RESUMEN
Epidermal growth factor receptor-targeted (EGFR-targeted) therapies show promise for non-small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild-type NSCLC. A genome-wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild-type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild-type NSCLC cells. Additionally, PAICS silencing led to cell-cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild-type NSCLC. PAICS silencing also caused DNA damage and cell-cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K-AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild-type NSCLC and represents a potential therapeutic target for this disease.
RESUMEN
Smart textiles with multifunction and highly stable performance are essential for their application in wearable electronics. Despite the advancement of various smart textiles through the decoration of conductive materials on textile surfaces, improving their stability and functionality remains a challenging topic. In this study, we developed an ionic textile (i-textile) with air permeability, water resistance, UV resistance, and sensing capabilities through in situ photopolymerization of ionogel onto the textile surface. The i-textile presents air permeability comparable to that of bare textile while possessing enhanced UV resistance. Remarkably, the i-textile maintains excellent electrical properties after washing 20 times or being subjected to 300 stretching cycles at 30% tension. When applied to human joint motion detection, the i-textile-based sensors can effectively distinguish joint motion based on their sensitivity and response speed. This research presents a novel method for developing smart textiles that further advances wearable electronics.
Asunto(s)
Dispositivos Electrónicos Vestibles , Humanos , Movimiento (Física) , Electrónica , Electrodos , TextilesRESUMEN
OBJECTIVE: Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia. METHODS: A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed. RESULTS: For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04). CONCLUSIONS: The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.
Asunto(s)
Coinfección , Neoplasias , Neumonía , Humanos , Líquido del Lavado Bronquioalveolar , Secuenciación de Nucleótidos de Alto Rendimiento , Consenso , Neumonía/diagnóstico , Neumonía/genética , Sensibilidad y Especificidad , Neoplasias/diagnóstico , Neoplasias/genéticaRESUMEN
BACKGROUND: Chronic kidney disease(CKD) is one of the most prevalent non-communicable health concerns in children and adolescents worldwide; however, data on its incidence, prevalence, disability-adjusted life years (DALYs) and trends in the population are limited. We aimed to assess the global, regional and national trends in CKD burden in children and adolescents. METHODS: In this trend analysis based on the 2019 Global Diseases, Injuries, and Risk Factors Study, CKD incidence, prevalence and DALYs rates per 100 000 population for children and adolescents were reported at the global, regional and national levels, as well as the average annual percentage change (AAPC). These global trends were analyzed by age, sex, region and socio-demographic index (SDI). RESULTS: Globally, the overall incidence of CKD (all stages including kidney replacement therapy) in children and adolescents showed an increasing trend [AAPC 0.44 (95% confidence interval 0.36-0.52)] between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend [AAPC 0.46 (0.42-0.51)]. However, the DALYs of CKD showed a continuous decreasing trend [AAPC -1.18 (-1.37 to -0.99)]. The population aged 15-19 years had the largest CKD incidence increase during this period. The largest increase in age-standardized incidence rate (ASIR) was in middle SDI countries [AAPC 0.56 (0.45-0.67)]. The relationship between the ASIR and SDI showed an inverse U-shaped correlation while the relationship between the age-standardized DALYs rate (ASDR) and SDI showed an inverse trend with SDI. Among adolescents (15-19 years), the ASIR continued to increase for five causes of CKD, owing to type 2 diabetes mellitus and hypertension. Most of the disease burden was concentrated in countries with a lower SDI. Andean Latin America and Central Latin America showed the largest increases in CKD ASIR between 1990 and 2019. CONCLUSION: The burden of CKD in children and adolescents has increased worldwide, especially in regions and countries with a lower SDI.
