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2.
Article in English | MEDLINE | ID: mdl-37906524

ABSTRACT

A novel light-absorbing material of high-entropy oxide (HEO) has been synthesized using the hydrothermal method. The HEO has six metals, namely, Fe, Ni, Mn, Cr, Mg, and Cu. The obtained HEO light absorber is demonstrated to show unprecedented broadband absorption, ranging from 310 to 1400 nm. The photodetector having a structure of Ag/HEO/n-Si has been evaluated for its performance. Under the illumination of various light wavelengths, the photodetector exhibits a remarkably wide range of photoresponse from 365 to 1050 nm, giving wide-spectrum photocurrent densities in the order of 1 mA/cm2, a responsibility as high as 3.5 A/W (850 nm), and an external quantum efficiency (EQE) of more than 700% (850 nm), outperforming all of the reported oxide-based photodetectors. The superior device performance is attributed to the excellent light absorbance and EQE of the oxygen vacancy-containing HEO. Moreover, a number of tests, including the abrasion test, temperature endurance, acidic resistance, on-off switching cycling, and 3 dB bandwidth measurement, show the excellent reliability of the obtained HEO-based photodetector.

3.
J Virol ; 96(17): e0083622, 2022 09 14.
Article in English | MEDLINE | ID: mdl-35946936

ABSTRACT

The mechanism by which avian reovirus (ARV)-modulated suppression of mTORC1 triggers autophagy remains largely unknown. In this work, we determined that p17 functions as a negative regulator of mTORC1. This study suggest novel mechanisms whereby p17-modulated inhibition of mTORC1 occurs via upregulation of p53, inactivation of Akt, and enhancement of binding of the endogenous mTORC1 inhibitors (PRAS40, FKBP38, and FKPP12) to mTORC1 to disrupt its assembly and accumulation on lysosomes. p17-modulated inhibition of Akt leads to activation of the downstream targets PRAS40 and TSC2, which results in mTORC1 inhibition, thereby triggering autophagy and translation shutoff, which is favorable for virus replication. p17 impairs the interaction of mTORC1 with its activator Rheb, which promotes FKBP38 interaction with mTORC1. It is worth noting that p17 activates ULK1 and Beclin1 and increases the formation of the Beclin 1/class III PI3K complex. These effects could be reversed in the presence of insulin or depletion of p53. Furthermore, we found that p17 induces autophagy in cancer cell lines by upregulating the p53/PTEN pathway, which inactivates Akt and mTORC1. This study highlights p17-modulated inhibition of Akt and mTORC1, which triggers autophagy and translation shutoff by positively modulating the tumor suppressors p53 and TSC2 and endogenous mTORC1 inhibitors. IMPORTANCE The mechanisms by which p17-modulated inhibition of mTORC1 induces autophagy and translation shutoff is elucidated. In this work, we determined that p17 serves as a negative regulator of mTORC1. This study provides several lines of conclusive evidence demonstrating that p17-modulated inhibition of mTORC1 occurs via upregulation of the p53/PTEN pathway, downregulation of the Akt/Rheb/mTORC1 pathway, enhancement of binding of the endogenous mTORC1 inhibitors to mTORC1 to disrupt its assembly, and suppression of mTORC1 accumulation on lysosomes. This work provides valuable information for better insights into p17-modulated inhibition of mTORC1, which induces autophagy and translation shutoff to benefit virus replication.


Subject(s)
Lysosomes , Mechanistic Target of Rapamycin Complex 1 , Orthoreovirus, Avian , Adaptor Proteins, Signal Transducing , Autophagy , Cell Line, Tumor , Humans , Lysosomes/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Orthoreovirus, Avian/physiology , Proto-Oncogene Proteins c-akt/metabolism , Tacrolimus Binding Proteins , Tuberous Sclerosis Complex 2 Protein , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
4.
J Virol ; 96(6): e0007422, 2022 03 23.
Article in English | MEDLINE | ID: mdl-35107368

