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1.
BMC Cardiovasc Disord ; 21(1): 323, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193057

RESUMO

BACKGROUND: Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. METHODS: In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. RESULTS: We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). CONCLUSIONS: COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

2.
Talanta ; 233: 122591, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215080

RESUMO

The existing CRISPR-mediated diagnostic tests require a two-step procedure (DNA or RNA amplification followed by CRISPR-mediated sequence-specific detection) for nucleic acid detection, which increases complexity and the risk of sample cross-contamination. Here, we report a new CRISPR-mediated test, called CRISPR-top (CRISPR-mediated testing in one-pot), which integrates simultaneous target pre-amplification with CRISPR/cas12b-mediated detection into a one-pot reaction mixture, performed at a constant temperature. The novel CRISPR-top assay was applied to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19 (coronavirus disease 2019). COVID-19 CRISPR-top targets the ORF1ab (opening reading frame 1a/b) and NP (nucleoprotein) genes of SARS-CoV-2, and operates at 59 °C for 40 min with minimal instrument. The COVID-19 CRISPR-top assay can return results within 60-min and is easily interpreted by visual fluorescence or lateral flow readouts. The analytical limit of detection (LoD) for COVID-19 CRISPR-top is 10 copies (for each detection target) per reaction with no cross-reactivity observed from non-SARS-CoV-2 templates. Among clinically collected non-COVID-19 samples, the assay's specificity was 100% (80/80 oropharynx swab samples). Among 52 COVID-19 positive clinical samples collected, the COVID-19 CRISPR-top assay yielded 38 (73.1%) positive results using fluorescence readout and 35 (67.3%) positive results with lateral-flow readout. These diagnostic results were similar to those obtained using RT-PCR (34 positive (65.4%)). These data indicate that COVID-19 CRISPR-top is a simple, rapid, accurate and highly sensitive method for SARS-CoV-2 detection which can be used in the clinic, field laboratories and primary care facilities in resource-challenged settings.


Assuntos
COVID-19 , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Humanos , Técnicas de Amplificação de Ácido Nucleico , RNA Viral/genética , SARS-CoV-2 , Sensibilidade e Especificidade
3.
Zhongguo Zhen Jiu ; 41(7): 730-4, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259403

RESUMO

OBJECTIVE: To evaluate the clinical therapeutic effect of electroacupuncture (EA) at Dong's Sanqixue combined with auricular point sticking on post-operative complications of complex anal fistula. METHODS: The data of 318 patients undergoing anal fistula surgery were analyzed retrospectively. In accordance with whether accepted the combined treatment with EA at bilateral Dong's Sanqixue and auricular point sticking or not after operation, they were divided into an observation group (157 cases) and a control group (161 cases). At the ratio of 1︰1, the nearest neighbor matching method was adopted to match 125 pairs of patients. The score of visual analogue scale (VAS) on day 1, 7 and 14 after operation, the incidence of urine retention on day 1 and 3 after operation, the anorectal dynamical indexs (anal resting pressure, rectal resting pressure, anal maximum systolic pressure and rectal minimum sensitivity) before and after operation, as well as the clinical therapeutic effect were compared in the patients between the two groups separately. RESULTS: For VAS score, there was an interaction between therapeutic method and treatment duration (P<0.05); the main effect was significant for therapeutic method (P<0.05), while, it was not significant for treatment time (P>0.05). On day 7 and 14 after operation, VAS scores were lower than those on day 1 in the two groups (P<0.05), and VAS scores on day 7 and 14 after operation in the observation group were lower than those in the control group (P<0.05). On day 3 after operation, the incidence of urine retention in the observation group was lower than that in the control group (0.8% [1/125] vs 9.6% [12/125], P<0.05). On day 14 after operation, anal resting pressure, anal maximum systolic pressure and rectal minimum sensitivity in the observation group were lower than those in the control group (P<0.05), and rectal resting pressure was higher than that in the control group (P<0.05). In 1 month after operation, the total effective rate was 96.0% (120/125) in the observation group, higher than 80.8% (101/125) in the control group (P<0.05). CONCLUSION: Electroacupuncture at Dong's Sanqixue combined with auricular point sticking therapy alleviates pain, reduces the incidence of urine retention, improves anal defecation function and clinical therapeutic effect in the patients after complex anal fistula surgery.

