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The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.
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Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Neuroblastoma , RNA Longo não Codificante , Humanos , DNA/genética , Reparo do DNA por Junção de Extremidades/genética , Reparo do DNA/genética , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , RNA Longo não Codificante/genéticaRESUMO
Robust, ultrathin, and environmental-friendliness papers that synergize high-efficiency electromagnetic interference (EMI) shielding, personal thermal management, and wearable heaters are essential for next-generation smart wearable devices. Herein, MXene nanocomposite paper with a nacre-like structure for EMI shielding and electrothermal/photothermal conversion is fabricated by vacuum filtration of Ti3 C2 Tx MXene and modified sawdust. The hydrogen bonding and highly oriented structure enhance the mechanical properties of the modified sawdust/MXene composite paper (SM paper). The SM paper with 50 wt% MXene content shows a strength of 23 MPa and a toughness of 13 MJ·M-3 . The conductivity of the SM paper is 10 195 S·m-1 , resulting in an EMI shielding effectiveness (SE) of 67.9 dB and a specific SE value (SSE/t) of 8486 dB·cm2 ·g-1 . In addition, the SM paper exhibits excellent thermal management performance including high light/electro-to-thermal conversion, rapid Joule heating and photothermal response, and sufficient heating stability. Notably, the SM paper exhibits low infrared emissivity and distinguished infrared stealth performance, camouflaging a high-temperature heater surface of 147-81 °C. The SM-based e-skin achieves visualization of Joule heating and realizes human motions monitoring. This work presents a new strategy for designing MXene-based wearable devices with great EMI shielding, artificial intelligence, and thermal management applications.
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BACKGROUND: Norovirus (NoV) GII.4 is the most common genotype for norovirus gastroenteritis worldwide. New variants or subgenotypes are continuously emerging, thus posing a serious threat to child health. METHODS: We compared retrospectively the clinical manifestations and complications of norovirus gastroenteritis in children from April, 2004 through December, 2012. NoV variants were analyzed to investigate the association of circulating viral strains with the complications. A modified disease severity score system based on Vesikari score system was devised and to evaluate disease severity. RESULTS: Compared to the outbreak in 2004/2005 winter, significant higher incidence of complications in the later periods are: convulsive disorder (p < 0.001) in 2006/2007 winter gastrointestinal hemorrhage (p = 0.047) and severe abdominal pain or irritability (p = 0.033) in 2008/09/10 winter; gastrointestinal hemorrhage (p = 0.030), severe abdominal pain or irritability (p = 0.014), and prominent hyperthermia (fever >39 °C, p = 0.001) in 2011/2012 winter. GII.4 Den_Haag_2006b, GII.4 2010, GII.4 Sydney 2012, and GII.4 2012b were the predominant strains in the outbreaks after 2006. By the modified severity score system, severe norovirus disease occurred in 28.5 %, 32 %, 33.3 %, and 30.2 % of the patients in the four periods. A longer duration of hospitalization (p = 0.02) were found in those with high score irrespective of the year of admission. CONCLUSIONS: Our study demonstrated NoV outbreaks in northern Taiwan caused by different GII.4 variants that were associated with specific complications and uncommon clinical presentations. A modified severity score system first proposed in this study was able to identify severe cases with a longer hospital stay in NoV-infected children.
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Infecções por Caliciviridae/complicações , Infecções por Caliciviridae/diagnóstico , Gastroenterite/complicações , Gastroenterite/diagnóstico , Norovirus , Índice de Gravidade de Doença , Doença Aguda , Adolescente , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Criança , Pré-Escolar , Surtos de Doenças , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Norovirus/genética , Estudos Retrospectivos , Taiwan/epidemiologia , Adulto JovemRESUMO
With the continuous advancement of communication technology, the escalating demand for electromagnetic shielding interference (EMI) materials with multifunctional and wideband EMI performance has become urgent. Controlling the electrical and magnetic components and designing the EMI material structure have attracted extensive interest, but remain a huge challenge. Herein, we reported the alternating electromagnetic structure composite films composed of hollow metal-organic frameworks/layered MXene/nanocellulose (HMN) by alternating vacuum-assisted filtration process. The HMN composite films exhibit excellent EMI shielding effectiveness performance in the GHz frequency (66.8 dB at Ka-band) and THz frequency (114.6 dB at 0.1-4.0 THz). Besides, the HMN composite films also exhibit a high reflection loss of 39.7 dB at 0.7 THz with an effective absorption bandwidth up to 2.1 THz. Moreover, HMN composite films show remarkable photothermal conversion performance, which can reach 104.6 °C under 2.0 Sun and 235.4 °C under 0.8 W cm-2, respectively. The unique micro- and macro-structural design structures will absorb more incident electromagnetic waves via interfacial polarization/multiple scattering and produce more heat energy via the local surface plasmon resonance effect. These features make the HMN composite film a promising candidate for advanced EMI devices for future 6G communication and the protection of electronic equipment in cold environments.
