Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
745,349
result(s) for
"An, Yu"
Sort by:
Acyl-Coenzyme A Synthetase Long-Chain Family Member 4 Is Involved in Viral Replication Organelle Formation and Facilitates Virus Replication via Ferroptosis
We provide the first evidence for the role of ACSL4 in enterovirus replication organelle formation. Moreover, both enteroviruses and coronaviruses induce ferroptosis via ACSL4. These findings establish a novel regulatory mechanism for viral replication. The inhibition of ACSL4 by ferroptosis inhibitors can reduce viral yields of enteroviruses and coronaviruses, including SARS-CoV-2, implying that ACSL4-mediated ferroptosis is a promising therapeutic target for viral diseases. Enterovirus infections can cause severe complications, such as poliomyelitis, encephalitis, myocarditis, meningitis, neurological pulmonary edema, and even death. Here, we used genome-wide CRISPR screens to gain new insight into the mechanism by which enteroviruses co-opt host pathways to potentiate replication and propagation. We found that acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) is involved in viral replication organelle formation. ACSL4 is a key component of ferroptosis, an iron-dependent, nonapoptotic programmed cell death. Our results indicated that enteroviruses and coronaviruses can induce ferroptosis via ACSL4. Most importantly, ferroptosis inhibitors, including two FDA-approved drugs, rosiglitazone (ROSI; ACSL4 inhibitor) and pioglitazone (PIO; ACSL4 inhibitor), decreased the viral load of human enteroviruses and coronaviruses, suggesting that ACSL4 is a target for counteracting viral infection. IMPORTANCE We provide the first evidence for the role of ACSL4 in enterovirus replication organelle formation. Moreover, both enteroviruses and coronaviruses induce ferroptosis via ACSL4. These findings establish a novel regulatory mechanism for viral replication. The inhibition of ACSL4 by ferroptosis inhibitors can reduce viral yields of enteroviruses and coronaviruses, including SARS-CoV-2, implying that ACSL4-mediated ferroptosis is a promising therapeutic target for viral diseases.
Journal Article
The Relationships between Physical Activity and Life Satisfaction and Happiness among Young, Middle-Aged, and Older Adults
Physical activity has benefits on physical and psychological health. The aims of this study were to investigate (1) the relationships between physical activity and life satisfaction and happiness in young, middle-aged, and older adults while controlling for demographic characteristics, and (2) the relationships between age and life satisfaction and happiness for different physical activity levels. A total of 2345 healthy adults were recruited. Demographic characteristic, physical activity, life satisfaction, and happiness were collected. Participants were divided into young, middle-aged, and older adult groups based on age, and physical activity was categorized as high, moderate, and low. After controlling for demographic characteristics, participants with high and moderate activity levels had significantly higher life satisfaction and happiness than those with a low activity level across the total population and the three age groups. Age squared was a significant predictor of a positive curvilinear between age and life satisfaction and happiness. Physical activity was significantly related to life satisfaction and happiness in young, middle-aged, and older adults. In addition, life satisfaction and happiness increased with increasing age. The results support the promotion of physical activity.
Journal Article
Assessing metastatic potential of breast cancer cells based on EGFR dynamics
Derailed transmembrane receptor trafficking could be a hallmark of tumorigenesis and increased tumor invasiveness, but receptor dynamics have not been used to differentiate metastatic cancer cells from less invasive ones. Using single-particle tracking techniques, we developed a phenotyping asssay named
T
ransmembrane
Re
ceptor
D
ynamics (TReD), studied the dynamics of epidermal growth factor receptor (EGFR) in seven breast epithelial cell lines and developed a phenotyping assay named
T
ransmembrane
Re
ceptor
D
ynamics (TReD). Here we show a clear evidence that increased EGFR diffusivity and enlarged EGFR confinement size in the plasma membrane (PM) are correlated with the enhanced metastatic potential in these cell lines. By comparing the TReD results with the gene expression profiles, we found a clear negative correlation between the EGFR diffusivities and the breast cancer luminal differentiation scores (r = −0.75). Upon the induction of epithelial-mesenchymal transition (EMT), EGFR diffusivity significantly increased for the non-tumorigenic MCF10A (99%) and the non-invasive MCF7 (56%) cells, but not for the highly metastatic MDA-MB-231 cell. We believe that the reorganization of actin filaments during EMT modified the PM structures, causing the receptor dynamics to change. TReD can thus serve as a new biophysical marker to probe the metastatic potential of cancer cells and even to monitor the transition of metastasis.
Journal Article
Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells
There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.
