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Purpose: Venous leg ulcers (VLUs) are prevalent chronic wounds with limited treatment options. This study aimed to investigate the potential of berberine to enhance endothelial progenitor cell (EPC) function in VLU healing. Methods: Histopathological changes and inflammatory cytokine levels in a deep venous thrombosis (DVT) mouse model were assessed using HE staining and ELISA assays. A luciferase reporter assay was employed to identify the miR-21-3p and RRAGB targeting relationship. EPC proliferation, migration, and tube formation were evaluated through CCK-8, Transwell, and tubule formation assays, while the mTOR pathway and autophagy-related proteins were analyzed by immunofluorescence staining and western blotting. Results: Berberine significantly improved EPC functions, such as proliferation, migration, and tube formation in vitro, and enhanced in vivo EPC-mediated wound healing in a DVT mouse model. Furthermore, miR-21-3p was downregulated in EPCs from VLU patients, and its overexpression improved model EPC functions. Mechanistically, RRAGB, which regulates the mTOR pathway, was identified as a potential miR-21-3p target in EPCs. Overexpression of RRAGB inhibited autophagic activity and impaired EPC function. Conclusion: Berberine shows promise in ameliorating EPC function and promoting wound healing in VLUs. The regulation of the miR-21-3p/RRAGB axis by berberine could offer a promising therapeutic approach for managing VLUs.
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Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C â T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.
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Anabaena , Sistemas CRISPR-Cas , Edición Génica , Synechocystis , Edición Génica/métodos , Synechocystis/genética , Anabaena/genética , Anabaena/metabolismo , Genoma Bacteriano , Cianobacterias/genética , Cianobacterias/metabolismoRESUMEN
BACKGROUND: This study aims to investigate the awareness rate of six common geriatric syndromes and related influencing factors among the older adults aged 65 and above in China. METHODS: This is a multicenter cross-sectional study involving 6,653 participants aged 65 and older from four regions who completed a questionnaire on geriatric syndrome awareness. The questionnaire covered demographic data, health information, medication usage, and an assessment scale for knowledge of six geriatric syndromes (GS Awareness Scale). RESULTS: A total of 6,653 respondents were surveyed, with 5,318 valid questionnaires collected (79.93%), including 1,311 from Zhejiang (24.7%), 1,356 from Beijing (25.5%), 1,373 from Sichuan (25.8%), and 1,278 from Fujian (24.0%). The highest awareness was for falls, with 3,295 individuals (62.0%), followed by dementia with 2,929 individuals (55.1%), malnutrition with 2,907 individuals (54.7%), frailty with 2,156 individuals (40.5%), urinary incontinence with 2,006 individuals (37.7%), and sarcopenia with 1,914 individuals (36.0%). Univariate analysis showed that factors such as region, age, marital status, living situation, educational level, source of respondents, income status, and smoking had statistically significant differences in awareness rates (P < 0.05). Multivariate logistic regression results indicated that the source of respondents significantly affected the awareness rates (P < 0.05), with the older adults from rural areas having an increased risk of lower awareness compared to urban areas; age also significantly influenced the awareness rates (P < 0.05), with older age groups (76-85, 86-95 years) having a higher risk of reduced awareness compared to those aged 65-75 years. CONCLUSIONS: The awareness of common geriatric syndromes among the older adults population aged 65 years and older in China is notably low. Consequently, there exists a critical need to enhance the formulation of policies regarding geriatric syndromes across various regions, aiming to elevate health literacy among this demographic.
