Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.647
Filtrar
1.
Reprod Biol ; 21(3): 100529, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34217103

RESUMO

Progestin and adipoQ receptor 7 (PAQR7) as an indispensable member of membrane progestin receptors in the Progestin and adipoQ receptor (PAQR) family that mediates nongenomic progesterone actions, initiated rapidly at the cell surface. Previous research demonstrated the distribution of PAQR7, which was mainly expressed in reproductive tissues, including ovary and testis. In the male reproductive system, PAQR7 is involved in progestin-induced sperm hypermotility. However, reports studying PAQR7 in female reproductive tissue mainly concentrate on oocyte maturation in fish, its expression in the ovary and gestational tissue, and regulation of uterine functions in mammals. Despite recent advances, many aspects of progestin signaling through PAQR7 are still unclear, especially in female reproductive tissue. Therefore, we reveal the structure and characteristics of PAQR7 and conclude the putative progestin-induced action mediated by PAQR7 in female reproductive tissue, such as the development of ovarian follicles, apoptosis of granulosa cells, oocyte maturation, and development of certain diseases, among others, to review the function of PAQR7 in the female reproductive system in detail.

2.
BMC Genomics ; 22(1): 490, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193045

RESUMO

BACKGROUND: Global climate oscillation, as a selection dynamic, is an ecologically important element resulting in global biodiversity. During the glacial geological periods, most organisms suffered detrimental selection pressures (such as food shortage and habitat loss) and went through population declines. However, during the mild interglacial periods, many species re-flourished. These temporal dynamics of effective population sizes (Ne) provide essential information for understanding and predicting evolutionary outcomes during historical and ongoing global climate changes. RESULTS: Using high-quality genome assemblies and corresponding sequencing data, we applied the Pairwise Sequentially Markovian Coalescent (PSMC) method to quantify Ne changes of twelve representative teleost species from approximately 10 million years ago (mya) to 10 thousand years ago (kya). These results revealed multiple rounds of population contraction and expansion in most of the examined teleost species during the Neogene and the Quaternary periods. We observed that 83% (10/12) of the examined teleosts had experienced a drastic decline in Ne before the last glacial period (LGP, 110-12 kya), slightly earlier than the reported pattern of Ne changes in 38 avian species. In comparison with the peaks, almost all of the examined teleosts maintained long-term lower Ne values during the last few million years. This is consistent with increasingly dramatic glaciation during this period. CONCLUSION: In summary, these findings provide a more comprehensive understanding of the historical Ne changes in teleosts. Results presented here could lead to the development of appropriate strategies to protect species in light of ongoing global climate changes.


Assuntos
Variação Genética , Genoma , Evolução Biológica , Mudança Climática , Ecossistema , Densidade Demográfica
3.
Sci Rep ; 11(1): 13564, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193907

RESUMO

Despite its considerable potential in the manufacturing industry, the application of artificial intelligence (AI) in the industry still faces the challenge of insufficient trust. Since AI is a black box with operations that ordinary users have difficulty understanding, users in organizations rely on institutional cues to make decisions about their trust in AI. Therefore, this study investigates trust in AI in the manufacturing industry from an institutional perspective. We identify three institutional dimensions from institutional theory and conceptualize them as management commitment (regulative dimension at the organizational level), authoritarian leadership (normative dimension at the group level), and trust in the AI promoter (cognitive dimension at the individual level). We hypothesize that all three institutional dimensions have positive effects on trust in AI. In addition, we propose hypotheses regarding the moderating effects of AI self-efficacy on these three institutional dimensions. A survey was conducted in a large petrochemical enterprise in eastern China just after the company had launched an AI-based diagnostics system for fault detection and isolation in process equipment service. The results indicate that management commitment, authoritarian leadership, and trust in the AI promoter are all positively related to trust in AI. Moreover, the effect of management commitment and trust in the AI promoter are strengthened when users have high AI self-efficacy. The findings of this study provide suggestions for academics and managers with respect to promoting users' trust in AI in the manufacturing industry.

