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1.
Mol Biol Rep ; 47(11): 8963-8973, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33161529

RESUMO

To investigate the functional role of fasudil in optic nerve crush (ONC), and further explore its possible molecular mechanism. After ONC injury, the rats were injected intraperitoneally either with fasudil or normal saline once a day until euthanized. RGCs survival was assessed by retrograde labeling with FluoroGold. Retinal glial cells activation and population changes (GFAP, iba-1) were measured by immunofluorescence. The expressions of cleaved caspase 3 and 9, p-ERK1/2 and p-AKT were detected by western blot. The levels of the pro-inflammatory cytokines were determined using real-time polymerase chain reaction. Fasudil treatment inhibited RGCs apoptosis and reduced RGCs loss demonstrated by the decreased apoptosis-associated proteins expression and the increased fluorogold labeling of RGCs after ONC, respectively. In addition, the ONC + fasudil group compared had a significantly lower expression of GFAP and iba1 compared with the ONC group. The levels of pro-inflammatory cytokines were significantly reduced in the ONC + fasudil group than in the ONC group. Furthermore, the phosphorylation levels of ERK1/2 and AKT (p-ERK1/2 and p-AKT) were obviously elevated by the fasudil treatment. Our study demonstrated that fasudil attenuated glial cell-mediated neuroinflammation by up-regulating the ERK1/2 and AKT signaling pathways in rats ONC models. We conclude that fasudil may be a novel treatment for traumatic optic neuropathy.

2.
Surg Endosc ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185766

RESUMO

BACKGROUND: This study was aimed to develop a computer-aided diagnosis (CAD) system with deep-learning technique and to validate its efficiency on detecting the four categories of lesions such as polyps, advanced cancer, erosion/ulcer and varices at endoscopy. METHODS: A deep convolutional neural network (CNN) that consists of more than 50 layers were trained with a big dataset containing 327,121 white light images (WLI) of endoscopy from 117,005 cases collected from 2012 to 2017. Two CAD models were developed using images with or without annotation of the training dataset. The efficiency of the CAD system detecting the four categories of lesions was validated by another dataset containing consecutive cases from 2018 to 2019. RESULTS: A total of 1734 cases with 33,959 images were included in the validation datasets which containing lesions of polyps 1265, advanced cancer 500, erosion/ulcer 486, and varices 248. The CAD system developed in this study may detect polyps, advanced cancer, erosion/ulcer and varices as abnormality with the sensitivity of 88.3% and specificity of 90.3%, respectively, in 0.05 s. The training datasets with annotation may enhance either sensitivity or specificity about 20%, p = 0.000. The sensitivities and specificities for polyps, advanced cancer, erosion/ulcer and varices reached about 90%, respectively. The detect efficiency for the four categories of lesions reached to 89.7%. CONCLUSION: The CAD model for detection of multiple lesions in gastrointestinal lumen would be potentially developed into a double check along with real-time assessment and interpretation of the findings encountered by the endoscopists and may be a benefit to reduce the events of missing lesions.

3.
Inorg Chem ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164506

RESUMO

Metal and nitrogen codoped carbon (M-Nx/C) materials with good metal dispersion in a carbon matrix have attracted great attention because they can efficiently catalyze various kinds of chemical/electrochemical reactions. However, the existing strategies for preparing M-Nx/C materials still face the challenge of metal site aggregation when the carbon skeleton in the precursor is substantially lost during pyrolysis. Herein, we propose a general strategy that the increase of metal site density and inhibition of metal aggregation could be realized by separating M-N4 units in metal-organic frameworks (MOFs). The metal sites can be well separated and distributed in carbon materials during the pyrolysis of a metal-coordinated block copolymer, one of the specific MOFs. The strategy can be widely applicable for the synthesis of M-Nx/C materials with dense metal sites, such as Fe-, Mn-, Ni-, and Co-Nx/C materials, which are potentially used as the efficient catalysts for various kinds of reactions. Taking Fe-Nx/C as a model oxygen reduction reaction (ORR) electrocatalyst, it shows the ORR half-wave potentials of 0.90 and 0.81 V vs RHE in alkaline and acidic electrolytes, respectively.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33225572

