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1.
Genes (Basel) ; 12(4)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810234

RESUMO

The litter size of domestic goats and sheep is an economically important trait that shows variation within breeds. Strenuous efforts have been made to understand the genetic mechanisms underlying prolificacy in goats and sheep. However, there has been a paucity of research on the genetic convergence of prolificacy between goats and sheep, which likely arose because of similar natural and artificial selection forces. Here, we performed comparative genomic and transcriptomic analyses to identify the genetic convergence of prolificacy between goats and sheep. By combining genomic and transcriptomic data for the first time, we identified this genetic convergence in (1) positively selected genes (CHST11 and SDCCAG8), (2) differentially expressed genes (SERPINA14, RSAD2, and PPIG at follicular phase, and IGF1, GPRIN3, LIPG, SLC7A11, and CHST15 at luteal phase), and (3) biological pathways (genomic level: osteoclast differentiation, ErbB signaling pathway, and relaxin signaling pathway; transcriptomic level: the regulation of viral genome replication at follicular phase, and protein kinase B signaling and antigen processing and presentation at luteal phase). These results indicated the potential physiological convergence and enhanced our understanding of the overlapping genetic makeup underlying litter size in goats and sheep.

2.
Preprint | bioRxiv | ID: ppbiorxiv-433919

RESUMO

Hematopoiesis is finely regulated to enable timely production of the right number and type of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential and new role of ubiquitin X domain containing gene 3B (UBXN3B) in balancing myelopoiesis and lymphopoiesis. Ubxn3b deficiency (Ubxn3b-/-) results in a remarkable increase in myeloid cells and neutrophil-to-lymphocyte ratio, along with a reduction in lymphocytes in steady-state mice. This dysregulation is exacerbated during viral infection and renders mice highly vulnerable to severe lung pathology induced by severe acute respiratory syndrome coronavirus 2 and arthritis by arthritogenic alphaviruses. Ubxn3b-/- mice present normal type I IFNs, higher viral loads and inflammatory mediators, lower virus-specific immunoglobulin G and slower resolution of disease, when compared to Ubxn3b+/+ littermates. Mechanistically, Ubxn3b-/- mice have fewer multipotent progenitors and common lymphoid progenitors, but more common myeloid progenitors. In particular, the precursor and immature B cell numbers are dramatically decreased in the bone marrow of Ubxn3b-/- mice. These data demonstrate that UBXN3B signaling is essential for restricting viral infection and immunopathogenesis by maintaining hematopoietic homeostasis.

3.
Animals (Basel) ; 11(2)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671790

RESUMO

Litter size is one of the most important economic traits in sheep. GDF9 and BMPR1B are major genes affecting the litter size of sheep. In this study, the whole coding region of GDF9 was sequenced and all the SNPs (single nucleotide polymorphisms) were determined in Luzhong mutton ewes. The FecB mutation was genotyped using the Sequenom MassARRAY®SNP assay technology. Then, the association analyses between polymorphic loci of GDF9 gene, FecB, and litter size were performed using a general linear model procedure. The results showed that eight SNPs were detected in GDF9 of Luzhong mutton sheep, including one novel mutation (g.41769606 T > G). The g.41768501A > G, g.41768485 G > A in GDF9 and FecB were significantly associated with litter size in Luzhong mutton ewes. The g.41768485 G > A is a missense mutation in the mature GDF9 protein region and is predicted to affect the tertiary structure of the protein. The results preliminarily demonstrated that GDF9 was a major gene affecting the fecundity of Luzhong mutton sheep and the two loci g.41768501A > G and g.41768485 G > A may be potential genetic markers for improving litter size.