4.
Huan Jing Ke Xue ; 42(7): 3166-3175, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212642

RESUMO

Microplastics have been found in many environmental media such as sea water, coastal tidal flats, terrestrial water, sediments, and organisms. Microplastics pollution in inland freshwater lakes have received extensive attention; however, the correlation between eutrophication and microplastics pollution in freshwater lakes remains unclear. In this study, 24 sampling sites were set up in the near shore surface waters of Dianchi Lake, and the pollution characteristics of microplastics such as abundance, composition, particle size, color, and form were evaluated. Water quality parameters related to eutrophication state were analyzed, and the eutrophication indices were further calculated. Specifically, sample pre-treatment was conducted according to the method issued by National Oceanic and Atmospheric Administration (NOAA) of the United States. The color and morphological characteristics of microplastic samples were observed using a stereoscopic microscope, and counts and particle size measurements were performed using Nano Measure 1.2 software. Parts of the samples were selected, and the polymer composition analysis was performed using micro-Fourier Transform infrared (µ-FTIR) spectroscopy. The indices related to eutrophication level evaluation were tested according to the experimental standard methods issued by the Ministry of Ecology and Environment of China. The results showed that the abundance of microplastics in the near shore waters of Dianchi Lake was between 800 and 6000 n·m-3, with an average value of 2867 n·m-3. The types of polymers detected were polyethylene terephthalate (PET), polyetherurethane (PEU), polypropylene (PP), polyethylene (PE), and polyvinyl acetate (PVAc), respectively. The diameter proportion of microplastics in the range of 0.2-0.5 mm was the highest. Fiber microplastics accounted for the most observed type, followed by fragments and films. Among the 24 monitoring sites, it was found that proportions of severe, moderate, and mild eutrophication and mesotrophication sites accounted for 8.33%, 58.33%, 29.17%, and 4.17% of the total sampling sites, respectively, and the main pollutant was total nitrogen (TN). Microplastics abundances in the near shore waters of Dianchi Lake were significantly positively correlated with TN concentrations (P<0.01), whereas they were negatively correlated with chlorophyll a(Chl-a)concentrations, not reaching a significant level (P>0.05). The microplastics abundance and TN concentrations in the north bank water near the main urban area of Kunming were significantly higher than those in the other three banks. Microplastics and TN were considered to potentially have the same origin and be attributed to the tail water discharge from WWTPs.


Assuntos
Microplásticos , Poluentes Químicos da Água , China , Clorofila A , Monitoramento Ambiental , Eutrofização , Sedimentos Geológicos , Lagos/análise , Plásticos , Poluentes Químicos da Água/análise
5.
Huan Jing Ke Xue ; 42(7): 3366-3374, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212662

RESUMO

Wastewater treatment plants (WWTPs) are considered important reservoirs of antibiotic resistance genes (ARGs) and function as the main sources of ARGs in the environment. Membrane bioreactors (MBRs) have been recognized as effective tools for removing ARGs in WWTPs.There are a large number of pathogens and resistance genes in colloids, particulate matter, suspended matter, and microbial metabolites in intercepted wastewater by MBR. However, the distribution characteristics of resistance genes in membrane cleaning sludge remains unclear. In this study, resistance genes of membrane cleaning sludge were analyzed using a metagenomic technique. The results showed that there were 39 phyla in the membrane cleaning sludge. Proteobacteria, Nitrospirae, and Actinobacteria were the dominant phyla. The dominant genera were Nitrospira, Pseudomonas, and Bradyrhizobium. The pathogens accounted for 10.54% of all bacteria in the sample, among which Pseudomonas had the highest abundance, accounting for 3.94%. A total of 17 types of antibiotic resistance genes and 16 types of metal resistance genes (MRGs) (15 types of single metal resistance genes and 1 types of multi-heavy metal resistance gene) were identified. Multidrug resistance genes had the highest abundance, accounting for 49.08%. Multi-heavy metal resistance genes were the most abundant, accounting for 34.58%. The copper resistance genes were the most abundant of the single metal resistance genes, accounting for 19.99%. The most important functional pathway of microbial community in the membrane cleaning sludge was metabolic related, and many genes identified were related to human diseases. The numbers of genes related to bacterial resistance and bacterial infectious diseases were the largest, accounting for 34.50% and 16.62%, respectively. These results indicate that there were abundant ARGs, MRGs, and pathogens in the membrane cleaning sludge, which has potential environmental health risks. It is necessary to strengthen the control of ARGs, MRGs, and pathogens in membrane cleaning sludge to provide guidance for selecting appropriate technologies for effectively removing ARGs, MRGs, and pathogens.


