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BACKGROUND & AIMS: High expression of phosphatidylinositol 4-kinase III alpha (PI4KIIIα) correlates with poor survival rates in patients with hepatocellular carcinoma. In addition, hepatitis C virus (HCV) infections activate PI4KIIIα and contribute to hepatocellular carcinoma progression. We aimed at mechanistically understanding the impact of PI4KIIIα on the progression of liver cancer and the potential contribution of HCV in this process. METHODS: Several hepatic cell culture and mouse models were used to study the functional importance of PI4KIIIα on liver pathogenesis. Antibody arrays, gene silencing, and PI4KIIIα-specific inhibitor were applied to identify the involved signaling pathways. The contribution of HCV was examined by using HCV infection or overexpression of its nonstructural protein. RESULTS: High PI4KIIIα expression and/or activity induced cytoskeletal rearrangements via increased phosphorylation of paxillin and cofilin. This led to morphologic alterations and higher migratory and invasive properties of liver cancer cells. We further identified the liver-specific lipid kinase phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2γ) working downstream of PI4KIIIα in regulation of the cytoskeleton. PIK3C2γ generates plasma membrane phosphatidylinositol 3,4-bisphosphate-enriched, invadopodia-like structures that regulate cytoskeletal reorganization by promoting Akt2 phosphorylation. CONCLUSIONS: PI4KIIIα regulates cytoskeleton organization via PIK3C2γ/Akt2/paxillin-cofilin to favor migration and invasion of liver cancer cells. These findings provide mechanistic insight into the contribution of PI4KIIIα and HCV to the progression of liver cancer and identify promising targets for therapeutic intervention.
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Fatores de Despolimerização de Actina , Carcinoma Hepatocelular , Movimento Celular , Citoesqueleto , Neoplasias Hepáticas , Invasividade Neoplásica , Paxilina , Transdução de Sinais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Humanos , Animais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Paxilina/metabolismo , Camundongos , Fatores de Despolimerização de Actina/metabolismo , Fatores de Despolimerização de Actina/genética , Fosforilação , Hepacivirus , Linhagem Celular Tumoral , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Células Hep G2 , Hepatite C/patologia , Hepatite C/metabolismo , Hepatite C/virologia , Interferência de RNARESUMO
Organic afterglow materials have significant applications in information security and flexible electronic devices with unique optical properties. It is vital but challenging to develop organic afterglow materials possessing controlled output with multi-stimuli-responsive capacity. Herein, dimethyl terephthalate (DTT) is introduced as a strong proton acceptor. The migration direction of NâH protons on two compounds Hs can be regulated by altering the excitation wavelength (Ex) or amine stimulation, thereby achieving dual-stimuli-responsive afterglow emission. When the Ex is below 300 nm, protons migrate to S1-2 DTT, where strong interactions induce phosphorescent emission of Hs, resulting in afterglow behavior. Conversely, when the Ex is above 300 nm, protons interact with the S0 DTT weakly and the afterglow disappears. In view of amine-based compounds with higher proton accepting capabilities, it can snatch proton from S1-2 DTT and redirect the proton flow toward amine, effectively suppressing the afterglow but obtaining a new redshifted fluorescence emission with Δλ over 200 nm due to the high polarity of amine. Moreover, it is successfully demonstrated that the applications of dual-stimuli-responsive organic afterglow materials in information encryption based on the systematic excitation-wavelength-dependent (Ex-De) behavior and amine selectivity detection.