4.
Zool Res ; 42(4): 502-513, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34254744

RESUMO

Persistent uplift means the Qinghai-Tibet Plateau (QTP) is an ideal natural laboratory to investigate genome evolution and adaptation within highland environments. However, how paleogeographic and paleoclimatic events influence the genome and population of endemic fish species remains unclear. Glyptosternon maculatum is an ancient endemic fish found on the QTP and the only critically endangered species in the Sisoridae family. Here, we found that major transposons in the G. maculatum genome showed episodic bursts, consistent with contemporaneous geological and climatic events during the QTP formation. Notably, histone genes showed significant expansion in the G. maculatum genome, which may be mediated by long interspersed nuclear elements (LINE) repetitive element duplications. Population analysis showed that ancestral G. maculatum populations experienced two significant depressions 2.6 million years ago (Mya) and 10 000 years ago, exhibiting excellent synchronization with Quaternary glaciation and the Younger Dryas, respectively. Thus, we propose that paleogeography and paleoclimate were dominating driving forces for population dynamics in endemic fish on the QTP. Tectonic movements and temperature fluctuation likely destroyed the habitat and disrupted the drainage connectivity among populations. These factors may have caused severe bottlenecks and limited migration among ancestral G. maculatum populations, resulting in the low genetic diversity and endangered status of the species today.

5.
Talanta ; 233: 122591, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1267931

RESUMO

The existing CRISPR-mediated diagnostic tests require a two-step procedure (DNA or RNA amplification followed by CRISPR-mediated sequence-specific detection) for nucleic acid detection, which increases complexity and the risk of sample cross-contamination. Here, we report a new CRISPR-mediated test, called CRISPR-top (CRISPR-mediated testing in one-pot), which integrates simultaneous target pre-amplification with CRISPR/cas12b-mediated detection into a one-pot reaction mixture, performed at a constant temperature. The novel CRISPR-top assay was applied to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19 (coronavirus disease 2019). COVID-19 CRISPR-top targets the ORF1ab (opening reading frame 1a/b) and NP (nucleoprotein) genes of SARS-CoV-2, and operates at 59 °C for 40 min with minimal instrument. The COVID-19 CRISPR-top assay can return results within 60-min and is easily interpreted by visual fluorescence or lateral flow readouts. The analytical limit of detection (LoD) for COVID-19 CRISPR-top is 10 copies (for each detection target) per reaction with no cross-reactivity observed from non-SARS-CoV-2 templates. Among clinically collected non-COVID-19 samples, the assay's specificity was 100% (80/80 oropharynx swab samples). Among 52 COVID-19 positive clinical samples collected, the COVID-19 CRISPR-top assay yielded 38 (73.1%) positive results using fluorescence readout and 35 (67.3%) positive results with lateral-flow readout. These diagnostic results were similar to those obtained using RT-PCR (34 positive (65.4%)). These data indicate that COVID-19 CRISPR-top is a simple, rapid, accurate and highly sensitive method for SARS-CoV-2 detection which can be used in the clinic, field laboratories and primary care facilities in resource-challenged settings.


Assuntos
COVID-19 , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Humanos , Técnicas de Amplificação de Ácido Nucleico , RNA Viral/genética , SARS-CoV-2 , Sensibilidade e Especificidade
6.
Cell ; 184(14): 3812-3828.e30, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214472

RESUMO

We study a patient with the human papilloma virus (HPV)-2-driven "tree-man" phenotype and two relatives with unusually severe HPV4-driven warts. The giant horns form an HPV-2-driven multifocal benign epithelial tumor overexpressing viral oncogenes in the epidermis basal layer. The patients are unexpectedly homozygous for a private CD28 variant. They have no detectable CD28 on their T cells, with the exception of a small contingent of revertant memory CD4+ T cells. T cell development is barely affected, and T cells respond to CD3 and CD2, but not CD28, costimulation. Although the patients do not display HPV-2- and HPV-4-reactive CD4+ T cells in vitro, they make antibodies specific for both viruses in vivo. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1. The control of HPV-2 and HPV-4 in keratinocytes is dependent on the T cell CD28 co-activation pathway. Surprisingly, human CD28-dependent T cell responses are largely redundant for protective immunity.