4.
J Am Coll Cardiol ; 77(6): 680-691, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33573737

RESUMO

BACKGROUND: Previous studies investigated the potential mechanism of embolic stroke of undetermined source (ESUS) from extracranial artery plaque, but there has been no study other than a case report on high-risk intracranial plaque in ESUS. OBJECTIVES: The aim of this study was to investigate the issue by evaluating the morphology and composition of intracranial plaque in patients with ESUS and small-vessel disease (SVD) using 3.0-T high-resolution magnetic resonance imaging. METHODS: Two hundred forty-three consecutive patients with ESUS and 160 patients with SVD-associated stroke between January 2015 and December 2019 were retrospectively enrolled. Multidimensional parameters involving the presence of plaque on both sides, including remodeling index (RI), plaque burden, presence of discontinuity of plaque surface, thick fibrous cap, intraplaque hemorrhage, and complicated American Heart Association type VI plaque at the maximal luminal narrowing site, were evaluated using intracranial high-resolution magnetic resonance imaging. RESULTS: Among 243 patients with ESUS, the prevalence of intracranial plaque was much higher in the ipsilateral than the contralateral side (63.8% vs. 42.8%; odds ratio [OR]: 5.25; 95% confidence interval [CI]: 2.83 to 9.73), a finding that was not evident in patients with SVD (35.6% vs. 30.6%; OR: 2.14; 95% CI: 0.87 to 5.26; p = 0.134). Logistic analysis showed that RI was independently associated with ESUS in model 1 (OR: 2.329; 95% CI: 1.686 to 3.217; p < 0.001) and model 2 (OR: 2.295; 95% CI: 1.661 to 3.172; p < 0.001). RI alone with an optimal cutoff of 1.162, corresponding to an area under the curve of 0.740, had good diagnostic efficiency for ESUS. CONCLUSIONS: The present study supports an etiologic role of high-risk nonstenotic intracranial plaque in ESUS.

5.
J Affect Disord ; 284: 217-228, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33609956

RESUMO

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

6.
BMC Cancer ; 21(1): 115, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541299

RESUMO

BACKGROUND: In recent decades, the 5-year survival rate of osteosarcoma remains poor, despite the variety of operations, and exploration of drug therapy has become the key to improvement. This study investigates the contribution of different aspects in osteosarcoma and cure, and predicts research hotspots to benefit future clinical outcomes. METHODS: The Web of Science and PubMed databases were queried to collect all relevant publications related to osteosarcoma and cure from 2009 to 2019. These data were imported into CiteSpace and the Online Analysis Platform of Literature Metrology for bibliometric analysis. Bi-clustering was performed on Bibliographic Item co-occurrence Matrix Builder (BICOMB) and gCLUTO to identify hotspots. Additionally, completed clinical trials on osteosarcoma with results past phase II were collated. RESULTS: A total of 2258 publications were identified in osteosarcoma and cure from 2009 to 2019. China has the largest number of publications (38.49%), followed by the United States (23.03%) with the greatest impact (centrality = 0.44). The centrality of most institutions is < 0.1, and Central South University and Texas MD Anderson Cancer Center possess the highest average citation rates of 3.25 and 2.87. BMC cancer has the highest average citation rate of 3.26 in 772 journals. Four authors (Picci P, Gorlick R, Bielack SS and Bacci G) made the best contributions. We also identified eight hotspots and collected 41 clinical trials related to drug research on osteosarcoma. CONCLUSIONS: The urgent need exists to strengthen global academic exchanges. Overcoming multidrug resistance in osteosarcoma is the focus of past, present and future investigations. Transformation of the metastasis pattern, microenvironment genetics mechanism, alternative methods of systemic chemotherapy and exploration of traditional Chinese medicine is expected to contribute to a new upsurge of research.

7.
Genes (Basel) ; 12(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477586

RESUMO

Ovine litter size (LS) is an important trait showing variability within breeds. It remains largely unknown whether inbreeding depression on LS exists based on genomic homozygous regions, and whether the homozygous regions resulted from inbreeding are significantly associated with LS in sheep. We here reanalyze a set of single nucleotide polymorphism (SNP) chip of six breeds to characterize the patterns of runs of homozygosity (ROH), to evaluate inbreeding levels and inbreeding depressions on LS, and to identify candidate homozygous regions responsible for LS. Consequently, unique ROH patterns were observed among six sheep populations. Inbreeding depression on LS was only found in Hu sheep, where a significant reduction of 0.016, 0.02, and 0.02 per 1% elevated inbreeding FROH4-8, FROH > 8 and the total inbreeding measure was observed, respectively. Nine significantly homozygous regions were found for LS in Hu sheep, where some promising genes for LS possibly via regulation of the development of oocytes (NGF, AKT1, and SYCP1), fertilization (SPAG17, MORC1, TDRD9, ZFYVE21, ADGRB3, and CKB), embryo implantation (PPP1R13B, INF2, and VANGL1) and development (DPPA2, DPPA4, CDCA4, CSDE1, and ADSSL1), and reproductive health (NRG3, BAG5, CKB, and XRCC3) were identified. These results from the present study would provide insights into the genetic management and complementary understandings of LS in sheep.

