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Birds are descended from non-avialan theropod dinosaurs of the Late Jurassic period, but the earliest phase of this evolutionary process remains unclear owing to the exceedingly sparse and spatio-temporally restricted fossil record1-5. Information about the early-diverging species along the avialan line is crucial to understand the evolution of the characteristic bird bauplan, and to reconcile phylogenetic controversies over the origin of birds3,4. Here we describe one of the stratigraphically youngest and geographically southernmost Jurassic avialans, Fujianvenator prodigiosus gen. et sp. nov., from the Tithonian age of China. This specimen exhibits an unusual set of morphological features that are shared with other stem avialans, troodontids and dromaeosaurids, showing the effects of evolutionary mosaicism in deep avialan phylogeny. F. prodigiosus is distinct from all other Mesozoic avialan and non-avialan theropods in having a particularly elongated hindlimb, suggestive of a terrestrial or wading lifestyle-in contrast with other early avialans, which exhibit morphological adaptations to arboreal or aerial environments. During our fieldwork in Zhenghe where F. prodigiosus was found, we discovered a diverse assemblage of vertebrates dominated by aquatic and semi-aquatic species, including teleosts, testudines and choristoderes. Using in situ radioisotopic dating and stratigraphic surveys, we were able to date the fossil-containing horizons in this locality-which we name the Zhenghe Fauna-to 148-150 million years ago. The diversity of the Zhenghe Fauna and its precise chronological framework will provide key insights into terrestrial ecosystems of the Late Jurassic.
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Aves , Dinosaurios , Fósiles , Animales , China , Dinosaurios/anatomía & histología , Dinosaurios/clasificación , Ecosistema , Mosaicismo , Filogenia , Aves/anatomía & histología , Aves/clasificación , Historia Antigua , Miembro PosteriorRESUMEN
Covalent organic frameworks (COFs) with flexible periodic skeletons and ordered nanoporous structures have attracted much attention as potential candidate electrode materials for green energy storage and efficient seawater desalination. Further improving the intrinsic electronic conductivity and releasing porosity of COF-based materials is a necessary strategy to improve their electrochemical performance. Herein, the employed graphene as the conductive substrate to in situ grow 2D redox-active COF (TFPDQ-COF) with redox activity under solvent-free conditions to prepare TFPDQ-COF/graphene (TFPDQGO) nanohybrids and explores their application in both supercapacitor and hybrid capacitive deionization (HCDI). By optimizing the hybridization ratio, TFPDQGO exhibits a large specific capacitance of 429.0 F g-1 due to the synergistic effect of the charge transport highway provided by the graphene layers and the abundant redox-active centers contained in the COF skeleton, and the assembled TFPDQGO//activated carbon (AC) asymmetric supercapacitor possesses a high energy output of 59.4 Wh kg-1 at a power density of 950 W kg-1 and good cycling life. Furthermore, the maximum salt adsorption capacity (SAC) of 58.4 mg g-1 and stable regeneration performance is attained for TFPDQGO-based HCDI. This study highlights the new opportunities of COF-based hybrid materials acting as high-performance supercapacitor and HCDI electrode materials.
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Defect engineering is recognized as an attractive method for modulating the electronic structure and physicochemical characteristics of carbon materials. Exploiting heteroatom-doped porous carbon with copious active sites has attracted great attention for capacitive deionization (CDI). However, traditional methods often rely on the utilization of additional heteroatom sources and strong corrosive activators, suffering from low doping efficiency, insufficient doping level, and potential biotoxicity. Herein, hydrogen-bonded organic frameworks (HOFs) are employed as precursors to synthesize N, O co-doped porous carbon via a simple and green reverse defect engineering strategy, achieving controllable heavy doping of heteroatoms. The N, O co-doping triggers significant pseudocapacitive contribution and the surface pore structure supports the formation of the electric double layer. Therefore, when HOF-derived N, O co-doped carbon is used as CDI electrodes, a superior salt adsorption capacity of 32.29 ± 1.42 mg g-1 and an outstanding maximum salt adsorption rate of 10.58 ± 0.46 mg g-1 min-1 at 1.6 V in 500 mg L-1 NaCl solution are achieved, which are comparable to those of state-of-the-art carbonaceous electrodes. This work exemplifies the effectiveness of the reverse nitrogen-heavy doping strategy on improving the carbon structure, shedding light on the further development of rational designed electrode materials for CDI.
