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A variety of azaheterocycle-fused piperidines and pyrrolidines bearing CF3 and CHF2 functionalities were obtained using CF3SO2Na and CHF2SO2Na by visible light photocatalysis. This protocol involves a radical cascade cyclization via tandem tri- and difluoromethylation-arylation of pendent unactivated alkenes. Benzimidazole, imidazole, theophylline, purine, and indole serve as applicable anchors, thereby enriching the structural diversity of piperidine and pyrrolidine derivatives. This method features mild, additive-free and transition metal-free conditions.
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A relatively green method for synthesizing 1-thioalkyl glycosides has been developed, where sodium alkanethiolates were used to react with per-O-acetylated sugars instead of odorous alkyl mercaptans in the presence of BF3·Et2O without the use of solvents under mild conditions. Furthermore, we found that 1,2-trans-ß-thioglycosides can be converted into corresponding 1,2-cis-α-thioglycosides in the presence of trifluoromethanesulfonic acid in nonpolar solvents under mild conditions. This provides a simple and efficient new approach for synthesizing challenging 1,2-cis-α-thioglycosides.
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Glicosídeos , Tioglicosídeos , Sódio , Solventes , AçúcaresRESUMO
The analysis of soil bacterial community has guiding significance for fully utilization of soil microbial resources. The results of high-throughput sequencing (HTS) showed that the bacteria in the three sulfometuron-methyl contaminated soil samples were mainly composed of 677 genera, including Phenylobacterium, Bacillus, belonging to 28 phyla, including Proteobacteria, Firmicutes. The diversity and richness of bacterial community decreased with the increase in sulfometuron-methyl concentration. In addition, sulfometuron-methyl could also affect the soil bacterial function based on PICRUSt functional predictive analysis. Combined with the results of HTS and phylogenetic molecular ecological networks (pMENs), 12 genera, including Ralstonia (Pi=0.64), were identified as the key soil microflora (intra-module connectivity Zi ≥ 2.5 or inter-module connectivity Pi ≥ 0.62), and the abundance of Ralstonia significantly increased with the concentration of sulfometuron-methyl, indicating that the strains of this genus might be the potential degrading bacteria and could form a stable relationship with indigenous microorganisms. Among the isolated bacteria of genus Ralstonia, one strain, named Ralstonia sp. JM-1, was verified to possess higher sulfometuron-methyl degradation efficiency, which completely degraded 20 mg L-1 of sulfometuron-methyl within 96 h. Furthermore, the immobilized strains generated by the mixture of 2.0 g bamboo charcoal and 3.0 mL bacterial suspension for 24 h had the highest sulfometuron-methyl degradation rate than that under other conditions, and the dynamic process degrading 10-30 mg L-1 of sulfometuron-methyl conforms to the zero-order kinetic equation. The bioremediation of contaminated soil showed the immobilized strains could completely degrade sulfometuron-methyl (1.39 mg kg-1) in contaminated soil within 9 d, which is higher than that application of strains in the free state (74.8%). This study could provide ideas for the isolation of functional strains and a theoretical basis for the bioremediation of STM and other contaminated soils.
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Poluentes do Solo , Solo , Bactérias/genética , Bactérias/metabolismo , Biodegradação Ambiental , Filogenia , Microbiologia do Solo , Poluentes do Solo/análise , Compostos de SulfonilureiaRESUMO
An improved method to efficiently synthesize 2-OH thioaryl glycosides starting from corresponding per-protected glycals was developed, where 1,2-anhydro sugars were prepared by the oxidation of glycals with oxone, followed by reaction of crude crystalline 1,2-anhydro sugars with NaBH4 and aryl disulfides. This method has been further used in a one-pot reaction to synthesize glycosyl donors having both "armed" and "NGP (neighboring group participation)" effects.
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Tioglicosídeos , Dissulfetos , Glicosídeos/química , Glicosilação , Açúcares , Tioglicosídeos/químicaRESUMO
BACKGROUND: Voltage-gated sodium channels are protein complexes composed of 2 subunits, namely, pore-forming α- and regulatory ß-subunits. A ß-subunit consists of 5 proteins encoded by 4 genes (i.e., SCN1B-SCN4B). SUMMARY: ß1-Subunits regulate sodium ion channel functions, including gating properties, subcellular localization, and kinetics. Key Message: Sodium channel ß1- and its variant ß1B-subunits are encoded by SCN1B. These variants are associated with many human diseases, such as epilepsy, Brugada syndrome, Dravet syndrome, and cancers. On the basis of previous research, we aimed to provide an overview of the structure, expression, and involvement of SCN1B in physiological processes and focused on its role in diseases.
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BACKGROUND: MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19-23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. SUMMARY: miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. Key Message: miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.
