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Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin−) cells. PBMCs and Lin− cells were cocultured with induced pluripotent stem cell‐derived MSCs (iPSC‐MSCs) under the stimulation of epithelial cytokines IL‐25 and IL‐33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS‐ICOSL pathway. iPSC‐MSCs successfully decreased the high levels of IL‐13, IL‐9, and IL‐5 in PBMCs in response to IL‐25, IL‐33, and the high percentages of IL‐13+ILC2s and IL‐9+ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC‐MSCs. However, iPSC‐MSCs were found directly to enhance ILC2 levels and functions via ICOS‐ICOSL interaction in Lin− cells and pure ILC2s. iPSC‐MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS‐ICOSL interaction. The MSC‐induced Treg cells then suppressed ILC2s by secreting IL‐10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS‐ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders., Human mesenchymal stem cells (MSCs) either directly promote group 2 innate lymphoid cell (ILC2) activation through upregulated ICOS‐ICOSL interaction. MSCs exert inhibitory effects on ILC2s via activating regulatory T (Treg) cells through ICOS‐ICOSL interaction. Treg cells prevent the promotion of MSCs on ILC2s via decreased ICOS‐ICOSL interaction between MSCs and ILC2s. IL‐10 is required for the MSC‐induced Treg cells in suppressing ILC2s alongside ICOS‐ICOSL interaction.

Commercially pure titanium (CP-Ti) has seen major applications in biomedical equipment. The use of selective laser melting (SLM) has become more common concerning the fabrication of CP-Ti components with a complicated shape in biomedical implants, where high strength and ductility are required. However, SLM manufactured CP-Ti often exhibits high strength and low ductility, as well as mechanical anisotropy because SLM process typically results in the formation of long columnar grains comprising of fine acicular α′ martensite. Heat treatment must be preceded to transform the acicular α′ to equiaxed α grain. This study demonstrated that annealing at 650 °C of SLM CP-Ti can create an equiaxed structure, resulting in a weakened texture. The formation of equiaxed grains occurred at two types of microstructural features, acicular α′ and irregular massive (α′m) martensite, which exhibited different sizes, morphologies, and contained different types of substructures under SLM as-fabricated condition. The formation mechanism of equiaxed grains in the α′ region is dominated by the coalescence of acicular α′ of the same variant and the dissolution of α′ into the matrix, whereas the formation mechanism in the α′m region is primarily dominated by the growth of the preexisting subgrains. A small number of equiaxed grains with new orientations were formed in the α′m region. The majority of equiaxed grains were formed in the acicular α′ region and inherited the grain orientations of the preexisting α′ or matrix. Therefore, a similar but weakened texture was inherited from the microstructure of the SLM CP-Ti after annealing.

BACKGROUND Surgical resection is regarded as the only potentially curative treatment option for patients with metastatic colorectal cancer (CRC). The National Comprehensive Cancer Network clinical practice guidelines do not recommend palliative surgery unless there is a risk of severe symptoms. However, accumulating evidence has shown that palliative surgery is associated with more favorable outcomes for patients with metastatic CRC. AIM To investigate the separate role of palliative primary tumor resection for patients with stage IVA (M1a diseases) and stage IVB (M1b diseases) colorectal adenocarcinoma (CRA). METHODS CRA patients diagnosed from 2010 to 2015 with definite M1a and M1b categories according to the 8th edition of American Joint Committee on Cancer staging system were selected from the Surveillance Epidemiology and End Results (SEER) database. To minimize potential selection bias, the data were adjusted by propensity score matching (PSM). Baseline characteristics, including gender, year of diagnosis, age, marital status, primary site, surgical information, race, grade, chemotherapy, and radiotherapy, were recorded and analyzed. Univariate and multivariate analyses were performed to explore the separate role of palliative surgery for patients with M1a and M1b diseases. RESULTS A total of 19680 patients with metastatic CRA were collected from the SEER database, including 10399 cases of M1a diseases and 9281 cases of M1b diseases. Common independent prognostic factors for both M1a and M1b patients included year of diagnosis, age, race, marital status, primary site, grade, surgery, and chemotherapy. After PSM adjustment, 3732 and 3568 matched patients in the M1a and M1b groups were included, respectively. Patients receiving palliative primary tumor resection had longer survival time than those without surgery (P < 0.001). For patients with M1a diseases, palliative resection could increase the median survival time by 9 mo; for patients with M1b diseases, palliative resection could prolong the median survival time by 7 mo. For M1a diseases, patients with lung metastasis had more clinical benefit from palliative resection than those with liver metastasis (15 mo for lung metastasis vs 8 mo for liver metastasis, P < 0.001). CONCLUSION CRA patients with M1a diseases gain more clinical benefits from palliative primary tumor resection than those with M1b diseases. Those patients with M1a (lung metastasis) have superior long-term outcomes after palliative primary tumor resection.

