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1.
J Mater Chem B ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33942817

RESUMEN

Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O2 in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO2-PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO2 NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H2O2 and produce O2. Based on the catalysis of MnO2 NPs, a large amount of oxygen was produced by MnO2-PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O2 relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO2 NPs were decomposed into Mn2+ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO2-PTX/Ce6@lips enhanced the efficacy of chemotherapy and photodynamic therapy (PDT) in bearing-tumor mice, even achieving complete cure. These results indicated the great potential of MnO2-PTX/Ce6@lips for the modulation of the TME and the enhancement of chemotherapy and PDT along with MRI tracing in the treatment of tumors.

2.
Talanta ; 230: 122348, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-33934797

RESUMEN

Carbohydrates are an indispensable part of early life evolution. The determination of their structures is a key step to analyze their critical roles in biological systems. A variation of composition, glycosidic linkage, and (or) configuration between carbohydrate isomers induces structure diversity and brings challenges for their structural determination. Ion mobility spectrometry (IMS), an emerging gas-phase ion separation technology, has been considered as a promising tool for performing carbohydrate structure elucidation. In this work, eight disaccharides were analyzed by trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) in the negative ion mode as the complexed form of [M + X]-, where M = disaccharide, and X = Cl, Br, and I. As compared to the positive ion analysis of the selected disaccharide in a sodiated form, a reversal charge state provided the ability to eliminate or even reverse the collision cross section (CCS) difference between disaccharide isomers. By the combination of TIMS analysis and the calculation of density functional theory, the only observed two conformers of ions [lactulose + I]- may result from different adduction sites for an iodide anion. Based on the comparison of different halogen adducts, the [M + I]- ion form exhibited more powerful ability for isomeric disaccharide differentiation with an average resolution (RP-P) of 1.17, which results in a 34.5% improvement as compared to the corresponding chloride adducts. This result indicates that the use of negative charge states, especially the complexation of an iodide anion, could be a supplemental strategy to commonly used positive ion analysis for carbohydrate separation.

3.
Hum Brain Mapp ; 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33939234

RESUMEN

Anxiety and depression are the most common withdrawal symptoms of methamphetamine (METH) abuse, which further exacerbate relapse of METH abuse. To date, no effective pharmacotherapy exists for METH abuse and its withdrawal symptoms. Therefore, understanding the neuromechanism underlying METH abuse and its withdrawal symptoms is essential for developing clinical strategies and improving patient care. The aims of this study were to investigate brain network abnormalities in METH abusers (MAs) and their associations with affective symptoms. Forty-eight male abstinent MAs and 48 age-gender matched healthy controls were recruited and underwent resting state functional magnetic resonance imaging (fMRI). The severity of patient anxiety and depressive symptoms were measured by Hamilton anxiety and depression rating scales, which decreased across the duration of abstinence. Independent component analysis was used to investigate the brain network functional connectivity (FC) properties. Compared with healthy controls, MAs demonstrated hypo-intra-network FC in the cerebellar network and hyper-intra-network FC in the posterior salience network. A whole-brain regression analysis revealed that FC strength of clusters located in the right rostral anterior cingulate cortex (rACC) within the ventromedial network (VMN) was associated with affective symptoms in the patients. Importantly, the intra-network FC strength of the rACC in VMN mediated the association between abstinence duration and the severity level of affective symptoms. Our results demonstrate alterations in brain functional networks underlying METH abuse, and that the FC of rACC within VMN serve as a neural substrate in the association between abstinence length and affective symptom severity in the MAs.

