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1.
Cell Cycle ; : 1-18, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064976

RESUMO

Prostate cancer (PC) is the most common malignancy in men. As per recent findings, microRNA-300 (miR-300) were found to be overexpressed in numerous types of cancers. In this study, we aimed to explore the effects of miR-300 on the adhesion, invasion, and migration of PC cells by targeting Disabled 1 (DAB1). Firstly, the regulatory role of miRNAs on DAB1 was predicted by screening PC-related differentially expressed genes (DEGs). Immunohistochemistry was applied to determine the positive protein expression of DAB1, after which the target relationship between miR-300 and DAB1 was examined. Loss-of-function and gain-of-function experiments were conducted to determine cell proliferation, adhesion, migration, invasion capability, and cell cycle of PC cells. Our data illustrated that DAB1 had a low expression, while miR-300 was expressed at a relatively high level in PC tissues. Moreover, our clinicopathological analysis revealed that there was a correlation between miR-300 and tumor, node, metastases stage, Gleason score, and lymph node metastasis of PC patients. DAB1 was also found to be poorly expressed in PC based on the findings from the microarray analysis. The results from dual-luciferase reporter gene assay corroborated that miR-300 interacts with DAB1. Importantly, overexpression of miR-300 and/or si-DAB1 resulted in the enhancement of RAC1, MMP2, MMP9, CyclinD1, and CyclinE expressions, whereas the expression of DAB1 and Rap was reduced in PC cells, thus suggesting that down-regulated miR-300 suppressed proliferation, adhesion, migration, and invasion of PC cells. Collectively, our results provided evidence that down-regulation of miR-300 inhibits the adhesion, migration, and invasion of PC cells.

2.
Mol Biol Rep ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068229

RESUMO

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

3.
Orthop Surg ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33015952

RESUMO

OBJECTIVE: To siscuss the clinical significance of the early diagnosis of knee varus and knee osteoarthritis with the combination of negative position and non-negative position and radiography. METHODS: One hundred and eighty patients whose femorotibial angles <182° (genu varus positive) measured by X-ray at the weight-bearing position and femorotibial angles ≥182° (genu varus negative) measured by X-ray at the non-weight-bearing position were selected as the sample group from those patients who received knee joint Magnetic resonance imaging (MRI) examination from July 2015 to July 2017. One hundred and eighty patients whose femorotibial angles ≥182° (genu varus negative) measured at both the weight-bearing position and the non-weight-bearing position were selected as the control group. Femorotibial angles of both groups were respectively measured, to respectively compare and analyze the effect of non-weight-bearing false-negative genu varus on the occurrence and severity of injury of medial meniscus and femorotibial articular cartilage. The two groups of patients had no previous history of knee surgery, and no lower limb fracture, inflammation, tumor, metabolic bone disease, or congenital disease. RESULTS: The weight-bearing tibiofemoral angles of the non-weight-bearing false-negative genu varus group and the negative genu varus group (180.998° ± 0.589°) were lower than the non-weight-bearing tibiofemoral angles (182.501° ± 0.290°), and they were positively correlated (t = -15.048, P < 0.01). The non-weight-bearing knee varus medial meniscus incidence of false- negative group. Medial meniscus injury that occurred in the sample group were 86.7% (156/180) in the anterior horn, 91.7% (165/180) in the body, 88.3% (159/180) in the posterior horn. Medial meniscus injury that occurred in the control group were 46.7% (84 /180) in the anterior horn, 40.6.3% (73/180) in the body, 43.3% (78/180) in the posterior horn. The incidence of degenerative groups, the differences were statistically significant. The incidence and severity of injury were as follows: medial meniscus anterior horn (χ2 = 41.966, P = 0.000), body (χ2 = 104.94, P = 0.000), posterior horn (χ2 = 81.025, P = 0.000). The incidence and severity of medial meniscus injury in the non-weight-bearing knee varus false negative group was higher than in the control group. The non-weight-bearing knee varus false-negative group medial tibiofemoral articular cartilage degeneration rate was 95.0% (171/180); in the control group, medial tibiofemoral articular cartilage degeneration was 65.1% (117/180). Two medial tibiofemoral articular cartilage degeneration incidence were statistically significant. The incidence and severity of injury were as follows: medial tibiofemoral articular cartilage (χ2 = 50.625, P = 0.000). The incidence and severity of medial tibiofemoral articular cartilage injury in the non-weight-bearing knee varus false negative group was higher than in the control group. CONCLUSION: The combined weight-bearing position and non-weight-bearing position imaging examination for diagnosing the non-weight-bearing false-negative genu varus patients at an early date is of significant importance to the early diagnosis and treatment of knee osteoarthritis.

