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Signaling networks are critical for virtually all cell functions. Our current knowledge of cell signaling has been summarized in signaling pathway databases, which, while useful, are highly biased toward well-studied processes, and do not capture context specific network wiring or pathway cross-talk. Mass spectrometry-based phosphoproteomics data can provide a more unbiased view of active cell signaling processes in a given context, however, it suffers from low signal-to-noise ratio and poor reproducibility across experiments. While progress in methods to extract active signaling signatures from such data has been made, there are still limitations with respect to balancing bias and interpretability. Here we present phuEGO, which combines up-to-three-layer network propagation with ego network decomposition to provide small networks comprising active functional signaling modules. PhuEGO boosts the signal-to-noise ratio from global phosphoproteomics datasets, enriches the resulting networks for functional phosphosites and allows the improved comparison and integration across datasets. We applied phuEGO to five phosphoproteomics data sets from cell lines collected upon infection with SARS CoV2. PhuEGO was better able to identify common active functions across datasets and to point to a subnetwork enriched for known COVID-19 targets. Overall, phuEGO provides a flexible tool to the community for the improved functional interpretation of global phosphoproteomics datasets.
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Fosfoproteínas , Proteómica , Transducción de Señal , Proteómica/métodos , Humanos , Fosfoproteínas/metabolismo , SARS-CoV-2/metabolismo , COVID-19/metabolismo , COVID-19/virología , Programas Informáticos , Fosforilación , Espectrometría de Masas/métodosRESUMEN
A polarization beam-splitting multimode filter using pixelated waveguides has been presented and experimentally demonstrated in this paper. Finite difference time domain method and direct binary search optimization algorithm are employed to optimize pixelated waveguides to realize compact size, broad bandwidth, large extinction ratio, low insertion loss, and good polarization extinction ratio. Measurement results show that, in a wavelength range from 1520 to 1560â nm, for the fabricated device working at transverse-electric polarization, the measured insertion loss is less than 1.23â dB and extinction ratio is larger than 15.14â dB, while for transverse-magnetic polarization, the corresponding insertion loss lower than 0.74â dB and extinction ratio greater than 15.50â dB are realized. The measured polarization extinction ratio larger than 15.02â dB is achieved. The device's length is only 15.4â µm.
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A polarization-insensitive multimode silicon waveguide crossing is investigated and experimentally characterized in this Letter. By employing the particle swarm optimization (PSO) algorithm and finite difference time domain (FDTD) method, the lengths and widths of the waveguides in the proposed device are optimized for attaining wide bandwidth, small insertion loss (IL), low cross talk (CT), and compact size. Measurement results reveal that the footprint of the presented device is 11.92 µm × 11.92â µm. From 1520 to 1600â nm, the measured insertion loss and cross talk are smaller than 0.67â dB and -28.6â dB in the case of the TE0 mode, lower than 0.65â dB and -28.7â dB in the case of the TE1 mode, less than 0.48â dB and -36.3â dB in the case of the TM0 mode, and lower than 0.62â dB and -28â dB in the case of the TM1 mode.
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AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.
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Interferón alfa-2 , Interferón-alfa , Janus Quinasa 2 , Policitemia Vera , Polietilenglicoles , Proteínas Recombinantes , Humanos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Polietilenglicoles/efectos adversos , Polietilenglicoles/administración & dosificación , Interferón alfa-2/administración & dosificación , Interferón alfa-2/efectos adversos , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/genética , Masculino , Femenino , Persona de Mediana Edad , Janus Quinasa 2/genética , Resultado del Tratamiento , Relación Dosis-Respuesta a Droga , Anciano , AdultoRESUMEN
In this Letter, a polarization-insensitive high-order mode pass filter is presented, designed, and experimentally demonstrated. When TE0, TM0, TE1, and TM1 modes are injected into the input port, TM0 and TE0 modes are filtered, and TE1 and TM1 modes exit from the output port. To attain compactness, broad bandwidth, low insertion loss, excellent extinction ratio, and polarization-insensitive property, the finite difference time domain method and direct-binary-search or particle swarm optimization algorithm are employed for the optimization of structural parameters of the photonic crystal region and the coupling region in the tapered coupler. Measurement results reveal that, for the fabricated filter working at TE polarization, the extinction ratio and insertion loss are 20.42 and 0.32â dB at 1550â nm. In the case of TM polarization, the corresponding extinction ratio and insertion loss are 21.43 and 0.30â dB. Within a bandwidth from 1520 to 1590â nm, insertion loss smaller than 0.86â dB and extinction ratio larger than 16.80â dB are obtained for the fabricated filter working at TE polarization, while in the case of TM polarization, insertion loss lower than 0.79â dB and extinction ratio greater than 17.50â dB are realized.
