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1.
Biochem Pharmacol ; 186: 114437, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33571503

RESUMO

MerTK has been identified as a promising target for therapeutic intervention in glioblastoma. Genetic studies documented a range of oncogenic processes that MerTK targeting could influence, however robust pharmacological validation has been missing. The aim of this study was to assess therapeutic potential of MerTK inhibitors in glioblastoma therapy. Unlike previous studies, our work provides several lines of evidence that MerTK activity is dispensable for glioblastoma growth. We observed heterogeneous responses to MerTK inhibitors that could not be correlated to MerTK inhibition or MerTK expression in cells. The more selective MerTK inhibitors UNC2250 and UNC2580A lack the anti-proliferative potency of less-selective inhibitors exemplified by UNC2025. Functional assays in MerTK-high and MerTK-deficient cells further demonstrate that the anti-cancer efficacy of UNC2025 is MerTK-independent. However, despite its efficacy in vitro, UNC2025 failed to attenuate glioblastoma growth in vivo. Gene expression analysis from cohorts of glioblastoma patients identified that MerTK expression correlates negatively with proliferation and positively with quiescence genes, suggesting that MerTK regulates dormancy rather than proliferation in glioblastoma. In summary, this study demonstrates the importance of orthogonal inhibitors and disease-relevant models in target validation studies and raises a possibility that MerTK inhibitors could be used to target dormant glioblastoma cells.

2.
J Mater Chem B ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33605286

RESUMO

A hybrid self-healing hydrogel (PM hydrogel), based on polyvinyl alcohol (PVA) and chemically exfoliated molybdenum disulfide (ce-MoS2) nanosheets, was prepared by a simple freeze-thaw method. Due to the excellent photothermal conversion properties of ce-MoS2 nanosheets, the PM hydrogel self-repaired rapidly under near infrared (NIR) light irradiation for only 3 min with a high healing efficiency of 91.8 ± 3.3%. The PVA content, ce-MoS2 nanosheet loading and light irradiation time played important roles in the self-healing performance. Additionally, the PM hydrogel also revealed good self-healing properties with a healing efficiency of 60.6 ± 3.6% after the cut surfaces were separated for 24 h. The present approach provides an effective strategy for fabricating fast light-triggered hydrogen-bond based self-healing systems. The as-prepared hybrid PM hydrogel has great potential as a soft biomaterial for long-term applications due to its biocompatibility and self-healing capability.

3.
Anal Chem ; 93(6): 3241-3249, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33539094

RESUMO

Mitophagy plays a crucial role in maintaining intracellular homeostasis through the removal of dysfunctional mitochondria and recycling their constituents in a lysosome-degradative pathway, which leads to microenvironmental changes within mitochondria, such as the pH, viscosity, and polarity. However, most of the mitochondrial fluorescence viscosity probes only rely on electrostatic attraction and readily leak out from the mitochondria during mitophagy with a decreased membrane potential, thus easily leading to an inaccurate detection of viscosity changes. In this work, we report a mitochondria-immobilized NIR-emissive aggregation-induced emission (AIE) probe CS-Py-BC, which allows for an off-on fluorescence response to viscosity, thus enabling the real-time monitoring viscosity variation during mitophagy. This system consists of a cyanostilbene skeleton as the AIE active core and viscosity-sensitive unit, a pyridinium cation for the mitochondria-targeting group, and a benzyl chloride subunit that induces mitochondrial immobilization. As the viscosity increased from 0.903 cP (0% glycerol) to 965 cP (99% glycerol), CS-Py-BC exhibited an about 92-fold increase in fluorescence intensity at 650 nm, which might be attributed to the restriction of rotation and inhibition of twisted intramolecular charge transfer in a high viscosity system. We also revealed that CS-Py-BC could be well immobilized onto mitochondria, regardless of the mitochondrial membrane potential fluctuation. Most importantly, using CS-Py-BC, we have successfully visualized the increased mitochondrial viscosity during starvation or rapamycin-induced mitophagy in real time. All these features render CS-Py-BC a promising candidate to investigate mitophagy-associated dynamic physiological and pathological processes.