We used selective laser melting (SLM) to produce a three-dimensional specimen of pure Ti and found that an equiaxed grain structure and weak crystallographic texture could be achieved simultaneously via subsequent heat treatment. These traits have never been attained simultaneously in pure Ti prepared by traditional methods such as casting and rolling. This remarkable achievement was possible because recrystallization occurred during heat treatment without plastic deformation; such deformation introduces stored energy that drives recrystallization but inevitably causes a strong texture to develop. The occurrence of recrystallization was attributed to unique features of the SLM process including a very high cooling rate and repetitive layer stacking. These features generated considerable stored energy by affecting solidification and the β → α phase transformation. Steep in-grain orientation gradients and a fine lath structure also contributed to the activation of recrystallization by facilitating recrystallization nucleation. The heat-treated specimen showed tensile properties with significantly reduced anisotropy. This finding will provide new strategies for developing isotropic metallic materials and may introduce new applications of SLM.

Bimodal grain structures are often produced in a metal by employing severe plastic deformation followed by low-homologous-temperature annealing (≤0.4Tm, where Tm is melting temperature). Here, a bimodal grain structure was achieved in a Co–20Cr–15W–10Ni–C superalloy via moderate cold rolling (strain ≈0.3) and ultrahigh-homologous-temperature annealing (≥0.8Tm). During annealing, carbide-assisted heterogeneous static-recrystallization played a key role in forming the bimodal grain structure. A 40% increase in combined strength and ductility was observed.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulated epigenome has been linked to increased susceptibility to age-related disorders. We aim to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. In this study, we focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed redistribution of of both histone marks, but the changes are more significant for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed “aging-associated repressive domains” (AARDs). These AARDs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Interestingly, maintenance of high H3K9me2 levels in these regions have been shown to correlate with longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear elements (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals, it is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.Author summaryHeterochromatin refers to the portion of the genome that is tightly packed where genes stay silent. Heterochromatin is typically decorated by particular chemical groups called histone modifications, such as trimethylation of lysine 9 or lysine 27 on histone 3 (H3K9me3 or H3K27me3). To understand how the heterochromatin landscape may change from a “youthful” to an “aged” state, we monitored the genome-wide patterns of H3K9me3 and H3K27me3 during aging using the genetic model soil worm C. elegans. We found that while H3K27me3 remained relatively stable with age, H3K9me3 showed profound genome-wide redistribution in aged worms. We observed that new H3K9me3-marked heterochromatin preferentially formed in specific gene-rich regions in aged worms. Interestingly, these particular regions were marked by high levels of three other histone modifications when worms were young. This result suggested that H3K9me3 gain during aging is influenced by the gene-specific landscape of histone modifications established at young age rather than occurs in a stochastic manner. In summary, our study discovered reproducible and gene-specific changes in histone modifications that likely contribute to the aging phenotypes.

