346 research outputs found

    Thinking on the Reasons and Countermeasures of the Failure and Misrepresentation of Science and Technology Transmission

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    This paper makes a comparative analysis of the phenomena of communication failure and misrepresentation in the East and the West history of science and technology communication. Based on the analysis, the authors find out the causes of this phenomenon and puts forward their own thinking and countermeasures. They expect to arouse the attention of scientific and technological media workers, so as to better inherit the knowledge and wisdom of human beings

    Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo

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    BACKGROUND: To evaluate whether PI3K/Akt pathway could effect on apoptosis and its mechanism in nasopharyngeal carcinoma cells. METHODS: The activation of the PI3K/Akt and its effect on CNE-2Z cells in vivo and in vitro was investigated by MTT assay, flow cytometry, western blot, ELISA, terminal deoxyribonucleotide transferase-mediated nick-end labeling assays (TUNEL), and immunohistochemical analyses, using PI3K inhibitor, LY294002. RESULTS: The results showed that LY294002 inhibited the phosphorylating of Akt (S473), cell proliferation, and induced apoptosis in CNE-2Z cells. However, our experiment results also demonstrated that apoptosis-induced LY294002 was directly regulated by caspase-9 activation pathway. CONCLUSION: These data suggested that PI3K inhibitor, LY294002, induced apoptosis by caspase-9 activation pathway and might be as a potentially useful target for therapeutic intervention in nasopharyngeal carcinoma patients

    Sull. 1)

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    ABSTRACT Response surface methodology(RSM) was employed to optimize conditions for ultrasound-assisted extraction(UAE) of antioxidantive components from Arundinagraminifolia. 1,1-diphenyl-2-picryl-hydrazyl(DPPH) free radical scavenging assay was used to evaluate the activity of antioxidative components. Based on the single-factor test, we identified extraction time, ethanol volume fraction, extraction temperature and liquid-solid ratio as the main variables that influence DPPH free radical scavenging activity of A. graminifolia extract. The optimal conditions to achieve the maximum activity were determined as follows: extraction time 35 min, extraction temperature46ºC, ethanol volume fraction 74%and liquid-solidratio27 mL.g -1 . The scavenging rateof 78.71%was achieved under the optimal extraction conditions, which was well in agreement with the optimal predicted values (79.16%). This extraction method was simple and efficient and provided a method of sample preparation to determine DPPH radical scavenging activity of total antioxidative components from A. graminifolia. The research also provided a reference for full utilization of A. graminifolia and identified a technique to extract antioxidative components

    TurboID-mediated proximity labeling technologies to identify virus co-receptors

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    Virus receptors determine the tissue tropism of viruses and have a certain relationship with the clinical outcomes caused by viral infection, which is of great importance for the identification of virus receptors to understand the infection mechanism of viruses and to develop entry inhibitor. Proximity labeling (PL) is a new technique for studying protein-protein interactions, but it has not yet been applied to the identification of virus receptors or co-receptors. Here, we attempt to identify co-receptor of SARS-CoV-2 by employing TurboID-catalyzed PL. The membrane protein angiotensin-converting enzyme 2 (ACE2) was employed as a bait and conjugated to TurboID, and a A549 cell line with stable expression of ACE2-TurboID was constructed. SARS-CoV-2 pseudovirus were incubated with ACE2-TurboID stably expressed cell lines in the presence of biotin and ATP, which could initiate the catalytic activity of TurboID and tag adjacent endogenous proteins with biotin. Subsequently, the biotinylated proteins were harvested and identified by mass spectrometry. We identified a membrane protein, AXL, that has been functionally shown to mediate SARS-CoV-2 entry into host cells. Our data suggest that PL could be used to identify co-receptors for virus entry

    Determination of diphenhydramine hydrochloride in rabbit plasma by LC-MS/MS and its application to a pharmacokinetic study

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    A sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of diphenhydramine hydrochloride in rabbit plasma was developed and validated. After addition of triazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 50 mm, 3.5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 255.8 → 166.6 for diphenhydramine hydrochloride and m/z 342.9 → 308.0 for the IS. Calibration plots were linear over the range of 5- 200 ng/mL for diphenhydramine hydrochloride in rabbit plasma. Lower limit of quantitation (LLOQ) for diphenhydramine hydrochloride was 5 ng/mL. RSD of intra-day and inter-day precisions were both less than 10 %. This developed method is successfully used in pharmacokinetic study of diphenhydramine hydrochloride in rabbit.Colegio de Farmacéuticos de la Provincia de Buenos Aire

    Rhizosphere phage communities drive soil suppressiveness to bacterial wilt disease