8.
BMC Vet Res ; 17(1): 12, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413374

RESUMO

BACKGROUND: Fecundity is important for farm blue fox (Vulpes lagopus), who with asthenospermia have be a problem in some of farms in China. A key symptom of asthenospermia is decreased sperm motility. The decreased secreting beta-defensin108 (vBD108) of blue fox is speculated be related to asthenospermia. To clarify this idea, the mRNA expression of vBD108 in testis and epididymis of blue foxes with asthenospermia were detected and compared to the healthy one. The antibody was prepared and analyzed by immunohistochemistry. RESULTS: The vBD108 in testis and epididymis was found both in blue fox with asthenospermia and healthy group by the method of immunohistochemistry. The expression of vBD108 mRNA in testes (P < 0.05) and epididymal corpus (P < 0.0001) in asthenospermia group was lower than that in healthy group. CONCLUSIONS: These results suggested that vBD108 deficiency may related to blue fox asthenospermia. Meanwhile, the study on the blue fox vBD108 provides a hopeful direction to explore the pathogenesis of blue fox asthenospermia in the future.

9.
Clin Res Hepatol Gastroenterol ; : 101529, 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33268035

RESUMO

BACKGROUND AND AIM: Achalasia patients usually present lower esophageal sphincter thickening, which can impact the expansibility of cardia. We aimed to investigate the effect of cardiac muscularis propria (MP) on perioperative adverse events (AEs) and treatment outcomes of patients treated with peroral endoscopic myotomy (POEM). METHODS: We retrospectively reviewed 114 patients with achalasia undergoing pre-POEM endoscopic ultrasonography (EUS) between May 2013 and November 2019. Cardiac MP thickness was measured using EUS. POEM failure was defined as Eckardt score >3. Risk factors for perioperative AEs and POEM failure were identified. RESULTS: Patients were divided into the thin (n = 52) and the thick group (n = 62) based on the median of cardiac MP thickness (3.0 mm). Perioperative AEs rate of the thin group seemed to be slightly higher than that of the thick group (11.5% vs. 4.8%, P = 0.30). During a median follow-up of 30 months (range 1-77), 100 patients completed follow-up, 16 (16%) of which occurred clinical failure. The clinical outcomes of patients in the thin group were significantly poorer than those patients in the thick group (P = 0.006). Cardiac MP thickness was an independent risk factor for POEM failure (hazard ratio 3.9, P = 0.02; Cox regression), but not the risk factor for perioperative AEs (odds ratio 2.6, P = 0.2; logistic regression). CONCLUSION: Cardiac MP thickness could be a novel predictive factor for POEM failure in patients with achalasia.

10.
ACS Nano ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33369384

RESUMO

It is a major challenge to achieve fast charging and high reversible capacity in potassium ion storing carbons. Here, we synthesized sulfur-rich graphene nanoboxes (SGNs) by one-step chemical vapor deposition to deliver exceptional rate and cyclability performance as potassium ion battery and potassium ion capacitor (PIC) anodes. The SGN electrode exhibits a record reversible capacity of 516 mAh g-1 at 0.05 A g-1, record fast charge capacity of 223 mA h g-1 at 1 A g-1, and exceptional stability with 89% capacity retention after 1000 cycles. Additionally, the SGN-based PIC displays highly favorable Ragone chart characteristics: 112 Wh kg-1at 505 W kg-1 and 28 Wh kg-1 at 14618 W kg-1 with 92% capacity retention after 6000 cycles. X-ray photoelectron spectroscopy analysis illustrates a charge storage sequence based primarily on reversible ion binding at the structural-chemical defects in the carbon and the reversible formation of K-S-C and K2S compounds. Transmission electron microscopy analysis demonstrates reversible dilation of graphene due to ion intercalation, which is a secondary source of capacity at low voltage. This intercalation mechanism is shown to be stable even at cycle 1000. Galvanostatic intermittent titration technique analysis yields diffusion coefficients from 10-10 to 10-12 cm2 s-1, an order of magnitude higher than S-free carbons. The direct electroanalytic/analytic comparison indicates that chemically bound sulfur increases the number of reversible ion bonding sites, promotes reaction-controlled over diffusion-controlled kinetics, and stabilizes the solid electrolyte interphase. It is also demonstrated that the initial Coulombic efficiency can be significantly improved by switching from a standard carbonate-based electrolyte to an ether-based one.