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With the rapid development of wearable devices and integrated systems, protection against electromagnetic waves is an issue. For solving the problems of poor flexibility and a tendency to corrode traditional electromagnetic interference (EMI) shielding materials, two-dimensional (2D) nanomaterial MXene was employed to manufacture next-generation EMI shielding materials. Vacuum-assisted filtration combined with the liquid nitrogen prefreezing strategy was adopted to prepare flexible MXene/cellulose nanofibers (CNFs) composite aerogel film with unique cellular structure. Here, CNFs were employed as the reinforcement, and such a cellular structure design can effectively improve the shielding effectiveness (SE). In particular, the composite shows an outstanding EMI SE of 54 dB. Furthermore, the MXene/CNFs composite aerogel film exhibited prominent and steady photothermal conversion ability, which could obtain the maximum equilibrium temperature of 89.4 °C under an 808 nm NIR laser. Thus, our flexible composite aerogel film with appealing cellular construction holds great promise for wearable EMI shielding materials and heating applications in a cold and complex practical environment.
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The remediation of heavy crude oil spills is a global challenge because frequent crude oil spills cause long-term damage to local living beings and marine ecosystems. Herein, a solar-driven and Joule-driven self-heated aerogel were developed as an all-weather adsorbent to efficiently absorb crude oil by obviously decreasing the viscosity of crude oil. The cellulose nanofiber (CNF)/MXene/luffa (CML) aerogel was fabricated via a simple freeze-drying method using CNF, MXene, and luffa as raw materials, and then coated with a layer of polydimethylsiloxane (PDMS) to make it hydrophobic and further increase oil-water selectivity. The aerogel can quickly reach 98 °C under 1 sun (1.0 kW/m2), which remains saturated temperature after 5 times photothermal heating/cooling cycles, indicating that the aerogel has great photothermal conversation capability and stability. Meanwhile, the aerogel can also rapidly rise to 110.8 °C with a voltage of 12 V. More importantly, the aerogel achieved the highest temperature of 87.2 °C under outdoor natural sunlight, providing a possibility for promising applications in practical situations. The remarkable heating capability enables the aerogel to decrease the viscosity of crude oil substantially and increase the absorption rate of crude oil by the physical capillary action. The proposed all-weather aerogel design provides a sustainable and promising solution for cleaning up crude oil spills.
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Luffa , Nanofibras , Petróleo , Nanofibras/química , Celulose/química , Ecossistema , Tempo (Meteorologia)RESUMO
Interfacial solar steam generation (ISSG) is considered to be an attractive technique to address the water shortage. However, developing a sustainable thermal management, salt rejection, and excellent mechanical strength ISSG device for long-term stability desalination is still a challenge. Herein, a biomass ISSG device with superb mechanical properties was prepared by introducing a luffa sponge as the skeleton and constructing the MXene/cellulose nanofibers (CNFs) aerogels via freeze-drying. The Janus MXene-decorated CNFs/luffa (JMCL) aerogels integrated the multifunction of fast water transport, good thermal management, and efficient photothermal conversion in a single module, to achieve high-efficiency desalination. 3D Janus structure endowed the JMCL aerogel with opposite wettability, which is feasible to construct the localized photothermal generation and self-floating. The mechanical strength of JMCL aerogels is 437 times that of MXene/CNFs aerogels. The JMCL aerogels delivered a water evaporation rate of 1.40 kg m-2h-1 and an efficiency of 91.20% under 1 sun illumination. The excellent salt resistance during 24 h working and long-term solar vapor generation of up to 28 days were achieved. The multifunctional JMCL aerogels with 3D Janus structure offer new insights for developing good durability and eco-friendly biopolymer-based steam generators.
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OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.
