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INTRODUCTION: While laparoscopic splenectomy (LS) has been widely used in benign splenic tumor, more concerns have been raised for postoperatively short-term and long-term complications. Laparoscopic partial splenectomy (LPS) is a surgical option, to preserve splenic function, and reduce postoperative complications. The aim of our study was to retrospectively identify the safety and feasibility of LPS compared with LS in patients with splenic benign tumor. MATERIALS AND METHODS: From 2014 to 2024, a total of 165 patients diagnosed with occupational splenic lesions underwent splenectomy, of whom 87 underwent LPS and 78 underwent LS. We compare the perioperative parameters and long term follow up between these two groups. RESULTS: The etiology of splenic space-occupying lesions was nonparasitic splenic cysts, followed by splenic lymphangioma and splenic hemangioma. Of the patients with LPS, 55 underwent conventional surgery with blockage of the splenic arterial branch and resection along the ischemic line (RAIL), and 32 underwent with our modified total splenic blood supply blockade followed by resection alone the tumor edge (RATE). The tumor size, the operative time and estimated blood loss were comparable between the LPS and LS groups. One patient developed abnormal signs during the LPS procedure and was promptly referred for LS. The LPS group had fewer pancreatic leakage, incision infection, and pulmonary infection. As for different vascular types, patients with LS under all branches of the splenic artery had a longer time to resume postoperative feeding. As for the comparison of RAIL and RATE, estimated blood and operative time were significantly reduced in patients receiving RATE. Postoperative complications were the same in patients underwent each surgical procedures. CONCLUSION: LPS is a viable approach for patients with splenic benign tumor. We introduce the tumor artery supply types to indicate the resection region. Our RATE technique has proven to be clinically effective and safety.
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To explore the patterns of differentially expressed genes (DEGs) associated with different growth rates in rock carp (Procypris rabaudi), transcriptome sequencing was performed on the muscle, liver, and brain tissues of rock carp. Subsequently, bioinformatics analysis was conducted, and 2129, 1380, and 415 DEGs were identified in the muscle, liver, and brain tissues, respectively. GO enrichment and KEGG pathway analysis revealed that genes related to appetite regulation, protein degradation and digestion, lipid transport and metabolisms, and glycolysis/gluconeogenesis were upregulated in individuals with slower growth rates. Differential expression analysis identified 21 genes associated with feeding and metabolism across three tissues, including mc4r, npy, and npry in brain tissue; fatp, fabp, pparα, and apo in liver tissue; and prss, ctrl, and cela in muscle tissue. All these genes were upregulated in the slow-growing fish. Furthermore, weighted gene co-expression network analyses, including three modules (yellow, turquoise, and brown), significantly associated with growth. A network map that included these three modules enabled the identification of a series of hub genes, including rp13a, ube2o, h6pd, etc. These genes may be key candidate genes regulating the growth of rock carp. This study contributes to a deeper understanding of the growth control mechanism in rock carp and offers a scientific basis for efficient breeding and species improvement.
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Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.
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Neoplasias del Colon , Herpesvirus Humano 1 , Interleucina-15 , Viroterapia Oncolítica , Virus Oncolíticos , Animales , Herpesvirus Humano 1/genética , Interleucina-15/genética , Interleucina-15/inmunología , Neoplasias del Colon/terapia , Neoplasias del Colon/inmunología , Viroterapia Oncolítica/métodos , Ratones , Virus Oncolíticos/genética , Virus Oncolíticos/inmunología , Línea Celular Tumoral , Ratones Endogámicos BALB C , Humanos , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/genética , Subunidad alfa del Receptor de Interleucina-15/genética , FemeninoRESUMEN
A previous study showed that kiwifruit polysaccharide (KFP) has benefits in relieving intestinal inflammation, while the underlying mechanism remains unresolved. The objective of this study was to investigate the regulatory effect of KFP on the gut microbiota metabolism and intestinal barrier of ulcerative colitis (UC) mice induced by dextran sulfate sodium (DSS). KFP significantly improved the UC symptoms including weight loss, shortened colon length, splenomegaly, diarrhea, hematochezia, and colon inflammation of mice. In addition, KFP could alleviate DSS-caused gut microbiota dysbiosis and increase the levels of short-chain fatty acids in the cecal contents of mice. Furthermore, the results of nontargeted and targeted metabolomics analysis combined with antibiotic treatment revealed that KFP could regulate gut microbiota-dependent tryptophan metabolism, activate the aryl hydrocarbon receptor (AhR) in colon cells, and enhance interleukin-22 production and tight junction proteins' (ZO-1, occludin, and claudin3) expression to repair the intestinal barrier in UC mice. Immunofluorescence results showed that KFP significantly upregulated the conjunction of lectin WGA and UEA1 in the UC mouse colon, implying that KFP promoted fucosylation in the colon. These results suggest that KFP alleviates UC primarily via targeting the gut microbiota involved in the AhR pathway and upregulating colon fucosylation.