Background To explore the dynamic distribution of pupil size and center,the eccentricity distribution of angle kappa, and its correlation with other biomechanics about suitable for excimer laser refractive surgery. Methods Randomly selected 225 patients (407 eyes) who underwent femtosecond laser combined with excimer laser in situkeratomileusis,preoperative use of Wavelight Allegro Topolyzer Corneal Topography ( Wavelight Laser Technologies AG, Erlangen, Germany ) to measure the pupil size and center position, the German Wavelight EX500 excimer Laser (500Hz) records the deviation between the pupil center and the coaxially sighted corneal light reflex when the patient is supine. Results The average displacement distribution of P-Dist (the eccentricity between the pupil center and the coaxially sighted corneal light reflex point) is 0.225 ± 0.102 mm, and 80% of the eyes are ≤ 0.30 mm.The coaxially sighted corneal light reflex point is mainly deviated to the superior temporal side of the corneal center (34%).Under the dark light condition, the x-axis of the left eye was: -0.046 ± 0.091 mm, the x-axis of the right eye was: -0.152 ± 0.084 mm, with statistical difference ( P = 0.015) (the right eye shifted to the temporal side), the y-axis direction had no statistical change ( P = 0.062). The WTW was positively correlated with changes of pupil diameter (dark pupil diameter-bright pupil diameter) ( r = 0.270, P

Background Several studies probed into the connection between esophageal cancer (EC) risk and PRKAA1 rs13361707 C/T polymorphism, but obtained insignificant findings. Methods In this study, 814 EC cases and 961 controls from Eastern China were recruited to validate the relationship between this polymorphism and EC susceptibility. Results Data suggested rs13361707 C/T polymorphism in PRKAA1 gene was significantly related with a lower risk for EC. Such significant connection was also uncovered in subgroups of males, smokers, drinkers and individuals with age ≥ 60 years. In addition, this polymorphism was linked with the pathological grading, distant metastasis, and histology of EC. Conclusion In summary, PRKAA1 rs13361707 C/T polymorphism is related to the risk and clinical properties of EC patients in East China.

Background Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. Methods The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. Results The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. Conclusion The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

We have performed quantitative analysis of {332}〈113〉 twinning in a β-Ti-15Mo (wt.%) alloy by in situ scanning electron microscopy and electron backscattering diffraction (EBSD). Microstructure-twinning relations were evaluated by statistical analysis of the evolving twin structure upon deformation at room temperature. Our analysis reveals that at the early stages of deformation (ε < 1.5 to 2.0%), primary twinning is mainly determined by the applied macroscopic stress resolved on the twin system. Most of the primary twins (~70–80% of the analyzed twins) follow Schmid’s law with respect to the macroscopic stress, and most of the growth twins (~ 85% of the analyzed twins) correspond to the higher stressed variant. In the grain size range studied here (40–120 μm), we find that several twin parameters such as number of twins per grain and number of twins per grain boundary area exhibit grain size dependence. We ascribe these effects to the grain size dependence of twin nucleation stress and apparent critical resolved shear stress for twinning, respectively.

Background Human induced pluripotent stem cells-derived mesenchymal stem cells (iPSC-MSCs) have been shown to be effective in Type 2 helper T cells (Th2)-dominant eosinophilic allergic airway inflammation. However, the role of iPSC-MSCs in Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation remains poorly studied. Therefore, this study was to explore the effects of iPSC-MSCs on an experimental mouse model of steroid-resistant neutrophilic airway inflammation and further determine the underlying mechanisms. Methods A mouse model of neutrophilic airway inflammation was established using ovalbumin (OVA) and lipopolysaccharide (LPS). Human iPSC-MSCs were systemically administered, and the lungs or bronchoalveolar lavage fluids (BALF) were collected at 4 h and 48 h post-challenge. The pathology and inflammatory cell infiltration, the T helper cells, T helper cells-associated cytokines, nuclear transcription factors and possible signaling pathways were evaluated. Human CD4+ T cells were polarized to T helper cells and the effects of iPSC-MSCs on the differentiation of T helper cells were determined. Results We successfully induced the mouse model of Th17 dominant neutrophilic airway inflammation. Human iPSC-MSCs but not dexamethasone significantly prevented the neutrophilic airway inflammation and decreased the levels of Th17 cells, IL-17A and p-STAT3. The mRNA levels of Gata3 and RORγt were also decreased with the treatment of iPSC-MSCs. We further confirmed the suppressive effects of iPSC-MSCs on the differentiation of human T helper cells. Conclusions iPSC-MSCs showed therapeutic potentials in neutrophilic airway inflammation through the regulation on Th17 cells, suggesting that the iPSC-MSCs could be applied in the therapy for the asthma patients with steroid-resistant neutrophilic airway inflammation. Electronic supplementary material The online version of this article (10.1186/s13287-018-0897-y) contains supplementary material, which is available to authorized users.

Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed “aging-specific repressive regions” (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology., Author summary Heterochromatin refers to the portion of the genome that is tightly packed where genes stay silent. Heterochromatin is typically decorated by particular chemical groups called histone modifications, such as trimethylation of lysine 9 or lysine 27 on histone 3 (H3K9me3 or H3K27me3). To understand how the heterochromatin landscape may change from a "youthful" to an "aged" state, we monitored the genome-wide patterns of H3K9me3 and H3K27me3 during aging using the genetic model soil worm C. elegans. We found that while H3K27me3 remained relatively stable with age, H3K9me3 showed substantial gain and loss at specific loci in aged worms. We observed that new H3K9me3-marked heterochromatin preferentially formed in specific gene-rich regions in aged worms. Interestingly, these particular regions were marked by high levels of three other histone modifications when worms were young. This result suggested that H3K9me3 gain during aging is influenced by the gene-specific landscape of histone modifications established at young age rather than that it occurs in a stochastic manner. In summary, our study discovered reproducible and gene-specific changes in histone modifications that likely contribute to the aging phenotypes.

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of long non-coding RNA (lncRNA) in mouse fibroblasts L929 cell line. Methods L929 cells were cultured in vitro and randomly divided into simulated microgravity (SMG) group and normal gravity (NG) group. Each group had three samples, the rotator axis of SMG group was paralleled to the ground rotation, while the rotator axis of NG group was vertical to the ground rotation, and the speed of rotation was consistent for the two groups. The samples of two groups were collected on 7th day of culture and the total RNAs were extracted, labeled and hybridized in sequence. The lncRNA and mRNA were detected by Agilent Mouse lncRNA Chips respectively. Differentially expressed lncRNA were identified and then validated by RT-qPCR. GO and Pathway analysis were applied to determine the functional distribution of these target genes. The integration predictions of the lncRNA and mRNA co-expression had been proposed to refine the functional lncRNA-mRNA relationships. Results There were 238 differentially ex-pressed lncRNAs including 134 lncRNAs up-regulated and 104 lncRNAs down-regulated, and 237 differentially expressed mRNAs including 53 mRNAs up-regulated and 184 mRNAs down-regulated significantly in mouse fibroblasts L929 cell line under simulated microgravity by RCCS. The RT-qPCR showed a high concordance with chip microarray results in 4 differentially expressed lncRNA. GO analysis showed that the differentially expressed lncRNAs were related to the biological processes such as negative regulation of megakaryocyte differentiation and negative regulation of wound healing. Pathway analysis showed that these target genes were related to the signal pathways of systemic lupus erythematosus and TGF-β. The lncRNA-mRNA co-expression networks were also established. Conclusion The simulated microgravity by RCCS could significantly affect the expression profiles of lncRNA and mRNA in mouse fibroblasts L929. The lncRNA target genes prediction and functional enrichment analysis based on gene chip technology may provide the theoretical basis for illustrating the mechanism and management of weightlessness stress injury. DOI: 10.11855/j.issn.0577-7402.2017.10.07

Backgrounds: Neratinib is a potent EGFR/HER2 kinase inhibitor. Gastrointestinal complications (i.e. diarrhea, vomiting and nausea) are the most common adverse events. In this study, we aimed to investigate (1) the overall incidence and relative risk (RR) of diarrhea, vomiting and nausea and (2) whether combination neratinib therapy increased the incidence of gastrointestinal complications versus neratinib alone. Methods: Relevant studies were identified from the PubMed database, from abstracts presented at the American Society of Clinical Oncology annual conference and from the Web of Science database. Incidences, RRs, and 95% confidence intervals (CIs) were calculated. Results: The incidences of all-grade diarrhea, vomiting and nausea in the neratinib groups were 89% (95% CI = 77–95%), 31% (95% CI = 25–37%) and 44% (95% CI = 33–55%), respectively. The neratinib arms significantly increased the risk of diarrhea and vomiting in comparison with the control groups (diarrhea: all-grade, RR = 2.06, 95% CI = 1.38–3.08, P = 0.0004; grade 3/4, RR = 8.77, 95% CI = 2.91–26.40, P = 0.0001; vomiting: all-grade, RR = 2.02, 95% CI = 1.10–3.71, P = 0.02; grade 3/4, RR = 7.10, 95% CI = 3.33–15.15, P Conclusions: Our meta-analysis demonstrates that the neratinib arms are associated with a significantly increased risk of diarrhea and vomiting.

