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1.
Cell Cycle ; : 1-16, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33651649

RESUMO

Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. With frequent mutations in CTNNB1 gene that encodes ß-catenin, hepatoblastoma has been considered as a Wnt/ß-catenin-activated malignant tumor. Altered glucose metabolism upon nutrient deprivation (glucose starvation) might also be a critical event in hepatoblastoma carcinogenesis. The present study provides a lncRNA NBR2/miR-22/TCF7 axis modulating proliferation, invasion, migration, and apoptosis of hepatoblastoma cells upon glucose starvation through Wnt and downstream TCF7 signaling pathways. The expression of NBR2 is significantly increased within hepatoblastoma tissue samples; moreover, under incubation with 0 mM glucose (glucose starvation), NBR2 expression is significantly upregulated. NBR2 silencing not only inhibited hepatoblastoma cell viability, invasion, and migration under normal culture condition but also promoted the cell apoptosis under glucose starvation. NBR2 silencing in hepatoblastoma cells also decreased TCF7 mRNA expression and TCF7 protein levels, as well as the protein levels of the cell cycle, glucose entrapment, and EMT markers. miR-22 is directly bound to both NBR2 and TCF7; lncRNA NBR2 counteracted miR-22-mediated repression on TCF7 via acting as a ceRNA. The effects of NBR2 silencing on TCF7 expression, hepatoblastoma cell phenotype, and cell cycle, glucose entrapment, and EMT markers were all significantly reversed by miR-22 inhibition. In conclusion, lncRNA NBR2 aggravates hepatoblastoma cell malignancy through competing with TCF7 for miR-22 binding, therefore counteracting miR-22-mediated repression on TCF7. LncRNA NBR2 might be a promising target to inhibit hepatoblastoma cell proliferation under glucose starvation.

2.
Sci Adv ; 7(4)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33523915

RESUMO

5-Methylcytosine (5mC) oxidases, the ten-eleven translocation (TET) proteins, initiate DNA demethylation, but it is unclear how 5mC oxidation is regulated. We show that the protein SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1) is found in complexes with TET proteins and negatively regulates TET activities. Removal of SMCHD1 from mouse embryonic stem (ES) cells induces DNA hypomethylation, preferentially at SMCHD1 target sites and accumulation of 5-hydroxymethylcytosine (5hmC), along with promoter demethylation and activation of the Dux double-homeobox gene. In the absence of SMCHD1, ES cells acquire a two-cell (2c) embryo-like state characterized by activation of an early embryonic transcriptome that is substantially imposed by Dux Using Smchd1/Tet1/Tet2/Tet3 quadruple-knockout cells, we show that DNA demethylation, activation of Dux, and other genes upon SMCHD1 loss depend on TET proteins. These data identify SMCHD1 as an antagonist of the 2c-like state of ES cells and of TET-mediated DNA demethylation.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 169-173, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627213

RESUMO

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS: Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33404689

RESUMO

This study aimed to analyze the influence of renal insufficiency on the anticoagulant effects and safety of warfarin in Chinese patients. Data on the creatinine levels of participants enrolled in a randomized controlled study were screened and divided into the non-renal insufficiency group, mild renal insufficiency group, and moderate renal insufficiency group, according to the creatinine clearance rate. The primary outcome measures were stable dose and average daily dose of warfarin. Secondary outcome measures were percentage of time in the therapeutic international normalized ratio (INR) (%TTR), and the first time to reach the therapeutic INR. Adverse events included bleeding events, thromboembolic events, and mortality. All participants with renal function test results and a baseline INR of less than 1.5 were included in the primary and secondary outcome analysis. The SPSS Statistics 21.0 software was used for statistical analysis. The randomized controlled trial was registered in Clinicaltrials.gov (NCT02211326). A total of 571 patients were included in this analysis. Multiple regression analysis showed that the renal function was correlated with stable dose, average daily dose, and the first time to reach therapeutic INR after adjusting for confounding factors. However, no correlation was noted between kidney function and %TTR. No significant differences were observed across the various safety parameters among the three groups. Renal function is an important consideration in patients using warfarin.