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Corneal neovascularization (CNV) is a vision-threatening disease that is becoming a growing public health concern. While Yes-associated protein (YAP) plays a critical role in neovascular disease and allow for the sprouting angiogenesis. Verteporfin (VP) is a classical inhibitor of the YAP-TEAD complex, which is used for clinical treatment of neovascular macular degeneration through photodynamic therapy. The purpose of this study is to explore the effect of verteporfin (VP) on the inhibition of CNV and its potential mechanism. Rat CNV model were established by suturing in the central cornea and randomly divided into three groups (control, CNV and VP group). Neovascularization was observed by slit lamp to extend along the corneal limbus to the suture line. RNA-sequencing was used to reveal the related pathways on the CNV and the results revealed the vasculature development process and genes related with angiogenesis in CNV. In CNV group, we detected the nuclear translocation of YAP and the expression of CD31 in corneal neovascular endothelial cells through immunofluorescence. After the application of VP, the proliferation, migration and the tube formation of HUVECs were significantly inhibited. Furthermore, VP showed the CNV inhibition by tail vein injection without photoactivation. Then we found that the expression of phosphorylated YAP significantly decreased, and its downstream target protein connective tissue growth factor (CTGF) increased in the CNV group, while the expression was just opposite in other groups. Besides, both the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and cofilin significantly increased in CNV group, and decreased after VP treatment. Therefore, we conclude that Verteporfin could significantly inhibited the CNV without photoactivation by regulating the activation of YAP.
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Neovascularización Coroidal , Neovascularización de la Córnea , Verteporfina , Animales , Ratas , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Neovascularización de la Córnea/tratamiento farmacológico , Células Endoteliales/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Verteporfina/farmacología , Verteporfina/uso terapéuticoRESUMEN
Infectious pancreatic necrosis virus (IPNV) is an important pathogen that is threatening the worldwide salmon and trout industry. But there is no therapeutic drug available for now. In this study, we demonstrate that MK-0608 is highly efficient against IPNV and low cytotoxic, with a 50 % effective concentration (EC50) of 0.20 µM and selectivity index (SI) of about 268. Time of addition assay illustrated that MK-0608 targeted the early stage of IPNV life cycle. Furthermore, we found that MK-0608 blocked IPNV attachment on the premise of sufficient pre-incubation time but MK-0608 did not influence viral internalization and release. MK-0608 could inhibit IPNV genome synthesis, and combination with ribavirin enhanced the inhibition effect, which might be functional via binding to IPNV RNA dependent RNA polymerase (RdRp), which was predicted by using molecular docking methods. In vivo test showed that IPNV was extremely suppressed in the rainbow trout (Oncorhynchus mykiss) with one single dose of MK-0608, and the higher dosage of 50 mg/kg could cause 3 log decrease of IPNV loads in fish tissues.
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Antivirales , Infecciones por Birnaviridae , Enfermedades de los Peces , Virus de la Necrosis Pancreática Infecciosa , Oncorhynchus mykiss , Replicación Viral , Virus de la Necrosis Pancreática Infecciosa/fisiología , Virus de la Necrosis Pancreática Infecciosa/efectos de los fármacos , Animales , Enfermedades de los Peces/virología , Infecciones por Birnaviridae/veterinaria , Infecciones por Birnaviridae/virología , Replicación Viral/efectos de los fármacos , Antivirales/farmacología , ARN Viral/genética , Replicación de ARNRESUMEN
Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.
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Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.
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Exuberant large T-cell proliferations in Kikuchi disease can potentially be misdiagnosed as lymphoma. In this study, we explore their clinicopathological features and summarize key points that can be used to distinguish them from T-cell lymphoma. The cohort consisted of 25 cases of Kikuchi disease with an exuberant large T-cell proliferation, which, in part, mimicked lymphoma. The median age was 25 years with a female:male ratio of 4:1. By B-scan ultrasonography, patients presented with either isolated lymphadenopathy (68%) involving the cervical and axillary regions or generalized lymphadenopathy (32%). Histologically, lymph nodes showed paracortical and interfollicular expansion by sheets of large cells associated with karyorrhectic debris. Histiocytes and plasmacytoid dendritic cells were present in the background. No case showed complete effacement of lymph node architecture. The large cells were CD8-positive cytotoxic T-cells with a high proliferation rate. These T-cells showed decreased BCL-2 in 17 (68%) cases. CD5 expression was decreased in 10 (40%) cases. Histiocytes in the background were positive for myeloperoxidase. Clonal TRG and/or TRB rearrangements were detected in 2 of 10 (20%) cases. In conclusion, large T-cell proliferations in Kikuchi disease can be alarming at the morphologic and immunophenotypic levels and need to be distinguished from T-cell lymphoma. Clinical features helpful in the differential diagnosis include young patients and lymphadenopathy involving the cervical and axillary regions. Major pathologic features helpful in this differential diagnosis include partial involvement of the lymph node and the presence of karyorrhectic debris, crescent-shaped histiocytes, and/or loose aggregates of plasmacytoid dendritic cells.