Assuntos
Genes Bacterianos , Esgotos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Humanos , Metagenômica , Águas Residuárias
6.
J Org Chem ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213904

RESUMO

We have developed an efficient formylation of pyrroloisoquinolines using bromoisobutyrate and dimethyl sulfoxide as carbonyl reagent. Various formylated pyrroloisoquinolines could be prepared in good yields (up to 94%). This formylation process can be easily scaled up to gram scale with good yield. In most cases of pyrroloisoquinolines without methoxy groups, the combination of bromoisobutyrate and dimethyl sulfoxide could act as a bromination reagent, delivering brominated pyrroloisoquinolines in acceptable to good yields (up to 82%).

7.
Sci Rep ; 11(1): 13749, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215790

RESUMO

Choroidal thickness is associated with many ocular conditions, interchangeability among different generations of optical coherence tomography is therefore important for both research purpose and clinical application. Hence, we compared choroidal thickness measurements between spectral-domain optical coherence tomography (SD-OCT) and swept-source optical coherence tomography (SS-OCT) in healthy paediatric eyes. A total of 114 children from the population-based Hong Kong Children Eye Study with mean age of 7.38 ± 0.82 years were included. Choroidal thickness of the right eye was measured by both devices. The central foveal choroidal thickness (CFCT) measured by SD-OCT and SS-OCT was 273.24 ± 54.29 µm and 251.84 ± 47.12 µm respectively. Inter-device correlation coefficient was 0.840 (95% CI 0.616-0.918). However, choroidal thickness obtained by SD-OCT was significantly thicker than that measured by SS-OCT with a mean difference of 21.40 ± 33.13 µm (P < 0.001). Bland-Altman limit of agreement on the relative difference scale for SD-OCT/SS-OCT was 86.33 µm. Validated conversion equation for translating SD-OCT CFCT measurement into SS-OCT was SS-OCT = 35.261 + 0.810 × SD-OCT. In conclusion, intra-class correlation coefficient (ICC) shows an acceptable agreement between SD-OCT and SS-OCT, however, there was a significant inter-device difference of choroidal thickness measurements in normal children eyes. Therefore, the measurements are not interchangeable.

8.
Oncoimmunology ; 10(1): 1938381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235004

RESUMO

The effect of anti-programmed cell death 1 (PD-1) antibody in Epstein-Barr virus-associated gastric cancer (EBVaGC) was debatable, and no predictive biomarkers for efficacy have been reported. Public reports on anti-PD-1 antibody monotherapy-treated EBVaGC with available programmed death ligand-1 (PD-L1) expression status were summarized and analyzed. Relevance with clinicopathologic characteristics of PD-L1 expression by immunohistochemistry was analyzed in 159 patients diagnosed with EBVaGC. Relevance with genomic transcriptome and mutation profile of PD-L1 status in EBVaGC was assessed with three datasets, the cancer genome atlas (TCGA), Gene Expression Omnibus (GEO) GSE51575, and GSE62254. Based on the data from 8 reports, patients with positive PD-L1 expression (n = 30) had significantly superior objective response rate (ORR) than patients with negative PD-L1 expression (n = 9) (63.3% vs. 0%, P = .001) in EBVaGC receiving anti-PD-1 antibody monotherapy. PD-L1 positivity was associated with less aggressive clinicopathological characteristics and was an independent predictor for a longer disease-free survival (hazard ratio [HR] and 95% CI: 0.45 [0.22-0.92], P = .03) and overall survival (HR and 95% CI: 0.17 [0.06-0.43], P < .001). Analysis of public EBVaGC transcriptome and mutation datasets revealed enhanced immune-related signal pathways in PD-L1high EBVaGC and distinct mutation patterns in PD-L1low EBVaGC. PD-L1 positivity indicates a subtype of EBVaGC with 'hot' immune microenvironment, lower aggressiveness, better prognosis, and higher sensitivity to anti-PD-1 immunotherapy.

9.
Dalton Trans ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241613

RESUMO

In this work, a novel multichromic cationic coordination polymer, named [Zn4(BTC)3(bcbpy)2]·5H2O (1), based on a new flexible viologen ligand 1,1'-bis(3-cyanobenzyl)-[4,4'-bipyridine]-1,1'-diium (H2bcbpy·2Cl), Zn(NO3)2·6H2O and pyromellitic acid (H4BTC) was synthesized. Compound 1 has good photosensitive activity and can respond to sunlight at room temperature. The colour of compound 1 changes rapidly in response to UV light and blue ray irradiation within 5 s. We rarely obtained the crystal structures after irradiation under UV light and blue ray. At the same time, compound 1 shows the hydrochromism phenomenon when heated at 120 °C, and it also shows the ability of detecting aniline and NO2- under low-concentration conditions (10-4 M).