5.
Ecotoxicol Environ Saf ; 211: 111881, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33444878

RESUMO

BACKGROUND: Cadmium is the most prevalent form of heavy metal contaminant globally and its exposure rises serious health concern. Chronic exposure to cadmium causes immune disturbances. However, few studies have addressed how it affects circulating immune cells, one of the most essential elements for the host defense system, at both population and molecular level. Therefore, this is the first single-cell transcriptomic analysis of the response of the human circulating immune system to plasma cadmium level. METHODS: We conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3283 individuals were eligible for analyzing the association between plasma cadmium levels and the monocyte counts and its subgroups. Another 780 individuals were assigned for validation. Thirty propensity-matched individuals without chronic disease from the lowest- and highest-quartile groups according to serum cadmium levels were selected for single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses. Moreover, the monocyte phenotypic alterations in the heavy metal-exposed population were validated with a cecal ligation and puncture sepsis mouse model. RESULTS: From August 2016 to July 2017, we conducted a cross-sectional study to identify phenotypic alterations in peripheral immune cells in cadmium polluted areas in China. Monocyte percentages were negatively associated with plasma cadmium levels in multivariable linear regression analysis. Peripheral blood mononuclear cell scRNA-seq revealed that the CD14+ monocyte subset was dramatically reduced in the highest-quartile cadmium-exposed group. Moreover, we assessed different hallmarks of immune cell dysfunction-such as host defense capability, apoptotic signaling, cellular diversity and malignant gene expression in monocytes. Importantly, cadmium induced phenotypic alterations in the immune system were validated in the cecal ligation and puncture sepsis mouse model, in which chronic exposure to cadmium not only increased the death rate but also decreased monocyte numbers and the ability to clear bacterial infections. CONCLUSION: This transcriptomic analysis provides molecular information about how the most important hallmarks of immune cell dysfunction are affected by plasma cadmium level. The significant phenotypic alterations in monocytes serving as early indicators of increased susceptibility to infectious and malignant diseases.


Assuntos
Cádmio/toxicidade , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Monócitos/efeitos dos fármacos , China , Estudos Transversais , Citometria de Fluxo , Humanos , Contagem de Leucócitos , Leucócitos Mononucleares , Masculino , Monócitos/citologia , Transcriptoma
6.
Methods Mol Biol ; 2198: 321-331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32822042

RESUMO

DNA cytosine modification is an important epigenetic mechanism that serves critical functions in a variety of biological processes in development and disease. 5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the two most common epigenetic marks found in the mammalian genome. 5hmC is generated from 5mC by the ten-eleven translocation (TET) family of dioxygenase enzymes. This modification can reach substantial levels in certain cell types such as embryonic stem cells and neurons. Standard bisulfite sequencing techniques cannot distinguish between 5mC and 5hmC. Therefore, the method of TET-assisted bisulfite sequencing has been developed for detecting 5hmC specifically. The method is based on protection of 5hmC by glycosylation followed by complete oxidation of both 5mC and 5fC to 5caC, which converts to uracil after bisulfite treatment leaving only 5hmC remaining as a cytosine signal after PCR and sequencing. The method requires a highly active TET protein for the conversion steps. Here, we present an efficient TET protein purification method and a streamlined TAB-sequencing protocol for 5hmC analysis at single base resolution.

7.
Small ; : e2006624, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284516

RESUMO

The performances of catalysts are highly dependent on their crystallinities. It is a significant challenge to successively manipulate the crystallinities of noble metal nanocatalysts due to the strong metallic bonds, especially under ambient conditions. Herein, a post-crystallization approach is developed for successive control of the crystallinity of Pd nanosheets via selective oxidation etching of the amorphous domains. This strategy can be extended to crystallize other Pd and Ru nanomaterials. By carefully modulating the crystallinity of Pd nanosheets, the time for the complete conversion of 4-nitrostyrene via hydrogenation is reduced by 20 times. Also, crystallization can turn the selectivity of the products and improve the stability of Pd nanosheets. These findings may advance the crystal engineering of metal nanomaterials for wide applications.

