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1.
Artigo em Inglês | MEDLINE | ID: mdl-33036755

RESUMO

Inorganic pyrophosphatase (PPase) plays an essential role in energy conservation and provides energy for many biosynthetic pathways. Here, we present two three-dimensional structures of PPase from Homo sapiens (Hu-PPase) at 2.38 Å and 3.40 Å in different crystallization conditions. One of the Hu-PPase structures complex of two magnesium metal ions was determined to be a monomer (Hu-PPase-mono) here, while the other one to be a dimer-dimer (Hu-PPase-dd). In each asymmetric unit of Hu-PPase-mono, there are four α-helices and ten ß-strands and folds as a barrel structure, and the active site contains two magnesium ions. Like PPases from many species, we found that Hu-PPase was able to undergo self-assembly. To our surprise, disruption of the self-assembly of Hu-PPase did not influence its enzymatic activity or the ability to promote cell growth. Our work uncovered that different structure forms of Hu-PPase and found that the pyrophosphatase activity of Hu-PPase is independent of its self-assembly.

2.
Sci Adv ; 6(41)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33036962

RESUMO

How much the observed long-term variability of tropical cyclone (TC) activity is due to anthropogenic global warming (GW) or internal climate variability remains unclear, limiting the confidence in projected future change in TC activity. Here, the relative contributions of GW and the Interdecadal Pacific Oscillation (IPO) to the long-term variability of TC track density (TCTD) over the North Pacific (NP) are quantified on the basis of statistical analyses and climate model simulations. Results show that historical GW mainly reduced (increased) TCTD over the western (eastern) NP, while the positive (negative) IPO corresponds to a NP basin-wide increase (decrease) in TCTD except in some coastal regions. The IPO has a much greater impact on TCTD over the western NP than GW, while the IPO and GW impacts are about equal over the eastern NP during 1960-2019. These findings have important implications for projecting future TC activity over the NP.

3.
J Craniofac Surg ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038180

RESUMO

This study summarized the literature regarding the application of pre-bent titanium miniplates in orthognathic surgery and evaluated the extra deformation of the manually pre-bent titanium miniplates via finite element analysis for acquiring higher surgical accuracy. The literature was reviewed with a chart. Three models of titanium miniplates with different thicknesses (1.0 mm, 0.8 mm, 0.6 mm) were created using COMSOL Multiphysics software for biomechanical behavior analysis. The 3 models were virtually bent into 5 angles (15 degree, 30 degree, 45 degree, 60 degree, 80 degree). respectively to simulate the preoperative virtual bending, then to simulate the practical manual bending via finite element analysis. The stresses and displacements of these models were recorded. The models from virtual bending simulation and manual bending simulation were registered to analyze the deviations. The results showed that the maximum stress and the displacement deviations between the virtual bending models and the manual bending models increased with the thickness and bending angle of the pre-bent miniplate models. To improve the surgical accuracy, measures should be applied to the manually pre-bent titanium miniplates to reduce the extra deformation when the plate being thicker and the bending angle being larger.

4.
Mol Ther ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068778

RESUMO

Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of pre-miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3ß ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/ß-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent upon ATG12 rather than the Wnt/ß-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC.

5.
Nanotechnology ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33065561

RESUMO

This study reports a facile fabrication of black TiO2-x/NiFe2O4 (Ti3+ self-doped titania coupled with nickel ferrite), an efficient sonocatalyst for ibuprofen (IBP) mitigation. Compared with TiO2-x or NiFe2O4, TiO2-x/NiFe2O4 heterojunction displayed higher sonocatalytic activity, and their immobilization onto diatomaceous earth (DE) further enhanced mitigation efficiency due to the synergy between adsorption and sonocatalysis. About 96.7% of 10 mg/L IBP was removed in 100 min using 0.7 g/L catalyst at pH=6, with the ultrasonic power of 144 W and frequency of 60 KHz. Quenching experiment results demonstrated the roles of reactive species. The intermediates during IBP sono-oxidation were determined by HPLC-MS method, and the acute toxicity was evaluated. Furthermore, the reaction mechanism was proposed. The sonocatalyst revealed excellent reusability, suggesting itself promising for wastewater treatment.