4.
J Ethnopharmacol ; : 114164, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33932516

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine (TCM) theory (Yi Xue Zheng Zhuan), the main factors associated with the pathogenesis of depression are deficiencies relating to five zang organs, Qi, and blood. Polygonatum sibiricum F. Delaroche (PS), which may avert these pathological changes, has been used in a variety of formulas to treat depression. However, the effects and mechanism of action of PS, alone, and especially those of its main active component PS polysaccharide (PSP), on depression remain unexplored. AIM OF THE STUDY: To determine the effects of PSP on depression-like behaviors and to elucidate its mechanism of action. METHODS: PSP was isolated from dried PS rhizomes and qualified using transmission electron microscopy and Fourier transform infrared spectroscopy. Lipopolysaccharide (LPS) and chronic unpredictable mild stress (CUMS)-induced depression models were used to evaluate the antidepressive effects of PSP. Veinal blood and brain tissue were collected to determine the levels of hippocampal 5-HT, serum cortisol (CORT), brain and serum cytokines, and hippocampal oxidation-related indicators. The protein expression levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), glial fibrillary acidic protein (GFAP), phosphorylated protein kinase B (p-Akt), phosphorylation of the mammalian target of rapamycin (mTOR), caspase-3, GluA1 and GluA2, and GluN2A and GluN2B were determined using western blotting and immunofluorescence. Nissl staining was performed to detect histopathological changes in brain tissues. RESULTS: Injection of LPS (i.p.) induced depression-like behaviors, reduced the level of hippocampal 5-HT, increased the serum CORT level and hippocampal oxidative stress (ROS), and prompted the activation of ERK1/2, NF-κB, and GFAP and an inflammatory response. Conversely, PSP administration reduced these changes and prevented depression-like behaviors. PSP administration also promoted hippocampal expression of p-Akt, p-mTOR, GluA1, and GluA2; reduced the expression of caspase-3, GluN2A, and GluN2B; and prohibited the loss of granular cells in the DG region. CONCLUSION: These results indicate that PSP prevents depression-like behaviors, and synaptic and neuronal damage probably by reducing ROS/HPA axis hyperfunction and the inflammatory response.

5.
BMC Pediatr ; 21(1): 212, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33931029

RESUMEN

BACKGROUND: Since the national clinical trials registry ( ClinicalTrials.gov ) launched in February 2000, more than 360,000 research studies in the United States and over 200 countries have registered. As the characteristics of pediatric clinical studies keep changing over time and the results-reporting mechanism is under evolving, to know about the relevant updates of data elements and the effect of policies on the quality of reporting results is significant. METHODS: In this research, 53,060 clinical studies related to children registered from January 2008 to December 2019 were downloaded from ClinicalTrials.gov on August 1st, 2020. Different types of studies and critical categorical variables were identified, based on which, Cochran-Armitage test was performed to explore temporal trend of study characteristics and common pediatric clinical conditions in four time subsets. Further, to examine heterogeneity among subgroups (funding sources, funding sites, pediatric clinical conditions,etc), chi-squared test was applied. RESULTS: A total of 36,136 clinical trials and 16,692 observational studies were identified during the study period. The pediatric clinical trials increased from 7,029 (January 2008-December 2010) to 11,738 (January 2017-December 2019). The number of missing data has declined, with the maximum extent decline from 3.7 to 0.0% (Z = - 15.90, p <  0.001). Drug trials decreased from 48.8 to 28.9% (Z = - 24.68, p <  0.001). Behavioral trials, on the other hand, increased from 12.6 to 20.4% (Z = 12.28, p <  0.001). Most pediatric clinical trials were small-scale (58.9% enrolling 1-100 participants), single-site (61.4%) and funded neither by industry nor by the NIH (59.2%). The proportion of reporting study results varied by study type (χ2 = 1,256.8, p <  0.001), lead sponsor (χ2 = 4,545.6, p <  0.001), enrollment (χ2 = 29.4, p <  0.001) and trial phase (χ2 = 218.8, p <  0.001). CONCLUSION: Pediatric clinical studies registered in ClinicalTrials.gov were dominated by small-scale interventional trials, containing significant heterogeneity in funding sources, funding sites, pediatric clinical conditions and study characteristics. Although the results database has evolved in the past decade, efforts to strengthen the practice of systematic reporting must be continued.

6.
J Dermatol Sci ; 2021 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-33933312

RESUMEN

BACKGROUND: REGγ acts as a proteasome activating factor mediating proteasome degradation of substrate proteins in an ATP and ubiquitination independent manner and also as an important regulator of cell cycle, proliferation and apoptosis. Hair cycle involves dynamic, continuous morphological changes of three stages (anagen, catagen and telogen). OBJECTIVE: The function of REGγ in hair cycling is still unclear. METHODS: Here, we used REGγ knockout 293 T cells, inducible 293WT and 293N151Y cell, REGγ knockout mice to identify the novel molecular mechanism of REGγ in regulating hair follicle stem cells. RESULTS: In the present study, we found that REGγ deletion markedly delayed the transition of hair follicles from telogen to anagen and hair regeneration in mice. We also observed significant decrease of hair follicle stem cell number, stem-like property and proliferation ability. Interestingly, the results from real-time PCR, FACS, Western Blot and immunofluorescent analysis showed that REGγ deletion could greatly downregulate Lgr5 expression in the hair follicles. Meanwhile, REGγ was demonstrated to directly interact with LHX2 and promotes its degradation. Importantly, REGγ specific deletion in Lgr5+ stem cells induced the marked delay of hair regeneration after depilation. CONCLUSION: These data together indicate that REGγ was a new mediator of Lgr5 expression in hair follicle at least partly by promoting the degradation of its suppressive transcription factor LHX2. It seemed that REGγ regulated hair anagen entry and hair regrowth by activating Lgr5 positive hair follicle stem cells.

