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As a sustainable and promising approach of removing of nitrogen oxides (NOx), catalytic reduction of NOx with H2 is highly desirable with a precise understanding to the structure-activity relationship of supported catalysts. In particular, the dynamic evolution of support at microscopic scale may play a critical role in heterogeneous catalysis, however, identifying the in situ structural change of support under working condition with atomic precision and revealing its role in catalysis is still a grand challenge. Herein, we visually capture the surface lattice expansion of WO3-x support in Pt-WO3-x catalyst induced by NO in the exemplified reduction of NO with H2 using in situ transmission electron microscopy and first reveal its important role in enhancing catalysis. We find that NO can adsorb on the oxygen vacancy sites of WO3-x and favorably induce the reversible stretching of W-O-W bonds during the reaction, which can reduce the adsorption energy of NO on Pt4 centers and the energy barrier of the rate-determining step. The comprehensive studies reveal that lattice expansion of WO3-x support can tune the catalytic performance of Pt-WO3-x catalyst, leading to 20% catalytic activity enhancement for the exemplified reduction of NO with H2. This work reveals that the lattice expansion of defective support can tune and optimize the catalytic performance at the atomic scale.
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OBJECTIVES: Seroma represents the most prevalent postoperative complication following laparoscopic inguinal hernia repair, particularly in the case of large inguinoscrotal hernias. This randomized controlled trial was undertaken with the objective of assessing the effects of internal orifice narrowing achieved by suturing the divided distal hernia sac in laparoscopic repair of indirect inguinoscrotal hernias. METHODS: A total of 58 patients aged 18 years or older, were randomized into two groups: Group I, which underwent internal orifice narrowing, and Group II, which served as the control without narrowing. The study's primary endpoint was the incidence and volume of seroma in the inguinal region on postoperative days 1 and 7, as well as at 1, 3, and 6 months following the procedure. Secondary outcomes encompassed metrics like total operative time, acute and chronic pain levels, duration of hospital stay, recurrence rates, and the occurrence of any additional complications. RESULTS: In comparison to the control group, the experimental group exhibited a significantly lower incidence of seroma formation at 7 days (P = 0.001). Furthermore, the ultrasonic assessment indicated a reduced seroma volume in the operative group on postoperative day 7 (8.84 ± 17.71 vs. 52.39 ± 70.78 mL; P < 0.001). Acute pain levels and hospital stay were similar between the two groups (1.22 ± 0.76 vs. 1.04 ± 0.53, P = 0.073; 1.22 ± 0.07 vs. 1.19 ± 0.08, P = 0.627, respectively). Notably, neither chronic pain nor early recurrence, nor any other postoperative complications were observed in either group throughout the follow-up period, which extended for at least 6 months (range: 6-18 months). CONCLUSION: In the context of laparoscopic inguinoscrotal hernia repair, the incidence and volume of seroma can be significantly reduced through the implementation of internal orifice narrowing achieved by suturing the divided distal hernia sac. And, this reduction in seroma formation was not associated elevation in postoperative pain levels or recurrence rates.
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Dor Crônica , Hérnia Inguinal , Laparoscopia , Humanos , Dor Crônica/cirurgia , Hérnia Inguinal/cirurgia , Hérnia Inguinal/complicações , Herniorrafia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Recidiva , Seroma/etiologia , Seroma/prevenção & controle , Telas Cirúrgicas/efeitos adversos , Método Duplo-CegoRESUMO
BACKGROUND: The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. RESULTS: The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. CONCLUSIONS: This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.