4.
Org Biomol Chem ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33566055

RESUMO

An isomer of lycoplanine A with a 6/10/5/5 tetracyclic skeleton was synthesized using D-A reaction and cascasde reaction to respectively construct the [9.2.2] pentadecane skeleton and the challenging 1-oxa-6-azaspiro[4.4]nonane spirocenter. Morever, detailed DFT calculations were conducted to explain the selectivity in the D-A reaction. This study may provide sufficient experience for the total synthesis of lycoplanine A and other alkaloids with similar spiro-N,O-acetal cores.

5.
Langmuir ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529533

RESUMO

In transfer printing, the loaded droplet on the probe has a significant influence on the dispensing resolution. A suitable loading approach for a high-viscous liquid is highly required. Herein, a novel electrostatic loading method is presented, in which the main aim is to control precisely the formation and breaking of a cone-shaped liquid bridge. An experimental device is developed. The influence of electrical and geometric parameters on the feature size of the liquid bridge is investigated in detail. In the formation of the liquid bridge, the increase of voltage or the decrease of the air gap can enhance the electric field intensity, thus reducing the formation period and increasing the initial cone tip diameter of the liquid cone. After the liquid bridge is formed, both the circuit current implying the liquid wetted area on the probe surface and the lifting velocity of the probe are utilized to further regulate the volume of the loaded droplet. Loaded droplets ranging from 60 to 600 pL are obtained via the method with a standard deviation of 4 to 30 pL. Moreover, a dot array is transferred with different loaded droplets. The minimum diameter of the printed dots is about 140 µm with a variation less than 5%. The advantages include the reduced risk of contamination, the droplet-size independent of the size of the probe, and the low cost of the device.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33568421

RESUMO

Infantile spasms are a potentially catastrophic form of epilepsy syndrome, which are usually associated with substantial developmental delay and commonly occur in children younger than 1 year. Infantile spasms usually associated with substantial developmental delay is a catastrophic form of all epilepsy syndromes that occur commonly in children younger than 1 year. Recent reports on four cases revealed that variants harbored in a novel gene CDK19 were causative for the syndromes. We report a fifth affected individual,case of a 10-month-old male patient who presented with clinically manifested witha neurodevelopmental syndrome characterized by infantile spasms. Wwe identified a novel de novo missense variant c.92C>A (p.Thr31Asn) in CDK19 which was classified as a likely pathogenic disease-causing variant. The characterized clinical phenotypes of the proband were similar to the previously reported four patients, but he had few variable features includinge earlier seizure onset age, and well-controlled seizures, earlier occurred developmental abnormality. Protein structure modeling analysis revealed that CDK19 variants may disable its kinase activity, which would further impede the transcriptional regulation, thus leading to detrimental pathologies. Our report expanded CDK19 genotype spectrum and further demonstrated that a CDK19 missense variant was causative of neurodevelopmental disorder clinically marked by infantile spasms.

7.
Nat Commun ; 12(1): 1142, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602941

RESUMO

Negative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.

8.
Cell Transplant ; 30: 963689721994808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33593080

RESUMO

Allogeneic stem cell transplantation is a cure for patients suffering from thalassemia major (TM). Historically, patients were limited by the selection of donors, while the advancement of haploidentical stem cell transplantation (haplo-SCT) has greatly expanded the donor pool. However, the outcomes of haplo-SCT in TM recipients vary between different programs. In this study, we retrospectively studied 73 pediatric TM patients (median age, 7 years; range, 3 to 14 years) who underwent haplo-cord transplantation. Both the estimated overall survival and transfusion-free survival were 95.26% (CI 95.77% to 96.23%). Neither primary nor secondary graft failures were observed. The median follow-up period was 811 days (range, 370 to 1433 days). Median neutrophil and platelet engraftment times were 22 days (range, 8 to 48 days) and 20 days (range, 8 to 99 days), respectively. Acute graft-versus-host disease (aGVHD) was observed in 52% of patients and of these, 25% developed grade III to IV aGVHD. Cord blood engraftment was associated with delayed immune recovery and increased aGVHD severity. Viral DNAemia occurred in a relatively high proportion of patients but only 7% of patients developed CMV disease, while another 7% of patients had post-transplantation lymphoproliferative disorder. Long-term complication outcomes were good. Only one patient developed extensive chronic GVHD. No surviving patients were reliant on blood transfusion by the time this manuscript was submitted. This is one of the largest studies on the outcomes of pediatric TM patients who received stem cell transplantations from alternative donors. The haplo-cord program is safe and practical for TM patients that do not have matched donors.