7.
Annu Rev Phytopathol ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33945695

RESUMEN

Hybrid necrosis in plants refers to a genetic autoimmunity syndrome in the progeny of interspecific or intraspecific crosses. Although the phenomenon was first documented in 1920, it has been unequivocally linked to autoimmunity only recently, with the discovery of the underlying genetic and biochemical mechanisms. The most common causal loci encode immune receptors, which are known to differ within and between species. One mechanism can be explained by the guard hypothesis, in which a guard protein, often a nucleotide-binding site-leucine-rich repeat protein, is activated by interaction with a plant protein that mimics standard guardees modified by pathogen effector proteins. Another surprising mechanism is the formation of inappropriately active immune receptor complexes. In this review, we summarize our current knowledge of hybrid necrosis and discuss how its study is not only informing the understanding of immune gene evolution but also revealing new aspects of plant immune signaling. Expected final online publication date for the Annual Review of Phytopathology, Volume 59 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

8.
Front Immunol ; 12: 620437, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936036

RESUMEN

T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We report here that Tsc1, a regulator for mTOR signaling, plays differential roles in Tfh cell/GC B cell responses in the steady state and in immune responses to antigen immunization. In the steady state, Tsc1 in T cells intrinsically suppresses spontaneous GC-Tfh cell differentiation and subsequent GC-B cell formation and autoantibody production. In immune responses to antigen immunization, Tsc1 in T cells is required for efficient GC-Tfh cell expansion, GC-B cell induction, and antigen-specific antibody responses, at least in part via promoting GC-Tfh cell mitochondrial integrity and survival. Interestingly, in mixed bone marrow chimeric mice reconstituted with both wild-type and T cell-specific Tsc1-deficient bone marrow cells, Tsc1 deficiency leads to enhanced GC-Tfh cell differentiation of wild-type CD4 T cells and increased accumulation of wild-type T regulatory cells and T follicular regulatory cells. Such bystander GC-Tfh cell differentiation suggests a potential mechanism that could trigger self-reactive GC-Tfh cell/GC responses and autoimmunity via neighboring GC-Tfh cells.

9.
Front Immunol ; 12: 645100, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936063

RESUMEN

Chronic kidney disease (CKD), which is associated with high morbidity, remains a worldwide health concern, while effective therapies remain limited. Hydroxychloroquine (HCQ), which mainly targets toll-like receptor-7 (TLR-7) and TLR-9, is associated with a lower risk of incident CKD. Taking into account that TLR-9 is involved in the development of renal fibrosis and serves as a potential therapy target for CKD, we investigated whether HCQ could attenuate CKD via TLR-9 signal pathway. The effects of HCQ on renal tubulointerstitial fibrosis were further explored using a mouse model of renal tubulointerstitial fibrosis after ischemia/reperfusion injury. Bone marrow-derived macrophages were isolated to explore the effects of HCQ in vitro. Judicious use of HCQ efficiently inhibited the activation of macrophages and MAPK signaling pathways, thereby attenuating renal fibrosis in vivo. In an in vitro model, results showed that HCQ promoted apoptosis of macrophages and inhibited activation of macrophages, especially M2 macrophages, in a dose-dependent manner. Because TLR-7 is not involved in the development of CKD post-injury, a TLR-9 knockout mouse was used to explore the mechanisms of HCQ. The effects of HCQ on renal fibrosis and macrophages decreased after depletion of TLR-9 in vivo and in vitro. Taken together, this study indicated that proper use of HCQ could be a new strategy for anti-fibrotic therapy and that TLR-9 could be a potential therapeutic target for CKD following acute kidney injury.

