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1.
Oncogene ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005973

RESUMO

Mitochondrial fusion and fission dynamics fine-tune cellular calcium homeostasis, ATP production capacity and ROS production and play important roles in cell proliferation and migration. Dysregulated mitochondrial dynamics is closely related to tumor development, but the mechanism of mitochondrial dynamics dysregulation and its role in the development of lung cancer remains unclear. Here, we demonstrate that the DNA sensor protein absent in melanoma 2 (AIM2) is highly expressed in non-small cell lung cancer (NSCLC) cells and that high AIM2 expression is associated with poor prognosis in patients with NSCLC. High expression of AIM2 contributes to tumor cell growth and proliferation independent of inflammasome activation in vitro and in vivo. Further studies have shown that AIM2 colocalizes with mitochondria in NSCLC cells and that AIM2 knockdown leads to enhanced mitochondrial fusion and decreased cell proliferation. Mechanistic studies have shown that AIM2 downregulation promotes MFN2 upregulation, thereby enhancing mitochondrial fusion. Moreover, we found that mitochondrial fusion driven by AIM2 knockdown leads to a decrease of cellular reactive oxygen species (ROS) production, which further causes inactivation of the MAPK/ERK signaling pathway. Together, we discovered a novel function of AIM2 in promoting NSCLC development by regulating mitochondrial dynamics and revealed its underlying mechanism. Our work provides new intervention targets for the treatment of NSCLC.

2.
J Mol Model ; 26(3): 47, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020344

RESUMO

The DFT theory is used to investigate the vibration forms of ε-CL-20 by discussing the phonon DOS and infrared and Raman spectra. By observing them, the detailed vibration forms can be obtained, and the vibrations are different in the different regions. Our calculated vibrational results are consistent with previous data. In order to deeply comprehend CL-20, we also investigate the thermodynamic properties, finding that entropy, enthalpy, Debye temperature, and heat capacity are increased with the rising temperature and the vibrational free energy decreases with the increasing temperature. The εxx, εyy, and εzz are similar, which reflects the small anisotropy among [100], [010], and [001]. Moreover, it can be noticed that the major contribution for static dielectric constants originates from the electronic contribution.

3.
Acupunct Med ; : 964528419900911, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028783

RESUMO

BACKGROUND: Evidence for treating postprandial distress syndrome with acupuncture is limited. AIM: We aimed to evaluate the feasibility of verum acupuncture versus sham acupuncture in patients with postprandial distress syndrome. METHODS: A total of 42 eligible patients were randomly allocated to either verum acupuncture or sham acupuncture groups in a 1:1 ratio. Each patient received 12 sessions over 4 weeks. The primary outcome was the response rate based on the overall treatment effect (OTE) 4 weeks after randomization. Secondary outcomes included dyspepsia symptom severity and adverse events. RESULTS: In each group, 19 patients (91.5%) completed the study. Thirteen patients receiving verum acupuncture and seven patients receiving sham acupuncture were classified as responders according to OTE (61.9% vs 33.3%; rate difference 28.6%; p = 0.06). Dyspepsia symptom severity at the end of treatment also differed significantly between verum acupuncture and sham acupuncture groups (5.9 units vs 3.7 units; between-group difference 2.2 (95% CI, 0.2-4.2); p = 0.04). No serious adverse events occurred. CONCLUSION: Four weeks of acupuncture may represent a potential treatment for postprandial distress syndrome. The treatment protocol and outcome measures used in this trial were feasible. Since this was a pilot study, the efficacy of acupuncture still needs to be determined by a larger, adequately powered trial.