9.
Clin Appl Thromb Hemost ; 27: 1076029621989813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523719

RESUMO

Brain-derived neurotrophic factor (BDNF) plays a functional role in vascular endothelium homeostasis and the alleviation of atherosclerosis. Matrix gla protein (MGP) and Nε-(1-carboxymethyl)-l-lysine (CML) are both confirmed to be VC predictors. This study investigated the association between BDNF, MGP, CML and coronary artery calcification (CAC). Plasma BDNF, MGP, and CML levels were measured in 274 patients who underwent computed tomography to determine the CAC score (Agatston score). It was found that patients with CAC exhibited lower BDNF and MGP and higher CML levels than those without CAC. Plasma BDNF levels in patients with diabetes or hypertension were lower compared with the control groups. In logistic regression analysis, age, hypertension, BDNF, and MGP were independent predictors of CAC. Plasma BDNF and MGP levels were both correlated with the Agatston score even after adjustment for age, total cholesterol level, triglycerides, low-density lipoprotein level, creatinine clearance rate, and the presence of hypertension and diabetes mellitus. In 167 patients with CAC, circulating BDNF level was inversely associated with CML level and positively related to MGP level. In the receiver operating characteristic analysis for CAC, the areas under the curves for BDNF, MGP, and CML were 0.757, 0.777 and 0.653, respectively. In summary, plasma BDNF levels are associated with the Agatston score, and BDNF further predicts the occurrence of CAC.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Doença da Artéria Coronariana/sangue , Calcificação Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Proteínas da Matriz Extracelular/sangue , Feminino , Humanos , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Calcificação Vascular/diagnóstico por imagem
10.
Medicine (Baltimore) ; 100(6): e24651, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578593

RESUMO

ABSTRACT: This study aimed to explore the significance and prognostic value of serum tumor-associated carbohydrate antigen 19-9 (CA19-9), D-dimer, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) in patients with pancreatic ductal adenocarcinoma (PDAC).Our study included 148 patients treated for PDAC at Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2012 to December 2016. Cutoff prognostic values were predicted using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to assess the survival rates of patients. Univariate and multivariate COX regression analyses were used to evaluate the prognostic factors.The recommended cutoff values of neutrophil-lymphocyte rate (NLR), platelet-lymphocyte rate (PLR), CA19-9, and D-dimer were 2.04 (sensitivity, 0.59; specificity, 0.9; area under the ROC curve [AUC], 0.749; P < .001), 52.94 (sensitivity, 0.73; specificity, 0.95; AUC, 0.829; P < .001), 176.66 U/mL (sensitivity, 0.7; specificity, 0.9; AUC, 0.794; P < .001), and 1.18 mg/L (sensitivity, 0.82; specificity, 0.9; AUC, 0.845; P < .001), respectively. Positive TNFAIP3/A20 expression was considered as an inclusion criterion. Serum CA19-9 expression was related with lymph node metastasis (P = .010), tumor-lymph node-metastasis (TNM) stage (P < .001), and survival rate (P < .001). D-dimer was correlated with tumor differentiation grade (P = .014), tumor size (P = .045), TNM stage (P < .001), and survival rate (P < .001). TNFAIP3/A20 was correlated with tumor differentiation grade (P < .001), body mass index (BMI) (P < .001), TNM stage (P = .014), and survival rate (P < .001). Kaplan-Meier curves showed that PDAC patients had significant differences in CA19-9, D-dimer, and TNFAIP3/A20 expressions (P < .05). CA19-9, D-dimer, TNM stage, tumor differentiation grade, and TNFAIP3/A20 were independent prognostic markers for PDAC in univariate and multivariate COX analyses.CA19-9, D-dimer, and TNFAIP3/A20 were found to be independent prognostic markers for PDAC patients.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/mortalidade , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , China/epidemiologia , Feminino , Humanos , Metástase Linfática/patologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neutrófilos/patologia , Prognóstico , Curva ROC , Sensibilidade e Especificidade , Taxa de Sobrevida
11.
Cell Res ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514914