10.
Sci Total Environ ; 773: 145668, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33940754

RESUMEN

Combustion-derived black carbon (BC) is increasingly recognized as a significant pollutant that can have adverse effects on the atmospheric environment, human health, and regional climate. Fossil fuel combustion is the main source of BC, yet understanding of the relative contributions to BC from coal and liquid fuel combustion remains incomplete. Moreover, few studies have assessed the relative contributions based on long-term continuous daily field observations. This study adopted a Bayesian model of a three-dimensional array of a stable carbon isotope and the ratios of non-sea-salt K+ to BC and ΔBC/ΔCO of one year's daily observations (from September 1, 2017 to August 31, 2018) to constrain source apportionment of BC in Beijing (China). Results showed that both the BC and the carbon isotope concentrations exhibited strong seasonal variability, and that the annual BC concentration has decreased significantly in recent years. The Bayesian model results also revealed that the relative contributions from the combustion of coal, liquid fuel, and biomass were 42% ± 18%, 42% ± 18%, and 16% ± 11%, respectively, with a larger contribution from coal (liquid fuel) combustion in winter and spring (summer and autumn). The seasonal variation of source appointment was attributed to local and regional fuel combustion coupled with meteorological conditions. With increasing PM2.5 level, the BC concentration derived from biomass burning increased fastest, followed by that derived from coal combustion. But concentration of secondary inorganic ions increased faster than BC as PM2.5 increased.

11.
Sci Total Environ ; 773: 145706, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33940765

RESUMEN

The hydrophilic biomaterial was constructed based on the soluble extracellular polysaccharides (s-EPS) secreted by Bacillus megaterium and zeolitic imidazolate framework-8 (ZIF-8), namely ZIF-8@s-EPS, wrapped in s-EPS shell with ZIF-8 as the core. ZIF-8@s-EPS was used as a novel multifunctional biomaterial in water treatment for the first time. Unexpectedly, results showed ZIF-8@s-EPS with strong synergistic effect presented multifunctional performances including descaling, antifouling and antibacterial. Scale inhibition efficiency reached 98.63% for CaCO3 and as high as 99.40% for CaSO4 at concentration 20.00 mg/L. The synergy of s-EPS and ZIF-8 demonstrated effective antibacterial activity against Pseudomonas aeruginosa and inhibitory effect on biofilms, and result presented that ZIF-8@s-EPS could inhibit the growth of nearly 89.4% P. aeruginosa. Therefore, the obtained insights will shed light on the development of s-EPS modified biomaterials in water treatment.

12.
Gastrointest Endosc ; 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33798538

RESUMEN

BACKGROUND AND AIMS: Now that the debate about the safety and effectiveness of laparoscopic versus open surgery is over, attention has turned to innovations that can verify whether minimizing the impact of laparoscopy on the abdominal wall can further reduce pain, improve patient comfort, lead to superior cosmesis, and reduce morbidity. The aim of this study was to further explore the application value of totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction (NOSE) and to evaluate the short-term efficacy of transcolonic NOSE surgery for resecting specimens of ascending colon cancer. METHODS: From January 2016 to May 2017, a retrospective study was conducted in Guangxi. Propensity score matching was used to minimize the bias from nonrandomized treatment assignment. Patients were followed up through May 2020. RESULTS: Forty-nine patients underwent totally laparoscopic right hemicolectomy with transcolonic NOSE, and 116 patients underwent laparoscopic right hemicolectomy with mini-laparotomy (ML) procedures at our institution. After propensity score matching, each group included 45 patients, and all the covariate imbalances were alleviated. The transcolonic NOSE group and the ML group did not differ significantly in terms of baseline clinical characteristics. The transcolonic NOSE group was associated with a shorter time to first flatus (NOSE 1.8 ± 0.5 vs ML 3.2 ± 0.8, p=0.032), a shorter length of hospital stay (NOSE 11.3 ± 2.5 days vs ML 13.0 ± 3.1 days, p=0.034), a shorter time to first liquid intake (NOSE 2.6 ± 0.8 vs ML 3.8 ± 0.9, p=0.068), less pain (NOSE 1.8 ± 0.8 vs ML 4.2 ± 0.7, p=0.013), less analgesia requirement (NOSE 6 (13.3%) vs ML 21 (46.7%), p=0.001), lower CRP levels on POD1 (NOSE 3.6 ± 1.7 vs ML 8.2 ± 2.2, p=0.001) and POD3 (NOSE 2.4 ± 1.4 vs ML 4.6 ± 1.7, p=1.7 vs ML 8.2 ± 2.2, p=0.001) than the POSE group. The median follow-up was 28.4 months (interquartile range, 18.0-36.0 months). The 3-year overall survival rates were similar between the transcolonic NOSE group and the ML group. CONCLUSION: In total, laparoscopic right hemicolectomy with transcolonic specimen extraction appears to be safe for selected patients with ascending colon cancer as a minimally invasive surgery.