7.
Biol Res ; 54(1): 19, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238380

RESUMO

In the era of climate change, due to increased incidences of a wide range of various environmental stresses, especially biotic and abiotic stresses around the globe, the performance of plants can be affected by these stresses. After oxygen, silicon (Si) is the second most abundant element in the earth's crust. It is not considered as an important element, but can be thought of as a multi-beneficial quasi-essential element for plants. This review on silicon presents an overview of the versatile role of this element in a variety of plants. Plants absorb silicon through roots from the rhizospheric soil in the form of silicic or monosilicic acid. Silicon plays a key metabolic function in living organisms due to its relative abundance in the atmosphere. Plants with higher content of silicon in shoot or root are very few prone to attack by pests, and exhibit increased stress resistance. However, the more remarkable impact of silicon is the decrease in the number of seed intensities/soil-borne and foliar diseases of major plant varieties that are infected by biotrophic, hemi-biotrophic and necrotrophic pathogens. The amelioration in disease symptoms are due to the effect of silicon on a some factors involved in providing host resistance namely, duration of incubation, size, shape and number of lesions. The formation of a mechanical barrier beneath the cuticle and in the cell walls by the polymerization of silicon was first proposed as to how this element decreases plant disease severity. The current understanding of how this element enhances resistance in plants subjected to biotic stress, the exact functions and mechanisms by which it modulates plant biology by potentiating the host defence mechanism needs to be studied using genomics, metabolomics and proteomics. The role of silicon in helping the plants in adaption to biotic stress has been discussed which will help to plan in a systematic way the development of more sustainable agriculture for food security and safety in the future.


Assuntos
Silício , Estresse Fisiológico , Agricultura , Plantas , Solo
8.
Stem Cells Dev ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271845

RESUMO

Given that the modification of stem cell-derived Extracellular Vesicles (EV) can enhance their regenerative efficiency, an increasing number of studies pay attention to the therapeutic potential of hypoxic preconditioning of stem cell-derived EVs (Hypo-EVs) in cardiac repair. Our meta-analysis aims to evaluate the cardiac repair of Hypo-EVs in preclinical animal models of Myocardial Infarction (MI). We searched PubMed, EMBASE, and the Web of Science up to January 2021. The primary outcome was left ventricular ejection fraction (LVEF). The second outcomes were left ventricular fractional shortening (LVFS) and infarct size. Random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Nine studies satisfied the inclusion criteria. Compared with the model group, pooled analyses demonstrated that stem cell-derived EVs culturing in normal oxygen environment (Nor-EVs) can improve LVEF (WMD 9.07, 95% CI 6.76 to 11.38, I2= 80.7%), LVFS (WMD 3.03, 95% CI 0.79 to 5.27, I2= 86.3%) and reduce infarct size (WMD -12.15, 95% CI -19.12 to -5.18, I2= 96.8%). Compared with Nor-EVs, Hypo-EVs can improve LVEF (WMD 5.11, 95% CI 1.63 to 8.60, I2= 95%), LVFS (WMD 6.54, 95% CI 4.08 to 8.99, I2= 90.6%), and reduce infarct size (WMD -7.42, 95% CI -12.97 to -1.87, I2= 97.2%). These results suggest that Hypo-EVs could show more improvement than Nor-EVs therapy on cardiac repair in the preclinical MI animal model. However, future well­designed large animal studies might be necessary to clarify the methods and effects of Hypo-EVs therapy to help provide new ideas for future engineered EVs design.

9.
Mamm Genome ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34272987

RESUMO

The heart is one of the most common organs involved in sepsis-induced organ dysfunction and about 50% septic patients complicated with myocardial injury. So far, the molecular mechanisms underlying sepsis-induced cardiac damage remain unclear. In this study we aimed to evaluate the effect of miR-642a on sepsis-induced cardiac injury in vitro and explore the possible lncRNA-microRNA mechanism. We first downloaded GSE101639 to identify differentially expressed genes (DEGs) in sepsis. The expression of miR-642a in LPS-induced H9C2 cells was detected by qRT-PCR. MTT assay, cell migration, flow cytometry analysis, ELISA, qRT-PCR and Western blotting analysis were applied to evaluating the effect of miR-642a mimic on LPS-induced H9C2 cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. The results showed miR-642a expression was decreased in septic patients and LPS-induced H9C2 cells. Besides, MiR-642a mimic promoted cell viability and migration, inhibited cell apoptosis of LPS-induced H9C2 cells. Bioinformatics analysis showed miR-642a directly targets with 3'-UTR of ROCK1. Moreover, LUCAT1 regulated ROCK1 expression act as a competing endogenous RNA (ceRNA) for miR-642a. Our data demonstrated that lncRNA LUCAT1 could function via sponging miR-642a to regulate ROCK1 expression in LPS-induced H9C2 cells. And knockdown of lncRNA LUCAT1 could suppress LPS-induced cardiac injury in vitro.

