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1.
Huan Jing Ke Xue ; 42(7): 3198-3205, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212645

RESUMO

According to a spatial distribution analysis of phosphorus in sediments from Honghu Wetland, it was found that TP content in sediments at the mouth of Honghu Lake was 781.31-1955.84 mg·kg-1 and the average value was(1287.21±437.28)mg·kg-1. TP content in sediments in the open water area was 438.33-1554.04 mg·kg-1, with an average value of(718.10±238.15)mg·kg-1. The TP content of sediments in lake inlet was significantly higher than that of sediments in the open water area(P<0.05), and that in the enclosed aquaculture was higher than in the open water area, although no significant difference was observed (P>0.05). The TP content of sediments to the northwest and northeast of Honghu Lake was higher than that to the southwest of Honghu Lake, and the TP content of sediments in The Four-lake main canal was significantly higher than that of Luoshan main canal(P<0.05). The phosphorus input in the Four-lake main canal may be the main source of phosphorus in Honghu Lake sediments. The phosphorus fraction composition in sediments from different sampling sites were significantly different. Fe/Al-P and Ca-P were the main forms of phosphorus in sediments from the lake inlet, while OP and Ca-P were the main forms of phosphorus in sediments from the open water area. The variation in spatial phosphorus form composition was related to the influence of human activity and the distribution of aquatic plants. Fe/Al-P and OP contents were used to estimate the content of biological available phosphorus (BAP) in evaluated sediments, and the proportion of BAP in TP was used to estimate the risk of phosphorus release in Honghu sediments. BAP/TP was 39.8%-69%, with an average of(56.5±7.23)%, indicating a high risk of phosphorus release. OP and BAP were significantly correlated with TP in overlying water(P<0.01), and the correlation between BAP and phosphate in the overlying water was the highest. The results showed that phosphorus concentration in the overlying water may be related to the release of Fe/Al-P and OP into water bodies.


Assuntos
Fósforo , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Lagos , Fósforo/análise , Poluentes Químicos da Água/análise , Áreas Alagadas
2.
Sci Total Environ ; 794: 148700, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34214810

RESUMO

Screening priority pollutants from vast anthropogenic contaminants discharged into aquatic environment is urgent for protecting water quality definitely. The multi-criteria scoring method involved in the occurrence (O), persistence (P), bioaccumulation (B), ecological risk (Eco-T), and human health risk (Hum-T), was established for pollutants prioritization in waters and applied in Dongping Lake, the final impoundment reservoir along the eastern route of China's South-to-North Water Diversion Project (SNWDP). A total of 170 chemicals including heavy metals (HMs), volatile organic chemicals (VOCs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), phthalate esters (PAEs), and antibiotics (ANTs) were investigated as the candidates. Accordingly, 42 chemicals including 8 PAEs, 7 OCPs, 7 PCBs, 5 PAHs, 13 HMs, and 2 VOCs were made up the list of priority pollutants for Dongping Lake, suggesting the necessity of routine monitoring high priority groups and revising the existing list. Multiple risk assessment indicated higher ecological and human health risks induced by HMs than by organic pollutants. Spatial distribution of risks stressed the retention of toxic organic chemicals by the lake body and the accumulation of HMs along the transfer route, respectively, thus triggering ecosystem responses and potential effects on the water-receiving areas as expected.

3.
Reprod Biol Endocrinol ; 19(1): 100, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215266

RESUMO

Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the "junk" of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

4.
Front Endocrinol (Lausanne) ; 12: 605797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234737

RESUMO

Pheochromocytoma (PCC) is a rare neuroendocrine tumor of the adrenal gland with a high rate of mortality if diagnosed at a late stage. Common symptoms of pheochromocytoma include headache, anxiety, palpitation, and diaphoresis. Different treatments are under observation for PCC but there is still no effective treatment option. Recently, the gene expression profiling of various tumors has provided new subtype-specific options for targeted therapies. In this study, using data sets from TCGA and the GSE19422 cohorts, we identified two distinct PCC subtypes with distinct gene expression patterns. Genes enriched in Subtype I PCCs were involved in the dopaminergic synapse, nicotine addiction, and long-term depression pathways, while genes enriched in subtype II PCCs were involved in protein digestion and absorption, vascular smooth muscle contraction, and ECM receptor interaction pathways. We further identified subtype specific genes such as ALK, IGF1R, RET, and RSPO2 for subtype I and EGFR, ESR1, and SMO for subtype II, the overexpression of which led to cell invasion and tumorigenesis. These genes identified in the present research may serve as potential subtype-specific therapeutic targets to understand the underlying mechanisms of tumorigenesis. Our findings may further guide towards the development of targeted therapies and potential molecular biomarkers against PCC.