4.
Adv Mater ; : e2003471, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33029855

RESUMO

As a common feature in a majority of malignant tumors, hypoxia has become the Achilles' heel of photodynamic therapy (PDT). The development of type-I photosensitizers that show hypoxia-tolerant PDT efficiency provides a straightforward way to address this issue. However, type-I PDT materials have rarely been discovered. Herein, a π-conjugated molecule with A-D-A configuration, COi6-4Cl, is reported. The H2 O-dispersible nanoparticle of COi6-4Cl can be activated by an 880 nm laser, and displays hypoxia-tolerant type I/II combined PDT capability, and more notably, a high NIR-II fluorescence with a quantum yield over 5%. Moreover, COi6-4Cl shows a negligible photothermal conversion effect. The non-radiative decay of COi6-4Cl is suppressed in the dispersed and aggregated state due to the restricted molecular vibrations and distinct intermolecular steric hindrance induced by its four bulky side chains. These features make COi6-4Cl a distinguished single-NIR-wavelength-activated phototheranostic material, which performs well in NIR-II fluorescence-guided PDT treatment and shows an enhanced in vivo anti-tumor efficiency over the clinically approved Chlorin e6, by the equal stresses on hypoxia-tolerant anti-tumor therapy and deep-penetration imaging. Therefore, the great potential of COi6-4Cl in precise PDT cancer therapy against hypoxia challenges is demonstrated.

5.
Plant Dis ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021909

RESUMO

Buckwheat (Fagopyrum tataricum) is a traditional short-season pseudocereal crop originating in southwest China and is cultivated around the world. Antioxidative substances in buckwheat have been shown to provide many potential cardiovascular health benefits. Between August and November in 2019, a leaf spot was found in several Tartary buckwheat cv. Pinku1 fields in Xiangxiang County, Hunan Province, China. The disease occurred throughout the growth cycle of buckwheat after leaves emerged, and disease incidence was approximately 50 to 60%. Initially infected leaves developed a few round lesions, light yellow to light brown spots. Several days later, lesions began to enlarge with reddish brown borders, and eventually withered and fell off. Thirty lesions (2×2 mm) collected from three locations with ten leaves in each location were sterilized in 70% ethanol for 10 sec, in 2% sodium hypochlorite for 30 sec, rinsed in sterile water for three times, dried on sterilized filter paper, and placed on a potato dextrose PDA with lactic acid (3 ml/L), and incubated at 28°C in the dark for 3 to 5 days. Fungal colonies were initially white and later turned black with the onset ofsporulation. Conidia were single-celled, black, smooth, spherical to subspherical, and measured 9.2 to 15.6 µm long, and 7.1 to 11.6 µm wide (n=30). Each conidium was terminal and borne on a hyaline vesicle at the tip of conidiophores. Morphologically, the fungus was identified as Nigrospora osmanthi (Wang et al. 2017). Identification was confirmed by amplifying and sequencing the ITS region, and translation elongation factor 1-alpha (TEF1-α) and partial beta-tublin (TUB2) genes using primers ITS1/ITS4 (Mills et al. 1992), EF1-728F/EF-2 (Carbone and Kohn 1999; O'Donnell et al. 1998) and Bt-2a/Bt-2b (Glass et al. 1995), respectively. BLAST searches in GenBank indicated the ITS (MT860338), TUB2 (MT882054) and TEF1-α (MT882055) sequences had 99.80%, 99% and 100% similarity to sequences KX986010.1, KY019461.1 and KY019421.1 of Nigrospora osmanthi ex-type strain CGMCC 3.18126, respectively. A neighbor-joining phylogenetic tree constructed using MEGA7.0 with 1,000 bootstraps based on the concatenated nucleotide sequences of the three genes indicated that our isolate was closely related to N. osmanthi. Pathogenicity test was performed using leaves of healthy F. tataricum plants. The conidial suspension (1 × 106 conidia/ml) collected from PDA cultures with 0.05% Tween 20 buffer was used for inoculation by spraying leaves of potted 20-day-old Tartary buckwheat cv. Pinku1. Five leaves of each plant were inoculated with spore suspensions (1 ml per leaf). An equal number of control leaves were sprayed with sterile water to serve as a control. The treated plants were kept in a greenhouse at 28°C and 80% relative humidity for 24 h, and then transferred to natural conditions with temperature ranging from 22 to 30°C and relative humidity ranging from 50 to 60%. Five days later, all N. osmanthi-inoculated leaves developed leaf spot symptoms similar to those observed in the field, whereas control leaves remained healthy. N. osmanthi was re-isolated from twelve infected leaves with frequency of 100%, fulfilling Koch's postulates. The genus Nigrospora has been regarded by many scholars as plant pathogens (Fukushima et al. 1998) and N. osmanthi is a known leaf blight pathogen for Stenotaphrum secundatum (Mei et al. 2019) and Ficus pandurata (Liu et al. 2019) but has not been reported on F. tataricum. Nigrospora sphaerica was also detected in vegetative buds of healthy Fagopyrum esculentum Moench (Jain et al. 2012). To our knowledge, this is the first report of N. osmanthi causing leaf spot on F. tataricum in China and worldwide. Appropriate strategies should be developed to manage this disease.