13.
Nanomaterials (Basel) ; 11(3)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802171

RESUMEN

AlN epilayers were grown on a 2-inch [0001] conventional flat sapphire substrate (CSS) and a nano-patterned sapphire substrate (NPSS) by metalorganic chemical vapor deposition. In this work, the effect of the substrate template and temperature on stress and optical properties of AlN films has been studied by using Raman spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-visible spectrophotometer and spectroscopic ellipsometry (SE). The AlN on NPSS exhibits lower compressive stress and strain values. The biaxial stress decreases from 1.59 to 0.60 GPa for AlN on CSS and from 0.90 to 0.38 GPa for AlN on NPSS sample in the temperature range 80-300 K, which shows compressive stress. According to the TEM data, the stress varies from tensile on the interface to compressive on the surface. It can be deduced that the nano-holes provide more channels for stress relaxation. Nano-patterning leads to a lower degree of disorder and stress/strain relaxes by the formation of the nano-hole structure between the interface of AlN epilayers and the substrate. The low crystal disorder and defects in the AlN on NPSS is confirmed by the small Urbach energy values. The variation in bandgap (Eg) and optical constants (n, k) with temperature are discussed in detail. Nano-patterning leads to poor light transmission due to light scattering, coupling, and trapping in nano-holes.

14.
Comput Intell Neurosci ; 2021: 6680833, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790959

RESUMEN

As a new type of artificial neural network model, HTM has become the focus of current research and application. The sparse distributed representation is the basis of the HTM model, but the existing spatial pool learning algorithms have high training time overhead and may cause the spatial pool to become unstable. To overcome these disadvantages, we propose a fast spatial pool learning algorithm of HTM based on minicolumn's nomination, where the minicolumns are selected according to the load-carrying capacity and the synapses are adjusted using compressed encoding. We have implemented the prototype of the algorithm and carried out experiments on three datasets. It is verified that the training time overhead of the proposed algorithm is almost unaffected by the encoding length, and the spatial pool becomes stable after fewer iterations of training. Moreover, the training of the new input does not affect the already trained results.

15.
Genome Med ; 13(1): 57, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33845891

RESUMEN

BACKGROUND: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. METHODS: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. RESULTS: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member ß-dystroglycan. CONCLUSIONS: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

16.
J Exp Med ; 218(6)2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-33830176

RESUMEN

Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite-infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.

17.
Chemistry ; 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33871112

RESUMEN

Single Mn atom on nitrogen-doped graphene (MnN4-G) has exhibited good structural stability and high activity for adsorption and dissociation of O2 molecule, herein becoming a promising SAC candidate for oxygen reduction reaction (ORR). However, the catalytic activity of MnN4-G for the ORR and the optimal reaction pathway remain obscure. In this work, density-functional theory calculations were employed to comprehensively investigate all possible pathways and intermediate reactions of the ORR on MnN4-G. The feasible active sites and the most stable adsorption configurations of intermediates and transition states during the ORR were identified. Screened from all the possibilities, three optimal four-electron O2  hydrogenation pathways with the ultralow energy barrier of 0.13 eV were discovered, which are energetically more favorable than O2  direct dissociation pathways. The analysis of free energy diagram further verified the thermodynamical feasibility of the three pathways. Therefore, MnN4-G possesses superior ORR activity. This study provides a fundamental understanding about design of highly efficient SACs for the ORR.