8.
Trials ; 21(1): 999, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276811

RESUMO

OBJECTIVES: A severe epidemic of COVID-19 has broken out in China and has become a major global public health event. We focus on the Acute Respiratory Distress Syndrome (ARDS)-like changes and overactivation of Th17 cells (these produce cytokines) in patients with COVID-19. We aim to explore the safety and efficacy of ixekizumab (an injectable drug for the treatment of autoimmune diseases) to prevent organ injury caused by the immune response to COVID-19. Ixekizumab is a human monoclonal antibody that binds to interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. TRIAL DESIGN: The experiment is divided into two stages. In the first stage, the open trial, 3 patients with COVID-19 are treated with ixekizumab, and the safety and efficacy are observed for 7 days. In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. This is a two-center, open-label, randomized controlled pilot trial with 2-arm parallel group design (1:1 ratio). PARTICIPANTS: Patients with COVID-19 aged 18-75 with increased Interleukin (IL)-6 levels will be enrolled, but patients with severe infections requiring intensive care will be excluded. The trial will be undertaken in two centers. The first stage is carried out in Xiangya Hospital of Central South University, and the second stage is carried out simultaneously in the Third Xiangya Hospital of Central South University. INTERVENTION AND COMPARATOR: In the first stage, three subjects are given ixekizumab ("Taltz") (80 mg/ml, 160 mg as a single hypodermic injection) and antiviral therapy (α-interferon (administer 5 million U by aerosol inhalation twice daily), lopinavir/ritonavir (administer 100mg by mouth twice daily, for the course of therapy no more than 10 days), chloroquine (administer 500mg by mouth twice daily, for the course of therapy no more than 10 days), ribavirin (administer 500mg by intravenous injection two to three times a day, for the course of therapy no more than 10 days), or arbidol (administer 200mg by mouth three times a day, for the course of therapy no more than 10 days), but not more than 3 types). The treatment course of the first stage is 7 days. In the second stage, 40 randomized patients will receive the following treatments--Group 1: ixekizumab (80 mg/ml, 160 mg as a single hypodermic injection) with antiviral therapy (the same scheme as in the first stage); Group 2: antiviral therapy alone (the same scheme as in the first stage). The length of the second treatment course is 14 days. MAIN OUTCOMES: The primary outcome is a change in pulmonary CT severity score (an imaging tool for assessing COVID-19, which scores on the basis of all abnormal areas involved). Pulmonary CT severity score is assessed on the 7th day, 14th day, or at discharge. RANDOMISATION: In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. The eLite random system of Nanjing Medical University is used for randomization. BLINDING (MASKING): The main efficacy indicator, the CT results, will be evaluated by the third-party blinded and independent research team. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. TRIAL STATUS: Trial registration number is ChiCTR2000030703 (version 1.7 as of March 19, 2020). The recruitment is ongoing, and the date recruitment was initiated in June 2020. The anticipated date of the end of data collection is June 2021. TRIAL REGISTRATION: The name of the trial register is the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000030703 ( http://www.chictr.org.cn/ ). The date of trial registration is 10 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

9.
Anal Chim Acta ; 1139: 138-145, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33190696

RESUMO

The detection of Salmonella Typhimurium (S.typhimurium) is of great importance in food safety field. Colorimetric strategy is particularly appealing for S. typhimurium identification because of its user-friendliness and instrument-free. However, the existing colorimetric strategies still meet the challenges of low sensitivity, tedious nucleic acid extraction and expensive labeling processes. Herein, a high sensitivity and label-free colorimetric sensing strategy for S. typhimurium detection without nucleic acid extraction is constructed. Specifically, the proposed strategy is based on three-way junction (3WJ) DNA branched structure combined with nicking enzyme signal amplification (NESA). In the presence of target, cascaded signal amplification is initiated through a series of toehold-mediated strand displacement reactions (TSDRs) to recycle the trigger DNA causing formation of the numerous 3WJ DNA branched structures (3WJ-TSDRs). Then, the branches of 3WJ-TSDRs are fully utilized to hybridize with the DNAzyme signal probes to initiate NESA in the presence of Nt. BbvCI, which making every branch has a function of signal amplification. Finally, DNAzyme signal probes (green) were completely split into two fragments (colorless). The application of NESA in the branches of 3WJ-TSDRs offers a highly sensitive detection of S. typhimurium with a low limit of detection of 42 CFU mL-1. Besides, the colorimetric sensing strategy also shows strong anti-interference. The capability of the colorimetric sensing strategy in spiked samples was also investigated, showing a more intuitive results and fast detection in compare with the traditional plate counting method. With these characteristics, the proposed sensing strategy based on 3WJ-TSDRs and NESA is a promising tool for new point-of-care (POC) applications in food safety.