6.
Sensors (Basel) ; 20(19)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33027897

RESUMO

Metamaterials, artificially engineered structures with extraordinary physical properties, offer multifaceted capabilities in interdisciplinary fields. To address the looming threat of stealthy monitoring, the detection and identification of metamaterials is the next research frontier but have not yet been explored. Here, we show that the crypto-oriented convolutional neural network (CNN) makes possible the secure intelligent detection of metamaterials in mixtures. Terahertz signals were encrypted by homomorphic encryption and the ciphertext was submitted to the CNN directly for results, which can only be decrypted by the data owner. The experimentally measured terahertz signals were augmented and further divided into training sets and test sets using 5-fold cross-validation. Experimental results illustrated that the model achieved an accuracy of 100% on the test sets, which highly outperformed humans and the traditional machine learning. The CNN took 9.6 s to inference on 92 encrypted test signals with homomorphic encryption backend. The proposed method with accuracy and security provides private preserving paradigm for artificial intelligence-based material identification.

7.
Mater Sci Eng C Mater Biol Appl ; 117: 111295, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919656

RESUMO

Zinc is a biodegradable metal, which exhibits more moderate biodegradability than magnesium and iron, so that it has great application potential in the field of biomedical materials. Alloying of zinc and iron may lead to producing a new type of implant material Zn-Fe alloy, which might be able to meet the requirements for a moderate degradation rate. However, due to the huge difference in the melting point between zinc and iron, the preparation of Zn-Fe alloy is quite challenging and hence rarely reported. In this study, we show that Zn-Fe alloys can be successfully prepared by electrodeposition technology. The microstructures, composition, degradation properties and biocompatibility of the Zn-Fe alloys were systematically studied. The results showed that the content of iron in the alloys ranged from 0 to 8 wt%, depending on the concentration of Fe ions and the current density. In the alloys, the major's phases were η, δ and Г1, and they were mainly affected by the ion concentration in the electrolyte. In the in vitro immersion tests, the Zn-Fe alloy ZF2-1 showed the highest immersion corrosion rate, while ZF3-1 showed the highest electrochemical corrosion rate. Moreover, we found that the corrosion rates of the alloys were significantly higher than that of the pure Fe. In the in vivo experiments, we confirmed that the Zn-Fe alloy possessed good biocompatibility. These results demonstrate that the electrodeposition technology is a good method to prepare Zn-Fe alloys, and the Zn-Fe alloys prepared by this method are potentially promising materials for biomedical applications.