11.
Am J Chin Med ; 48(8): 1787-1802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33308097

RESUMO

Stroke is the leading fatal disease in China. This retrospective study aimed to explore the optimal acupuncture intervention time for long-term efficacy on motor dysfunction in patients suffering from acute ischemic stroke through 1-year of follow-up. Three hundred and nine patients collected at Longhua Hospital from January 2016 to December 2017 were classified into 3 groups based on the acupuncture intervention time, including groups A (within 2 days), B (within 3-7 days) and C (within 8-14 days). All patients had received standard treatment combined with acupuncture therapy. Specifically, acupuncture was performed at the acupoints including LI4 (Hegu), ST40 (Fenglong), DU20 (Baihui), and motor area of the scalp, followed by 2 electroacupuncture protocols based on different muscle tensions once a day for 5 days consecutively. The time-effect relationship was assessed using both the Fugl-Meyer Assessment (FMA) and the modified Barthel index (MBI) on the 90th day and 1st year, respectively. Meanwhile, the modified Rankin scale (mRS), high-sensitivity C-reactive protein (hs-CRP), and fibrinogen (FIB) were also measured during the 1-year follow-up. The favorable outcome rate was 74.4%. One-way univariate analysis of variance (ANOVA) revealed significant differences in FMA and MBI on the 90th day among the 3 groups ([Formula: see text] < 0.05), while no significant differences were observed in FMA, MBI or mRS at the 1st year between groups A and B. The levels of hs-CRP and FIB ([Formula: see text] < 0.05) were markedly reduced. Binary logistic regression analysis suggested that patients with atrial fibrillation (AF) (odds ratio (OR): 3.156), chronic kidney disease (CKD) (OR: 2.563), diabetes mellitus (DM) (OR: 2.174) or stroke history (OR: 1.883) were more inclined to recover poorly from nerve function deficit ([Formula: see text] < 0.05). Earlier acupuncture intervention may have a better long-term effect on motor dysfunction and inflammation during the 1-year follow-up. Moreover, acupuncture within 2 days is probably the optimal treatment time for early recovery on the 90th day.

12.
Front Cell Infect Microbiol ; 10: 535310, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330117

RESUMO

Background: Multiple studies have shown that an imbalance in the intestinal microbiota is related to bone metabolism, but the role of the intestinal microbiota in postmenopausal osteoporosis remains to be elucidated. We explored the effect of the intestinal microbiota on osteoporosis. Methods: We constructed a postmenopausal osteoporosis mouse model, and Micro CT was used to observe changes in bone structure. Then, we identified the abundance of intestinal microbiota by 16S RNA sequencing and found that the ratio of Firmicutes and Bacteroidetes increased significantly. UHPLC-MS analysis was further used to analyze changes in metabolites in feces and serum. Results: We identified 53 upregulated and 61 downregulated metabolites in feces and 2 upregulated and 22 downregulated metabolites in serum under OP conditions, and interestedly, one group of bile acids showed significant differences in the OP and control groups. Network analysis also found that these bile acids had a strong relationship with the same family, Eggerthellaceae. Random forest analysis confirmed the effectiveness of the serum and fecal models in distinguishing the OP group from the control group. Conclusions: These results indicated that changes in the gut microbiota and metabolites in feces and serum were responsible for the occurrence and development of postmenopausal osteoporosis. The gut microbiota is a vital inducer of osteoporosis and could regulate the pathogenesis process through the "microbiota-gut-metabolite-bone" axis, and some components of this axis are potential biomarkers, providing a new entry point for the future study on the pathogenesis of postmenopausal osteoporosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33210413