RESUMO

In addition to their common planktonic lifestyle, bacteria frequently live in surface-associated habitats. Surface motility is essential for exploring these habitats for food sources. However, many bacteria are found on surfaces, even though they lack features required for migrating along surfaces. How these canonical non-motile bacteria adapt to the environmental fluctuations on surfaces remains unknown. Here, we report a previously unknown surface motility mode of the canonical non-motile bacterium, Dietzia sp. DQ12-45-1b, which is triggered by interaction with a dimorphic prosthecate bacterium, Glycocaulis alkaliphilus 6B-8T. Dietzia cells exhibits "sliding"-like motility in an area where the strain Glycocaulis cells was pre-colonized with a sufficient density. Our analysis also demonstrates that Dietzia degrade n-alkanes and provide Glycocaulis with the resulting metabolites for survival, which in turn induced directional migration of Dietzia towards nutrient-rich environments. Such interaction-triggered migration was also found between Dietzia and Glycocaulis strains isolated from other habitats, suggesting that this mutualistic relationship ubiquitously occurs in natural environments. In conclusion, we propose a novel model for such a 'win-win' strategy, whereby non-motile bacteria pay metabolites to dimorphic prosthecate bacteria in return for migrating to seek for nutrients, which may represent a common strategy for canonically non-motile bacteria living on a surface. This article is protected by copyright. All rights reserved.

5.
Autophagy ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213267

RESUMO

The function of mitophagy in cancer is controversial. ULK1 is critical for induction of macroautophagy/autophagy and has a more specific role in mitophagy in response to hypoxia. Here, we show that ULK1 deficiency induces an invasive phenotype of breast cancer cells under hypoxia and increases osteolytic bone metastasis. Mechanistically, ULK1 depletion attenuates mitophagy ability during hypoxia. As a result, the accumulation of damaged, ROS-generating mitochondria leads to activation of the NLRP3 inflammasome, which induces abnormal soluble cytokines secretion, then promotes the differentiation and maturation of osteoclasts, and ultimately results in bone metastasis. Notably, phosphorylation of ULK1 by MAPK1/ERK2-MAPK3/ERK1 kinase triggers its interaction with BTRC and subsequent K48-linked ubiquitination and proteasome degradation. Also, a clearly negative correlation between the expression levels of ULK1 and p-MAPK1/3 was observed in human breast cancer tissues. The MAP2K/MEK inhibitor trametinib is sufficient to restore mitophagy function via upregulation of ULK1, leading to inhibition of NLRP3 inflammasome activation, thereby reduces bone metastasis. These results indicate that ULK1 knockout-mediated mitophagy defect promotes breast cancer bone metastasis and provide evidence to explore MAP2K/MEK- MAPK1/3 pathway inhibitors for therapy, especially in cancers displaying low levels of ULK1.

6.
World J Gastroenterol ; 26(38): 5749-5758, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33132632

RESUMO

Since the outbreak of the coronavirus disease 2019 (COVID-19), various measures have been taken to protect against the infection. As droplet and contact transmission are the main routes of COVID-19 infection, endoscopy centers are considered to be high-risk areas for exposure to COVID-19. We have undertaken several countermeasures in our endoscopic center during the pandemic, and have gained significant experience in terms of prevention and control of COVID-19. We here present our experience and strategies adopted for preventing hospital infection in our endoscopy center during the COVID-19 pandemic. We describe our management of the environment, endoscope, patients, and medical staff, and our self-made masks.