6.
Zhongguo Zhen Jiu ; 40(10): 1057-60, 2020 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-33068345

RESUMO

OBJECTIVE: To observe the effect of scraping on head and face combined with stepping technique of tuina along lower limbs on fatigue symptom and mental state in patients with chronic fatigue syndrome. METHODS: A total of 100 patients with chronic fatigue syndrome were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 2 cases dropped off). In the control group, oryzanol tablets and compound vitamin B tablets were taken orally, both 2 tablets every time, 3 times every day for 30 days. On the basis of the treatment in the control group, scraping on head and face combined with stepping technique of tuina along lower limbs of three yin meridians of foot were applied in the observation group, once every 3 days, 10 times were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and somatic and psychological health report (SPHERE) were observed, and the clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the scores of FS-14 and SPHERE were reduced in the two groups (P<0.05), and the changes of those indexes in the observation group were larger than the control group (P<0.05). The total effective rate was 91.7% (44/48) in the observation group, which was superior to 54.2% (26/48) in the control group (P<0.05). CONCLUSION: Scraping on head and face combined with stepping technique of tuina along lower limbs can improve fatigue symptom and mental state in patients with chronic fatigue syndrome.

7.
Cell Biol Int ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079401

RESUMO

Breast cancer, one of the most frequently diagnosed and aggressive malignancies, is the major cause of cancer-related death greatly threatening women health. Polypeptide N-acetylgalactosaminyltransferase 4 (ppGalNAc-T4), responsible for the initial step of mucin-type O-glycosylation, has been reported to be implicated in diverse types of human tumors. However, the biological role of ppGalNAc-T4 in breast cancer is still undetermined. In this study, we investigate the effects and mechanism of ppGalNAc-T4 to the breast cancer cell proliferation. From analysis of high throughput RNA sequencing datasets of GEO and ArrayExpress, a positive correlation between ppGalNAc-T4 and the recurrence-free survival was observed in multigroup of human breast cancer datasets. Moreover, transcriptomes analysis using RNA-sequencing in MCF7 cells revealed that cell cycle-related genes induced the effects of ppGalNAc-T4 on breast cancer cell proliferation. Additionally, investigations showed that ppGalNAc-T4 impaired cell proliferation in MCF-7 and MDA-MB-231 breast cells. Furthermore, our results suggested that ppGalNAc-T4 knockout activated Notch signaling pathway and enhanced cell proliferation. Collectively, our data indicated that ppGalNAc-T4 affected proliferation of human breast cancer cells, which appears to be a novel target for understanding the underlying molecular mechanism of breast cancer. This article is protected by copyright. All rights reserved.

8.
Fam Process ; 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981036

RESUMO

There is a well-established bidirectional, negative association between couple satisfaction and depressive symptoms. Yet, a family systems perspective emphasizes the role of the therapist in interrupting this recursive cycle between couple satisfaction and depressive symptoms. The current study utilized longitudinal data to explore the bidirectional associations between depressive symptoms and couple satisfaction, moderated by the therapeutic alliance over the course of therapy. The study included 108 couples participating in couple therapy at a university training clinic. Couples rated their depressive symptoms and couple satisfaction separately before the intake session and at the end of the fourth session, and they also reported their individual therapeutic alliance with the therapist at the end of the second and third sessions. Actor-partner interdependence moderation model analysis revealed several moderation effects. In general, with low therapeutic alliance, couples with higher initial symptoms (such as depressive symptoms and low couple satisfaction) reported more severe symptoms at the fourth session, compared to those who had fewer initial symptoms. The moderating effect of alliance on a couple's symptoms was found both among individuals, and between partners. Systemic clinical implications and suggestions for future research are discussed.

9.
Chem Commun (Camb) ; 56(77): 11410-11413, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32940259

RESUMO

The autocatalytic HCR-DNAzyme platform was constructed as a versatile amplification platform for intracellular microRNA imaging by integrating hybridization chain reaction (HCR) circuit with DNAzyme biocatalysis. The HCR-assembled multifunctional DNAzyme nanowires produce new HCR triggers and numerous transducer DNAzyme amplifier, and thus shows great promise in earlier cancer diagnosis.

10.
Acta Pharmacol Sin ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901086

RESUMO

Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used 68Ga, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by 68Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of 89Zr and 68Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of 68Ga-labeled CAR T cells is only one twenty-fourth of 89Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of 68Ga instead of 89Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32888172