RESUMO

Granular materials, composed of densely packed particles, are known to possess unique mechanical properties that are highly dependent on the surface structure of the particles. A microscopic understanding of the structure-property relationship in these systems remains unclear. Here, supra-nanoparticle clusters (SNPCs) with precise structures are developed as model systems to elucidate the structure-property relationship. SNPCs are prepared by coordination-driven assembly of polyhedral oligomeric silsesquioxane (POSS) with metal-organic polyhedron. Due to the disparity in sizes, the POSS-MOP assemblies, like their classic nanoparticles counterparts, ordering is suppressed, and the POSS-MOP mixtures will vitrify or jam as a function of decreasing temperature. An unexpected elasticity is observed for the SNPC assemblies with a high modulus that is maintained at temperatures far beyond the glass transition temperature. From studies on the dynamics of the hierarchical structures of SNPCs and molecular dynamic simulation, the elasticity has its origins in the interpenetration of POSS-ended arms. The physical molecular interpenetration and inter-locking phenomenon favors the convenient solution or pressing processing of the novel cluster-based elastomers.

14.
Aging (Albany NY) ; 12(19): 19440-19454, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052139

RESUMO

The present study sought to identify potential hub genes and pathways of acute coronary syndrome (ACS). We downloaded the dataset (GSE56045) from the Gene Expression Omnibus (GEO) database and analyzed weighted gene coexpression networks (WGCNA). Gene Ontology annotation, Disease Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R software. The protein-protein interaction (PPI) network was constructed using Cytoscape, and the Molecular Complex Detection app was employed to identify significant modules and hub genes. The hub genes were then validated in other microarrays and patients by RT-PCR. Two modules were identified and associated with coronary artery disease (CAD) and included 219 genes. After function and PPI analyses, 24 genes were identified to be potentially associated with CAD. Linear correlation was performed to calculate the relationship between the gene expression levels and coronary artery calcification score and found that CCR7 (R = -0.081, P = 0.0065), CD2 (R = -0.075, P = 0.0012), CXCR5 (R = -0.065, P = 0.029) and IL7R (R = -0.06, P = 0.043) should be validated in other dataset. By comparing the gene expression levels in different groups in GSE23561, GSE34822, GSE59867, GSE60993 and GSE129935, only two genes (CCR7 and CXCR5) showed significance. The nomogram showed that CXCR5 showed the risk of ACS. Further analysis in chest patients found CXCR5 played a key role resulting in ACS. Our WGCNA analysis identified CXCR5 as a risk factor for ACS, and the potential pathogenesis may be associated with immune inflammation.

15.
ACS Omega ; 5(41): 26817-26828, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33111008

RESUMO

In this paper, the influence of Stefan flow on different reactivity coke solution loss reaction (Ccoke + CO2 = 2CO) at different temperatures were analyzed and compared to deeply understand the mechanism of the coke solution loss reaction. Isothermal experiments of carbon dioxide gasification with Coke A (low reactivity), Coke B (medium reactivity), and Coke C (high reactivity), respectively, were carried out at 1100-1300 °C. After calculation, it is concluded that the external diffusion coefficients and the mass transfer coefficients with Stefan flow of three kinds of coke were decreased, and their minimum average deviations with and without Stefan flow were 44.57/43.27/43.23 and 42.57/39.47/39.15%, respectively. As the coke reactivity increased, the diffusion and mass transfer capacity of carbon dioxide with Stefan flow in the boundary layer decreased. The carbon dioxide concentration on the outer surface of three kinds of coke with Stefan flow was less than that without Stefan flow. The influence of Stefan flow on carbon dioxide concentration on the outer surface of coke was increased with the increase of coke reactivity. The area of carbon dioxide concentration region in the three kinds of coke declined after modification, and the deviations of the carbon dioxide concentration region area before and after modification of three kinds of coke ranged from 6.62 to 22.85%, 7.74 to 25.17%, and 8.62 to 26.74%. The influence of Stefan flow on the carbon dioxide concentration region increased as coke reactivity increased.