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Algoritmos , FotonesRESUMEN
PURPOSE: Transjugular intrahepatic portosystemic shunt (TIPS) and splenectomy with periesophagogastric devascularization (SPD) are widely used to treat cirrhotic portal hypertension (PH) and prevent variceal rebleeding. However, direct comparisons between these two approaches are rare. This study was designed to compare the long-term outcomes of TIPS and SPD in patients with cirrhotic PH and variceal rebleeding. METHODS: The study included cirrhotic PH patients with a history of gastroesophageal variceal bleeding between 18 and 80 years of age who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2012 to January 2022. Patients were enrolled into two groups according to TIPS or SPD was performed. Baseline characteristics were matched using propensity score matching (PSM). RESULTS: A total of 230 patients underwent TIPS, while 184 underwent SPD. PSM was carried out to balance available covariates, resulting in a total of 83 patients in the TIPS group and 83 patients in the SPD group. Patients in SPD group had better liver function during 60 months follow-up. Five-year overall survival rates in SPD group and TIPS group were 72 and 27%, respectively, at 2 years were 88 and 86%, respectively. The 2- and 5-year freedom from variceal rebleeding rates were 95 and 80% in SPD group and 80 and 54% in TIPS group. CONCLUSIONS: SPD is clearly superior to TIPS in terms of OS and freedom from variceal rebleeding in patients with cirrhotic PH. In addition, SPD improved liver function in patients with cirrhotic PH.
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Várices Esofágicas y Gástricas , Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Derivación Portosistémica Intrahepática Transyugular/métodos , Esplenectomía , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Hipertensión Portal/complicaciones , Hipertensión Portal/cirugía , Enfermedad CrónicaRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of initially unresectable hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and to preliminarily explore the mechanism of rapid growth of the future liver remnant (FLR). METHODS: Twenty-four patients with HBV-associated HCC who underwent ALPPS in our hospital from August 2014 to January 2021 were retrospectively studied. Propensity score matching was used to compare oncologic outcomes of patients treated with ALPPS and transarterial chemoembolization (TACE). The expression of YAP and JNK in liver tissue after two stages of ALPPS were detected. RESULTS: The median standard liver volume (SLV) was 1471.4 ml. Before second stage of ALPPS, the median FLR increased by 74.4%, and the median FLR/SLV increased from 26.1 to 41.6%. Twenty-two patients (91.7%) received staged hepatectomy after a median interval of 15 (9-24) d. The total incidence of postoperative complications in ALPPS group was 54.5%, and of Clavien-Dindo ≥ IIIb postoperative complications (requiring surgical, endoscopic or radiological intervention under general anesthesia) was 9.1%. There was no significant difference in total complications between ALPPS group and TACE group, but there were lower rate of above grade III complications in the TACE group than that in the ALPPS group. The incidence of complications was lower in laparoscopic-ALPPS than that in open surgery. In ALPPS group, the 1-year, 2-year and 5-year overall survival rate were respectively 71.4%, 33.3% and 4.8%. Interval time was an independent risk factor associated with overall survival rate. There was no significant difference in overall survival rate between ALPPS group and TACE group. For advanced HCC (BCLC stage B and C), ALPPS group was not superior to TACE group in overall survival rate. The expression of YAP and p-JNK in the residual liver tissue after second stage procedure was higher than that after first stage procedure, and the co-expression of YAP and p-JNK was observed in the residual liver tissue. CONCLUSION: ALPPS is a safe and effective treatment for initially unresectable HBV-associated HCC. Laparoscopic technique might improve the effect of ALPPS. YAP and JNK pathway might take a role in rapid FLR increase in ALPPS procedure.