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Fasciola , Proteínas de Helminto , Insulina , Transdução de Sinais , Animais , Fasciola/genética , Fasciola/metabolismo , Insulina/metabolismo , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genéticaRESUMO
BACKGROUND: Sleep disordered breathing (SDB) is broadly recognized to be associated with neurobehavioral deficits, which have significant impacts on developing-aged children and adolescents. Therefore, our study aimed to quantify the proportion of neurobehavioral impairments attributed to SDB in general children and adolescents by population attributable fraction (PAF). METHODS: The study was registered at PROSPERO (ID: CRD42023388143). We collected two types of literature on the prevalence of SDB and the risk of SDB-related neurobehavioral deficits from ten electronic databases and registers, respectively. The pooled effect sizes (Pe, Pc, RR) by random-effects meta-analysis were separately substituted into Levin's formula and Miettinen's formula to calculate PAFs. RESULTS: Three prevalence literature and 2 risk literature, all with moderate/high quality, were included in the quantitative analysis individually. The prevalence of SDB was 11% (95%CI 2%-20%) in children and adolescents (Pe), while the SDB prevalence was 25% (95%CI 7%-42%) in neurobehavioral patients (Pc). SDB diagnosis at baseline was probably associated with about threefold subsequent incidence of neurobehavioral deficits (pooled RR 3.24, 95%CI 1.25-8.41), after multi-adjustment for key confounders. Up to 19.8% or 17.3% of neurobehavioral consequences may be attributed to SDB from Levin's formula and Miettinen's formula, respectively. CONCLUSIONS: A certain number of neurobehavioral consequences may be attributable to SDB. It is essential for clinicians to identify and treat SDB timely, as well as screen for SDB in patients with neurobehavioral impairments. More longitudinal studies of SDB and neurobehavioral deficits are needed in the future to further certify the association between them.
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Síndromes da Apneia do Sono , Adolescente , Criança , Humanos , Incidência , Prevalência , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/complicaçõesRESUMO
Biochar preparation and application is an anticipated pathway for the resource utilization of biogas residue. In this study, biochars were prepared by the pyrolysis of biogas residue from food waste anaerobic digestion (named as BRBCs) under various pyrolysis temperatures (300, 500, 700, and 900 °C), and the effect of pyrolysis temperatures on the physicochemical characteristics of BRBCs was examined. The adsorption performance toward ciprofloxacin (CIP), a typical antibiotic in waterbodies, was also investigated. The results showed that pyrolysis temperature significantly changed the physicochemical properties of BRBCs. In addition, the minerals in the biogas residue, especially SiO2, were rearranged to form a mesoporous structure in biochar through a self-template strategy (without activator). BRBC prepared at 900 °C exhibited a high specific surface area and pore volume, well-developed mesopore structure, and more carbon structure defects, and exhibited the largest CIP adsorption capacity with 70.29 mg g-1, which was ascribed to the combined interaction of pore diffusion, π-π interactions, hydrogen bonding, complexation, and electrostatic forces. Furthermore, the adsorption of CIP by BRBC900 was well described by two-compartment kinetic and Langmuir isotherm models. BRBC900 showed good adsorption performance toward CIP at pH 7-9. The adsorption of CIP by BRBC is a spontaneous, exothermic, entropy-increasing process. Moreover, BRBC also presented a good recycling potential. Therefore, the preparation of mesoporous biochar based on a self-template strategy not only provides an option for the resource utilization of biogas residue but also offers a new option for the treatment of antibiotic wastewater.
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Biocombustíveis , Carvão Vegetal , Ciprofloxacina , Pirólise , Ciprofloxacina/química , Carvão Vegetal/química , Biocombustíveis/análise , Adsorção , Poluentes Químicos da Água/química , Temperatura , Porosidade , CinéticaRESUMO
OBJECTIVE: To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation. METHODS: This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024. The ureteral stent with thread group, in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation. On the 9th day after the operation, the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed. The ureteral stent could be removed along with the suture. As to the cystoscope group, a ureteral stent was routinely placed during kidney transplantation, and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation. The pain scores [numerical rating scale (NRS)-11] during catheter removal and the incidence of urinary tract infections were observed and compared between the two groups. t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups, and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups. P < 0.05 was considered statistically significant. RESULTS: As of March 2024, all the recipients were followed up for an average of 6 months (3 to 12 months) postoperatively. A total of 46 kidney transplantation patients were included, with 21 in the ureteral stent with thread group and 25 in the cystoscope group. There were no statistically significant differences between the two groups in age distribution, male-to-female ratio, and deceased versus live donor grafts. Three months after renal transplantation, there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group (P=0.007). No significant urinary fistula, wound infection, or ureteral stenosis occurred in either group. No stent-related complications, stent migration, or stone formation were observed. The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4, respectively, with no statistically significant difference (t=0.29, P=0.773). However, the pain scores during ureteral stent removal were 4.9±1.6 and 3.0±1.0 in the two groups, respectively, with a statistically significant diffe-rence (t=5.017, P < 0.001). The total costs of indwelling and removing ureteral stents in the cystoscopy group and the ureteral stent with thread group were 6 452.0 (5 539.5, 6 452.0) yuan and 3 225.0 (3 225.0, 3 225.0) yuan, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Compared with the conventional transplanted kidney ureteral stent, the self-discharge ureteral stent technique with sutures is simpler, has a shorter ureteral stent inlay time, reduces the symptoms of bladder spasms, significantly reduces the cost of catheterization, and has fewer postoperative urinary system complications. It is a worthy improved surgical method to be promoted.