8.
Nutrients ; 12(9)2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32932868

RESUMO

We compared the sodium intake and systolic blood pressure (SBP) relationship from complete 24-h urine samples determined by several methods: self-reported no-missed urine, creatinine index ≥0.7, measured 24-h urine creatinine (mCER) within 25% and 15% of Kawasaki predicted urine creatinine, and sex-specific mCER ranges (mCER 15-25 mg/kg/24-h for men; 10-20 mg/kg/24-h for women). We pooled 10,031 BP and 24-h urine sodium data from 2143 participants. We implemented multilevel linear models to illustrate the shape of the sodium-BP relationship using the restricted cubic spline (RCS) plots, and to assess the difference in mean SBP for a 100 mmol increase in 24-h urine sodium. The RCS plot illustrated an initial steep positive sodium-SBP relationship for all methods, followed by a less steep positive relationship for self-reported no-missed urine, creatinine index ≥0.7, and sex-specific mCER ranges; and a plateaued relationship for the two Kawasaki methods. Each 100 mmol/24-h increase in urinary sodium was associated with 0.64 (95% CI: 0.34, 0.94) mmHg higher SBP for self-reported no-missed urine, 0.68 (95% CI: 0.27, 1.08) mmHg higher SBP for creatinine index ≥0.7, 0.87 (95% CI: 0.07, 1.67) mmHg higher SBP for mCER within 25% Kawasaki predicted urine creatinine, 0.98 (95% CI: -0.07, 2.02) mmHg change in SBP for mCER within 15% Kawasaki predicted urine creatinine, and 1.96 (95% CI: 0.93, 2.99) mmHg higher SBP for sex-specific mCER ranges. Studies examining 24-h urine sodium in relation to health outcomes will have different results based on how urine collections are deemed as complete.

9.
Hypertension ; 76(5): 1580-1588, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981359

RESUMO

This study aimed to assess current level of sodium and potassium intake and their associations with blood pressure (BP) using the 24-hour urinary data in a large sample of China. Data from participants aged 18 to 75 years were collected as the baseline survey of Action on Salt China in 2018. Of 5454 adults, 5353 completed 24-hour urine collection. The average sodium, potassium excretion, and sodium-to-potassium molar ratio were 4318.1±1814.1 mg/d (equivalent to 11.0±4.6 g/d of salt), 1573.7±627.1 mg/d, and 5.0±2.1, respectively. After adjusting for potential confounding factors and correcting for regression dilution, each 1000-mg increase in sodium excretion was associated with increased systolic BP (1.32 mm Hg [95% CI, 0.92-1.81]) and diastolic BP (0.34 mm Hg [95% CI, 0.09-0.60]). Each 1000-mg increase in potassium excretion was inversely associated with systolic BP (-3.19 mm Hg [95% CI, -4.38 to -2.20]) and diastolic BP (-1.56 mm Hg [95% CI, -2.29 to -0.90]). Each unit increase in sodium-to-potassium molar ratio was associated with an increase of systolic BP by 1.21 mm Hg (95% CI, 0.91-1.60) and diastolic BP by 0.44 mm Hg (95% CI, 0.24-0.64). The relationships between sodium and BP mostly increase with the rise of BP quantiles. Potassium shows the opposite trend. The current sodium intake in Chinese adults remains high and potassium intake is low. Sodium and sodium-to-potassium ratio were positively associated with BP, whereas potassium was inversely associated with BP. Registration- URL: https://tinyurl.com/vdr8rpr; Unique identifier: ChiCTR1800017553. URL: https://tinyurl.com/w8c7x3w; Unique identifier: ChiCTR1800016804. URL: https://tinyurl.com/s3ajldw; Unique identifier: ChiCTR1800018119.

10.
Can J Gastroenterol Hepatol ; 2020: 5716981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908852

RESUMO

Aims: The over-the-scope clip (OTSC) has recently emerged as a new endoscopic device for treating gastrointestinal bleeding, perforations, fistulas, and leaks. A modified OTSC device (full-thickness resection device, FTRD) has been widely used for endoscopic full-thickness resection. However, there is less experience regarding the indications and methods for OTSC removal. We aimed to summarize the existing methods and indications for OTSC removal. Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov to identify relevant publications on OTSC removal. The details of OTSC removal, including the methods, indications, success rates, adverse events, and failure causes, were extracted and summarized. A meta-analysis of pooled success rates was conducted using STATA 15.0. Results: Eighteen articles were included. The reported methods for OTSC removal included (1) grasping forceps, (2) the Nd : YAG laser, (3) argon plasma coagulation, (4) the remOVE system, (5) endoscopic mucosal resection/endoscopic submucosal dissection, and (6) ice-cold saline solution. Indications for OTSC removal were (1) poor healing, (2) OTSC misplacement, (3) repeat biopsy/therapy or further treatment, (4) adverse events after OTSC implantation, (5) removal after recovery, and (6) patient wishes. The pooled success rate of OTSC removal was 89% in patients treated with the remOVE system. Minor bleeding, superficial thermal damage, and superficial mucosal tears were common adverse events. Mucosal overgrowth was the main cause of OTSC removal failure. Conclusions: The remOVE system is the best investigated method, with sufficient efficacy and safety for OTSC removal. This is the first systematic review of OTSC removal and provides significant guidance for clinical practice.