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Linfadenitis Necrotizante Histiocítica , Linfoma de Células T , Linfoma , Humanos , Femenino , Masculino , Adulto , Linfadenitis Necrotizante Histiocítica/diagnóstico , Linfocitos T , Proliferación CelularRESUMEN
Infectious pancreatic necrosis virus (IPNV) is the pathogen of infectious pancreatic necrosis (IPN), which can cause high mortality in salmonids, harm the healthy development of salmon-trout aquaculture, and lead to huge economic losses. However, in China, there is currently neither a commercially available vaccine to prevent IPNV infection nor antiviral drugs to treat IPNV infection. The genome of IPNV consists of two segments of dsRNA named A and B. Segment B encodes the RNA-dependent RNA-polymerase (RdRp) VP1 which is essential for viral RNA replication and is therefore considered an important target for the development of antiviral drugs. In this study, we investigate whether 2'-C-methylcytidine (2CMC), a nucleoside analog which target viral polymerases, has an inhibitory effect on IPNV both in vitro and in vivo. The results show that 2CMC inhibits IPNV infection by inhibiting viral RNA replication rather than viral internalization or attachment. In vivo experiment results showed that 2CMC could inhibit viral RNA replication and reduce viral load in rainbow trout (Oncorhynchus mykiss). In our study, we have revealed that 2CMC has a potent inhibitory effect against IPNV infection. Our data suggest that 2CMC is an attractive anti-IPNV drug candidate which will be highly valuable for the development of potential therapeutics for IPNV.
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Infecciones por Birnaviridae , Enfermedades de los Peces , Virus de la Necrosis Pancreática Infecciosa , Oncorhynchus mykiss , Animales , ARN , Antivirales/farmacologíaRESUMEN
PURPOSE: To evaluate the accuracy of newer generation intraocular lens (IOL) power calculation formulas (EVO 2.0 and Kane) with established formulas (Barrett Universal II, Haigis and SRK/T) in pediatric cataract patients. METHODS: Retrospective study. We enrolled 110 eyes (110 patients) in Eye Hospital of Wenzhou Medical University. All patients underwent uneventful cataract surgery and implanted with posterior chamber IOL in the bag. We calculate the mean prediction errors (PE) and percentage within 1 diopter (D) at 1 month to assess the accuracy, and percentage > 2D was defined as prediction accident. Then, we performed subgroup analysis according to age and axial length (AL). RESULTS: The mean age and AL were 37.45 ± 23.28 months and 21.16 ± 1.29 mm. The mean PE for all patients was as follows: Barrett (- 0.30), EVO (0.18), Haigis (- 0.74), Kane (- 0.36), and SRK/T (0.58), p < 0.001. In addition, EVO and SRK/T formulas were relatively accurate in patients younger than 24 months and with AL ≤ 21 mm, while EVO got lower prediction accident rate than SRK/T (3/41 vs 8/41, 4/52 vs 5/52). Moreover, Barrett, EVO, and Kane formulas achieved better accuracy and lower prediction accident rate in patients older than 24 months and with AL > 21 mm (both > 51/69 and 43/58, and < 3/69 and 3/58). CONCLUSIONS: In patients older than 24 months and with AL > 21 mm, Barrett, EVO, and Kane formulas were relatively accurate, while in patients younger than 24 months and with AL ≤ 21 mm, EVO was more accurate, followed by SRK/T formula.
