen deficiency. Strong PMA is achieved in the YIG film with an η of only 0.4% and a film thickness up to 60 nm, representing the strongest PMA for such a small η reported so far. Combining transmission electron microscopy analyses, magnetic measurements, and a theoretical model, it is demonstrated that the enhancement of PMA physically originates from the reduction of saturation magnetization and the increase of magnetostriction coefficient induced by oxygen deficiency. The Gilbert damping values of the 60-nm-thick YIG films with PMA are on the order of 10-4. This strategy improves the flexibility for the practical applications of YIG-based magnonic devices and provides promising insights for the theoretical understanding and the experimental enhancement of PMA in garnet films.

4.
J Control Release ; 365: 583-601, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38048963

ABSTRACT

The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood-brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/miR-195 complex (DPMT@PEI/miR-195) that was engineered through dual modifications to contain P-aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/miR-195 or donepezil alone. Furthermore, DPMT@PEI/miR-195 effectively attenuated the positive signals of Aß, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.


Subject(s)
Alzheimer Disease , MicroRNAs , Humans , Mice , Animals , Infant , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Liposomes/therapeutic use , Amyloid beta-Protein Precursor/metabolism , Donepezil/therapeutic use , Mice, Transgenic , MicroRNAs/genetics , MicroRNAs/therapeutic use , MicroRNAs/metabolism , Disease Models, Animal , Amyloid beta-Peptides/metabolism
5.
Plant Cell Rep ; 42(12): 2011-2022, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37812280

ABSTRACT

KEY MESSAGE: OsERF096 negatively regulates rice cold tolerance and mediates IAA biosynthesis and signaling under cold stress. The APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors play important roles in regulating plant tolerance to abiotic stress. OsERF096 was previously identified as a direct target of miR1320, and was suggested to negatively regulate rice cold tolerance. In this study, we performed RNA-sequencing and targeted metabolomics assays to reveal the regulatory roles of OsERF096 in cold stress response. GO and KEGG analysis of differentially expressed genes showed that the starch and sucrose metabolism, plant-pathogen interaction, and plant hormone signal transduction pathways were significantly enriched. Quantification analysis confirmed a significant difference in sugar contents among WT and OsERF096 transgenic lines under cold treatment. Targeted metabolomics analysis uncovered that IAA accumulation and signaling were modified by OsERF096 in response to cold stress. Expectedly, qRT-PCR assays confirmed significant OsIAAs and OsARFs expression changes in OsERF096 transgenic lines. Finally, we identified three targets of OsERF096 based on RNA-seq, qRT-PCR, and dual-LUC assays. In summary, these results revealed the multiple regulatory roles of OsERF096 in cold stress response.


Subject(s)
Oryza , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Cold-Shock Response/genetics , Oryza/genetics , Oryza/metabolism , Gene Expression Regulation, Plant , Ethylenes , Plant Proteins/genetics , Plant Proteins/metabolism
6.
Adv Sci (Weinh) ; 10(23): e2302490, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37300359

ABSTRACT

Organic electrode materials for lithium-ion batteries have attracted significant attention in recent years. Polymer electrode materials, as compared to small-molecule electrode materials, have the advantage of poor solubility, which is beneficial for achieving high cycling stability. However, the severe entanglement of polymer chains often leads to difficulties in preparing nanostructured polymer electrodes, which is vital for achieving fast reaction kinetics and high utilization of active sites. This study demonstrates that these problems can be solved by the in situ electropolymerization of electrochemically active monomers in nanopores of ordered mesoporous carbon (CMK-3), combining the advantages of the nano-dispersion and nano-confinement effects of CMK-3 and the insolubility of the polymer materials. The as-prepared nanostructured poly(1-naphthylamine)/CMK-3 cathode exhibits a high active site utilization of 93.7%, ultrafast rate capability of 60 A g-1 (≈320 C), and an ultralong cycle life of 10000 cycles at room temperature and 45000 cycles at -15 °C. The study herein provides a facile and effective method that can simultaneously solve both the dissolution problem of small-molecule electrode materials and the inhomogeneous dispersion issue of polymer electrode materials.