10.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209973

RESUMO

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.

11.
Anal Chem ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229431

RESUMO

Lipid droplets (LDs) and lysosomes are crucial for maintaining intracellular homeostasis. But single fluorescent probes (SFPs) capable of simultaneous and discriminative visualizing of two organelles above and their interaction in living cells are still challenging due to the lack of rational design strategies. To break this bottleneck, herein, we develop a reliable strategy based on a pH-sensitive intramolecular spirocyclization. As a proof of concept, an SFP CMHCH, which possesses a switchable hemicyanine/spiro-oxazine moiety induced by pH, has been designed and synthesized. In acidic environments, the ring-open form CMHCH exhibits red-shift emission and low logP value, whereas the ring-closed form CMHC displays blue-shift emission and high logP value in neutral or basic environments. Thus, the distinct different hydrophilicity/hydrophobicity and absorption/emission properties of these two forms enable targeting LDs and lysosomes simultaneously and discriminatingly. Very importantly, the dynamic process of lipophagy can be directly monitored with CMHCH. The success of CMHCH indicated that the spirocyclization strategy is efficient for constructing SFPs to LDs and lysosomes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34281088

RESUMO

Agricultural water use accounts for the largest proportion of water withdrawal, so improving agricultural water use efficiency is an important way to alleviate water shortage. However, the expected water saving by the improved agricultural water use efficiency may be offset by the rebound effect, which means the goal of water saving by improving agricultural water use efficiency is not achieved. Based on the definition of the rebound effect of agricultural water use, this paper first uses a fixed model to measure the causal effect of agricultural water use efficiency on agricultural water use to analyze the agricultural water rebound effect, then analyses the heterogeneity and mechanism of the effect of agricultural water use efficiency on agricultural water use with the panel data from 30 provinces or cities in China from 2000 to 2017. The results show that, firstly, the agricultural water use efficiency has a significant negative effect on agricultural water use, but the average agricultural water rebound effect is 88.81%. Secondly, the effect of agricultural water use efficiency on agricultural water use is heterogeneous, in which the improvement of agricultural water use efficiency in humid or major grain-producing areas will have a lower agricultural water rebound effect. Finally, agricultural water use efficiency can affect agricultural water use through planting area and planting structure. An increase in agricultural water use efficiency will expand the planting area to increase water use. However, this will change the planting structure to decrease water use. The implication for agricultural water management is that the irrigation agricultural scale has to be controlled under the condition of available water resource, while improving agricultural water use efficiency.

13.
J Hazard Mater ; 420: 126532, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252653

RESUMO

Dissolved organic matter (DOM), as the most active ingredient in compost, directly determines the speciation and environmental behavior of HMs. Here, the binding properties of DOM derived from chicken-manure compost (CHM), cow-manure compost (COM) and pig-manure compost (PIM) with HMs were explored by analyses of Fluorescence excitation-emission matrix parallel factor (EEM-PARAFAC) and two-dimensional correlation Fourier transform infrared spectroscopy (2D-FTIR-COS). Results showed that the binding characteristics vary with origin of DOM and type of HMs. The fulvic-like component dominated the transformation of HMs speciation, and CHM-DOM had higher affinity with HMs and greater risk causing pollution due to its higher aromaticity, molecular weight and distribution of fluorescent components. Moreover, Cu(II) can efficiently bind to DOM with the stability constants (log kM) ranging from 4.53 to 5.38, followed by Pb(II) (3.34-3.57), whereas Cd(II) can hardly bind to DOM. The amide and polysaccharide were the predominant sites for HMs binding in CHM-DOM, and polysaccharide and phenolic in COM-DOM, while phenolic and amide in PIM-DOM, respectively. Although the proportion of protein-like components and non-fluorescent polysaccharides in DOM were low, their role in HMs binding should not be ignored. In brief, the environmental risk caused by livestock manure compost may originate from interactions between DOM and HMs.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34246549

RESUMO

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of non-alcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportion of non-alcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