5.
Acta Pharmacol Sin ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234269

RESUMO

Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.

6.
Mol Cancer Ther ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253595

RESUMO

Dual bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4 and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of GI toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain (BD2) of the four BET family proteins. In contrast to the broad antiproliferative activities observed with DbBi, ABBV-744 displayed significant antiproliferative activities largely although not exclusively in cancer cell lines derived from AML and androgen receptor (AR) positive prostate cancer. Studies in AML xenograft models demonstrated anti-tumor efficacy for ABBV-744 that was comparable to the pan-BET inhibitor ABBV-075 but with an improved therapeutic index. Enhanced anti-tumor efficacy was also observed with the combination of ABBV-744 and the BCL-2 inhibitor, venetoclax compared to monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical Trials.gov identifier: NCT03360006).

7.
Biophys Chem ; 277: 106652, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1283249

RESUMO

Favipiravir (T-705) has been developed as a potent anti-influenza drug and exhibited a strong inhibition effect against a broad spectrum of RNA viruses. Its active form, ribofuranosyl-triphosphate (T-705-RTP), functions as a competitive substrate for the RNA-dependent RNA polymerase (RdRp) of the influenza A virus (IAV). However, the exact inhibitory mechanisms of T-705 remain elusive and subject to a long-standing debate. Although T-705 has been proposed to inhibit transcription by acting as a chain terminator, it is also paradoxically suggested to be a mutagen towards IAV RdRp by inducing mutations due to its ambiguous base pairing of C and U. Here, we combined biochemical assay with molecular dynamics (MD) simulations to elucidate the molecular mechanism underlying the inhibitory functions exerted by T-705 in IAV RdRp. Our in vitro transcription assay illustrated that IAV RdRp could recognize T-705 as a purine analogue and incorporate it into the nascent RNA strand. Incorporating a single T-705 is incapable of inhibiting transcription as extra natural nucleotides can be progressively added. However, when two consecutive T-705 are incorporated, viral transcription is completely terminated. MD simulations reveal that the sequential appearance of two T-705 in the nascent strand destabilizes the active site and disrupts the base stacking of the nascent RNA. Altogether, our results provide a plausible explanation for the inhibitory roles of T-705 targeting IAV RdRp by integrating the computational and experimental methods. Our study also offers a comprehensive platform to investigate the inhibition effect of antivirals and a novel explanation for the designing of anti-flu drugs.

8.
Work ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34275918

RESUMO

BACKGROUND: The quality and safety of drinking water directly affect the health of the local population. However, due to the limited conditions in poor rural areas, the safety of drinking water is more prominent. OBJECTIVE: It aimed to ensure the safety of drinking water quality and population health in poor rural areas. METHODS: A rural poor area was taken as an example, the drinking water plants were monitored during wet season and dry season, respectively, and the water quality indicators of rural drinking water in the city in 2019 were detected and analyzed. Finally, based on the non-carcinogenic risk and carcinogenic risk evaluation model proposed, the health risk assessment of chemical pollutants in drinking water was carried out. RESULTS: In 2019, the qualified rate of drinking water in rural areas of the city was generally low. The average annual carcinogenic risk of drinking water in poor rural areas of the city was 1.57×10-6 (a-1), and the average annual non-carcinogenic risk was 5.38×10-9 (a-1). CONCLUSION: The health risk assessment model proposed can well evaluate the health risks of drinking water. The research provides a scientific basis for the risk management of drinking water of relevant departments.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34279658

