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Based on the longitudinal manipulation of polarization, a special vector optical beam (VOB) with customized polarization variation in propagation direction can be generated, whose properties and applications remain to be studied. Here, the self-healing propagation behaviors of the longitudinally varying VOB after an opaque object are investigated, and the localized polarization responses on the object distance are revealed. On this basis, characteristic parameters are defined to measure the distance of object, achieving a minimum relative error of 0.63% in a longitudinal range of 300 mm. Besides, the correlations and uncoupling methods of object distance and size are discussed. Our studies open new ways to use the structural properties of VOB and may be instructive for laser measurement.
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Different from the scalar optical field with spatially uniform polarization, the vector optical field exhibits inhomogeneous distribution of polarization on the cross section. Manipulating the variation of polarization in a single optical beam is important to acquire a flexible and controllable focused optical field. Previous studies mainly focused on the vector optical field with its polarization varying along a circular trajectory of the Poincaré sphere. Here, we demonstrate the tight focusing behaviors of the vector optical field with the polarization varying along complex curves of the Poincaré sphere, which is generated by the joint modulation of azimuthal phase and amplitude distributions of orthogonally polarized components. The longitudinal polarization component with a multipolar pattern in rotational symmetry can be achieved with similar distribution of the total focused field. The transverse and longitudinal spin angular momentum distributions in the focal space are discussed. Approximately pure transverse spin angular momentum can be constructed and manipulated in the focal space, which provides the possibility to manipulate the 3D spin flux for the applications of nano and spin photonics.
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OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.
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Necrose da Cabeça do Fêmur , Osteonecrose , Ratos , Animais , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/metabolismo , Células Endoteliais/metabolismo , Farmacologia em Rede , Fator de von Willebrand/efeitos adversos , Ratos Sprague-Dawley , OsteogêneseRESUMO
BACKGROUND: Many clinical studies have reported a relatively high incidence of osteoporosis and fragility fractures in patients with Cushing syndrome (CS). However, few papers have investigated osteoporosis and CS in terms of pathogenesis, so this study explores the association between the 2 and predicts upstream micro-ribonucleic acids (miRNAs) through bioinformatics, which provides potential targets for simultaneous pharmacological interventions in both diseases and also provides a basis for pathological screening. METHODS: We used Genecards, Online Mendelian Inheritance in Man and Therapeutic Target Database databases to screen the targets of osteoporosis and Cushing syndrome; import target genes to Database for Annotation, Visualization and Integrated Discovery for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis; the intersecting genes were uploaded to Search Tool for the Retrieval of Genes and Genomes database to construct protein-protein interaction network; Cytoscape software was used to screen core genes, and Molecular Complex Detection module was used to analyze cluster modules; finally, the NetworkAnalyst data platform was used to predict the miRNAs that interact with core genes. RESULTS: The core genes of osteoporosis and Cushing syndrome were insulin, tumor necrosis factor, signal transducer and activator of transcription 3 (STAT3), interleukin-6, insulin-like growth factor 1, etc. A total of 340 upstream miRNAs including hsa-let-7a-5p, hsa-mir-30a-5p and hsa-mir-125b-5p were predicted. The biological processes involved include regulating the transcription of ribonucleic acid polymerase II promoter and participating in the transduction of cytokine signaling pathways, which focus on the binding of nerve system ligand, JAK-STAT signaling pathway, Rap1 signaling pathway, PI3K-Akt signaling pathway, etc. CONCLUSION: Osteoporosis and Cushing syndrome are closely related in terms of targets and molecular mechanisms. In this study, bioinformatics methods were used to identify their targets and mechanisms, providing potential targets for drug simultaneous regulation of the 2 diseases, and providing a new direction for exploring the relationship between diseases.
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Síndrome de Cushing , MicroRNAs , Osteoporose , Humanos , Biologia Computacional/métodos , Síndrome de Cushing/complicações , Síndrome de Cushing/genética , Fosfatidilinositol 3-Quinases , MicroRNAs/genética , Osteoporose/genéticaRESUMO
BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a cause of poor prognosis in several lung diseases and after lung transplantation. In LIRI, matrix metalloproteinases and pyroptosis indicators change in parallel, both of them involvement of inflammatory modulation, but it is unclear whether they are related to each other. METHODS: We analyzed the matrix metalloproteinases (MMPs) changes from RNA sequencing (RNA-Seq) data of human transplantation and rat ischemia-reperfusion lung tissues in the Group on Earth Observations (GEO) database. Then established the mouse LIRI model to validate the changes. Further, the severity of lung injury was measured after intervening the matrix metalloproteinases changes with their selective inhibitor during Lung ischemia-reperfusion. Meanwhile, lung, pyroptosis was assessed by assaying the activity of Caspase-1 and interleukin 1ß (IL-1ß) before and after intervening the matrix metalloproteinases changes. RESULTS: The RNA-Seq data revealed that matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9) mRNA expression was elevated both in human lung transplantation and rat lung ischemia-reperfusion tissues, consistent with the change in our mouse model. At the same time, the activity of Caspase-1 and IL-1ß were increased after LIRI. While, the lung injury was attenuated for the use of MMP2 and MMP9 selective inhibitor SB-3CT. Likewise, lung pyroptosis alleviated when treatment the mice with SB-3CT in LIRI. CONCLUSION: We conclude that MMP2 and MMP9 are involved in the process of LIRI, the mechanism of which is related to the promotion of lung pyroptosis.