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Multiple distinct specialized regions shape the architecture of maize leaves. Among them, the fringe-like and wedge-shaped auricles alter the angle between the leaf and stalk, which is a key trait in crop plant architecture. As planting density increased, a small leaf angle (LA) was typically selected to promote crop light capture efficiency and yield. In the present study, we characterized two paralogous INDETERMINATE DOMAIN (IDD) genes, ZmIDD14 and ZmIDD15, which contain the Cys2-His2 zinc finger domain and function redundantly to regulate auricle development and LA in maize. Loss-of-function mutants showed decreased LA by reducing adaxial sclerenchyma thickness and increasing the colourless cell layers. In addition, the idd14;idd15 double mutant exhibited asymmetrically smaller auricles, which might cause by a failed maintenance of symmetric expression of the key auricle size controlling gene, LIGULELESS(LG1). The transcripts of ZmIDD14 and ZmIDD15 enriched in the ligular region, where LG1 was highly expressed, and both proteins physically interacted with ZmILI1 to promote LG1 transcription. Notably, the idd14;idd15 enhanced the grain yield of hybrids under high planting densities by shaping the plant architecture with a smaller LA. These findings demonstrate the functions of ZmIDD14 and ZmIDD15 in controlling the abaxial/adaxial development of sclerenchyma in the midrib and polar development along the medial-lateral axes of auricles and provide an available tool for high-density and high-yield breeding in maize.
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BACKGROUND & AIMS: Hepatitis A virus (HAV) infections are considered not to trigger innate immunity in vivo, in contrast to hepatitis C virus (HCV). This lack of induction has been imputed to strong interference by HAV proteases 3CD and 3ABC. We aimed to elucidate the mechanisms of immune activation and counteraction by HAV and HCV in vivo and in vitro. METHODS: Albumin-urokinase-type plasminogen activator/severe combined immunodeficiency (Alb/uPA-SCID) mice with humanised livers were infected with HAV and HCV. Hepatic cell culture models were used to assess HAV and HCV sensing by Toll-like receptor 3 and retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 (RIG-I/MDA5), respectively. Cleavage of the adaptor proteins TIR-domain-containing adapter-inducing interferon-ß (TRIF) and mitochondrial antiviral-signalling protein (MAVS) was analysed by transient and stable expression of HAV and HCV proteases and virus infection. RESULTS: We detected similar levels of interferon-stimulated gene induction in hepatocytes of HAV- and HCV-infected mice with humanised liver. In cell culture, HAV induced interferon-stimulated genes exclusively upon MDA5 sensing and depended on LGP2 (laboratory of genetics and physiology 2). TRIF and MAVS were only partially cleaved by HAV 3ABC and 3CD, not sufficiently to abrogate signalling. In contrast, HCV NS3-4A efficiently degraded MAVS, as previously reported, whereas TRIF cleavage was not detected. CONCLUSIONS: HAV induces an innate immune response in hepatocytes via MDA5/LGP2, with limited control of both pathways by proteolytic cleavage. HCV activates Toll-like receptor 3 and lacks TRIF cleavage, suggesting that this pathway mainly contributes to HCV-induced antiviral responses in hepatocytes. Our results shed new light on the induction of innate immunity and counteraction by HAV and HCV. IMPACT AND IMPLICATIONS: Understanding the mechanisms that determine the differential outcomes of HAV and HCV infections is crucial for the development of effective therapies. Our study provides insights into the interplay between these viruses and the host innate immune response in vitro and in vivo, shedding light on previously controversial or only partially investigated aspects. This knowledge could tailor the development of new strategies to combat HCV persistence, as well as improve our understanding of the factors underlying successful HAV clearance.
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Hepatite A , Hepatite C , Evasão da Resposta Imune , Imunidade Inata , Vírus da Hepatite A , Hepacivirus , Animais , Camundongos , Camundongos SCIDRESUMO
One-dimensional shaped ZnGa2O4, ZnO and ZnGa2O4/ZnO nanofibers were successfully prepared by electrostatic spinning technique and the photocatalytic degradation performance of tetracycline hydrochloride (TC-HCl) were studied. It was found that the S-scheme heterojunction formed in the ZnGa2O4/ZnO could greatly reduce the recombination of the photogenerated carriers and therefore improve the photocatalytic performance. By optimizing the ratio of the ZnGa2O4 and ZnO, the largest degradation rate could reach 0.0573 min-1, which was 20 times of the self-degradation rate of TC-HCl. It was verified that the h+ played the key role in the reactive groups for the high performance decomposition of TC-HCl by capture experiments. This work provides a new method for the highly efficient photocatalytic degradation of TC-HCl.