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Transplante de Rim , Stents , Ureter , Humanos , Transplante de Rim/efeitos adversos , Stents/efeitos adversos , Ureter/cirurgia , Estudos Prospectivos , Feminino , Masculino , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Suturas , Pessoa de Meia-IdadeRESUMO
We experimentally investigated and demonstrated an ultralow noise hybrid amplifier that combines second-order distributed Raman amplifier (DRA) and first-order lumped Raman amplifier (LRA) in a cascaded approach. This approach allows for the reutilization of pump light from the LRA as the seed light in the second-order DRA, and simultaneous full-band dispersion compensation is realized by using dispersion compensation fiber in the LRA. This approach also supports broadband gain flattening based on the separated DRA and LRA configuration. The transmission application of the proposed amplifier was investigated using a set of 10 external cavity lasers (ECLs) in the C-band and 8 ECLs in the L-band. Ranging from 1531.12â nm to 1595.49â nm across C + L band, the proposed hybrid amplifier gives a maximum on-off gain of 27.2â dB and an average gain of 23.4â dB, with an extremely low effective noise figure (NF) of lower than -2.9â dB. Intensity modulation direct detection (IMDD) signal transmission is carried out at two different data rates across these 18 wavelengths in the C + L band: (1) 56 Gbps/λ PAM-4 signal; (2) 112 Gbps/λ PAM-4 signal. The results show that the error free transmissions are demonstrated over 101.6â km EX2000 fiber using both signals with 7% HD-FEC and 20% SD-FEC, respectively.
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We report ultralow-noise transmission over a 102-km single-mode fiber using a purely nonlinear amplification scheme consisting of a second-order distributed Raman amplifier (DRA) and a phase-sensitive amplifier (PSA) based on periodically poled LiNbO3 waveguides. The hybrid DRA/PSA features a broadband gain over the C and L bands and an ultralow-noise advantage, with a less than -6.3â dB effective noise figure in the DRA stage and a 1.6â dB optical signal-to-noise ratio (OSNR) improvement in the PSA stage. Compared with the unamplified link, the OSNR is improved by 10.2â dB for a 20-Gbaud 16QAM signal in the C band, resulting in error-free detection (a bit-error rate of less than 3.8 × 10-3) for the signal with a low link input power of -25 dBm. Mitigation of nonlinear distortion is also achieved by the proposed nonlinear amplified system due to the subsequent PSA.
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Long noncoding RNAs (lncRNAs) emerge as important orchestrators of biological processes in embryonic stem cells (ESCs). LncRNA Lx8-SINE B2 was recently identified as an ESC-specific lncRNA that marks pluripotency. Here, we studied the function of lncRNA Lx8-SINE B2 in ESCs. Depletion of Lx8-SINE B2 disrupted ESC proliferation, repressed the expression of pluripotency genes, activated differentiation genes, and inhibited reprogramming to induced pluripotent stem cells. The reduction of the colony formation ability of ESCs upon Lx8-SINE B2 knockdown was accompanied by the elongation of the G1 phase and the shortening of the S phase. Transcriptome analysis revealed that Lx8-SINE B2 deficiency affected multiple metabolic pathways, particularly glycolysis. Mechanistically, Lx8-SINE B2 functions as a cytoplasmic lncRNA and interacts with the glycolytic enzyme Eno1 as shown by RNA pull-down and RNA localization analysis. Lx8-SINE B2 and Eno1 interact with and regulate each other's expression, hence promoting the expression of metabolic genes and influencing glycolysis. In conclusion, we have identified lncRNA Lx8-SINE B2 as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.