RESUMO

Cathepsin D (cathD) is traditionally regarded as a lysosomal protease that degrades substrates in acidic compartments. Here we report cathD plays an unconventional role as a cofilin phosphatase orchestrating actin remodeling. In neutral pH environments, the cathD precursor directly dephosphorylates and activates the actin-severing protein cofilin independent of its proteolytic activity, whereas mature cathD degrades cofilin in acidic pH conditions. During development, cathD complements the canonical cofilin phosphatase slingshot and regulates the morphogenesis of actin-based structures. Moreover, suppression of cathD phosphatase activity leads to defective actin organization and cytokinesis failure. Our findings identify cathD as a dual-function molecule, whose functional switch is regulated by environmental pH and its maturation state, and reveal a novel regulatory role of cathD in actin-based cellular processes.

12.
Future Oncol ; 17(5): 529-539, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33401980

RESUMO

Aim: This initial study was conducted with the aim of constructing an accurate nomogram for gastric marginal zone lymphoma patients. Methods: Data from 4414 patients diagnosed with gastric mucosa-associated lymphoid tissue lymphoma from 2004 to 2015 were retrieved from the Surveillance, Epidemiology and End Results database. Multivariate analyses were conducted for the construction of the nomogram. Results: Age, sex, race, marital status, Ann Arbor stage and radiotherapy were significantly associated with overall survival, while age, marital status, Ann Arbor stage, surgery, chemotherapy and radiotherapy were independent prognostic predictors of cause-specific survival. Stratified analysis indicated that radiotherapy alone resulted in better overall survival and cause-specific survival than chemotherapy alone. However, the present study also has several limitations; for example, patients' Helicobacter pylori infection status and the chemotherapy regimen used were unknown. Conclusion: This study constructed and validated an accurate prognostic nomogram for gastric mucosa-associated lymphoid tissue lymphoma patients.

13.
Acta Crystallogr D Struct Biol ; 77(Pt 1): 108-116, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404530

RESUMO

Apical sodium-dependent bile acid transporter (ASBT) mediates the uptake of bile acids from the ileum lumen into enterocytes and presents a potential target for the treatment of several metabolic diseases, including type 2 diabetes. It has been proposed that the underlying mechanism for transport by ASBT is an elevator-style alternating-access model, which was deduced mainly by comparing high-resolution structures of two bacterial ASBT homologs (ASBTNM from Neisseria meningitides and ASBTYf from Yersinia frederiksenii) in different conformations. However, one important issue is that the only outward-facing structure (PDB entry 4n7x) was obtained with an Na+-binding site mutant of ASBTYf, which severely cripples its transport function, and therefore the physiological relevance of the conformation in PDB entry 4n7x requires further careful evaluation. Here, another crystal structure is reported of ASBTYf that was captured in a state closely resembling the conformation in PDB entry 4n7x using an engineered disulfide bridge. The introduced cysteine mutations avoided any proposed Na+- or substrate-binding residues, and the resulting mutant retained both structural and functional integrity and behaved similarly to wild-type ASBTYf. These data support the hypothesis that the PDB entry 4n7x-like structure represents a functional outward-facing conformation of ASBTYf in its transport cycle.