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Nanofibras , Óxido de Zinco , TetraciclinaRESUMO
BACKGROUND: Both closed platform and open platform robotic-assisted total hip arthroplasty (THA) have recently been recommended as a viable treatment option for achieving accurate positioning of components. Yet, limited studies paid attention to the differences between the closed platform robotic system and the open platform robotic system. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and learning curve of two systems. MATERIALS AND METHODS: We retrospectively included 62 patients (31 closed robotic system and 31 open robotic system) who underwent THA between February 2021 and January 2023. The demographics, operating time, cup positioning, complications and hip Harris score were evaluated. Learning curves of operation time was conducted using cumulative sum (CUSUM) analysis. RESULTS: There were no differences in surgical time (76.7 ± 12.1 min vs. 72.3 ± 14.8 min), estimated blood loss (223.2 ± 13.2 ml vs. 216.9 ± 17 ml) and Harris Hip score (HHS) between closed platform robotic system and the open platform robotic system. The closed robotic system and the open robotic system were associated with a learning curve of 9 cases and 7 cases for surgical time respectively, based on the satisfying rate of Lewinnek's safe zone outliers (1/31, 96.8%) and no occurrence of complication. Both robotic systems had significant reduction in overall surgical time, the duration of acetabulum registration, and estimated blood loss between learning phase and proficiency phase. CONCLUSION: The authors suggest that the surgical outcomes and safe zone outlier rate of the open robotic-assisted THA were similar to those of the closed robotic-assisted THA. These two robotic-assisted are associated with comparable learning curves and both have the precise positioning of acetabular component. From learning phase to proficiency phase, the rate of positions within the safe zone differed only marginally (88.9-100% vs. 85.7-100%) based on a rather low number of patients. This is not a statistically significant difference. Therefore, we suggest that THA undergoing with the robotic-assisted system is the relatively useful way to achieve planned acetabular cup position so far.
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Artroplastia de Quadril , Procedimentos Cirúrgicos Robóticos , Humanos , Curva de Aprendizado , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , AcetábuloRESUMO
BACKGROUND: The bitter taste receptor gene TAS2R38 is a member of the human TAS2R gene family. Polymorphisms in TAS2R38 affect the ability to taste the bitterness of phenylthiourea (PTC) compounds, thus affecting an individual's food preference and health status. METHODS: We investigated polymorphisms in the TAS2R38 gene and the sensitivity to PTC bitterness among healthy Chinese college students in Hubei province. The association of TAS2R38 polymorphisms and PTC sensitivity with body mass index (BMI), food preference, and health status was also analyzed. A total of 320 healthy college students were enrolled (male: 133, female: 187; aged 18-23 years). The threshold value method was used to measure the perception of PTC bitterness, and a questionnaire was used to analyze dietary preferences and health status. Polymerase chain reaction (PCR) was used to analyze polymorphisms at three common TAS2R38 loci (rs713598, rs1726866, and rs10246939). RESULTS: In our study population, 65.00% of individuals had medium sensitivity to the bitterness of PTC; in contrast, 20.94% were highly sensitive to PTC bitterness, and 14.06% were not sensitive. For the TAS2R38 gene, the PAV/PAV and PAV/AAI diplotypes were the most common (42.19% and 40.63%, respectively), followed by the homozygous AVI/AVI (8.75%) and PAV/AVI (5.00%) diplotypes. CONCLUSION: There was a significant correlation between the sensitivity to PTC bitterness and sex, but there was no correlation between the common diplotypes of TAS2R38 and gender. Polymorphisms in the TAS2R38 gene were associated with the preference for tea, but not with one's native place, BMI, health status, or other dietary preferences. There was no significant correlation between the perception of PTC bitterness and one's native place, BMI, dietary preference, or health status. We hope to find out the relationship between PTC sensitivity and TAS2R38 gene polymorphisms and dietary preference and health status of Chinese population through this study, providing relevant guidance and suggestions for dietary guidance and prevention of some chronic diseases in Chinese population.