4.
J Agric Food Chem ; 68(5): 1354-1363, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31933364

RESUMO

Carotenoids are essential phytonutrients synthesized by all photosynthetic organisms. Acyclic lycopene is the first branching point for carotenoid biosynthesis. Lycopene ß- and ε-cyclases (LCYB and LCYE, respectively) catalyze the cyclization of its open ends and direct the metabolic flux into different downstream branches. Carotenoids of the ß,ß-branch (e.g., ß-carotene) are found in all photosynthetic organisms, but those of the ß,ε-branch (e.g., lutein) are generally absent in cyanobacteria, heterokonts, and some red algae. Although both LCYBs and LCYEs have been characterized from land plants, there are only a few reports on LCYs from cyanobacteria and algae. Here, we cloned four LCY genes from Porphyra umbilicalis and Pyropia yezoensis (susabi-nori) of Bangiales, the most primitive red algal order that synthesizes lutein. Our functional characterization in both Escherichia coli and Arabidopsis thaliana demonstrated that each species has a pair of LCYB and LCYE. Similar to LCYs from higher plants, red algal LCYBs cyclize both ends of lycopene, and their LCYEs only cyclize a single end. The characterization of LCYEs from red algae resolved the first bifurcation step toward ß-carotene and lutein biosynthesis. Our phylogenetic analysis suggests that LCYEs of the green lineage and the red algae originated separately during evolution.

5.
Biomed Pharmacother ; 122: 109777, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918261

RESUMO

Sepsis is a critical illness that contributes a high mortality, while Xijiao Dihuang decoction (XJDHT) has been used in treatment against sepsis for many years by clinical doctors. Clinical studies confirmed a good efficacy of XJDHT against sepsis. The aim of this study is to observe the efficacy of XJDHT in sepsis model rats and macrophages activated by LPS, and to verify the underlying mechanisms. The key components of XJDHT and its targets against sepsis were analyzed and selected by network pharmacology. The potential mechanisms that XJDHT regulates the progress of sepsis were verified in sepsis rats and NR8383 cell lines. XJDHT at a dose of 25 mg/kg was administrated to rats which endured cecal ligation and perforation (CLP). After MTT assay, XJDHT at a dose of 4 mg/mL was selected to treat NR8383 cell lines activated by LPS. In vivo experiment, the survival of the rats was assessed. The content of cytokine in serum were assessed by Enzyme-linked immunosorbent assays (ELISA). Contents of cytokine and key molecules in relative signaling pathway were assessed by immunohistochemical method. The pathway protein expressions were detected by Western blotting. In vitro experiment, immunofluorescence was used to assess the content of cytokine and signaling pathway. A total of 42 targets of XJDHT against sepsis were identified by network pharmacology. After eliminating overlapping compounds and proteins, there were 8 compounds in XJDHT that associating with the 42 sepsis-related targets. NF-κB and HIF-1α signaling pathway were recognized to play important role for XJDHT against sepsis. XJDHT improved survival rate in the XJDHT group compared with the model group. The contents of IL-6 increased in the model group compared with the control group with ELISA and immunohistochemistry, while XJDHT reduced the content of IL-6. The expressions of p65 and HIF-1α reduced significantly in the XJDHT group compared with the model group. In vitro study, the content of IL-6 elevated significantly after LPS stimulation, while XJDHT reduced this increase. Furthermore, expressions of protein of p65 and HIF-1α decreased significantly compared with the LPS group. To conclude, our study demonstrated that XJDHT at a dose of 25 g/kg is capable of improving the survival of sepsis via regulating the NF-κB and HIF-1α signaling pathway.