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Conocimientos, Actitudes y Práctica en Salud , Humanos , Estudios Transversales , Anciano , Masculino , Femenino , China/epidemiología , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Encuestas y Cuestionarios , Síndrome , ConcienciaciónRESUMEN
Elymus nutans Griseb. (E. nutans), a pioneer plant for the restoration of high quality pasture and vegetation, is widely used to establish artificial grasslands and ecologically restore arid and salinized soils. To investigate the effects of drought stress and salt stress on the physiology and endogenous hormones of E. nutans seedlings, this experiment configured the same environmental water potential (0 (CK), - 0.04, - 0.14, - 0.29, - 0.49, - 0.73, and - 1.02 MPa) of PEG-6000 and NaCl stress to investigate the effects of drought stress and salt stress, respectively, on E. nutans seedlings under the same environmental water potential. The results showed that although the physiological indices and endogenous hormones of the E. nutans seedlings responded differently to drought stress and salt stress under the same environmental water potential, the physiological indices of E. nutans shoots and roots were comprehensively evaluated using the genus function method, and the physiological indices of the E. nutans seedlings under the same environmental water potential exhibited better salt tolerance than drought tolerance. The changes in endogenous hormones of the E. nutans seedlings under drought stress were analyzed to find that treatment with gibberellic acid (GA3), gibberellin A7 (GA7), 6-benzyladenine (6-BA), 6-(y,y-dimethylallylaminopurine) (2.IP), trans-zeatin (TZ), kinetin (KT), dihydrozeatin (DHZ), indole acetic acid (IAA), and 2,6-dichloroisonicotininc acid (INA) was more effective than those under drought stress. By analyzing the amplitude of changes in the endogenous hormones in E. nutans seedlings, the amplitude of changes in the contents of GA3, GA7, 6-BA, 2.IP, TZ, KT, DHZ, IAA, isopentenyl adenosine (IPA), indole-3-butyric acid (IBA), naphthalene acetic acid (NAA), and abscisic acid was larger in drought stress compared with salt stress, which could be because the endogenous hormones are important for the drought tolerance of E. nutans itself. The amplitude of the changes in the contents of DHZ, TZR, salicylic acid, and jasmonic acid was larger in salt stress compared with drought stress. Changes in the content of melatonin were larger in salt stress compared with drought stress, which could indicate that endogenous hormones and substances are important for the salt tolerance of E. nutans itself.
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Sequías , Reguladores del Crecimiento de las Plantas , Estrés Salino , Plantones , Plantones/fisiología , Plantones/efectos de los fármacos , Plantones/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Estrés Fisiológico , Raíces de Plantas/fisiología , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Tolerancia a la Sal , Ácidos Indolacéticos/metabolismo , Poaceae/fisiología , Poaceae/efectos de los fármacos , Poaceae/metabolismoRESUMEN
Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.
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Regulación Bacteriana de la Expresión Génica , Homeostasis , Hierro , Regiones Promotoras Genéticas , Synechocystis , Hierro/metabolismo , Synechocystis/metabolismo , Synechocystis/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Cianobacterias/metabolismo , Cianobacterias/genética , Perfilación de la Expresión GénicaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.
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Antígeno CD47 , Carcinoma Ductal Pancreático , Transición Epitelial-Mesenquimal , Trampas Extracelulares , Neoplasias Hepáticas , Macrófagos , Necroptosis , Neoplasias Pancreáticas , Proteínas Quinasas , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Animales , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/genética , Ratones , Macrófagos/metabolismo , Macrófagos/inmunología , Línea Celular Tumoral , Antígeno CD47/metabolismo , Antígeno CD47/genética , Proteínas Quinasas/metabolismo , Trampas Extracelulares/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Masculino , Transducción de Señal , Femenino , Acrilamidas , SulfonamidasRESUMEN
BACKGROUND: The rapid growth of cities has been accompanied by problems with urban air quality, making air pollution challenging to manage. In this situation, people focus on indoor building materials to improve air quality. OBJECTIVE: In this paper, a novel bola-type surfactant was synthesized and used as a template, using ethyl orthosilicate and sodium meta-aluminate as the silicon and aluminum source, in the ratio of n(NaOH): n(NaAIO2): n(SiO2): n(SDA): n(H2O) as 30:2.5:120:5:4800. METHODS: Hydrothermal preparation of ZSM-5 molecular sieves with a nanosheet structure (H-ZSM-5) was accomplished. The manufactured lamellar ZSM-5 molecular sieves were examined using X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and adsorption and desorption techniques. RESULTS: Traditional microporous ZSM-5 had a considerably lower static adsorption of formaldehyde molecules. The findings demonstrated that the nano-lamellar H-ZSM-5 molecular sieve can purify and eliminate larger molecular VOCs inside because it has the ability to adsorb larger molecular diameter VOCs. Additionally, the effectiveness of the adsorption was assessed using toluene vapour molecules with higher molecular diameters. CONCLUSION: The findings demonstrate that the nanosheet H-ZSM-5 molecular sieve can remove bigger molecule VOCs from indoor air and can be utilised to purify indoor spaces. This study offers a fresh approach to indoor environmental cleanup by demonstrating the capability of nano-lamellar H-ZSM-5 molecular sieves for molecular adsorption.
