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1.
J Hazard Mater ; 419: 126454, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34198221

RESUMO

Nanoplastics (NPs) cause various adverse effects on marine fish. However, effects of dietary NPs exposure on liver lipid metabolism and muscle nutritional quality of carnivorous marine fish are not fully understood. In this study, a 21-day feeding test was conducted to simulate the food chain transfer of polystyrene nanoplastics (PS NPs) and then evaluate effects of different dietary PS NPs levels on the survival, growth performance, liver lipid metabolism, and muscle nutritional quality of large yellow croaker Larimichthys crocea. Results indicated that the survival and growth of large yellow croaker decreased with the increase of PS NPs levels. Moreover, PS NPs induced excessive liver lipid accumulation by down-regulating the expression of lipolysis-related genes and inhibiting the AMPK-PPARα signaling pathway. In vitro, PS NPs could be accumulated in hepatocytes, reduce cell viability, and disrupt lipid metabolism of hepatocytes. Also, we found for the first time that PS NPs altered fatty acid composition and texture of fish muscle by enhancing oxidative stress and disrupting lipid metabolism. Overall, this study indicated that PS NPs induced liver lipid deposition by inhibiting lipolysis, and demonstrated that PS NPs altered the nutritional quality of fish, which might cause potential health effects for human consumers.

2.
Oxid Med Cell Longev ; 2021: 6644238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221235

RESUMO

This study investigated whether the mitochondrial-targeted peptide SS-31 can protect against cigarette smoke- (CS-) induced airway inflammation and oxidative stress in vitro and in vivo. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, and those in the experimental group were pretreated with SS-31 1 h before CS exposure. Pathologic changes and oxidative stress in lung tissue, inflammatory cell counts, and proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. The mechanistic basis for the effects of SS-31 on CS extract- (CSE-) induced airway inflammation and oxidative stress was investigated using BEAS-2B bronchial epithelial cells and by RNA sequencing and western blot analysis of lung tissues. SS-31 attenuated CS-induced inflammatory injury of the airway and reduced total cell, neutrophil, and macrophage counts and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, and matrix metalloproteinase (MMP) 9 levels in BALF. SS-31 also attenuated CS-induced oxidative stress by decreasing malondialdehyde (MDA) and myeloperoxidase (MPO) activities and increasing that of superoxide dismutase (SOD). It also reversed CS-induced changes in the expression of mitochondrial fission protein (MFF) and optic atrophy (OPA) 1 and reduced the amount of cytochrome c released into the cytosol. Pretreatment with SS-31 normalized TNF-α, IL-6, and MMP9 expression, MDA and SOD activities, and ROS generation in CSE-treated BEAS-2B cells and reversed the changes in MFF and OPA1 expression. RNA sequencing and western blot analysis showed that SS-31 inhibited CS-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway in vitro and in vivo. Thus, SS-31 alleviates CS-induced airway inflammation and oxidative stress via modulation of mitochondrial function and regulation of MAPK signaling and thus has therapeutic potential for the treatment of airway disorders caused by smoking.

3.
Front Immunol ; 12: 614773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276642

RESUMO

Human leukocyte antigen G (HLA-G) is known as a novel immune checkpoint molecule in cancer; thus, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. The aim of this study was to systematically identify the roles of checkpoint HLA-G molecules across various types of cancer. ONCOMINE, GEPIA, CCLE, TRRUST, HAP, PrognoScan, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, STRING, GeneMANIA, DAVID, TIMER, and CIBERSORT were utilized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In this study, we comprehensively analysed the heterogeneous expression of HLA-G molecules in various types of cancer and focused on genetic alterations, coexpression patterns, gene interaction networks, HLA-G interactors, and the relationships between HLA-G and pathological stage, prognosis, and tumor-infiltrating immune cells. We first identified that the mRNA expression levels of HLA-G were significantly upregulated in both most tumor tissues and tumor cell lines on the basis of in-depth analysis of RNAseq data. The expression levels of HLA-G were positively associated with those of the other immune checkpoints PD-1 and CTLA-4. Abnormal expression of HLA-G was significantly correlated with the pathological stage of some but not all tumor types. There was a significant difference between the high and low HLA-G expression groups in terms of overall survival (OS) or disease-free survival (DFS). The results showed that HLA-G highly expressed have positive associations with tumor-infiltrating immune cells in the microenvironment in most types of tumors (P<0.05). Additionally, we identified the key transcription factor (TF) targets in the regulation of HLA-G expression, including HIVEP2, MYCN, CIITA, MYC, and IRF1. Multiple mutations (missense, truncating, etc.) and the methylation status of the HLA-G gene may explain the differential expression of HLA-G across different tumors. Functional enrichment analysis showed that HLA-G was primarily related to T cell activation, T cell regulation, and lymphocyte-mediated immunity. The data may provide novel insights for blockade of the HLA-G/ILT axis, which holds potential for the development of more effective antitumour treatments.