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Feniltioureia , Receptores Acoplados a Proteínas G , Paladar , Feminino , Humanos , Masculino , Povo Asiático/genética , Receptores Acoplados a Proteínas G/genética , Estudantes , Paladar/genéticaRESUMO
BACKGROUND: Patients with poliomyelitis underwent total hip arthroplasty (THA) are known to be at higher risk of dislocation on account of muscular atrophy. This study aimed to investigate clinical outcomes, radiographic outcomes, complication rates, and survivorship of dual mobility THA in displaced femoral neck fractures of elderly with poliomyelitis. MATERIALS AND METHODS: We retrospectively included 17 patients (17 hips) with residual poliomyelitis who underwent THA with dual mobility articulation. Clinical outcomes were assessed with the visual analog scale (VAS) pain score, Oxford hip score, and University of California Los Angeles activity (UCLA) score. Radiographic outcomes were examined by radiographs. Complications and re-operations following THA were recorded. RESULTS: The mean follow-up period was 77.05 months. The mean VAS, Oxford hip score, and UCLA score were improved significantly. In all but one patient, no complications were occurred. Re-operation was carried out in one patient due to posterior dislocation. The Kaplan-Meier survivorship with an end point of re-operation for any reason was 94.1%. CONCLUSIONS: THA with dual mobility system is proved to be effective in strengthening stability and reducing the risk of dislocation, which is suitable for patients with neuromuscular disease. Hence, in elderly with residual poliomyelitis, dual mobility THA is a valid choice as a treatment for displaced femoral neck fractures.
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Artroplastia de Quadril , Fraturas do Colo Femoral , Luxação do Quadril , Prótese de Quadril , Poliomielite , Idoso , Fraturas do Colo Femoral/cirurgia , Luxação do Quadril/cirurgia , Humanos , Poliomielite/complicações , Desenho de Prótese , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Performing postoperative laboratory tests following joint arthroplasty is a regular practice. However, the role of routine postoperative laboratory tests in primary hip arthroplasty is currently in doubt. This study aimed to assess the role of routine postoperative laboratory tests for femoral neck fractures in elderly patients who underwent hip hemiarthroplasty and to evaluate the risk factors for postoperative laboratory testing abnormalities and related interventions. METHODS: This retrospective study reviewed 735 consecutive patients with femoral neck fractures (FNFs) who underwent hip hemiarthroplasty at a single tertiary academic organization. Patient characteristic features and laboratory testing values were recorded. Logistic regression models were calculated to identify risk factors. RESULTS: A total of 321 elderly patients (> 75 years of age) were ultimately enrolled for analysis. Abnormal postoperative laboratory tests were found in 265 patients (82.6%). Only a minority of the included patients (7.5%) needed medical intervention to treat postoperative laboratory testing abnormalities. Multivariate logistic regression analysis reported that a higher Charlson comorbidity index (CCI) (P = 0.03), abnormal preoperative haemoglobin level (P < 0.01), higher intraoperative blood loss (P < 0.01) and less frequent tranexamic acid use (P = 0.05) were risk factors for abnormal postoperative laboratory tests. Furthermore, a higher CCI has been identified as a risk factor for patients needing clinical interventions related to laboratory abnormalities. CONCLUSIONS: Because 92.5% of laboratory tests did not influence postoperative management, the authors suggest that routine laboratory tests after hip hemiarthroplasty for FNFs are less instructive for the majority of elderly patients. Nevertheless, for patients with identified risk factors, postoperative laboratory tests are still required to identify the abnormalities that need to be managed.
