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1.
Transl Androl Urol ; 10(10): 3815-3825, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804824

RESUMO

Background: The diagnostic methods of prostate cancer (PCa) present major drawbacks in that serum prostate specific antigen (PSA) testing lacks specificity for PCa and prostate needle biopsy is a painful and highly invasive procedure for patients. Thus, new alternative screening methods which are specific and non-invasive both in the early detection and in the clinical definitive diagnosis of PCa are in urgent need. Long non-coding RNA MYU has been shown to promote PCa cell proliferation and migration, and is significantly upregulated both at the cellular and tumor tissue level. Therefore, long non-coding RNA MYU may be a new potential diagnostic biomarker for PCa. Methods: In the present study, we successfully developed a highly sensitive digital PCR assay to detect long non-coding RNA in clinical urine samples. dPCR was carried out using Qx200 ddPCR EvaGreen Supermix (Bio-Rad) according to the manufacturer's instructions. Results: Our results indicated that the digital PCR assay showed better linearity, repeatability, and reproducibility when compared with real-time quantitative PCR. In addition, we identified the normalized MYU level and used the digital PCR assay to measure it in 100 clinical urine samples. Our study showed that the normalized MYU level is a promising diagnostic biomarker for predicting and evaluating the malignancy of PCa. Conclusions: Our findings presented a non-invasive liquid biopsy method to detect an alternative diagnostic parameter which can assist the diagnosis of PCa in clinical practice.

2.
Cancers (Basel) ; 13(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34831013

RESUMO

Intraocular surgery is tabooed in retinoblastoma management, due to the concern of lethal extraocular spread. We reviewed the outcomes of consecutive children with intraocular retinoblastoma diagnosed at 29 Chinese centers between 2012-2014. We compared the outcomes of three categories of treatment: eye salvage including tylectomy (Group I), eye salvage without tylectomy (Group II), and primary enucleation (Group III). A total of 960 patients (1243 eyes) were diagnosed: 256 in Group I, 370 in Group II, and 293 in Group III; 41 patients abandoned treatment upfront. The estimated 5-year overall survivals (OS) were, for Group I, 94%, for Group II 89%, and for Group III 95%. The estimated 5-year disease-specific survivals (DSS) were, for Group I, 96%, for Group II 90%, and for Group III 95%. Patients in Group I had a significantly higher 5-year DSS than patients in Group II (p = 0.003) and not significantly different than patients in Group III (p = 0.367). Overall survival was not compromised by the inclusion of tylectomy in eye salvage therapy compared to eye salvage without tylectomy or primary enucleation. Disease-specific survival was better when tylectomy was included in eye salvage treatments. Tylectomy as part of multimodal treatment may contribute to the care of retinoblastoma patients with chemotherapy-resistant tumor, eyes with concomitant ocular complications, or at the risk of treatment abandonment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34831695

RESUMO

The fatigue of air traffic controllers (ATCOs) on duty seriously threatens air traffic safety and needs to be managed. ATCOs perform several different types of work, with each type of work having different characteristics. Nonetheless, the influence of work type on an ATCO's fatigue has yet to be demonstrated. Here, we present a field study in which the fatigue of ATCOs working in two types of work was compared based on an optimized data-driven method that was employed to detect the percentage of eyelid closure over the pupil over time (PERCLOS). Sixty-seven ATCOs working within two typical jobs (i.e., from the terminal control unit (TCU) and area control unit (ACU)) were recruited, and their fatigue was detected immediately before and after shift work using PERCLOS. Using a Spearman correlation test analysis, the results showed that the influence of work type on an ATCO's fatigue had interesting trends. Specifically, the ATCOs at the TCU who handle departures and arrivals, which include converging with and maneuvering around conflicts, retain normal circadian rhythms. Their fatigue was significantly influenced by the various demands from tasks focusing on sequencing and conflict resolution and by the time phase of a normal circadian rhythm. At the ACU, ATCOs manage flights that are mainly on route, causing monotonous monitoring and routine reporting tasks, and the ATCOs generally have frequent night shifts to handle overflights. Their fatigue was significantly influenced by the demand characteristics from tasks, but changes in fatigue rule were not consistent with a normal circadian rhythm, revealing that the ATCOs' circadian rhythms may have already been slightly disturbed. Furthermore, the interactions between task demand and circadian rhythm with an ATCO's fatigue were significantly observed in ATCOs working in the TCU but not in those in the ACU. This study provides first evidence that an ATCO's work type influences his or her fatigue. This discovery may incite stakeholders to consider work type in the management of employee fatigue, not only in the civil aviation industry but also in other transport industries.