10.
Neurotoxicology ; 82: 100-107, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33249123

RESUMO

BACKGROUND: The influence of chronic arsenic exposure on cognitive impairment has been explored broadly by previous studies. However, most of them focused mainly on children rather than adults. In addition, in China, studies in this field are not sufficient. To illustrate how long-term arsenic exposure affects cognitive function, we designed a cross-sectional study involving 1556 adults. METHODS: All of them came from three locations around the Realgar Plant. The cognitive function of the participants was evaluated using a Chinese version of the Mini-mental state Examination (MMSE). The participants' internal arsenic exposure status (hair arsenic concentrations) and the external arsenic exposure status (the distance between the participants' location of residence and the Realgar Plant) were measured. RESULTS: Our research revealed that both of hair arsenic concentrations and the prevalence of arsenicosis, two important indexes, were significantly higher in the cognitive-impaired (CI) group than in the cognitive-normal (CN) group (P < 0.05). In addition, distance from the Realgar Plant was positively correlated with the MMSE scores and was negatively correlated with the prevalence of cognitive impairment. Moreover, our results demonstrated that there was a negative correlation between hair arsenic concentrations and MMSE scores. We conducted a two-level Logistic regression analysis and further confirmed that even after adjusting for potential confounding variables, arsenicosis retained a risk factor for cognitive impairment (odds ratio (OR) = 1.84, P < 0.05). CONCLUSIONS: Our results indicated that chronic arsenic exposure could impair adults' cognitive function in a dose-dependent manner. Additionally, arsenicosis could be an independent risk factor for cognitive impairment.

11.
Ecotoxicol Environ Saf ; 208: 111435, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038727

RESUMO

OBJECTIVE: Several heavy metals have been reported to be associated with metabolic syndrome(MetS) in general population, while effects of multiple metals exposure on MetS in residents living in heavy metal polluted regions have not been investigated. We aimed to assess the association of 23 metal levels and MetS among population living in China's heavy metal polluted regions. METHODS: From August 2016 to July 2017, a total of 2109 eligible participants were consecutively enrolled in our study in Hunan province, China. The levels of plasma and urine metals were measured by inductively coupled plasma mass spectrometer (ICP-MS). MetS was defined by the criteria of the International Diabetes Federation. Multivariable regression models were applied to analysis the potential relationship. RESULTS: In the overall population, crude model showed positive relationship of plasma titanium (Ti) with MetS and negative association of urine vanadium, iron, and selenium with MetS. After adjusted for potential confounders, only plasma Ti was positive associated with MetS (adjusted OR for Q4 versus Q1: 1.46; 95% CI: 1.06-1.99), and this positive correlation was explained by abdominal obesity (OR = 1.84, 95% CI: 1.41-2.39) and high triglycerides (OR = 2.23, 95% CI: 1.68-2.96). Further linear regression analysis revealed significant association of plasma Ti levels with waist circumference (ß = 0.0056, 95% CI: 0.0004-0.0109, P = 0.036) and triglycerides (ß = 0.0012, 95% CI: 0.0006-0.0019, P < 0.001), respectively. CONCLUSION: High plasma Ti level was associated with increased risk of MetS via increasing waist circumference and triglycerides in people under high metal exposure.

12.
Chemosphere ; 264(Pt 2): 128505, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33068969

RESUMO

We sought to evaluate whether essential and toxic metals are cross-sectionally related to blood lipid levels using data among adults from Shimen (n = 564) and Huayuan (n = 637), two counties with different exposure profiles in Hunan province of China. Traditional and grouped weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were performed to assess association between exposure to a mixture of 22 metals measured in urine or plasma, and lipid markers. Most of the exposure levels of metals were significantly higher in Shimen area than those in Huayuan area (all P-values < 0.001). Traditional WQS regression analyses revealed that the WQS index were both significantly associated with lipid markers in two areas, except for the HDL-C. Grouped WQS revealed that essential metals group showed significantly positive associations with lipid markers except for HDL-C in Huayuan area, while toxic metals group showed significantly negative associations except for HDL-C and LDL-C in Huayuan area. There were no significant joint effects, but potential non-linear relationships between metals mixture and TC or LDL-C levels were observed in BKMR analyses. Although consistent significantly associations of zinc and titanium with TG levels were found in both areas, the metals closely related to other lipid markers were varied by sites. Additionally, the BKMR analyses revealed an inverse U shaped association of iron with LDL-C levels and interaction effects of zinc and cadmium on LDL-C in Huayuan area. The relationship between metal exposure and blood lipid were not identical against different exposure profiles.