16.
ACS Appl Mater Interfaces ; 12(44): 50068-50076, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33085900

RESUMO

The high water content of hydrogels makes them important as synthetic biomaterials, and tuning the mechanical properties of hydrogels to match those of natural tissues without changing chemistry is usually difficult. In this study, we have developed a series of hydrogels with varied stiffness, strength, and toughness based on a combination of poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS), a strong acidic polyelectrolyte, and poly-N-(carboxymethyl)-N,N-dimethyl-2-(methacryloyloxy) ethanaminium) (PCDME), a polyzwitterion with a weak acidic moiety. We demonstrate that modifying the true molar ratio, R, of PCDME to PAMPS results in four unique categories of hydrogels with different swelling ratios and Young's moduli. When R < 1, a negatively charged polyelectrolyte gel (PE) is formed; when 1 < R < 3, a tough and viscoelastic polyelectrolyte complex gel (PEC) is formed; when 3 < R < 6.5, a conventional, elastic interpenetrating network gel (IPN) is formed; and when R > 6.5, a tough and stiff double-network gel (DN) is formed. Both the PEC and DN gels exhibit high toughness and fracture stress, up to 1.8 and 1.5 MPa, respectively. Importantly, the PEC gels exhibit strong recovery properties along with high toughness, distinguishing them from DN gels. Without requiring a change in chemistry, we can tune the mechanical response of hydrogels over a wide spectrum, making this a useful system of soft and hydrated biomaterials.

17.
Front Oncol ; 10: 1715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014850

RESUMO

Objective: To generate virtual non-contrast (VNC) computed tomography (CT) from intravenous enhanced CT through convolutional neural networks (CNN) and compare calculated dose among enhanced CT, VNC, and real non-contrast scanning. Method: 50 patients who accepted non-contrast and enhanced CT scanning before and after intravenous contrast agent injections were selected, and two sets of CT images were registered. A total of 40 and 10 groups were used as training and test datasets, respectively. The U-Net architecture was applied to learn the relationship between the enhanced and non-contrast CT. VNC images were generated in the test through the trained U-Net. The CT values of non-contrast, enhanced and VNC CT images were compared. The radiotherapy treatment plans for esophageal cancer were designed, and dose calculation was performed. Dose distributions in the three image sets were compared. Results: The mean absolute error of CT values between enhanced and non-contrast CT reached 32.3 ± 2.6 HU, and that between VNC and non-contrast CT totaled 6.7 ± 1.3 HU. The average CT values in enhanced CT of great vessels, heart, lungs, liver, and spinal cord were all significantly higher than those of non-contrast CT (p < 0.05), with the differences reaching 97, 83, 42, 40, and 10 HU, respectively. The average CT values of the organs in VNC CT showed no significant differences from those in non-contrast CT. The relative dose differences of the enhanced and non-contrast CT were -1.2, -1.3, -2.1, and -1.5% in the comparison of mean doses of planned target volume, heart, great vessels, and lungs, respectively. The mean dose calculated by VNC CT showed no significant difference from that by non-contrast CT. The average γ passing rate (2%, 2 mm) of VNC CT image was significantly higher than that of enhanced CT image (0.996 vs. 0.973, p < 0.05). Conclusion: Designing a treatment plan based on enhanced CT will enlarge the dose calculation uncertainty in radiotherapy. This paper proposed the generation of VNC CT images from enhanced CT images based on U-Net architecture. The dose calculated through VNC CT images was identical with that obtained through real non-contrast CT.