6.
Biomaterials ; 230: 119616, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31837823

RESUMO

As hepatic stellate cells (HSCs) are essential for hepatic fibrogenesis, HSCs targeted nano-drug delivery system is a research hotspot in liver fibrosis therapy. However, the excessive deposition of fibrosis collagen (mainly collagen I) in the space of Disse associated with hepatic fibrogenesis would significantly hinder nano-formulation delivery to HSCs. Here, we have prepared a collagenase I and retinol co-decorated polymeric micelle that possess nanodrill-like and HSCs-target function based on poly-(lactic-co-glycolic)-b-poly (ethylene glycol)-maleimide (PLGA-PEG-Mal) (named CRM) for liver fibrosis therapy. Upon encountering collagen I barrier, CRM exerted a nanodrill-like function, efficiently degrading pericellular collagen I and showing greater uptake by human HSCs than other micelle formulations. Besides, CRM could realize excellent accumulation in the fibrotic liver and accurate targeting to activated HSCs in mouse hepatic fibrosis model. Moreover, CRM loaded with nilotinib (CRM/NIL), a second-generation tyrosine kinase inhibitor used in the treatment of liver fibrosis, showed optimal antifibrotic activity. This work suggests that CRM with dual function is an efficient carrier for liver fibrosis drug delivery and collagenase I decorating could be a new strategy for building more efficient HSCs targeted nano-drug delivery system.

7.
J Clin Lab Anal ; : e23142, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793735

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive inheritance muscle dystrophy disease, associated with pathogenic variants in the DMD gene. MLPA, DHPLC and DMD sequence studies fail to found the causative alteration in two cases. This study intends to evaluate the disease-causing mutations and explains the correlation genotype-phenotype. METHODS: The mRNA analysis and Long-range PCR with sequencing were used for molecular diagnosis. RESULTS: In case one, an insertion of 78 nucleotides between exons 40 and 41 (r.5739_5740insMN602429:r415_492) was identified in case one. The insertion sequences were highly homologous to the intron 40 (NG_012232.1:g.1001760_g.1001837). Long-range PCR with sequencing analysis showed that a novel deep intronic DMD mutation (NG_012232.1:g.1001838A>G) was identified, generating a premature stop codon and terminating protein translation. The likely pathogenic mutation was detected in fetal sample. In case two, an insertion of 74 nucleotides which located inside the consensus sequence AG/GT was detected between exons 2 and 3 (r.93_94insMN584887:r61_134), which resulted in a premature stop codon. The insertion sequences were traceable in the intron 2 of DMD gene (NG_012232.1:g.415926_g.415999). We did not perform prenatal DMD gene diagnosis for case two due to lack of sufficient genetic information. CONCLUSION: These findings clarify importance of proceeding to the mRNA analysis when no causative mutations were found neither by MLPA/DHPLC nor gene sequencing so as to reach the molecular confirmation of DMD and carry out an accurate genetic assessment/ carrier status testing.

8.
Food Sci Biotechnol ; 28(6): 1617-1625, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31807334

RESUMO

Tea catechins have attracted strong interests in pharmacological field for their extensive biological activities; however, their bioavailability in vivo is relatively low. Recent studies have shown tea catechins can modulate the composition of intestinal microbiota and help to improve hosts' health. Meanwhile, the gut flora plays a crucial role in regulating the production of the metabolites of tea catechins and their biological activity. Although the activities of tea catechins to promote intestinal micro-ecology have been extensively studied, little is known about the two-way phenol-microbial interactions. This review focuses on the modulatory effect of tea catechins on intestinal microbiota as well as the microbial degradation of tea catechins and the metabolites formed. Finally, the potential effects of tea catechins on chronic intestinal inflammation are emphasized.