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Hepatectomía/métodos , Carcinoma Hepatocelular/cirugía , Vena Porta/cirugía , Estudios Retrospectivos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/complicaciones , Complicaciones Posoperatorias/etiologíaRESUMEN
Two-dimensional (2D) topological materials, including quantum spin/anomalous Hall insulators, have attracted intense research efforts owing to their promise for applications ranging from low-power electronics and high-performance thermoelectrics to fault-tolerant quantum computation. One key challenge is to fabricate topological materials with a large energy gap for room-temperature use. Stanene-the tin counterpart of graphene-is a promising material candidate distinguished by its tunable topological states and sizeable bandgap. Recent experiments have successfully fabricated stanene, but none of them have yet observed topological states. Here we demonstrate the growth of high-quality stanene on Cu(111) by low-temperature molecular beam epitaxy. Importantly, we discovered an unusually ultraflat stanene showing an in-plane s-p band inversion together with a spin-orbit-coupling-induced topological gap (~0.3 eV) at the Γ point, which represents a foremost group-IV ultraflat graphene-like material displaying topological features in experiment. The finding of ultraflat stanene opens opportunities for exploring two-dimensional topological physics and device applications.
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BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion. METHODS: Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. RESULTS: Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). CONCLUSIONS: YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.
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Hepatopatías , Daño por Reperfusión , Humanos , Ratones , Animales , Hígado/metabolismo , Hepatopatías/etiología , Hepatocitos/patología , Daño por Reperfusión/metabolismo , Autofagia , Isquemia/metabolismoRESUMEN
Background: Acute rejection (AR) after liver transplantation (LT) remains an important factor affecting the prognosis of patients. CD8+ T cells are considered to be important regulatory T lymphocytes involved in AR after LT. Our previous study confirmed that autophagy mediated AR by promoting activation and proliferation of CD8+ T cells. However, the underlying mechanisms regulating autophagy in CD8+ T cells during AR remain unclear. Methods: Human liver biopsy specimens of AR after orthotopic LT were collected to assess the relationship between JNK and CD8+ T cells autophagy. The effect of JNK inhibition on CD8+ T cells autophagy and its role in AR were further examined in rats. Besides, the underlying mechanisms how JNK regulated the autophagy of CD8+ T cells were further explored. Results: The expression of JNK is positive correlated with the autophagy level of CD8+ T cells in AR patients. And similar findings were obtained in rats after LT. Further, JNK inhibitor remarkably inhibited the autophagy of CD8+ T cells in rat LT recipients. In addition, administration of JNK inhibitor significantly attenuated AR injury by promoting the apoptosis and downregulating the function of CD8+ T cells. Mechanistically, JNK may activate the autophagy of CD8+ T cells through upregulating BECN1 by inhibiting the formation of Bcl-2/BECN1 complex. Conclusion: JNK signaling promoted CD8+ T cells autophagy to mediate AR after LT, providing a theoretical basis for finding new drug targets for the prevention and treatment of AR after LT.