18.
Scand J Immunol ; : e12988, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047375

RESUMO

The Toll-like receptor (TLR) family acts as a bridge connecting innate and acquired immunity. TLR10 remains one of the least understood members of this family. Some studies have examined TLR10 ligands, dimerization of TLR10 with other TLRs, and downstream signalling pathways and functions, but they have often arrived at conflicting conclusions. TLR10 can induce the production of proinflammatory cytokines by forming homodimers with itself or heterodimers with TLR1 or other TLRs, but it can also inhibit proinflammatory responses when co-expressed with TLR2 or potentially other TLRs. Mutations in the Toll/Interleukin 1 receptor (TIR) domain of TLR10 alter its signalling activity. Polymorphisms in the TLR10 gene can change the balance between pro- and anti-inflammatory responses and hence modulate the susceptibility to infection and autoimmune diseases. Understanding the full range of TLR10 ligands and functions may allow the receptor to be exploited as a therapeutic target in inflammation- or immune-related diseases. Here, we summarize recent findings on the pro- and anti-inflammatory roles of TLR10 and the molecular pathways in which it is implicated. Our goal is to pave the way for future studies of the only orphan TLR thought to have strong potential as a target in the treatment of inflammation-related diseases.

19.
Mol Med Rep ; 22(2): 1179-1186, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32626973

RESUMO

Idiopathic scoliosis (IS) is a spinal 3­dimensional deformity with an unknown cause. Melatonin is secreted by the pineal body and contributes to the occurrence and progression of IS. In our previous preliminary study, it was reported that high concentrations of melatonin can induce osteoblast apoptosis, thus acting as an IS treatment, but the mechanism of action is unknown. Therefore, the present study was performed to further investigate the possible mechanism underlying the efficacy of melatonin as a treatment for IS. The present results indicated that high concentrations of melatonin mediate endoplasmic reticulum stress (ERS)­induced apoptosis in hFOB 1.19 cells, and this resulted in a significant and dose­dependent increase in the expression of Septin4, as well as the expression levels of glucose­regulated protein (GRP)78, GRP94 and cleaved caspase­3. Furthermore, osteoblasts were overexpressed with Septin4 and the mechanism via which melatonin induces osteoblast ERS was demonstrated to be via the regulation of Septin4. In addition, it was indicated that cytoskeleton destruction, cell morphology changes and the decrease in the number of cells were aggravated after osteoblasts were overexpressed with Septin4, as indicated by phalloidin and DAPI staining. Collectively, the present results suggest that the Septin4 protein may be a target of ERS in melatonin­induced osteoblast apoptosis, which is involved in bone metabolism diseases, thus providing novel evidence for clinical melatonin treatment of IS.

20.
Life Sci ; 257: 118044, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622944

RESUMO

AIMS: High-dose glucocorticoid (GC) administration causes osteoporosis. Many previous studies from our group and other groups have shown that melatonin participates in the regulation of osteoblast proliferation and differentiation, especially low concentrations of melatonin, which enhance osteoblast osteogenesis. However, the role of melatonin in glucocorticoid-induced osteoblast differentiation remains unknown. MATERIALS AND METHODS: An examination of the expression of osteoblast differentiation markers (ALP, OCN, COLL-1), as well as alkaline phosphatase staining and alkaline phosphatase enzymatic activity assay to measure osteoblast differentiation and quantifying Alizarin red S staining to measure mineralization, were performed to determine the effects of dexamethasone (Dex) and melatonin on the differentiation of MC3T3-E1 cells. We used immunofluorescence staining to detect the expression of Runx2 in melatonin-treated MC3T3-E1 cells. The expression of mRNA was determined by qRT-PCR, and protein levels were measured by western blotting. KEY FINDINGS: In the present study, we found that 100 µM Dex significantly reduced osteoblast differentiation and mineralization in MC3T3-E1 cells and that 1 µM melatonin attenuated these inhibitory effects. We found that only inhibition of PI3K/AKT (MK2206) and BMP/Smad (LDN193189) signalling abolished melatonin-induced differentiation and mineralization. Meanwhile, MK2206 decreased the expression of P-AKT and P-Smad1/5/9 and LDN193189 decreased the expression of P-Smad1/5/9 but had no obvious effect on P-AKT expression in melatonin-treated and Dex-induced MC3T3-E1 cells. SIGNIFICANCE: These findings suggest that melatonin rescues Dex-induced inhibition of osteoblast differentiation in MC3T3-E1 cells via the PI3K/AKT and BMP/Smad signalling pathways and that PI3K/AKT signalling may be the upstream signal of BMP/Smad signalling.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Melatonina/metabolismo , Osteoblastos/metabolismo , Animais , Biomineralização/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Linhagem Celular , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Melatonina/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo
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