7.
Appl Radiat Isot ; 197: 110791, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37054664

ABSTRACT

The accuracy of activity determination for activated nuclide 56Mn is the key to the manganese bath method applying to the characterization of radionuclide neutron source. As an alternative to the 4π(C)-γ method, TDCR-Cerenkov method could also be applied to the measurement of 56Mn in the manganese bath device, if the existing calculation model is extended. There are two difficulties when the existing TDCR-Cerenkov method is applied to the activity determination of 56Mn. One is that the efficiency computation of gamma transitions, and the other is the interference contributed by Cerenkov photons emitted in the photomultiplier windows induced by Compton scattering. In this study, the above two difficulties are solved by extending the calculation model. For efficiency computation, the decay scheme of 56Mn is taken into account in the calculation of efficiency. Among them, the efficiency of gamma transition is calculated from the simulated secondary electronic spectra. In addition, Cerenkov photons emitted in photomultiplier windows are corrected by additional light proof experiment and improved calculation model. The results derived from this extended method are in good agreement with other standardization technique.

8.
Blood Adv ; 7(5): 778-799, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36399523

ABSTRACT

Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. However, targeted studies on this vulnerable population are scarce. Here, we applied multiomics single-cell analyses of immune profiles from matching airways and blood samples of Black/AA patients during acute SARS-CoV-2 infection. Transcriptional reprogramming of infiltrating IFITM2+/S100A12+ mature neutrophils, likely recruited via the IL-8/CXCR2 axis, leads to persistent and self-sustaining pulmonary neutrophilia with advanced features of acute respiratory distress syndrome (ARDS) despite low viral load in the airways. In addition, exacerbated neutrophil production of IL-8, IL-1ß, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to acute respiratory distress syndrome in a well-defined patient population disproportionally affected by severe COVID-19.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/pathology , Neutrophils , Interleukin-8 , SARS-CoV-2 , Viral Load , Lung/pathology , Membrane Proteins
9.
Inflamm Bowel Dis ; 29(2): 274-285, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36206201

ABSTRACT

BACKGROUND: Crohn's disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn's. METHODS: Ileal biopsies were obtained from (1) control subjects (n = 6), (2) treatment-naïve patients (n = 7), and (3) established (n = 14) Crohn's patients along with remission (n = 3) and refractory (n = 11) treatment groups. The biopsies processed using 10x Genomics single cell 5' yielded 139 906 cells. Gene expression count matrices of all samples were analyzed by reciprocal principal component integration, followed by clustering analysis. Manual annotations of the clusters were performed using canonical gene markers. Cell type proportions, differential expression analysis, and gene ontology enrichment were carried out for each cell type. RESULTS: We identified 3 cellular compartments with 9 epithelial, 1 stromal, and 5 immune cell subtypes. We observed differences in the cellular composition between control, treatment-naïve, and established groups, with the significant changes in the epithelial subtypes of the treatment-naïve patients, including microfold, tuft, goblet, enterocyte,s and BEST4+ cells. Surprisingly, fewer changes in the composition of the immune compartment were observed; however, gene expression in the epithelial and immune compartment was different between Crohn's phenotypes, indicating changes in cellular activity. CONCLUSIONS: Our study identified cellular and transcriptional signatures associated with treatment-naïve Crohn's disease that collectively point to dysfunction of the intestinal barrier with an increase in inflammatory cellular activity. Our analysis also highlights the heterogeneity among patients within the same disease phenotype, shining a new light on personalized treatment responses and strategies.


Subject(s)
Crohn Disease , Humans , Crohn Disease/pathology , Intestinal Mucosa/pathology , Ileum/pathology , Intestines/pathology , Inflammation/pathology
10.
Front Psychol ; 13: 1048943, 2022.
Article in English | MEDLINE | ID: mdl-36507012

ABSTRACT

Auditory over visual advantage in temporal processing is generally appreciated, such as the well-established auditory superiority in sensorimotor timing. To test for a possible visual superiority in temporal processing, here, we present a data set composed of a large 60 subjects sample and a data set including eight smaller samples of approximately 15 subjects, showing that synchronization to a temporally regular sequence was more stable for a visual bouncing ball (VB) than for auditory tones (ATs). The results demonstrate that vision can be superior over audition in sensorimotor timing under optimized conditions, challenging the generally believed auditory superiority in temporal processing. In contrast to the auditory-specific biological substrates of timing in sensorimotor interaction, the present finding points to tight visual-motor cortical coupling in sensorimotor timing.