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A human induced pluripotent stem cell (iPSC) line was generated from patient with type 1 neurofibromatosis (NF-1), carrying heterozygous mutation in NF1 gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of KFL4, OCT4, SOX2, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and is able to differentiate into three germ layers in vitro. This iPSC line represents a valuable cell model for NF1 in humans.
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Histone lysine isonicotinylation (Kinic) induced by isoniazid (INH) was recently identified as a post-translational modification in cells. However, global cellular non-histone proteins Kinic remains unclear. Using proteomic technology, we identified 11,442 Kinic sites across 2,792 proteins and demonstrated that Kinic of non-histone proteins is involved in multiple function pathways. Non-histone proteins Kinic can be regulated by isonicotinyl-transferases, including CBP and Tip60, and deisonicotinylases, including HDAC8 and HDAC6. In particular, the Kinic of poly (ADP-ribose) (PAR) polymerase 1 (PARP1) can be catalyzed by CBP and deisonicotinylation can be catalyzed by HDAC8. Tip60 and HDAC6 are isonicotinyl-transferase and the deisonicotinylase of SMAD3, respectively. Importantly, we found the K378inic of SMAD3 increases its phosphorylation, activates TGFß pathway, and promotes liver cancer cells migration and invasion. In conclusion, our study demonstrated non-histone proteins Kinic occur extensively in cells and plays an important role in regulation of various cellular functions, including cancer progression.
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Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.
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Antiinflamatorios , Diterpenos de Tipo Kaurano , Isodon , Lipopolisacáridos , Óxido Nítrico , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Ratones , Animales , Células RAW 264.7 , Isodon/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Estructura Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Conformación Molecular , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificaciónRESUMEN
Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/ß-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF.
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Cornus , Análisis de Componente Principal , Espectrometría de Masas en Tándem , Vino , Vino/análisis , Cromatografía Líquida de Alta Presión/métodos , Cornus/química , Espectrometría de Masas en Tándem/métodos , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Ácido Gálico/química , Ácido Gálico/análisis , Frutas/química , Análisis de los Mínimos CuadradosRESUMEN
Corn ear rot and fumonisin caused by Fusarium verticillioides pose a serious threat to food security. To find more highly active fungicidal and antitoxic candidates with structure diversity based on naturally occurring lead xanthatin, a series of novel spiropiperidinyl-α-methylene-γ-butyrolactones were rationally designed and synthesized. The in vitro bioassay results indicated that compound 7c showed broad-spectrum in vitro activity with EC50 values falling from 3.51 to 24.10 µg/mL against Rhizoctonia solani and Alternaria solani, which was more active than the positive controls xanthatin and oxathiapiprolin. In addition, compound 7c also showed good antitoxic efficacy against fumonisin with a 48% inhibition rate even at a concentration of 20 µg/mL. Fluorescence quenching and the molecular docking validated both 7c and oxathiapiprolin targeting at FvoshC. RNA sequencing analysis discovered that FUM gene cluster and protein processing in endoplasmic reticulum were downregulated. Our studies have discovered spiropiperidinyl-α-methylene-γ-butyrolactone as a novel FvoshC target-based scaffold for fungicide lead with antitoxin activity.