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Catarata , Lentes Intraoculares , Facoemulsificación , Humanos , Niño , Refracción Ocular , Agudeza Visual , Estudios Retrospectivos , Óptica y Fotónica , Catarata/complicaciones , Biometría , Longitud Axial del OjoRESUMEN
Infectious hematopoietic necrosis virus (IHNV) is an important pathogen that causes significant economic losses to salmon trout farming. Although vaccines have been invented for the treatment of IHNV, findings from our previous survey show that breeding enterprises and farmers require effective oral drugs or immune enhancers. However, studies on the development of oral drugs are limited. In the present study, we used bioinformatics methods to predict the protein targets of andrographolide (Andro) in IHNV. Cells were infected with IHNV, and the effect of andrographolide was explored by evaluating the expression levels of genes implicated in oxidative stress, activities of antioxidant enzymes, and the expression of genes implicated in apoptosis and necrosis. In the present study, cells were divided into NC, IHNV, IHNV+10 µM andrographolide, and IHNV+20 µM andrographolide groups. qRT-PCR was performed to determine the expression level of genes, and an antioxidant enzyme detection kit was used to evaluate the activities of antioxidant enzymes. Fluorescent staining was performed using a reactive oxygen species detection kit (ROS) and Hoechst 33342/PI double staining kit, and the mechanism of alleviation of apoptosis and oxidative stress andrographolide after IHNV infection was determined. The results indicated that andrographolide inhibits viral growth by binding to the NV protein of IHNV and increasing the antioxidant capacity of the body through the CTSK/BCL2/Cytc axis, thereby inhibiting the occurrence of IHNV-induced apoptosis. This is the first study to explore the antagonistic mechanism of action of andrographolide in alleviating IHNV infection. The results provide valuable information on alternative strategies for the treatment of IHNV infection during salmon family and provide a reference for the use of andrographolide as an antioxidant agent in agricultural settings.
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Antioxidantes , Diterpenos , Virus de la Necrosis Hematopoyética Infecciosa , Antioxidantes/farmacología , Estrés Oxidativo , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/genéticaRESUMEN
BACKGROUND: The resistance to radiotherapy remains a major obstacle that limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study aims to illustrate the molecular mechanism underlying the role of LINC00665 in the radiosensitivity of NSCLC, which involves ubiquitin C-terminal hydrolase L3 (UCHL3). METHODS AND RESULTS: The expression of UCHL3 was determined in clinical tissue samples collected from NSCLC patients and NSCLC cell lines. We found that UCHL3 overexpression occurred in both NSCLC tissues and cells, associated with poor prognosis in NSCLC patients. Mechanistically, UCHL3 stabilized aryl hydrocarbon receptor (AhR) protein through deubiquitination, thereby promoting PD-L1 expression. UCHL3 reduced the radiosensitivity of NSCLC cells by stabilizing AhR protein. Upstream microRNAs (miRNAs) and lncRNAs of UCHL3 were predicted by microarray profiling and validated by functional experiments. LINC00665 functioned as a sponge of miR-582-5p and thus up-regulated the expression of the miR-582-5p target UCHL3. Gain- and loss- of function assays were performed to assess the effects of LINC00665, UCHL3 and miR-582-5p on the in vitro cell malignant behaviors and immune escape as well as on the in vivo tumor growth. Silencing LINC00665 or overexpressing miR-582-5p enhanced the sensitivity of NSCLC cells to radiotherapy. LINC00665 augmented the immune escape of NSCLC cells in vitro and in vivo through stabilizing AhR protein via the miR-582-5p/UCHL3 axis. CONCLUSIONS: Overall, LINC00665 reduced the radiosensitivity of NSCLC cells via stabilization of AhR through the miR-582-5p/UCHL3 axis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , MicroARNs/genética , MicroARNs/metabolismo , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Ubiquitina TiolesterasaRESUMEN
Ischemia/reperfusion (I/R) caused by ischemic stroke treatments leads to brain injury and its pathological mechanism is related to autophagy. The underlying mechanism of kaempferol on cerebral I/R injury needs to be explored. To establish I/R injury, we used a middle cerebral artery occlusion-reperfusion (MCAO) model in rats. MCAO rats were treated with the same amount of saline (I/R group); Treatment group rats were treated orally with kaempferol (50, 100, 200 mg/kg) for 7 days before surgery. After reperfusion for 24 h, the scores of neurological deficits and infarct volume in each group were evaluated. LC3, Beclin-1 p62, AMPK and mTOR protein expression levels were examined by TTC staining, immunofluorescence staining, qRT-PCR and western blotting assay. H&E and TTC staining showed that compared with model group, the infarction size of rats in kaempferol group was markedly reduced. Meanwhile, the results showed that kaempferol had a dose-dependent nerve function repairability. Nissl and TUNEL staining showed that kaempferol could reduce neuronal apoptosis and ameliorate neuronal impairment after I/R. Western blotting and qRT-PCR results showed that kaempferol could protect the brain from ischemia reperfusion by activating autophagy. In addition, add AMPK inhibitor, western blotting and immumohistochemical staining showed that kaempferol mediated AMPK/mTOR signal pathway in MCAO rats. Kaempferol could mediate the AMPK signal pathway to regulate autophagy and inhibit apoptosis to protect brain against I/R injury.