10.
J Antibiot (Tokyo) ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234284

RESUMO

The superbug infection caused by metallo-ß-lactamases (MßLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-ß-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones (1a-1m) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC50 in the range of 0.88-20.2 µM, and 1a and 1f were found to be the potent inhibitors (IC50 = 1.79 and 0.88 µM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 µg ml-1) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.

11.
Genome Biol ; 22(1): 207, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256809

RESUMO

BACKGROUND: The full biosphere structure and functional exploration of the microbial communities of the Challenger Deep of the Mariana Trench, the deepest known hadal zone on Earth, lag far behind that of other marine realms. RESULTS: We adopt a deep metagenomics approach to investigate the microbiome in the sediment of Challenger Deep, Mariana Trench. We construct 178 metagenome-assembled genomes (MAGs) representing 26 phyla, 16 of which are reported from hadal sediment for the first time. Based on the MAGs, we find the microbial community functions are marked by enrichment and prevalence of mixotrophy and facultative anaerobic metabolism. The microeukaryotic community is found to be dominated by six fungal groups that are characterized for the first time in hadal sediment to possess the assimilatory and dissimilatory nitrate/sulfate reduction, and hydrogen sulfide oxidation pathways. By metaviromic analysis, we reveal novel hadal Caudovirales clades, distinctive virus-host interactions, and specialized auxiliary metabolic genes for modulating hosts' nitrogen/sulfur metabolism. The hadal microbiome is further investigated by large-scale cultivation that cataloged 1070 bacterial and 19 fungal isolates from the Challenger Deep sediment, many of which are found to be new species specialized in the hadal habitat. CONCLUSION: Our hadal MAGs and isolates increase the diversity of the Challenger Deep sediment microbial genomes and isolates present in the public. The deep metagenomics approach fills the knowledge gaps in structure and diversity of the hadal microbiome, and provides novel insight into the ecology and metabolism of eukaryotic and viral components in the deepest biosphere on earth.

12.
Neurotherapeutics ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34258749

RESUMO

Aggregation of α-synuclein is associated with neurodegeneration and a hallmark pathology in synucleinopathies. These aggregates are thought to function as prion-like particles where the conformation of misfolded α-synuclein determines the traits of the induced pathology, similar to prion diseases. Still, little is known about the molecular targets facilitating the conformation-specific biological effects, but their identification could form the basis for new therapeutic interventions. High-throughput screening of annotated compound libraries could facilitate mechanistic investigation by identifying targets with impact on α-synuclein aggregation. To this end, we developed a FRET-based cellular reporter in HEK293T cells, with sensitivity down to 6.5 nM α-synuclein seeds. Using this model system, we identified GF109203X, SB202190, and SB203580 as inhibitors capable of preventing induction of α-synuclein aggregation via inhibition of p38 MAPK and PKC, respectively. We further investigated the mechanisms underlying the protective effects and found alterations in the endo-lysosomal system to be likely candidates of the protection. We found the changes did not stem from a reduction in uptake but rather alteration of lysosomal abundance and degradative capacity. Our findings highlight the value high-throughput screening brings to the mechanistic investigation of α-synuclein aggregation while simultaneously identifying novel therapeutic compounds.

13.
Toxicology ; : 152859, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34273449

RESUMO

Vanadium dioxide nanoparticles (VO2 NPs) have been massively produced and widely applied due to their excellent metal-insulator transition property, making it extremely urgent to evaluate their safety, especially for low-dose long-term respiratory occupational exposure. Here, we report a comprehensive cytotoxicity and genotoxicity study on VO2 NPs to lung cell lines A549 and BEAS-2B following a long-term exposure. A commercial VO2 NP, S-VO2, was used to treat BEAS-2B (0.15-0.6 µg/mL) and A549 (0.3-1.2 µg/mL) cells for four exposure cycles, and each exposure cycle lasted for 4 consecutive days; then various bioassays were performed after each cycle. Significant proliferation inhibition was observed in both cell lines after long-term exposure of S-VO2 at low doses that did not cause apparent acute cytotoxicity; however, the genotoxicity of S-VO2, characterized by DNA damage and micronuclei, was only observed in A549 cells. These adverse effect of S-VO2 was exposure time-, dose- and cell-dependent, and closely related to the solubility of S-VO2. The oxidative stress in cells, i.e., enhanced reactive oxygen species (ROS) generation and suppressed reduced glutathione, was the main toxicity mechanism of S-VO2. The ROS-associated mitochondrial damage and DNA damage led to the genotoxicity, and cell proliferation retard, resulting in the cellular viability loss. Our results highlight the importance and urgent necessity of the investigation on the long-term toxicity of VO2 NPs.