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Trasplante de Hígado , Ratas , Humanos , Animales , Trasplante de Hígado/efectos adversos , Linfocitos T CD8-positivos , Sistema de Señalización de MAP Quinasas , Apoptosis , AutofagiaRESUMEN
Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p < 0.001; AFP: 4.90 vs. 3.00 ng/ml, p < 0.001) and there is a significant correlation between PIVKA-II and AFP (R = 0.901, p < 0.001). PIVKA-II showed better accuracy than AFP in the diagnosis of overall recurrent HCC (AUC: 0.883 vs. 0.672; p < 0.0001), but also in patients with negative PIVKA-II before curative resection (AUC: 0.878 vs. 0.680, p = 0.001). Clinician should pay more attention to serum PIVKA-II values when following patients after curative HCC resection to detect early recurrence.Clinical trial registration: ChiCTR2300070874.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Precursores de Proteínas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , alfa-Fetoproteínas/metabolismo , Biomarcadores , Protrombina , Biomarcadores de TumorRESUMEN
Ships are important sources of carbon dioxide (CO2) emissions in Guangdong Province. The study of historical evolutions, drivers, and projected pathways of CO2 emissions can provide scientific support for the development of carbon peaking and carbon neutral strategies in Guangdong Province. The emission factor method, log-average index (LMDI) method, and scenario analysis method were adopted to estimate CO2 emissions, identify the drivers, and explore the mitigation potential from ships in Guangdong Province, separately. The results showed that:â CO2 emissions from ships in Guangdong Province increased from 3.319 4 million tons to 6.392 9 million tons from 2006 to 2020, with dry bulk carriers and container ships being the main ship types causing the increase in emissions. â¡ The positive drivers of CO2 emissions from ships in Guangdong Province from 2006 to 2020 were transport intensity (51%) and economic factors (49%), and the negative drivers were energy intensity (93%) and cargo class structure (7%). ⢠Carbon peaking would not be reached by 2030 if Guangdong Province maintains the current policy (baseline scenario) for ship transportation. ⣠Simultaneous optimization of the energy structure and promotion of the energy intensity (energy-efficient and low-carbon scenario) had a 56.51% potential to reduce CO2 emissions from ships compared to the baseline scenario. This can provide scientific support for Guangdong Province to develop a carbon peaking and carbon neutral control strategy for the shipping industry.
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Melanoma, the most perilous form of skin cancer, is known for its inherent resistance to chemotherapy. Even with advances in tumor immunotherapy, the survival of patients with advanced or recurrent melanomas remains poor. Over time, melanoma tumor cells may produce excessive angiogenic factors, necessitating the use of combinations of angiogenesis inhibitors, including broad-spectrum options, to combat melanoma. Among these inhibitors, Endostatin is one of the most broad-spectrum and least toxic angiogenesis inhibitors. We found Endostatin significantly increased the infiltration of CD8+ T cells and reduced the infiltration of M2 tumor-associated macrophages (TAMs) in the melanoma tumor microenvironment (TME). Interestingly, we also observed high expression levels of programmed death 1 (PD-1), an essential immune checkpoint molecule associated with tumor immune evasion, within the melanoma tumor microenvironment despite the use of Endostatin. To address this issue, we investigated the effects of a plasmid expressing Endostatin and PD-1 siRNA, wherein Endostatin was overexpressed while RNA interference (RNAi) targeted PD-1. These therapeutic agents were delivered using attenuated Salmonella in melanoma-bearing mice. Our results demonstrate that pEndostatin-siRNA-PD-1 therapy exhibits optimal therapeutic efficacy against melanoma. We found that pEndostatin-siRNA-PD-1 therapy promotes the infiltration of CD8+ T cells and the expression of granzyme B in melanoma tumors. Importantly, combined inhibition of angiogenesis and PD-1 significantly suppresses melanoma tumor progression compared with the inhibition of angiogenesis or PD-1 alone. Based on these findings, our study suggests that combining PD-1 inhibition with angiogenesis inhibitors holds promise as a clinical strategy for the treatment of melanoma.
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Melanoma , Neoplasias Cutáneas , Humanos , Ratones , Animales , Endostatinas/genética , Endostatinas/uso terapéutico , Endostatinas/metabolismo , Receptor de Muerte Celular Programada 1/genética , Factor A de Crecimiento Endotelial Vascular/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Linfocitos T CD8-positivos/metabolismo , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Plásmidos , Salmonella/genética , Microambiente TumoralRESUMEN
Many cell biological and biochemical mechanisms controlling the fundamental process of eukaryotic cell division have been identified; however, the temporal dynamics of biosynthetic processes during the cell division cycle are still elusive. Here, we show that key biosynthetic processes are temporally segregated along the cell cycle. Using budding yeast as a model and single-cell methods to dynamically measure metabolic activity, we observe two peaks in protein synthesis, in the G1 and S/G2/M phase, whereas lipid and polysaccharide synthesis peaks only once, during the S/G2/M phase. Integrating the inferred biosynthetic rates into a thermodynamic-stoichiometric metabolic model, we find that this temporal segregation in biosynthetic processes causes flux changes in primary metabolism, with an acceleration of glucose-uptake flux in G1 and phase-shifted oscillations of oxygen and carbon dioxide exchanges. Through experimental validation of the model predictions, we demonstrate that primary metabolism oscillates with cell-cycle periodicity to satisfy the changing demands of biosynthetic processes exhibiting unexpected dynamics during the cell cycle.