ABSTRACT

In this work we have determined that heat shock protein 90 (Hsp90) is essential for avian reovirus (ARV) replication by chaperoning the ARV p17 protein. p17 modulates the formation of the Hsp90/Cdc37 complex by phosphorylation of Cdc37, and this chaperone machinery protects p17 from ubiquitin-proteasome degradation. Inhibition of the Hsp90/Cdc37 complex by inhibitors (17-N-allylamino-17-demethoxygeldanamycin 17-AGG, and celastrol) or short hairpin RNAs (shRNAs) significantly reduced expression levels of viral proteins and virus yield, suggesting that the Hsp90/Cdc37 chaperone complex functions in virus replication. The expression levels of p17 were decreased at the examined time points (2 to 7 h and 7 to 16 h) in 17-AAG-treated cells in a dose-dependent manner while the expression levels of viral proteins σA, σC, and σNS were decreased at the examined time point (7 to 16 h). Interestingly, the expression levels of σC, σA, and σNS proteins increased along with coexpression of p17 protein. p17 together with the Hsp90/Cdc37 complex does not increase viral genome replication but enhances viral protein stability, maturation, and virus production. Virus factories of ARV are composed of nonstructural proteins σNS and µNS. We found that the Hsp90/Cdc37 chaperone complex plays an important role in accumulation of the outer-capsid protein σC, inner core protein σA, and nonstructural protein σNS of ARV in viral factories. Depletion of Hsp90 inhibited σA, σC, and p17 proteins colocalized with σNS in viral factories. This study provides novel insights into p17-modulated formation of the Hsp90/Cdc37 chaperone complex governing virus replication via stabilization and maturation of viral proteins and accumulation of viral proteins in viral factories for virus assembly. IMPORTANCE Molecular mechanisms that control stabilization of ARV proteins and the intermolecular interactions among inclusion components remain largely unknown. Here, we show that the ARV p17 is an Hsp90 client protein. The Hsp90/Cdc37 chaperone complex is essential for ARV replication by protecting p17 chaperone from ubiquitin-proteasome degradation. p17 modulates the formation of Hsp90/Cdc37 complex by phosphorylation of Cdc37, and this chaperone machinery protects p17 from ubiquitin-proteasome degradation, suggesting a feedback loop between p17 and the Hsp90/Cdc37 chaperone complex. p17 together with the Hsp90/Cdc37 complex does not increase viral genome replication but enhances viral protein stability and virus production. Depletion of Hsp90 prevented viral proteins σA, σC, and p17 from colocalizing with σNS in viral factories. Our findings elucidate that the Hsp90/Cdc37 complex chaperones p17, which, in turn, promotes the synthesis of viral proteins σA, σC, and σNS and facilitates accumulation of the outer-capsid protein σC and inner core protein σA in viral factories for virus assembly.


Subject(s)
Cell Cycle Proteins , Chaperonins , HSP90 Heat-Shock Proteins , Orthoreovirus, Avian , Viral Proteins , Virus Replication , Animals , Capsid Proteins/genetics , Capsid Proteins/metabolism , Cell Cycle Proteins/metabolism , Chaperonins/metabolism , Genome, Viral , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Orthoreovirus, Avian/physiology , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Viral Envelope Proteins/metabolism , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Replication/genetics
5.
Vet Microbiol ; 264: 109277, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34826648

ABSTRACT

Avian reoviruses (ARVs) are important pathogens that cause considerable economic losses in poultry farming. To date, host factors that control stabilization of ARV proteins remain largely unknown. In this work we determined that the eukaryotic chaperonin T-complex protein-1 (TCP-1) ring complex (TRiC) is essential for avian reovirus (ARV) replication by stabilizing outer-capsid protein σC, inner core protein σA, and the non-structural protein σNS of ARV. TriC serves as a chaperone of viral proteins and prevent their degradation via the ubiquitin-proteasome pathway. Furthermore, reciprocal co-immunoprecipitation assays confirmed the association of viral proteins (σA, σC, and σNS) with TRiC. Immunofluorescence staining indicated that the TRiC chaperonins (CCT2 and CCT5) are colocalized with viral proteins σC, σA, and σNS of ARV. In this study, inhibition of TRiC chaperonins (CCT2 and CCT5) by the inhibitor HSF1A or shRNAs significantly reduced expression levels of the σC, σA, and σNS proteins of ARV as well as virus yield, suggesting that the TRiC complex functions in stabilization of viral proteins and virus replication. This study provides novel insights into TRiC chaperonin governing virus replication via stabilization of outer-capsid protein σC, inner core protein σA, and the non-structural protein σNS of ARV.


Subject(s)
Chaperonin Containing TCP-1 , Orthoreovirus, Avian , Viral Proteins , Virus Replication , Animals , Capsid Proteins/metabolism , Chaperonin Containing TCP-1/metabolism , Orthoreovirus, Avian/genetics , Proteasome Endopeptidase Complex/metabolism , RNA-Binding Proteins/metabolism , Ubiquitin/metabolism , Viral Core Proteins/metabolism , Viral Proteins/metabolism , Viral Regulatory and Accessory Proteins/metabolism , Virus Replication/genetics
6.
Vet Res ; 51(1): 112, 2020 Sep 09.
Article in English | MEDLINE | ID: mdl-32907618