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We conducted a phase 1 study evaluating 3 dose levels of quizartinib (30â¯mg, 40â¯mg or 60â¯mg) in combination with azacitidine for HMA-naïve or relapsed/refractory MDS or MDS/MPN with FLT3 or CBL mutations. Overall, 12 patients (HMA naïve: n=9, HMA failure: n=3) were enrolled; 7 (58â¯%) patients had FLT3 mutations and 5 (42â¯%) had CBL mutations. The maximum tolerated dose was not reached. Most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (n=5, 42â¯%), anemia (n=4, 33â¯%), lung infection (n=2, 17â¯%), skin infection (n=2, 17â¯%), hyponatremia (n=2, 17â¯%) and sepsis (n=2, 17â¯%). The overall response rate was 83â¯% with median relapse-free and overall survivals of 15.1 months (95â¯% CI 0.0-38.4 months) and 17.5 months (95â¯% CI NC-NC), respectively. FLT3 mutation clearance was observed in 57â¯% (n=4) patients. These data suggest quizartinib is safe and shows encouraging activity in FLT3-mutated MDS and MDS/MPN. This study is registered at Clinicaltrials.gov as NCT04493138.
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Azacitidina , Benzotiazoles , Mutación , Síndromes Mielodisplásicos , Compuestos de Fenilurea , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Masculino , Anciano , Femenino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Benzotiazoles/administración & dosificación , Benzotiazoles/uso terapéutico , Benzotiazoles/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Azacitidina/administración & dosificación , Azacitidina/efectos adversos , Azacitidina/uso terapéutico , Anciano de 80 o más Años , Proteínas Proto-Oncogénicas c-cbl/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , AdultoRESUMEN
The presence of BRAF mutation in hematological malignancies, excluding Hairy cell leukemia, and its significance as a driver mutation in myeloid neoplasms (MNs) remains largely understudied. This research aims to evaluate patient characteristics and outcomes of BRAF-mutated MNs. Among a cohort of 6667 patients, 48 (0.7%) had BRAF-mutated MNs. Notably, three patients exhibited sole BRAF mutation, providing evidence supporting the hypothesis of BRAF's role as a driver mutation in MNs. In acute myeloid leukemia, the majority of patients had secondary acute myeloid leukemia, accompanied by poor-risk cytogenic and RAS pathway mutations. Although the acquisition of BRAF mutation during disease progression did not correlate with unfavorable outcomes, its clearance through chemotherapy or stem cell transplant exhibited favorable outcomes (median overall survival of 34.8 months versus 10.4 months, p = 0.047). Furthermore, G469A was the most frequently observed BRAF mutation, differing from solid tumors and hairy cell leukemia, where V600E mutations were predominant.
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Mutación , Proteínas Proto-Oncogénicas B-raf , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto , Incidencia , Pronóstico , Anciano de 80 o más Años , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/diagnóstico , Adulto Joven , Resultado del TratamientoRESUMEN
Various psychosocial and psychological interventions have been developed to reduce schizophrenia relapse prevention. A better understanding of these active interventions is important for clinical practice and for meaningful allocation of resources. However, no bibliometric analysis of this area has been conducted. Studies were retrieved from the Web of Science Core Collection database. The publication outputs and cooperation of institutions were visualized with Origin 2021. Global cooperation was visualized using ArcGIS Pro3.0. VOSviewer was used to generate visualizations of network of authors and keywords. The number of annual publications generally showed a fluctuating upward trend over the past 20 years. Germany published the most relevant articles (361, 26.76%). The Technical University of Munich was the most productive institution (70, 9.86%). Leucht Stefan published the most articles (46, 6.48%) and had the highest number of citations (4,375 citations). Schizophrenia Research published the most studies (39, 5.49%). Keywords were roughly classified into three clusters: cognitive behavioral therapy (CBT), family interventions and family psychoeducation and other factors related to interventions. The findings provided the current status of research on psychosocial and psychological interventions for schizophrenia relapse prevention from a bibliometric perspective. Recent research has mainly focused on CBT, family interventions and family psychoeducation.