9.
J Neuroinflammation ; 16(1): 278, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883532

RESUMO

BACKGROUND: Uveitis is a potentially sight-threatening form of ocular inflammation that affects the uvea in the wall of the eye. Currently available treatments for uveitis have exhibited profound adverse side effects. However, KS23 is a novel 23-amino-acid anti-inflammatory peptide derived from adiponectin that may have the capability to function as a safe alternative to these existing treatment options. We, therefore, evaluated the preventive effect of KS23 in experimental autoimmune uveitis (EAU). METHODS: EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 161-180 (IRBP161-180). KS23 was then administered every 2 days via intraperitoneal injection to induce protection against EAU. Clinical and histopathological scores were employed to evaluate the disease progression. Inflammatory cytokines were also quantified using ELISA, and the expression levels of specific chemokines and chemokine receptors were assessed via qRT-PCR. In addition, the proportions of Th1 and Th17 cells were detected via flow cytometry, and the expression levels of specific proteins were quantified from the retina of mice using western blot analysis, to elucidate the specific mechanism of action employed by KS23 to suppress the inflammation associated with EAU. RESULTS: KS23 was found to significantly improve EAU-associated histopathological scores, while decreasing the expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6, and IL-17A), chemokines (LARC, RANTES, MIG, IP-10), and chemokine receptors (CCR6 and CXCR3). The proportions of Th1 and Th17 cells were also suppressed following intraperitoneal injection with KS23. The anti-inflammatory mechanism employed by KS23 was determined to be associated with the activation of AMPK and subsequent inhibition of NF-κB. CONCLUSIONS: KS23 decreased the proportions of Th1 and Th17 cells to effectively ameliorate the progression of EAU. It may, therefore, serve as a promising potential therapeutic agent for uveitis.

10.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4448-4453, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872631

RESUMO

Musk,with unique and intense perfume,was a kind of deep brown precious medicinal material in traditional Chinese medicine. However,the immature musk in musk pot was white and stench. Given the fact that bacterial diversity generated odorous metabolites in animal hosts,in this study,musk samples at three different mature stages,including MJ( the end of June),MA( the end of August) and MO( the end of October) were harvested from three male forest musk deer,and then next-generation sequencing was used to intensively survey the bacterial communities in musk harvested at different mature stages. RESULTS: indicated that the average OTUs per sample at the end of June,August and October were 47 116. 00 ± 1 567. 24( SE),52 009. 00 ± 8 958. 75( SE) and50 004. 67±4 135. 57( SE),respectively. Feature of the musk 16 S rRNA gene showed a total of 418 genera belonging to 52 phyla were observed in all samples. The main microbiota was bacteria,which accounted for 98. 82%,99. 95% and 99. 58% in MJ,MA and MO,respectively. At phylum level,Firmicutes was the most abundant bacterial of MA( 32. 75%) and MO( 39. 19%). While,the major bacterial in MJ was Proteobacteria( 49. 14%). PICRUSt analysis revealed the functions of bacterial in MJ were mainly involved in secretion,while bacterial functions of MA and MO were mainly involved in amino acid or other substance metabolism,which was in accord with the musk secretion physiological process of forest musk deer. This is the first study involved in the bacterial diversity in musk of forest musk deer across the maturation process,while may provide a new insight into the musk generation mechanism.


Assuntos
Cervos/microbiologia , Ácidos Graxos Monoinsaturados , Animais , Florestas , Sequenciamento de Nucleotídeos em Larga Escala , Masculino
11.
Artigo em Inglês | MEDLINE | ID: mdl-31781277

RESUMO

Objectives: To evaluate the efficacy and safety of compound Kushen injection (CKI) combined with chemo treatment (chemo) for non-small-cell lung cancer (NSCLC). Methods: We systematically searched the literature published in seven databases, including Embase, PubMed, central, MEDLINE, CNKI, Wanfang, and VIP, from their inception to April 2019 for all randomized controlled trials (RCTs) comparing CKI plus chemo with chemo alone in patients with NSCLC. Our main end point was clinical efficiency and the secondary outcomes were Karnofsky performance score (KPS), immune function, and adverse events. The Cochrane risk of bias tool was applied for quality assessment. Results: 10 studies involving 1019 participants were included. The clinical response rate (relative risk (RR) = 1.21, 95% confidence interval (CI): 1.06 to 1.37; P=0.003), KPS (RR = 2.18, 95% CI: 1.49 to 3.17; P < 0.0001), immune function (mean differences (MD) = 0.82, 95% CI: 0.12 to 1.52; P=0.02) and adverse effects (RR = 0.67, 95% CI: 0.60 to 0.74; P < 0.00001) in the CKI plus chemo group showed significant differences when compared with chemo alone. Conclusions: CKI combined with chemo can improve clinical efficiency, KPS, and immune function and reduce adverse reactions in patients with NSCLC when compared with chemo alone. However, more rigorously designed RCTs are needed to validate this benefit, as some of the included RCTs are of low methodological quality.