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Artroplastia de Quadril , Fraturas do Colo Femoral , Hemiartroplastia , Idoso , Artroplastia de Quadril/efeitos adversos , Fraturas do Colo Femoral/diagnóstico , Fraturas do Colo Femoral/epidemiologia , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Humanos , Período Pós-Operatório , Estudos RetrospectivosRESUMO
The search for heavy-metal-free quantum-dot light-emitting diodes (QD-LEDs) has greatly intensified in the past few years because device performance still falls behind that of CdSe-based QD-LEDs. Apart from the effects of nanostructures of the emitting materials, the unbalanced charge injection and transport severely affects the performance of heavy-metal-free QD-LEDs. In this work, we presented solution-processed double hole transport layers (HTLs) for improving the device performance of heavy-metal-free Cu-In-Zn-S(CIZS)/ZnS-based QD-LEDs, in which N,N'-Bis(3-methylphenyl)-N,N'-bis(phenyl)benzidine (TPD) as an interlayer was incorporated between the emitting layer and the HTL. Through optimizing the thickness of poly(9,9-dioctylfluorene-co-N-(4-butylphenyl)diphenyl-amine (TFB) and TPD layers, a maximum external quantum efficiency (ηEQE) of 3.87% and a current efficiency of 9.20 cd A-1 were achieved in the solution-processed QD-LEDs with double-layered TFB/TPD as the HTLs, which were higher than those of the devices with pristine TFB, TPD and TFB:TPD blended layers. The performance enhancement could be attributed to the synergistic effects of the reduction of the hole injection barrier, the increase of the hole mobility and suppressed charge transfer between the HTL and the emitting layer. Furthermore, the best ηEQE of 5.61% with a mean ηEQE of 4.44 ± 0.73% was realized in the Cu-In-Zn-S-based QD-LEDs by varying the annealing temperature of TPD layer due to the more balanced charge injection and transport as well as smooth surface of TPD layer.
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PURPOSE: To investigate the value of diffusion-weighted imaging (DWI) in assessing dynamic changes of major salivary gland function during follow-up post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: 31 consecutive patients with pathologically confirmed NPC scheduled for RT underwent six routine follow-up MRI examinations including DWI sequence prior to (pre-RT) and 1, 3, 6, 9, and 12 months post RT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Objective measurement of salivary flow rate (SFR) under unstimulated (uSFR) and stimulated conditions (sSFR) as well as subjective xerostomia assessment according to a patient-rated questionnaire were conducted before each MRI. Variance analysis was used to evaluate dynamic changes of ADC, SFR and xerostomia questionnaire summary scores (XQ-sum) at different timepoints and the correlation between ADC and XQ-sum. Pearson's correlation test was used to evaluate the correlations between pre- and post-RT changes of ADC (ΔADC) and SFR (ΔSFR) or mean RT dose. RESULTS: At each timepoint, ADCs of PGs were significantly lower than of SMGs, uSFR was significantly lower than sSFR. For both PGs and SMGs, ADCpost-RT were all higher than ADCpre-RT, with significant differences. ADC1m-post-RT initially increased and changed little to ADC3m-post-RT, ADC6m-post-RT, ADC9m-post-RT, and ADC12m-post-RT, then gradually declined over time. The dynamic change trends of SFR were negatively paralleled to those of ADC, while that of XQ-sum was similar. Dose-response relationships were detected between salivary gland mean RT dose and ΔADC. In PGs, negative correlations between ΔsSFR9m-post-RT and ΔADC9m-post-RT, and ΔsSFR12m-post-RT and ΔADC12m-post-RT were detected. In SMGs, negative correlations between ΔsSFR12m-post-RT and ΔADC12m-post-RT, and ΔuSFR12m-post-RT and ΔADC12m-post-RT were also detected. The ADCs of patients with severe subjective xerostomia were significantly higher, while patients with moderate subjective xerostomia presented a tendency toward higher ADCs compared to those with mild xerostomia from 6 to 12 months post RT. CONCLUSION: As part of routine follow-up MRI in NPC patients, DWI might be a promising modality for follow-up assessing the dynamic changes of major salivary gland function and might be more powerful in the late post-RT period.