14.
Bioorg Chem ; 114: 105138, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34229201

RESUMO

The expression of ß-lactamases, especially metallo-ß-lactamases (MßLs) in bacteria is one of the main causes of drug resistance. In this work, an effective N-acylhydrazone scaffold as MßL inhibitor was constructed and characterized. The biological activity assays indicated that the synthesized N-acylhydrazones 1-11 preferentially inhibited MßL NDM-1, and 1 was found to be the most effective inhibitor with an IC50 of 1.2 µM. Analysis of IC50 data revealed a structure-activity relationship, which is that the pyridine and hydroxylbenzene substituents at 2-position improved inhibition of the compounds on NDM-1. ITC and enzyme kinetics assays suggested that it reversibly and competitively inhibited NDM-1 (Ki = 0.29 ± 0.05 µM). The synthesized N-acylhydrazones showed synergistic antibacterial activities with meropenem, reduced 4-16-fold MIC of meropenem on NDM-1- producing E. coli BL21 (DE3), while 1 restored 4-fold activity of meropenem on K. pneumonia expressing NDM-1 (NDM-K. pneumoniae). The mice experiments suggested that 1 combined meropenem to fight against NDM-K. pneumoniae infection in the spleen and liver. Cytotoxicity assays showed that 1 and 2 have low cytotoxicity. This study offered a new framework for the development of NDM-1 inhibitors.

15.
J Hematol Oncol ; 14(1): 112, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34274028

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are important epigenetic regulators, which play critical roles in diverse physiological and pathological processes. However, the regulatory mechanism of lncRNAs in lung carcinogenesis remains elusive. Here, we characterized a novel oncogenic lncRNA, designated as Lung Cancer Associated Transcript 3 (LCAT3). METHODS: We predicted and validated LCAT3 by analyzing RNA-sequencing (RNA-seq) data of lung cancer tissues from TCGA. Methylated RNA immunoprecipitation was performed to assess m6A modification on LCAT3. The LCAT3-FUBP1-MYC axis was assessed by dual-luciferase reporter, RNA immunoprecipitation and Chromatin immunoprecipitation assays. Signaling pathways altered by LCAT3 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT3 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro. RESULTS: LCAT3 was found to be up-regulated in lung adenocarcinomas (LUAD), and its over-expression was associated with the poor prognosis of LUAD patients. LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. Biologically, loss-of-function assays revealed that LCAT3 knockdown significantly suppressed lung cancer cell proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo. LCAT3 knockdown induced cell cycle arrest at the G1 phase. Mechanistically, LCAT3 recruited Far Upstream Element Binding Protein 1 (FUBP1) to the MYC far-upstream element (FUSE) sequence, thereby activating MYC transcription to promote proliferation, survival, invasion and metastasis of lung cancer cells. CONCLUSIONS: Taken together, we identified and characterized LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-MYC axis as a potential therapeutic target for LUAD.

16.
Pak J Pharm Sci ; 34(2): 561-565, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34275830

RESUMO

This study was aimed to investigate differences in antioxidant and anti-inflammatory effects of propofol at two commonly used dosing schedules on morbidly obese patients. Twenty-two morbidly obese patients were randomly divided into two groups, namely, TBW (dosing based on total body weight) and LBW (dosing based on lean body weight) groups. Three biomarkers, i.e. superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were measured as indicators of the level of oxidation stress reaction. Pro-inflammatory cytokines including Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were used to describe the degree of inflammation. Plasma levels of SOD, MDA and NO were increased and reached a peak value 0.5h after anesthesia induction, but the increase was smaller in the LBW group compared with the TBW group. Besides, plasma concentrations of IL-6 and IL-8 were also increased and attained a peak level 0.5h after anesthesia induction, but the increase was higher in the TBW group compared with the LBW group. The LBW-based dosing of propofol had more potent antioxidant and anti-inflammatory effects than the TBW-based dosing during anesthesia induction period on morbidly obese patients. This study provided a dosing recommendation of propofol for morbidly obese patients.