11.
Liver Transpl ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918858

RESUMO

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to prevention and treatment. We aim to describe the clinical characteristics and risk factors of COVID-19 patients needing use assisted ventilation therapy. METHODS: In this retrospective cohort study, we included 288 adult inpatients diagnosed with COVID-19 in Guangzhou Eighth People's Hospital. We extracted and compared characteristics between patients using continuous positive airway pressure (CPAP) or not. A binary logistic regression model was used to identify risk factors associated with using CPAP therapy. RESULTS: COVID-19 patients with CPAP therapy were older and had higher levels of white blood cells (WBC), procalcitonin (PCT), C-reactive protein (CRP), alanine aminotransferase (ALT), D-dimer, but had lymphopenia. They were also more prone to appear bilateral pneumonia, develop into severe or critically severe cases, and receive ICU admission. Multivariate regression analysis showed that each 1-year increase in age (OR, 1.04; 95%CI, 1.01-1.08; P = 0.013), respiratory rate over 24 times per min (OR, 4.78; 95%CI, 1.08-13.17; P = 0.037), diarrhea (OR, 9.62; 95%CI, 1.57-18.31; P = 0.011), ALT greater than 50 U/L (OR, 6.59; 95%CI, 1.35-15.89; P = 0.003), WBC greater than 10×109/L (OR, 5.42; 95%CI, 2.04-14.75; P = 0.008), PCT greater than 0.05 ng/mL (OR, 7.22; 95%CI, 1.64-18.51; P = 0.018), and CRP greater than 10 mg/L (OR, 8.58; 95%CI, 2.28-20.36; P = 0.030) were risk factors for COVID-19 inpatients with assisted ventilation. CONCLUSION: The older age, tachypnea, and gastrointestinal infections showing as diarrhea, elevated ALT, and elevated white blood cells, procalcitonin and C-reactive protein were risk factors for COVID-19 inpatients with assisted ventilation. Investigating and monitoring these factors could help clinicians identify patients with poor prognosis at an early stage and take proactive assisted ventilation to benefit patients.

12.
Water Res ; 186: 116379, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32911268

RESUMO

Submerged macrophyte restoration is the key stage in the reestablishment of an aquatic ecosystem. Previous studies have paid considerable attention to the effect of multiple environmental factors on submerged macrophytes. Meanwhile, few studies have been conducted regarding the spatial and seasonal characteristics of water and sediment properties and their long-term relationship with submerged macrophytes after the implementation of the submerged macrophytes restoration project. On a monthly basis, we monitored the spatial and seasonal variation in water parameters, sediment properties, and the submerged macrophyte characteristics of West Lake in Hangzhou from August 2013 to July 2019. From these measurements, we characterized the relationship between environmental factors and submerged macrophytes. Water nutrient concentrations continuously decreased with time, and the accumulation of sediment nutrients was accelerated as the submerged macrophyte communities developed on a long-term scale. The results indicated that the difference in water parameters was due to seasonal changes and land-use types in the watershed. The differences in the sediment properties were mainly attributed to seasonal changes and changes in the flow field. Redundancy analysis showed that the influence of water nutrients on the submerged macrophyte distribution was greater than that of sediment nutrients. The result also suggested that the developed root system, high stoichiometric homeostasis coefficients of P, and compensation ability of substantial leaf tissue may lead to a large distribution of Vallisneria natans in West Lake in Hangzhou. The correlation of water parameters and sediment properties with submerged macrophytes for a long time was very important as the restoration was achieved. To ensure the stability of the aquatic ecosystem after performing the submerged macrophyte restoration, a greater emphasis must be placed on reestablishing the entire ecosystem, including the restoration of aquatic animals and fish stocks. We expect these findings to serve as a reference for researchers and government agencies in the field of aquatic ecosystem restoration.