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This study aimed to evaluate the influence of ultrasonic degradation on the physicochemical and biological characteristics of Polygonatum cyrtonema polysaccharide (PCP, 8.59 kDa). PCP was subjected to ultrasonic treatment for 8, 16, and 24 h and yielded the degraded fractions PCP-8, PCP-16, and PCP-24 (5.06, 4.13, and 3.69 kDa), respectively. Compared with the intact PCP, PCP-8, PCP-16 and PCP-24 had a reduced particle size (decrements of 28.03 %, 46.15 % and 62.54 %, respectively). Although ultrasonic degradation did not alter the primary structure of PCP, its triple helical and superficial structures were disrupted, with degraded fractions demonstrating reduced thermal stability and apparent viscosities compared with those of the intact PCP. Furthermore, the functional properties of the degraded fractions were different. PCP-16 most favourably affected GLP-1 secretion, while PCP-8 and PCP-24 exhibited the strongest antioxidant and enzyme inhibitory activities, respectively. Hence, controlled ultrasound irradiation is an appealing approach for partially degrading PCP and enhancing its bioactivity as a functional agent.
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Antioxidantes , Peptídeo 1 Semelhante ao Glucagon , Polygonatum , Polissacarídeos , Ondas Ultrassônicas , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Tamanho da Partícula , Polygonatum/química , Polissacarídeos/química , Polissacarídeos/farmacologia , ViscosidadeRESUMO
Hypoxic-ischemic brain injury contributes to major neurodevelopmental disorders and is one of the leading causes of seizures, which substantially results in neurodevelopmental impairments with long-lasting outcomes and is one of the main causes of death in neonates. We aimed to investigate the correlation between miRNA-210 and SCN1B, a voltage-gated sodium channel gene, in brain tissue of fetal rats with hypoxic-ischemic brain injury. We found that after 10 min of hypoxia-ischemia, all reperfusion groups showed different degrees of damage. The degree of the injury increased in all the groups after 30 min of hypoxia-ischemia. Those changes include changes in the pericellular lumen, capillaries in the cortex, erythrocytes, enlarged pericellular lumen, the enlarged pericapillary lumen in the cortex, edema around glial cells, enlarged gap to form multiple necrotic foci, deformation of neurons, and loss of cell structure. The expression levels of HIF-1α, miRNA-210, and HIF-1α mRNA were higher in the hypoxic-ischemic groups than that in the control groups, among which the expression levels in the severe group were higher than that in mild group. SCN1B is down-regulated in both the mild and severe groups, and the lowest level was found at 30 min after hypoxia in both groups. MiRNA-210 plays a role in the development of hypoxic-ischemic encephalopathy (HIE) by regulating the expression changes of SCN1B. The brain tissue of fetal rats in the hypoxic-ischemic animal model showed pathological changes of brain injury.
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Lesões Encefálicas , Hipóxia-Isquemia Encefálica , MicroRNAs , Animais , Ratos , Hipóxia-Isquemia Encefálica/genética , Encéfalo/patologia , Neurônios/metabolismo , Lesões Encefálicas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-ß-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15 min (mild) and 30 min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia-ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.
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Sulfeto de Hidrogênio , Hipóxia-Isquemia Encefálica , MicroRNAs , Criança , Humanos , Ratos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Hipóxia-Isquemia Encefálica/genética , Cistationina , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Ratos Sprague-Dawley , Sulfeto de Hidrogênio/metabolismoRESUMO
OBJECTIVE: To investigate the effects of echinacoside on the extracellular striatal levels of norepinephrine (NE), dopamine (DA), homovanillic acid (HVA), 3, 4-dihydroxyphenylethanoid acid (DOPAC), 5-hydroxyindoleacetic acid (HIAA), and 5-hydroxytryptamine(5-HT) in middle cerebral artery occlusion (MCAO rats. METHODS: The middle cerebral artery was occluded in male Sprague-Dawley rats. Three days later microdialysis probes were placed into the right striatum of MCAO rat brains and the brains were perfused with Ringer's solution at a rate of 1.5 microL/min. Cerebral microdialysates were collected every 30 minutes from awake and freely moving rats before assaying for NE, DA, HVA, DOPAC, HIAA, and 5-HT levels by reverse phase HPLC with electrochemistry. RESULTS: Three days after MCAO, the extracellular striatal levels of NE, DA, DOPAC, HIAA, HVA, and 5-HT of the MCAO rats increased significantly (at least P < 0.05 vs. control). However, simultaneous treatment with echinacoside (30.0 or 15.0 mg/kg) attenuated these increases (at least P < 0.05 vs. non-treated model rats). CONCLUSION: These results imply that echinacoside may protect striatal dopa minergic neurons from the injury induced by MCAO and may help prevent and treat cerebral ischemic diseases.