4.
Food Chem ; 365: 130512, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243121

RESUMO

Pullulan is widely applied in the food industry due to its unique physicochemical properties, but little information is known about its effects on the quality of frozen cooked noodles (FCNs), nor the underlying mechanism. In this study, the addition of 0.3% and 0.5% pullulan resulted in better texture and cooking properties, and minor chrominance differences, and it significantly (P < 0.05) decreased the freezable water content and retarded the water migration. Pullulan inhibited the depolymerization of the glutenin macropolymer during 0-8 weeks of frozen storage. Meanwhile, pullulan caused slightly decreased α-helixes and increased ß-turns, as well as decreased degradation temperature, further suggesting that pullulan influenced the gluten network. A more compact microstructure was shown in the pullulan-fortified FCNs. This study provides a theoretical basis for the positive effects of pullulan on the quality of FCNs from the perspectives of water state and protein structure.

5.
Chem Commun (Camb) ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291778

RESUMO

An efficient Pd-catalysed ß-C(sp3)-H arylation of diverse native amides with aryl iodides was developed. This protocol overcomes the necessity of the Thorpe-Ingold effect and features broad substrate scope and good functional group tolerance. The potential application of this protocol is collectively demonstrated by gram-scale synthesis and the synthesis of several bioactive molecules.

6.
Pediatr Rheumatol Online J ; 19(1): 112, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247641

RESUMO

OBJECTIVE: To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA). METHODS: In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well. RESULTS: A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42-15.42) and the median duration of disease was 2.38 months (range, 1.53-49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores. CONCLUSIONS: Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA.

7.
Mol Med Rep ; 24(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278489

RESUMO

Alzheimer's disease (AD), one of the most common types of chronic neurodegenerative diseases, is pathologically characterized by the formation of amyloid ß (Aß) peptide­containing plaques and neurofibrillary tangles. Among Aß peptides, Aß1­42 induces neuronal toxicity and neurodegeneration. In our previous studies, Cdk5 was found to regulate Aß1­42­induced mitochondrial fission via the phosphorylation of dynamin­related protein 1 (Drp1) at Ser579. However, whether blockage of Drp1 phosphorylation at Ser579 protects neurons against Aß1­42­induced degeneration remains to be elucidated. Thus, the aim the present study was to examine the effect of mutant Drp1­S579A on neurodegeneration and its underlying mechanism. First, the phosphorylation­defect (phospho­defect) mutant, Lenti­Drp1­S579A was constructed. Phospho­defect Drp1­S579A expression was detected in primary cultures of mouse cortical neurons infected with Lenti­Drp1­S579A using western blotting and it was found to successfully attenuate the phosphorylation of endogenous Drp1 at Ser579. In primary neuronal cultures, the neuronal processes were evaluated under microscopy. Treatment with 10 µM Aß1­42 significantly decreased dendritic density and length, spine outgrowth and synapse number. As expected, infection of neurons with Lenti­Drp1­S579A efficiently alleviated the inhibitory effect of Aß1­42 on neurite outgrowth and synapse density. In addition, infection with Lenti­Drp1­S579A abolished the cleavage of caspase­3 and apoptosis in neurons exposed to Aß1­42. Thus, the current data demonstrated that blockage of Drp1 phosphorylation at Ser579 may be an effective strategy to protect neurons against Aß1­42­induced degeneration and apoptosis. These findings underline the therapeutic potential of targeting Drp1 in the treatment of AD.