11.
Front Oncol ; 12: 989316, 2022.
Article in English | MEDLINE | ID: mdl-36185225

ABSTRACT

Objective: To explore the prognostic value of radiological features and serum indicators in patients treated with postoperative adjuvant transarterial chemoembolization (PA-TACE) and develop a prognostic model to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC) treated with PA-TACE. Method: We enrolled 112 patients (75 in the training cohort and 37 in the validation cohort) with HCC treated with PA-TACE after surgical resection at the Affiliated Hospital of Nantong University between January 2012 and June 2015. The independent OS predictors were determined using univariate and multivariate regression analyses. Decision curve analyses and time-dependent receiver operating characteristic curve analysis was used to verify the prognostic performance of the different models; the best model was selected to establish a multi-dimensional nomogram for predicting the OS of HCC patients treated with PA-TACE. Result: Multivariate regression analyses indicated that rim-like arterial phase enhancement (IRE), peritumor capsule (PTC), and alanine aminotransferase to hemoglobin ratio (AHR) were independent predictors of OS after PA-TACE. The combination of AHR had the best clinical net benefit and we constructed a prognostic nomogram based on IRE, PTC, and AHR. The calibration curve showed good fit between the predicted nomogram's curve and the observed curve. Conclusion: Our preliminary study confirmed the prognostic value of AHR, PTC, and IRE and established a nomogram that can predict the OS after PA-TACE treatment in patients with HCC.

12.
iScience ; 25(10): 105123, 2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36185375

ABSTRACT

Single-cell transcriptomics enables the definition of diverse human immune cell types across multiple tissues and disease contexts. Further deeper biological understanding requires comprehensive integration of multiple single-cell omics (transcriptomic, proteomic, and cell-receptor repertoire). To improve the identification of diverse cell types and the accuracy of cell-type classification in multi-omics single-cell datasets, we developed SuPERR, a novel analysis workflow to increase the resolution and accuracy of clustering and allow for the discovery of previously hidden cell subsets. In addition, SuPERR accurately removes cell doublets and prevents widespread cell-type misclassification by incorporating information from cell-surface proteins and immunoglobulin transcript counts. This approach uniquely improves the identification of heterogeneous cell types and states in the human immune system, including rare subsets of antibody-secreting cells in the bone marrow.

13.
Comput Biol Med ; 148: 105908, 2022 09.
Article in English | MEDLINE | ID: mdl-35872411

ABSTRACT

During COVID-19 prevention and control, people need to be aware of the outbreak situation in their area to avoid being inconvenienced by the outbreak and even becoming infected. Thus, this project constructs a knowledge graph with COVID-19 infector activity information, by using the official flow information of the infected people from the provincial and municipal websites. This knowledge graph is the basis of the COVID-19 applications for tracing, visualization and reporting proposes. In the implementation process, we (1) collect a dataset with the information on COVID-19 cases from the prevention and control centers, (2) extract the entity elements with a Bert + BILSTM + CRF-based model, and (3) pre-process the dataset and construct a knowledge graph with manual annotation and human-based review. Finally, we use the knowledge graph to develop a web-based application to implement the question and answer, query, transmission path tracking and the "No.0" tracing infector functions.


Subject(s)
COVID-19 , Humans , Pattern Recognition, Automated , Software
14.
Cell Rep ; 39(11): 110945, 2022 06 14.
Article in English | MEDLINE | ID: mdl-35688145

ABSTRACT

SARS-CoV-2-infected subjects are generally asymptomatic during initial viral replication but may suffer severe immunopathology after the virus has receded and monocytes have infiltrated the airways. In bronchoalveolar lavage fluid from severe COVID-19 patients, monocytes express mRNA encoding inflammatory mediators and contain SARS-CoV-2 transcripts. We leverage a human small airway model of infection and inflammation, whereby primary blood monocytes transmigrate across SARS-CoV-2-infected lung epithelium to characterize viral burden, gene expression, and inflammatory mediator secretion by epithelial cells and monocytes. In this model, lung-infiltrating monocytes acquire SARS-CoV-2 from the epithelium and upregulate expression and secretion of inflammatory mediators, mirroring in vivo data. Combined use of baricitinib (Janus kinase inhibitor) and remdesivir (nucleoside analog) enhances antiviral signaling and viral clearance by SARS-CoV-2-positive monocytes while decreasing secretion of proneutrophilic mediators associated with acute respiratory distress syndrome. These findings highlight the role of lung-infiltrating monocytes in COVID-19 pathogenesis and their importance as a therapeutic target.