13.
Environ Pollut ; 267: 115380, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32892006

RESUMO

The effects of maifanite on the physiological and phytochemical process of submerged macrophytes Hydrilla verticillate (H.verticillata) were investigated for the first time in the study. The growth index: plant biomass, root length, plant height and leaf spacing, and physiological and phytochemical indexes: chlorophyll, soluble protein, malondialdehyde (MDA), peroxidase (POD), superoxide dismutase (SOD) content and vitality of the roots of H.verticillata were tested. The results found that maifanite can significantly promote the growth of H.verticillata. The modified maifanite were more conducive to plant growth compared with the raw maifanite, and the MM1 group had the best growth promoting effect. The physiological and phytochemical indexes showed that maifanite can delay the aging process of H.verticillata (P < 0.05). The possible reasons for promoting H.verticillata growth were that maifanite can provide excellent propagation conditions for plant rhizosphere microorganisms, contains abundant major and microelements, and improve the sediment microenvironment. This study may provide a technique for the further application of maifanite in the field of ecological restoration.

14.
Nat Prod Res ; : 1-8, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32927980

RESUMO

Penicillium polonicum MCCC3A00951 is a fungus with influenza neuraminidase (NA) inhibition activity derived from a sediment of the mangrove forest of Zhangjiangkou in Fujian province, China. Chemical investigation on an ethyl acetate extract of its fermentation led to the isolation of a new compound, 7-hydroxy-3,10-dehydrocyclopeptine (1), and 13 known compounds (2-14). The new compound was comprehensively characterised by high-resolution electrospray ionisation-mass spectrometry, and 1D, 2D nuclear magnetic resonance (NMR) spectra. The anti-influenza NA assay was performed to evaluate the potential biological activity. Surprisingly, Cyclopenin (2) showed potent influenza NA inhibition with an IC50 value of 5.02 µM. Besides, molecular docking simulation was performed to investigate the binding model of cyclopenin (2) with influenza NA. Consequently, cyclopenin (2) could be further optimised to be a potential anti-influenza NA candidate.

15.
Nucleic Acids Res ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32986831

RESUMO

Nucleotide excision repair (NER) removes various DNA lesions caused by UV light and chemical carcinogens. The DNA helicase XPB plays a key role in DNA opening and coordinating damage incision by nucleases during NER, but the underlying mechanisms remain unclear. Here, we report crystal structures of XPB from Sulfurisphaera tokodaii (St) bound to the nuclease Bax1 and their complex with a bubble DNA having one arm unwound in the crystal. StXPB and Bax1 together spirally encircle 10 base pairs of duplex DNA at the double-/single-stranded (ds-ss) junction. Furthermore, StXPB has its ThM motif intruding between the two DNA strands and gripping the 3'-overhang while Bax1 interacts with the 5'-overhang. This ternary complex likely reflects the state of repair bubble extension by the XPB and nuclease machine. ATP binding and hydrolysis by StXPB could lead to a spiral translocation along dsDNA and DNA strand separation by the ThM motif, revealing an unconventional DNA unwinding mechanism. Interestingly, the DNA is kept away from the nuclease domain of Bax1, potentially preventing DNA incision by Bax1 during repair bubble extension.

16.
Aging Dis ; 11(4): 763-769, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32765943

RESUMO

Previous studies on coronavirus disease 2019 (COVID-19) have focused on the general population. However, cardiovascular disease (CVD) is a common comorbidity that has rarely been investigated in detail. This study aims to describe clinical characteristics and determine risk factors for intensive care unit (ICU) admission of COVID-19 patients with CVD. In this retrospective cohort study, we included 288 adult patients with COVID-19 in Guangzhou Eighth People's Hospital from January 15, 2020 to March 10, 2020. Demographic characteristics, laboratory results, radiographic findings, complications, and treatments were recorded and compared between CVD and non-CVD groups. A binary logistic regression model was used to identify risk factors associated with ICU admission for infected patients with underlying CVD. COVID-19 patients in the CVD group were older and had higher levels of troponin I (TnI), C-reactive protein (CRP), and creatinine. They were also more prone to develop into severe or critically severe cases, receive ICU admission, and require respiratory support treatment. Multivariate regression analysis showed that the following were risk factors for ICU admission in COVID-19 patients with CVD: each 1-year increase in age (odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.17; p = 0.018); respiratory rate over 24 times per min (OR, 25.52; 95% CI, 5.48-118.87; p < 0.0001); CRP higher than 10 mg/L (OR, 8.12; 95% CI, 1.63-40.49; p = 0.011); and TnI higher than 0.03 µg/L (OR, 9.14; 95% CI, 2.66-31.43; p < 0.0001). Older age, CRP greater than 10 mg/L, TnI higher than 0.03 µg/L, and respiratory rate over 24 times per minute were associated with increasing odds of ICU admission in COVID-19 patients with CVD. Investigating and monitoring these factors could assist in the risk stratification of COVID-19 patients with CVD at an early stage.