12.
J Mol Model ; 25(12): 356, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768652

RESUMO

Energy-containing materials have aroused people's widespread concern because of its admirable performance in recent years. In this paper, the electronic structure, vibrational, and thermodynamic properties of 1,3-diamino-2,4,6-trinitrobenzene (DATB) are systematically investigated by adopting the first-principle calculations. We find that lattice parameters are in excellent agreement with the previous calculated and experimental values. The vibration spectra are described in detail and the peaks in the Raman and infrared spectra are assigned to different vibration modes. Phonon dispersion curves indicate that the DATB is dynamically stable. According to the vibrational properties, the thermodynamic functions such as enthalpy (H), constant volume heat capacity (CV), Helmholtz free energy (F), Debye temperature (Θ), and entropy (S) are analyzed. No corresponding experimental values have been found so far, and therefore, knowledge of these properties will provide a reference and guidance for the follow-up research.

13.
Invest Ophthalmol Vis Sci ; 60(14): 4792-4802, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743936

RESUMO

Purpose: The purpose of this study was to describe the normative values, distribution patterns, and correlated factors of macular ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and outer retinal layer (ORL) thicknesses in Chinese children. Methods: A sample of 3000 healthy children with different refractive status aged 6 to 19 years was consecutively examined. Demographics were recorded, and a comprehensive ophthalmic examination including refractive error and axial length (AL) was taken from all participants. The GCIPL, GCC, and ORL thicknesses were measured using swept source-optical coherence tomography (OCT), and multiple linear regression was used to determine which factors were associated with the thickness of each layer. Results: The average thickness was 77.00 ± 4.78 µm (95% confidence interval [CI]: 69.56-84.56 µm) in the GCIPL, 107.68 ± 5.95 µm (95% CI: 98.45-117.21 µm) in the GCC, and 178.57 ± 9.02 µm (95% CI: 164.33-192.56 µm) in the ORL. Multiple regression analysis indicated that GCIPL thickness was associated with sex (ß = 0.168, P < 0.001), age (ß = 0.126, P < 0.001), axial length (ß = -0.181, P < 0.001), and refractive error (ß = 0.233, P < 0.001). Age (ß = 0.154, P < 0.001), sex (ß = 0.102, P < 0.001), and refractive error (ß = 0.149, P < 0.001) were associated independently with GCC thickness after adjusting for the other factors. Furthermore, age (ß = 0.100, P < 0.001), sex (ß = 0.163, P < 0.001), AL (ß = -0.283, P < 0.001), and refractive error (ß = 0.207, P < 0.001) were the independent factors associated with ORL thickness. Conclusions: The present study established a normative pediatric database for macular layer thicknesses in healthy Chinese children, advancing the ability of OCT in diseases diagnosis and monitoring among children.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Fibras Nervosas , Retina/anatomia & histologia , Células Ganglionares da Retina/citologia , Adolescente , Criança , China/epidemiologia , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Masculino , Valores de Referência , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto Jovem
14.
Nat Prod Res ; : 1-6, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617784

RESUMO

A new diketopiperazine cyclo-(L-Phe-N-ethyl-L-Glu) (1), along with two known diketopiperazines cyclo-(L-Pro-L-Leu) (2) and cyclo-(L-Pro-L-Phe) (3) were isolated from the cultures of an endophytic fungus Aspergillus aculeatus F027. The structures of these compounds were elucidated based on spectroscopic data. The configurations of these compounds were determined by advanced Marfey's analysis. Antibacterial activity of the diketopiperazines against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were also evaluated.

