RESUMO
BACKGROUND: 5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection. METHODS: 5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy. RESULTS: In this study, the WNT/ß-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells. CONCLUSIONS: These data underscored the activation of the WNT/ß-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Fluoruracila , Neoplasias Bucais , Via de Sinalização Wnt , Proteína Wnt3 , Humanos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Linhagem Celular Tumoral , Proteína Wnt3/metabolismo , Proteína Wnt3/genética , beta Catenina/metabolismo , beta Catenina/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antimetabólitos Antineoplásicos/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Objective: To investigate the effect of emergency plans and first aid procedures on injury control and precise treatment in patients with acute traumatic cervical spinal cord injury. Given the challenges in managing acute traumatic cervical spinal cord injuries and the need for efficient emergency plans and first aid procedures, the importance of this study is self-evident. Methods: A total of 103 patients with acute traumatic cervical spinal cord injury were enrolled in our study from January 2017 to December 2022, and these patients were divided into two groups according to the time of admission: 51 cases from January 2017 to December 2019 were in the control group, and 52 cases from January 2020 to December 2022 were in the study group. The control group was given routine emergency care. The study group received emergency plans and first aid procedures that included rapid assessment, optimized patient handling and transport, and immediate medical intervention. We compared the International Classification of Functioning, Disability and Health (ICF) scores, the Short Form Health Survey (SF-36) scores, the Activities of Daily Living (ADL) scores, and the occurrence of adverse events 3 months after rescue between the two groups. Results: The study group demonstrated significantly shorter times for prehospital emergency rescue, waiting time upon admission, time from admission to treatment, mechanical ventilation duration, and ICU stay when compared to the control group (P < .05). The intubation rate and mortality rate in the research group were 28.85% and 11.54%, respectively, compared to 31.37% and 13.73% in the control group, with no statistically significant differences (P > .05). Three months after the rescue, the study group showed significantly lower scores in environmental factors, activities and participation, body structure, and body function compared to the control group (P < .05). Three months after the rescue, the research group had significantly higher SF-36 scores (P < .05), and their ADL scores were significantly lower than those of the control group (P < .05). The research group had an adverse event rate of 3.85%, significantly lower than the control group's rate of 19.61% (P < .05). The study group experienced improvements in emergency response and hospital procedure times, higher SF-36 and ADL scores, and lower rates of adverse events, suggesting significant potential for improving patient outcomes in cases of acute traumatic cervical spinal cord injury. This demonstrates the effectiveness of the emergency plans that have been implemented and may influence the approach to emergency medical care in similar situations in the future. Conclusions: Emergency plans and first aid procedures can effectively shorten the first aid time, promote rehabilitation, reduce adverse events, and improve the quality of daily life in patients with acute traumatic cervical spinal cord injury. Based on these findings, future practice or policy may need to be adjusted to further enhance patient care quality.
RESUMO
INTRODUCTION: Research on heterogeneous pathways in school-to-work transitions (SWT), particularly longitudinal research, has been limited, as have empirical studies examining effective interventions for facilitating multiple SWT pathways among non-engaged youth (NEY), who are generally at risk of being not in education, employment, or training (NEET). METHODS: To develop a typology of SWT pathways, we conducted sequence analysis with longitudinal data from a sample of 630 NEY aged 14-29 (M = 19.78; 63.65% males) in Hong Kong during a 22-month period beginning in September 2020. We also performed multinomial logistic regressions to assess the impact of career and life development (CLD) interventions on SWT outcomes. RESULTS: Our analysis yielded a fivefold typology of SWT pathways: the Employment/Entrepreneurship cluster (31.27%), the Vocational Education and Training cluster (13.49%), the Generic Education cluster (16.83%), the Serious Leisure Development cluster (15.24%), and the long-term NEET cluster (23.17%). NEY in the intervention group receiving CLD services, inspired by the expanded notion of work (ENOW) and youth development and intervention framework (YDIF), demonstrated significantly higher likelihoods of being in the Employment/Entrepreneurship (OR = 34.5, 95% CI [10.53, 105.08]), Generic Education (OR = 3.74, 95% CI [1.81, 7.74]), Vocational Education and Training (OR = 1.55, 95% CI [1.05, 6.26]), and Serious Leisure Development (OR = 1.77, 95% CI [1.04, 4.46]) clusters than the long-term NEET cluster. CONCLUSIONS: Our findings highlight the dynamic, heterogeneous nature of NEY's CLD journeys, including that CLD interventions based on ENOW-YDIF have had a beneficial effect on NEY's multiple SWT pathways.