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Glicosídeos/farmacologia , Infarto da Artéria Cerebral Média , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Pituitary metastasis is an uncommon manifestation of systemic malignant tumors. Moreover, hyperprolactinemia and overall hypopituitarism caused by metastatic spread leading to the initial symptoms are rare. CASE SUMMARY: A 53-year-old male patient was admitted to our hospital with complaints of bilateral blurred vision, dizziness, polyuria, nocturia, severe fatigue and somnolence, decreased libido, and intermittent nausea and vomiting for more than 6 mo. During the last 7 d, the dizziness had worsened. Laboratory investigations revealed overall hypofunction of the pituitary gland, but the patient had an elevated serum prolactin level (703.35 mg/mL). Preoperative magnetic resonance imaging revealed a tumor in the sellar region, accompanied by intratumoral hemorrhage and calcification. Thus, transnasal subtotal resection of the lesion in the sellar region was performed. The histopathological and immunohistochemical examinations of the resected lesion revealed metastasis of lung adenocarcinoma to the pituitary gland. Oral hydrocortisone (30 mg/d) and levothyroxine (25 mg/d) were given both pre- and postoperatively. Post-operatively, the clinical symptoms were significantly improved. However, 4 mo following the surgery, the patient succumbed due to multiple organ failure. CONCLUSION: Hyperprolactinemia is one of the markers of poor prognosis in patients with carcinoma that metastasizes to the pituitary gland. Exogenous hormone supplementation plays a positive role in relieving the symptoms of patients and improving quality of life.
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INTRODUCTION: Microribonucleic acids (miRNAs) have short (approximately 18 to 25) nucleotides and are evolutionarily conserved and endogenously expressed RNAs belonging to a family of noncoding RNA molecules. miRNA-373 regulates cell proliferation, migration, apoptosis, invasion, and repairing damaged DNA after hypoxia stress. Neonatal hypoxic-ischemic encephalopathy (HIE) refers to perinatal asphyxia caused by partial or complete hypoxia, reduced or suspended cerebral blood flow, and fetal or neonatal brain damage. We aim to investigate the relationship between miRNA-373 and HIF-1α, between miRNA-373 MMP-9, and between miRNA-373 VEGF in the occurrence and development of HIE. METHODS: Human (children) samples were divided into four groups (n = 15 in each group) according to HIE severity. The patient group was divided into middle, moderate, and severe HIE groups. The control group included healthy children or children with nonneurological diseases. The expressions of miRNA-373, HIF-1α, MMP-9, and VEGF were assayed in the serum samples. RESULTS: Our study showed a strong relationship between miRNA-373 and HIF-1α, between miRNA-373 and MMP-9, and between miRNA-373 and VEGF. The expression levels of miRNA-373, HIF-1α, MMP-9, and VEGF in the HIE groups were much higher than those of the control group. CONCLUSION: The increased change in miRNA-373 expression has a certain diagnostic significance on neonatal HIE. In the occurrence and development of HIE, miRNA-373 is positively correlated with HIF-1α, MMP-9, and VEGF.
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Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Biologia Computacional , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/fisiopatologia , Recém-Nascido , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/fisiopatologia , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/genética , MicroRNAs/sangue , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Alveolar soft-part sarcoma (ASPS) is a rare malignant soft tissue tumor of uncertain cellular origin. We reported the case of a 21-year-old man with ASPS presenting itself as a markedly vascular tumor of the prostate. Immunohistochemistry showed positive nuclear staining for TFE3, positive cytoplasm staining for MyoD1 and neuron-specific enolase, and negative for S100, CK, synaptophysin, chromogranin A, myogenin and PSA. A dual-color, break-apart fluorescence in situ hybridization (FISH) assay identified the presence of a TFE3 gene fusion in the tumor cells. RT-PCR was performed to confirm the ASPSCR1 (ASPL)/TFE3 fusion transcript product in the tumor tissue. The patient suffered bone metastases 8 months after surgery and died of cachexia 14 months later. ASPS of the prostate should be discussed in terms of differential diagnosis from clinicopathological characteristics, immunophenotypes, and molecular genetic features.
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Substantial evidence suggests that the epithelial-mesenchymal transition (EMT) phenotype is associated with the invasive characteristics of cancer stem cells (CSCs),which possess an EMT phenotype that may predominate in tumor invasion and metastasis. However, the mechanisms for the generation and regulation of these CSCs have not been clearly defined. As hypoxia and EMT-related factors may have important functions in EMT-like CSCs, the aim of this study was to investigate the effects of hypoxia on these cells. CSCs were established from the gastric cancer cell lines MGC-803 and SGC7901, and the relationship between hypoxia and EMT-like CSCs was investigated in gastric cancer. After hypoxia treatment, some gastric CSCs exhibited a marked increase in hypoxia-inducible factor-1α (HIF-1α)expression and increased migration and invasion capabilities compared with the normoxic control. These CSCs were defined by activation of the mesenchymal cell marker Vimentin and by inhibition of the epithelial cell marker E-cadherin. Our analyses also show that HIF-1α was responsible for activating EMT via increased expression of the transcription factor Snail in gastric CSCs. Moreover, inhibition of Snail by shRNA reduced HIF-1α-induced EMT in gastric CSCs. The results demonstrated that hypoxia-induced EMT-like CSCs rely on HIF-1αto activate Snail, which may result in recurrence and metastasis of gastric cancer.