ABSTRACT

To increase expression levels of the PCV2 Cap(d41) protein, novel baculovirus surface display vectors with multiple expression cassettes were constructed to create recombinant baculoviruses BacSC-Cap(d41), BacDD-2Cap(d41), BacDD-3Cap(d41), and BacDD-4Cap(d41). Our results reveal that the recombinant baculovirus BacDD-4Cap(d41) was able to express the highest levels of Cap(d41) protein. Optimum conditions for expressing the PCV2 Cap(d41) protein were determined, and our results show that 107 of Sf-9 infected with the recombinant baculovirus BacDD-4Cap(d41) at an MOI of 5 for 3 days showed the highest level of protein expression. Mice immunized with the 4Cap(d41) vaccine which was prepared from the recombinant baculovirus-infected cells (107) elicited higher ELISA titers compared to the Cap (d41) vaccine. The 4Cap(d41) vaccine could elicit anti-PCV2 neutralizing antibodies and IFN-γ in mice, as confirmed by virus neutralization test and IFN-γ ELISA. Moreover, the swine lymphocyte proliferative responses indicated that the 4Cap(d41) vaccine was able to induce a clear cellular immune response. Flow cytometry analysis showed that the percentage of CD4+ T cells and CD4+/CD8+ ratio was increased significantly in SPF pigs immunized with the 4Cap(d41) vaccine. Importantly, the 4Cap(d41) vaccine induced an IFN-γ response, further confirming that its effect is through cellular immunity in SPF pigs. An in vivo challenge study revealed that the 4Cap(d41) and the commercial vaccine groups significantly reduce the viral load of vaccinated pigs as compared with the CE negative control group. Taken together, we have successfully developed a 4Cap(d41) vaccine that may be a potential subunit vaccine for preventing the disease associated with PCV2 infections.


Subject(s)
Baculoviridae , Circoviridae Infections/veterinary , Circovirus/immunology , Immunogenicity, Vaccine , Swine Diseases/immunology , Viral Proteins/immunology , Animals , Circoviridae Infections/immunology , Genetic Vectors/administration & dosage , Mice , Specific Pathogen-Free Organisms , Sus scrofa , Swine , Viral Proteins/administration & dosage
7.
Surg Laparosc Endosc Percutan Tech ; 29(6): e88-e93, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31568254

ABSTRACT

BACKGROUND: Transoral endoscopic parathyroidectomy vestibular approach for secondary hyperparathyroidism (SHPT) is controversial with regard to the time consumed, safety, and feasibility. We present our initial experience with modified transoral endoscopic parathyroidectomy vestibular approach (m-TOEPVA) procedure for SHPT using total parathyroidectomy with autotransplantation. MATERIALS AND METHODS: We retrospectively reviewed 10 patients with SHPT who underwent the m-TOEPVA procedure from December 2017 to April 2018 at our center. RESULTS: There were a total of 6 male individuals and 4 female individuals with a median age of 58.5 years. Among whom, 5 were on hemodialysis and 5 on peritoneal dialysis. The median length of hospital stay and operative time was 5 (4, 5) days, and 321.5 (302.75, 362.25) minutes, respectively. Successful removal of 4 parathyroid glands was achieved in 8 of 10 patients (80%) and, in 8 patients (8/10, 80%), the intact parathyroid hormone successfully dropped to <300 pg/mL at 3 months postoperatively. Two patients with ectopic parathyroid gland in the superior mediastinum were noted preoperatively by MIBI scan and subsequently had successful removal. Except for 1 patient with prolonged hospital stay (11 d) due to hungry bone syndrome, there were no other major complications. CONCLUSION: m-TOEPVA by total parathyroidectomy with autotransplantation for SHPT is feasible, safe, and offers optimal cosmetic results. The most valuable part is that m-TOEPVA provides direct visualization and successful removal of the ectopic parathyroid glands in the superior mediastinum.


Subject(s)
Choristoma/surgery , Hyperparathyroidism, Secondary/surgery , Mediastinal Diseases/surgery , Natural Orifice Endoscopic Surgery/methods , Parathyroid Glands , Parathyroidectomy/methods , Adult , Aged , Choristoma/complications , Choristoma/diagnosis , Female , Humans , Hyperparathyroidism, Secondary/diagnosis , Hyperparathyroidism, Secondary/etiology , Male , Mediastinal Diseases/complications , Mediastinal Diseases/diagnosis , Middle Aged , Mouth , Retrospective Studies , Ultrasonography/methods
8.
J Virol ; 93(20)2019 10 15.
Article in English | MEDLINE | ID: mdl-31375578