Subject(s)
COVID-19 Drug Treatment , Azetidines , Humans , Inflammation Mediators , Lung/pathology , Monocytes , Purines , Pyrazoles , SARS-CoV-2 , Sulfonamides
15.
J Microsc ; 287(2): 61-68, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35570411

ABSTRACT

Electron energy-loss spectroscopy (EELS) is widely applied combining with transmission electron microscopes with high spatial resolution, but its interpretation is a challenging task. One of the reasons is that the factors affecting EELS are very complicated. In this paper, we focus on the several factors involved in density functional theory (DFT) calculations. The sensitivity of calculated energy-loss near-edge structure (ELNES) to spin order, pressure and on-site Coulomb energy U has been discussed. Since EELS technique detects the local environment of atoms, the influence of spin order cannot be ignored. The chemical shifts and peak intensity of ELNES are also closely related to corresponding pressure. The correlation effects are very important for transition metal compounds and play a key role in EELS simulations. An overview of the effects of these factors on the ELNES is presented with the help of Wien2k code. The antiferromagnetic order results in the decreasing of intensities of related peaks and the moving of the peaks to high energy loss. The decreasing of lattice parameters causes the ELNES peaks to shift to high energy loss, and the peak shifts at the higher energy loss are more significant. The increase of correlation effect leads to the ELNES peaks to shift to high energy loss accompanied by the increase of the relative intensity of the peaks which locate at higher energy loss. Our work helps to understand how these factors affect EELS and to explain and predict the experimental EELS spectra. Through the discussion of these factors, we propose that some factors could not be ignored in EELS simulations.

16.
Plant Physiol ; 189(4): 2500-2516, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35522026

ABSTRACT

MicroRNAs play key roles in abiotic stress response. Rice (Oryza sativa L.) miR1320 is a species-specific miRNA that contributes to miR168-regulated immunity. However, it is still unknown whether miR1320 is involved in rice response to abiotic stress. In this study, we illustrated that the miR1320 precursor generated two mature miR1320s, miR1320-3p, and miR1320-5p, and they both displayed decreased expression under cold stress. Genetic evidence showed that miR1320 overexpression resulted in increased cold tolerance, while miR1320 knock down (KD) reduced cold tolerance. Furthermore, an APETALA2/ethylene-responsive factor (ERF) transcription factor OsERF096 was identified as a target of miR1320 via 5'-RACE and dual luciferase assays. OsERF096 expression was altered by miR1320 overexpression and KD and exhibited an opposite pattern to that of miR1320 in different tissues and under cold stress. Consistently, OsERF096 negatively regulated cold stress tolerance. Furthermore, we suggested that OsERF096 could bind to the GCC and DRE cis-elements and act as a transcriptional activator in the nucleus. Based on RNA-sequencing and targeted metabolomics assays, we found that OsERF096 modified hormone content and signaling pathways. Finally, phenotypic and reverse transcription-quantitative PCR assays showed that jasmonic acid (JA) methyl ester application recovered the cold-sensitive phenotype and JA-activated expression of three Dehydration Responsive Element Binding genes in the OsERF096-OE line. Taken together, our results strongly suggest that the miR1320-OsERF096 module regulates cold tolerance by repressing the JA-mediated cold signaling pathway.


Subject(s)
Oryza , Transcription Factors , Cold Temperature , Cold-Shock Response/genetics , Ethylenes/metabolism , Gene Expression Regulation, Plant , Oryza/genetics , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism , Signal Transduction/genetics , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
17.
Immunohorizons ; 6(2): 144-155, 2022 02 16.
Article in English | MEDLINE | ID: mdl-35173021

ABSTRACT

Due to the severity of COVID-19 disease, the U.S. Centers for Disease Control and Prevention and World Health Organization recommend that manipulation of active viral cultures of SARS-CoV-2 and respiratory secretions from COVID-19 patients be performed in biosafety level (BSL)3 laboratories. Therefore, it is imperative to develop viral inactivation procedures that permit samples to be transferred to lower containment levels (BSL2), while maintaining the fidelity of complex downstream assays to expedite the development of medical countermeasures. In this study, we demonstrate optimal conditions for complete viral inactivation following fixation of infected cells with commonly used reagents for flow cytometry, UVC inactivation in sera and respiratory secretions for protein and Ab detection, heat inactivation following cDNA amplification for droplet-based single-cell mRNA sequencing, and extraction with an organic solvent for metabolomic studies. Thus, we provide a suite of viral inactivation protocols for downstream contemporary assays that facilitate sample transfer to BSL2, providing a conceptual framework for rapid initiation of high-fidelity research as the COVID-19 pandemic continues.