RESUMO

Using a radial frequency discrimination task that has not been tested in many previous studies, we examined the dependence of the pattern radius (4 to 16 deg) on the radial frequency thresholds of two different types of concentric radial frequency (RF) patterns: constant circular contour frequency (CCF) RF patterns with different radii, which have the constant physical length of modulation cycle in external real-world space, and constant radial frequency magnified RF patterns with different radii, which have the constant cortical length of modulation cycles. These two types RF patterns used as the reference stimuli had an equal maximum orientation difference from circularity regardless of change in radius. The discrimination threshold expressed by the frequency ratio between RF patterns of different frequencies vs. radius functions for the constant CCF RF patterns indicated different functional forms dependent on the modulation amplitude of the RF patterns. The thresholds increased with increasing pattern radius for small modulation amplitude RF patterns but were relatively flattened for large-amplitude RF patterns. This dependence was ascribed to the eccentricity effect wherein the deformation thresholds for discriminating the RF pattern from a circle increase with increasing stimulus eccentricity (Feng et al. 2020). The discrimination thresholds vs. radius functions for the magnified RF patterns were also flattened for different modulation amplitudes and frequencies. The thresholds (frequency ratio) were similar at all eccentricities. Cortical magnification neutralized the eccentricity effect observed for the constant CCF patterns.

12.
Genome Biol ; 21(1): 228, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873321

RESUMO

BACKGROUND: The central nervous system (CNS) is vulnerable to viral infection, yet few host factors in the CNS are known to defend against invasion by neurotropic viruses. Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in a wide variety of biological processes and are highly abundant in the mammalian brain, but their roles in defending against invasion of pathogens into the CNS remain unclear. RESULTS: We report here that multiple neurotropic viruses, including rabies virus, vesicular stomatitis virus, Semliki Forest virus, and herpes simplex virus 1, elicit the neuronal expression of a host-encoded lncRNA EDAL. EDAL inhibits the replication of these neurotropic viruses in neuronal cells and rabies virus infection in mouse brains. EDAL binds to the conserved histone methyltransferase enhancer of zest homolog 2 (EZH2) and specifically causes EZH2 degradation via lysosomes, reducing the cellular H3K27me3 level. The antiviral function of EDAL resides in a 56-nt antiviral substructure through which its 18-nt helix-loop intimately contacts multiple EZH2 sites surrounding T309, a known O-GlcNAcylation site. EDAL positively regulates the transcription of Pcp4l1 encoding a 10-kDa peptide, which inhibits the replication of multiple neurotropic viruses. CONCLUSIONS: Our findings show that a neuronal lncRNA can exert an effective antiviral function via blocking a specific O-GlcNAcylation that determines EZH2 lysosomal degradation, rather than the traditional interferon-dependent pathway.

13.
J Craniofac Surg ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881824

RESUMO

The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.

14.
Ann Rheum Dis ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958509

RESUMO

OBJECTIVES: To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs). METHODS: sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05. RESULTS: Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment. CONCLUSION: Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.

15.
Cell Death Dis ; 11(9): 781, 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32951003

RESUMO

Drug-induced liver injury is the major cause of acute liver failure. However, the underlying mechanisms seem to be multifaceted and remain poorly understood, resulting in few effective therapies. Here, we report a novel mechanism that contributes to acetaminophen-induced hepatotoxicity through the induction of ferroptosis, a distinctive form of programmed cell death. We subsequently identified therapies protective against acetaminophen-induced liver damage and found that (+)-clausenamide ((+)-CLA), an active alkaloid isolated from the leaves of Clausena lansium (Lour.) Skeels, inhibited acetaminophen-induced hepatocyte ferroptosis both in vivo and in vitro. Consistently, (+)-CLA significantly alleviated acetaminophen-induced or erastin-induced hepatic pathological damages, hepatic dysfunctions and excessive production of lipid peroxidation both in cultured hepatic cell lines and mouse liver. Furthermore, treatment with (+)-CLA reduced the mRNA level of prostaglandin endoperoxide synthase 2 while it increased the protein level of glutathione peroxidase 4 in hepatocytes and mouse liver, confirming that the inhibition of ferroptosis contributes to the protective effect of (+)-CLA on drug-induced liver damage. We further revealed that (+)-CLA specifically reacted with the Cys-151 residue of Keap1, which blocked Nrf2 ubiquitylation and resulted in an increased Nrf2 stability, thereby leading to the activation of the Keap1-Nrf2 pathway to prevent drug-induced hepatocyte ferroptosis. Our studies illustrate the innovative mechanisms of acetaminophen-induced liver damage and present a novel intervention strategy to treat drug overdose by using (+)-CLA.

16.
Biomark Med ; 14(11): 1031-1045, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32940073

RESUMO

Progress on glycosylation and tumor markers has not been extensively reported. Glycosylation plays an important part in post-translational modification. Previous research on glycosylation-modified biomarkers has lagged behind due to insufficient understanding of glycosylation-related regulations. However, some new methods and ideas illustrated in recent research may provide new inspirations in the field. This article aims to review current advances in revealing relationship between tumors and abnormal N-glycosylation and discuss leading-edge applications of N-glycosylation in developing novel tumor biomarkers.