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Linfoma não Hodgkin , Humanos , Incidência , Ásia Meridional , Linfoma não Hodgkin/epidemiologiaRESUMO
Remediation of crude oil spills is a great challenge owing to the poor mobility and high viscosity of crude oil. Herein, a porous polydimethylsiloxane@wood sponge/MXene (PDMS@WSM) with outstanding compressibility and hydrophobic/lipophilic ability was demonstrated as crude oil absorbent. The surface temperature of PDMS@WSM could quickly rise to 80 °C with a working voltage of 4 V and to 66 °C under simulated sunlight irradiation of 1.5 KW m-2, respectively. Due to the excellent Joule heating and photothermal conversion effect, the PDMS@WSM displayed maximum adsorption capacity of 11.2×105 g m-3 within 6 min. The PDMS@WSM showed preferable reusability and cycle stability because of its brilliant compressibility. Moreover, the oil-collecting device based on PDMS@WSM could continuously collect crude oil spills, achieving an active collection of 25 mL crude oil within 150 s. Therefore, the porous PDMS@WSM absorbent exhibited great potential for crude oil spills remediation, energy regulation, and desalination of hypersaline water.
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Poluição por Petróleo , Petróleo , Calefação , Poluição por Petróleo/análise , Titânio , MadeiraRESUMO
The photothermal materials have a broad range of applications in crude oil spills treatment, desalination, and photothermal therapy. However, the rational construction of aerogels with exceptional photothermal performance is highly desired yet still challenging. Herein, a class of stable aerogels comprised of molybdenum disulfide (MoS2) nanoflowers and cellulose nanofibers (CNFs) was fabricated, affording extraordinary light-to-heat energy conversion capability. Benefiting from the intercalated porous structure, the resultant cellulose nanofibers/molybdenum disulfide (CNF/MoS2) aerogels deliver an ultrahigh temperature output up to 260.4 °C with near infrared (NIR) laser power densities of 0.8 W cm-2. Remarkably, when NIR laser power density increased to 1.0 W cm-2, the aerogels began to burn, achieving the superhigh surface temperature of â¼ 690 °C. The combustion process of CNF/MoS2 composite aerogels was evaluated in detail. Therefore, this work provides experiment evidence and theoretical basis for the rational applications of photothermal materials at high temperature in future.
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Molibdênio , Nanofibras , Celulose/química , Dissulfetos/química , Molibdênio/química , Nanofibras/químicaRESUMO
Zeolitic imidazolate frameworks (ZIFs) have been considered as advanced adsorption materials to alleviate dye pollution. However, the application range is limited due to the powder characteristics of ZIFs. The conjugation of ZIFs with nanocellulose is an attractive strategy to construct profitable materials. Herein, we report an in situ anchoring method for preparing novel ZIFs@carboxymethylated bacterial cellulose (ZCMBC) composite films. The resulting ZCMBC composite films show a high ZIFs loading rate and satisfactory selective indigo carmine removal efficiency. With simple methanol washing, ZCMBC composite films retain a high removal efficiency after regeneration. In addition, ZCMBC composite films also show excellent mechanical properties. The proposed adsorption mechanism and the universality of this in situ anchoring method are also discussed, indicating their application potential in the dye-contaminated wastewater treatment field.
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Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.
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Processamento Alternativo/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Células A549 , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromossomos Humanos Par 3/genética , Variações do Número de Cópias de DNA/genética , Fator de Transcrição E2F1/metabolismo , Células HCT116 , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Humanos , Células MCF-7 , Neoplasias/patologia , Correpressor 2 de Receptor Nuclear/genética , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
OBJECTIVE: To investigate the association of TGF beta1 and AT1R gene polymorphisms with hereditary susceptibility and clinical phenotype of HBV-induced liver cirrhosis. METHODS: Peripheral blood samples were collected from 102 patients with HBV-induced liver cirrhosis and 106 healthy blood donors. The polymorphisms of the promoter site -509C/T of TGF beta1 and 1166A/C of AT1R gene were determined by PCR-RFLP. RESULTS: The frequency of the homozygote CC of -509C/T of TGF beta1 gene in the group of liver cirrhosis was higher than that the control group (P<0.05); and the frequency rate of homozygote CC was higher in group C than in group A and group B of liver cirrhosis (P<0.05), but there was no significant difference in allele frequency among these group (P>0.05). There was no significant difference in genotypes and allele frequency of AT1R gene 1166A/C between the liver cirrhosis group and the control group (P>0.05). CONCLUSION: The polymorphism of the promoter site -509C/T of TGF beta1 gene is associated with hereditary susceptibility to liver cirrhosis and severity of HBV-induced liver cirrhosis; the polymorphism of AT1R gene 1166A/C is not associated with hereditary susceptibility to HBV-induced liver cirrhosis.