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Oxígeno , Saccharomycetales , Ciclo Celular , División Celular , Transporte BiológicoRESUMEN
BACKGROUND: Melanoma, a highly malignant skin cancer, is a hot topic in oncology treatment research. Nowadays, tumor immunotherapy, especially immunotherapy combined with other therapies, has attracted more and more attention. Indoleamine 2,3-dioxygenase 2 (IDO2), a ratelimiting enzyme of the tryptophan metabolism pathway in the urine of dogs with immunosuppression, is highly expressed in melanoma tissue. Additionally, IDO2 significantly inhibits the anti-tumor immunity of the body and has become a novel target of melanoma treatment. Nifuroxazide, as an intestinal antibacterial agent, was found to be able to inhibit Stat3 expression and exert an anti-tumor effect. Therefore, the present study aimed to examine the therapeutic effect of a self-designed IDO2-small interfering RNA (siRNA) delivered by attenuated Salmonella combined with nifuroxazide on melanoma- bearing mice, as well as determine its underlying mechanism. METHODS: The effect of nifuroxazide on melanoma was detected by flow cytometry, CCK-8 and colony- forming ability assays, respectively, in vitro. The plasmid of siRNA-IDO2 was constructed, and the mice-bearing melanoma model was established. After the treatment, the tumor growth and survival rate were monitored, and the morphological changes of tumor tissue were detected by HE staining. The expression of related proteins was detected by Western blotting, and the expression of CD4 and CD8 positive T cells in tumor tissue was detected by IHC and IF, and the proportion of CD4 and CD8 positive T cells in spleen was detected by flow cytometry. RESULTS: The results demonstrated that the combination therapy effectively inhibited the phosphorylation of Stat3 and the expression level of IDO2 in melanoma cells, which effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice. The mechanistic study revealed that, compared with control groups and monotherapy groups, the combination treatment group reduced the atypia of tumor cells, increased the apoptotic rate, enhanced the infiltration of T lymphocytes in tumor tissue and increased the CD4+ and CD8+ T lymphocytes in the spleen, suggesting that the mechanism may be associated with the inhibition of tumor cell proliferation, the increase of apoptosis and the enhancement of the cellular immunity. CONCLUSION: In conclusion, IDO2-siRNA combined with nifuroxazide therapy could serve a significant role in the treatment of melanoma-bearing mice, enhance the tumor immunity and provide an experimental basis for identifying a novel combination method for the treatment of melanoma clinically.
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Melanoma , Nitrofuranos , Animales , Ratones , Perros , ARN Interferente Pequeño/genética , Melanoma/tratamiento farmacológico , Nitrofuranos/farmacología , Nitrofuranos/uso terapéutico , Hidroxibenzoatos/farmacología , Hidroxibenzoatos/uso terapéutico , Línea Celular TumoralRESUMEN
Laparoscopic cholecystectomy and percutaneous transhepatic gallbladder drainage (PTGBD) are common treatments for patients with acute cholecystitis. However, the safety and efficacy of emergency laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC) after PTGBD in patients with acute cholecystitis remain unclear. The PubMed, EMBASE, and Cochrane Library databases were searched through October 2019. The quality of the included nonrandomized studies was assessed using the Methodological Index for Nonrandomized Studies (MINORS). The meta-analysis was performed using STATA version 14.2. A random-effects model was used to calculate the outcomes. A total of fifteen studies involving 1780 patients with acute cholecystitis were included in the meta-analysis. DLC after PTGBD was associated with a shorter operative time (SMD - 0.51; 95% CI - 0.89 to - 0.13; P = 0.008), a lower conversion rate (RR 0.43; 95% CI 0.26 to 0.69; P = 0.001), less intraoperative blood loss (SMD - 0.59; 95% CI - 0.96 to - 0.22; P = 0.002) and longer time of total hospital stay compared to ELC (SMD 0.91; 95% CI 0.57-1.24; P < 0.001). There was no difference in the postoperative complications (RR 0.68; 95% CI 0.48-0.97; P = 0.035), biliary leakage (RR 0.65; 95% CI 0.34-1.22; P = 0.175) or mortality (RR 1.04; 95% CI 0.39-2.80; P = 0.933). Compared to ELC, DLC after PTGBD had the advantages of a shorter operative time, a lower conversion rate and less intraoperative blood loss.