15.
Biomed Pharmacother ; 141: 111883, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246955

RESUMO

Lung metastasis of Triple-negative breast cancer (TNBC) causes severe breath-related events and poor prognosis. Ruyiping (RYP), a traditional Chinese medicine prescription, is used to treat breast cancer lung metastasis in clinical practice. This study was to explore the anti-lung-metastatic activities and mechanism of RYP extract by regulating macrophage polarization. The results showed that RYP can inhibit the viability and induce the apoptosis of TNBC cells. In in vitro experiments, RYP significantly inhibited the invasion and migration ability of TNBC cells promoted by M2, the subtype of macrophage which increased TNBC metastasis related genes. In in vivo experiments, RYP reduced the TNBC progression and lung metastasis. M2/M1 ration in the lung and M2 in the tumor was reduced by RYP, as well as M2 master regulator Stat6. Therefore, RYP extract may exhibit anti-lung metastasis function by reducing M2 in both tumor and lung through reducing Stat6.

16.
Bioengineered ; 12(1): 3398-3409, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34224316

RESUMO

Our previous study found that in nasopharyngeal carcinoma (NPC) cells, overexpression of Notch2 can inhibit epithelial-mesenchymal transition (EMT), which plays a vital role in mediating radiosensitivity. The purpose of this study was to explore the radiosensitizing efficacy of the Notch2 gene in NPC cells and its potential mechanism. We used the recombinant plasmid transfection technique to establish Notch2-overexpressing 5-8 F and CNE-2 NPC cells. Cell proliferation, radiosensitivity, apoptosis and cell cycle distribution were assessed by cell counting kit-8 (CCK-8) experiments, colony formation experiments and flow cytometry. The levels of proteins related to cell cycle, apoptosis, and the AKT/mTOR signaling pathway were evaluated by using Western blotting. The results suggested that Notch2 overexpression increased the radiosensitivity of NPC cells, with sensitizing enhancement ratios (SERs) of 1.24 (5-8 F cells) and 1.34 (CNE-2 cells). Flow cytometry indicated that the level of apoptosis and percentage of cells in G2/M-phase were highest in NPC cells overexpressing Notch2 and treated with radiotherapy compared to cells overexpressing Notch2 alone or administered radiotherapy alone. Western blotting showed that compared to that of cells treated with Notch2 overexpression or radiotherapy alone, the levels of γH2AX, Bax, Bcl-2, Cyclin D1 and AKT/mTOR signaling pathway-related proteins were modified in NPC cells overexpressing Notch2 and treated with radiotherapy. These findings showed that overexpression of Notch2 can increase the radiosensitivity of NPC cells by inhibiting the AKT/mTOR pathway.AbbreviationsNPC: Nasopharyngeal carcinoma; EMT: Epithelial-mesenchymal transition; CCK8: Cell counting kit-8; EBV: Epstein-Barr virus; FBS: Fetal bovine serum; PE: Plating efficiency; SF: Survival fraction; SER: Sensitizing enhancement ratio; DSBs: DNA double-strand breaks[Figure: see text].

17.
Artigo em Inglês | MEDLINE | ID: mdl-34227007

RESUMO

To investigate the latent relation between technology innovation and eco-environmental systems and promote their coordinated development, we integrated the coupling coordination model and panel vector autoregressive model to examine the evidence from China. The research reveals that the technology innovation benefit and eco-environmental governance and endowment are the prominent factors for optimizing the two systems. Moreover, the findings show that the coupling coordination degree of eco-environment and technology innovation in China presents an upward trend. In terms of the dynamic interaction between technology innovation and eco-environment, the influence of the former on the latter is timely while that of the latter on the former is lagging (except for the central region). The weak coupling coordination degree implies that the mutual promotion of technology innovation and eco-environmental systems has not yet formed. The policy implications are proposed accordingly to promote coordinated development of eco-environment and technology innovation in China.