5.
Biomed Res Int ; 2021: 5565549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34664026

RESUMO

Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus causing substantial morbidity and mortality worldwide. We performed a cross-sectional investigation of SARS-CoV-2 clusters in Suzhou to determine the transmissibility of the virus among close contacts and to assess the demographic and clinical characteristics between index and secondary cases. Methods: We review the clustered patients with SARS-CoV-2 infections in Suzhou between 22 January and 29 February 2020. The demographic and clinical characteristics were compared between index and secondary cases. We calculated the basic reproduction number (R 0) among close contacts with SLI model. Results: By 22 February, 87 patients with SARS-CoV-2 infection were reported, including 50 sporadic and 37 clustered cases, who were generated from 13 clusters. On admission, 5 (20.8%) out of 24 secondary cases were asymptomatic. The male ratio of index cases was significantly higher than that of secondary cases. Additionally, the index cases were more likely to have fever and increased CRP levels than the secondary cases. The R 0 values of clusters displayed a significantly declining trend over time for all clusters. The relative risk of infection in blood-related contacts of cases versus unrelated contacts was 1.60 for SARS-CoV-2 (95% CI: 0.42-2.95). Conclusions: In conclusion, SARS-CoV-2 has great person-to-person transmission capability among close contacts. The secondary cases are more prone to have mild symptoms than index cases. There is no increased RR of secondary infection in blood relatives versus unrelated contacts. The high rate of asymptomatic SARS-CoV-2 infections highlights the urgent need to enhance active case finding strategy for early detection of infectious patients.


Assuntos
COVID-19/epidemiologia , Busca de Comunicante , Características da Família , SARS-CoV-2 , Adulto , COVID-19/transmissão , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
6.
Front Oncol ; 11: 705905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604041

RESUMO

Background and Purpose: This study aimed to quantify the differences between pre- and post-contrast agent (CA) CT for CyberKnife brain SRS plans. Materials and Methods: Twenty-five patients were retrospectively analyzed. They were divided into two categories, inhomogeneous cases (13 patients) and homogeneous cases (12 patients), according to whether the tumor was close to the cavity and inhomogeneous tissues or not. The pre-CA and post-CA plans were designed and calculated using the same monitor unit and paths as those in the ray-tracing algorithm, respectively. Results: The CT number difference of tumor between pre- and post-CA was significant (on average, 24.78 ± 18.56 HU, P-value < 0.01). The deviation value of the target was the largest at approximately 37 HU (inhomo-) and 13 HU (homo-) (P < 0.01), and the values of the organs at risk (OARs) were not statistically significant (P-value > 0.05). However, it was not statistically significant for the dose difference between the two groups with the injection of CA (P-value > 0.05). The absolute effective depth difference generally remained at a level of 1 mm, but the dose difference was quitely fluctuated sometimes more than 20%. The absolute effective depth difference of the inhomo-case (0.62 mm) was larger than that of the homo-case (0.37 mm) on median, as well as the variation amplitude (P-value < 0.05). Moreover, the relative dose differences between the two cases were 0.38% (inhomo-) and 0.2% (homo-), respectively (P-value < 0.05). At the criterion of 1 mm/1%, the gamma pass rate of the homo-case (95.89%) was larger than that of the inhomo-case (93.79%). For the OARs, except for the cochlea, the two cases were almost the same (>98.85%). The tumor control probability of the target was over 99.99% before and after injection of a CA, as well as the results for the homo-case and inhomo-case. Conclusions: Considering the difference of evaluation indexes between pre- and post-CA images, we recommended plain CT to be employed as the primary image for improving the CK treatment accuracy of brain SRS, especially when the target was close to CA-sensitive OARs and cavity.