Assuntos
Desinfecção , Endoscopia Gastrointestinal/métodos , Planejamento Ambiental , Controle de Infecções/organização & administração , Admissão e Escalonamento de Pessoal , Betacoronavirus , China , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Humanos , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão
7.
Virol J ; 17(1): 166, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121509

RESUMO

BACKGROUND: Chronic active Epstein-Barr virus (CAEBV) infection is a type of lymphoproliferative disorder characterized by chronic or recurrent infectious mononucleosis (IM)-like symptoms, which can have less-frequent clinical presentations. The prognosis of CAEBV is poor, and hematopoietic stem cell transplantation (HSCT) has been shown to be the only potentially effective treatment. In this article, we present a special CAEBV case of a patient who had no typical IM-like symptoms at the early stage, but manifested with severe and progressive coronary artery aneurysm (CAA), abdominal aortic lesions, and severe uveitis. These manifestations were uncommon features and could only be blocked by HSCT. CASE PRESENTATION: A 4-year-old girl with no special medical history complained of decreased vision for 10 months and cough after physical activities for three months. The blurred vision grew rapidly worse within one month, until only light perception remained. She was diagnosed with uveitis and cataract, and received prednisone and ciclosporin A treatment. However, her vision did not improve. Physical examination showed slight hepatosplenomegaly. Ultrasonic cardiogram showed bilateral CAA (5.0 mm and 5.7 mm for inner diameters), and abdominal CT scan revealed a thickened aortic wall, as well as stenosis and dilation of the segmental abdominal aorta. Other significant findings were increased EBV-DNA (3.29 × 104 copies/mL) from peripheral blood, positive EBV antibodies (EBV-CA-IgG, EBV-EA-IgA, and EBV-NA-IgG), and positive EBV-encoded small RNAs found by bone marrow biopsy. Based on her clinical manifestations and evidence for EBV infection, we diagnosed CAEBV. She received allogeneic HSCT, and the cataract operation was performed after HSCT. EBV-DNA could not be detected in peripheral blood after HSCT. Her CAAs did not progress, and uveitis was well controlled. Her vision recovered gradually over the 3 years after HSCT. CONCLUSIONS: We present a rare CAEBV case of a patient who suffered from uncommon and severe cardiovascular and ocular involvement that was relieved by HSCT. Therefore, early recognition and diagnosis of CAEBV are of vital importance to improve its prognosis. In summary, this atypical CAEBV case could help us recognize similar cases more easily, make the right diagnosis as early as possible, and deliver proper and timely treatment.

8.
Biomolecules ; 10(10)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081293

RESUMO

Cochlear hair cells in human beings cannot regenerate after loss; however, those in fish and other lower species can. Recently, the role of inflammation in hair cell regeneration has been attracting the attention of scientists. In the present study, we investigated how suppression of inflammatory factors affects hair cell regeneration and the functional recovery of regenerated hair cells in zebrafish. We killed hair cells in the lateral line of zebrafish larvae with CuSO4 to induce an inflammatory response and coapplied BRS-28, an anti-inflammatory agent to suppress the inflammation. The recovery of the hair cell number and rheotaxis was slower when CuSO4 and BRS-28 were coapplied than when CuSO4 was applied alone. The recovery of hair cell count lagged behind that of the calcium imaging signal during the regeneration. The calcium imaging signal in the neuromasts in the inflammation-inhibited group was weaker than that in the noninflammation-inhibited group at the early stage of regeneration, although it returned to normal at the late stage. Our study demonstrates that suppressing inflammation by BRS-28 delays hair cell regeneration and functional recovery when hair cells are damaged. We suspect that BRS-28 inhibits pro-inflammatory factors and thereby reduces the migration of macrophages to delay the regeneration of hair cells.

9.
Neurosci Bull ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33123984

RESUMO

Dual oxidase (duox)-derived reactive oxygen species (ROS) have been correlated with neuronal polarity, cerebellar development, and neuroplasticity. However, there have not been many comprehensive studies of the effect of individual duox isoforms on central-axon regeneration in vivo. Here, we explored this question in zebrafish, an excellent model organism for central-axon regeneration studies. In our research, mutation of the duox gene with CRISPR/Cas9 significantly retarded the single-axon regeneration of the zebrafish Mauthner cell in vivo. Using deep transcriptome sequencing, we found that the expression levels of related functional enzymes in mitochondria were down-regulated in duox mutant fish. In vivo imaging showed that duox mutants had significantly disrupted mitochondrial transport and redox state in single Mauthner-cell axon. Our research data provide insights into how duox is involved in central-axon regeneration by changing mitochondrial transport.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33109343