We have studied {332} detwinning mechanism in a bcc-Ti–10Mo–xFe (x = 1–3 wt%) multilayered alloy upon annealing treatment at 900 °C by electron backscatter diffraction and electron channeling contrast imaging. Our analysis reveals that in the present material the detwinning process consists of two independent detwinning events that occur at two different microstructural regions, namely twin tips located at grain interiors and grain boundaries. Boundary dissociation reactions and mobilities were analyzed by tracking the evolution of the twin structure upon thermal annealing. We find that the first detwinning process is characterized by the evolution of incoherent twin boundaries into a Σ3 boundary and its subsequent migration. The second detwinning event is characterized by the detachment of the twin crystal from a grain boundary by the formation and migration of Σ11 {113} incoherent twin boundaries. Both detwinning modes can be explained from a thermodynamic standpoint where the boundary dissociation processes minimize the boundary free energy.

Purpose. To analyze the distribution of the offset between the pupil center and the coaxially sighted corneal light reflex (P-Dist), the effects of 50% and 100% angle kappa adjustments on refractive and visual quality in patients with moderate myopia were investigated. Methods. A randomly selected 254 patients (254 eyes) with moderate myopia who underwent femtosecond laser-combined LASIK were examined. During the operation, the P-Dist of the patients was recorded by the x- and y-axis eyeball-tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system. Preoperatively and 3 months postoperatively, the WaveLight® ALLEGRO Topolyzer was used to measure the pupil size and center position, and the wavefront sensor was used to measure the wavefront aberrations. The visual function tester (OPTEC 6500) measured contrast sensitivity. Results. The average P-Dist was 0.220 ± 0.102 mm. When the P-Dist >0.220 mm, the postoperative residual cylinder was 0.29 ± 0.34 D in the group with the 50% adjustment and 0.40 ± 0.32 D in the 100% group, which was significantly higher than the 50% group P = 0.036 . The coma was 0.21 ± 0.17 μm in the 50% adjusted group and 0.34 ± 0.25 μm in the 100% group, which was significantly higher than that in the 50% group P = 0.021 . At the 1.5 c/d spatial frequency, contrast sensitivity in the adjusted 100% group was significantly lower than that in the 50% group under visual glare conditions P = 0.039 . Conclusion. The postoperative visual acuity and spherical equivalent were not affected in the two groups. However, when P-Dist >0.220 mm, the residual astigmatism and coma were lower in the 50% group. Individualized operations for those with moderate myopia and large-angle kappa in which 100% adjustment is chosen may not result in a better visual quality effect than 50%.

Pigment epithelium-derived factor (PEDF) is an oncogene found in various types of cancers. However, how PEDF affects the development of human esophageal squamous cell carcinoma (ESCC) is unknown. This study investigates the role of PEDF in ESCC cell proliferation, migration, and cell cycle both in vitro and in vivo. The PEDF expression was examined in patient tumor samples and ESCC cell lines. Short hairpin RNA technology was used to inhibit the PEDF expression in ESCC EC9706 and KYSE150 cells. In vitro cell proliferation and migration assays were performed. The effects of PEDF on tumor growth and progression were examined in vivo in murine subcutaneous xenograft tumor models. It was found that PEDF was overexpressed in esophageal cancer cells and patient tumor tissues compared to normal control samples. PEDF enhanced cell cycle progression and inhibited cell apoptosis. Knock down of PEDF inhibited esophageal cell proliferation and migration in vitro. Moreover, Inhibition of PEDF significantly reduced tumor growth and tumor size in vivo. These results indicate that PEDF induce tumorigenesis in ESCC and can be a potential therapeutic target for cancer treatment.