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Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.
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Neoplasias de la Mama , Mamoplastia , Femenino , Humanos , Persona de Mediana Edad , Mama/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Mamoplastia/métodos , Mastectomía , Recurrencia Local de Neoplasia/patología , Adulto , AncianoRESUMEN
Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.
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The alcohol extraction of P. sibiricum has exhibited significant inhibitory effects on the production of free radicals and the proliferation of non-small-cell lung carcinoma (NSCLC) A549 cells. Despite the diverse components found in alcohol extraction of P. sibiricum and its multiple targets, the active components and associated targets remain largely unidentified. Hence, there is a need for additional investigation into the pharmacodynamic elements and mechanisms of action. This study aimed to analyze and identify the components responsible for the anti-tumor activity of alcohol extraction from P. sibiricum using UPLC-Q-TOF-MS/MS for the first time. Subsequently, the targets of the active components were predicted using the SwissTargetPrediction database, whereas the targets for NSCLC were sourced from the Online Mendelian Inheritance in Man database (OMIM) and the GeneCards database. Next, the targets of chemical composition were integrated with disease targets via Venny online. GO and KEGG pathway enrichment analyses were performed utilizing DAVID. Subsequently, a network analysis of "components-targets-pathways" was established using Cytoscape 3.8.2 and assessed with the "network analyzer" plug-in. Molecular docking was conducted utilizing Autodock 1.5.6. The study aimed to examine the anti-proliferative impacts and underlying mechanisms of alcohol extraction from P. sibiricum on NSCLC through in vivo and in vitro investigations utilizing an animal model of transplanted tumor, CCK8 assay, cell scratch test, RT-qPCR, and western blotting. The study unveiled that 17 active components extracted from P. sibiricum alcohol demonstrated anti-non-small cell lung cancer (NSCLC) effects through the modulation of 191 targets and various significant signaling pathways. These pathways include Endocrine resistance, PI3K/AKT, Chemical carcinogenesis-receptor activation, Proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, AMPK signaling pathway, and other related signaling pathways. Network analysis and molecular docking results indicated that specific compounds such as (25S)-26-O-(ß-d-glucopyranosyl)-furost-5-en3ß,22α,26-triol3-O-ß-d-glucopyranosyl-(1â2)-ß-d-glucopyranosyl-(1â4)-ß-d-glucopyranoside, Timosaponin H1, Deapi-platycodin D3, (3R)-5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxybenzyl)-chroman-4-one, Disporopsin, Funkioside F, Kingianoside E, Parisyunnanoside H, and Sibiricoside B primarily targeted 17 key proteins (BCL2, EGFR, ESR1, ESR2, GRB2, IGF1R, JUN, MAP2K1, MAPK14, MAPK8, MDM2, MMP9, mTOR, PIK3CA, RAF1, RPS6KB1, and SRC) collectively. In conclusion, the alcohol extraction of P. sibiricum demonstrated inhibitory effects on cell proliferation, induction of apoptosis, and inhibition of metastasis through various pathways.