RESUMO

Cisplatin is used in a wide variety of malignancies, but cisplatin-induced ototoxicity remains a major issue in clinical practice. Experimental evidence indicates that ferroptosis plays a key role in mediating the unwanted cytotoxicity effect caused by cisplatin. However, the role of ferroptosis in cisplatin-induced ototoxicity requires elucidation. Ferrostatin-1 (Fer-1) was identified as a potent inhibitor of ferroptosis and radical-trapping antioxidant with its ability to reduce the accumulation of lipid peroxides and chain-carrying peroxyl radicals. In the current study, we investigated the effects of Fer-1 in cisplatin-induced ototoxicity in in vitro, ex vivo, and in vivo models. We found, for the first time that Fer-1 efficiently alleviated cisplatin-induced cytotoxicity in HEI-OC1 cells via a concentration-dependent manner. Furthermore, Fer-1 mitigated cisplatin cytotoxicity in transgenic zebrafish sensory hair cells. In HEI-OC1 cells, Fer-1 pretreatment not only drastically reduced the generation of intracellular reactive oxygen species but also remarkably decreased lipid peroxidation levels induced by cisplatin. This was not only ascribed to the inhibition of 4-hydroxynonenal, the final product of lipid peroxides, but also to the promotion of glutathione peroxidase 4, the protein marker of ferroptosis. MitoTracker staining and transmission electron microscopy of mitochondrial morphology suggested that in HEI-OC1 cells, Fer-1 can effectively abrogate mitochondrial damage resulting from the interaction with cisplatin. In addition, Fer-1 pretreatment of cochlear explants substantially protected hair cells from cisplatin-induced damage. Therefore, our results demonstrated that ferroptosis might be involved in cisplatin ototoxicity. Fer-1 administration mitigated cisplatin-induced hair cell damage, further investigations are required to elucidate the molecular mechanisms of its otoprotective effect.

12.
World J Clin Cases ; 8(19): 4624-4632, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083427

RESUMO

BACKGROUND: Esophageal carcinosarcoma, usually presenting as a pedunculated polypoid mass, is a rare malignancy with coexisting sarcomatoid and carcinomatous components. Its imaging and endoscopic characteristics are similar to those of leiomyosarcoma, liposarcoma and so forth. The diagnosis needs histological confirmation. Surgical resection is the traditional therapy. Endoscopic resection is minimally invasive but still controversial. This paper reports the case of a patient with a giant esophageal carsinosarcoma who underwent a palliative endoscopic resection. CASE SUMMARY: A 55-year-old male patient presented with dysphagia and weight loss for 1 mo. Imaging and endoscopy showed a gray-white, polypoid, stalk-like mass, with a bulky pedicle located in the middle and lower esophagus. The mass almost filled the whole esophageal lumen, but the endoscope could still pass through. Despite the suspicion of a malignancy, repeated biopsies indicated necrosis and inflammation. After multidisciplinary team consultation, an endoscopic resection to diagnose and relieve the obstruction was recommended. The pedicle of the mass was cut off, the bleeding was stopped, and the mass was cut into pieces and pulled out. The mass was 26 cm × 5 cm × 4 cm in size. The final diagnosis was esophageal carcinosarcoma. No postoperative complications occurred. After 1 mo, the patient gained 6 kg and endoscopic reexamination revealed no obstruction. Radical surgery with lymph node dissection was carried out successfully. This lesion was the largest endoscopically resected esophageal carcinosarcoma reported to date. CONCLUSION: Endoscopic palliative resection can help obtain adequate tissue for diagnosis and relieve obstructions in patients with giant esophageal carcinosarcoma.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33075006