Subject(s)
COVID-19/prevention & control , Specimen Handling/methods , Virus Inactivation , Hot Temperature , Humans , Metabolomics/methods , Pandemics/prevention & control , SARS-CoV-2 , Ultraviolet Rays
18.
ACS Chem Neurosci ; 12(19): 3672-3682, 2021 10 06.
Article in English | MEDLINE | ID: mdl-34505505

ABSTRACT

Protein kinase C (PKC) isozymes play essential roles in biological processes, and activation of PKC is proposed to alleviate the symptoms of a variety of diseases. It would be of great significance to find effective pharmacological modulators of PKC isozymes that can be translated for clinical use. Here, using in vitro activity assay, we demonstrated that green tea extract (-)-epigallocatechin-3-gallate (EGCG) dose-dependently activated PKCα with a half effective concentration (EC50) of 0.49 µM. We also performed surface plasmon resonance analysis and found that EGCG binds PKCα with an equilibrium dissociation constant (KD) value of 4.11 × 10-6 mol/L. Further computational flexible docking analysis revealed that EGCG interacted with the catalytic C3-C4 domain of PKCα (PDB: 4RA4) through establishing polar hydrogen bonds with V420, T401, E387, and K368 of PKCα, and the benzene ring group of EGCG hydrophobically interacted with the hydrophobic pocket formed by L345, M470, I479, and V353 of PKCα. Interestingly, the PKCα-selective blocker Ro-32-0432 could compete with EGCG for the same substrate-binding pocket of PKCα. Moreover, we found that EGCG dose-dependently improved the spatial memory, object recognition ability, and hippocampal long-term potentiation of ovariectomized mice, which was offset by Ro-32-0432. Collectively, our findings reveal a novel PKCα agonist and open the way to a new perspective on PKCα pharmacology and the treatment of PKCα-related diseases, including cognitive impairment.


Subject(s)
Catechin , Protein Kinase C-alpha , Animals , Catechin/analogs & derivatives , Catechin/pharmacology , Cognition , Estrogens , Mice
19.
Cell Rep ; 36(3): 109414, 2021 07 20.
Article in English | MEDLINE | ID: mdl-34260965

ABSTRACT

Although T cells are likely players in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe coronavirus disease 2019 (COVID-19). We analyze T cells from 34 individuals with COVID-19 with severity ranging from mild (outpatient) to critical, culminating in death. Relative to individuals who succumbed, individuals who recovered from severe COVID-19 harbor elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 cases display elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells, as assessed by longitudinal sampling. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of individuals with severe COVID-19, these results support a model where lung-homing T cells activated through bystander effects contribute to immunopathology, whereas a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.

20.
Front Psychol ; 12: 526972, 2021.
Article in English | MEDLINE | ID: mdl-34177673

ABSTRACT

The visual system is capable of recognizing objects when object information is widely separated in space, as revealed by the Kanizsa-type illusory contours (ICs). Attentional involvement in perception of ICs is an important topic, and the present study examined whether and how the processing of ICs is interfered with by a distractor. Discrimination between thin and short deformations of an illusory circle was investigated in the absence or presence of a central dynamic patch, with difficulty of discrimination varied in three levels (easy, medium, and hard). Reaction time (RT) was significantly shorter in the absence compared to the presence of the distractor in the easy and medium conditions. Correct rate (CR) was significantly higher in the absence compared to the presence of the distractor in the easy condition, and the magnitude of the difference between CRs of distracted and non-distracted responses significantly reduced as task difficulty increased. These results suggested that perception of ICs is more likely to be vulnerable to distraction when more attentional resources remain available. The present finding supports that attention is engaged in perception of ICs and that distraction of IC processing is associated with perceptual load.

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