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Lesão Pulmonar , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Traumatismo por Reperfusão , Animais , Caspases/metabolismo , Modelos Animais de Doenças , Humanos , Pulmão/metabolismo , Lesão Pulmonar/etiologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Piroptose , RatosRESUMO
PURPOSE: To evaluate viral loads in children with human adenovirus (HAdV) pneumonia at different stages of disease and compare the viral load between upper and lower respiratory tract samples. METHODS: We prospectively enrolled children who required invasive ventilation for HAdV pneumonia. Nasopharyngeal aspirate (NPA) and tracheal aspirate (TA) samples were collected throughout the entire period of invasive ventilation. Viral detection and quantification were performed using quantitative real-time polymerase chain reaction. RESULTS: Ninety-four children were enrolled. The median age of the children was 12.0 months (IQR: 11.0-24.0), and > ninety percent of patients were aged between 6 and 59 months. Seven hundred and nine paired NPA-TA samples were collected. The median viral loads of the NPA and TA samples were 7.31 log10 and 7.50 log10 copies/mL, respectively. Viral loads generally decreased steadily over time. The median viral load after 1, 2, 3, and > 3 weeks of the disease course was 8.65, 7.70, 6.69, and 5.09 log10 copies/mL, respectively, in NPA samples and 8.67, 7.79, 7.08, and 5.53 log10 copies/mL, respectively, in TA samples. Viral load showed a significant negative correlation with time since symptom onset in both NPA samples (Spearman r = - 0.607, P = 0.000) and TA samples (Spearman r = - 0.544, P = 0.000). The predicted duration of HAdV shedding was 60.17 days in the NPA group and 65.81 days in the TA group. Viral loads in NPA and TA from the same subjects correlated well with each other (R2 = 0.694). HAdV loads in NPA and TA were most comparable during the early phase of infection (95% limits of agreement, - 1.36 to 1.30 log10 copies/mL, R2 = 0.746). Variation increased during the late phase of infection (i.e., in follow-up samples), with viral loads remaining significantly higher in TA than NPA. CONCLUSIONS: In children with HAdV pneumonia, viral loads in both NPA and TA steadily decreased during the course of the disease, and the predicted duration of viral shedding was more than 2 months. The HAdV DNA load of NPA is highly correlated with that of TA, especially in the initial phase of infection.
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Adenovírus Humanos , Ventilação não Invasiva , Pneumonia , Infecções Respiratórias , Adenovírus Humanos/genética , Criança , Pré-Escolar , Humanos , Lactente , Nasofaringe , Carga ViralRESUMO
OBJECTIVE: MiRNAs have been recently implicated in the pathogenesis of ischemia-reperfusion (IR) injury. This study aimed to investigate the miRNA expression profiles in the early stages after lung transplantation (LT) and to study the involvement of the Toll-like receptor (TLR) signaling pathway in lung IR injury following LT. METHODS: We established the left LT model in mice and selected the miRNA-122 as a research target. The mice were injected with a miRNA-122-specific inhibitor, following which pathological changes in the lung tissue were studied using different lung injury indicators. In addition, we performed deep sequencing of transplanted lung tissues to identify differentially expressed (DE) miRNAs and their target genes. These target genes were used to further perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: A total of 12 DE miRNAs were selected, and 2476 target genes were identified. The GO enrichment analysis predicted 6063 terms, and the KEGG analysis predicted 1554 biological pathways. Compared with the control group, inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung wet/dry ratio (P<0.05). In addition, the activity of myeloperoxidase and the expression levels of tumor necrosis factor-alpha and TLR2/4 were decreased (P<0.05); whereas the expression of interleukin-10 was increased (P<0.05). Furthermore, the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway. CONCLUSION: Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT. Of these, miRNA-122 promoted IR injury following LT, whereas its inhibition prevented IR injury in a TLR-dependent manner.