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In recent years, nanomaterials have gained widespread use in the biomedical field, with ZIF-8 and ZnO emerging as promising candidates due to their remarkable performance in osteogenesis, angiogenesis, and antimicrobial therapy. However, before advancing these nanomaterials for clinical applications, it is imperative to evaluate their biocompatibility. In particular, comparing nanomaterials with similar biomedical functions is crucial for identifying the most suitable nanomaterials for further development and market entry. Our study aimed to compare the biocompatibility of nano-ZIF-8 and nano-ZnO under the same conditions. We found that nano-ZIF-8 exhibited lower toxicity both in vitro and in vivo compared to nano-ZnO. To gain insights into the underlying mechanisms responsible for this difference, we conducted further experiments to investigate lysosome damage, mitochondrial change, and the occurrence of ferroptosis. Additionally, we performed transcriptome sequencing to analyze the expression of relevant genes, thereby providing robust validation for our findings. In summary, our study highlighted the importance of evaluating nanomaterials with similar biomedical effects. Through this comparative study, we have not only shed light on the superior biocompatibility of nano-ZIF-8 over nano-ZnO, but also contributed valuable insights and methodological references for future material screening endeavors. Ultimately, our study served as a stepping stone toward the development of safer and more effective nanomaterials for various biomedical applications.
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Materiales Biocompatibles , Óxido de Zinc , Óxido de Zinc/química , Óxido de Zinc/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Ratones , Humanos , Zinc/química , Zinc/farmacología , Ferroptosis/efectos de los fármacos , Ensayo de Materiales , Nanoestructuras/química , Nanoestructuras/toxicidad , Supervivencia Celular/efectos de los fármacos , Zeolitas/química , Zeolitas/farmacologíaRESUMEN
Targeted therapy development for acute myeloid leukaemia (AML) requires an understanding of specific expression profiles. We collected flow cytometry data on 901 AML patients and recorded aberrant CD7 expression on leukaemic blasts. 263 (29.2%) had blasts positive for CD7. CD7+ AML was more likely to be adverse risk (64.6% vs. 55.6%, p = 0.0074) and less likely to be favourable risk (15.2% vs. 24.1%, p = 0.0074) by European LeukemiaNet 2022 criteria. Overall survival was inferior (11.9 [95% CI, 9.7-15.9] vs. 19.0 months [95% CI, 16.1-23.0], p = 0.0174). At relapse, 30.4% lost and 19.0% gained CD7, suggesting moderate instability over time.
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Antígenos CD7 , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Antígenos CD7/análisis , Antígenos CD7/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Adulto Joven , Citometría de Flujo , Adolescente , Pronóstico , InmunofenotipificaciónRESUMEN
Background: Ropivacaine (Ropi) is a widely utilized anesthetic in cesarean sections (CS), however its optimal dosage remains controversial. Objective: To assess the efficacy and safety of varying doses (10mg, 5mg, 4mg, and 3mg) of Ropi in subarachnoid block (SA) for CS. Methods: A prospective cohort study was conducted, and a total of 74 pregnant women undergoing CS at Nantong Maternal and Child Health Care Hospital between January and June 2023 were selected as the study population. Participants were stratified into groups based on Ropivacaine dosage: Group A (10 mg, n=18), Group B (5 mg, n=26), Group C (4 mg, n=15), and Group D (3 mg, n=15). The total Ropivacaine dosage administered via SA was consistently 10 mg across all groups. We measured anesthetic efficacy, safety profiles, abdominal wall muscle relaxation, pre- and post-anesthesia stress and inflammatory responses before and after anesthesia and compared among the four groups. Results: Group A exhibited the shortest onset time for block initiation and longest recovery duration (P < .05). Group D displayed the highest incidence of patients requiring additional anesthetics and experiencing adverse reactions, whereas the utilization rate of vasopressors was most pronounced in Group A (P < .05). Notably, Group D reported the lowest satisfaction rate regarding abdominal wall muscle relaxation (P < .05). Stress responses were significantly lower in Groups A, B, and C compared to Group D, while the levels of inflammatory factors in Groups B and C were higher than those in Group A but lower than those in Group D (P < .05). Conclusions: Administration of 4 mg hyperbaric Ropi in SA can achieve an optimal anesthesia effect in CS with a high level of safety, along with inducing mild abdominal wall muscle relaxation and attenuating stress and inflammatory responses pre- and post-anesthesia. Thus, it is recommended for clinical application.