17.
J Nat Prod ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34279099

RESUMO

Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 µM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 µM).

18.
Sci Rep ; 11(1): 13820, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226578

RESUMO

The study aims to determine the prevalence of strabismus and its risk factors among school children in Hong Kong. This is a cross-sectional study involving 6-8 year old children from different districts in Hong Kong. 4273 children received comprehensive ophthalmological examination, cycloplegic auto-refraction, best corrected visual acuity (BCVA), anterior segment examination, cover/uncover test, ocular motility, and fundus examination. Demographic information, pre- and post- natal background, parental smoking status, and family history of strabismus were obtained through questionnaires. Strabismus was found among 133 children (3.11%, 95% CI 2.59-3.63%), including 117 (2.74%) exotropia and 12 (0.28%) esotropia cases (exotropia-esotropia ratio: 9.75:1). There was no significant difference in prevalence across age (6-8 years) and gender. Multivariate analysis revealed associations of strabismus with myopia (≤ - 1.00D; OR 1.61; 95% CI 1.03-2.52; P = 0.037) hyperopia (≥ + 2.00D; OR 2.49; 95% CI 1.42-4.39; P = 0.002), astigmatism (≥ + 2.00D; OR 2.32; 95% CI 1.36-3.94; P = 0.002), and anisometropia (≥ 2.00D; OR 3.21; 95% CI 1.36-7.55; P = 0.008). Other risk factors for strabismus included maternal smoking during pregnancy (OR 4.21; 95% CI 1.80-9.81; P = 0.001), family history of strabismus (OR 6.36; 95% CI 2.78-14.50, P < 0.0001) and advanced maternal age at childbirth (> 35 years; OR 1.65; CI 1.09-2.49, P = 0.018). The prevalence of strabismus among children aged 6-8 years in Hong Kong is 3.11%. Refractive errors, family history of strabismus and maternal smoking history during pregnancy are risk factors. Early correction of refractive errors and avoidance of maternal smoking during pregnancy are potentially helpful in preventing strabismus.

19.
Rev Med Virol ; 31(4): e2195, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260780

RESUMO

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.

20.
J Proteome Res ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34270897

RESUMO

Opisthorchis viverrini (Ov) infection causes hepatobiliary diseases and is a major risk factor for cholangiocarcinoma. While several omics approaches have been employed to understand the pathogenesis of opisthorchiasis, effects of Ov infection on the host systemic metabolism and fecal microbiota have not been fully explored. Here, we used a 1H NMR spectroscopy-based metabolic phenotyping approach to investigate Ov infection-induced metabolic disturbances at both the acute (1 month postinfection, 1 mpi) and chronic (4 mpi) stages in hamsters. A total of 22, 3, and 4 metabolites were found to be significantly different in the liver, serum, and urine, respectively, between Ov+ and Ov- groups. Elevated levels of hepatic amino acids and tricarboxylic acid (TCA)-cycle intermediates (fumarate and malate) were co-observed with liver injury in acute infection, whereas fibrosis-associated metabolites (e.g., glycine and glutamate) increased at the chronic infection stage. Lower levels of lipid signals ((CH2)n and CH2CH2CO) and higher levels of lysine and scyllo-inositol were observed in serum from Ov+ hamsters at 1 mpi compared to Ov- controls. Urinary levels of phenylacetylglycine (a host-bacterial cometabolite) and tauro-ß-muricholic acid were higher in the Ov+ group, which coexisted with hepatic and mild kidney fibrosis. Furthermore, Ov+ animals showed higher relative abundances of fecal Methanobrevibacter (Archaea), Akkermansia, and Burkholderia-Paraburkholderia compared to the noninfected controls. In conclusion, along with liver and kidney pathologies, O. viverrini infection resulted in hepatic and mild renal pathologies, disturbed hepatic amino acid metabolism and the TCA cycle, and induced changes in the fecal microbial composition and urinary host-microbial cometabolism. This study provides the initial step toward an understanding of local and systemic metabolic responses of the host to O. viverrini infection.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...