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Predisposição Genética para Doença , Hepatite B/complicações , Cirrose Hepática/genética , Fenótipo , Polimorfismo Genético , Receptor Tipo 1 de Angiotensina/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Hepatite B/genética , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the relationship between interleukin 10 (IL10) gene -627 polymorphisms and serum IL10 level and early-onset coronary heart disease (CHD). METHODS: The genotype and allele frequency of IL10 gene -627 site was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). DNA samples were obtained from 163 patients with CHD and 112 controls. Serum IL10 level was detected by ELISA. RESULTS: No significant difference was found in the distribution of IL10 genotype and allele frequency between the healthy controls and the patients with CHD; Chi-square values were 1.9324 and 1.5703 respectively, P > 0.05. Stratification analyses based on different sex still found no significant difference in the distribution of IL10 genotype and allele frequency between the healthy controls and the CHD patients; the Chi-square values in male groups were 1.2708 versus 0.8595, and in female groups were 0.8254 versus 0.7127, P > 0.05. Serum IL10 level showed significant differences among AA genotype, AC genotype and CC genotype, but no significant difference was noted between healthy controls and CHD patients. CONCLUSION: These results suggest that IL10 gene -627 polymorphisms are not associated with an increased risk of CHD, but it might assume a role in IL10 gene expression.
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Doença das Coronárias/genética , Interleucina-10/genética , Polimorfismo Genético , Adulto , Idade de Início , Povo Asiático/genética , Distribuição de Qui-Quadrado , China/epidemiologia , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
The work is to explore the relationship between the polymorphism of angiotensin converting enzyme (ACE) gene and hypertensive kidney lesion/PAI-1 in hypertension patients. ACE genotyping with polymorase chain reaction (PCR) was performed in 96 unrelated healthy controls, 67 hypertensives without kidney lesion and 70 hypertensives complicated with kidney lesion. The plasma PAI-1 were determined with ELISA. No significant differences could be detected between ACE gene I/D polymorphism and hypertension. However, the frequencies of DD genotype and deletion allele among the hypertensives complicated with kidney lesion were higher than those among the healthy controls and those among the hypertensives without kidney lesion."chi2" values were 6.8589,5.6162 and 5.9085,5.372 respectively. The plasma PAI-1 level showed significant differences among DD genotype,ID genotype and II genotype(P<0.05). The DD genotype of ACE gene may be a risk for hypertensive kidney lesion. The plasma PAI-1 level is associated with ACE gene polymorphism.
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BACKGROUND & OBJECTIVE: The chronic infection of hepatitis B virus (HBV) is a recognized risk factor for the development of hepatocellular carcinoma (HCC); however, the precise mechanism of carcinogenesis is unknown. In order to better understand the molecular mechanism of hepatocarcinogenesis, this study was designed to investigate the relationship between the gene mutation on precore region of integrated HBV DNA, the mutation of p53 gene and the development of HCC. METHODS: The integrated HBV DNA, gene mutation on precore region of HBV DNA and p53 gene mutation were detected in 80 specimens of HCC, paratumor cirrhosis, liver cirrhosis, and normal liver tissue using polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) technique. RESULTS: (1) The positive rates of integrated HBV DNA in HCC tissues, paratumor cirrhosis tissues, cirrhotic liver tissues, and normal liver tissues were 96.43%, 96.43%, 66.67%, and 6.66%, respectively. There were significant differences of the positive rates between normal liver tissues group and each of the other three groups (P< 0.005). (2) The gene mutation rates on precore region of HBV DNA in the four groups were 70.37%, 48.15%, 25.00%, and 0%, respectively. There were significant differences of the gene mutation rates among the four groups (P< 0.05). (3) The mutation rate (57.14%)of p53 gene in HCC was significantly higher than that in liver cirrhosis (16.67%) (P< 0.05). (4) The p53 gene mutation was positively associated with positivity of integrated HBV DNA and mutation on precore region of integrated HBV DNA in different liver tissues. CONCLUSION: The HBV DNA integration and its gene mutation on precore region and p53 gene mutation probably play synergic roles in the development of HCC.