Abstract The necessity of helping older employees achieve career success in the digital workplace has drastically increased. Drawing on self‐affirmation theory, we postulate that using enterprise ...social media (ESM) to conduct intergenerational knowledge sharing (IGKS) is a generativity and self‐affirmation behaviour in the digital workplace, and investigate how it would help older employees enhance job performance and thus achieve successful ageing at work. Study 1 (a three‐wave time‐lagged survey study with 262 older employees over 40 years old) demonstrates that, older employees' IGKS in ESM positively affects their job performance via personal needs‐job supplies fit. Perceived younger colleagues' knowledge disseminative capacity can weaken, but perceived younger colleagues' knowledge absorptive capacity can strengthen the above indirect effect. We replicated the first study's findings in Study 2 using a two‐wave survey with 161 older employees over 50 years old. Additionally, we found that older employees' IGKS in ESM positively influences their job performance via a serial mediation of organization‐based self‐esteem and needs‐supplies fit. Perceived younger colleagues' knowledge disseminative capacity can weaken, but knowledge absorptive capacity can strengthen the serial mediation relationship. These findings contribute to integrating IGKS and ESM literature to improve the theoretical framework of successful ageing at work.
Abstract
Background
Graphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular ...structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation.
Results
The cytosolic iron overload, glutathione (GSH) depletion, excessive reactive oxygen species (ROS) production and lipid peroxidation (LPO) were observed in microglial BV2 cells treated with N-GQDs, which indicated that N-GQDs could damage the iron metabolism and redox balance in microglia. The pre-treatments of a specific ferroptosis inhibitor Ferrostatin-1 (Fer-1) and an iron chelater Deferoxamine mesylate (DFO) not only inhibited cell death, but also alleviated iron overload, LPO and alternations in ferroptosis biomarkers in microglia, which were caused by N-GQDs. When assessing the potential mechanisms of N-GQDs causing ferroptosis in microglia, we found that the iron content, ROS generation and LPO level in mitochondria of BV2 cells all enhanced after N-GQDs exposure. When the antioxidant ability of mitochondria was increased by the pre-treatment of a mitochondria targeted ROS scavenger MitoTEMPO, the ferroptotic biological changes were effectively reversed in BV2 cells treated with N-GQDs, which indicated that the N-GQDs-induced ferroptosis in microglia could be attributed to the mitochondrial oxidative stress. Additionally, amino functionalized GQDs (A-GQDs) elicited milder redox imbalance in mitochondria and resulted in less ferroptotic effects than N-GQDs in microglia, which suggested a slight protection of amino group functionalization in GQDs causing ferroptosis.
Conclusion
N-GQDs exposure caused ferroptosis in microglia via inducing mitochondrial oxidative stress, and the ferroptotic effects induced by A-GQDs were milder than N-GQDs when the exposure method is same. This study will not only provide new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs.
Missing data imputation aims to accurately impute the unobserved regions with complete data in the real world. Although many current methods have made remarkable advances, the local homogenous ...regions, especially in boundary, and the reason of the imputed data are still the two most challenging issues. To address these issues, we propose a novel Generative Adversarial Guider Imputation Network (GAGIN) based on generative adversarial network (GAN) for unsupervised imputation, which is composed of a Global-Impute-Net (GIN), a Local-Impute-Net (LIN) and an Impute Guider Model (IGM). The GIN looks at the entire missing regions to generate and impute data as a whole. Considering the reason of the GIN results, IGM is assigned to capture coherent information between global and local and guide the LIN to look only at a small area centered at the missing focused regions. After processing these three modules, the local imputed results are concatenated to those global imputed results, which impute the rational values and refine the local details from rough to accurate. The comprehensive experiments demonstrate our proposed method is significantly superior to the other three state-of-the-art approaches and seven traditional methods, and we achieve the best RMSE surpass the second-best method on both numeric datasets (17.3%) and image dataset (24.1%). Besides, the extensive ablation study validates the superior performance for dealing with missing data imputation.
The generation of large numbers of functional human hepatocytes for cell-based approaches to liver disease is an important and unmet goal. Direct reprogramming of fibroblasts to hepatic lineages ...could offer a solution to this problem but so far has only been achieved with mouse cells. Here, we generated human induced hepatocytes (hiHeps) from fibroblasts by lentiviral expression of FOXA3, HNF1A, and HNF4A. hiHeps express hepatic gene programs, can be expanded in vitro, and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity and biliary drug clearance. Upon transplantation into mice with concanavalin-A-induced acute liver failure and fatal metabolic liver disease due to fumarylacetoacetate dehydrolase (Fah) deficiency, hiHeps restore the liver function and prolong survival. Collectively, our results demonstrate successful lineage conversion of nonhepatic human cells into mature hepatocytes with potential for biomedical and pharmaceutical applications.
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•FOXA3, HNF1A, and HNF4A convert human fibroblasts to hepatocyte-like cells•hiHep cells display functions of mature hepatocytes, including biliary excretion•hiHep cells can be expanded in culture•hiHep cells can be used to treat acute liver failure and metabolic liver disease
Huang et al. demonstrate direct conversion of human fibroblasts to hepatocyte-like cells, which can be expanded in culture and used to treat acute liver failure and metabolic liver disease.