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Células-Tronco Pluripotentes Induzidas , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células-Tronco Embrionárias/metabolismo , Diferenciação Celular/genética , Perfilação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismoRESUMO
The highly conserved COP9 signalosome (CSN), composed of 8 subunits (Cops1 to Cops8), has been implicated in pluripotency maintenance of human embryonic stem cells (ESCs). Yet, the mechanism for the CSN to regulate pluripotency remains elusive. We previously showed that Cops2, independent of the CSN, is essential for the pluripotency maintenance of mouse ESCs. In this study, we set out to investigate how Cops5 and Cops8 regulate ESC differentiation and tried to establish Cops5 and Cops8 knockout (KO) ESC lines by CRISPR/Cas9. To our surprise, no Cops5 KO ESC clones were identified out of 127 clones, while three Cops8 KO ESC lines were established out of 70 clones. We then constructed an inducible Cops5 KO ESC line. Cops5 KO leads to decreased expression of the pluripotency marker Nanog, proliferation defect, G2/M cell-cycle arrest, and apoptosis of ESCs. Further analysis revealed dual roles of Cops5 in maintaining genomic stability of ESCs. On one hand, Cops5 suppresses the autophagic degradation of Mtch2 to direct cellular metabolism toward glycolysis and minimize reactive oxygen species (ROS) production, thereby reducing endogenous DNA damage. On the other hand, Cops5 is required for high DNA damage repair (DDR) activities in ESCs. Without Cops5, elevated ROS and reduced DDR activities lead to DNA damage accumulation in ESCs. Subsequently, p53 is activated to trigger G2/M arrest and apoptosis. Altogether, our studies reveal an essential role of Cops5 in maintaining genome integrity and self-renewal of ESCs by regulating cellular metabolism and DDR pathways.
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Complexo do Signalossomo COP9/metabolismo , Reparo do DNA , Células-Tronco Embrionárias/enzimologia , Instabilidade Genômica , Peptídeo Hidrolases/metabolismo , Animais , Apoptose , Complexo do Signalossomo COP9/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular , Técnicas de Inativação de Genes , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Fosforilação Oxidativa , Peptídeo Hidrolases/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.
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In the present study, we reconstructed the transforming growth factor beta (TGF-ß) signaling pathway for Fasciola gigantica, which is a neglected tropical pathogen. We defined the components involved in the TGF-ß signaling pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (FgESP) was predicted via signal peptide annotation. The core components of the TGF-ß signaling pathway have been detected in F. gigantica; classical and nonclassical single transduction pathways were constructed. Four ligands have been detected, which may mediate the TGF-ß signaling pathway and BMP signaling pathway. Two ligand-binding type II receptors were detected, and inhibitory Smad7 was not detected. TLP, BMP-3, BMP-1, and ActRIb showed higher transcription in 42-day juvenile and 70-day juvenile, while ActRIIa, Smad1, ActRIIb, Smad8, KAT2B, and PP2A showed higher transcription in egg. TLM, Ski, Smad6, BMPRI, p70S6K, Smad2, Smad3, TgfßRI, Smad4, and p300 showed higher transcription in metacercariae. Four ligands, 2 receptors and 3 Smads are predicted to be present in the FgESP, suggesting their potential extrinsic function. This study should help to understand signal transduction in the TGF-ß signaling pathway in F. gigantica. In addition, this study helps to illustrate the complex mechanisms involved in developmental processes and F. gigantica - host interaction and paves the way for further characterization of the signaling pathway in trematodes.