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Quimiorradioterapia , Imagem de Difusão por Ressonância Magnética , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Radioterapia de Intensidade Modulada , Glândulas Salivares/diagnóstico por imagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Imagem de Difusão por Ressonância Magnética/métodos , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Irradiação Linfática , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/secundário , Estudos Prospectivos , Lesões por Radiação/etiologia , Glândulas Salivares/fisiopatologia , Salivação/efeitos da radiação , Xerostomia/etiologia , Adulto JovemRESUMO
In this work, a dense γ-In2Se3 nanosheet array has been fabricated using the chemical vapor deposition method under atmospheric pressure. Compared with crystal silicon, the photodetector based on the γ-In2Se3/p-Si heterojunction exhibits a high responsivity (96.7 mA W-1) at the near-infrared region, a presentable current on/off ratio (â¼1000) and excellent detectivity (2.03 × 1012 jones). Simultaneously, the obtained photodetector demonstrated a fast response speed (0.15 ms/0.5 ms) and a broadband sensitive wavelength from ultraviolet (340 nm) to near-infrared (1020 nm). The photoelectric experimental data of the device shows that its high performance is attributed to the high-light absorption capacity of the material, the rational energy band structures of γ-In2Se3 and p-Si, and the effective separation of photo-generated carriers caused by the formed type-II heterojunction. Our work provides the primary experimental basis for the photodetection application of the γ-In2Se3 nanostructure.
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OBJECTIVE: To observe the intervention effect of Jujing Gouju Granules (JGG) on teratozoospermia (TZ) in rats and explore its action mechanism. METHODS: Thirty-two male SD rats were randomly divided into four groups of an equal number: normal control, TZ model control, high-dose JGG and low-dose JGG. The TZ model was established in the latter three groups of rats by intragastric administration of methyl methanesulfonate at 4 mg/100 g body weight/day for 7 consecutive days. After successful modeling, the animals in the high- and low-dose JGG groups were treated with JGG at 0.288 and 0.072g/100 g body weight/d, respectively, while the normal controls with the same dose of normal saline, all for 48 days. At two days after medication, all the rats were sacrificed and the right epididymides harvested for sperm counting, sperm motility analysis, observation the sperm morphology, and determination of contents of fructose, zinc, α-glucosidase and superoxide dismutase (SOD) in the epididymal suspension, the levels of IL-6, IL-8 and TNF-α in the seminal plasma, and that of reactive oxygen species (ROS) in the sperm. RESULTS: Both sperm concentration and motility were significantly increased and the percentage of morphologically abnormal sperm decreased in the JGG groups compared with the model controls, even more significantly in the high- than in the low-dose JGG group (P < 0.05). No statistically significant difference was found in the contents of fructose and zinc in the epididymal suspension among the four groups, but that of α-glucosidase was remarkably lower in the TZ model than in the normal controls (ï¼»50.31 ± 2.12ï¼½ vs ï¼»67.23 ± 3.54ï¼½ U/L, P < 0.05), but higher in the high- and low-dose JGG groups (ï¼»79.36 ± 2.35ï¼½ and ï¼»56.25 ± 3.44ï¼½ U/L) than in the model control group (P < 0.05). The level of ROS was markedly higher and that of SOD lower in the TZ model than in the normal controls, while the former was lower and the latter was higher in the JGG groups than in the TZ model controls (P < 0.05), even more significantly in the in the high- than in the low-dose JGG group (P < 0.05). Compared with the TZ model controls, the rats in the JGG groups showed dramatically decreased levels of IL-6, IL-8 and TNF-α in the seminal plasma, even more significantly in the high- than in the low-dose JGG group (P < 0.05). CONCLUSIONS: Jujing Gouju Granules can improve sperm morphology in teratozoospermia rats, possibly by regulating oxidative stress and inflammation-related factors.
