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Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.
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Lagartos , Melaninas , Animales , Melaninas/genética , Lagartos/genética , Pez Cebra , Regulación de la Temperatura Corporal/genética , Pigmentación de la Piel/genética , ColorRESUMEN
Gastric cancer results in great cancer mortality worldwide, and inducing ferroptosis dramatically improves the malignant phenotypes of gastric cancer. DNA polymerase epsilon subunit 2 (POLE2) plays indispensable roles in tumorigenesis; however, its involvement and molecular basis in ferroptosis and gastric cancer are not clear. Human gastric cancer cells were infected with lentiviral vectors to knock down or overexpress POLE2, and cell ferroptosis was detected. To further validate the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4), lentiviral vectors were used. POLE2 expression was elevated in human gastric cancer cells and tissues and closely correlated with clinicopathological features in gastric cancer patients. POLE2 knockdown was induced, while POLE2 overexpression inhibited ferroptosis of human gastric cancer cells, thereby modulating the malignant phenotypes of gastric cancer. Mechanistic studies revealed that POLE2 overexpression elevated NRF2 expression and activity and subsequently activated GPX4, which then prevented lipid peroxidation and ferroptosis in human gastric cancer cells. In contrast, either NRF2 or GPX4 silence significantly prevented POLE2 overexpression-mediated inductions of cell proliferation, migration, invasion and inhibition of ferroptosis. POLE2 overexpression inhibits ferroptosis in human gastric cancer cells through activating NRF2/GPX4 pathway, and inhibiting POLE2 may be a crucial strategy to treat gastric cancer.
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Ferroptosis , Neoplasias Gástricas , Humanos , Lentivirus , Factor 2 Relacionado con NF-E2 , Nucleotidiltransferasas , Subunidades de ProteínaRESUMEN
Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.
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A meta-analysis was conducted comprehensively to investigate the impact of evidence-based nursing (EBN) interventions on pressure injury (PI) in the intensive care unit (ICU) patients. Computer searches were performed, from databases inception to November 2023, in Wanfang, PubMed, China National Knowledge Infrastructure, Google Scholar, Embase, and Cochrane Library for randomized controlled trials (RCTs) on the application of EBN interventions in ICU patients. Two independent researchers conducted screenings of the literature, extracted data, and carried out quality evaluations. Stata 17.0 software was employed for data analysis. Overall, 25 RCTs, involving 2494 ICU patients, were included. It was found that compared to conventional care methods, the implementation of EBN interventions in ICU patients markedly decreased the occurrence of PI (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.17-0.30, p < 0.001), delayed the onset time of pressure ulcers (standardized mean difference [SMD]: -1.61, 95% CI: -2.00 to -1.22, p < 0.001), and also improved nursing satisfaction (OR: 1.18, 95% CI: 1.14-1.23, p < 0.001). Our findings suggest the implementation of EBN interventions in the care of PI in ICU patients is highly valuable, can reduce the occurrence of PI, can delay the time of appearance, and is associated with relatively higher nursing satisfaction, making it worthy of promotion.
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Enfermería Basada en la Evidencia , Unidades de Cuidados Intensivos , Úlcera por Presión , Úlcera por Presión/enfermería , Úlcera por Presión/prevención & control , Humanos , Enfermería Basada en la Evidencia/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Genomic prediction (GP) or genomic selection is a method to predict the accumulative effect of all quantitative trait loci (QTLs) in a population by estimating the realized genomic relationships between the individuals and by capturing the linkage disequilibrium between markers and QTLs. Thus, marker preselection is considered a promising method to capture Mendelian segregation effects. Using QTLs detected in a genome-wide association study (GWAS) may improve GP. Here, we performed GWAS and GP in a population with 904 clones from 32 full-sib families using a newly developed 50 k SNP Norway spruce array. Through GWAS we identified 41 SNPs associated with budburst stage (BB) and the largest effect association explained 5.1% of the phenotypic variation (PVE). For the other five traits such as growth and wood quality traits, only 2 - 13 associations were observed and the PVE of the strongest effects ranged from 1.2% to 2.0%. GP using approximately 100 preselected SNPs, based on the smallest p-values from GWAS showed the greatest predictive ability (PA) for the trait BB. For the other traits, a preselection of 2000-4000 SNPs, was found to offer the best model fit according to the Akaike information criterion being minimized. But PA-magnitudes from GP using such selections were still similar to that of GP using all markers. Analyses on both real-life and simulated data also showed that the inclusion of a large QTL SNP in the model as a fixed effect could improve PA and accuracy of GP provided that the PVE of the QTL was ≥ 2.5%.