Abstract
Pseudomonas syringae
is a Gram-negative and model pathogenic bacterium that causes plant diseases worldwide. Here, we set out to identify binding motifs for all 301 annotated transcription ...factors (TFs) of
P. syringae
using HT-SELEX. We successfully identify binding motifs for 100 TFs. We map functional interactions between the TFs and their targets in virulence-associated pathways, and validate many of these interactions and functions using additional methods such as ChIP-seq, electrophoretic mobility shift assay (EMSA), RT-qPCR, and reporter assays. Our work identifies 25 virulence-associated master regulators, 14 of which had not been characterized as TFs before.
Compound Kushen injection (CKI) is the most widely used traditional Chinese medicine preparation for the comprehensive treatment of colorectal cancer (CRC) in China, but its underlying molecular ...mechanisms of action are still unclear. The present study employed a network pharmacology approach, in which we constructed a "bioactive compound-target-pathway" network. Experimental RNA sequencing (RNA-Seq) analysis was performed to identify a key "bioactive compound-target-pathway" network for subsequent experimental validation. Cell cycle, proliferation, autophagy, and apoptosis assays and a model of azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in mice were employed to detect the biological effect of CKI on CRC. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were performed to verify the selected targets and pathways. We constructed a predicted network that included 82 bioactive compounds, 34 targets, and 33 pathways and further screened an anti-CRC CKI "biological compound (hesperetin 7-O-rutinoside, genistein 7-O-rutinoside, and trifolirhizin)-target (p53 and checkpoint kinase 1 CHEK1)" network that targeted the "cell cycle pathway". Validation experiments showed that CKI effectively induced the cell-cycle arrest of CRC cells in vitro and suppressed the development of CRC in vivo by downregulating the expression of p53 and CHEK1. Our findings confirmed that inducing cell-cycle arrest by CKI is an important mechanism of its anti-CRC action, which provides a direct and scientific experimental basis for the clinical application of CKI.
Propiconazole is a triazole fungicide that has been widely used in agriculture and has been detected in the aquatic environment. This study aimed to investigate the effects of propiconazole exposure ...on lipid metabolism in the early life stages of zebrafish for 120 h postfertilization (hpf). Using the early life stages of zebrafish to address scientific questions is lower in cost, more efficient, and suitable to meeting current legislation than those in other traditional fish species. Exposure to propiconazole significantly inhibited the development of zebrafish embryos and larvae. This exposure also caused reduced locomotor activities in zebrafish. Furthermore, total cholesterol levels, lipoprotein lipase, and fatty acid synthase activities were significantly decreased. The expression levels of genes involved in lipid metabolism were significantly up-regulated in response to propiconazole exposure. GC-MS/MS analysis revealed that fatty acids were significantly decreased. Together, the findings indicate the potential environmental risks of propiconazole exposure in the aquatic ecosystem.
Flexible thin films of poly(nickel‐ethylenetetrathiolate) prepared by an electrochemical method display promising n‐type thermoelectric properties with the highest ZT value up to 0.3 at room ...temperature. Coexistence of high electrical conductivity and high Seebeck coefficient in this coordination polymer is attributed to its degenerate narrow‐bandgap semiconductor behavior.
Objective:
Electroacupuncture (EA) pretreatment appears useful in the treatment of chronic myocardial ischemia (CMI). The goal of this study was to investigate the effect of EA preconditioning on the ...regulation of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) proteins in a CMI model of vascular regeneration.
Methods:
A CMI model was established by subcutaneous injection of isoprinosine hydrochloride (ISO) for 14 days in 45 Wistar rats, which had been randomly divided into a model group (n = 15), a CMI group pretreated with sham EA for 21 days (CMI + Sham group, n = 15) and a CMI group pretreated with verum EA for 21 days (CMI + EA, n = 15) prior to modeling. An additional 15 Wistar rats received 0.9% sodium chloride via intraperitoneal injection for 14 consecutive days (control group). Serum levels of VEGF and HIF-1α were measured by ELISA, while protein expression of VEGF and HIF-1α in the area of myocardial infarction was measured by Western blotting. The area of myocardial infarction and fibrosis of the myocardial tissue in the study groups were visualized by hematoxylin-eosin (HE) staining and Masson staining, respectively.
Results:
EA pretreatment improved cardiac function by regulating left ventricular end-diastolic diameter and left ventricular end-systolic diameter, left ventricular ejection fraction and the ST segment voltage of the electrocardiogram. EA pretreatment promoted vascular regeneration by increasing serum levels of VEGF and HIF-1α and by increasing protein expression of HIF-1α and VEGF in the infarcted region of the myocardium, leading to a reduction in the area of myocardial infarction on HE staining and reduction of myocardial fibrosis on Masson staining.
Conclusion:
EA pretreatment promotes protein expression of HIF-1α and VEGF in areas of ischemic myocardium, which may represent useful biomarkers for coronary collateral establishment and offer potential targets for therapeutic angiogenesis in patients with CMI.
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