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Motilidade dos Espermatozoides , Espermatozoides , Animais , Epididimo , Masculino , Ratos , Ratos Sprague-Dawley , Contagem de EspermatozoidesRESUMO
RNA-remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their in vitro activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-strand RNA viruses in the family Caliciviridae and constitute a significant and potentially fatal threat to human health. Here, we report that the protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA-chaperoning activity that can remodel structured RNAs and facilitate strand annealing. Moreover, NS3 can facilitate viral RNA synthesis in vitro by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA-remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound, and, more importantly, that it reduces the replication of the norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA-remodeling activities encoded by Caliciviridae and highlight the functional significance of NS3 in the noroviral life cycle.IMPORTANCE Noroviruses are a diverse group of positive-strand RNA viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. For RNA viruses, cellular or virus-encoded RNA helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. However, neither RNA helicase nor chaperoning activity has been demonstrated to be associated with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular RNA helicases/chaperones. We found that a norovirus protein, NS3, not only has ATP-dependent helicase activity, but also acts as an ATP-independent RNA chaperone. Also, NS3 can facilitate in vitro viral RNA synthesis, suggesting the important role of NS3 in norovirus replication. Moreover, NS3 activities can be inhibited by an FDA-approved compound, which also suppresses norovirus replicon replication in human cells, raising the possibility that NS3 could be a target for antinoroviral drug development.
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Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Norovirus/enzimologia , Norovirus/genética , RNA Helicases/genética , RNA Helicases/metabolismo , Proteínas não Estruturais Virais/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Guanidina/antagonistas & inibidores , Humanos , Estágios do Ciclo de Vida , Chaperonas Moleculares/efeitos dos fármacos , Norovirus/efeitos dos fármacos , Norovirus/crescimento & desenvolvimento , Nucleosídeo-Trifosfatase/genética , Nucleosídeo-Trifosfatase/metabolismo , Ligação Proteica , Dobramento de Proteína , RNA Helicases/efeitos dos fármacos , RNA Viral/química , RNA Viral/efeitos dos fármacos , RNA Viral/genética , RNA Viral/metabolismo , Replicon/efeitos dos fármacos , Alinhamento de Sequência , Análise de Sequência , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/efeitos dos fármacos , Proteínas não Estruturais Virais/genética , Replicação Viral/efeitos dos fármacos , Replicação Viral/fisiologiaRESUMO
BACKGROUND: Argonaute (AGO) protein is a kind of RNA binding protein that plays an integral role in the gene-silencing pathways guided by small RNAs. But there are few studies about the regulation of AGO genes responded to diverse abiotic stress in maize. RESULTS: In this study, we analyzed the expression of seventeen ZmAGO genes under heat, cold, salinity, drought and ABA treatments using quantitative PCR (qPCR). All ZmAGOs showed differential expression modes under various abiotic stress treatments. Two ZmAGOs (ZmAGO1a and ZmAGO5d) and other fifteen ZmAGOs exhibited specific up-regulation in response to heat separately. Several ZmAGO genes are very sensitive to cold stress, but many ZmAGO genes are slow to respond to NaCl treatment. Nine ZmAGO genes (ZmAGO1f, ZmAGO2b, ZmAGO4, ZmAGO5a/b/c, ZmAGO7, ZmAGO9 and ZmAGO18a/b) presented definite up-regulation in response to drought, which were similar to the pattern of gene regulation under abscisic acid (ABA) treatment. CONCLUSIONS: Various ZmAGO genes respond to different abiotic stress treatments. These results provide fundamental information and insights for the further study on the role of abiotic stress resistance genes in maize and provide basis for further study on the function of AGO genes in response to abiotic stress in maize.