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Picea , Sitios de Carácter Cuantitativo , Humanos , Estudio de Asociación del Genoma Completo/métodos , Desequilibrio de Ligamiento , Genómica/métodos , Fenotipo , Picea/genética , Noruega , Polimorfismo de Nucleótido Simple , GenotipoRESUMEN
The purging of deleterious alleles has been hypothesized to mitigate inbreeding depression, but its effectiveness in endangered species remains debatable. To understand how deleterious alleles are purged during population contractions, we analyzed genomes of the endangered Chinese crocodile lizard (Shinisaurus crocodilurus), which is the only surviving species of its family and currently isolated into small populations. Population genomic analyses revealed four genetically distinct conservation units and sharp declines in both effective population size and genetic diversity. By comparing the relative genetic load across populations and conducting genomic simulations, we discovered that seriously deleterious alleles were effectively purged during population contractions in this relict species, although inbreeding generally enhanced the genetic burden. However, despite with the initial purging, our simulations also predicted that seriously deleterious alleles will gradually accumulate under prolonged bottlenecking. Therefore, we emphasize the importance of maintaining a minimum population capacity and increasing the functional genetic diversity in conservation efforts to preserve populations of the crocodile lizard and other endangered species.
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Lagartos , Alelos , Animales , Especies en Peligro de Extinción , Variación Genética , Endogamia , Lagartos/genética , Densidad de PoblaciónRESUMEN
BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Hepáticas/patología , PronósticoRESUMEN
The study was performed to evaluate the effects of the reduced lactate production by sodium oxamate (SO) on growth performance, lactate and glucose and lipid metabolism, and glucose tolerance of Micropterus salmoides fed high-carbohydrate (CHO) diets. In in vitro study, primary hepatocytes were incubated for 48 h in a control medium (5.5 mM glucose), a high-glucose medium (25 mM glucose, HG), or a SO-containing high-glucose medium (25 mM glucose + 50 mM SO, HG-SO). Results indicated lactate and triglyceride (TG) levels, and lactate dehydrogenase a (LDH-a) expression in the HG-SO group were remarkably lower than those of the HG group. In in vivo study, M. salmoides (5.23 ± 0.03 g) were fed four diets containing a control diet (10% CHO, C) and three SO contents [0 (HC), 100 (HC-SO1), and 200 (HC-SO2) mg·kg-1, respectively] of high-CHO diets (20% CHO) for 11 wk. High-CHO diets significantly reduced weight gain rate (WGR), specific growth rate (SGR), p-AMPK-to-t-AMPK ratio, and expression of insulin receptor substrate 1 (IRS1), insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), fructose-1,6-biphosphatase (FBPase), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl transferase 1α (CPT1α) compared with the C group, whereas the opposite was true for plasma levels of glucose, TG, lactate, tissue glycogen, and lipid contents, and expression of LDH-a, monocarboxylate transporter 1 and 4 (MCT1 and MCT4), insulin, glucokinase (GK), pyruvate dehydrogenase E1 subunit (PDH), sterol-regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). The HC-SO2 diets remarkably increased WGR, SGR, p-AMPK-to-t-AMPK ratio, and expression of IRS1, IGF-I, IGF-IR, GK, PDHα, PDHß, FAS, acetyl-CoA carboxylase 1 (ACC1), PPARα, and CPT1α compared with the HC group. Besides, HC-SO2 diets also enhanced glucose tolerance of fish after a glucose loading. Overall, the reduced lactate production by SO benefits growth performance and glucose homeostasis of high-CHO-fed M. salmoides through the enhancement of glycolysis, lipogenesis, and fatty acid ß-oxidation coupled with the suppression of glycogenesis and gluconeogenesis.