RESUMO

(+)-Nootkatone is an important functional sesquiterpene and is comprehensively used in pharmaceutical, cosmetic, agricultural and food flavor industries. However, (+)-nootkatone is accumulated trace amounts in plants, and the demand for industry is mainly met by chemical methods which is harmful to the environment. The oxygen-containing sesquiterpenes prepared using microbial methods can be considered as 'natural'. Microbial transformation has the advantages of mild reaction conditions, high efficiency, environmental protection and strong stereoselectivity, and has become an important method for the production of natural spices. The microbial biosynthesis of (+)-nootkatone from the main precursor (+)-valencene is summarized in this paper. Whole-cell systems of fungi, bacteria, microalgae and plant cells have been employed. It was described that the enzymes involved in the microbial biosynthesis of (+)-nootkatone, including cytochrome p450 enzymes, laccase, lipoxygenase and so on. More recently, the related enzymes were expressed in microbial hosts to heterologous produce (+)-nootkatone, such as Escherichia coli, Pichia pastoris, Yarrowia lipolytica and Saccharomyces cerevisiae. Finally, the development direction of research for realizing industrialization of microbial transformation was summarized and it provided many options for future improved bioprocesses.

10.
Eur J Pharmacol ; : 174338, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34270984

RESUMO

Neuropsychiatric dysfunction and reactive microglia are hallmarks of high-fat diet (HFD)-induced obesity, yet whether these reactive microglia contribute to HFD-induced obesity-related behavioral abnormalities and the underlying mechanisms remain unclear. Here, we show that HFD feeding causes social deficits and anxiety-like behaviors with impaired neuronal activity and alters the gut microbiota, particularly by depleting Lactobacillus reuteri (L. reuteri), in mice. The profiles of microbiome and metabolome in HFD-fed mice predict that specific microbial taxa and their metabolites regulate HFD-induced obesity-related behavioral abnormalities. Oral treatment with the L. reuteri reduces microglial activation and increases dendritic spine density, thus ameliorates social deficits and anxiety in HFD-fed mice. HFD-fed mice that are administered L. reuteri are also found to accumulate butyrate in their gut, sera and brain. Moreover, supplementation of butyrate improves behavioral abnormalities and modulates microglial homeostasis in HFD-fed mice. In addition, selectively removal of microglia through a pharmacologic approach can rescue dendritic spine loss and increase neuronal activity that profoundly alleviates social deficits and anxiety arising from HFD-induced obesity. Overall, this study reveals an unexpected pivotal role of gut commensal-derived butyrate in HFD-induced social deficits and anxiety-like behaviors through regulation of microglial homeostasis and identifies a potential probiotic treatment for HFD-induced obesity-related behavioral abnormalities.

11.
Free Radic Biol Med ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34271106

RESUMO

Reactive oxygen species (ROS)/reactive nitrogen species (RNS)-mediated ferroptosis becomes a novel effective target for anti-cancer treatment. In the present study, we tested the hypothesis that 18-ß-glycyrrhetinic acid (GA), an active compound from medicinal herbal Licorice, could induce the production of ROS/RNS, increase lipid peroxidation and trigger ferroptosis in MDA-MB-231 triple negative breast cancer cells. To confirm the GA's anti-cancer effects, we detected cell viability, apoptosis and ferroptosis in the MDA-MB-231 cells. To explore the effects of GA on inducing ferroptosis, we measured ROS/RNS production, lipid peroxidation, ferrous ion, glutathione (GSH), System Xc-, GPX4, glutathione peroxidases (GPX), NADPH oxidase and iNOS in the MDA-MB-231 cells. The major discoveries are included as below: (1) GA treatment selectively decreased cell viability and induced ferroptosis companied with the increased lipid peroxidation and ferrous ion in the MDA-MB-231 triple negative breast cancer cells. Iron chelator deferoxamine mesylate (DFO) and ferroptosis inhibitor Ferrostatin-1 abolished the effects of GA. (2) GA treatment up-regulated the expression and activity of NADPH oxidase and iNOS, and increased ROS/RNS productions (O2•-, •OH, NO and ONOO-) in the MDA-MB-231 cells; (3) GA down-regulated the expression of SLC7A11 of System Xc-, decreased glutathione (GSH) level and inhibited GPX activity. Taken together, GA could promote the productions of ROS and RNS via activating NADPH oxidases and iNOS, and decreasing GSH and GPX activity, subsequently aggravating lipid peroxidation and triggering ferroptosis in triple-negative breast cancer cells.