17.
Life Sci ; 260: 118424, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32949586

RESUMO

AIMS: Cannabinoid receptor 2 (CB2R) is an important regulator of immunoinflammatory responses. Interestingly, studies have demonstrated that CB2R was expressed in metabolically active tissue, so we speculated that CB2R might have a crucial impact on energy balance. We thus examined the anti-inflammatory activities of CB2R and a CB2R agonist, JWH-133, in diet-induced obese in mice as well as in cultured macrophages. MATERIALS AND METHODS: We evaluated the in vivo effect of JWH-133 on diet-induced adipose tissue inflammation. We also assessed the in vitro effects of JWH-133 on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages, with a focus on the nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway. KEY FINDINGS: We found that JWH-133 reduced body weight gain, relieved glucose tolerance, and enhanced insulin sensitivity in a mouse model. It also down-regulated the expression of M1 macrophage biomarkers (tumor necrosis factor-α, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), IL-1ß, CC motif chemokine ligand 2, and C-X-C motif chemokine 10) in vivo and in vitro, but up-regulated levels of M2 macrophage biomarkers (IL-10 and arginase-1) in both mice and cultured macrophages. Furthermore, the underlying mechanisms were studied in an LPS-treated RAW264.7 cell line. We found a role for JWH-133 in controlling M1 macrophage polarization by activating the Nrf2/HO-1 pathway, while the effect of JWH-133 was diminished by a HO-1 inhibitor, Sn(IV) protoporphyrin IX dichloride. SIGNIFICANCE: JWH-133 showed anti-obesity effects that ameliorated pro-inflammatory M1 macrophage polarization through the Nrf2/HO-1 pathway. Therefore, our results provide a new proof for the potential use of the CB2R agonist, JWH-133, in the treatment of obesity.

18.
Chemosphere ; 258: 127276, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947657

RESUMO

It is crucial for water environment security to remove its p-arsanilic acid (p-ASA) efficiently. Namely, removing p-arsanilic acid from aqueous media through magnetic separation, has become a novel method of removing toxic pollutants from water. Batch adsorption experiments demonstrated a higher adsorption of lignin-based magnetic activated carbon (201.64 mg g-1) toward p-ASA. In addition, LMAC nanoparticles exhibited typical magnetism (35.63 emu g-1 of saturation magnetization) and could be easily separated from the aqueous solution. Meanwhile, the endothermic adsorption of p-ASA over LMAC could spontaneously proceed and be well described by the pseudo-first-order and pseudo-second-order model as well as the intra-particle diffusion model. Moreover, the mechanisms during p-ASA adsorption over LMAC included the electrostatic attraction, surface complexation, π-π stacking and hydrogen bonding interaction. Importantly, lignin-based magnetic activated carbon has high absorbability and preferable reusability in real water samples. Consequently, this paper provides insights into preparation of the lignin-based magnetic activated carbon may be potential adsorbents for the remediation of organoarsenic compounds.


Assuntos
Ácido Arsanílico/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Adsorção , Carvão Vegetal , Cinética , Lignina , Fenômenos Magnéticos , Magnetismo , Imãs , Água , Poluentes Químicos da Água/análise
20.
Curr Eye Res ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990055

RESUMO

PURPOSE: The aim of this study was to investigate the developmental tendencies and distribution of ocular biometric parameters in premature infants without retinopathy of prematurity (ROP). Axial length (AL), anterior chamber depth (ACD), lens thickness (LT) and vitreous length (VL) were measured, and their relationships with birth weight (BW) and postmenstrual age (PMA) were analyzed during their earliest weeks of life. METHODS: This cross-sectional cohort study included 633 premature infants. They were divided into nine groups according to their PMA: 32 weeks, 33 weeks, 34 weeks, and onward to 40 weeks. All participants underwent portable slit lamp examination, RetCam3 and A-scan ultrasound biometry. The following ocular biometric parameters were recorded: AL, ACD, LT and VL. The t-test, one-way analysis of variance, and the multiple regression analysis model were used to analyze the data. RESULTS: The increases in AL, ACD, LT and VL were 0.14 mm, 0.028 mm, 0.0025 mm and 0.11 mm per week, respectively. AL, ACD, LT and VL were positively correlated with BW (ß=0.000337, 4.234E-5, 2.697E-5, 0.000278, respectively) and PMA (ß=0.142, 0.026, 0.011, 0.103, respectively). CONCLUSIONS: With maturation, AL and VL increased and ACD deepened, but there was no significant change in LT. The ocular growth parameters were positively correlated with BW and PMA however the correlations were not strong.

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