Asunto(s)
Salud Global , Insuficiencia Renal Crónica , Humanos , Adolescente , Niño , Insuficiencia Renal Crónica/epidemiología , Masculino , Femenino , Incidencia , Prevalencia , Preescolar , Salud Global/estadística & datos numéricos , Costo de Enfermedad , Lactante , Factores de Riesgo , Años de Vida Ajustados por Discapacidad , Recién NacidoRESUMEN
In the present study, we introduced the H 2O 2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine (GEM) to synthesize a new target compound named GEM-ZZQ, and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H 2O 2 to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM. For the lung cancer cell lines that are resistant to the epidermal growth factor receptor (EGFR)-targeting inhibitor osimertinib, GEM-ZZQ showed less growth inhibition than GEM; however, GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups. In summary, we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.
RESUMEN
The traceability of quality mineral fingerprints in the viscera of Tan sheep from northwest China was studied. Twenty-five mineral elements in the heart and liver samples of Tan sheep were determined using an inductively coupled plasma mass spectrometer (ICP-MS), and the characteristics of the mineral elements in the visceral tissues of the Tan sheep were further analyzed in combination with a principal component analysis (PCA), hierarchical cluster analysis (HCA), and linear discriminant analysis (LDA) to establish a discriminant model and verify it. The results show that 11 elements (137Ba, 43Ca, 63Cu, 56Fe, 39K, 31P, 60Ni, 78Se, 118Sn, 125Te, and 66Zn) in the Tan sheep heart samples had significant differences among different regions (p < 0.05), and the results of the LDA show that the accuracy rate of the return-generation examination was 85.70%, and the accuracy rate of the hand-over-fork examination was 87.50%; 10 elements (111Cd, 59Co, 52Cr, 56Fe, 39K, 55Mn, 95Mo, 23Na, 121Sb, and 78Se) in the Tan sheep liver samples had significant differences among different regions (p < 0.05), and the results of the LDA showed that the accuracy rate of the return-generation examination was 96.30%, and the accuracy rate of the hand-over-fork examination was 86.25%. This indicates that the multi-element analysis has potential for determining the origin of Tan sheep viscera in certain regions.
RESUMEN
Electrochemical reduction of CO2 (CO2 RR) into value-added products is a promising strategy to reduce energy consumption and solve environmental issues. Formic acid/formate is one of the high-value, easy-to-collect, and economically viable products. Herein, the reconstructed Bi2 O2 CO3 nanosheets (BOCR NSs) are synthesized by an in situ electrochemical anion exchange strategy from Bi2 O2 SO4 as a pre-catalyst. The BOCR NSs achieve a high formate Faradaic efficiency (FEformate ) of 95.7% at -1.1 V versus reversible hydrogen electrode (vs. RHE), and maintain FEformate above 90% in a wide potential range from -0.8 to -1.5 V in H-cell. The in situ spectroscopic studies reveal that the obtained BOCR NSs undergo the anion exchange from Bi2 O2 SO4 to Bi2 O2 CO3 and further promote the self-reduction to metallic Bi to construct Bi/BiO active site to facilitate the formation of OCHO* intermediate. This result demonstrates anion exchange strategy can be used to rational design high performance of the catalysts toward CO2 RR.
RESUMEN
IL-33, a member of the IL-1 family, acts as an alarmin in immune response. Epithelial-mesenchymal transition and transforming growth factor-ß (TGF-ß)induced fibroblast activation are key events in the development of renal interstitial fibrosis. The current study found increased expression of IL-33 and interleukin-1 receptor-like 1 (IL1RL1, alias ST2), the receptor for IL-33, in human fibrotic renal tissues. In addition, IL-33 or ST2-deficient mice showed significantly reduced levels of fibronectin, α-smooth muscle actin, and vimentin, and increased E-cadherin levels. In HK-2 cells, IL-33 promotes the phosphorylation of the TGF-ß receptor (TGF-ßR), Smad2, and Smad3, and the production of extracellular matrix (ECM), with reduced expression of E-cadherin. Blocking TGF-ßR signaling or suppressing ST2 expression impeded Smad2 and Smad3 phosphorylation, thereby reducing ECM production, suggesting that IL-33induced ECM synthesis requires cooperation between the two pathways. Mechanistically, IL-33 treatment induced a proximate interaction between ST2 and TGF-ßRs, activating downstream Smad2 and Smad3 for ECM production in renal epithelial cells. Collectively, this study identified a novel and essential role for IL-33 in promoting TGF-ß signaling and ECM production in the development of renal fibrosis. Therefore, targeting IL-33/ST2 signaling may be an effective therapeutic strategy for renal fibrosis.