12.
Environ Sci Technol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269570

RESUMO

Black carbon (BC) emissions, derived primarily from incomplete fuel combustion, significantly affect the global and regional climate. Mass absorption efficiency (MAE) is one important parameter in evaluating the climate impacts of BC. Here, values and variabilities in the MAE of BC (MAEBC) from real-world residential emissions were investigated from a field campaign covering 163 burning events for different fuel-stove combinations. MAEBC (average: 12 ± 5 m2/g) was normally distributed and varied greatly by 2 orders of magnitude. Statistically significant differences in MAEBC were found for various fuels, while no significant differences were observed among different stoves. The fuel difference explained 72 ± 7% of the MAEBC variation. MAEBC did not correlate with the modified combustion efficiency but positively correlated with the ratio of organic carbon (OC) to elemental carbon (EC) and negatively correlated with char-EC. The OC/EC ratio was not always lower in coal emissions in comparison to biomass burning emissions. Coal- and biomass-burning emissions had different profiles of carbon fractions. Char-EC, OC, OC/EC, and char-EC/soot-EC can explain 68.7% of the MAEBC variation, providing the potential for predicting MAEBC from the carbon fractions, since they are more commonly measured and available.

13.
Sci Rep ; 11(1): 13962, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234240

RESUMO

Fish has poor utilization capacity for glucose metabolism. The possible reasons are related to the core regulatory elements of glucose metabolism: transport proteins. Studies on the species and functions of Sglt1 in aquatic animals are scarce, therefore further studies are needed. In this study, the full length of blunt snout bream (Megalobrama amblycephala) sglt1 (Masglt1) was 2965 bp including 5'-UTR region of 168 bp and a 3'-UTR region of 820 bp. Masglt1 have a highest sequence homology in Cypriniformes fish. MaSglt1 protein was identified as a transmembrane protein with 14 α-helix structures locating plasma membrane by the methods of predicted tertiary structure and immunohistochemical staining. MaSglt1 protein has a hollow channel forms which could be specifically coupled with two Na+ ions to recognize glucose and carry out transmembrane transport. High sglt1 mRNA was found in the intestine and kidney. The mRNA levels of intestinal sglt1 had a positive correlation with dietary starch levels at 3 h after feeding, and the mRNA was significantly higher than that at 24 h, however, the mRNA levels of renal sglt1 presented results opposite to those of intestinal sglt1. The mRNA levels of renal sglt1 had a positive correlation with dietary starch levels at 24 h after feeding, and the expression was significantly higher than that at 3 h. These results confirmed that Masglt11 was mainly found in the intestine and kidney and was located in the cell membrane, playing a role in glucose homeostasis.

14.
J Magn Reson Imaging ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245075

RESUMO

BACKGROUND: The pathophysiological changes in the remote myocardium after acute myocardial infarction (MI) remains less understood. PURPOSE: To assess the inflammation in the remote myocardium post-MI and its association with left ventricular (LV) remodeling using T2 mapping. STUDY TYPE: Prospective. ANIMAL MODEL AND SUBJECTS: Twelve pigs at 3-day post-MI, 6 pigs at 3-month post-MI, 6 healthy pigs; 54 patients at 3-day and 3-month post-MI, 31 healthy volunteers; FIELD STRENGTH/SEQUENCE: A 3 T MRI/ steady-state free-precession sequence for T2 mapping (animals: 0, 30, and 55 msec; human: 0, 25, and 55 msec), phase-sensitive inversion recovery gradient echo for late gadolinium enhancement (LGE), balanced steady free-precession sequence for cine. ASSESSMENT: Infarcted myocardium was defined on LGE, remote T2 was measured on T2 maps. LV remodeling was evaluated as LV end-diastolic volume change index between two scans using cine. CD68 staining was conducted to detect monocyte/macrophage. STATISTICAL TESTS: Student-t test and one-way ANOVA were used to compare remote T2 with normal controls. The association of remote T2 with LV remodeling was assessed using linear regression. P values of <0.05 were used to denote statistical significance. RESULTS: Compared with healthy pigs, remote T2 significantly increased from 3 days to 3 months post-MI (31.43 ± 0.67 vs. 33.53 ± 1.15 vs. 36.43 ± 1.07 msec). CD68 staining demonstrated the inflammation in remote myocardium post-MI but not in healthy pigs. Significant remote myocardial alterations in T2 were also observed in human group (40.51 ± 1.79 vs. 41.94 ± 1.14 vs. 42.52 ± 1.71 msec). In patients, the 3-month remote T2 (ß = 0.432) and remote T2 variation between two scans (ß = 0.554) were both independently associated with LV remodeling. CONCLUSION: T2 mapping could characterize the abnormalities in the remote myocardium post-MI, which was potentially caused by the inflammatory response. Moreover, variations in remote T2 were associated with LV remodeling. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