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Proteínas Argonautas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Estresse Fisiológico/genética , Zea mays/genética , Perfilação da Expressão Gênica , Genes de Plantas , Resposta ao Choque Térmico/genética , FenótipoRESUMO
A gold-induced NH4Cl-assisted vapor-based route is proposed and developed to achieve vertically aligned submicron Se crystals on lattice-matched (111)-oriented silicon substrates, based on which a high-performance large-area silicon-compatible photodetector is constructed. Thanks to the energy band structure and the strongly asymmetrical depletion region, the fabricated Se/Si device maintains a similar wavelength cutoff to that of selenium devices before the IR region, along with a high-performance broadband photoresponse in the UV-to-visible region. The large-area photodetector maintains a very low leakage current under a -2 V bias, and a high on/off ratio of 103-104 is obtained with a high photocurrent of 62 nA at 500 nm. A photoresponse is clearly observed when the bias voltage is removed. The pulse response precisely provides a high response speed (τrise + τfall ≈ 1.975 ms), exceeding the fastest Se-based photodetectors in current reports. The enhanced photoelectric properties and the self-power photoresponse mainly derive from the integrated high-quality Se/n-Si p-n heterojunctions with both lattice match and type II energy band match.
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A novel self-powered UV photodetector based on electrospun ZnO nanofiber arrays is introduced. Aligned pure ZnO nanofibers and Ag-doped p-type ZnO nanofibers are processed perpendicular to each other, and p-n junction arrays of ZnO nanofibers are fabricated as a result. Owing to the intrinsic intervals between nanofibers, the device is fully transparent on quartz substrate. Various characterization methods including TEM, XRD, and XPS are used to testify the existence form of Ag element in ZnO nanofibers, and a field effect transistor is constructed to judge their conductivity. It is discovered that the Ag doping process not only transforms ZnO to p-type conductivity, making it possible to build this self-powered photodetector, but also forms Ag nanoparticles in ZnO nanofibers and thus helps reduce the response time. Benefiting from the abovementioned dual effects, this UV detector is found to have an enhanced performance, with the on-off ratio up to 104 at zero bias and a rather short rise/decay time of 3.90 s/4.71 s.
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A feasible strategy for hybrid photodetector by integrating an array of self-ordered TiO2 nanotubes (NTs) and selenium is demonstrated to break the compromise between the responsivity and response speed. Novel heterojunction between the TiO2 NTs and Se in combination with the surface trap states at TiO2 help regulate the electron transport and facilitate the separation of photogenerated electron-hole pairs under photovoltaic mode (at zero bias), leading to a high responsivity of ≈100 mA W-1 at 620 nm light illumination and the ultrashort rise/decay time (1.4/7.8 ms). The implanting of intrinsic p-type Se into TiO2 NTs broadens the detection range to UV-visible (280-700 nm) with a large detectivity of over 1012 Jones and a high linear dynamic range of over 80 dB. In addition, a maximum photocurrent of ≈107 A is achieved at 450 nm light illumination and an ultrahigh photosensitivity (on/off ratio up to 104 ) under zero bias upon UV and visible light illumination is readily achieved. The concept of employing novel heterojunction geometry holds great potential to pave a new way to realize high performance and energy-efficient optoelectronic devices for practical applications.
RESUMO
A novel CdMoO4 -ZnO composite film is prepared by spin-coating CdMoO4 microplates on ZnO film and is constructed as a heterojunction photodetector (PD). With an optimized loading amount of CdMoO4 microplates, this composite film PD achieves a ≈18-fold higher responsivity than pure ZnO film PD at 5 V bias under 350 nm (0.15 mW cm-2 ) UV light illumination, and its decay time shortens to half of the original value. Furthermore, Au nanoparticles are then deposited to modify the CdMoO4 -ZnO composite film, and the as-constructed photodetector with an optimized deposition time of Au nanoparticles yields an approximately two-fold higher photocurrent under the same condition, and the decay time reduces by half. The introduced CdMoO4 microplates form type-II heterojunctions with ZnO film and improve the photoelectric performance. The hot electrons from Au nanoparticles are injected into the CdMoO4 -ZnO composite film, leading to the increased photocurrent. When the light is off, the Schottky barriers formed between Au nanoparticles and CdMoO4 -ZnO composite film block the carrier transportation and accelerate the decay process of current. The study on Au-nanoparticle-modified CdMoO4 -ZnO composite film provides a facile method to construct ZnO film based PD with novel structure and high photoelectric performance.