8.
Neurol Res ; : 1-10, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313185

RESUMO

OBJECTIVE: To explore the whole cerebral perfusion and microstructure alteration patterns in Parkinson's disease (PD) and the associations of these patterns with clinical features. METHODS: Forty-one subjects [20 PD patients and 21 healthy controls (HCs)] underwent arterial spin labeling (ASL), diffusion tensor imaging (DTI) and 3D T1-weighted imaging (T1WI) MRI. The cerebral blood flow (CBF) of the whole brain and the fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) of subcortical and cerebellar regions were measured and compared between groups. Pearson's correlation was calculated between MRI measurements and clinical features [Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS III, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and olfactory test scores]. RESULTS: Compared to HCs, PD patients showed lower CBF in the frontal, parietal and temporal lobes but higher CBF in bilateral hippocampi, red nuclei, right substantia nigra, thalamus and most cerebellar regions. The MD in the right thalamus and several regions in the cerebellum increased in PD compared to HCs. In PD patients, the total UPDRS, UPDRS III, MoCA, MMSE and olfactory test scores were related to FA or CBF in cerebellum. (all p < 0.05). CONCLUSION: Hypoperfusion in cortical regions, together with hyperperfusion in subcortical and cerebellar regions may be the characteristic perfusion pattern in advanced PD patients. The microstructures of the right thalamus and cerebellum were changed in PD patients. The cognitive, motor and olfactory performance of PD patients is closely related to the perfusion and microstructure of the brain, especially the cerebellum.

9.
Chem Commun (Camb) ; 57(52): 6424-6427, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34095920

RESUMO

A new and efficient strategy for ring-opening reactions of nitrocyclopropanes is developed for the first time for the divergent synthesis of enynes and enesters via in situ generated highly reactive electron-deficient intermediate allenes. Controllable approaches resulted in enynes and enesters with up to 89% and 90% yields, respectively. The reaction features easy operation, involves green solvents and simple inorganic bases, and is transition-metal free.

10.
Cell Biol Toxicol ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34189720

RESUMO

Dexamethasone is a commonly used synthetic glucocorticoid in the clinic. As a compound that can cross the placental barrier to promote fetal lung maturation, dexamethasone is extensively used in pregnant women at risk of premature delivery. However, the use of glucocorticoids during pregnancy increases the risk of neurodevelopmental disorders. In the present study, we observed anxiety- and depressive-like behavior changes and hyperexcitability of hippocampal neurons in adult rat offspring with previous prenatal dexamethasone exposure (PDE); the observed changes were related to in utero damage of parvalbumin interneurons. A programmed change in neuregulin 1 (NRG1)-Erb-b2 receptor tyrosine kinase 4 (ErbB4) signaling was the key to the damage of parvalbumin interneurons in the hippocampus of PDE offspring. Anxiety- and depressive-like behavior, NRG1-ErbB4 signaling activation, and damage of parvalbumin interneurons in PDE offspring were aggravated after chronic stress. The intervention of NRG1-ErbB4 signaling contributed to the improvement in dexamethasone-mediated injury to parvalbumin interneurons. These results suggested that PDE might cause anxiety- and depressive-like behavior changes in male rat offspring through the programmed activation of NRG1-ErbB4 signaling, resulting in damage to parvalbumin interneurons and hyperactivity of the hippocampus. Intrauterine programming of neuregulin 1 (NRG1)-Erb-b2 receptor tyrosine kinase 4 (ERBB4) overactivation by dexamethasone mediates anxiety- and depressive-like behavior in male rat offspring.