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Transplante de Pulmão , MicroRNAs/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo , Animais , Lesão Pulmonar/prevenção & controle , Camundongos , MicroRNAs/genética , Traumatismo por Reperfusão/prevenção & controleRESUMO
At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.
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Quirópteros/virologia , Recombinação Genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sequência de Aminoácidos , Animais , China , Genoma Viral , Filogenia , SARS-CoV-2/classificação , Alinhamento de Sequência , Proteínas Virais/genéticaRESUMO
Mice are the most widely used model organism for the study of gene functions and disease mechanisms through the generation of gene-modified mice. Since the 1980s, different genetic manipulation technologies have been developed to reveal gene functions in vivo, including homologous recombination strategies mediated by embryonic stem cells, transgenic strategies mediated by gametes, and the latest genetic modification strategies based on CRISPR/Cas9 technology. Semi-cloning technology mediated by "artificial spermatids" (androgenetic haploid embryonic stem cells, also termed sperm-like stem cells) is developed by Chinese scientists in 2012. In combination with CRISPR/Cas9, semi-cloning technology enables one-step generation of gene-modified mice through injection of "artificial spermatids" with specific gene modifications into oocytes. It has the characteristics of short construction cycle, high efficiency, low cost, and high application compatibility. In 2017, the Center for Excellence in Molecular Cell Science (CEMCS) of CAS has launched the genome tagging project (GTP) based on "artificial spermatid"-mediated semi-cloning technology. The ambitious goal of GTP is to tag every protein in mice and construct a unique mouse library that maintains the genome-wide protein-tagging mouse models. Subsequently, the GTP center was established at CEMCS to pursue the project. GTP center developed strategies to generate protein-tagging cells and mice. Briefly, a tag sequence is precisely inserted in a specific protein- coding gene endogenously in cultured "artificial spermatids"in vitro to build a cell library, in which, each cell line carrying a specific protein tag. The tagged cells could be further used as a sperm replacement to produce tagged mice in one step upon injection into oocytes. The tagged mouse library enables global analysis of protein expression, localization, and complexes using standard tag-based assays in vivo. By April 2021, the GTP center has generated 1532 tagged cell lines, 277 of which have been successfully used to produce tagged mice through oocyte injection. A total of 242 tagged mouse strains have been distributed to 66 research teams in 32 research institutions of 15 districts in 3 countries. The database of tagging product resources has been established and released regularly on the GTP website for scientists to inquire and order. Later, more information about GTP products, such as mouse breeding, protein tissue expression map, published literature, etc., will also be successively published on the GTP website. The GTP center will provide a standardized platform for protein function research, which may dramatically promote the development of life science and clinical transformation.
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Sistemas CRISPR-Cas , Edição de Genes , Animais , Animais Geneticamente Modificados , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Genoma , Masculino , CamundongosRESUMO
Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11PM/Y) identified in azoospermia patients exhibited meiotic arrest due to aberrant chromosome segregation. Tex11PM/Y SSCs could be isolated and expanded in vitro normally, and the mutation was corrected by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated endonuclease 9 (Cas9), leading to the generation of repaired SSC lines. Whole-genome sequencing demonstrated that the mutation rate in repaired SSCs is comparable with that of autonomous mutation in untreated Tex11PM/Y SSCs, and no predicted off-target sites are modified. Repaired SSCs could restore spermatogenesis in infertile males and give rise to fertile offspring at a high efficiency. In summary, our study establishes a paradigm for the treatment of male azoospermia by combining in vitro expansion of SSCs and gene therapy.
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Células-Tronco Germinativas Adultas/metabolismo , Infertilidade Masculina/genética , Mutação/genética , Animais , Azoospermia/genética , Infertilidade Masculina/terapia , Masculino , Camundongos , Espermatogênese/genéticaRESUMO
To understand host-pathogen interactions and develop effective prevention and control strategies for human adenovirus (HAdV), it is essential to explore the characteristics of HAdV shedding. Hospitalized children <14 years who had severe HAdV pneumonia were tested for HAdV DNA by quantitative real-time PCR in nasopharyngeal aspirate (NPA). A total of 132 children were enrolled, including 102 patients with HAdV type 7 (HAdV-7) infection and 12 patients with HAdV type 3 (HAdV-3) infection. A total of 1372 qualified NPA samples were collected. There was a significant negative correlation between the viral load of HAdV and the course of the disease (Spearman r = -0.547, p = .000). HAdV-7 load decreased at a rate of 0.089 log10 copies/mL per day (95% CI: -0.096 to -0.081; R 2 = 0.332), and the duration of viral shedding was predicted to be 96.9 days (y = 8.624-0.089x). However, HAdV-3 load decreased more quickly (95% CI: - 0.229 to - 0.143; R 2 = 0.403), and the duration of viral shedding was 51.4 days (y = 9.558-0.186x). The median viral load of the HAdV-7 group at weeks 2 and 3, and more than 3 weeks postinfection was higher than that of the HAdV-3 group. No significant differences in the duration of viral shedding were found in different gender, age (>2 vs. ≤2 years), and with or without underlying diseases groups. Viral shedding in children with severe HAdV pneumonia persisted, among which HAdV-7 lasted longer than 3 months and the viral load decreased slowly than HAdV-3.