Asunto(s)
Interleucina-33 , Enfermedades Renales , Ratones , Humanos , Animales , Interleucina-33/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/uso terapéutico , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Enfermedades Renales/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteína smad3/metabolismo , Fibrosis , Cadherinas/metabolismo , Factores de Crecimiento Transformadores/metabolismo , Factores de Crecimiento Transformadores/farmacología , Factores de Crecimiento Transformadores/uso terapéutico , Factor de Crecimiento Transformador beta1/metabolismo , Transición Epitelial-MesenquimalRESUMEN
Kidney fibrosis is the common final pathway of chronic kidney disease (CKD), and it is distinguished by inflammation, mesenchymal transition with myofibroblast formation, and epithelial-to-mesenchymal transition (EMT). Macrophages are protuberant inflammatory cells in the kidney, and their roles are dependent on their phenotypes. However, it remains unclear whether tubular epithelial cells (TECs) undergoing EMT can influence the phenotypes of macrophages and the underlying mechanisms during the development of kidney fibrosis. Here, we investigated the characteristics of TECs and macrophages during kidney fibrosis with a focus on EMT and inflammation. We found that the coculture of exosomes from transforming growth factor-beta (TGF-ß)-induced TECs with macrophages induced macrophage M1 polarization, while exosomes from TECs without TGF-ß stimulation or stimulation with TGF-ß alone did not induce an increase in M1 macrophage-related markers. Notably, TECs induced to undergo EMT by TGF-ß treatment released more exosomes than the other groups. Furthermore, it is noteworthy that when we injected exosomes from TECs undergoing EMT into mice, in addition to the high level of inflammatory response and the activation of M1 macrophages, the indicators of EMT and renal fibrosis in mouse kidney tissue were correspondingly elevated. In summary, exosomes from TECs undergoing EMT by TGF-ß treatment induced M1 polarization and led to a positive feedback effect for further EMT and the development of renal fibrosis. Therefore, the obstacle to the release of such exosomes may be a novel therapeutic strategy for CKD.
RESUMEN
Efficient catalysts are highly desirable for the selective electrochemical CO2 reduction reaction (CO2RR). Ni single-atom catalysts are known as promising CO2RR catalysts, while Ni NPs are expected to catalyze the competing HER. In this work, we have modified the Ni NPs by encapsulating them into porous Ni-N-C nanosheets (Ni@Ni-N-C), to boost the synergy between Ni NPs and dispersed Ni-N species towards CO2RR. The CO faradaic efficiency (FECO) reached 96.4% at -0.9 V and retained over 90% in a wide potential window. More importantly, FECO values of over 94% have been obtained from -50 to -170 mA cm-2 with a peak FECO of 99% in a flow cell. Our work demonstrates that the surface modification of Ni NPs can inhibit the unexpected HER and activate the surface sites, offering a practical design strategy for CO2RR catalysts.