11.
Neuroreport ; 32(11): 918-924, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34132705

RESUMO

Glucocerebrosidase (GBA) mutations occur frequently in Parkinson's disease (PD) patients. This study aims to identify potential crucial genes and pathways associated with GBA mutations in patients with PD and to further analyze new molecular mechanisms related to the occurrence of gene mutations from the perspective of bioinformatics. Gene expression profiles of datasets GSE53424 and GSE99142 were acquired from the Gene Expression Ominibus database. Differentially expressed genes (DEGs) were detected, using the 'limma' package in R, comparing IDI-PD 1 (idiopathic PD patients) and GBA-PD 1 [PD patients with heterozygous GBA mutations (GBA N370S)] group samples. The functions of top modules were assessed using the DAVID, whereas gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Protein-protein interaction networks were assembled with Cytoscape software and separated into subnetworks using the Molecular Complex Detection Algorithm. Data from GSE53424 and GSE99142 were also extracted to verify our findings. There were 283 DEGs identified in PD patients heterozygous for GBA mutations. Module analysis revealed that GBA mutations in PD patients were associated with significant pathways, including Calcium signaling pathway, Rap1 signaling pathway and Cytokine-cytokine receptor interaction. Hub genes of the two modules were corticotropin-releasing hormone (CRH) and Melatonin receptor 1B (MTNR1B). The expression of CRH was downregulated, whereas that of MTNR1B was upregulated in PD patients with GBA mutations. The expression of CRH and MTNR1B has diagnostic value for PD patients with heterozygous GBA mutations. Novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of heterozygous GBA mutations in PD patients.

12.
Dev Comp Immunol ; 124: 104130, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34081942

RESUMO

Fish peptidoglycan recognition proteins (PGRPs) play important roles in microbial recognition, and bacterial elimination. In the present study, a short-type PGRP from large yellow croaker, LcPGRP5 was cloned and its functions were characterized. LcPGRP5 gene encodes a protein containing conserved PGRP domain, but no signal peptide. Phylogenetic analysis shows that LcPGRP5 is clustered with other short PGRPs identified in other teleosts. LcPGRP5 is constitutively expressed in all tissues examined, with the highest expression being detected in the head kidney. Recombinant LcPGRP5 protein features amidase activity and bactericidal activity. Notably, LcPGRP5 could enhance the phagocytosis of the bacteria by large yellow croaker macrophage, with higher phagocytic capacity being observed in Staphylococcus aureus compared to Escherichia coli. Moreover, overexpression of LcPGRP5 suppresses pro-inflammatory effects elicited by bacterial exposure in the macrophage cell line. Overall, the present results clearly indicate the important roles of LcPGRP5 played in the innate immune responses against bacterial infection.

13.
Sci Total Environ ; 789: 147691, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082199

RESUMO

Ovarian dysfunction has an intrauterine origin, and prenatal caffeine exposure (PCE) could lead to abnormal follicle counts in offspring after birth. However, the effect of PCE on offspring ovarian function and its mechanism of intrauterine programming have not been reported thus far. In this study, pregnant Wistar rats were intragastrically administered caffeine (30 and 120 mg/kg·d) at gestational days 9-20 (GD9-20). Certain tests were performed on the blood, ovaries and hypothalamus of female offspring at different time points. PCE female offspring had ovarian dysfunction in adulthood compared with the control. Further results showed that in utero ovarian morphological development and estradiol synthesis were inhibited but rapidly increased during puberty in the PCE group. The histone 3 lysine 27 acetylation (H3K27ac) level of the insulin-like growth factor 1 (IGF1) promoter region and its expression were decreased in the ovary, which was due to exposure to high levels of fetal blood corticosterone, and the H3K27ac level of IGF1 and its expression shifted to increase after birth with a decrease in serum corticosterone levels. Chronic stress led to increased serum corticosterone levels in adult offspring, whereas ovarian morphological development, the H3K27ac level of IGF1 and its expression, and estradiol synthesis were significantly inhibited. Moreover, the activity of the hypothalamic-pituitary-ovarian (HPO) axis was increased in the early postnatal period of PCE offspring, and chronic stress reversed these changes. In the KGN cell line, it was found that cortisol could promote the translocation of the glucocorticoid receptor (GR) into the nucleus and upregulate histone deacetylase 10 (HDAC10) to inhibit the H3K27ac level of IGF1 and its expression and estradiol synthesis. In summary, PCE is associated with ovarian dysfunction in female adult offspring, and the potential mechanism is related to intrauterine high glucocorticoid exposure by activating the GR and recruiting HDAC10 to affect ovarian glucocorticoid-IGF1 axis programming and to inhibit estradiol synthesis.