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Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/fisiologia , Pneumonia Viral/virologia , Eliminação de Partículas Virais , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Cinética , Masculino , Nasofaringe/virologia , Sorogrupo , Carga ViralRESUMO
Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat (Rhinolophus thomasi) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo. Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.
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COVID-19 , Quirópteros , Rhabdoviridae , Humanos , Animais , Camundongos , China/epidemiologia , Filogenia , SARS-CoV-2 , Mamíferos , Genoma ViralRESUMO
OBJECTIVE: To investigate the mechanism underlying the regulation of the invasion and metastasis of oral squamous cell carcinoma (OSCC) by long-chain noncoding RNA (lncRNA) PCGEM1 through the transforming growth factor (TGF) ß2/Smad2 signaling pathways. METHODS: A total of 60 OSCC cases were collected. Cancer tissues and normal tissues more than 2 cm away from cancer tissues were also collected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-148a and lncRNA PCGEM1 in OSCC, adjacent normal tissues, oral mucosa epithelial cells, KB, BcaCD885, SCC-4, CAL27, and SCC-15. The relationship between the expression of lncRNA PCGEM1 and miR-148a and the clinicopathological information of patients was analyzed. The lncRNA PCGEM1-silenced cell line KB-siPCGEM1 and negative control (KB-NC) group were constructed, and KB was used as the blank control group. The effects of lncRNA PCGEM1 on the proliferation, invasion, and migration of KB cells were determined via MTT, Transwell, and scratch assays. The bioinformatics website starBase was used to predict the complementary binding microRNA (miRNA) of lncRNA PCGEM1. Furthermore, the genes that the miRNA could target and bind were predicted in accordance with the website www.microRNA.org. Western blotting analysis was used to detect the expression of TGF ß2/Smad2 signaling pathway proteins. RESULTS: qRT-PCR results showed that the expression level of lncRNA PCGEM1 and miR-148a in OSCC tissues was higher than that in normal tissues (P<0.05). The expression of lncRNA PCGEM1 and miR-148a in the cancer tissues of patients with different TNM grades, lymph node metastasis, and tissue differentiation was statistically significant (P<0.05). Compared with those in the blank control group and the KB-NC group, OD492 nm value was significantly decreased and cell mobility was significantly reduced in the KB-siPCGEM1 group (P<0.05). Bioinformatics predictions showed that lncRNA PCGEM1 could bind to miR-148a in a complementary manner and that miR-148a had a targeted binding site with TGF ß2. qRT-PCR and Western blotting analysis results showed that the expression levels of miR-148a, TGF ß2, and p-Smad2 in the KB-siPCGEM1 group were significantly lower than those in the blank control and KB-NC groups (P<0.05), and no statistically significant difference between the blank control group and the KB-NC group was observed (P>0.05). CONCLUSIONS: LncRNA PCGEM1 is highly expressed in OSCC. The high expression of lncRNA PCGEM1 may enhance the TGF ß2/Smad2 signaling pathway by upregulating miR-148a, thus promoting the development of OSCC.