18.
Genet Med ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34194003

RESUMO

PURPOSE: Congenital hypothyroidism (CH) is a common congenital endocrine disorder in humans. CH-related diseases such as athyreosis, thyroid ectopy, and hypoplasia are primarily caused by dysgenic thyroid development. However, the underlying molecular mechanisms remain unknown. METHODS: To identify novel CH candidate genes, 192 CH patients were enrolled, and target sequencing of 21 known CH-related genes was performed. The remaining 98 CH patients carrying no known genes were subjected to exome sequencing (ES). The functions of the identified variants were confirmed using thyroid epithelial cells in vitro and in zebrafish model organisms in vivo. RESULTS: Four pathogenic GBP1 variations from three patients were identified. In zebrafish embryos, gbp1 knockdown caused defective thyroid primordium morphogenesis and hypothyroidism. The thyroid cells were stuck together and failed to dissociate from each other to form individual follicles in gbp1-deficient embryos. Furthermore, defects were restored with wild-type human GBP1 (hGBP1) messenger RNA (mRNA) except for mutated hGBP1 (p.H150Y, p.L187P) overexpression. GBP1 promoted ß-catenin translocation into the cytosol and suppressed the formation of cellular adhesion complexes. Suppression of cell-cell adhesion restored the thyroid primordium growth defect observed in gbp1-deficient zebrafish embryos. CONCLUSION: This study provides further understanding regarding thyroid development and shows that defective cellular remodeling could cause congenital hypothyroidism.

19.
Mar Pollut Bull ; 169: 112551, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34119960

RESUMO

Increasing human activities have caused the accumulation of dissolved organic nitrogen (DON) in the ocean, which can alter dominant coastal phytoplankton species. However, insights into DON's effects on marine phytoplankton growth are insufficient compared with those of dissolved inorganic nitrogen (DIN), especially regarding the role of specific DON components. Therefore, in this study, the effects of the hydrophilic (Hic) and low molecular weight (LMW) components of two anthropogenic DON sources on the growth and bioavailable nitrogen uptake of phytoplankton were studied using in situ cultural experiments conducted in Jiaozhou Bay, China. Animal-derived DON from domestic and livestock breeding showed a higher bioavailability compared with that of vegetal DON derived from agricultural sources, with bioavailable component proportions of 76% ± 4% and 66% ± 3%, respectively. Both forms of DON could be absorbed by Skeletonema costatum, stimulating it to become the dominant species in the mesocosm ecosystem; the hydrophilic components of DON contributed approximately 75% of the uptake of DON by S. costatum. The bioavailability of LMW DON was significantly (p < 0.05) lower than that of the Hic DON. The high bioavailability of the Hic DON was mainly associated with its protein-like T1 and T2 components, identified using parallel factor analysis on the excitation-emission-matrix spectra, while the low bioavailability of LMW DON was mainly associated with the humus-like A component. The protein-like T2 components may be directly absorbed by algae, while T1 may be transformed through mineralization and algal absorption. Understanding the impacts of anthropogenic DON and its components on phytoplankton will help improve coastal environmental management. More knowledge of the effect of anthropogenic DON on the phytoplankton community structure in coastal waters should be accumulated in the future.

20.
Surg Oncol ; 38: 101610, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34091268

RESUMO

INTRODUCTION: There is currently no consensus regarding the best techniques or surgical strategies with which to maximize intercalary allograft reconstruction outcomes. The purpose of the current study was to assess which techniques and methods are being utilized by North American orthopaedic oncologists. METHODS: Members of the Musculoskeletal Tumor Society (MSTS) were invited to complete an anonymous online questionnaire. The survey presented participants with two clinical scenarios and interrogated them on their preferred type of allograft, method of compression and fixation, and additional techniques used. RESULTS: One hundred and twenty-six physicians completed the questionnaire. The majority studied in the United States (82%) and worked at an academic medical center (71%). Over half (54%) reported seeing over 10 primary bone tumors every year. Respondents were split between preferring a structural allograft alone or using a combined allograft-vascularized fibular graft. A majority indicated a preference for plate(s) and screw fixation but were divided between the use of two compression plates with a spanning plate, a single compression plate with a spanning plate, and two compression plates with an intramedullary nail. Screw fixation preferences were split between the use of unicortical locking only, bicortical locking only, and a combination of unicortical and bicortical locking. Almost equal percentages of respondents reported they would have used two, three, or four screws in both scenarios. Respondents were split between placing screws equidistantly and placing them peripherally within the allograft, adjacent to the allograft-host junction. DISCUSSION: There is no clear surgical preference for intercalary reconstruction following tumor extirpation within this sample of orthopaedic oncologists. The current survey demonstrates variability across nearly every aspect of allograft reconstruction, which may, in part, explain the wide spectrum of outcomes reported within the literature. Prospective studies are warranted to better evaluate technique-specific outcomes in an effort to maximize reconstructive longevity and minimize allograft related complications.

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