RESUMO
In order to achieve efficient recognition of 3D images and reduce the complexity of network parameters, we proposed a novel 3D image recognition method combining deep neural networks with fractional-order Chebyshev moments. Firstly, the fractional-order Chebyshev moment (FrCM) unit, consisting of Chebyshev moments and the three-term recurrence relation method, is calculated separately using successive integrals. Next, moment invariants based on fractional order and Chebyshev moments are utilized to achieve invariants for image scaling, rotation, and translation. This design aims to enhance computational efficiency. Finally, the fused network embedding the FrCM unit (FrCMs-DNNs) extracts depth features to analyze the effectiveness from the aspects of parameter quantity, computing resources, and identification capability. Meanwhile, the Princeton Shape Benchmark dataset and medical images dataset are used for experimental validation. Compared with other deep neural networks, FrCMs-DNNs has the highest accuracy in image recognition and classification. We used two evaluation indices, mean square error (MSE) and peak signal-to-noise ratio (PSNR), to measure the reconstruction quality of FrCMs after 3D image reconstruction. The accuracy of the FrCMs-DNNs model in 3D object recognition was assessed through an ablation experiment, considering the four evaluation indices of accuracy, precision, recall rate, and F1-score.
RESUMO
Evaluating the impact of large-scale human activities on carbon storage through land use changes is of growing interest in terrestrial ecosystem assessments. The Huaihe River Basin, a vital Chinese grain production area, has undergone marked land use changes amid socio-economic acceleration. Evaluating the impacts of land use change on carbon storage and future carbon sequestration is imperative for regional ecosystem sustainability and Chinese food security, simultaneously, furnishing data support to regional land use planning and decision-making processes. Nonetheless, the mechanisms linking land use changes to carbon storage and the future carbon reservoir responses remain unclear. We utilized a multi-source dataset and representative scenarios, integrating PLUS, InVEST models, and Geodetector to assess land use change impacts on carbon storage in the Huaihe River Basin (2000-2030). The data indicates the following: (1) from 2000 to 2020, cultivated land decreased by 28,344.69 km2, construction land increased by 26,914.56 km2, and other land types changed little. (2) Land use change resulted a carbon loss of 1.17 × 108 t, primarily due to the expansion of construction land. (3) All four simulation scenarios exhibited diminished carbon storage relative to 2020, with the economic development scenario recording the lowest at 4.98 × 109 t and the ecological protection scenario the highest at 5.06 × 109 t. (4) Elevation predominantly drives carbon storage changes, with its interaction with NPP having the greatest impact. The factors synergistically enhance their explanatory power. The research provides a scientific basis for strategies aimed at augmenting regional carbon sequestration and refining low-carbon land management, safeguarding ecosystem stability.
Assuntos
Sequestro de Carbono , Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Rios , China , Rios/química , Monitoramento Ambiental/métodos , Conservação dos Recursos Naturais/métodos , Carbono/análise , Agricultura/métodosRESUMO
OBJECTIVES: The distal stent-induced new entry (distal SINE) is a life-threatening device-related complication after thoracic endovascular aortic repair (TEVAR). However, risk factors for distal SINE are not fully determined, and prediction models are lacking. This study aimed to establish a predictive model for distal SINE based on the preoperative dataset. METHODS: Two hundred and six patients with Stanford type B aortic dissection (TBAD) that experienced TEVAR were involved in this study. Among them, thirty patients developed distal SINE. Pre-TEVAR morphological parameters were measured based on the CT-reconstructed configurations. Virtual post-TEVAR morphological and mechanical parameters were computed via the virtual stenting algorithm (VSA). Two predictive models (PM-1 and PM-2) were developed and presented as nomograms to help risk evaluation of distal SINE. The performance of the proposed predictive models was evaluated and internal validation was conducted. RESULTS: Machine-selected variables for PM-1 included key pre-TEVAR parameters, and those for PM-2 included key virtual post-TEVAR parameters. Both models showed good calibration in both development and validation subsamples, while PM-2 outperformed PM-1. The discrimination of PM-2 was better than PM-1 in the development subsample, with an optimism-corrected area under the curve (AUC) of 0.95 and 0.77, respectively. Application of PM-2 in the validation subsample presented good discrimination with an AUC of 0.9727. The decision curve demonstrated that PM-2 was clinically useful. CONCLUSION: This study proposed a predictive model for distal SINE incorporating the CT-based VSA. This predictive model could efficiently predict the risk of distal SINE and thus might contribute to personalized intervention planning. CLINICAL RELEVANCE STATEMENT: This study established a predictive model to evaluate the risk of distal SINE based on the pre-stenting CT dataset and planned device information. With an accurate VSA tool, the predictive model could help to improve the safety of the endovascular repair procedure. KEY POINTS: ⢠Clinically useful prediction models for distal stent-induced new entry are still lacking, and the safety of the stent implantation is hard to guarantee. ⢠Our proposed predictive tool based on a virtual stenting algorithm supports different stenting planning rehearsals and real-time risk evaluation, guiding clinicians to optimize the presurgical plan when necessary. ⢠The established prediction model provides accurate risk evaluation for vessel damage, improving the safety of the intervention procedure.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Incidência , Stents/efeitos adversos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X/efeitos adversos , Estudos Retrospectivos , Prótese Vascular/efeitos adversosRESUMO
It is critical to discover a non-noble metal catalyst with high catalytic activity capable of replacing palladium in electrochemical reduction. In this work, a highly efficient single-atom Co-N/C catalyst was synthesized with metal-organic frameworks (MOFs) as a precursor for electrochemical dehalogenation. X-ray absorption spectroscopy (XAS) revealed that Co-N/C exhibited a Co-N4 configuration, which had more active sites and a faster charge-transfer rate and thus enabled the efficient removal of florfenicol (FLO) at a wide pH, achieving a rate constant 3.5 and 2.1 times that of N/C and commercial Pd/C, respectively. The defluorination and dechlorination efficiencies were 67.6 and 95.6%, respectively, with extremely low Co leaching (6 µg L-1), low energy consumption (22.7 kWh kg-1), and high turnover frequency (TOF) (0.0350 min-1), demonstrating excellent dehalogenation performance. Spiking experiments and density functional theory (DFT) verified that Co-N4 was the active site and had the lowest energy barrier for forming atomic hydrogen (H*) (ΔGH*). Capture experiments, electron paramagnetic resonance (EPR), electrochemical tests, and in situ Fourier transform infrared (FTIR) proved that H* and direct electron transfer were responsible for dehalogenation. Toxicity assessment indicated that FLO toxicity decreased significantly after dehalogenation. This work develops a non-noble metal catalyst with broad application prospects in electrocatalytic dehalogenation.
Assuntos
Cobalto , Paládio , Catálise , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
AIM: Lysine-Specific Demethylase 1 (LSD1) inhibitors have been developed and reached the clinic, but its effect in combination with cytotoxic chemotherapy is unclear. Here, we investigated the anti-tumor effect of LSD1 inhibitor GSK-LSD1 and its anti-tumor effect with the DNA damage drug doxorubicin (DOX) in gastric cancer (GC) cells. METHODS: Cells were treated with different concentrations of GSK-LSD1 to examine the anti-tumor effect versus cell viability by MTT and cell cycle arrest by flow cytometry. To explore whether LSD1 inhibitors can increase the anti-tumor effect of DNA damage drugs, cells were treated with DOX for 48 h after pretreatment with GSK-LSD1 for 48 h. Cell viability was detected by MTT and apoptosis-related proteins were examined by Western blot. Furthermore, anti-tumor efficacy of combination GSK-LSD1 with DOX was also measured in MGC-803 xenografts model in nude mice. RESULTS: The results showed that LSD1 was highly expressed in GC cell lines. Inhibition of LSD1 has a weak effect on cell viability and cell cycle. Moreover, LSD1 inhibitors pretreatment could significantly increase the anti-tumor effect of DOX. Further study found that inhibition of LSD1 can significantly enhance DOX-induced the apoptosis, accompanied by down-regulation of antiapoptotic Bcl-2 expression and up-regulation of proapoptotic Bax expression. We also confirmed that inhibition of LSD1 can sensitize the anti-tumor effect of DOX in vivo. CONCLUSION: Our findings suggest that the LSD1 inhibitor GSK-LSD1 has a weak inhibitory effect on the viability and cell cycle of GC cells, but can enhance the sensitivity of DOX.
Assuntos
Neoplasias Gástricas , Animais , Camundongos , Humanos , Neoplasias Gástricas/tratamento farmacológico , Lisina/farmacologia , Camundongos Nus , Doxorrubicina/farmacologia , Apoptose , Histona Desmetilases/metabolismo , Histona Desmetilases/farmacologia , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.
Assuntos
Diferenciação Celular , Nanopartículas , Plantas , Plantas/química , Bicamadas LipídicasRESUMO
BACKGROUND: White matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH. METHODS: Mice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1's function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot. RESULTS: Kv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitating microglia polarization into M2-like microglia, which exerts this beneficial effect. CONCLUSIONS: PAP-1 reduced pro-inflammatory cytokines accumulation and increased anti-inflammatory factors by facilitating M2-like microglia polarization via the NF-κB signaling pathway. Thus, the current study shows that the Kv1.3 blockade is capable of ameliorating WMI by facilitating M2-like phenotype microglia polarization after ICH.
Assuntos
Lesões Encefálicas , Canal de Potássio Kv1.3 , Substância Branca , Animais , Camundongos , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Citocinas/metabolismo , Hematoma , NF-kappa B/metabolismo , Fenótipo , Transdução de Sinais/fisiologia , Canal de Potássio Kv1.3/antagonistas & inibidoresRESUMO
Cross-chain interoperability can expand the ability of data interaction and value circulation between different blockchains, especially the value interaction and information sharing between industry consortium blockchains. However, some current public blockchain cross-chain technologies or data migration schemes between consortium blockchains need help to meet the consortium blockchain requirements for efficient two-way data interaction. The critical issue to solve in cross-chain technology is improving the efficiency of cross-chain exchange while ensuring the security of data transmission outside the consortium blockchain. In this article, we design a cross-chain architecture based on blockchain oracle technology. Then, we propose a bidirectional information cross-chain interaction approach (CCIO) based on the former architecture, we novelly improve three traditional blockchain oracle patterns, and we combine a mixture of symmetric and asymmetric keys to encrypt private information to ensure cross-chain data security. The experimental results demonstrate that the proposed CCIO approach can achieve efficient and secure two-way cross-chain data interactions and better meet the application needs of large-scale consortium blockchains.
RESUMO
The prediction of the spatiotemporal dynamic evolution of vegetation cover in the Huainan mining area and the quantitative evaluation of its driving factors are of great significance for protecting and restoring the environment in this area. This study uses the Landsat 5 TM and Landsat 8 OLI time-series data to estimate the vegetation cover and uses the transition matrix to analyze the spatiotemporal transfer of vegetation cover from 1989 to 2004, 2004 to 2021, and 2021 to 2030. In addition, a structural equation model (SEM) was established in this study to assess the driving factors of vegetation cover. The quantitative analysis and the cellular automata (CA)-Markov model were performed to predict the future vegetation cover in the Huainan mining area. The results are as follows: (1) In different periods, the vegetation cover types were mainly high cover types transferred to other vegetation cover types; (2) human activities are the key factors affecting the vegetation growth, while topographical factor is the most influential factor promoting the vegetation growth; (3) highly consistent CA-Markov and multi-criteria evaluation (MCE) predicted results of vegetation cover in 2030 compared to that in 2021. The proportion of bare soil and low cover types had increased significantly, mainly concentrated in the internal area of the mines. The prediction of the spatiotemporal evolution of vegetation cover in the Huainan mining area and the quantitative change in driving factors are of significant importance for the restoration of the environment in mining areas.
Assuntos
Monitoramento Ambiental , Solo , Humanos , Monitoramento Ambiental/métodos , Modelos Teóricos , Mineração , ChinaRESUMO
Trifluoromethyl-bearing 5-membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp3 )-H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF3 -α-alkyl carbene insertion into C(sp3 )-H bonds of a broad range of substrates to access 7 types of CF3 -bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C-H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to the synthesis of chiral CF3 analogues of bioactive molecules. Ruthenium α-CF3 -α-alkyl carbene complexes underwent stoichiometric reactions to give C-H insertion products, lending evidence for the involvement of metal α-CF3 -α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the πâ â â π attraction and intra-carbene C-Hâ â â F hydrogen bond elucidate the origin of selectivity of the benzylic C-H insertion reactions.
RESUMO
Double hydrosilylation of alkynes represents a straightforward method to synthesize bis(silane)s, yet it is challenging if α-substituted vinylsilanes act as the intermediates. Here, a cobalt-catalyzed regiodivergent double hydrosilylation of arylacetylenes is reported for the first time involving this challenge, accessing both vicinal and geminal bis(silane)s with exclusive regioselectivity. Various novel bis(silane)s containing Si-H bonds can be easily obtained. The gram-scale reactions could be performed smoothly. Preliminarily mechanistic studies demonstrated that the reactions were initiated by cobalt-catalyzed α-hydrosilylation of alkynes, followed by cobalt-catalyzed ß-hydrosilylation of the α-vinylsilanes to deliver vicinal bis(silane)s, or hydride-catalyzed α-hydrosilylation to give geminal ones. Notably, these bis(silane)s can be used for the synthesis of high-refractive-index polymers (nd up to 1.83), demonstrating great potential utility in optical materials.
RESUMO
A novel Gram-stain-negative, oxidase-positive, catalase-positive, non-motile, facultatively anaerobic, rod-shaped bacterium, designated WB101T, was isolated from a marine solar saltern located in Wendeng, PR China. Strain WB101T shared a high level of 16S rRNA gene sequence similarity with Rhodohalobacter barkolensis 15182T (93.5%), R. halophilus JZ3C29T (93.2%), and 'R. mucosus' 8A47T (92.1%). Strain WB101T formed a species-level branch within the genus Rhodohalobacter in both phylogenetic and phylogenomic topologies. The DNA G + C content was 42.0%. Strain WB101T was found to have menaquinone-7 as the only respiratory quinone. The dominant cellular fatty acid (≥ 10%) was iso-C15:0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. Characterisation based on phylogenetic, physiological, and biochemical properties indicated that strain WB101T represents a novel species of the genus Rhodohalobacter, and the name Rhodohalobacter sulfatireducens sp. nov. is proposed. The type strain is WB101T (= KCTC 92204T = MCCC 1H00518T).
Assuntos
Salinidade , Microbiologia da Água , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Modic changes (MCs) are radiographic manifestations of lumbar degenerative diseases. Various types of MCs are often associated with endplate osteosclerosis. Osteal tissue macrophages (Osteomacs) were reported to be crucial for bone homeostasis and bone repair, but whether osteomacs participate in the endplate osteosclerosis in MCs remained unclear. In this study, we tried to explore the critical role of osteomacs in regulating osteogenesis in MCs. We collected MCs from patient samples and developed a Propionibacterium acnes-induced rat MCs model, using microcomputed tomography and immunohistochemistry to detect the endplate bone mass and distribution of osteomacs. In patients' MCs, osteomacs increased in endplate subchondral bone, especially in Modic type II. Endplate in Modic type III presented a stable osteosclerosis. In rat MCs model, osteomacs increased in the bone hyperplasia area but not in the inflammation area of the endplate region, whereas the distribution of osteomacs was consistent with the area of osteosclerosis. To further explore the functions of osteomacs in vitro, we isolated osteomacs using MACS technology and found osteomacs secreted oncostatin M (OSM) and strongly promoted osteoblast differentiation rather than osteoclast through the mechanism of OSM-mediated tyrosine phosphorylation and interaction of STAT3 and Yes-associated protein 1 (YAP1). STAT3 phosphorylation inhibition or YAP1 knockdown attenuated OSM-mediated osteoblast differentiation. Finally, we confirmed that blockade of OSM in vivo using anti-OSM-neutralizing Ab prevented endplate osteosclerosis in rat MCs model. Taken together, these findings confirmed that endplate osteosclerosis in MCs was accompanied by an increased number of osteomacs, which regulated osteogenesis via the OSM-STAT3/YAP1 signaling axis.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Macrófagos/metabolismo , Oncostatina M/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Animais , Osso e Ossos/metabolismo , Diferenciação Celular/fisiologia , Feminino , Humanos , Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/fisiologia , Osteosclerose/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas de Sinalização YAPRESUMO
Osteoporosis deteriorates bone mass and biomechanical strength and is life-threatening to the elderly. In this study, we show that methyl 3,4-dihydroxybenzoate (MDHB), an antioxidant small-molecule compound extracted from natural plants, inhibits receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in vitro. Furthermore, MDHB attenuates the activation of mitogen-activated protein kinase (MAPK) and NF-κB pathways by reducing the levels of reactive oxygen species (ROS), which leads to downregulated protein expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). We also confirm that MDHB upregulates the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), an important transcription factor involved in ROS regulation, by inhibiting the ubiquitination-mediated proteasomal degradation of Nrf2. Next, animal experiments show that MDHB has an effective therapeutic effect on lipopolysaccharide (LPS)- and ovariectomized (OVX)-induced bone loss in mice. Our study demonstrates that MDHB can upregulate Nrf2 and suppress excessive osteoclast activity in mice to treat osteoporosis.
Assuntos
Osteólise , Osteoporose , Animais , Antioxidantes/farmacologia , Feminino , Humanos , Hidroxibenzoatos , Ligantes , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogênese , Osteólise/tratamento farmacológico , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Ovariectomia , Espécies Reativas de Oxigênio/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/farmacologiaRESUMO
LncRNAs are associated with tumorigenesis of liver cancer. LncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) was identified as an oncogenic lncRNA and involved in tumor growth and metastasis. The role of CRNDE in liver cancer was investigated. CRNDE was elevated in liver cancer cells. Knockdown of CRNDE decreased cell viability and inhibited proliferation of liver cancer. Moreover, knockdown of CRNDE reduced levels of extracellular acidification rate, glucose consumption, and lactate production to repress glycolysis of liver cancer. Silence of CRNDE enhanced the expression of miR-142 and reduced enhancer of zeste homolog 2 (EZH2) and hypoxia-inducible factor 1α (HIF-1α). Over-expression of HIF-1α attenuated CRNDE silence-induced decrease of glucose consumption and lactate production. Injection with sh-CRNDE virus reduced in vivo tumor growth of liver cancer through up-regulation of miR-142 and down-regulation of EZH2 and HIF-1α. In conclusion, knockdown of CRNDE suppressed cell proliferation, glycolysis, and tumor growth of liver cancer through EZH2/miR-142/HIF-1α.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Lactatos , Glicólise , Hipóxia/genética , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
LaF3 and NaLaF4 crystals were selectively precipitated in the SiO2-Al2O3-AlF3-Na2O-NaF-LaF3-ErF3 glass system by adjusting their compositions. The structural evolution at the atomic level driven by heat treatment and glass compositions was studied using the state-of-the-art magic-angle spinning nuclear magnetic resonance technique. From a comprehensive local structural study, we found that LaF3 and NaLaF4 crystals compete in crystallization in these glasses. The crystallization ability of NaLaF4 increases with the increase of the content of Na+ ions within the F-enriched phase, but for LaF3 crystals, it is reverse. These two crystals can be selectively precipitated in the glasses by adjusting the content of these Na+ ions within the F-enriched phase. When the crystallization ability of these two crystals becomes similar, none of them can be precipitated due to their mutual interference in crystallization. Intense single green upconversion luminescence occurs in glasses precipitating LaF3 or NaLaF4 crystals. The underlying relationship between compositions, structures, crystallization, and upconversion luminescence properties is unearthed based on the structural evolution, crystallization mechanism, and luminescence properties. This relationship will facilitate the compositional design of these kinds of glasses. It is inferred that it will be better to precipitate LaF3 rather than NaLaF4 crystals for achieving highly efficient upconversion luminescence.
RESUMO
PURPOSES: To explore the function of endplate epiphyseal ring in OLIF stand-alone surgery using a biomechanical model to reduce the complications of endplate collapse and cage subsidence. METHODS: In total, 24 human cadaveric lumbar function units (L1-2 and L3-4 segments) were randomly assigned to two groups. The first group was implanted with long fusion cages which engaged with both inner and outer regions of epiphyseal ring (Complete Span-Epiphyseal Ring, CSER). Those engaged with only the inner half of epiphyseal ring were the second group (Half Span-Epiphyseal Ring, HSER). Each group was divided into two subgroups [higher cage-height (HH) and normal cage-height (NH)]. Specimens were fixed in testing cups and compressed at approximately 2.5 mm/s, until the first sign of structural failure. Trabecular structural damage was analyzed by Micro-CT, as well as the difference of bone volume fraction (BV/TV), trabecular thickness (Tb.Th) et al. in different regions. RESULTS: Endplate collapse was mainly evident in the inner region of epiphyseal ring, where trabecular injury of sub-endplate bone was most concentrated. Endplate collapse incidence was significantly higher in HSER than CSER specimens (P = 0.017). A structural failure occurred at a lower force in HSER (1.41 ± 0.34 KN) compared with CSER (2.44 ± 0.59 KN). HH subgroups failed at a lower average force than NH subgroups. Micro-CT results showed a more extensive trabecular fracture in HSER specimens compared to CSER specimens, especially in HH subgroup. CONCLUSIONS: Endplate collapse is more likely to occur with short half span cages than complete span cages, and taller cages compared with normal height cages. During OLIF surgery, we should choose cages matching intervertebral disc space height and place the cages spanning over the whole epiphyseal ring to improve support strength.