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    Publisher Copyright: © 2023, The Author(s).Background: Bacterial viruses, phages, play a key role in nutrient turnover and lysis of bacteria in terrestrial ecosystems. While phages are abundant in soils, their effects on plant pathogens and rhizosphere bacterial communities are poorly understood. Here, we used metagenomics and direct experiments to causally test if differences in rhizosphere phage communities could explain variation in soil suppressiveness and bacterial wilt plant disease outcomes by plant-pathogenic Ralstonia solanacearum bacterium. Specifically, we tested two hypotheses: (1) that healthy plants are associated with stronger top-down pathogen control by R. solanacearum-specific phages (i.e. ‘primary phages’) and (2) that ‘secondary phages’ that target pathogen-inhibiting bacteria play a stronger role in diseased plant rhizosphere microbiomes by indirectly ‘helping’ the pathogen. Results: Using a repeated sampling of tomato rhizosphere soil in the field, we show that healthy plants are associated with distinct phage communities that contain relatively higher abundances of R. solanacearum-specific phages that exert strong top-down pathogen density control. Moreover, ‘secondary phages’ that targeted pathogen-inhibiting bacteria were more abundant in the diseased plant microbiomes. The roles of R. solanacearum-specific and ‘secondary phages’ were directly validated in separate greenhouse experiments where we causally show that phages can reduce soil suppressiveness, both directly and indirectly, via top-down control of pathogen densities and by alleviating interference competition between pathogen-inhibiting bacteria and the pathogen. Conclusions: Together, our findings demonstrate that soil suppressiveness, which is most often attributed to bacteria, could be driven by rhizosphere phage communities that regulate R. solanacearum densities and strength of interference competition with pathogen-suppressing bacteria. Rhizosphere phage communities are hence likely to be important in determining bacterial wilt disease outcomes and soil suppressiveness in agricultural fields. [MediaObject not available: see fulltext.].Peer reviewe

    Single-cell RNA-seq reveals T cell exhaustion and immune response landscape in osteosarcoma

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    BackgroundT cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear.MethodsIn our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups.ResultsThe findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group.ConclusionIn summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients

    In situ correction of various β-thalassemia mutations in human hematopoietic stem cells

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    β-thalassemia (β-thal) is the most common monogenic disorder caused by various mutations in the human hemoglobin β (HBB) gene and affecting millions of people worldwide. Electroporation of Cas9 and single-guide RNA (sgRNA)–ribonucleoprotein (RNP) complex-mediated gene targeting in patient-derived hematopoietic stem cells (HSCs), followed by autologous transplantation, holds the promise to cure patients lacking a compatible bone marrow donor. In this study, a universal gene correction method was devised to achieve in situ correction of most types of HBB mutations by using validated CRISPR/sgRNA–RNP complexes and recombinant adeno-associated viral 6 (rAAV6) donor-mediated homology-directed repair (HDR) in HSCs. The gene-edited HSCs exhibited multi-lineage formation abilities, and the expression of β-globin transcripts was restored in differentiated erythroid cells. The method was applied to efficiently correct different mutations in β-thal patient-derived HSCs, and the edited HSCs retained the ability to engraft into the bone marrow of immunodeficient NOD-scid-IL2Rg−/− (NSI) mice. This study provides an efficient and safe approach for targeting HSCs by HDR at the HBB locus, which provides a potential therapeutic approach for treating other types of monogenic diseases in patient-specific HSCs

    Breast mass as the first sign of metastasis from rectal carcinoma: a case report and review of the literature

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    We present a case report of a 41-year-old woman who developed a left breast mass 18 months after undergoing Dixon rectal cancer surgery. The purpose of this case report is to highlight the possibility of breast metastases in patients with colorectal cancer and emphasize the importance of careful evaluation and follow-up as well as timely and accurate diagnosis and management of the metastatic disease. During the physical examination in 2021, we noted that the lower border of the mass was 9 cm from the anal verge and that it occupied approximately one-third of the intestinal lumen. A pathological biopsy revealed the mass in the patient’s intestinal lumen was a rectal adenocarcinoma. The patient underwent Dixon surgery for rectal cancer and received subsequent chemotherapy. The patient had no prior history of breast-related medical conditions or a family history of breast cancer. During the current physical examination, we discovered multiple lymphadenopathies in the patient’s left neck, bilateral axillae, and left inguinal region, but none elsewhere. We observed a large erythema of about 15x10 cm on the patient’s left breast, with scattered hard nodes of varying sizes. Palpation of the area beyond the upper left breast revealed a mass measuring 3x3 cm. We conducted further examinations of the patient, which revealed the breast mass and lymphadenopathy on imaging. However, we did not find any other imaging that had significant diagnostic value. Based on the patient’s conventional pathology and immunohistochemical findings, combined with the patient’s past medical history, we strongly suspected that the patient’s breast mass was of rectal origin. This was confirmed by the abdominal CT performed afterward. The patient was treated with a chemotherapy regimen consisting of irinotecan 260 mg, fluorouracil 2.25 g, and cetuximab 700 mg IV drip, which resulted in a favorable clinical response. This case illustrates that colorectal cancer can metastasize to unusual sites and underscores the importance of thorough evaluation and follow-up, particularly when symptoms are atypical. It also highlights the importance of timely and accurate diagnosis and management of metastatic disease to improve the patient’s prognosis
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