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Fasciola , Animais , Fasciola/genética , Fasciola/metabolismo , Fator de Crescimento Transformador beta/genética , Transdução de SinaisRESUMO
Background and Objectives: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are malignant disorders with adverse prognoses for advanced patients. Anoikis, which is involved in tumor metastasis, facilitates the survival and separation of tumor cells from their initial site. Unfortunately, it is rarely studied, and in the literature, studies have only addressed the prognosis character of anoikis for patients with CESC. Materials and Methods: We utilized anoikis-related genes (ANRGs) to construct a prognostic signature in CESC patients that were selected from the Genecards and Harmonizome portals. Furthermore, we revealed the underlying clinical value of this signature for clinical maneuvers by providing clinical specialists with an innovative nomogram on the basis of ANRGs. Finally, we investigated the immune microenvironment and drug sensitivity in different risk groups. Results: We screened six genes from fifty-eight anoikis-related differentially expressed genes in the TCGA-CESC cohort, and we constructed a prognostic signature. Then, we built a nomogram combined with CESC clinicopathological traits and risk scores, which demonstrated that this model may improve the prognosis of CESC patients in clinical therapy. Next, the prognostic risk scores were confirmed to be an independent prognostic indicator. Additionally, we programmed a series of analyses, which included immune infiltration analysis, therapy-related analysis, and GSVA enrichment analysis, to identify the functions and mechanisms of the prognostic models during the progression of cancer in CESC patients. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the six ANRGs. Conclusions: The present discovery verified that the predictive 6-anoikis-related gene (6-ANRG) signature and nomogram serve as imperative factors that might notably impact a CESC patient's prognosis, and they may be able to provide new clinical evidence to assume the role of underlying biological biomarkers and thus become indispensable indicators for prospective diagnoses and advancing therapy.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias de Tecido Conjuntivo , Neoplasias do Colo do Útero , Feminino , Humanos , Anoikis , Prognóstico , Estudos Prospectivos , Microambiente TumoralRESUMO
The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa-miR-370-3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL-8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR-370-3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL-8-mediated modification of miR-370-3p. Gain- and loss-of-function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro- and antitumor activities. Interleukin-8 and miR-370-3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL-8 experienced more metastasis and shorter survival. Interleukin-8 induced epithelial-mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA-370-3p interacted with its cognate mRNA within the 3'-UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL-8 protumoral effects on liver cancer cells. Interleukin-8 negatively modulated miR-370-3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR-370-3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR-370-3p and low IL-8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL-8/STAT3/miR-370-3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR-370-3p in HCC metastasis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Interleucina-8/genética , Interleucina-8/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Mensageiro , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismoRESUMO
BACKGROUND: The bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration. METHODS: RNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The "survival" and "survminer" packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis. RESULTS: Transcriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT. CONCLUSIONS: MTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Antígenos B7 , Carcinoma de Células de Transição/genética , Humanos , Oncogenes , Prognóstico , Bexiga UrináriaRESUMO
A "hotspot"-rich Ag-nanoparticle-decorated three-dimensional polymer substrate was fabricated, exhibiting an excellent surface-enhanced Raman scattering (SERS) activity. 4-Mercaptobenzoic acid (MBA) was selected as a probe molecule for comparing the SERS activity on selected substrates. The proposed detection chip with the adsorption of tetramethylthiuram disulfide (TTD) shows an excellent sensitivity for the quantitative determination of TTD and mercury ions (Hg2+). This chip exhibited a high sensitivity for the trace detection of the targets. Interestingly, we found that the adsorbed TTD is selectively sensitive to Hg2+. The SERS band had a significant frequency shift of 11 cm-1 as the concentration of Hg2+ increased from 10-10 to 10-3 mol L-1. More importantly, the frequency shift of the SERS band exhibited an excellent linear relationship with the concentration of Hg2+, and the determination limit for Hg2+ was 10-10 mol L-1. Furthermore, the proposed detection chip shows great application potential for the determination of pesticides and Hg2+.
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Mercúrio , Nanopartículas Metálicas , Polímeros , Análise Espectral Raman , TiramRESUMO
RNA translation is the rate-limiting step when cells synthesize proteins. Elevating translation efficiency (TE) is intuitively beneficial. Particularly, when viruses invade host cells, how to compete with endogenous RNAs for efficient translation is a major issue to be resolved. We collected millions of worldwide SARS-CoV-2 sequences during the past year and traced the dynamics of allele frequency of every mutation. We defined adaptive and deleterious mutations according to the rise and fall of their frequencies along time. For 5'UTR and synonymous mutations in SARS-CoV-2, the selection on TE is evident near start codons. Adaptive mutations generally decrease GC content while deleterious mutations increase GC content. This trend fades away with increasing distance to start codons. Mutations decreasing GC content near start codons would unravel the complex RNA structure and facilitate translation initiation, which are beneficial to SARS-CoV-2, and vice versa. During this evolutionary arms race between human and virus, SARS-CoV-2 tries to improve its cis elements to compete with host RNAs for rapid translation.