8.
Adv Sci (Weinh) ; 8(22): e2102845, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34633769

RESUMO

The electron transport layer (ETL) is a key component of regular perovskite solar cells to promote the overall charge extraction efficiency and tune the crystallinity of the perovskite layer for better device performance. The authors present a novel protocol of ETL engineering by incorporating a composition of the perovskite precursor, methylammonium chloride (MACl), or formamidine chloride (FACl), into SnO2 layers, which are then converted into the crystal nuclei of perovskites by reaction with PbI2 . The SnO2 -embedded nuclei remarkably improve the morphology and crystallinity of the optically active perovskite layers. The improved ETL-to-perovskite electrical contact and dense packing of large-grained perovskites enhance the carrier mobility and suppress charge recombination. The power conversion efficiency increases from 20.12% (blank device) to 21.87% (21.72%) for devices with MACl (FACl) as an ETL dopant. Moreover, all the precursor-engineered cells exhibit a record-high fill factor (82%).

9.
PLoS One ; 16(10): e0258336, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34637475

RESUMO

Decontaminating N95 respirators for reuse could mitigate shortages during the COVID-19 pandemic. Although the United States Center for Disease Control has identified Ultraviolet-C irradiation as one of the most promising methods for N95 decontamination, very few studies have evaluated the efficacy of Ultraviolet-C for SARS-CoV-2 inactivation. In addition, most decontamination studies are performed using mask coupons that do not recapitulate the complexity of whole masks. We sought to directly evaluate the efficacy of Ultraviolet-C mediated inactivation of SARS-CoV-2 on N95 respirators. To that end we created a portable UV-C light-emitting diode disinfection chamber and tested decontamination of SARS-CoV-2 at different sites on two models of N95 respirator. We found that decontamination efficacy depends on mask model, material and location of the contamination on the mask. Our results emphasize the need for caution when interpreting efficacy data of UV-C decontamination methods.


Assuntos
Descontaminação , Desinfecção , Máscaras , Respiradores N95 , Raios Ultravioleta , Descontaminação/instrumentação , Descontaminação/métodos , Desinfecção/instrumentação , Desinfecção/métodos , Reutilização de Equipamento
10.
Pharmgenomics Pers Med ; 14: 1141-1150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552348

RESUMO

Background: Valproic acid (VPA) is recommended as a first-line treatment for children with epilepsy. GABRG2 polymorphism is found to be associated with epilepsy susceptibility and therapeutic response of anti-seizure medications (ASM); however, the role of GABRG2 in VPA treatment still remains unknown. Objective: The purpose of this study was to explore the association of GABRG2 gene polymorphism with the drug response and adverse drug reactions (ADRs) related to VPA. Methods: A retrospective study including 96 Chinese children with epilepsy treated by VPA was carried out. The ADRs were collected during VPA therapy and GABRG2 rs211037 in enrolled patients was genotyped using Sequenom MassArray system. A network pharmacological analysis involved protein-protein interaction and enrichment analysis was constructed to investigate the potential targets and pathways of GABRG2 on VPA-related ADRs. Results: Among 96 patients, 41 individuals were defined as seizure together with 49 patients with seizure-free and 6 patients unclassified. Carriers of homozygote GABRG2 rs211037 CC genotype exhibited seizure-free to VPA (P = 0.042), whereas those with CT genotype showed seizure. Furthermore, CC genotype had predisposition to digestive ADRs (P = 0.037) but was a protective factor for VPA-associated weight gain (P = 0.013). Ten key genes related to digestive ADRs and weight gain induced by VPA were identified by network pharmacological analysis and mainly involved in "GABAergic synaptic signaling", "GABA receptor signaling", and "taste transduction" pathways/processes through enrichment analysis. Conclusion: This study revealed that GABRG2 variation exerted a predictable role in the efficacy and safety of VPA treatment for Chinese children with epilepsy.