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Lubina , Factor I del Crecimiento Similar a la Insulina , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lubina/metabolismo , Ácido Láctico/metabolismo , PPAR alfa , Proteínas Quinasas Activadas por AMP/metabolismo , Lactato Deshidrogenasa 5/metabolismo , Lactato Deshidrogenasa 5/farmacología , Dieta , Glucosa/metabolismo , Homeostasis , Hígado/metabolismoRESUMEN
Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.
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Carcinoma Hepatocelular , Carga Glucémica , Hepatitis C , Neoplasias Hepáticas , Humanos , Índice Glucémico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Glucemia , Factores de Riesgo , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Dieta , Carbohidratos de la Dieta/efectos adversosRESUMEN
BACKGROUND: Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. METHODS: We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74-3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47-3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55-2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36-2.49, P = 0.906). CONCLUSION: sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.
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Antígeno B7-H1 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Receptor de Muerte Celular Programada 1 , Apoptosis , Antígeno B7-H1/análisis , Biomarcadores de Tumor , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Pronóstico , Receptor de Muerte Celular Programada 1/análisisRESUMEN
Vast population movements induced by recurrent climatic cycles have shaped the genetic structure of plant species. During glacial periods species were confined to low-latitude refugia from which they recolonized higher latitudes as the climate improved. This multipronged recolonization led to many lineages that later met and formed large contact zones. We utilize genomic data from 5000 Picea abies trees to test for the presence of natural selection during recolonization and establishment of a contact zone in Scandinavia. Scandinavian P. abies is today made up of a southern genetic cluster originating from the Baltics, and a northern one originating from Northern Russia. The contact zone delineating them closely matches the limit between two major climatic regions. We show that natural selection contributed to its establishment and maintenance. First, an isolation-with-migration model with genome-wide linked selection fits the data better than a purely neutral one. Second, many loci show signatures of selection or are associated with environmental variables. These loci, regrouped in clusters on chromosomes, are often related to phenology. Altogether, our results illustrate how climatic cycles, recolonization and selection can establish strong local adaptation along contact zones and affect the genetic architecture of adaptive traits.
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Abies , Selección Genética , Árboles , Fenotipo , Demografía , Variación GenéticaRESUMEN
Thickness reduction or loss of the calcareous eggshell is one of major phenotypic changes in the transition from oviparity to viviparity. Whether the reduction of eggshells in viviparous squamates is associated with specific gene losses is unknown. Taking advantage of a newly generated high-quality genome of the viviparous Chinese crocodile lizard (Shinisaurus crocodilurus), we found that ovocleidin-17 gene (OC-17), which encodes an eggshell matrix protein that is essential for calcium deposition in eggshells, is not intact in the crocodile lizard genome. Only OC-17 transcript fragments were found in the oviduct transcriptome, and no OC-17 peptides were identified in the eggshell proteome of crocodile lizards. In contrast, OC-17 was present in the eggshells of the oviparous Mongolia racerunner (Eremias argus). Although the loss of OC-17 is not common in viviparous species, viviparous squamates show fewer intact eggshell-specific proteins than oviparous squamates. Our study implies that functional loss of eggshell-matrix protein genes may be involved in the reduction of eggshells during the transition from oviparity to viviparity in the crocodile lizard.
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Caimanes y Cocodrilos , Lagartos , Animales , Viviparidad de Animales no Mamíferos , Cáscara de Huevo , Oviparidad , Lagartos/genética , ChinaRESUMEN
Postsynthetic modification (PSM) of the metal-organic framework (MOF) has been demonstrated to be an effective strategy to enhance performance. In this particular work, the anion framework Mn-MOF {[Mn3O(H2O)3(HTC)]2-} (HTC6- = (5'-(3,5-dicarboxyphenyl)-[1,1':3',1â³-terphenyl]-3,3â³,5,5â³-tetracarboxylate] was obtained, and NH2(CH3)2+ ions were filled within the pores to balance the charge. In order to release the internal pores of Mn-MOF, the trivalent Fe(III) was introduced instead of Mn(II) nodes, resulting in the porous Mn1-xFex-MOF, and the NH2(CH3)2+ ions were simultaneously deported from the pores. The content of Fe(III) in Mn1-xFex-MOF was highly dependent on the concentration of Fe(III) solution, and the maximum could be up to Mn0.05Fe0.95-MOF with a BET surface area of 1209.457 m2 g-1. Compared to the amorphization of dense Mn-MOF at 0.8 GPa in a diamond anvil cell, the mechanical stability of porous Mn0.05Fe0.95-MOF has been dramatically enhanced, and the framework integrity could be maintained up to 16.5 GPa. The proton conductivity for the Mn1-xFex-MOF series was also investigated, where Mn0.93Fe0.07-MOF showed the best performance of 1.47 × 10-2 S cm-1 under 70 °C and 98% RH due to the onset of reversed charge from the anionic framework to cationic framework and the formation of the most compact hydrogen bonding net. This work has not only provided an example for the PSM strategy but also illustrated that the versatile functionalities of MOF materials were mainly ascribed to the tunable porosity.