RESUMO

BACKGROUND: A reliable large animal model of benign biliary stricture (BBS) is essential to study endoscopic management of BBS. The aim of this study was to establish a swine BBS model of endobiliary electrothermal injury with a diathermic sheath and screen out the optimal energy dose. MATERIALS AND METHODS: Twelve swine were equally randomized into a low (20 W), a medium (30 W), and a high (40 W)-dose group. Endobiliary electrothermal injury was applied to the common bile duct using a diathermic sheath at different energy doses for 20 seconds via endoscopic retrograde cholangiopancreatography. Cholangiographic findings and liver function were evaluated weekly after thermal injury. Two animals from each group were sacrificed at 2 weeks and the other 2 sacrificed 4 weeks after thermal injury for histopathologic evaluation. RESULTS: BBS was established successfully in 10 of the 12 animals. Two of the 4 animals in low-dose group did not produce biliary stricture at 4 weeks; in medium-dose group, BBS was induced in both animals at 2 weeks without causing severe complications; and in high-dose group, BBS was produced in 4 animals at 2 weeks, causing perforation and abdominal abscess formation in 1 animal. CONCLUSIONS: A safe and reproducible swine model of BBS could be established successfully by applying endobiliary electrothermal injury with a diathermic sheath at 30 W for 20 seconds.

14.
Sci Rep ; 10(1): 17848, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082509

RESUMO

To evaluate the imaging features of subungual glomus tumors using 18 MHz high-frequency ultrasound with CDFI (Color Doppler Flow Imaging). 20 patients treated by surgical resection and examined by ultrasound between January 2008 and December 2019. All eligible cases are divided into two groups: Group A used the probe frequency of 9-14 MHz from January 2008 to December 2014, and Group B used the probe frequency of 18 MHz from January 2015 to December 2019. Patient demographics, clinical records, pathologic specimens and sonography features were reviewed. 50% of tumors in Group A and 100% of tumors in Group B showed clear boundary and regular shape. Blood flow signals were identified inside 50% tumors in Group A (3 in 6), all 14 cases with blood flow signals detected in Group B (14 in 14,100%). 2 cases were misdiagnosed and 1 case escaped diagnosis in Group A, no case was misdiagnosed in Group B. The accuracy of diagnosis rate of Group B is significantly higher than that of Group A. 18-MHz ultrasound combined with CDFI may be a practical useful tool for detecting subungual glomus tumors. More importantly 18-MHz ultrasound can obviously improve the diagnostic accuracy.

15.
Pediatr Infect Dis J ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33044433

RESUMO

BACKGROUND: There are limit studies about pediatric brain abscess in China. The aim of this study was to analyze clinical characteristics and outcomes of pediatric brain abscess in recent years in China. METHODS: The clinical information of children with brain abscess hospitalized in Beijing Children's Hospital between January 1, 2007 and December 31, 2016 were retrospectively reviewed. RESULTS: Ninety-four children were enrolled in this study. A Streptococcus milleri group (13.8%) was identified as the most common causative organisms, followed by Staphylococcus aureus (6.4%). The overall mortality was 21.6%, with 50.0% of deaths happening in the first week after diagnosis. Long-term outcomes of 74 patients were assessed with Glasgow Outcome Scale-Extended Pediatric Reversion: 50 patients with a score of 1-2 (favorable outcome) and 24 patients with a score of 3-8 (unfavorable outcome). Patients with multiple abscesses (P = 0.029) and intraventricular rupture of brain abscess/hydrocephalus (P = 0.024) had higher risk of unfavorable outcomes. CONCLUSIONS: Brain abscess is a serious disease with high mortality in children; more aggressive treatments should be considered in the first week of diagnosis because of high risk of death, and for patients with multiple brain abscesses and intraventricular rupture of brain abscess/hydrocephalus because of their higher risk of unfavorable.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33059922

RESUMO

Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases.

17.
Diagn Microbiol Infect Dis ; 98(4): 115199, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979617

RESUMO

COVID-19 positive (194) and negative (212) pneumonia patients were selected to analyze bacterial pathogens coinfection. Results showed that 50% of COVID-19 patients were coinfected or carried bacterial pathogens. Bordetella pertussis infection rate was significantly higher in positive patients. Consequently, preventions should be taken to control bacterial pathogens coinfection in COVID-19 patients.