Assuntos
Cafeína , Efeitos Tardios da Exposição Pré-Natal , Animais , Corticosterona , Feminino , Glucocorticoides , Gravidez , Ratos , Ratos Wistar
14.
Drug Metab Dispos ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183378

RESUMO

Silybin is widely used as a hepatoprotective agent in various liver disease therapies and has been previously identified as a CYP3A inhibitor. However, little is known about the effect of silybin on CYP3A and the regulatory mechanism during high-fat-diet (HFD)-induced liver inflammation. In our study, we found that silybin restored CYP3A expression and activity that were decreased by HFD and conditioned medium (CM) from palmitate (PA)-treated Kupffer cells. Moreover, silybin suppressed liver inflammation in HFD-fed mice and inhibited NF-κB translocation into the nucleus through elevation of SIRT2 expression and promotion of p65 deacetylation. This effect was confirmed by overexpression of SIRT2, which suppressed p65 nuclear translocation and restored CYP3A transcription affected by CM. The hepatic NAD+ concentration markedly decreased in HFD-fed mice and CM-treated hepatocytes/HepG2 cells but increased after silybin treatment. Supplementing NMN as an NAD+ donor inhibited p65 acetylation, decreased p65 nuclear translocation, and restored cyp3a transcription in both HepG2 cells and mouse hepatocytes. These results suggest that silybin regulates metabolic enzymes during liver inflammation by a mechanism related to the increase in NAD+ and SIRT2 levels. In addition, silybin enhanced the intracellular NAD+ concentration by decreasing PARP1 expression. In summary, silybin increased NAD+ concentration, promoted SIRT2 expression and lowered p65 acetylation both in vivo and in vitro, which supported the recovery of CYP3A expression. These findings indicate that the NAD+/SIRT2 pathway plays an important role in CYP3A regulation during NAFLD. Significance Statement This research revealed the differential regulation of CYP3A by silybin under physiological and fatty liver pathological conditions. In the treatment of NAFLD, silybin restored, not inhibited, CYP3A expression and activity through the NAD+/SIRT2 pathway in accordance with its anti-inflammatory effect.

15.
Front Public Health ; 9: 668774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136457

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic, quarantine hotel employees face a higher risk of infection while they host quarantine guests from overseas. This is the first research to empirically investigate the psychological effects of operating a quarantine hotel on its employees. The empirical results indicate that heightened fear of COVID-19 leads to adverse mental health issues for quarantine hotel employees and confirm that depression, anxiety, and stress have a significant influence on turnover intention. These findings contribute to the extant knowledge base by uncovering the role of mental health in employee turnover intention. Based on the results, implications are presented for practitioners.


Assuntos
COVID-19 , Quarentena , China/epidemiologia , Depressão/epidemiologia , Medo , Humanos , Intenção , Saúde Mental , Reorganização de Recursos Humanos , SARS-CoV-2
16.
Zool Res ; 42(4): 412-416, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34075734

RESUMO

Functional diversity is an integrative approach to better understand biodiversity across space and time. In the present study, we investigated the spatiotemporal patterns (i.e., elevation and season) and environmental determinants of anuran functional diversity on Tianping Mountain, northwest Hunan, China. Specifically, 10 transects were established from low (300 m a.s.l.) to high (1 492 m a.s.l.) elevations, and anuran communities were sampled in spring, early summer, midsummer, and autumn in 2017. Four functional diversity indices were computed for each transect in each season using ecomorphological functional traits. Our results demonstrated that these indices had contrasting responses to increasing elevations. However, they did not differ significantly among seasons in terms of temporal patterns. Interestingly, the unique spatiotemporal functional diversity patterns were impacted by distinct environmental variables, such as leaf litter cover, water temperature, number of trees, and water conductivity.