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BACKGROUND AND AIM: The purpose of the present study was to evaluate the effect of direct-acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC). METHODS: We searched multiple electronic databases from database inception to June 14, 2021. Meta-analyses were performed separately for HCC recurrence and overall survival (OS). RESULTS: A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41-0.74, P < 0.001; I2 = 66.6%, P < 0.001) and improving OS (adjusted HR = 0.36, 95% CI 0.16-0.83, P = 0.017; I2 = 90.7%, P < 0.001) of HCV-related HCC patients. Compared with non-responders, patients with sustained virologic response (SVR) had greater benefit from DAAs therapy in reducing recurrence (HR = 0.37, 95% CI 0.16-0.84, P = 0.017; I2 = 58.8%, P = 0.088) and improving OS (HR = 0.17; 95% CI 0.06-0.50; P = 0.001; I2 = 56.4%, P = 0.130). Though DAAs did not show significant advantages over IFN in reducing recurrence (adjusted HR = 0.96, 95% CI 0.72-1.28, P = 0.784; I2 = 0.0%, P = 0.805), there seems to be a trend toward OS benefit from DAAs therapy (adjusted HR = 0.11, 95% CI 0.01-1.19, P = 0.059). CONCLUSION: DAAs therapy can prevent recurrence and improve OS of HCV-related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/efectos adversos , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Respuesta Virológica SostenidaRESUMEN
Methylisothiazolinone (MIT) is frequently used as antimicrobial in household and industrial products, and poses ecological and health risks to aquatic organisms and humans. In this study, vacuum ultraviolet (VUV)/ultraviolet (UV) irradiation was found highly efficient for removal of MIT. The rate constant of MIT degradation (kobs) under VUV/UV irradiation was 3.75 µEinstein-1 cm2, which was around 12.5 times higher than that under UV irradiation. The â¢OH concentration during the VUV/UV process was 1.0 × 10-12 M. The contributions of UV photolysis and â¢OH oxidation to MIT degradation under VUV/UV irradiation were 7.3% and 92.7%, respectively. The optimum solution pH (6.0-7.1) gave kobs 33%-39% higher than those at pH 3.9 and 9.3. CO32-/HCO3- inhibited MIT degradation and the kobs decreased by 74% when the concentration of CO32-/HCO3- was increased to 1 mM. The order of MIT removal efficiency under VUV/UV irradiation was ultrapure water > secondary effluent > reverse osmosis (RO) concentrate, because of the light screening and â¢OH quenching effect of actual wastewater. In RO concentrate, the rate constant of MIT degradation under VUV/UV irradiation was 22% higher than that obtained under UV irradiation. The reduction of TOC, UV254, and total fluorescence regional integration of the RO concentrate during VUV/UV process were 7.2%, 34.9%, and 52.3%, respectively. Twelve main transformation products of MIT were identified after VUV/UV degradation. The main degradation mechanisms of MIT were sulfur atom oxidation and hydroxyl addition. Quantitative structure-activity relationship analysis showed that VUV/UV degradation was an efficient method to remove the toxicity of MIT.
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Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Peróxido de Hidrógeno/química , Cinética , Oxidación-Reducción , Tiazoles , Rayos Ultravioleta , Vacio , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodosRESUMEN
BACKGROUND AND AIMS: Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB-EGF to promote angiogenesis and HCC progression. APPROACH AND RESULTS: A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB-EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia-inducible factor 1 α signaling pathway. In addition, HB-EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3-kinase/Akt signaling pathway. The level of HB-EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence-free survival, which suggests that HB-EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB-EGF inhibitor cross-reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression. CONCLUSIONS: HB-EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB-EGF inhibitor cross-reacting material 197 with sorafenib might be used for individualized treatment of HCC.