Background: To investigate the characteristics and distribution of anterior and posterior surface wavefront aberrations in patients suitable for corneal refractive surgery. Methods: A total of 121 myopic patients (121 eyes, 14-46 years old) who underwent corneal refractive surgery were randomly selected by the Pentacam anterior segment analysis system with a spherical equivalent (SE) of -1.50 to -12.00 D. The corneal anterior and posterior aberrations (higher-order aberration, HOA; spherical aberration, SA; Coma; Trefoil) and Q and K values were detected, and a correlation analysis of the relevant parameters was carried out. Results: The root-mean-square (RMS) of the third to sixth order aberrations of the ocular and corneal wave surface aberrations at a 6.0-mm pupil showed a decreasing trend in patients suitable for the corneal refractive surgery, and the RMS of the third order aberrations accounted for 62.92% of the total HOAs. The coma ratio (coma ratio: coma/total cornea higher-order aberrations) was increased with the increasing diopters, while the spherical aberration ratio (spherical aberration/ total cornea higher-order aberrations) was not changed. In addition, the spherical aberration was 0.203± 0.082 μm (range: 0.061 to 0.503 μm), and the Q30 was -0.19±0.03 (range: -0.58 to 0.31). There were significant differences in the coma aberrations of preoperative corneal anterior surface (3, 1) between the low, middle and high myopia groups (P=0.013). The spherical equivalent was positively correlated with the corneal coma of the preoperative anterior corneal surfaces (R=-0.241, P=0.009), and the Q value was positively correlated with the total higher-order aberrations (R=0.326, P

Background To investigate the characteristics and distribution of anterior and posterior surface wavefront aberrations in patients suitable for corneal refractive surgery. Methods Sixty myopic patients (120 eyes, 14-46 years old) who underwent corneal refractive surgery were randomly selected by the Pentacam anterior segment analysis system with a spherical equivalent (SE) of -1.50 to -12.00 D. The corneal anterior and posterior aberrations (higher-order aberration, HOA; spherical aberration, SA; Coma; Trefoil) and Q and K values were detected, and a correlation analysis of the relevant parameters was carried out. Results The root mean square (RMS) values from 3 to 6 (RMS 3 to 6) of the whole eye higher-order wave surface aberrations at a 6.0 mm pupil diameter showed a decreasing trend in patients with corneal refractive surgery, and an RMS value of 3 accounted for 62.92% of the total HOAs. The coma ratio increased with increasing diopter, while the spherical aberration ratio was not changed. In addition, the spherical aberration was 0.203 ± 0.082 μm (range: 0.061 to 0.503 μm), and the Q30 was -0.19 ± 0.03 (range: -0.58 to 0.31), which showed a normal distribution. There were significant differences in coma aberrations (3, 1) in the low, middle and high myopia groups (P=0.013). The spherical equivalent was positively correlated with corneal coma (R = -0.241, P = 0.009), and the Q value was positively correlated with total higher-order as well as spherical aberrations (R = 0.326, P

Objective: To explore the influence of vascular endothelial function and inflammatory cytokines on patients with transumbilical single-port access laparoscopic cholecystectomy (TSPALC). Methods: A total of 86 cases with laparoscopic cholecystectomy, they were divided into single span treatment group (n=46) and normal group (n=40) according to the treatment. Patients in single span treatment group were treated with TSPALC, while patients in normal group were treated with normal LC. Surgery and postoperative recovery, tested and compared vascular endothelial function index: nitric oxide (NO), endothelin (ET) and inflammation factors: interleukin-6 (IL-6) and interleukin-8 (IL-8), high sensitivity C-reactive protein (hs-CRP) before and after surgery at different time points were compared. Results: VAS score at 6 h after surgery was similar between the two groups, while the VAS score at 12 h, 24 h after surgery in two groups were significantly reduce than 6h after surgery, and the VAS score at same point in single span treatment group were significantly lower than normal group, the difference had statistical significance (P0.05). Conclusions: The vascular endothelial function injury and inflammation stress are similar between normal LC and TSPALC, but TSPALC has small trauma. The postoperative pain is light, it’s worth clinical promotion positively.