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Alternaria , Fungicidas Industriales , Fusarium , Simulación del Acoplamiento Molecular , Rhizoctonia , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/síntesis química , Alternaria/efectos de los fármacos , Fusarium/efectos de los fármacos , Rhizoctonia/efectos de los fármacos , Relación Estructura-Actividad , Enfermedades de las Plantas/microbiología , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/farmacología , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Receptores de Esteroides/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/química , Descubrimiento de Drogas , Zea mays/química , Zea mays/microbiología , Estructura MolecularRESUMEN
The construction of ecological networks within the context of urbanization is an effective approach to cope with the challenges of urban biodiversity decline, representing a crucial goal in urban planning and development. However, existing studies often overlook the richness and uniqueness within species communities by homogenizing traits of species in the same class. This study proposes a framework for constructing and optimizing ecological networks focused on differential conservation within the same class. By classifying birds into three groups (specialists of water, forest or urban areas) based on their ecological requirements and urbanization tolerance, we constructed an ecological network tailored to their distinct migratory dispersal patterns. We then identified strategic areas including pinch points, barriers, and breakpoints specific to each bird group. Our findings reveal notable variations in suitable habitat distribution among different bird groups in urban environments. Corridor layouts varied according to habitat preferences and migratory dispersal patterns. Despite these differences, urban built-up areas persist as central hubs for the distribution of suitable habitats for 75% of bird species, with peripheral mountain-plain transition areas constituting 63% of crucial dispersal corridors. This emphasizes the critical role of urban built-up areas in maintaining biodiversity and ecological connectivity. Prioritizing connectivity between central urban areas and distant natural spaces is imperative. Our approach innovatively classifies and constructs networks to identify strategic areas with diverse species-specific attributes, providing valuable spatial information for land planning and guiding solutions to enhance target species. While the primary focus is on bird conservation in Beijing, our framework is broadly applicable to global biodiversity management and green planning under urbanization challenges. Overall, this study offers innovative insights for urban planning development and serves as decision support for prioritizing urban actions.
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Biodiversidad , Conservación de los Recursos Naturales , Ecosistema , Urbanización , Conservación de los Recursos Naturales/métodos , Animales , AvesRESUMEN
A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 µM.
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Diarilheptanoides , Dioscorea , Glicósidos , Fitoquímicos , Rizoma , Dioscorea/química , Rizoma/química , Diarilheptanoides/aislamiento & purificación , Diarilheptanoides/química , Diarilheptanoides/farmacología , Ratones , Células RAW 264.7 , Estructura Molecular , Animales , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/química , Glicósidos/aislamiento & purificación , Glicósidos/química , Glicósidos/farmacología , Óxido Nítrico/metabolismo , ChinaAsunto(s)
Hemangioma , Propranolol , Humanos , Propranolol/uso terapéutico , Propranolol/administración & dosificación , Lactante , Hemangioma/tratamiento farmacológico , Femenino , Masculino , Resultado del Tratamiento , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/administración & dosificación , Neoplasias de los Párpados/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
A novel real-time optical phase sensing method based on the Mach-Zehnder interference principle has been proposed for the detection of calreticulin (CRT) levels in human serum samples. In this approach, anti-CRT antibodies are utilized to capture CRT molecules in serum, leading to a phase shift in both the measuring and reference arms of the system. By employing the concept of weak amplification within the framework of weak measurements, it becomes feasible to continuously monitor the response of CRT in real-time, allowing for the precise determination of serum CRT content at the picomolar level. Our achievement may pave the way in establishing CRT as a diagnostic biomarker for a wide range of medical applications, including rheumatoid arthritis.
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Natural products derived from medicinal plants offer convenience and therapeutic potential and have inspired the development of antimicrobial agents. Thus, it is worth exploring the combination of nanotechnology and natural products. In this study, silver nanoparticles (AgNPs) were synthesized from the leaf extract of Ginkgo biloba (Gb), having abundant flavonoid compounds. The reaction conditions and the colloidal stability were assessed using ultraviolet-visible spectroscopy. X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy (FTIR) were used to characterize the AgNPs. AgNPs exhibited a spherical morphology, uniform dispersion, and diameter ranging from ~8 to 9 nm. The FTIR data indicated that phytoconstituents, such as polyphenols, flavonoids, and terpenoids, could potentially serve as reducing and capping agents. The antibacterial activity of the synthesized AgNPs was assessed using broth dilution and agar well diffusion assays. The results demonstrate antibacterial effects against both Gram-positive and Gram-negative strains at low AgNP concentrations. The cytotoxicity of AgNPs was examined in vitro using the CCK-8 method, which showed that low concentrations of AgNPs are noncytotoxic to normal cells and promote cell growth. In conclusion, an environmentally friendly approach for synthesizing AgNPs from Gb leaves yielded antibacterial AgNPs with minimal toxicity, holding promise for future applications in the field of biomedicine.