Assuntos
Distribuição Animal , Anuros/classificação , Biodiversidade , Clima , Florestas , Altitude , Animais , Anuros/fisiologia
17.
Phys Chem Chem Phys ; 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34095922

RESUMO

Hydrogen passivation is an important method used to stabilize a specific graphene edge. Although several hydrogen-terminated graphene edges have been proposed in theory, a comprehensive exploration of highly stable hydrogen-terminated graphene edges is still absent. According to the bare graphene-edge databases, a series of hydrogen-terminated graphene edges have been proposed. The energy stability of hydrogen-terminated zigzag and armchair graphene edges is fully investigated. The six most stable hydrogen-terminated zigzag edges and six armchair edges of graphene are determined. Hydrogen passivation makes hydrogen-terminated graphene edges energetically more stable than bare graphene edges. The additional hydrogen atoms balance the dangling bonds of carbon atoms at edges by forming hydrogen-carbon covalent bonds. Hydrogen-terminated graphene edges with six-membered carbon rings have better global stability than those composed of non-hexagonal structural units. The effects of the experimental temperatures and hydrogen partial pressures on the stability of hydrogen-terminated graphene edges are fully investigated. Furthermore, hydrogen passivation can open the band gap of graphene effectively. These results provide a deep understanding of hydrogen-terminated graphene nanostructures.

18.
Chem Commun (Camb) ; 57(37): 4544-4547, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33956008

RESUMO

The Pd-cataylsed direct ortho-C(sp2)-H fluorination of aromatic ketones has been developed for the first time. The reaction features good regioselectivity and simple operations, constituting an alternative shortcut to access fluorinated ketones. A concise synthesis of anacetrapib has also been achieved by using late-stage C-H fluorination as a key step.


Assuntos
Cetonas/química , Oxazolidinonas/síntese química , Paládio/química , Catálise , Halogenação , Estrutura Molecular , Oxazolidinonas/química
19.
Clin Exp Rheumatol ; 39(4): 721-726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34001308

RESUMO

OBJECTIVES: Scleroderma renal crisis (SRC) is a life-threatening syndrome. The early identification of patients at risk is essential for timely treatment to improve the outcome. Therefore, it is of great interest to provide a personalised tool to predict risk of SRC in systemic sclerosis (SSc). METHODS: We tried to set up a SRC prediction model based on the PKUPH-SSc cohort of 302 SSc patients. The least absolute shrinkage and selection operator (Lasso) regression was used to optimise disease features. Multivariable logistic regression analysis was applied to build a SRC prediction model incorporating the features of SSc selected in the Lasso regression. Then, a multi-predictor nomogram combining clinical characteristics was constructed and evaluated by discrimination and calibration, with further assessment by external validation in a validation cohort composed of 400 consecutive SSc patients from other 4 tertiary hospitals. RESULTS: A multi-predictor nomogram for evaluating the risk of SRC was successfully developed. In the nomogram, four easily available predictors were contained, including disease duration <2 years, cardiac involvement, anaemia and corticosteroid >15mg/d exposure. The nomogram displayed good discrimination with an area under the curve (AUC) of 0.843 (95% CI: 0.797-0.882) and good calibration. High AUC value of 0.854 (95% CI: 0.690-1.000) could still be achieved in the external validation. The model is now available online for research use. CONCLUSIONS: The multi-predictor nomogram for SRC could be reliably and conveniently used to predict the individual risk of SRC in SSc patients, and be a step towards more personalised medicine.


Assuntos
Escleroderma Sistêmico , Estudos de Coortes , Humanos , Nomogramas , Estudos Retrospectivos , Medição de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia
20.
J Org Chem ; 86(10): 7271-7279, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33978408

RESUMO

Nortriterpenoids isolated from Walsura cochinchinensis have attracted much attention from both synthetic and medicinal chemists, yet only recently have efficient synthetic approaches to any members appeared. Shown here is that the common intermediate with a 6/6/5/6-fused tetracyclic ring nucleus can be converted to walsucochin family members. The first total syntheses of (±)-walsucochin A, (±)-walsucochinoids C-F, and their analogues were achieved in this work.


Assuntos
Meliaceae , Triterpenos
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