Asunto(s)
Dióxido de Carbono , Nanopartículas , CatálisisRESUMEN
Hepatocyte growth factor receptor (HGFR or Met) upregulation has been proven to play important roles in non-small cell lung carcinoma (NSCLC). Interestingly, chemoresistance against epidermal growth factor receptor (EGFR) inhibitors including erlotinib and gefitinib was also related to Met. Targeting bromodomain and extra terminal domain (BET) proteins, especially BRD4, has shown inhibitory effects on lung cancer, but the mechanism is unclear. Herein, we found that JQ1 (BET inhibitor) suppressed NSCLC cell growth, reduced the Met expression, and contributed to inactivation of PI3K/Akt and MAPK/ERK pathways. Moreover, another BET protein inhibitor I-BET151, or BRD4 depletion, also inhibited NSCLC cell growth and downregulated Met. JQ1 inhibited HGF-induced cell growth and Met/PI3K/Akt activation, also inhibited A549 tumor growth in xenograft mouse models, in parallel with Met downregulation. Moreover, JQ1 inhibited the growth of paired erlotinib-sensitive and resistant HCC827 cells in parallel with Met downregulation and PI3K/Akt signaling inactivation. JQ1 also exerted inhibitory influences on the growth of erlotinib-sensitive and resistant HCC827 tumors in xenograft mouse models. These results suggested that targeting BET proteins inhibited NSCLC via downregulating Met and inactivating PI3K/AKT pathway. Our findings reveal a novel mechanism of BET proteins implicated in NSCLC progression with Met taken into consideration.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Clorhidrato de Erlotinib/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Nucleares/metabolismo , Regulación hacia Abajo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Neoplasias Pulmonares/patología , Proliferación Celular , Resistencia a Antineoplásicos , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Ciclo Celular/metabolismoRESUMEN
Chronic hepatitis B (CHB) remains a relatively major public health problem. Simultaneously, an unhealthy lifestyle causes a series of metabolic abnormalities, the most critical of which are metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Therefore, it is increasingly common for MS and NAFLD to coexist with CHB. MS is a cluster of metabolic disorders, while NAFLD is always considered as the manifestation of MS in the liver. The aim of this article is to review recent advances to explain the complex relationship among MS, NAFLD, and hepatitis B virus (HBV) infection. MS and NAFLD both have obesity and insulin resistance as central factors and both can lead to adverse hepatic and extrahepatic outcomes. However, there is insufficient evidence to associate NAFLD with all components of MS, and genetically related NAFLD has little association with MS. Incidences of MS and NAFLD are inversely associated with HBV infection. However, the effect of HBV infection on the risk of insulin resistance and dyslipidemia is not well understood. Evidence from both clinical studies and animal experiments suggested that hepatic steatosis inhibits HBV replication. MS and NAFLD may have adverse effects on CHB disease progression and prognosis. Furthermore, in related studies of CHB with normal alanine aminotransferase (ALT), the roles of MS and NAFLD should also be emphasized. In conclusion, there are complicated interactions that are not yet fully defined among MS, NAFLD, and CHB. To control chronic liver disease effectively, the relationship among the three must be clarified.
RESUMEN
This study aimed to investigate the factors affecting the success rate of full pulpotomy in permanent posterior teeth with pulpitis. The study included 105 permanent posterior teeth clinically diagnosed as reversible or irreversible pulpitis in 92 patients aged 18-82 years. All teeth underwent a full pulpotomy using mineral trioxide aggregate as a capping material and were recalled for clinical and radiographic evaluation at 3, 6, 12, and 24 months postoperatively. The overall success rate after the 12-month review was above 90%, and failed cases mainly occurred during the first 12 months after treatment. In this study, the treatment outcome of pulpotomy was not related to sex, or tooth position and the cause of pulpitis. To analyze the influence of age on the treatment outcome, all the teeth were allocated to three groups: group 1 (18-39 years); group 2 (40-59 years); and group 3 (≥ 60 years). A significant difference in success rate was found between groups 1 and 3 (P = 0.014). These results suggest that pulpotomy can be used as an alternative treatment for permanent mature teeth diagnosed with pulpitis and that aging is one factor affecting the treatment outcome.