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Isquemia Encefálica , Daño por Reperfusión , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Autofagia , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevención & control , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Quempferoles/farmacología , Quempferoles/uso terapéutico , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Infectious hematopoietic necrosis virus (IHNV) is the vital pathogen that has caused the great economic loss in salmonid fisheries. To date, there is limited information concerning the changes of lncRNAs in RTG-2 cells infected by IHNV. In this study, a comparative transcriptome analysis of lncRNAs was performed in RTG-2 cells with and without IHNV infection to determine their changes and the effects on IHNV infection. The results showed that IHNV infection significantly changed the expression levels of lncRNAs and mRNAs, including 3693 differentially expressed lncRNAs (DE-lncRNAs) and 3503 differentially expressed mRNAs (DE-mRNAs) respectively. These DE-lncRNAs and DE-mRNAs induced by IHNV were mostly associated with immune response, RNA processing, and viral diseases related pathways. Further analysis found that some DE-lncRNAs might participate in the regulation of extracellular matrix metabolism, apoptosis, lipid synthesis, autophagy, and immune responses referring to the functions of their target genes. Afterwards, 349 co-expression relationships were constructed by 223 DE-lncRNAs and 271 DE-mRNAs, of which LTCONS_00146935 was the pivotal node in the interaction networks, and was together with its target genes modulated the immune responses under the IHNV infection. RT-qPCR results showed that the changes of the selected immune-related DEGs were in consistent with the RNA-seq data, suggesting that the sequencing data was relatively reliable. In summary, this is the first study to determine the changes and interactions of lncRNA-mRNA in RTG-2 cells under the IHNV infection. The results provided the valuable information concerning the lncRNAs in salmonid fish, which will benefit for future study on uncovering the roles of lncRNAs-mRNAs during the viral infection.
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Virus de la Necrosis Hematopoyética Infecciosa , ARN Largo no Codificante , Infecciones por Rhabdoviridae/veterinaria , Transcriptoma , Animales , Línea Celular/virología , Enfermedades de los Peces/genética , Enfermedades de los Peces/virología , Perfilación de la Expresión Génica/veterinaria , Oncorhynchus mykiss , ARN Largo no Codificante/genética , ARN Mensajero , RNA-Seq , Infecciones por Rhabdoviridae/genéticaRESUMEN
Infectious pancreatic necrosis virus (IPNV), belonging to the genus Aquabirnavirus within the family Birnaviridae, causes huge economic loss to the global salmonid industry every year. Recently, outbreaks of disease caused by genogroup I IPNV were found in many rainbow trout (Oncorhynchus mykiss) farms worldwide. An inactivated vaccine was prepared using a genogroup I IPNV isolate with an optimized procedure as incubation with ß-propanolactone (BPL) at the final concentration of 0.5% at room temperature for 48 h. The inactivated vaccine was used to immunize rainbow trout, and the protection efficiency was evaluated by viral loads determination, immune-related genes quantification, and neutralizing antibody tests. The viral loads in immunized rainbow trout were significantly decreased and the strongest antiviral effect was observed on 30 days post-immunization (d.p.i). The expression of innate immune-related genes IFN-1, and Mx-1 genes were significantly up-regulated on 3, 7, and 15 d.p.i (p < 0.05), and adaptive immune-related genes CD4, CD8, and IgM genes were significantly up-regulated on 15 and 30 d.p.i (p < 0.05). Neutralizing antibodies were firstly detected on 30 d.p.i and the highest titer was observed on 45 d.p.i, which began to decrease on 60 d.p.i, but was still significantly higher than that in negative control fish. The results indicated that the vaccine prepared in this study could stimulate the non-specific and specific immune response and provide significant immune protection to the vaccinated rainbow trout.
