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"Lin, Mei"
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Elevation of CD109 promotes metastasis and drug resistance in lung cancer via activation of EGFR‐AKT‐mTOR signaling
Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients. CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Journal Article
An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases
Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.
Journal Article
An Appraisal Perspective of Teacher Burnout: Examining the Emotional Work of Teachers
K-12 teaching is a profession characterized by high levels of burnout and emotional exhaustion. Teacher burnout has been widely reviewed and studied; however, only limited literature examines the emotional aspects of teachers' lives and its connection with teacher burnout. The purpose of this article is to review the literature on teacher burnout and teachers' emotions and to examine the role of teachers' appraisal of their emotional exhaustion. Through reviewing the literature on teacher burnout and emotions, I argue that the habitual patterns in teachers' judgments about student behavior and other teaching tasks may contribute significantly to teachers' repeated experience of unpleasant emotions and those emotions may eventually lead to burnout. In order to ease teacher burnout, I argue that more studies on the antecedent appraisals that teachers make are necessary to help teachers better understand how their emotions were triggered and then learn how to regulate those emotions.
Journal Article
Toward a theoretical model to understand teacher emotions and teacher burnout in the context of student misbehavior: Appraisal, regulation and coping
Compared with other professions, teachers in P-12 schools appear to experience a higher level of emotional exhaustion (see review in Maslach et al. in Ann Rev Psychol 52(1):397,
2001
; Schaufeli and Enzmann in The burnout companion to study and practice: a critical analysis, Taylor & Francis, Philadelphia,
1998
). The purpose of this study is to examine teacher emotions within the context of teachers’ appraisals and the ways they regulate and cope with their emotions. The study explores teachers’ appraisals of disruptive classroom behavior situations and investigates the adaptive coping and emotion regulation strategies that ease teacher burnout. Data were collected from 492 teachers in the US Midwest and subjected to hypothesis testing using structural equation modeling. The model provides evidence supporting a pathway between teachers’ antecedent judgments and their experience of emotion, as well as providing evidence for how the consequent emotions contribute to teachers’ feelings of burnout. This study further validates the relationships between the appraisals teachers make about an incident and the correlative intensity of emotions. Several hypotheses are either supported or partially supported after testing alternate models. Discussion and implications regarding teacher emotion regulation and coping are provided.
Journal Article
Organophotocatalytic selective deuterodehalogenation of aryl or alkyl chlorides
Development of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.
Deuterodehalogenation of organic chlorides is a useful strategy to install deuterium atoms at specific positions, however, it has several drawbacks. In this study, the authors report an organophotocatalytic system consisting of an aryl-amine-based photocatalyst and a common disulfide co-catalyst, for efficient deuteration of a wide range of aryl chlorides, alkyl chlorides and other halides, at room temperature in air.
Journal Article
Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts
Chronic mitochondrial stress associates with major neurodegenerative diseases. Recovering stressed mitochondria constitutes a critical step of mitochondrial quality control and thus energy maintenance in early stages of neurodegeneration. Here, we reveal Mul1-Mfn2 pathway that maintains neuronal mitochondrial integrity under stress conditions. Mul1 deficiency increases Mfn2 activity that triggers the first phasic mitochondrial hyperfusion and also acts as an ER-Mito tethering antagonist. Reduced ER-Mito coupling leads to increased cytoplasmic Ca
2+
load that activates calcineurin and induces the second phasic Drp1-dependent mitochondrial fragmentation and mitophagy. Overexpressing Mfn2, but not Mfn1, mimics Mul1-deficient phenotypes, while expressing PTPIP51, an ER-Mito anchoring protein, suppresses Parkin-mediated mitophagy. Thus, by regulating mitochondrial morphology and ER-Mito contacts, Mul1-Mfn2 pathway plays an early checkpoint role in maintaining mitochondrial integrity. Our study provides new mechanistic insights into neuronal mitochondrial maintenance under stress conditions, which is relevant to several major neurodegenerative diseases associated with mitochondrial dysfunction and altered ER-Mito interplay.
Little is known about the pathways that maintain mitochondrial structure and function under neuronal stress conditions. Here, authors demonstrate that the Mul1-Mfn2 pathway plays a checkpoint role in maintaining mitochondrial integrity and energy maintenance by ensuring ER-mitochondrial tethering and preventing mitophagy.
Journal Article
Arsenene-mediated multiple independently targeted reactive oxygen species burst for cancer therapy
The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/As
x
O
y
NSs) with type II heterojunction are fabricated with efficient ·O
2
−
and
1
O
2
production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of As
x
O
y
with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O
2
from H
2
O
2
, but also inactivates main anti-oxidants to cut off the “retreat routes” of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/As
x
O
y
@PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/As
x
O
y
@PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy.
Multifunctional materials with a number of effects are important for dealing with the complex environment in cancer therapy. Here, the authors report on surface-oxidized arsenene nanosheets coated with polydopamine and cancer cell membrane as a multi theranostic tumour targeting cancer therapy.
Journal Article
Three-dimensional holey-graphene/niobia composite architectures for ultrahigh-rate energy storage
Nanostructured materials have shown extraordinary promise for electrochemical energy storage but are usually limited to electrodes with rather low mass loading (~1 milligram per square centimeter) because of the increasing ion diffusion limitations in thicker electrodes. We report the design of a three-dimensional (3D) holey-graphene/niobia (Nb₂O₅) composite for ultrahigh-rate energy storage at practical levels of mass loading (>10 milligrams per square centimeter). The highly interconnected graphene network in the 3D architecture provides excellent electron transport properties, and its hierarchical porous structure facilitates rapid ion transport. By systematically tailoring the porosity in the holey graphene backbone, charge transport in the composite architecture is optimized to deliver high areal capacity and high-rate capability at high mass loading, which represents a critical step forward toward practical applications.
Journal Article
Heterojunction Nanomedicine
Exogenous stimulation catalytic therapy has received enormous attention as it holds great promise to address global medical issues. However, the therapeutic effect of catalytic therapy is seriously restricted by the fast charge recombination and the limited utilization of exogenous stimulation by catalysts. In the past few decades, many strategies have been developed to overcome the above serious drawbacks, among which heterojunctions are the most widely used and promising strategy. This review attempts to summarize the recent progress in the rational design and fabrication of heterojunction nanomedicine, such as semiconductor–semiconductor heterojunctions (including type I, type II, type III, PN, and Z–scheme junctions) and semiconductor–metal heterojunctions (including Schottky, Ohmic, and localized surface plasmon resonance–mediated junctions). The catalytic mechanisms and properties of the above junction systems are also discussed in relation to biomedical applications, especially cancer treatment and sterilization. This review concludes with a summary of the challenges and some perspectives on future directions in this exciting and still evolving field of research. This review summarizes the recent progress in the rational design and fabrication of heterojunction nanomedicine. The catalytic mechanisms and properties of applied heterojunction systems are also discussed in relation to biomedical applications, especially cancer treatment and sterilization. This review concludes with a summary of the challenges and perspectives on future directions in this evolving field of research.
Journal Article