Journal Article
Detection of Dental Apical Lesions Using CNNs on Periapical Radiograph
Apical lesions, the general term for chronic infectious diseases, are very common dental diseases in modern life, and are caused by various factors. The current prevailing endodontic treatment makes use of X-ray photography taken from patients where the lesion area is marked manually, which is therefore time consuming. Additionally, for some images the significant details might not be recognizable due to the different shooting angles or doses. To make the diagnosis process shorter and efficient, repetitive tasks should be performed automatically to allow the dentists to focus more on the technical and medical diagnosis, such as treatment, tooth cleaning, or medical communication. To realize the automatic diagnosis, this article proposes and establishes a lesion area analysis model based on convolutional neural networks (CNN). For establishing a standardized database for clinical application, the Institutional Review Board (IRB) with application number 202002030B0 has been approved with the database established by dentists who provided the practical clinical data. In this study, the image data is preprocessed by a Gaussian high-pass filter. Then, an iterative thresholding is applied to slice the X-ray image into several individual tooth sample images. The collection of individual tooth images that comprises the image database are used as input into the CNN migration learning model for training. Seventy percent (70%) of the image database is used for training and validating the model while the remaining 30% is used for testing and estimating the accuracy of the model. The practical diagnosis accuracy of the proposed CNN model is 92.5%. The proposed model successfully facilitated the automatic diagnosis of the apical lesion.
Journal Article
Superior ferroelectricity and nonlinear optical response in a hybrid germanium iodide hexagonal perovskite
Abundant chemical diversity and structural tunability make organic–inorganic hybrid perovskites (OIHPs) a rich ore for ferroelectrics. However, compared with their inorganic counterparts such as BaTiO
3
, their ferroelectric key properties, including large spontaneous polarization (
P
s
), low coercive field (
E
c
), and strong second harmonic generation (SHG) response, have long been great challenges, which hinder their commercial applications. Here, a quasi-one-dimensional OIHP DMAGeI
3
(DMA = Dimethylamine) is reported, with notable ferroelectric attributes at room temperature: a large
P
s
of 24.14 μC/cm
2
(on a par with BaTiO
3
), a low
E
c
below 2.2 kV/cm, and the strongest SHG intensity in OIHP family (about 12 times of KH
2
PO
4
(KDP)). Revealed by the first-principles calculations, its large
P
s
originates from the synergistic effects of the stereochemically active 4
s
2
lone pair of Ge
2+
and the ordering of organic cations, and its low kinetic energy barrier of small DMA cations results in a low
E
c
. Our work brings the comprehensive ferroelectric performances of OIHPs to a comparable level with commercial inorganic ferroelectric perovskites.
The authors report on a quasi-one-dimensional organic-inorganic hybrid perovskite, DMAGeI
3
(DMA = Dimethylamine), with notable ferroelectric attributes at room temperature including large spontaneous polarisation, low coercive field, and strong second harmonic generation response.
Journal Article
Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors
The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex, and disruption of host responses. We report a substantive body of structural, biochemical, and virus replication studies that identify several inhibitors of the SARS-CoV-2 enzyme. We determined the high resolution structure of wild-type PLpro, the active site C111S mutant, and their complexes with inhibitors. This collection of structures details inhibitors recognition and interactions providing fundamental molecular and mechanistic insight into PLpro. All compounds inhibit the peptidase activity of PLpro in vitro, some block SARS-CoV-2 replication in cell culture assays. These findings will accelerate structure-based drug design efforts targeting PLpro to identify high-affinity inhibitors of clinical value.
The SARS-CoV-2 papain-like protease (PLpro) is of interest as an antiviral drug target. Here, the authors synthesize and characterise naphthalene-based inhibitors for PLpro and present the crystal structures of PLpro in its apo state and with the bound inhibitors, which is of interest for further structure-based drug design efforts.
Journal Article
Significant Hall–Petch effect in micro-nanocrystalline electroplated copper controlled by SPS concentration
Electroplated Cu has been extensively applied in advanced electronic packaging, and its mechanical properties are critical for reliability. In this study, Cu foils fabricated through electroplating with various bis-(3-sulfopropyl) disulfide (SPS) concentrations are examined using tensile tests. The SPS concentration affects the grain size of the electroplated Cu foils, resulting in different mechanical properties. A significant Hall–Petch effect,
σ
y
=
197.4
+
0.12
d
-
1
2
, is demonstrated for the electroplated Cu foils. The different concentrations of impurities identified through time-of-flight secondary ion mass spectrometry correspond to the different grain sizes, determining the transgranular and intergranular fracture during the tensile test. The results demonstrate that the SPS concentration controlling the microstructures of the electroplated Cu results in a Hall–Petch effect on the mechanical properties of the electroplated Cu foils.
Journal Article
Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice
Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear. Here, we isolated dermal adipocytes and characterized dermal fat at the cellular and molecular level. Together with dWAT's dynamic responses to external stimuli, we established that dermal adipocytes are a distinct class of white adipocytes with high plasticity. By combining pulse-chase lineage tracing and single-cell RNA sequencing, we observed that mature dermal adipocytes undergo dedifferentiation and redifferentiation under physiological and pathophysiological conditions. Upon various challenges, the dedifferentiated cells proliferate and redifferentiate into adipocytes. In addition, manipulation of dWAT highlighted an important role for mature dermal adipocytes for hair cycling and wound healing. Altogether, these observations unravel a surprising plasticity of dermal adipocytes and provide an explanation for the dynamic changes in dWAT mass that occur under physiological and pathophysiological conditions, and highlight the important contributions of dWAT toward maintaining skin homeostasis.
Journal Article