18.
Atherosclerosis ; 312: 43-53, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32971395

RESUMO

BACKGROUND AND AIMS: Long noncoding RNAs (lncRNAs) have recently been implicated in many biological and disease processes, but the exact mechanism of their involvement in atherosclerosis is unclear. The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. This study aimed to investigate the potential effects of lncRNA ZNF800, a previously uncharacterized lncRNA, on VSMC proliferation and migration. METHODS: The expression of lncRNA ZNF800 in atherosclerotic plaque tissues was detected using reverse transcription-quantitative PCR (RT-qPCR), while the role and mechanism of lncRNA ZNF800 in proliferation and migration of VSMCs were investigated by CCK8 assay, transwell assay, scratch wound assay, RT-qPCR and Western blot. RESULTS: We found that lncRNA ZNF800 was significantly more abundant in atherosclerotic plaque tissues, and substantially suppressed the proliferation and migration of VSMCs. LncRNA ZNF800 had no effect on phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mRNA expression but dramatically increased the levels of PTEN protein. Enhanced lncRNA ZNF800 expression inhibited the activity of the AKT/mTOR/HIF-1α signaling pathway, downregulated the expression of vascular endothelial growth factor α (VEGF-α) and matrix metalloproteinase 1 (MMP1), and suppressed VSMC proliferation and migration. These inhibitory effects of lncRNA ZNF800 were abolished by knockdown of PTEN. The inhibitory effects of lncRNA ZNF800 on cell proliferation and migration and the expression of VEGF-α and MMP1 were exacerbated by HIF-1α knockdown in VSMCs. CONCLUSIONS: These findings demonstrated that lncRNA ZNF800 suppressed VSMC proliferation and migration by interacting with PTEN through a mechanism involving AKT/mTOR/HIF-1α signaling. Therefore, it may play a key atheroprotective role and represent a potential therapeutic target for atherosclerosis-related diseases.

19.
J Org Chem ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32865421

RESUMO

Ru-catalyzed cross-coupling of secondary alcohols with only byproducts H2 and H2O provides a green synthetic strategy to prepare ß-disubstituted ketones. Density functional theory (DFT) calculations were performed with the coupling of 1-phenylethanol and cyclohexanol as a model reaction to gain deeper mechanistic insights herein. The mechanistic details of the main reaction and the key steps of possible side reactions were clarified, and the obtained results are consistent with reported selectivity. Hydrogenation of α,ß-unsaturated ketones and dehydrogenation of ruthenium hydride intermediate are direct chemoselectivity-determining stages. The hydrogenation via 1,4-addition generates more stable intermediates, being favored over that via 1,2-addition, and thus avoids the formation of alkene products. The conjugation and π-π stacking effects of phenyl and the weak electronic effect of alkyls explain the dominance of specific ketone products in the hydrogenation stage. Hydrogenation of ketone products is kinetically operative but not exergonic enough to stop the irreversible dihydrogen release in an open reaction system, and thus alcohol products are absent. Furthermore, water evaporation in aldol condensation is found to be a double-edged sword, as it can accelerate the hydrogenation stage to prevent α,ß-unsaturated ketones from being the main products but decrease the selectivity therein from thermodynamics overall.

20.
Inflammation ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32892306

RESUMO

Sepsis-induced acute kidney injury (SAKI) is a common complication of hospitalized patients, often leading to unacceptable mortality. Limited effective treatment or diagnosis biomarkers are available and the underlying mechanism remains unclear. The miR-30c-5p is considered as a critical mediator of kidney diseases and aberrantly decreased in patients with SAKI, while the mechanism is still unclear. For this purpose, the role of miR-30c-5p in SAKI has been investigated in this study. Here, we first confirmed that miR-30c-5p expression decreased in our septic models and was associated with the activation of NLRP3/caspase-1-mediated pyroptosis. Overexpression of miR-30c-5p alleviated the kidney injury via suppressing HK-2 cell pyroptosis. Furthermore, we identified that TXNIP was a direct target of miR-30c-5p. Upregulation of miR-30c-5p repressed the expression of TXNIP, which inhibited NLRP3, ASC, and caspase-1 expression, as well as secretion of inflammatory cytokines. In conclusion, our data suggested that miR-30c-5p negatively controlled the NLRP3 signal pathway-related pyroptosis and sepsis-induced injury via TXNIP, indicating that this axis might be a positive therapeutic target for the patient with SAKI.

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