16.
Adv Mater ; : e1904163, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31592566

RESUMO

Light-emitting diodes (LEDs) based on solution-processed metal halide perovskites have shown great application potential in energy-efficient lighting and displays. Multiple-quantum-well (MQW) perovskites simultaneously possess high photoluminescence quantum efficiency and good film morphology and stability, making it attractive for high-performance perovskite LEDs. Here, merits of MQW perovskites and the progress in MQW perovskite LEDs are reviewed. Challenges and future directions of perovskite LEDs are also discussed.

17.
mBio ; 10(5)2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575768

RESUMO

Group A streptococcus (GAS) is an important human pathogen which can cause fatal diseases after invasion into the bloodstream. Although antibiotics and immune surveillance are the main defenses against GAS infection, GAS utilizes internalization into cells as a major immune evasion strategy. Our previous findings revealed that light chain 3 (LC3)-associated single membrane GAS-containing vacuoles in endothelial cells are compromised for bacterial clearance due to insufficient acidification after fusion with lysosomes. However, the characteristics and the activation mechanisms of these LC3-positive compartments are still largely unknown. In the present study, we demonstrated that the LC3-positive GAS is surrounded by single membrane and colocalizes with NADPH oxidase 2 (NOX2) complex but without ULK1, which are characteristics of LC3-associated phagocytosis (LAP). Inhibition of NOX2 or reactive oxygen species (ROS) significantly reduces GAS multiplication and enhances autolysosome acidification in endothelial cells through converting LAP to conventional xenophagy, which is revealed by enhancement of ULK1 recruitment, attenuation of p70s6k phosphorylation, and formation of the isolation membrane. We also clarify that the inactivation of mTORC1, which is the initiation signal of autophagy, is inhibited by NOX2- and ROS-activated phosphatidylinositol 3-kinase (PI3K)/AKT and MEK/extracellular signal-regulated kinase (ERK) pathways. In addition, streptolysin O (SLO) of GAS is identified as a crucial inducer of ROS for ß1 integrin-mediated LAP induction. After downregulation of ß1 integrin, GAS multiplication is reduced, accompanied with LAP inhibition and xenophagy induction. These results demonstrate that GAS infection preferentially induces ineffective LAP to evade xenophagic killing in endothelial cells through the SLO/ß1 integrin/NOX2/ROS pathway.IMPORTANCE Our previous reports showed that the LC3-associated GAS-containing single membrane vacuoles are inefficient for bacterial clearance in endothelial cells, which may result in bacteremia. However, the characteristics and the induction mechanisms of these LC3-positive vacuoles are still largely unknown. Here we provide the first evidence that these LC3-positive GAS-containing single membrane compartments appear to be LAPosomes, which are induced by NOX2 and ROS. Through NOX2- and ROS-mediated signaling, GAS preferentially induces LAP and inhibits bacteriostatic xenophagy in endothelial cells. We also provide the first demonstration that ß1 integrin acts as the receptor for LAP induction through GAS-produced SLO stimulation in endothelial cells. Our findings reveal the underlying mechanisms of LAP induction and autophagy evasion for GAS multiplication in endothelial cells.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31517310

RESUMO

Objective: The aim of this study was to use whole genome sequencing (WGS) help detect de novo mutations or pathogenic genes of Mayer-Rokitansky-Küster-Hauser syndrome type 1(MRKH syndrome type 1). Study design: This was a case-parent trios study. Nine unrelated probands, with MRKH syndrome type 1 and their parents were enrolled. The enrollment, sequencing process, establishment of the de novo mutations detecting procedure and experiment part were performed over a 2-year period. Results: we detected 632 de novo single nucleotide variants (SNVs), 267 de novo small insertions/deletions (indels), 39 de novo structural variations (SVs) and 28 de novo copy number alterations (CNAs). Three novel damaging coding de novo SNVs with three damaging coding de novo genes (PIK3CD, SLC4A10 and TNK2) were revealed. Two SNVs were annotated of the promoter region of gene NBPF10 and 3'UTR of NOTCH2NL, potentially contributing to the pathogenesis of MRKH. Conclusion: We identified five de novo mutations in BAZ2B, KLHL18, PIK3CD, SLC4A10 and TNK2 by performing WGS, the functional involvement of all deleterious mutations in MRKH candidate genes of the trios warrant further study. WGS may complement conventional array to capture the complete landscape of the genome in MRKH.