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Using coconut shell and boric acid as raw materialsï¼ a new boron-doped coconut shell mesoporous carbon material ï¼B-CSCï¼ was prepared using a simple one-step pyrolysis method for efficient adsorption and removal of tetracycline pollutants in water. The effects of pyrolysis temperature and boron-carbon mass ratio on the adsorption performance under key preparation conditions were systematically studiedï¼ and their microstructure and physicochemical properties were characterized using a specific surface area and pore size analyzer ï¼BETï¼ï¼ field emission scanning electron microscopy ï¼SEMï¼ï¼ X-ray photon spectroscopy ï¼XPSï¼ï¼ Raman spectrometer ï¼Ramanï¼ï¼ and Zeta potentiometer ï¼Zetaï¼. The effects of initial pHï¼ different metal cationsï¼ and different background water quality conditions on the adsorption effect were systematically investigated. Combined with material characterization and correlation analysisï¼ the enhanced adsorption mechanism was discussed and analyzed in depth. The results showed that one-step pyrolysis could incorporate boron into the surface and crystal lattice of coconut shell charcoalï¼ resulting in a larger specific surface area and pore volumeï¼ and the main forms of boron introduced were H3BO3ï¼ B2O3ï¼ Bï¼ and B4C. The adsorption capacity of B-CSC to tetracycline reached 297.65 mg·g-1ï¼ which was 8.9 times that of the original coconut shell mesoporous carbon ï¼CSCï¼. At the same timeï¼ the adsorption capacity of B-CSC for rhodamine B ï¼RhBï¼ï¼ bisphenol Aï¼BPAï¼ï¼ and methylene blue ï¼MBï¼ï¼ common pollutants in aquatic environmentsï¼ was as high as 372.65ï¼ 255.24ï¼ and 147.82 mg·g-1ï¼ respectively. The adsorption process of B-CSC to tetracycline was dominated by physicochemical interactionï¼ mainly involving liquid film diffusionï¼ surface adsorptionï¼ mesoporous and microporous diffusionï¼ and active site adsorptionï¼ and H3BO3 was the main adsorption site. The adsorption strengthening mechanism mainly reduced the chemical inertness of the carbon network and enhanced its π-π interaction and hydrogen bonding with tetracycline molecules.
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To investigate the safety and effect of Tubridge flow diverter deployment for the treatment of intracranial aneurysms, 85 patients with intracranial aneurysms treated with the Tubridge flow diverter were retrospectively enrolled. The clinical data including the baseline data, aneurysm parameters before and after treatment, and follow-up outcomes were assessed. Among 85 patients, there were 35 (41.2%) males and 50 females (58.8%) aged 17-77 (mean 56.7 ± 11.1) years with 110 aneurysms. Five (5.9%) patients initially presented with subarachnoid hemorrhage from aneurysm rupture. The aneurysm size was 2-30 (mean 8.6) mm, and the aneurysm neck was 2-10.6 (mean 5.7 ± 2.3) mm. Ninety-three Tubridge stents were deployed. Twenty-five (29.4%) patients experienced adjunctive loose coiling. Blood flow was significantly reduced from entering the aneurysm after stent deployment. Periprocedural complications occurred in three (3.5%) patients, including in-stent thrombosis during embolization in one patient (1.2%), conjunctiva edema on the right in one patient (1.2%), and acute multiple cerebral infarctions in one patient (1.2%). Angiographic follow-up was conducted in 67 (78.8%) patients 3-36 (mean 15.3 ± 5.6) months later. In 11 (16.4% or 11/67) patients, blood flow still entered the aneurysm with the O'Kelly-Marotta (OKM) grade B in two (3.0%) patients and grade C in nine (13.4%), whereas complete occlusion (OKM grade D) was achieved in the other 56 (83.6% or 56/67) aneurysms. In-stent stenosis was present in five (7.5%) patients with approximately 25% stenosis in three (4.5%) patients and 50% in two (3.0%). In conclusion, the Tubridge flow diverter can be safely and efficiently applied in the treatment of small and large intracranial aneurysms, with a low periprocedural complication rate, a high occlusion degree, and a low in-stent stenosis rate at follow-up even though large aneurysms may necessitate a longer surgical time and adjunctive coiling.