18.
Med Sci Monit ; 27: e929074, 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33837172

RESUMEN

BACKGROUND In pregnant women with advanced maternal age (AMA) and fetuses with ultrasonographic (USG) soft markers it is always challenging to decide whether to implement chromosomal microarray analysis (CMA) or not. It is unclear whether CMA should be used in the fetuses with isolated USG soft markers, and there is still a lack of extensive sample research. MATERIAL AND METHODS We enrolled 1521 cases in our research and divided them into 3 groups as follows: pregnant women with isolated AMA (group 1, n=633), pregnant women whose fetuses had isolated USG soft markers (group 2, n=750), and pregnant women with AMA whose fetuses had isolated USG soft markers (group 3, n=138). All pregnant women underwent prenatal ultrasound and amniocentesis, and fetal cells in the amniotic fluid were used for genetic analysis of CMA. All participants signed a written informed consent prior to CMA. RESULTS Abnormal findings were detected by CMA in 330 (21.70%) fetuses, including 37 (2.43%) clinically significant copy number variations (CNVs), 52 (3.42%) benign or likely benign CNVs, and 240 (15.78%) variants of unknown significance. The frequency of clinically significant CNVs in group 1 and group 2 were significantly lower than that in group 3 (2.37% and 2.0% vs 5.07%, P<0.01). More than a half (59.46%, 22/37) of the pregnant women decided to continue their pregnancy despite having a fetus diagnosed with clinically significant CNV. CONCLUSIONS CMA can increase the diagnostic yield of fetal chromosomal abnormality for pregnant women with isolated AMA or/and their fetuses had isolated USG soft markers.

19.
J Colloid Interface Sci ; 596: 431-441, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33848747

RESUMEN

The separation and transfer of photogenerated charge carriers are the crucial process in photocatalysis, and the realization of multiple charge separation and transfer routes in a single catalyst structure is very promising to achieve high-efficiency catalytic performance. We herein report a simple strategy to synthesize CdS/CoP hybrid nanorods (HNRs) via a one-step phosphorization treatment of the CdS/Co(OH)2 precursors, in which the gradient-P-doped-CdS NRs and CoP cocatalyst can be synchronously obtained (denoted as gP-CdS/CoP HNRs). The gradient P doping gradually reduced the band gap of CdS as well as elevated Fermi level with doping concentration up, resulting in the formation of a built-in electric field in the CdS NRs. The built-in electric field points from the surface towards the interior of the CdS NRs, which facilities the separation of photogenerated charge carriers in CdS and the transfer of electrons to the CdS/CoP interface. The transferred electrons are then captured by the CoP cocatalysts, leading to further separation of the charge carriers. Owing to the coupling of gradient-P-doped CdS nanorods with the CoP cocatalysts, the optimized gP-CdS/CoP HNRs exhibit remarkably enhanced photocatalytic water reduction performance, with a H2 production rate of 22.95 mmol g-1 h-1 which is 28.7 and 3.2 times higher than that of pristine CdS and gP-CdS, respectively. This work demonstrates the synergetic effects of charge carrier separation in the coupled nanostructure of the gradient-P-doped CdS NRs with the CoP cocatalyst, which provides a new platform for developing heterostructures with multiple charge separation and transfer routes for photocatalysis.

20.
Cell Biol Toxicol ; 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33880675

RESUMEN

OBJECTIVE: Due to the tissue specificity of the liver, long-term exposure to a high concentration of 27-hydroxycholesterol (27HC) is a special characteristic of the tumour microenvironment in hepatocellular carcinoma (HCC). However, what occurs after HCC cells are long-term exposure to 27HC and the molecular mechanisms involved remain largely unexamined. METHODS: A long-term 27HC-treated HepG2 cell line and the xenografts in nude mice were used as experimental models. Molecular mechanisms were investigated using bioinformatics analysis and molecular biological experiments. RESULTS: Here, we found that by inducing an increase in oxidative stress signalling, 27HC activated glucose-regulated protein 75 (GRP75). On the one hand, GRP75 resulted in a change in the redox balance by regulating ROS generation and antioxidant system activity via affecting MMP, NRF2, HO-1, and NQO1 levels. On the other hand, GRP75 modified the metabolic reprogramming process by regulating key factors (HIF-1α, p-Akt, and c-myc) and glucose uptake, facilitating HCC cell growth in the inhospitable microenvironment. These two factors caused HCC cells to resist 27HC-induced cytotoxicity and attain multidrug resistance (MDR). CONCLUSIONS: Our present study not only identified 27HC, a characteristic component of the neoplastic microenvironment of HCC that causes MDR via GRP75 to regulate the redox balance and metabolic reprogramming, but also revealed that targeted intervention by the "switch"-like molecule GRP75 could reverse the effect of 27HC from cancer promotion to cytotoxicity in HCC, suggesting a new strategy for specific intervention of HCC.

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