ABSTRACT

Avian reovirus (ARV) p17 protein continuously shuttles between the nucleus and the cytoplasm via transcription-dependent and chromosome region maintenance 1 (CRM1)-independent mechanisms. Nevertheless, whether cellular proteins modulate nucleocytoplasmic shuttling of p17 remains unknown. This is the first report that heterogeneous nuclear ribonucleoprotein (hnRNP) A1 serves as a carrier protein to modulate nucleocytoplasmic shuttling of p17. Both in vitro and in vivo studies indicated that direct interaction of p17 with hnRNP A1 maps within the amino terminus (amino acids [aa] 19 to 40) of p17 and the Gly-rich region of the C terminus of hnRNP A1. Furthermore, our results reveal that the formation of p17-hnRNP A1-transportin 1 carrier-cargo complex is required to modulate p17 nuclear import. Utilizing sequence and mutagenesis analyses, we have identified nuclear export signal (NES) 19LSLRELAI26 of p17. Mutations of these residues causes a nuclear retention of p17. In this work, we uncovered that the N-terminal 21 amino acids (aa 19 to 40) of p17 that comprise the NES can modulate both p17 and hnRNP A1 interaction and nucleocytoplasmic shuttling of p17. In this work, the interaction site of p17 with lamin A/C was mapped within the amino terminus (aa 41 to 60) of p17 and p17 colocalized with lamin A/C at the nuclear envelope. Knockdown of hnRNP A1 or lamin A/C led to inhibition of nucleocytoplasmic shuttling of p17 and reduced virus yield. Collectively, the results of this study provide mechanistic insights into hnRNP A1 and lamin A/C-modulated nucleocytoplasmic shuttling of the ARV p17 protein.IMPORTANCE Avian reoviruses (ARVs) cause considerable economic losses in the poultry industry. The ARV p17 protein continuously shuttles between the nucleus and the cytoplasm to regulate several cellular signaling pathways and interacts with several cellular proteins to cause translation shutoff, cell cycle arrest, and autophagosome formation, all of which enhance virus replication. To date the mechanisms underlying nucleocytoplasmic shuttling of p17 remain largely unknown. Here we report that hnRNP A1 and lamin A/C serve as carrier and mediator proteins to modulate nucleocytoplasmic shuttling of p17. The formation of p17-hnRNP A1-transportin 1 carrier-cargo complex is required to modulate p17 nuclear import. Furthermore, we have identified an NES-containing nucleocytoplasmic shuttling domain (aa 19 to 40) of p17 that is critical for binding to hnRNP A1 and for nucleocytoplasmic shuttling of p17. This study provides novel insights into how hnRNP A1 and lamin A/C modulate nucleocytoplasmic shuttling of the ARV p17 protein.


Subject(s)
Heterogeneous Nuclear Ribonucleoprotein A1/metabolism , Host-Pathogen Interactions , Lamin Type A/metabolism , Orthoreovirus, Avian/physiology , Reoviridae Infections/metabolism , Reoviridae Infections/virology , Viral Matrix Proteins/metabolism , Active Transport, Cell Nucleus , Animals , Cell Nucleus/metabolism , Cytoplasm/metabolism , Humans , Models, Biological , Protein Binding
9.
Cell Microbiol ; 20(12): e12946, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30156372

ABSTRACT

Adenosine triphosphate (ATP) is an energy source for many types of viruses for facilitating virus replication. This is the first report to demonstrate that the structural protein σA of avian reovirus (ARV) functions as an activator of cellular energy. Three cellular factors, isocitrate dehydrogenase 3 subunit beta (IDH3B), lactate dehydrogenase A (LDHA), and vacuolar-type H+-ATPase (vATPase) co-immunoprecipitated with ARV σA and were identified by 2D-LC/MS/MS. ARV enhances glycolytic flux through upregulation of glycolytic enzymes. Increased ATP levels in both ARV-infected and σA-transfected cells were observed by a fluorescence resonance energy transfer-based genetically encoded indicator, Ateams. Furthermore, σA upregulates IDH3B and glutamate dehydrogenase (GDH) to promote glutaminolysis, activating HIF-1α. Both HIF-1α level and viral yield in IDH3B-depleted and glutamine-deprived cells, and inhibition of glutaminolysis was significantly reduced. The σAR155/273A mutant loses its ability to enter the nucleolus, impairing its ability to regulate glycolysis. In addition, we have identified the conserved untranslated regions (UTR) of the 5'- and 3'-termini of the ARV genome segments that are required for viral protein synthesis in an ATP-dependent manner. Deletion of either the 5'- or 3'-UTR impaired viral protein synthesis. Knockdown of σA reduced the ATP level and significantly decreased virus yield, suggesting that σA enhances ATP formation to promote virus replication. Collectively, this study provides novel insights into σA-modulated suppression of LDHA and activation of IDH3B and GDH to activate the mTORC1/eIF4E/HIF-1α pathways to upregulate glycolysis and the TCA cycle for virus replication.