19.
PLoS One ; 14(9): e0222684, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31545836

RESUMO

The improved split Hopkinson pressure bar (SHPB) was used to study the dynamic mechanical properties and failure characteristics of surrounding rock in deep rock mass engineering that is under high stress and affected by blasting excavation and other dynamic disturbances. In a three-dimensional high static load and frequent dynamic disturbance test, the preload high axial pressure and confining pressure are used to simulate the high crustal stress of deep rock, and the effect of small disturbances on the rock is simulated by the low impact load. The results show that there are two types of dynamic stress-strain curves of deep rock: an elastic-plastic curve and plastic-elastic-plastic curve. The curves consists of five parts: the compaction stage, micro-crack steady development stage, micro-crack unstable propagation stage, fatigue damage stage, and fatigue failure stage. Reductive phenomena of constringent strain after dynamic peak stress appear because of the different degrees of rock damage. Moreover, these phenomena include two conditions, namely, whether rebound occurs or not. The impact resistance of rock is strongest when the ratio of the confining pressure to axial pressure is optimal, and the dynamic average strength of rock and accumulative impact times decrease with the increase of the preloaded axial compression and increase with the increase of the preloaded confining pressure. Both the dynamic deformation modulus and dynamic peak stress decrease with the increase of the accumulative impact time, while the maximum strain and the dynamic peak strain increase. The corresponding rebound strain as a whole first increases and then decreases with the increasing impact times. For deep rock, tensile failure and single-bevel plane shear failure are the main failure modes, and pull-compression mixed friction failure is the auxiliary failure mode. Additionally, the lumpiness of broken rock decreases with the increase of the preloaded axial compression and increases with the increase of the preloaded confining pressure.

20.
FASEB J ; 33(12): 13346-13357, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545913

RESUMO

Endothelial glycocalyx plays a significant role in the development and progression of diabetic complications. Endomucin (EMCN) is an anti-inflammatory membrane glycoprotein that is mainly expressed in venous and capillary endothelial cells. However, the function of EMCN in diabetic retinopathy (DR) progression is still completely unknown. We first investigated the change of EMCN expression in the retina and human retinal microvascular endothelial cells. We then overexpressed EMCN in the retina with adeno-associated virus and induced DR with streptozotocin (STZ). We analyzed EMCN's effect on the integrity of endothelial glycocalyx under conditions of DR. Furthermore, we investigated EMCN's protective effect against inflammation and blood-retinal barrier (BRB) destruction. We found that EMCN is specifically expressed in retinal endothelial cells and that its levels are decreased during hyperglycemia in vitro and in vivo. Overexpression of EMCN can restore the retinal endothelial glycocalyx of STZ-induced diabetic rats. Furthermore, EMCN overexpression can decrease leukocyte-endothelial adhesion to ameliorate inflammation and stabilize the BRB to inhibit vessel leakage in rats with DR. EMCN may protect patients with diabetes from retinal vascular degeneration by restoring the endothelial glycocalyx. EMCN may thus represent a novel therapeutic strategy for DR because it targets endothelial glycocalyx degradation associated with this disease.-Niu, T., Zhao, M., Jiang, Y., Xing, X., Shi, X., Cheng, L., Jin, H., Liu, K. Endomucin restores depleted endothelial glycocalyx in the retinas of streptozotocin-induced diabetic rats.

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