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Carcinoma de Células Escamosas , Neoplasias Bucais , RNA Longo não Codificante , Carcinoma de Células Escamosas/genética , Proliferação de Células , Células Epiteliais , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Transdução de Sinais , Proteína Smad2 , Fator de Crescimento Transformador beta2RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Calculus bovis (C. bovis), a widespread known traditional animal drug in China and Japan, has been widely used for a long time to treat various diseases, including high fever, convulsion and stroke. The aim of the present paper is to comprehensively review knowledge about C. bovis in terms of traditional usages, origin, chemical constituents, pharmacological activities and toxicology to seek an applicable substitute for NCB and provide potential new strategies utilizing C. bovis. Additionally, directions and perspectives for future investigations regarding C. bovis are also discussed. MATERIALS AND METHODS: In this paper, the traditional usages, origin, chemical constituents, pharmacology, and toxicology of C. bovis are comprehensively and systematically summarized by searching scientific databases, including Web of Science, PubMed, ScienceDirect, Springer, CNKI, Baidu Scholar and others. Additionally, some classic books of Chinese herbal medicine, academic papers authored by individuals with MSc and PhD degrees, local government reports as well as the state of local drug standards are also retrieved. RESULTS: Currently, C. bovis mainly derives from four sources: natural Calculus bovis (NCB), Calculus bovis sativus (CBS), Cultured calculus bovis (CCB) and Calculus bovis artifactus (CBA). Owing to their different formation processes, the chemical constituents of the four kinds of C. bovis show certain differences. Additionally, over 44 chemical constituents have been isolated and identified from C. bovis, mainly including bile pigments, bile acids, cholesterols and amino acids. Further investigations have revealed a wide range of pharmacological effects of C. bovis, with effects on the nervous system, cardiovascular system, respiratory system, digestive system, immune system and others. Furthermore, NCB and CBA show hypotoxicity, but high concentrations of bilirubin can cause neurotoxicity and hearing impairment. Additionally, pharmacokinetic data for C. bovis are still lacking. CONCLUSION: CBS contains analogous types and amounts of constituents and exerts similar therapeutic effects to NCB. Thus, CBS might be used as a sustainable substitute for NCB. Furthermore, the configuration and concentration of bile acids and bilirubin in C. bovis are responsible for the difference in pharmacological effects in the four types C. bovis. Further studies should focus on the structure-function relationship of bile acids and bilirubin in C. bovis by employing pharmacokinetics.
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Produtos Biológicos/efeitos adversos , Produtos Biológicos/análise , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Animais , China , Etnofarmacologia , Humanos , Japão , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Stress is the non-specific systemic response that occurs when the body is stimulated by various factors, and it can affect multiple systems of the body. Recent studies have shown that gut microbiota is an essential part of human microecology, and plays a pivotal role in keeping the body healthy. Stress can result in gut dysbiosis by affecting the function of intestinal mucosal barrier, intestinal immune and gastrointestinal motility. This article reviewed the alteration of gut microbiota caused by stress and the possible mechanisms involved.
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Humanos , Disbiose , Microbioma Gastrointestinal , Motilidade Gastrointestinal , Mucosa IntestinalRESUMO
A Ni-catalyzed Suzuki-type cross-coupling of boronic acids with epoxides without an exogenous base and with broad substrate scope has been developed. The product selectivity of styrenyl epoxides is different from that of previous work. This methodology uses readily available starting materials to access a range of substituted alcohols, which are valuable feedstock chemicals.
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A Pd-catalyzed decarboxylative cross-coupling of α,ß-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both ß-monosubstituted and ß-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,ß-unsaturated carboxylic acids.
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While nasopharyngeal carcinoma (NPC) commonly presents lymphoid metastases, the enormous cervical metastasis causing dysphagia and limitation of neck motion is not a familiar symptom for most of NPC cases. We report a 23-year-old male with undifferentiated carcinoma of the nasopharynx, stage III (T3N2M0), who had undergone aggressive surgical resection of bilateral huge cervical mass first followed by concurrent chemo-radiotherapy with cisplatin-based regimens. The postoperative clinical course was uneventful and follow-up, 2 years later, revealed no recurrence of primary lesion and neck metastases. We recommend that aggressive surgical resection may be considered when NPC patients significantly suffer clinical symptoms from a huge cervical metastasis.
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The discovery and analysis of pathogens carried by non-human primates are important for understanding zoonotic infections in humans. We identified a highly divergent astrovirus (AstV) from fecal matter from a rhesus monkey in China, which has been tentatively named "monkey-feces-associated AstV" (MkAstV). The full-length genome of MkAstV was determined to be 7377 nt in length. It exhibits the standard genomic AstV organization of three open reading frames (ORFs) and is most closely related to duck AstV (28%, 49%, and 35% amino acid sequence identity in ORF1a, ORF1b, and ORF2, respectively). Coincidentally, while this report was being prepared, an astrovirus sequence from Hainan black-spectacled toad became available in the GenBank database, showing 95%, 94% and 92% aa sequence identity in ORF1a, ORF1b and ORF2, respectively, to the corresponding ORFs of MkAstV. Phylogenetic analysis of ORF1a, ORF1b, and ORF2 indicated that MkAstV and the amphibian-related astroviruses formed an independent cluster in the genus Avastrovirus. The host of MkAstV remains unknown. Epidemiological and serological studies of this novel virus should be undertaken in primates, including humans.