11.
Plant Sci ; 311: 111014, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34482917

RESUMO

Flax (Linum usitatissimum) seed oil is rich in polyunsaturated fatty acids (PUFAs), particularly linolenic acid, which is converted from linoleic acid. Studies have indicated that the biosynthesis of linoleic acid and linolenic acid is controlled by FAD2 and FAD3, respectively. However, the functional distinctions of different LuFAD2 and LuFAD3 copies from L. usitatissimum in governing the biosynthesis of linoleic acid or linolenic acid, respectively, remain unclear. In this study, five LuFAD2 and three LuFAD3 cDNAs were cloned from the L. usitatissimum cultivar 'Longya 10', and GC-MS results demonstrated that LuFAD2A and LuFAD3A play predominant roles in the accumulation of linoleic acid and linolenic acid, respectively. Their simultaneous overexpression in Arabidopsis thaliana seeds led to a significant increase in fatty acid contents, especially PUFAs. Additionally, LuFAD2A and LuFAD3A promoted the biosynthesis of jasmonic acid by increasing the levels of linolenic acid, which, in turn, enhanced plant cold tolerance. When the amount of linolenic acid is not sufficient, plants adapt to low temperature via the accumulation of anthocyanins. These findings provide insights into the higher accumulation of PUFAs in L. usitatissimum seeds, and provide potential targets for improving oil quality of other oil-producing crops through molecular manipulation.


Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Temperatura Baixa , Ácidos Graxos/biossíntese , Linho/genética , Plântula/metabolismo , Sementes/metabolismo , Arabidopsis/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Ácidos Graxos/genética , Linho/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Plantas Geneticamente Modificadas/metabolismo , Análise de Sequência de Proteína
12.
Environ Sci Technol ; 55(17): 11970-11978, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488354

RESUMO

Reducing the poisoning effect arising from alkali metals over catalysts for selective catalytic reduction (SCR) of NOx by NH3 is still an urgent issue to be solved. Herein, alkali-resistant NOx reduction over B-doped CeO2/TiO2 catalysts (Ce-B/TiO2) with Ce-O-B alkali-capture sites was originally demonstrated. It was noted that boron was confirmed to be doped into the lattice of CeO2 to form the Ce-O-B structure. In this way, more active Ce(III) species and oxygen vacancies were generated from B-doped CeO2, thus accelerating the redox cycle and enhancing the adsorption/activation of NO. Gratifyingly, the created Ce-O-B sites as alkali-capture sites could be effectively combined with K and release the poisoned Ce active sites, which maintained efficient NH3 and NO adsorption/activation over K poisoned Ce-B/TiO2. This work paves a way for designing highly efficient and alkali-resistant SCR catalysts in both academic and industrial fields.


Assuntos
Álcalis , Amônia , Catálise , Oxirredução , Titânio
13.
Hum Gene Ther ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34555961

RESUMO

Hemophilia A (HA) is a monogenic disease characterized by plasma clotting factor 8 (F8) deficiency due to F8 mutation. We have been attempting to cure HA permanently using a CRISPR-Cas9 gene-editing strategy. Here, we induced targeted integration of BDDF8 (B-domain-deleted F8) gene into the albumin locus of HA mice by hydrodynamic tail vein injection of editing plasmid vectors. One week after treatment, a high F8 activity ranging from 70% to 280% of normal serum levels was observed in all treated HA mice but dropped to background levels 3-5 weeks later. We found that the humoral immune reaction targeting F8 is the predominant cause of the decreased F8 activity. We hypothesized that hydrodynamic injection-induced liver damage triggered the release of large quantities of inflammatory cytokines. However, co-injection of plasmids expressing a dozen immunomodulatory factors failed to curtail the immune reaction and stabilize F8 activity. The spCas9 plasmid carrying a miR-142-3p target sequence alleviated the cellular immune response but was unable to deliver therapeutic efficacy. Strikingly, immunosuppressant cyclo-phosphamide virtually abolished the immune response, leading to a year-long stable F8 level. Our findings should have important implications in developing therapies in mouse models using the hydrodynamic gene delivery approach, highlighting the ne-cessity of modulating the innate immune response triggered by liver damage.