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Proteínas Bacterianas/farmacología , Carcinoma Hepatocelular , Factor de Crecimiento Similar a EGF de Unión a Heparina/metabolismo , Neoplasias Hepáticas , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptores ErbB/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Patológica/prevención & control , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Transducción de Señal , Sorafenib/farmacologíaRESUMEN
BACKGROUND AND AIM: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. RESULTS: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC. CONCLUSION: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma Hepatocelular/genética , Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Pronóstico , Tasa de SupervivenciaRESUMEN
AIM: This study aimed to explore the effect of organisational innovation climate on nurse innovation behaviour and the mediating role of psychological empowerment. BACKGROUND: Encouraging nurses to generate more innovative behaviours has become an important development direction for improving the quality of nursing services. METHOD: We employed a self-report questionnaire to collect data in Jinan City, China. A total of 2018 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. RESULT: The mean values of innovation behaviour and organisational innovation climate were 35.29 and 83.30, respectively. Psychological empowerment was found to have partially mediating effect on the relationship between organisational innovation climate and innovation behaviour. CONCLUSION: Organisational innovation climate has significant impact on innovation behaviour, and it can indirectly affect innovation behaviour via the mediating role of psychological empowerment. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should enhance innovation climate through formal rules, procedures and training activities. They can establish resource guarantee system and information sharing platform, and strengthen work autonomy for nurses to improve their psychological empowerment.
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Enfermeras Administradoras , Enfermeras y Enfermeros , China , Estudios Transversales , Humanos , Innovación Organizacional , Encuestas y CuestionariosRESUMEN
Norway spruce is a boreal forest tree species of significant ecological and economic importance. Hence there is a strong imperative to dissect the genetics underlying important wood quality traits in the species. We performed a functional genome-wide association study (GWAS) of 17 wood traits in Norway spruce using 178 101 single nucleotide polymorphisms (SNPs) generated from exome genotyping of 517 mother trees. The wood traits were defined using functional modelling of wood properties across annual growth rings. We applied a Least Absolute Shrinkage and Selection Operator (LASSO-based) association mapping method using a functional multilocus mapping approach that utilizes latent traits, with a stability selection probability method as the hypothesis testing approach to determine a significant quantitative trait locus. The analysis provided 52 significant SNPs from 39 candidate genes, including genes previously implicated in wood formation and tree growth in spruce and other species. Our study represents a multilocus GWAS for complex wood traits in Norway spruce. The results advance our understanding of the genetics influencing wood traits and identifies candidate genes for future functional studies.
Asunto(s)
Genes de Plantas/genética , Estudio de Asociación del Genoma Completo/métodos , Picea/genética , Sitios de Carácter Cuantitativo/genética , Madera/genética , Algoritmos , Genómica/métodos , Genotipo , Desequilibrio de Ligamiento , Noruega , Fenotipo , Picea/clasificación , Polimorfismo de Nucleótido Simple , Madera/clasificaciónRESUMEN
OBJECTIVE: To compare a new method "one-glass test" with the international gold standard "four-glass test" for the classification of chronic prostatitis (CP). METHODS: Totally, 360 CP patients were randomly assigned to receive "one-glass test" (n = 240) and "four-glass test" (n = 120) for the classification of the disease. Urine and expressed prostatic secretion (EPS) samples were collected from all the patients for microscopic and bacteriological examination and the results were subjected to statistical analysis, followed by comparison of the safety, procedures and costs of the two strategies. RESULTS: Compared with the "four-glass test", the urethal membrane "one-glass test" showed a significantly higher accuracy in the classification of types â ¡ (8.6%), â ¢A (50.0%) and â ¢B prostatitis (41.4%) (P < 0.05), simpler procedures and lower costs, reducing RMB ¥412 (61.24%) per case. CONCLUSIONS: The "one-glass test" has a high accuracy in the diagnosis and classification of chronic prostatitis and the advantages of simple operation and low cost, and therefore can be used in place of the "four-glass test" and widely promoted clinically.