15.
Anal Chem ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255475

RESUMO

Sentinel lymph node (SLN) detection is of great significance for the prevention and treatment of cancer metastasis. Herein, we introduce silicon nanoparticles (SiNPs)-based exosome (SiNPs@EXO) probes for distinguishing normal and metastatic SLNs. Typically, SiNPs are suitable for stable and long-term tracking of exosomes, while cancer cell-driven exosomes with a tumor-homing effect allow targeting metastatic SLNs. Remarkably, the as-fabricated SiNPs@EXO has the ability to label metastatic SLNs, i.e., the fluorescence signal in SLNs reaches the peak within 0.5 h and remains up to 3 h. Comparatively, SLN tracers (e.g., indocyanine green) used clinically can illuminate SLNs 1 h post injection, whereas the signal witnesses a sharp fall then. Moreover, evaluations based on preclinical data confirm the negligible side effects of the SiNPs@EXO. Our results provide new tools for targeting SLNs and predicting lymphatic metastasis of tumor.

16.
J Diabetes Investig ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34228900

RESUMO

BACKGROUND: To explore the relationship between handgrip strength per weight (HGS/W) and triglyceride glucose index (TyG) and diabetes metabolism (DM), and whether the lower HGS levels precede TyG in China elderly population. METHODS: Two linear regression models were employed to explore the association of whether baseline HGS/W predicted follow-up variation of TyG or baseline TyG predicted follow-up variation of HGS/W. The logistic regression model was used to examine the relationship between baseline HGS/W and future DM. RESULTS: A total of 4,561 participants in the China Health and Retirement Longitudinal Study were enrolled, of which 47.0% were men, and the mean age was 58.7 (standard deviation, 8.68) years. A lower baseline HGS/W significantly correlated with a higher level of follow-up TyG (ß = -0.173, P = 0.002). The baseline level of HGS/W was significantly negatively associated with the incidence risk of DM (rate ratio = 0.375, P = 0.004). However, in gender stratification, the statistical association between HGS/W and TyG and DM was only in the male. CONCLUSIONS: Our results demonstrated that the HGS/W was inversely associated with TyG and DM, and lower HGS/W levels preceded TyG levels in the elderly population. However, the effect was inconsistent between males and females, and the possible mechanism would need further clarification.

17.
Neurol Res ; : 1-10, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229565

RESUMO

Background: Gadolinium enhancement on high resolution magnetic resonance imaging (HR-MRI) has been considered a sign of instability and inflammation of intracranial atherosclerotic plaques. Our research objective was to explore the relationship between the extent of plaque enhancement (PE), the degree of intracranial artery stenosis, and acute ischemic stroke events.Methods: HR-MRI was performed in 91 patients with intracranial vascular stenosis to determine the existence and intensity of PE.Results: Among 91 patients enrolled in the trial, there were 43 patients in the acute/subacute group (≤1 month from ischemic stroke event), 15 patients in the chronic group (>1 month from ischemic stroke event), and 33 patients in the non-culprit plaques group (no ischemic stroke event). A total of 105 intracranial atherosclerotic plaques were detected in 91 patients. 14 (13.3%) were mild-stenosis plaques, 22 (21.0%) were moderate-stenosis plaques, and 69 (65.7%) were severe-stenosis plaques. There were 12 (11.4%), 18 (17.1%), and 75 (71.4%) plaques in the non-enhanced plaque group, the mild-enhancement group, and the significant-enhancement group, respectively. The degree of PE among the acute/subacute group, the chronic group, and the non-culprit plaque group had a significant difference (P = 0.005). Enhanced plaques were more often observed in culprit plaques (acute/subacute group and chronic group) than non-culprit plaques (96.7% vs 77.3%). Non-enhanced plaques were more often observed in non-culprit plaques than culprit plaques (acute/subacute group and chronic group) (22.7% vs 3.3%). And 36.6% of the enhanced plaques were non-culprit plaques. After performing univariate and multivariate logistic regression analysis, the results showed that strong plaque enhancement (P = 0.025, odds ratio [OR] 3.700, 95% confidence interval [95% CI] 1.182-11.583) and severe stenosis (P = 0.008, OR 4.393, 95%CI 1.481-13.030) were significantly associated with acute ischemic events.Conclusion: Enhanced plaques were more often observed in culprit plaques, and non-enhanced plaques were more often observed in non-culprit plaques. Moreover, significant plaque enhancement and severe ICAS were closely associated with acute ischemic events.