13.
J Hum Hypertens ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973309

RESUMO

We aimed to investigate the association of self-reported nighttime sleep duration and daytime napping duration with hypertension in rural areas of China. The participants, who were from rural areas of Hunan Province in China, were enrolled during 2016-2017. Nighttime sleep duration (<7 h, 7-8 h, and ≥9 h) and daytime napping duration(no nap, 0-1 h, and >1 h) were determined by a self-reported questionnaire. Hypertension was defined as a mean systolic blood pressure ≥140 mmHg and/or a mean diastolic blood pressure ≥90 mmHg or a self-reported physician diagnosis of hypertension and current use of antihypertensive medication. Of 1763 enrolled participants, 52% had hypertension. A total of 640 (36%) were male and 1123 (64%) were female; the mean age was 56 years. After adjusting for potential confounders, participants who slept for ≥9 h per night had a 1.29-fold (95% CI: 1.03, 1.60) increased odds of hypertension compared to the reference group (7-8 h per night). Daytime napping >1 h was negatively associated with hypertension, with an adjusted OR (95% CI) of 0.70 (0.51, 0.97), and the protective effect of longer daytime napping was still found in the subgroup sleeping 7-8 h per night. Among the rural population in China, long nighttime sleep duration is associated with a higher prevalence of hypertension, and longer daytime napping is related to a decreased prevalence of hypertension.

14.
ACS Sens ; 5(10): 2977-3000, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32945653

RESUMO

With the continuous development of biosensors, researchers have focused increasing attention on various signal amplification strategies to pursue superior performance for more applications. In comparison with other signal amplification strategies, hybridization chain reaction (HCR) as a powerful signal amplification technique shows its certain charm owing to nonenzymatic and isothermal features. Recently, on the basis of conventional HCR, this technique has been developed and improved rapidly, and a variety of HCR-based biosensors with excellent performance have been reported. Herein, we present a systematic and critical review on the research progress of HCR in biosensors in the last five years, including the newly developed HCR strategies such as multibranched HCR, migration HCR, localized HCR, in situ HCR, netlike HCR, and so on, as well as the combination strategies of HCR with isothermal signal amplification techniques, nanomaterials, and functional DNA molecules. By illustrating some representative works, we also summarize the advantage and challenge of HCR in biosensors, and offer a deep discussion of the latest progress and future development trends of HCR in biosensors.

15.
BMC Plant Biol ; 20(1): 354, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727357

RESUMO

BACKGROUND: The non-structural carbohydrates (NSCs), carbon (C), nitrogen (N), and phosphorus (P) are important energy source or nutrients for all plant growth and metabolism. To persist in shaded understory, saplings have to maintain the dynamic balance of carbon and nutrients, such as leaf NSCs, C, N and P. To improve understanding of the nutrient utilization strategies between shade-tolerant and shade-intolerant species, we therefore compared the leaf NSCs, C, N, P in response to shade between seedlings of shade-tolerant Schima superba and shade-intolerant Cunninghamia lanceolate. Shading treatments were created with five levels (0, 40, 60, 85, 95% shading degree) to determine the effect of shade on leaf NSCs contents and C:N:P stoichiometry characteristics. RESULTS: Mean leaf area was significantly larger under 60% shading degree for C. lanceolata while maximum mean leaf area was observed under 85% shading degree for S. superba seedlings, whereas leaf mass per area decreased consistently with increasing shading degree in both species. In general, both species showed decreasing NSC, soluble sugar and starch contents with increasing shading degree. However shade-tolerant S. superba seedlings exhibited higher NSC, soluble sugar and starch content than shade-intolerant C. lanceolate. The soluble sugar/starch ratio of C. lanceolate decreased with increasing shading degree, whereas that of S. superb remained stable. Leaf C:N ratio decreased while N:P ratio increased with increasing shading degree; leaf C:P ratio was highest in 60% shading degree for C. lanceolata and in 40% shading degree for S. superba. CONCLUSION: S. superba is better adapted to low light condition than C. lanceolata through enlarged leaf area and increased carbohydrate reserves that allow the plant to cope with low light stress. From mixed plantation viewpoint, it would be advisable to plant S. superba later once the canopy of C. lanceolata is well developed but allowing enough sunlight.