14.
Acta Crystallogr D Struct Biol ; 77(Pt 1): 117-125, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404531

RESUMO

Apical sodium-dependent bile acid transporter (ASBT) retrieves bile acids from the small intestine and plays a pivotal role in enterohepatic circulation. Currently, high-resolution structures are available for two bacterial ASBT homologs (ASBTNM from Neisseria meningitides and ASBTYf from Yersinia frederiksenii), from which an elevator-style alternating-access mechanism has been proposed for substrate transport. A key concept in this model is that the substrate binds to the central cavity of the transporter so that the elevator-like motion can expose the bound substrate alternatingly to either side of the membrane during a transport cycle. However, no structure of an ASBT has been solved with a substrate bound in its central cavity, so how a substrate binds to ASBT remains to be defined. In this study, molecular docking, structure determination and functional analysis were combined to define and validate the details of substrate binding in ASBTYf. The findings provide coherent evidence to provide a clearer picture of how the substrate binds in the central cavity of ASBTYf that fits the alternating-access model.

15.
Aging (Albany NY) ; 13(3): 4096-4114, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33493138

RESUMO

Due to the difficulties in early diagnosis of pancreatic adenocarcinoma (PAAD), many patients fail to receive optimal therapeutic regimens. The Secretory-Carrier-Membrane-Proteins (SCAMPs) are known to be dysregulated in a range of human diseases due to their characterized roles in mammalian cell exocytosis inferred from their functions as integral membrane proteins. However, the expression and prognostic value of SCAMPs in PAAD is poorly characterized. We compared cancer vs. healthy tissue and found that the expression of SCAMPs1-4 was upregulated in PAAD compared to normal tissue. In contrast, SCAMP5 expression was downregulated in PAAD. Moreover, the expression of SCAMPs1-4 was enhanced in PAAD cell lines according to Cancer Cell Line public database. Furthermore, the HPA, GEPIA databases and immunohistochemical analysis from 238 patients suggested that the loss of SCAMP1 led to improved overall survival (OS), whilst lower SCAMP5 levels led to a poorer OS. The univariate and multivariate analysis showed that SCAMP1 and SCAMP5 expression were independent prognostic factors of PAAD. In addition, the cBioPortal for Cancer Genomics, LinkedOmics datasets, and the GEPIA were used to identify the co-expression genes of SCAMP1,5 and the correlation between SCAMPs members. We conclude that SCAMPs 1 and 5 significantly represent promising diagnosis and prognostic biomarkers.

16.
Nanoscale Res Lett ; 16(1): 15, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475898

RESUMO

GaAs nanostructures have attracted more and more attention due to its excellent properties such as increasing photon absorption. The fabrication process on GaAs substrate was rarely reported, and most of the preparation processes are complex. Here, we report a black GaAs fabrication process using a simple inductively coupled plasma etching process, with no extra lithography process. The fabricated sample has a low reflectance value, close to zero. Besides, the black GaAs also displayed hydrophobic property, with a water contact angle of 125°. This kind of black GaAs etching process could be added to the fabrication workflow of photodetectors and solar cell devices to further improve their characteristics.

17.
J Mol Med (Berl) ; 99(2): 193-212, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33392633

RESUMO

Although gastric cancer (GC) is one of the most common cancers with high incidence and mortality rates, its pathogenesis is still not elucidated. GC carcinogenesis is complicated and involved in the activation of oncoproteins and inactivation of tumor suppressors. The ubiquitin-proteasome system (UPS) is crucial for protein degradation and regulation of physiological and pathological processes. E3 ubiquitin ligases are pivotal enzymes in UPS, containing various subfamily proteins. Previous studies report that some E3 ligases, including SKP2, CUL1, and MDM2, act as oncoproteins in GC carcinogenesis. On the other hand, FBXW7, FBXL5, FBXO31, RNF43, and RNF180 exert as tumor suppressors in GC carcinogenesis. Moreover, E3 ligases modulate cell growth, cell apoptosis, and cell cycle; thus, it is complicated to confer cisplatin resistance/sensitivity in GC cells. The intrinsic and acquired cisplatin resistance limits its clinical application against GC. In this review, we explore oncogenic and tumor suppressive roles of E3 ligases in GC carcinogenesis and focus on the effects of E3 ligases on cisplatin resistance in GC cells, which will provide novel therapeutic targets for GC therapy, especially for cisplatin-resistant patients.