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Nanopartículas del Metal , Plata , Plata/farmacología , Plata/química , Ginkgo biloba , Nanopartículas del Metal/química , Antibacterianos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
The GRAS (GAI\RGA\SCL) gene family encodes plant-specific transcription factors that play crucial roles in plant growth and development, stress tolerance, and hormone network regulation. Plant dwarfing symptom is mainly regulated by DELLA proteins of the GRAS gene subfamily. In this study, the association between the GRAS gene family and Paulownia witches' broom (PaWB) was investigated. A total of 79 PfGRAS genes were identified using bioinformatics methods and categorized into 11 groups based on amino acid sequences. Tandem duplication and fragment duplication were found to be the main modes of amplification of the PfGRAS gene family. Gene structure analysis showed that more than 72.1% of the PfGRASs had no introns. The genes PfGRAS12/18/58 also contained unique DELLA structural domains; only PfGRAS12, which showed significant response to PaWB phytoplasma infection in stems, showed significant tissue specificity and responded to gibberellin (GA3) in PaWB-infected plants. We found that the internodes were significantly elongated under 100 µmol·L-1 GA3 treatment for 30 days. The subcellular localization analysis indicated that PfGRAS12 is located in the nucleus and cell membrane. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays confirmed that PfGRAS12 interacted with PfJAZ3 in the nucleus. Our results will lay a foundation for further research on the functions of the PfGRAS gene family and for genetic improvement and breeding of PaWB-resistant trees.
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Cytisus , Lamiales , Magnoliopsida , Phytoplasma , Magnoliopsida/genética , Enfermedades de las Plantas/genética , Phytoplasma/genética , Fitomejoramiento , Lamiales/genéticaRESUMEN
Effective treatment of drug-resistant bacteria infected wound has been a longstanding challenge for healthcare systems. In particular, the development of novel strategies for controllable delivery and smart release of antimicrobial agents is greatly demanded. Herein, the design of biodegradable microcapsules carrying bactericidal gold nanoclusters (AuNCs) as an attractive platform for the effective treatment of drug-resistant bacteria infective wounds is reported. AuNC capsules are fabricated via the well-controlled layer-by-layer strategy, which possess intrinsic near-infrared fluorescence and good biocompatibility. Importantly, these AuNC capsules exhibit strong, specific antibacterial activity toward both S. aureus and methicillin-resistant S. aureus (MRSA). Further mechanistic studies by fluorescence confocal imaging and inductively coupled plasma mass spectrometry reveal that these AuNC capsules will be degraded in the S. aureus environment rather than E. coli, which then controllably release the loaded cationic AuNCs to exert antibacterial effect. Consequently, these AuNC capsules show remarkable therapeutic effect for the MRSA infected wound on a mouse model, and intrinsic fluorescence property of AuNC capsules enables in situ visualization of wound dressings. This study suggests the great potential of microcapsule-based platform as smart carriers of bactericidal agents for the effective treatment of drug-resistant bacterial infection as well as other therapeutic purposes.