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Infecciones por Birnaviridae , Enfermedades de los Peces , Virus de la Necrosis Pancreática Infecciosa , Oncorhynchus mykiss , Vacunas Virales , Animales , Anticuerpos Neutralizantes , Infecciones por Birnaviridae/prevención & control , Infecciones por Birnaviridae/veterinaria , Vacunas de Productos InactivadosRESUMEN
This study is aimed at investigating the role of ß-galactoside-α2,3-sialyltransferase III (ST3GAL3) in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), as well as its potential mechanism of action. The Gene Expression Omnibus (GEO) database and gene set enrichment analysis (GSEA) were used to analyse the expression of ST3GAL3 and the enrichment signalling pathways associated with ST3GAL3 in RA. The effects of ST3GAL3 on tumour necrosis factor- (TNF-) α and interleukin- (IL-) 1ß-treated MH7A cells were determined using methyl thiazolyl tetrazolium (MTT), transwell, and enzyme-linked immunosorbent assays (ELISA). The expression of proliferation-associated proteins and Toll-like receptor (TLR) pathway-enriched proteins was analysed using western blotting. As a main result, ST3GAL3 was screened as an overlapping upregulated gene from GSE101193 and GSE94519 datasets. ST3GAL3 expression in MH7A cells significantly increased with increasing treatment time with TNF-α or IL-1ß. TLR9/myeloid differentiation primary response protein 88 (MyD88) is a downstream activation pathway of ST3GAL3. ST3GAL3 overexpression promoted MH7A cell proliferation and migration. Additionally, ST3GAL3 overexpression upregulated the expression of proliferation-associated proteins (cyclinD, cyclinE, and proliferating cell nuclear antigen) and TLR pathway enrichment factors (TLR9 and MyD88) and increased the production of matrix metallopeptidase (MMP) 1, MMP3, interleukin- (IL-) 6, and IL-8, whereas si-ST3GAL3 had the opposite effect. The addition of TLR9 agonists (CpG 2216 and CpG 2006) reversed the effects of si-ST3GAL3 on MH7A cell proliferation, migration, and inflammation. TLR9-specific siRNA reversed the effects of ST3GAL3 overexpression on MH7A cell proliferation, migration, and inflammation. In conclusion, ST3GAL3 is likely involved in RA pathogenesis by activating the TLR9/MyD88 pathway.
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Artritis Reumatoide , Sinoviocitos , Humanos , Sinoviocitos/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 9/metabolismo , Artritis Reumatoide/metabolismo , Fibroblastos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Inflamación/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Interleucinas/metabolismoRESUMEN
In this retrospective study, we collected 282 bladder cancer patients diagnosed from 2011 to 2018. Two mechanisms, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), were used to detect programmed death molecule ligand 1 (PD-L1) expression, and these analyses were performed on different platforms using different antibodies (22C3, 28-8, and SP263). The results were compared, and related clinical parameters were analysed to explore the consistencies and correlations between different detection methods, clonal antibodies and platforms for the detection of PD-L1 in bladder cancer patients to more effectively identify patients who are suitable for immunotherapy. The rate of PD-L1 positivity with 28-8 (42.3 %) was higher than that with 22C3 (22.1 %) or SP263 (22.1 %). The rate of PD-L1 positivity with SP263 was consistent with that of 22C3, and patients with positive PD-L1 expression detected by SP263 had longer overall survival in clinical parameter analysis. However, the rate of PD-L1 positivity with FISH was only 2.10 %, and the rate of agreement between FISH and IHC was only 1.06 %. In conclusion, the detection of PD-L1 with SP263 and IHC was more consistent and had a higher prognostic value, providing guidance for clinical diagnosis and treatment. The clinical application of FISH for PD-L1 detection needs to be further explored.