18.
Viruses ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200968

RESUMO

Plant viruses transmitted by hemipteran vectors commonly cause losses to crop production. Rice stripe virus (RSV) and rice black streaked dwarf virus (RBSDV) are transmitted to rice plants by the same vector, the small brown planthopper (SBPH), Laodelphax striatellus Fallén, in a persistent propagative manner. However, rarely do the respective diseases they cause occur simultaneously in a field. Here, we determined the acquisition efficiency of RSV and RBSDV when acquired in succession or simultaneously by SBPH. When RBSDV was acquired first, RSV acquisition efficiency was significantly lower than when only acquiring RSV. However, RBSDV acquisition efficiency from insects that acquired RSV first was not significantly different between the insects only acquiring RBSDV. Immunofluorescence assays showed that the acquisition of RBSDV first might inhibit RSV entry into midgut epithelial cells, but RSV did not affect RBSDV entry. SBPHs were more likely to acquire RBSDV when they were feeding on plants coinfected with the two viruses. When RBSDV was acquired before RSV, RBSDV titer was significantly higher and RSV titer first declined, then increased compared to when only acquiring RBSDV or RSV. Only 5% of the SBPHs acquired both viruses when feeding on plants coinfected with RSV and RBSDV. These results provide a better understanding of the interaction between two persistent viruses when present in the same vector insect and explain why RSV and RBSDV occur in intermittent epidemics.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34252028

RESUMO

Independent mobility poses a great challenge to the visually impaired individuals. This paper proposes a novel system to understand dynamic crosswalk scenes, which detects the key objects, such as crosswalk, vehicle, and pedestrian, and identifies pedestrian traffic light status. The indication of where and when to cross the road is provided to the visually impaired based on the crosswalk scene understanding. Our proposed system is implemented on a head-mounted mobile device (SensingAI G1) equipped with an Intel RealSense camera and a cellphone, and provides surrounding scene information to visually impaired individuals through audio signal. To validate the performance of the proposed system, we propose a crosswalk scene understanding dataset which contains three sub-datasets: a pedestrian traffic light dataset with 7447 images, a dataset of key objects on the crossroad with 1006 images and a crosswalk dataset with 3336 images. Extensive experiments demonstrated that the proposed system was robust and outperformed the state-of-the-art approaches. The experiment conducted with the visually impaired subjects shows that the system is practical useful.

20.
Biophys Chem ; 277: 106652, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34237555

RESUMO

Favipiravir (T-705) has been developed as a potent anti-influenza drug and exhibited a strong inhibition effect against a broad spectrum of RNA viruses. Its active form, ribofuranosyl-triphosphate (T-705-RTP), functions as a competitive substrate for the RNA-dependent RNA polymerase (RdRp) of the influenza A virus (IAV). However, the exact inhibitory mechanisms of T-705 remain elusive and subject to a long-standing debate. Although T-705 has been proposed to inhibit transcription by acting as a chain terminator, it is also paradoxically suggested to be a mutagen towards IAV RdRp by inducing mutations due to its ambiguous base pairing of C and U. Here, we combined biochemical assay with molecular dynamics (MD) simulations to elucidate the molecular mechanism underlying the inhibitory functions exerted by T-705 in IAV RdRp. Our in vitro transcription assay illustrated that IAV RdRp could recognize T-705 as a purine analogue and incorporate it into the nascent RNA strand. Incorporating a single T-705 is incapable of inhibiting transcription as extra natural nucleotides can be progressively added. However, when two consecutive T-705 are incorporated, viral transcription is completely terminated. MD simulations reveal that the sequential appearance of two T-705 in the nascent strand destabilizes the active site and disrupts the base stacking of the nascent RNA. Altogether, our results provide a plausible explanation for the inhibitory roles of T-705 targeting IAV RdRp by integrating the computational and experimental methods. Our study also offers a comprehensive platform to investigate the inhibition effect of antivirals and a novel explanation for the designing of anti-flu drugs.

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