16.
Colloids Surf B Biointerfaces ; 194: 111166, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32521461

RESUMO

In this work, a pH-responsive and tumor targeted multifunctional drug delivery system (RB-DOX@HMSNs-N = C-HA) was designed to realize chemo-photodynamic combination therapy. Hollow mesoporous silica nanoparticles (HMSNs) was served as the host material to encapsulate doxorubicin (DOX) and photosensitizer rose bengal (RB). Hyaluronic acid (HA) was modified on the surface of HMSNs via pH-sensitive Schiff base bonds as gatekeeper as well as targeted agent. Characterization results indicated the successful preparation of HMSNs-N = C-HA with appropriate diameter of 170 nm around and the nanocarriers displayed superior drug loading capacity (15.30 % for DOX and 12.78 % for RB). Notably, the results of in vitro drug release experiments confirmed that the system possessed good pH-sensitivity, which made it possible to release cargoes in slight acid tumor micro-environments. Significantly, the in vitro cell uptake and cytotoxicity assay results fully proved that RB-DOX@HMSNs-N = C-HA could precisely target murine mammary carcinoma (4T1) cells and effectively inhibit tumor cells viability with chemo-photodynamic synergistic therapy. Overall, our work (RB-DOX@HMSNs-N = C-HA) provides an efficient approach for the development of chemo-photodynamic combination therapy.

17.
Circ Genom Precis Med ; 13(4): e002602, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32510984

RESUMO

BACKGROUND: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients. METHODS: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy. RESULTS: A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1-24.4]). The incidence of adverse events was low in both groups. CONCLUSIONS: The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.

18.
Talanta ; 217: 121056, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32498903

RESUMO

DNA-modified gold nanoparticles (AuNPs) are useful nanomaterials for detecting multiple molecules. However, their performance is greatly dependent on the density of probe DNA on the surface of AuNPs. Here, we used Poly-adenine (PolyA) to regulate the surface density of probe DNA to achieve a highly efficient DNA walking biosensor system to detection miRNA-21. The movement track of the biosensor system consists of PolyA-DNA probe was connected to AuNPs, and exonuclease III (Exo III) acted as a motor driving the walker movement to achieve signal amplification. By optimizing the length of PolyA, the surface density of probe DNA was changed, thereby affecting the target binding and enzymatic processing of the bound probes, which ultimately enhanced the sensitivity and reduced timeliness of the DNA walker. Furthermore, the designed PolyA-DNA probe exhibits an outstanding sensitivity, due to the effect of density regulation, which is 7.9 times and 11.1 times lower than those of the SH-DNA and the free-DNA, respectively. In addition, the hairpin structure of DNA probe locates fluorophore at a zone adjacent to AuNPs surface, which reduces the background signal by 1.1 times compared with traditional straight probe. In this work, the biosensor system shows a high selectivity towards miRNA-21. Moreover, the biosensor system has been demonstrated to be potentially useful for the miRNA-21 detection in human serum with the recoveries of 93.2%-110.0% and has high repeatability. Considering these advantages, this PolyA-regulated DNA walking biosensor system has great potential as a routine tool for miRNA detection and has wide applications in the field of biomedical analysis.

20.
Environ Sci Pollut Res Int ; 27(27): 34412-34420, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557026

RESUMO

Ambient particulate matter (PM) newly has been regarded as a conceivable hazard for public health. A large number of studies have described that PM, exceptionally PM2.5, is correlated with respiratory, cardiovascular, and metabolic diseases, etc. PM2.5-induced hepatocyte steatosis previously has been uncovered both in cellular and murine models. Nevertheless, less is known about the underlying mechanism. Here, we found that PM2.5 could cause the downregulation of farnesoid X receptor (FXR), a key transcription factor for lipid metabolism. FXR could regulate the accumulation of lipid droplets induced by PM2.5 in vitro. Moreover, FXR-/- mice were exposed to PM2.5 for 2 months to investigate the role of FXR in pathogenesis of PM2.5-induced hepatic steatosis in vivo. The results showed that exposure of wild-type (WT) mice to PM2.5 caused mild liver steatosis compared with the mice exposure to filtered air (FA). Furthermore, the content of triglyceride (TG) and total cholesterol (TC) was elevated in WT mice liver triggered by the inhalation of PM2.5. However, there was no statistical difference in TG and TC content between FXR-/- mice with and without PM2.5 exposure. Overall, our finding suggested FXR mediated PM2.5-induced hepatic steatosis.


Assuntos
Fígado Gorduroso , Animais , Hepatócitos , Metabolismo dos Lipídeos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado
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