17.
Bioorg Chem ; 103: 104109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768741

RESUMO

Histone deacetylases (HDACs) have been indicated important roles in neurodegenerative disorders including Alzheimer's disease (AD). Herein, a series of novel compounds that contain a memantine moiety were designed to target HDACs and N-methyl-d-aspartate receptor (NMDAR) which are related to the treatment of AD. Biological characterization established that compound 9d exhibited a balanced inhibitory activity on NMDAR and HDACs. This compound is relatively selective to HDAC6 with IC50 of 0.18 µM and also maintains comparable activity on NMDAR (Ki = 0.59 µM) as memantine. Functionally, treatment with 9d increased the level of AcTubulin in MV4-11 cells and rescued PC-12 cells from H2O2-induced cytotoxicity with EC50 of 0.94 µM. Studies in mice also demonstrated that compound 9d efficiently penetrates the blood brain barrier to reach the brain tissue. Collectively, the results strongly encourage further development of 9d as a potential therapeutic agent for AD.

18.
Phys Rev Lett ; 125(7): 073202, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32857561

RESUMO

Interaction of a strong laser pulse with matter transfers not only energy but also linear momentum of the photons. Recent experimental advances have made it possible to detect the small amount of linear momentum delivered to the photoelectrons in strong-field ionization of atoms. We present numerical simulations as well as an analytical description of the subcycle phase (or time) resolved momentum transfer to an atom accessible by an attoclock protocol. We show that the light-field-induced momentum transfer is remarkably sensitive to properties of the ultrashort laser pulse such as its carrier-envelope phase and ellipticity. Moreover, we show that the subcycle-resolved linear momentum transfer can provide novel insights into the interplay between nonadiabatic and nondipole effects in strong-field ionization. This work paves the way towards the investigation of the so-far unexplored time-resolved nondipole nonadiabatic tunneling dynamics.

19.
Trends Plant Sci ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32861572

RESUMO

Activation of plant respiratory burst oxidase homologs (RBOHs) to generate reactive oxygen species (ROS) is a crucial defense signaling event. RBOH activation occurs predominantly through N-terminal phosphorylation and the binding of a small GTPase. Two recent papers reported that C-terminal phosphorylation and ubiquitination modulates AtRBOHD activity, which extends our understanding of the fine-tuning of RBOH signaling in plant immunity.

20.
Brain Inj ; 34(10): 1339-1349, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32811203

RESUMO

OBJECTIVE: Mild TBI (mTBI) and posttraumatic stress disorder (PTSD) are independent risk factors for suicidal behaviour (SB). Further, co-occurring mTBI and PTSD increase one's risk for negative health and psychiatric outcomes. However, little research has examined the role of comorbid mTBI and PTSD on suicide risk. METHODS: The present study utilized data from the Injury and TRaUmatic STress (INTRuST) Consortium to examine the prevalence of suicidal ideation (SI) and behaviours among four groups: 1) comorbid mTBI+PTSD, 2) PTSD only, 3) mTBI only, and 4) healthy controls. RESULTS: Prevalence of lifetime SI, current SI, and lifetime SB for individuals with mTBI+PTSD was 40%, 25%, and 19%, respectively. Prevalence of lifetime SI, current SI, and lifetime SB for individuals with PTSD only was 29%, 11%, and 11%, respectively. Prevalence of lifetime SI, current SI, and lifetime SB for individuals with mTBI only was 14%, 1%, and 2%, respectively. Group comparisons showed that individuals with mTBI alone experienced elevated rates of lifetime SI compared to healthy controls. History of mTBI did not add significantly to risk for suicidal ideation and behaviour beyond what is accounted for by PTSD. CONCLUSION: Findings suggest that PTSD seems to be driving risk for suicidal behaviour.

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