18.
Respir Res ; 22(1): 1, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407436

RESUMO

BACKGROUND: ALI/ARDS is a severe lung injury leading to refractory respiratory failure, accounting for high morbidity and mortality. However, therapeutic approaches are rather limited. Targeting long non-coding RNA MALAT1 and microRNA miR-181a-5p might be potential option for ALI/ARDS intervention. OBJECTIVE: We aimed to investigate the role of MALAT and miR-181a-5p in the pathogenesis of ALI/ARDS, and test the therapeutic effects of targeting MALAT and miR-181a-5p for ALI/ARDS intervention in vitro. METHODS: MALAT1 and miR-181a-5p levels were measured in plasma from ALI/ARDS patients. In vitro human pulmonary microvascular endothelial cell (HPMEC) injury was induced by LPS treatment, and molecular targets of MALAT1 and miR-181a-5p were explored by molecular biology approaches, mainly focusing on cell apoptosis and vascular inflammation. Interaction between MALAT1 and miR-181a-5p was also detected. Finally, the effects of targeting MALAT1 and miR-181a-5p for ALI/ARDS intervention were validated in a rat ALI/ARDS model. RESULTS: MALAT1 upregulation and miR-181a-5p downregulation were observed in ALI/ARDS patients. Transfection of mimic miR-181a-5p into HPMECs revealed decreased Fas and apoptosis, along with reduced inflammatory factors. Fas was proved to be a direct target of miR-181a-5p. Similar effects were also present upon MALAT1 knockdown. As for the interaction between MALAT1 and miR-181a-5p, MALAT1 knockdown increased miR-181a-5p expression. Knocking down of MALAT1 and miR-181a-5p could both improve the outcome in ALI/ARDS rats. CONCLUSION: MALAT1 antagonism or miR-181a-5p could both be potential therapeutic strategies for ALI/ARDS. Mechanistically, miR-181a-5p directly inhibits Fas and apoptosis, along with reduced inflammation. MALAT1 negatively regulates miR-181a-5p.

19.
J Phys Chem B ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33412855

RESUMO

We use the pulse current thermoplastic forming technique based on joule heating to rejuvenate the atomic structure of a La62Al14Ag2.34Ni10.83Co10.83 bulk metallic glass (BMG). The pulse-formed sample exhibits more pronounced ß-relaxation than the as-cast one due to the increased free volume. Instead, the sub-Tg annealing clearly weakens the ß-relaxation and also makes it more isolated from the α-relaxation, showing contributions from free volume and preferred structure. However, both treatments exhibit little influence on the following α-relaxation and high temperature crystallization kinetics. Our results open an effective way to rejuvenate the structure of BMGs and provide an in-depth understanding of the relationship between structural relaxations and crystallization kinetics of BMGs.

20.
Nat Commun ; 12(1): 46, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397902

RESUMO

The exploration of highly efficient processes to convert renewable biomass to fuels and value-added chemicals is stimulated by the energy and environment problems. Herein, we describe an innovative route for the production of methylcyclopentadiene (MCPD) with cellulose, involving the transformation of cellulose into 3-methylcyclopent-2-enone (MCP) and subsequent selective hydrodeoxygenation to MCPD over a zinc-molybdenum oxide catalyst. The excellent performance of the zinc-molybdenum oxide catalyst is attributed to the formation of ZnMoO3 species during the reduction of ZnMoO4. Experiments reveal that preferential interaction of ZnMoO3 sites with the C=O bond instead of C=C bond in vapor-phase hydrodeoxygenation of MCP leads to highly selective formations of MCPD (with a carbon yield of 70%).


Assuntos
Celulose/química , Ciclopentanos/química , Óxidos/química , Oxigênio/química , Adsorção , Catálise , Relação Estrutura-Atividade , Difração de Raios X
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