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Antibacterianos , Oro , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Animales , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Oro/química , Nanopartículas del Metal/química , Cápsulas/química , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Cationes/química , Pruebas de Sensibilidad MicrobianaRESUMEN
Smad3 is the key mediator of TGF-ß1-triggered signal transduction and the related biological responses, promoting cell invasion and metastasis in various cancers, including lung cancer. However, the deubiquitinase stabilizing Smad3 remains unknown. In this study, we present a paradigm in which POH1 is identified as a novel deubiquitinase of Smad3 that plays a tumor-promoting role in lung adenocarcinoma (LUAD) by regulating Smad3 stability. POH1 markedly increased Smad3 protein levels and prolonged its half-life. POH1 directly interacted and colocalized with Smad3, leading to the removal of poly-deubiquitination of Smad3. Functionally, POH1 facilitated cell proliferation, migration, and invasion by stabilizing Smad3. Importantly, POH1 also promoted liver metastasis of lung cancer cells. The protein levels of both POH1 and Smad3 were raised in the tumor tissues of patients with LUAD, which predicts poor prognosis. Collectively, we demonstrate that POH1 acts as an oncoprotein by enhancing TGF-ß1/Smad3 signaling and TGF-ß1-mediated metastasis of lung cancer.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteína smad3/genética , Proteína smad3/metabolismo , Línea Celular Tumoral , Adenocarcinoma del Pulmón/genética , Enzimas Desubicuitinizantes/metabolismo , Movimiento CelularRESUMEN
Introduction: The horizontal transfer of antibiotic resistance genes mediated by plasmids seriously hinders the effectiveness of modern medical treatment, and thus has attracted widespread attention. Additionally, the co-selection mechanism of antibiotic resistance genes (ARGs) and heavy metal resistance genes (MRGs) on mobile elements may further exacerbate the horizontal transfer of resistance genes. Methods: In this study, a multidrug-resistant Pseudomonas aeruginosa strain, termed BJ86 (CHPC/NPRC1.4142), was isolated from a patient's sputum specimen. In vitro tests for antimicrobial susceptibility, conjugation, whole-genome sequencing, and bioinformatics analysis were used to explore the potential mechanisms of resistance and its spread. Results and discussion: Sequencing analysis indicates that P. aeruginosa BJ86 carries an amazing 522.5 kb-length megaplasmid, pBJ86, which contained a 93.5 kb-length multiple resistance region (MRR); 18 kinds of genes were identified as ARGs in this region, including tmexCD-oprJ, blaDIM-1, qnrVC6 that mediate resistance to multiple antibiotics and the operons mer that mediates heavy metal mercury resistance. In addition, there is also an 80 kb variable region (VR) on the plasmid pBJ86, and the genes encoding relaxase and type IV coupling protein (T4CP) were determined in this region, both of which are related to the conjugation and transfer ability of the plasmid. Bioinformatics analysis shows that many functional genes have insertion sequences and transposases on their flanks, which may have accumulated in the plasmid pBJ86 after multiple acquisition events. Conjugated transfer and in vitro tests for antimicrobial susceptibility verified the mobility and plasmid pBJ86-mediated resistance. To our knowledge, we are the first to report a mobilizable megaplasmid that simultaneously carried tmexCD-oprJ, blaDIM-1, qnrVC6, and the operons mer and can be transferred with frequencies of 6.24 × 10-7 transconjugants per donor cell.
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INTRODUCTION: Whole genome sequencing (WGS) holds significant promise for epidemiological inquiries, as it enables the identification and tracking of pathogenic origins and dissemination through comprehensive genome analysis. This method is widely preferred for investigating outbreaks and monitoring pathogen activity. However, the effective utilization of microbiome sequencing data remains a challenge for clinical and public health experts. Through the National Pathogen Resource Center, we have constructed a dynamic and interactive online analysis platform to facilitate the in-depth analysis and use of pathogen genomic data, by public health and associated professionals, to support infectious disease surveillance framework building and capacity warnings. METHOD: The platform was implemented using the Java programming language, and the front-end pages were developed using the VUE framework, following the MVC (Model-View-Controller) pattern to enable interactive service functionalities for front-end data collection and back-end data computation. Cloud computing services were employed to integrate biological information analysis tools for conducting fundamental analysis on sequencing data. RESULT: The platform achieved the goal of non-programming analysis, providing an interactive visual interface that allows users to visually obtain results by setting parameters in web pages. Moreover, the platform allows users to export results in various formats to further support their research. DISCUSSION: We have established a dynamic and interactive online platform for bioinformatics analysis. By encapsulating the complex background experiments and analysis processes in a cloud-based service platform, the complex background experiments and analysis processes are presented to the end-user in a simple and interactive manner. It facilitates real-time data mining and analysis by allowing users to independently select parameters and generate analysis results at the click of a button, based on their needs, without the need for a programming foundation.
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Programas Informáticos , Interfaz Usuario-Computador , Genómica/métodos , Biología Computacional/métodos , GenomaRESUMEN
BACKGROUND: PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC). METHODS: In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments. RESULTS: PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial-mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy. CONCLUSIONS: PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC.