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Objective: Tibial plateau fractures are common intra-articular fractures that pose classification and treatment challenges for orthopedic surgeons. Objective: This study examines the value of 3D printing for classifying and planning surgery for complex tibial plateau fractures. Methods: We reviewed 54 complex tibial plateau fractures treated at our hospital from January 2017 to January 2019. Patients underwent preoperative spiral CT scans, with DICOM data processed using Mimics software. 3D printing technology created accurate 1:1 scale models of the fractures. These models helped subdivide the fractures into seven types based on the tibial plateau's geometric planes. Surgical approaches and simulated operations, including fracture reduction and plate placement, were planned using these models. Results: The 3D models accurately depicted the direction and extent of fracture displacement and plateau collapse. They facilitated the preoperative planning, allowing for precise reconstruction strategies and matching intraoperative details with the pre-printed models. Post-surgery, the anatomical structure of the tibial plateau was significantly improved in all 54 cases. Conclusion: 3D printing effectively aids in the classification and preoperative planning of complex tibial plateau fractures, enhancing surgical outcomes and anatomical restoration. Level of Evidence IV, Prospective Study.
Objetivo: As fraturas do planalto tibial são fraturas intra-articulares comuns de classificação e tratamento desafiadores aos cirurgiões ortopédicos. Objetivo: Este estudo investiga o uso de impressão 3D para classificar e planejar a cirurgia de fraturas complexas do planalto tibial. Métodos: 54 fraturas complexas do planalto tibial tratadas em nosso hospital de janeiro de 2017 a janeiro de 2019 foram revisadas. Os pacientes foram submetidos a tomografias computadorizadas em espiral pré-operatórias, com dados DICOM processados usando o software Mimics. A tecnologia de impressão 3D gerou modelos precisos em escala 1:1 das fraturas. Estes modelos ajudaram a subdividir as fraturas em sete tipos com base nos planos geométricos do planalto tibial. As abordagens cirúrgicas e as operações simuladas, incluindo a redução da fratura e a colocação de placa, foram planejadas utilizando estes modelos. Resultados: Os modelos 3D representaram com precisão a direção e a extensão da deslocação da fratura e do colapso do planalto. Os modelos facilitaram o planejamento pré-operatório, viabilizando estratégias de reconstrução precisas e a correspondência dos detalhes intraoperatórios com os modelos pré-impressos. Após a cirurgia, a estrutura anatômica do planalto tibial melhorou significativamente em todos os 54 casos. Conclusão: A impressão 3D ajuda na classificação e no planejamento pré-operatório de fraturas complexas do planalto tibial, melhorando os resultados cirúrgicos e a restauração anatômica. Nível de Evidência IV, Estudo Prospectivo.
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Hepatocellular carcinoma (HCC) is the major cause of cancer-associated mortality worldwide. Despite great advances have been made on the treatment of HCC, the survival rate of patients remains poor. Spindle apparatus coiled-coil protein 1 (SPDL1) is involved in the development of various cancers in humans. However, the role of SPDL1 in HCC remains unclear. In this study, we found high expression of SPDL1 in HCC tissues as compared to normal samples. In vitro, silencing of SPDL1 induced HCC cell apoptosis, and suppressed HCC cell propagation and migration. In vivo, knockdown of SPDL1 inhibited the tumor growth of HCC cells. These findings indicated the tumor-promoting role of SPDL1 in HCC. Mechanistically, we identified farnesyltransferase-beta (FNTB) as the downstream target protein of SPDL1 based on immunoprecipitation and mass spectrometry, which were confirmed by western blotting. Rescue assay determined that FNTB played a tumor promoting role in SPDL1-trigger HCC cell growth. Overexpression of FNTB recovered HCC cell viability and migration in SPDL1 knockdown cells. We also found that silencing of SPDL1 increased the sensitivity of Huh7 cells to sorafenib and lenvatinib, suggesting that SPDL1 is a new therapeutic target in HCC. Collectivity, the present study identified a new axis SPDL1/FNTB involved in the progression of HCC. Hence, SPDL1/FNTB is a potential target for the treatment of HCC.
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Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing â¼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated ß-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.
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Altitud , Haplotipos , Animales , Ovinos/genética , Haplotipos/genética , Adaptación Fisiológica/genética , Transcriptoma/genética , Polimorfismo de Nucleótido Simple/genética , Proteómica/métodos , Globinas beta/genética , Aclimatación/genética , Tibet , MultiómicaRESUMEN
The purpose of this study was to compare the predictive value of different lymph node staging systems and to develop an optimal prognostic nomogram for predicting distant metastasis in pancreatic ductal adenocarcinoma (PDAC). Our study involved 6364 patients selected from the Surveillance, Epidemiology, and End Results (SEER) database and 126 patients from China. Independent risk factors for distant metastasis were screened by univariate and multivariate logistic regression analyses, and a model-based comparison of different lymph node staging systems was conducted. Furthermore, we developed a nomogram for predicting distant metastasis using the optimal performance lymph node staging system. The lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), age, primary site, grade, tumor size, American Joint Committee on Cancer (AJCC) 7th Edition T stage, and radiotherapy recipient status were significant predictors of distant metastasis in PDAC patients. The model with the LODDS was a better fit than the model with the LNR. We developed a nomogram model based on LODDS and six clinical parameters. The area under the curve (AUC) and concordance index (C-index) of 0.753 indicated that this model satisfied the discrimination criteria. Kaplan-Meier curves indicate a significant difference in OS among patients with different metastasis risks. LODDS seems to have a superior ability to predict distant metastasis in PDAC patients compared with the AJCC 8th Edition N stage, PLN and LNR staging systems. Moreover, we developed a nomogram model for predicting distant metastasis. Clinicians can use the model to detect patients at high risk of distant metastasis and to make further clinical decisions.
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Carcinoma Ductal Pancreático , Metástasis Linfática , Estadificación de Neoplasias , Nomogramas , Neoplasias Pancreáticas , Programa de VERF , Humanos , Masculino , Carcinoma Ductal Pancreático/patología , Femenino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Anciano , Metástasis Linfática/patología , Ganglios Linfáticos/patología , Pronóstico , Adulto , China/epidemiología , Factores de Riesgo , Estimación de Kaplan-MeierRESUMEN
The widespread use of plastic products in daily life has raised concerns about the health hazards associated with nanoplastics (NPs). When exposed, NPs are likely to infiltrate the bloodstream, interact with plasma proteins, and trigger macrophage recognition and clearance. In this study, we focused on establishing a correlation between the unique protein coronal signatures of high-density (HDPE) and low-density (LDPE) polyethylene (PE) NPs with their ultimate impact on macrophage recognition and cytotoxicity. We observed that low-density and high-density lipoprotein receptors (LDLR and SR-B1), facilitated by apolipoproteins, played an essential role in PE-NP recognition. Consequently, PE-NPs activated the caspase-3/GSDME pathway and ultimately led to pyroptosis. Advanced imaging techniques, including label-free scattered light confocal imaging and cryo-soft X-ray transmission microscopy with 3D-tomographic reconstruction (nano-CT), provided powerful insights into visualizing NPs-cell interactions. These findings underscore the potential risks of NPs to macrophages and introduce analytical methods for studying the behavior of NPs in biological systems.
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Macrófagos , Polietileno , Corona de Proteínas , Macrófagos/metabolismo , Corona de Proteínas/metabolismo , Corona de Proteínas/química , Animales , Ratones , Nanopartículas/química , HumanosRESUMEN
Macrophages are plastic and play a key role in the maintenance of tissue homeostasis. In cancer progression, macrophages also take part in all processes, from initiation to progression, to final tumor metastasis. Although energy deprivation and autophagy are widely used for cancer therapy, most of these strategies do not target macrophages, resulting in undesired effects and unsatisfactory outcomes for cancer immunotherapy. Herein, we developed a lanthanum nickel oxide (LNO) nanozyme with phosphatase-like activity for ATP hydrolysis. Meanwhile, the autophagy of macrophages induced by LNO promotes the polarization of macrophages from M2-like macrophages (M2) to M1-like macrophages (M1) and reduces tumor-associated macrophages in tumor-bearing mice, exhibiting the capability of killing tumor-associated macrophages and antitumor effects in vivo. Furthermore, pre-coating the surface of LNO with a myeloid cell membrane significantly enhanced antitumor immunity. Our findings demonstrate that phosphatase-like nanozyme LNO can specifically induce macrophage autophagy, which improves therapeutic efficacy and offers valuable strategies for cancer immunotherapy.
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Microtubules are recognized as an appealing target for cancer treatment. We designed and synthesized of novel tubulin colchicine binding site inhibitors based on millepachine. Biological evaluation revealed compound 5h exhibited significant antiproliferative activity against osteosarcoma cell U2OS and MG-63. And compound 5h also remarkably inhibited tubulin polymerization. Further investigations indicated compound 5h not only arrest U2OS cells cycle at the G2/M phases, but also induced U2OS cells apoptosis in dose-dependent manners. Moreover, compound 5h was verified to inhibit cell migration and angiogenesis of HUVECs, induce mitochondrial membrane potential decreased and promoted the elevation of ROS levels. Furthermore, compound 5h exhibited remarkable effects on tumor growth in vivo, and the TGI rate was up to 84.94 % at a dose of 20 mg/kg without obvious toxicity. These results indicated that 5h may be an appealing tubulin inhibitor for treatment of osteosarcoma.
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Sensing is a critical function of artificial cells; however, this is challenging to realize using bottom-up approaches. Here, we present a protocol for building protocell membranes that sense cues important for redox biochemistry and signaling by combining synthetic phospholipids and natural lipids. We detail procedures for building giant unilamellar vesicles as protocell models that fluoresce in response to the biologically significant redox agents peroxynitrite, hydrogen peroxide, and hydrogen sulfide. For complete details on the use and execution of this protocol, please refer to (i) Gutierrez and Aggarwal et al.1 as well as (ii) Erguven and Wang et al.2.
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The burgeoning need for extensive data processing has sparked enthusiasm for the development of a novel optical logic gate platform. In this study, junction field-effect phototransistors based on molybdenum disulfide/Germanium (MoS2/Ge) heterojunctions are constructed as optical logic units. This device demonstrates a positive photoresponse that is attributed to the photoconductivity effect occurring upon irradiation with visible (Vis) light. Under the illumination of near-infrared (NIR) optics with wavelengths within the communication band, the device shows a negative photoresponse, which is associated with the interlayer Coulomb interactions. The current state of the device can be effectively modulated as different logical states by precisely tuning the wavelength and power density of the optical. Within a 3 × 3 MoS2/Ge phototransistor array, five essentially all-optical logic gates ("AND," "OR," "NAND," "NOT," and "NOR") can be achieved in every signal unit. Furthermore, three complex all-optical logical operations are demonstrated by integrating two MoS2/Ge phototransistors in series. Compared to electronic designs, these all-optical logic devices offer a significant reduction in transistor number, with savings of 50-94% when implementing the above-mentioned functions. These results present opportunities for the development of photonic chips with low power consumption, high fidelity, and large volumes.
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Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 and promoting the degradation of the PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy is a selective form of autophagy for removal of damaged and superfluous mitochondria via the autophagy-lysosome pathway. Here, we report a surprising discovery that, while spautin-1 remains as an effective autophagy inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, spautin-1 facilitates the stabilization and activation of the full-length PINK1 at the outer mitochondrial membrane (OMM) via binding to components of the TOMM complex (TOMM70 and TOMM20), leading to the disruption of the mitochondrial import of PINK1 and prevention of PARL-mediated PINK1 cleavage. Moreover, spautin-1 induces neuronal mitophagy in Caenorhabditis elegans (C. elegans) in a PINK-1-PDR-1-dependent manner. Functionally, spautin-1 is capable of improving associative learning capability in an Alzheimer disease (AD) C. elegans model. In summary, we report a novel function of spautin-1 in promoting mitophagy via the PINK1-PRKN pathway. As deficiency of mitophagy is closely implicated in the pathogenesis of neurodegenerative disorders, the pro-mitophagy function of spautin-1 might suggest its therapeutic potential in neurodegenerative disorders such as AD.Abbreviations: AD, Alzheimer disease; ATG, autophagy related; BafA1, bafilomycin A1; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; COX4/COX IV, cytochrome c oxidase subunit 4; EBSS, Earle's balanced salt; ECAR, extracellular acidification rate; GFP, green fluorescent protein; IA, isoamyl alcohol; IMM, inner mitochondrial membrane; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MMP, mitochondrial membrane potential; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; O/A, oligomycin-antimycin; OCR, oxygen consumption rate; OMM, outer mitochondrial membrane; OPTN, optineurin; PARL, presenilin associated rhomboid like; PINK1, PTEN induced kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; p-Ser65-Ub, phosphorylation of Ub at Ser65; TIMM23, translocase of inner mitochondrial membrane 23; TOMM, translocase of outer mitochondrial membrane; USP10, ubiquitin specific peptidase 10; USP13, ubiquitin specific peptidase 13; VAL, valinomycin; YFP, yellow fluorescent protein.
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Background: Diffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics. Methods: Datasets from the Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factors that influenced the prognosis. Drug-sensitive prediction was performed to evaluate the value of the model. Results: VCAN, CD3G, and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68 + macrophages and CD8 + T cells was associated with better prognosis. In addition, CD3G+T cells ratio was significantly correlated with CD68 + macrophages, CD4 + T cells, and CD8 +T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB, and CD3G work well in predicting the prognosis and drug sensitivity. Conclusions: VCAN, CD3G, and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients. Funding: This work is supported by the Shenzhen High-level Hospital Construction Fund and CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-062).
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Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/inmunología , Pronóstico , Femenino , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Although the photoresponse cut-off wavelength of Si is about 1100 nm due to the Si bandgap energy, the internal photoemission effect (IPE) of the Au/Si junction in Schottky detector can extend the absorption wavelength, which makes it a promising candidate for the Si-based infrared detector. However, due to low light absorption, low photon-electron interaction, and poor electron injection efficiency, the near-infrared light detection efficiency of the Schottky detector is still insufficient. The synergistic effect of Si nano/microstructures with a strong light trapping effect and nanoscale Au films with surface plasmon enhanced absorption may provide an effective solution for improving the detection efficiency. In this paper, a large-area periodic Si microcone array covered by an Au film has successfully been fabricated by one-time dry etching based on the mature polystyrene microspheres lithography technique and vacuum thermal deposition, and its properties for hot electron-based near infrared photodetection are investigated. Optical measurements show that the 20 nm-thick Au covered Si microcone array exhibits a low reflectance and a strong absorption (about 85%) in wide wavelength range (900-2500 nm), and the detection responsivity can reach a value as high as 17.1 and 7.0 mA W-1at 1200 and 1310 nm under the front illumination, and 35.9 mA W-1at 1310 nm under the back illumination respectively. Three-dimensional finite difference time domain (3D-FDTD) simulation results show that the enhanced local electric field in the Au layer distributes near the air/Au interface under the front illumination and close to the Au/Si interface under the back illumination. The back illumination favors the injection of photo-generated hot electrons in Au layer into Si, which can explain the higher responsivity under the back illumination. Our research is expected to promote the practical application of Schottky photodetectors to Si-compatible near infrared photodetectors.
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Counterfeit Baijiu has been emerging because of the price variances of real-aged Chinese Baijiu. Accurate identification of different vintages is of great interest. In this study, the combination of gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy was applied for the comprehensive analysis of chemical constituents for Maotai-flavor Baijiu. Furthermore, a novel data fusion strategy combined with machine learning algorithms has been established. The results showed that the midlevel data fusion combined with the random forest algorithm were the best and successfully applied for classification of different Baijiu vintages. A total of 14 differential compounds (belonging to fatty acid ethyl esters, alcohols, organic acids, and aldehydes) were identified, and used for evaluation of commercial Maotai-flavor Baijiu. Our results indicated that both volatiles and nonvolatiles contributed to the vintage differences. This study demonstrated that GC-MS and 1H NMR spectra combined with a data fusion strategy are practical for the classification of different vintages of Maotai-flavor Baijiu.
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Cromatografía de Gases y Espectrometría de Masas , Cromatografía de Gases y Espectrometría de Masas/métodos , Aromatizantes/química , Espectroscopía de Protones por Resonancia Magnética/métodos , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/análisis , Vino/análisis , Vino/clasificación , Espectroscopía de Resonancia Magnética/métodosRESUMEN
Fractures of the contralateral hip may easily occur in elderly patients after an initial hip fracture. The aim of this study was to investigate the clinical characteristics and major predisposing risk factors of contralateral hip fracture after initial hip fracture in the elderly, to provide a clinical basis for preventing contralateral hip fracture. The data of 1586 patients who had sustained first or second hip fractures and had been surgically treated in our department were retrospectively analyzed. Potential predictive factors for contralateral hip fracture and descriptive statistics associated with surgery (such as blood loss, operation time, and length of hospital stay) were recorded. Of these patients, 133 (8.4%) suffered contralateral hip fracture. The rates of contralateral fracture after femoral neck and intertrochanteric fracture were 5.4% and 10.7% respectively (P < 0.01). Fifty-four cases of contralateral hip fracture occurred within one year, an incidence of 40.6%, while 95 cases (71.4%) and 105 cases (78.9%) occurred within two and three years, respectively, with a interval duration of 21.6 months. The risk factors for contralateral hip fracture were found to be age, type of first fracture, bone mineral density, the Singh index, and concomitant internal medical diseases, which were found to be significantly associated with an increased risk of contralateral hip fracture in multivariate logistic regression analysis (P < 0.05). In conclusion, the presence of concomitant internal diseases, type of first fracture, bone mineral density, the Singh index, and age were found to be significant predictors of the risk of contralateral hip fracture in elderly patients after a first hip fracture.
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Fracturas de Cadera , Humanos , Fracturas de Cadera/epidemiología , Fracturas de Cadera/cirugía , Fracturas de Cadera/etiología , Fracturas de Cadera/complicaciones , Masculino , Femenino , Factores de Riesgo , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Densidad Ósea , Incidencia , Tiempo de InternaciónRESUMEN
Regorafenib is a second-line standard treatment for hepatocellular carcinoma (HCC). However, the efficacy of regorafenib is often limited due to drug resistance, individual differences among patients, and irrational drug use. Radiotherapy (RT) is an important method of localized HCC treatment, and combining RT with other therapies may exert a synergetic antitumor effect. Platelet-derived growth factor receptor-like (PDGFRL) is a tumor suppressor in various solid tumors. However, the function of PDGFRL in HCC is still unknown. In this study, we explored whether regorafenib and RT exert a synergetic effect on the treatment of HCC. The antitumor effect and mechanisms of the combination of regorafenib and RT were verified in a xenograft mouse model in vivo and in HCC cells in vitro. The combination treatment significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. PDGFRL, a potential target of regorafenib, was increased after cumulative treatment in HCC cells, and PDGFRL suppressed HCC cell proliferation and promoted apoptosis by inhibiting STAT3 pathway activation. Furthermore, the cumulative antitumor effect was dependent on the upregulated expression of PDGFRL and inhibition of STAT3 signaling pathway activation in HCC cells. This study increased the understanding of the molecular mechanism underlying the effect of regorafenib plus RT on HCC and provided a theoretical basis for the clinical practice of HCC.
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Apoptosis , Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Compuestos de Fenilurea , Piridinas , Ensayos Antitumor por Modelo de Xenoinjerto , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/metabolismo , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Animales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/metabolismo , Humanos , Ratones , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Factor de Transcripción STAT3/metabolismo , Ratones Desnudos , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Masculino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases oxygen consumption of islets and enhances insulin secretion. However, the underlying mechanism for the protective role of MSCs in α-cell mitochondrial dysfunction remains unclear. Here, human umbilical cord MSCs (hucMSCs) were used to treat 2 kinds of T2DM mice and αTC1-6 cells to explore the role of hucMSCs in improving α-cell mitochondrial dysfunction and hyperglucagonemia. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function of α cells was assessed by the Seahorse Analyzer. To investigate the underlying mechanisms, Sirtuin 1 (SIRT1), Forkhead box O3a (FoxO3a), glucose transporter type1 (GLUT1), and glucokinase (GCK) were assessed by Western blotting analysis. In vivo, hucMSC infusion improved glucose and insulin tolerance, as well as hyperglycemia and hyperglucagonemia in T2DM mice. Meanwhile, hucMSC intervention rescued the islet structure and decreased α- to ß-cell ratio. Glucagon secretion from αTC1-6 cells was consistently inhibited by hucMSCs in vitro. Meanwhile, hucMSC treatment activated intracellular SIRT1/FoxO3a signaling, promoted glucose uptake and activation, alleviated mitochondrial dysfunction, and enhanced ATP production. However, transfection of SIRT1 small interfering RNA (siRNA) or the application of SIRT1 inhibitor EX-527 weakened the therapeutic effects of hucMSCs on mitochondrial function and glucagon secretion. Our observations indicate that hucMSCs mitigate mitochondrial dysfunction and glucagon hypersecretion of α cells in T2DM via SIRT1/FoxO3a signaling, which provides novel evidence demonstrating the potential for hucMSCs in treating T2DM.
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Diabetes Mellitus Tipo 2 , Proteína Forkhead Box O3 , Glucagón , Células Madre Mesenquimatosas , Mitocondrias , Transducción de Señal , Sirtuina 1 , Sirtuina 1/metabolismo , Animales , Células Madre Mesenquimatosas/metabolismo , Proteína Forkhead Box O3/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Mitocondrias/metabolismo , Ratones , Humanos , Glucagón/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Células Secretoras de Glucagón/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Ratones Endogámicos C57BLRESUMEN
In this paper, we demonstrate a comprehensive study of NF3-based selective etching processes for inner spacer formation and for channel release, enabling stacked horizontal gate-all-around Si nanosheet transistor architectures. A cyclic etching process consisting of an oxidation treatment step and an etching step is proposed and used for SiGe selective etching. The cyclic etching process exhibits a slower etching rate and higher etching selectivity compared to the direct etching process. The cycle etching process consisting of Recipe 1, which has a SiGe etching rate of 0.98 nm/cycle, is used for the cavity etch. The process achieved good interlayer uniformity of cavity depth (cavity depth ≤ 5 ± 0.3 nm), while also obtaining a near-ideal rectangular SiGe etch front shape (inner spacer shape = 0.84) and little Si loss (0.44 nm@ each side). The cycle etching process consisting of Recipe 4 with extremely high etching selectivity is used for channel release. The process realizes the channel release of nanosheets with a multi-width from 30 nm to 80 nm with little Si loss. In addition, a selective isotropic etching process using NF3/O2/Ar gas mixture is used to etch back the SiN film. The impact of the O2/NF3 ratio on the etching selectivity of SiN to Si and the surface roughness of SiN after etching is investigated. With the introduction of O2 into NF3/Ar discharge, the selectivity increases sharply, but when the ratio of O2/NF3 is up to 1.0, the selectivity tends to a constant value and the surface roughness of SiN increases rapidly. The optimal parameter is O2/NF3 = 0.5, resulting in a selectivity of 5.4 and a roughness of 0.19 nm.
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Activity-based detection of hydrogen sulfide in live cells can expand our understanding of its reactivity and complex physiological effects. We have discovered a highly efficient method for fluorescent probe activation, which is driven by H2S-triggered 1,6-elimination of an α-CF3-benzyl to release resorufin. In detecting intracellular H2S, 4-azido-(α-CF3)-benzyl resorufin offers significantly faster signal generation and improved sensitivity compared to 4-azidobenzyl resorufin. Computed free energy profiles for the 1,6-elimination process support the hypothesis that a benzylic CF3 group can reduce the activation energy barrier toward probe activation. This novel probe design allows for near-real-time detection of H2S in HeLa cells under stimulation conditions.
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Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a well-known mitotic protein, has been linked to carcinogenesis in several cancers. This study investigated the role of TPX2 in hepatocellular carcinoma (HCC) from various aspects using bioinformatic analyses. TPX2 expression and its prognostic value in pan-cancers were analyzed using SangerBox. TPX2 expression and its association with prognosis, immune infiltration, tumor mutations, and signaling pathways in HCC were analyzed using UALCAN, BoxKaplan-Meier Plotter, GEPIA, Human Protein Atlas, TIMER 2.0, and SangerBox. Genes co-expressed with TPX2 in HCC were analyzed using the HCCDB database, followed by functional enrichment using SangerBox. Clinical predictive models were established based on TPX2 and its co-expressed genes using the ACLBI database. TPX2 expression significantly increased in pan-cancers and was associated with survival in nearly half of the cancer types. High TPX2 expression has been linked to poor survival outcomes in patients with HCC. TPX2 expression was positively correlated with abundant infiltration of immune cells (including B cells, CD4 + /CD8 + T cells, macrophages, neutrophils, and dendritic cells), TP53 mutation, and carcinogenesis-related pathways, such as the PI3K/AKT/mTOR pathway, cellular response to hypoxia, and tumor proliferation signature. Nineteen genes were found to be co-expressed with TPX2 in HCC, and these genes showed close positive correlations and were mainly implicated in cell cycle-related functions. A prognostic model established using TPX2 and its expressed genes could stratify HCC patients into high- and low-risk groups, with a significantly shorter survival time in high-risk groups. The prognostic model performed well in predicting 1-, 3-, and 5-year survival of patients with HCC, with areas under the curve of 0.801, 0.725, and 0.711, respectively. TPX2 functions as an oncogene in HCC, and its high expression is detrimental to the survival of patients with HCC. Thus, TPX2 may be a prognostic biomarker and potential therapeutic target for HCC.