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Neoplasias Pulmonares , Neoplasias de la Vejiga Urinaria , Anticuerpos , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Humanos , Hibridación Fluorescente in Situ , Indicadores y Reactivos , Ligandos , Neoplasias Pulmonares/metabolismo , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/diagnósticoRESUMEN
The study aimed to evaluate the safety and function of poly(lactic-acid-co-ε-caprolactone) (PLCL)/fibrinogen nanofibers (P/F-Ns), and provide theoretical basis for the clinical application. The surface morphology, mechanical properties, the hydrophilicity and the fibrinogen content of P/F-Ns were tested by scanning electron microscope, the material testing machine, the contact angle meter and the microplate reader, respectively. The cell adhesion, proliferation and ligament remodeling genes expression of Hig-82 cells on P/F-Ns were conducted through cell counting kit-8 (CCK-8) and real-time quantitative PCR analyses, respectively. The results showed that with the increase of the fibrinogen content, the pore sizes and hydrophilicity of three P/F-Ns increased, but the mechanical properties decreased. Cell adhesion and proliferation tests showed that P/F-N-2 held the best ability to promote cell adhesion and proliferation. The ligament remodeling genes expressions of Hig-82 cells on P/F-N-1, P/F-N-2 and P/F-N-3 were all up-regulated compared to P/F-N-0 on days 3 and 7. All the three P/F-Ns containing fibrinogen (P/F-N-1, P/F-N-2 and P/F-N-3) had better biocompatibility compared to P/F-N-0, and could be efficiently applied to the reconstruction of anterior cruciate ligament.
Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Nanofibras , Adhesión Celular , Fibrinógeno , Ensayo de MaterialesRESUMEN
Krukenberg tumor (KT) refers to a rare ovarian tumor that has metastasized from a primary site. Patients with KTs have a poorer prognosis and worse survival. Thus far, little is known about the frequency of receptor tyrosine kinase (RTK) gene amplification and the concordance of gene amplification between primary tumors, lymph-node metastases, and KTs. Herein, 50 paired samples, including primary cancers, metastatic lymph nodes, and KTs were collected, and RTK gene amplification was tested by fluorescence in situ hybridization (FISH). There were four cases positive for human epidermal growth factor receptor type 2 (HER2) amplification, all of which showed conversion of HER2 status between different lesions. Of the two cases with c-mesenchymal-epithelial transition (c-MET) amplification, the primary tumors and lymph nodes were negative while the right involved ovaries were positive. Inconsistent fibroblast growth factor receptor 2 (FGFR2) status in different lesions was observed in three of the six FGFR2-amplified cases. Co-amplification of RTK genes was identified in only one patient for primary cancer and two for KTs. Collectively, there were 46, 48, 50, and 44 cases negative for HER2, c-MET, EGFR, and FGFR2 amplification in all lesions, respectively. There was no significant difference in overall survival between KTs of gastric origin and colorectal origin. However, of all synchronous cancers, KTs of colorectal origin had a better prognosis than those of gastric origin. In conclusion, the positive rate of RTK gene amplification in KTs was low. Intratumoral heterogeneity was frequent in KTs with RTK gene amplification. A mutually exclusive pattern of RTK gene amplification was dominant in primary cancers, lymph-node metastases, and KTs. There was no survival difference between KTs of gastric origin and colorectal origin. However, of all synchronous cancers, KTs of colorectal origin had a better prognosis than those of gastric origin.
Asunto(s)
Neoplasias Colorrectales/genética , Tumor de Krukenberg/genética , Metástasis Linfática/genética , Neoplasias Ováricas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Neoplasias Colorrectales/secundario , Femenino , Amplificación de Genes , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/secundarioRESUMEN
Maize (Zea mays) endosperm is a primary tissue for nutrient storage and is highly differentiated during development. However, the regulatory networks of endosperm development and nutrient metabolism remain largely unknown. Maize opaque11 (o11) is a classic seed mutant with a small and opaque endosperm showing decreased starch and protein accumulation. We cloned O11 and found that it encodes an endosperm-specific bHLH transcription factor (TF). Loss of function of O11 significantly affected transcription of carbohydrate/amino acid metabolism and stress response genes. Genome-wide binding site analysis revealed 9885 O11 binding sites distributed over 6033 genes. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 259 O11-modulated target genes. O11 was found to directly regulate key TFs in endosperm development (NKD2 and ZmDOF3) and nutrient metabolism (O2 and PBF). Moreover, O11 directly regulates cyPPDKs and multiple carbohydrate metabolic enzymes. O11 is an activator of ZmYoda, suggesting its regulatory function through the MAPK pathway in endosperm development. Many stress-response genes are also direct targets of O11. In addition, 11 O11-interacting proteins were identified, including ZmIce1, which coregulates stress response targets and ZmYoda with O11. Therefore, this study reveals an endosperm regulatory network centered around O11, which coordinates endosperm development, metabolism and stress responses.