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Colecistectomía Laparoscópica , Colecistitis Aguda , Colecistectomía , Colecistitis Aguda/cirugía , Drenaje , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous hepatobiliary tumor with poor prognosis, and it lacks reliable prognostic biomarkers and effective therapeutic targets. Long non-coding RNAs (lncRNAs) have been documented to be involved in the progression of various cancers. However, the role of lncRNAs in ICC remains largely unknown. In the present work, we used bioinformatics analysis to identify the differentially expressed lncRNAs in human ICC tissues, among which lncRNA-PAICC was found to be an independent prognostic marker in ICC. Moreover, lncRNA-PAICC promoted the proliferation and invasion of ICC cells. Mechanistically, lncRNA-PAICC acted as a competitive endogenous RNA (ceRNA) that directly sponged the tumor suppressive microRNAs miR-141-3p and miR-27a-3p. The competitive binding property was essential for lncRNA-PAICC to promote tumor growth and metastasis through activating the Hippo pathway. In summary, our results highlighted the important role of the lncRNA-PAICC-miR-141-3p/27a-3p-Yap1 axis in ICC, which offers a novel perspective on the molecular pathogenesis and may serve as a potential target for antimetastatic molecular therapies of ICC.
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Recent evidence suggests that the eukaryotic metabolism is an autonomous oscillator. Together with oscillating elements of the cyclin/CDK machinery, this oscillator might form a coupled oscillator system, from which cell-cycle control emerges. The topology of interactions between the metabolic oscillator and the elements of the cyclin/CDK machinery, however, remains unknown. Using single-cell metabolic and cell-cycle dynamics in yeast, and solving an inverse problem with a system of Kuramoto oscillators, we inferred how the metabolic oscillator interacts with the cyclin/CDK machinery. The identified and experimentally validated interaction topology shows that the early and late cell cycle are independently driven by metabolism. While in this topology, the S phase is coordinated by START. We obtained no support for a strong interaction between early and late cell cycle. The identified high-level interaction topology will guide future efforts to discover the molecular links between metabolism and the cell cycle.
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Relojes Biológicos/fisiología , Ciclo Celular/fisiología , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Metabolómica/métodos , Saccharomyces cerevisiae/fisiología , Análisis de la Célula Individual/métodos , Modelos Biológicos , Unión Proteica , Transducción de SeñalRESUMEN
Black phosphorus is a promising candidate for future nanoelectronics with a moderate electronic band gap and a high carrier mobility. Introducing the magnetism into black phosphorus will widely expand its application scope and may present a bright prospect in spintronic nanodevices. Here, we report our first-principles calculations of spin-polarized electronic structure of monolayer black phosphorus (phosphorene) adsorbed on a magnetic europium oxide (EuO) substrate. Effective spin injection into the phosphorene is realized by means of interaction with the nearby EuO(111) surface, i.e., proximity effect, which results in spin-polarized electrons in the 3p orbitals of phosphorene, with the spin polarization at Fermi level beyond 30%, together with an exchange-splitting energy of â¼0.184 eV for conduction-band minimum of the adsorbed phosphorene corresponding to an energy region where only one spin channel is conductive. The energy region of these exchange-splitting and spin-polarized band gaps of the adsorbed phosphorene can be effectively modulated by in-plane strain. Intrinsically high and anisotropic carrier mobilities at the conduction-band minimum of the phosphorene also become spin-polarized mainly due to spin polarization of deformation potentials and are not depressed significantly after the adsorption. These extraordinary properties would endow black phosphorus with great potentials in the future spintronic nanodevices.