Asunto(s)
Pulpitis , Humanos , Pulpitis/diagnóstico por imagen , Pulpitis/cirugía , Pulpotomía/métodos , Dentición Permanente , Resultado del TratamientoRESUMEN
The wide spread of drug-resistant bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), poses a tremendous threat to global health. Of particular concern, resistance to vancomycin, linezolid, and daptomycin has already been reported in clinical MRSA strains. New antibacterial agents are urgently needed to overcome this crisis. Here, we designed and synthesized a series of ruthenium-based antibacterial agents via targeting bacterial membrane integrity. Structure-activity relationship studies demonstrated that both the lipophilicity/hydrophilicity ratio and biphenyl group play an important role in elevating the antibacterial activity. To characterize the antibacterial mechanism, we combined scanning electron microscopy, propidium iodide dyeing, and DNA leakage assays. The results demonstrated that Ru2 could destroy the integrity of bacterial cell membranes. In addition, Ru2 can efficiently inhibit biofilm formation and α-hemolysin secretion from Staphylococcus aureus. Finally, in both a mouse skin infection model and a G. mellonella wax worm infection model, Ru2 showed significant antibacterial activity in vivo. Moreover, the Ru2 complex was almost non-toxic. Thus, this work demonstrated that ruthenium-based complexes bearing a biphenyl group are promising agents to combat bacterial infection.
Asunto(s)
Daptomicina , Staphylococcus aureus Resistente a Meticilina , Rutenio , Infecciones Estafilocócicas , Animales , Antibacterianos/metabolismo , Antibacterianos/farmacología , Compuestos de Bifenilo , Daptomicina/metabolismo , Daptomicina/farmacología , Proteínas Hemolisinas/metabolismo , Linezolid/metabolismo , Ratones , Pruebas de Sensibilidad Microbiana , Propidio/metabolismo , Rutenio/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , Vancomicina/metabolismo , Vancomicina/farmacologíaRESUMEN
Four new ruthenium polypyridyl complexes, [Ru(bpy)2(BPIP)](PF6)2 (Ru(II)-1), [Ru(dtb)2(BPIP)](PF6)2 (Ru(II)-2), [Ru(dmb)2(BPIP)](PF6)2 (Ru(II)-3) and [Ru(dmob)2(BPIP)](PF6)2 (Ru(II)-4) (bpy = 2,2'-bipyridine, dtb = 4,4'-di-tert-butyl-2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dmob = 4,4'-dimethoxy-2,2'-bipyridine and BPIP = 2-(3,5-bis(benzyloxyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) had been synthesized and characterized. Their antimicrobial activities were investigated against Staphylococcus aureus (S. aureus) and four complexes showed obvious antibacterial effect, especially the minimum inhibition concentration (MIC) value of Ru(II)-3 was only 4 µg/mL. In addition, Ru(II)-3 was able to kill bacteria quickly and inhibit the formation of biofilm. Meanwhile, the cooperative effect between Ru(II)-3 and general antibiotics were tested and the results showed that Ru(II)-3 could enhance the susceptibility of S. aureus to different types of antibiotics. Most importantly, Ru(II)-3 hardly showed cytotoxicity to mammalian erythrocytes both in homelysis experiment and G. mellonella model. After being injected with high doses of the Ru(II)-3in vivo, the G. mellonella worms still exhibited high survival rates. Finally, a mouse skin infection model and G. mellonella infection model was built to determine the antibacterial activity of Ru(II)-3in vivo. The antibacterial mechanism of Ru(II)-3 was probably related to the membrane-disruption. Taken together, ruthenium polypyridine complexes with benzyloxyl groups had the potential to develop an attractive and untraditional antibacterial agent with new mode of action.
Asunto(s)
Complejos de Coordinación , Rutenio , 2,2'-Dipiridil/farmacología , Animales , Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Mamíferos , Ratones , Fenantrolinas/farmacología , Rutenio/farmacología , Staphylococcus aureusRESUMEN
Developing a new and efficient catalytic route for the production of alkanes by upgrading the aqueous phenolic biofuels still remains a challenge. Here, we designed and synthesized a bifunctional catalyst that uses natural montmorillonite (MMT) as support and combines metal active sites and BrÓ§nsted acid sites in the MMT via ion exchange and reduction roasting process. The catalytic activity of the as-synthesized Pd-MMT (H+) was evaluated by the hydrodeoxygenation (HDO) of a series of lignin-derived phenolic compounds in water. Our model reaction study reveals that the HDO of phenol undergoes an initial hydrogenation of aromatic rings to produce cyclohexanol and cyclohexanone, followed by the dehydration of cyclohexanol to provide intermediate cyclohexene and a final hydrogenation of cyclohexene to create a cyclohexane product. The combination of high metal catalytic activity and BrÓ§nsted acidity in Pd-MMT (H+) synergistically accelerated the HDO of phenol. Furthermore, good catalytic activity and recycling ability were also observed for other lignin-derived phenolic compounds.