Subject(s)
Glycolysis/physiology , L-Lactate Dehydrogenase/metabolism , Orthoreovirus, Avian/physiology , RNA-Binding Proteins/metabolism , Viral Core Proteins/metabolism , Virus Replication/physiology , 3' Untranslated Regions , 5' Untranslated Regions , Adenosine Triphosphate/metabolism , Animals , Chlorocebus aethiops , Citric Acid Cycle/physiology , Eukaryotic Initiation Factor-4E/genetics , Eukaryotic Initiation Factor-4E/metabolism , Genome, Viral , Glutamine/metabolism , Host-Pathogen Interactions/physiology , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Isocitrate Dehydrogenase/genetics , Mechanistic Target of Rapamycin Complex 1/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Orthoreovirus, Avian/pathogenicity , Reoviridae Infections/metabolism , Vero Cells
10.
J Nanosci Nanotechnol ; 18(5): 3518-3522, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29442860

ABSTRACT

In this study, zinc indium tin oxide thin-film transistors (ZITO TFTs) were fabricated by the radio frequency (RF) sputtering deposition method. Adding indium cations to ZnO by co-sputtering allows the development of ZITO TFTs with improved performance. Material characterization revealed that ZITO TFTs have a threshold voltage of 0.9 V, a subthreshold swing of 0.294 V/decade, a field-effect mobility of 5.32 cm2/Vs, and an on-off ratio of 4.7 × 105. Furthermore, an investigation of the photosensitivity of the fabricated devices was conducted by an illumination test. The responsivity of ZITO TFTs was 26 mA/W, with 330-nm illumination and a gate bias of -1 V. The UV-to-visible rejection ratio for ZITO TFTs was 2706. ZITO TFTs were observed to have greater UV light sensitivity than that of ZnO TFTs. We believe that these results suggest a significant step toward achieving high photosensitivity. In addition, the ZITO semiconductor system could be a promising candidate for use in high performance transparent TFTs, as well as further sensing applications.

11.
Materials (Basel) ; 10(2)2017 Feb 04.
Article in English | MEDLINE | ID: mdl-28772487

ABSTRACT

We investigated the electrical and optoelectronic properties of a magnesium zinc oxide thin-film phototransistor. We fabricate an ultraviolet phototransistor by using a wide-bandgap MgZnO thin film as the active layer material of the thin film transistor (TFT). The fabricated device demonstrated a threshold voltage of 3.1 V, on-off current ratio of 105, subthreshold swing of 0.8 V/decade, and mobility of 5 cm²/V·s in a dark environment. As a UV photodetector, the responsivity of the device was 3.12 A/W, and the rejection ratio was 6.55 × 105 at a gate bias of -5 V under 290 nm illumination.

12.
Nanomaterials (Basel) ; 7(7)2017 Jun 26.
Article in English | MEDLINE | ID: mdl-28672868

ABSTRACT

Indium titanium zinc oxide (InTiZnO) as the channel layer in thin film transistor (TFT) grown by RF sputtering system is proposed in this work. Optical and electrical properties were investigated. By changing the oxygen flow ratio, we can suppress excess and undesirable oxygen-related defects to some extent, making it possible to fabricate the optimized device. XPS patterns for O 1s of InTiZnO thin films indicated that the amount of oxygen vacancy was apparently declined with the increasing oxygen flow ratio. The fabricated TFTs showed a threshold voltage of -0.9 V, mobility of 0.884 cm²/Vs, on-off ratio of 5.5 × 105, and subthreshold swing of 0.41 V/dec.

13.
Sensors (Basel) ; 16(12)2016 Dec 15.
Article in English | MEDLINE | ID: mdl-27983694

ABSTRACT

A metal-semiconductor-metal ultraviolet photodetector has been fabricated with a radiofrequency (RF)-sputtered InGaO thin film. Results for the devices fabricated under different oxygen partial pressure are here in discussed. Under low oxygen partial pressure, the devices work in the photoconductive mode because of the large number of subgap states. Therefore, the devices exhibit internal gain. These defects in the films result in slow switching times and lower photo/dark current ratios. A higher flow ratio of oxygen during the sputtering process can effectively restrain the oxygen vacancies in the film. The responsivity of the photodetector fabricated under an oxygen flow ratio of 20% can reach 0.31 A/W. The rise time and decay time can reach 21 s and 27 s, respectively.

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