Assuntos
Evolução Molecular , RNA Viral , SARS-CoV-2 , Seleção Genética , Regiões 5' não Traduzidas , COVID-19/virologia , Códon de Iniciação , Humanos , Mutação , RNA Viral/genética , SARS-CoV-2/genéticaRESUMO
Endogenous retroviruses (ERVs) were usually silenced by various histone modifications on histone H3 variants and respective histone chaperones in embryonic stem cells (ESCs). However, it is still unknown whether chaperones of other histones could repress ERVs. Here, we show that H2A/H2B histone chaperone FACT plays a critical role in silencing ERVs and ERV-derived cryptic promoters in ESCs. Loss of FACT component Ssrp1 activated MERVL whereas the re-introduction of Ssrp1 rescued the phenotype. Additionally, Ssrp1 interacted with MERVL and suppressed cryptic transcription of MERVL-fused genes. Remarkably, Ssrp1 interacted with and recruited H2B deubiquitinase Usp7 to Ssrp1 target genes. Suppression of Usp7 caused similar phenotypes as loss of Ssrp1. Furthermore, Usp7 acted by deubiquitinating H2Bub and thereby repressed the expression of MERVL-fused genes. Taken together, our study uncovers a unique mechanism by which FACT complex silences ERVs and ERV-derived cryptic promoters in ESCs.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Retrovirus Endógenos/genética , Proteínas de Grupo de Alta Mobilidade/fisiologia , Chaperonas de Histonas/fisiologia , Regiões Promotoras Genéticas , Fatores de Transcrição/fisiologia , Animais , Linhagem Celular , Regulação da Expressão Gênica , Histonas/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas , Peptidase 7 Específica de Ubiquitina/fisiologiaRESUMO
Buffaloes, as highly susceptible definitive hosts of Fasciola gigantica, suffer from a high infection rate of fasciolosis, which causes enormous economic losses. Repeat infection is responsible for this high rate; thus, elucidating the protective immunity mechanism in repeat infection is decisive in fasciolosis prevention. Herein, a secondary experimental infection model was established to preliminarily reveal the protective immunity that occurs in repeat infection. In brief, animals were assigned to three groups: group A (uninfected control), group B (primary infection) and group C (secondary infection). Buffaloes were autopsied 20 weeks post-infection for measurements of the recovered flukes and hepatic examination. In addition, the detection of specific antibody (IgG) responses to F. gigantica excretory-secretory product (FgESP) throughout the whole period and weight gain throughout the first 4 months as a percentage (%) of the starting weight were also determined. The serum hepatic enzyme gamma glutathione transferase (GGT) levels were monitored to assess hepatic damage throughout the study period. Infection establishment was compared between group B and group C. Similar specific IgG patterns were observed between group B and group C, and hepatic damage was more severe in group C than group B. Significant differences in weight gain as a percentage of the start weight were observed between group A and group B at the 3rd and 4th months postprimary infection, while significant differences were not observed between group A and group C or group B and group C. Our results suggest that challenge infection cannot induce resistance against F. gigantica in buffaloes, which is consistent with the protective immunity against Fasciola hepatica reinfection observed in sheep and goats.
Assuntos
Bison , Fasciola , Fasciolíase , Doenças dos Ovinos , Animais , Anticorpos Anti-Helmínticos , Búfalos , Fasciolíase/veterinária , Imunoglobulina G , Ovinos , Aumento de PesoRESUMO
Developing low-cost and efficient electrocatalysts to accelerate oxygen evolution reaction (OER) kinetics is vital for water and carbon-dioxide electrolyzers. The fastest-known water oxidation catalyst, Ni(Fe)OxHy, usually produced through an electrochemical reconstruction of precatalysts under alkaline condition, has received substantial attention. However, the reconstruction in the reported catalysts usually leads to a limited active layer and poorly controlled Fe-activated sites. Here, we demonstrate a new electrochemistry-driven F-enabled surface-reconstruction strategy for converting the ultrathin NiFeOxFy nanosheets into an Fe-enriched Ni(Fe)OxHy phase. The activated electrocatalyst shows a low OER overpotential of 218 ± 5 mV at 10 mA cm-2 and a low Tafel slope of 31 ± 4 mV dec-1, which is among the best for NiFe-based OER electrocatalysts. Such superior performance is caused by the effective formation of the Fe-enriched Ni(Fe)OxHy active-phase that is identified by operando Raman spectroscopy and the substantially improved surface wettability and gas-bubble-releasing behavior.