RESUMEN
Background: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods: A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results: To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients. Conclusions: Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.
Asunto(s)
Neoplasias Laríngeas , Receptor Notch1 , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Humanos , Inmunidad/genética , Neoplasias Laríngeas/complicaciones , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/cirugía , Mutación , Recurrencia Local de Neoplasia/patología , Receptor Notch1/genética , Receptor Notch1/inmunologíaRESUMEN
The secondary C(OH)-C bonds are abundant in biomass such as lignin and cellulose. Thus, selective cleavage of the C(OH)-C bonds into value chemicals attracted much attention. Molecular iodine has received considerable attention as an inexpensive and readily available catalyst to yield the corresponding products in excellent yields with high selectivity, but it is highly corrosive and toxic, making its use somewhat unattractive. In this study, I2 was generated in situ from Fe(NO3)3.9H2O/NaI, which was further combined with Fe(NO3)3.9H2O to catalyze the oxidation process. In the reaction, the H2O molecule from the reaction and Fe(NO3)3.9H2O attacked the phenylglyoxal to form benzaldehyde, which was further oxidized to benzoic acid. Aryl primary and secondary benzylic alcohols from lignin were successfully transformed into aryl carboxylic acids by Fe(NO3)3.9H2O/NaI/DMSO. The catalytic system was green and efficient, avoiding the usage of toxic and corrosive molecular I2. From the experiments, it was clear that the yield of the product from the substrates with an electron-donating group was higher than that of electron-withdrawing substituted substrates, which was similar to the aryl secondary alcohols. Aryl alkyl ketones were also successfully conducted by the Fe(NO3)3.9H2O/NaI/DMSO catalytic system.
RESUMEN
This article analyzes the relationship between cell division cycle (CDC20) molecules and oncology outcomes in patients with renal clear cell carcinoma (KIRC). CDC20 appears to act as a regulatory protein interacting with many other proteins at multiple points in the cycle. The RNA sequencing data and corresponding clinical information of CDC20 molecules were obtained from The Cancer Genome Atlas (TCGA) database. The expression of CDC20 in kidney renal clear cell carcinoma tissue and adjacent normal tissue was detected by immunohistochemical methods. Logistic analysis was performed to analyze the role of CDC20 in the clinicopathological characteristics and prognosis of KIRC. Gene Set Enrichment Analysis (GSEA) was used to identify the signal pathways which were related to CDC20. Independent prognostic factors were evaluated using univariate and multivariate Cox regression analysis. A nomogram involved in CDC20 expression and clinicopathological variables was conducted to predict overall survival (OS) in KIRC patients at 1, 3, and 5 years. Furthermore, the relation between CDC20 and immunity was also studied. Our results showed that CDC20 was upregulated in kidney renal clear cell carcinoma tissues, accompanying shorter OS (all P < 0.05). According to the results obtained by immunohistochemistry and TCGA database, CDC20 was significantly upregulated in kidney renal clear cell carcinoma tissues compared with neighboring normal kidney tissues. Univariate and multivariate Cox regression analysis showed that high expression of CDC20 was an independent prognostic factor of poor prognosis in kidney renal clear cell carcinoma patients (all P < 0.05). GSEA analysis suggested that the high expression of CDC20 was related to eight multiple signaling pathways. In addition, CDC20 was linked to tumour mutation burden (TMB), immune checkpoint molecules, tumour microenvironment, and immunological infiltration.