14.
Biomed Pharmacother ; 143: 112167, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560535

RESUMO

Liquiritigenin (LQ) has protective effects against various hepatotoxicities. However, its specific role on arsenic trioxide (ATO)-induced hepatotoxicity and the related biomolecular mechanisms remain unclear. The purpose of this study is to explore the protective actions of LQ on ATO-induced hepatotoxicity and its biomolecular mechanisms in mice. LQ was administered orally at 20 and 40 mg/kg per day for seven consecutive days with an intraperitoneal injection of ATO (5 mg/kg). Liver injury was induced by ATO and was alleviated by treatment with LQ as reflected by reduced histopathological damage of liver and decreased serum ALT, AST, and ALP levels. The generation of intracellular ROS induced by ATO was attenuated after LQ treatment. The levels of SOD, CAT, and GSH were elevated with LQ administration while MDA levels decreased. LQ mitigated elevated TNF-α and IL-6 levels as well as the hepatic mitochondrial damage caused by ATO. Moreover, LQ upregulated the expression of LC3-II and enhanced autophagy in the liver of ATO-induced mice. Further studies indicated that LQ significantly suppressed the expression of p-PI3K, p-AKT, and p-mTOR in ATO-induced mice. In conclusion, our findings show that LQ protects against ATO-induced hepatotoxicity due to its antioxidant and anti-inflammatory activities and enhancement of autophagy mediated by the PI3K/AKT/mTOR signaling pathway in mice.

15.
Adv Sci (Weinh) ; 8(20): e2102500, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34473430

RESUMO

Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19 F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19 F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.

16.
J Healthc Eng ; 2021: 2917226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567480

RESUMO

To explore the application of natural convalescent factors combined with exercise intelligence management in blood pressure control of patients with hypertension, 102 patients with hypertension who were admitted from January 2017 to August 2019 were selected as the research subjects. According to the odd-even number method, they were divided into two groups with 51 cases in each group. The control group was treated with natural convalescent factor therapy alone, and the observation group was treated with natural convalescent factor combined with motor intelligence management. The application effects of the two groups were compared. Before sports intelligence management, the levels of systolic blood pressure (SBP) in control group and observation group were (145.45 ± 8.44) mmHg (1 mmHg = 0.133 kPa) and (146.55 ± 8.37) mmHg, respectively; the diastolic blood pressure (DBP) levels of the control group and the observation group were (98.47 ± 3.48) mmHg and (98.94 ± 3.48) mmHg, respectively, with no statistical significance (P > 0.05). After the exercise intelligence management, the SBP levels of the control group and the observation group were (132.76 ± 4.48) mmHg and (130.06 ± 2.48) mmHg, respectively. The DBP levels of the control group and the observation group were (85.48 ± 5.38) mmHg and (83.47 ± 3.35) mmHg, respectively. The difference was statistically significant (P < 0.05). The scores of each index of quality of life in the observation group were higher than those in the control group, and the differences of physical function and psychological/mental scores were significant. The scores of physical function in the two groups before administration were (48.36 ± 1.69) and (48.74 ± 1.62), and the differences were not statistically significant (P > 0.05). After management, the physiological function scores of the two groups were (40.32 ± 1.33) and (32.15 ± 1.54) and the difference was statistically significant (P < 0.05). There were no significant differences in the psychological (30.75 ± 1.26)/mental scores (30.26 ± 1.48) between the two groups before management (P > 0.05), but there were significant differences in the psychological (25.30 ± 1.02)/mental scores (18.76 ± 1.36) between the two groups after management (P < 0.05). The combination of natural convalescent factors and intelligent exercise management can effectively control the blood pressure level and improve the quality of life of patients with hypertension, and the clinical application effect is good.


Assuntos
Hipertensão , Qualidade de Vida , Pressão Sanguínea , Exercício Físico , Humanos , Hipertensão/tratamento farmacológico , Inteligência
17.
Front Immunol ; 12: 717785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484222

RESUMO

Background: Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis. Objective: To investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA. Methods: We profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated in vitro. Results: RP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients (P = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and in vitro overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes (HSPA1A and HSPA1B) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis (HSPA1A (P = 4.39E-08, Fold change = 4.17), HSPA1B (P = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and HNRNPH3 knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1ß, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA. Conclusion: Our results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 via binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA.

18.
Front Oncol ; 11: 626663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336642

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases globally. Despite continuous improvement of treatment methods, high postoperative recurrence rate remains an urgent problem. In order to determine the mechanism underlying recurrence of liver cancer and identify prognostic genes, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated and analyzed. Differentially expressed genes (DEGs) between HCC tissue and normal liver tissue were identified, and a protein-protein interaction network was constructed to find hub genes. Clinical correlation analysis and disease-free survival (DFS) analysis were performed using the R language and GEPIA to identify relapse-related genes. Correlation analysis was used to identify a potential regulatory axis. Dual-luciferase reporter gene assay was used to confirm the reliability of the long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory axis. Immune infiltration analysis was performed using the TIMER database. Correlations between immune gene markers and ASF1B were verified using quantitative real-time polymerase chain reaction (RT-qPCR). In this work, we found that nine lncRNAs and five mRNAs were significantly overexpressed in HCC tissues from patients with recurrence. SNHG3, LINC00205, ASF1B, AURKB, CCNB1, CDKN3, and DTL were also closely related to HCC grade and stage. Survival analysis showed that these seven DEGs were significantly correlated with poor DFS. Correlation analysis identified SNHG3-miR-214-3p-ASF1B as a potential regulatory axis. Dual-luciferase reporter gene assay showed that SNHG3 and ASF1B directly bound to miR-214-3p. ASF1B was negatively regulated by miRNA-214-3p, and overexpression of SNHG3 could inhibit the expression of miRNA-214-3p. In addition, ASF1B was positively correlated with immune infiltration. A reduction in ASF1B could markedly inhibit the expression of CD86, CD8, STAT1, STAT4, CD68, and PD1 in HCC cells. Flow cytometry showed that SNHG3 promoted the PD-1 expression by regulating ASF1B. Meanwhile, elevated ASF1B predicted poor prognosis of HCC patients in subgroups with decreased B cells, CD8+ T cells, or neutrophils, and those with enriched CD4+ T cells. In conclusion, we found that a novel lncRNA SNHG3/miR-214-3p/ASF1B axis could promote the recurrence of HCC by regulating immune infiltration.

19.
Waste Manag ; 133: 37-48, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34364151

RESUMO

This study uses the Tapio elastic decoupling analysis method and an empirical model of the environmental Kuznets curve (EKC) to analyze the decoupling between municipal solid waste (MSW) generation and economic development in 285 of China's cities from 2002 to 2017. The decoupling analysis results show that the decoupling states in China's cities generally improved first and then deteriorated in 2002-2017. The proportion of cities experiencing deterioration of decoupling states had increased to 60.00% by 2014-2017, and cities with a higher economic development level generally had more serious deterioration. The empirical test results support the N-shaped EKC hypothesis of MSW, which can explain why the decoupling state changed from improvement to deterioration. The difference of the economic level of sample cities (which determines their position on EKC) can also explain the spatial heterogeneity of the decoupling state and its changes; for example, the proportion of cities that have crossed the inflection point of Tapio decoupling elasticity (the per capita GDP is 13,130.89 yuan) to enter the deterioration stage is highest (100/101) in the economically developed eastern region, and is lowest (66/75) in the economically backward western region of China. In general, the empirical results of EKC can effectively support and explain the results of decoupling analysis.


Assuntos
Desenvolvimento Econômico , Resíduos Sólidos , China , Cidades , Resíduos Sólidos/análise
20.
Genome Biol ; 22(1): 236, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416913

RESUMO

BACKGROUND: After repairing double-strand breaks (DSBs) caused by CRISPR-Cas9 cleavage, genomic damage, such as large deletions, may have pathogenic consequences. RESULTS: We show that large deletions are ubiquitous but are dependent on editing sites and cell types. Human primary T cells display more significant deletions than hematopoietic stem and progenitor cells (HSPCs), whereas we observe low levels in induced pluripotent stem cells (iPSCs). We find that the homology-directed repair (HDR) with single-stranded oligodeoxynucleotides (ssODNs) carrying short homology reduces the deletion damage by almost half, while adeno-associated virus (AAV) donors with long homology reduce large deletions by approximately 80%. In the absence of HDR, the insertion of a short double-stranded ODN by NHEJ reduces deletion indexes by about 60%. CONCLUSIONS: Timely bridging of broken ends by HDR and NHEJ vastly decreases the unintended consequences of dsDNA cleavage. These strategies can be harnessed in gene editing applications to attenuate unintended outcomes.

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