Near alpha titanium alloys have been widely used in the aerospace industry owing to their high special strength, low-density and excellent corrosion resistance. Ti–3Al–2.5V is a typical near alpha titanium alloy that was usually used in the form of a tube in aircraft due to its excellent cold workability. In the present study, the microstructural evolution and detwinning behavior of cold-rolled Ti–3Al–2.5V alloy tubes during annealing were investigated. Upon annealing, the microstructure evolution strongly depends on the annealing temperature and holding time, which play important roles in the kinetics of the static recovery and recrystallization. In addition, there are two independent detwinning mechanisms involved during annealing. The first one is that detwinning occurs along the twin shear direction at grain boundaries, resulting in a shortening effect. The second one is that detwinning occurs in the center of twins, resulting in a thinning effect of twins. The understanding of the detwinning behavior and microstructural evolution during annealing helps with the tube processing and their applications in aircraft.

Background It has been demonstrated previously that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs) have immunosuppressive effects on activated T cells. However, the effects of iPSC-MSCs on quiescent T cells are still unknown. The aim of this study was to identify the immunomodulatory role of iPSC-MSCs on resting peripheral blood mononuclear cells (PBMCs) from allergic rhinitis (AR) patients. Methods PBMCs were cocultured with iPSC-MSCs without any stimulation, following which lymphocyte proliferation, activation of T cells, TH1/TH2 and regulatory T (Treg) cell differentiation, and Treg cell function were analyzed. The roles of soluble factors and cell–cell contact were examined to investigate the mechanisms involved. Results iPSC-MSCs promoted the proliferation of resting lymphocytes, activated CD4+ and CD8+ T cells, and upregulated and activated Treg cells without any additional stimulation. In addition, iPSC-MSCs balanced biased TH1/TH2 cytokine levels. Cell–cell contact was confirmed to be a possible mechanism involved. NF-κB was identified to play an important role in the immunomodulatory effects of iPSC-MSCs on quiescent T cells. Conclusions iPSC-MSCs activate quiescent T cells and elevate regulatory T-cell response in AR patients, suggesting different immunomodulatory functions of iPSC-MSCs according to the phases of diseases. Therefore, iPSC-MSCs are a potential therapeutic candidate for treating allergic airway inflammation. Electronic supplementary material The online version of this article (10.1186/s13287-018-0896-z) contains supplementary material, which is available to authorized users.

Accumulating evidence indicates that Nanog plays a central role in modulating the biological behaviors of human hepatocellular carcinoma (HCC). However, the underlying mechanisms remain unclear. In the present study, we employed transcription activator-like effector nucleases (TALEN) to disrupt Nanog expression in HepG2 cells and obtained subcloned cells with diallelic Nanog mutations. Significantly, we found that the expression of pluripotency factors Sox2, Oct4 and Klf4, as well as expression of cancer stem cell (CSC) marker CD133, in the Nanog-targeted HepG2 cells was markedly downregulated. This finding suggests that Nanog may play an important role in maintaining the pluripotency and malignancy of HepG2 cells. We also revealed that Nanog regulated cell proliferation by modulating the expression of cyclin D1/D3/E1 and CDK2, respectively. Additionally, the disruption of Nanog resulted in the downregulation of epithelial-mesenchymal transition (EMT) regulators Snail and Twist, which contributed to the elevated level of epithelial marker E-cadherin, and to the decreased level of mesenchymal markers N-cadherin and vimentin in the HepG2 cells. In addition, the Nanog-targeted HepG2 cells exhibited reduced ability of invasion, migration and chemoresistance in vitro. In conclusion, the disruption of Nanog expression results in less proliferation, invasiveness, migration, more chemosensitivity and reversal of EMT in HepG2 cells, by which Nanog plays crucial roles in influencing the malignant phenotype of HepG2 cells.

Objective To study the effect of cell-mediated immune suppression effect of rocket kerosene (RK) through dermal application in mice. Methods Skin delayed type hypersensitivity (DTH) was used to observe the relation of the RK amount the skin exposed and the cellular immune inhibitory function. Different amount of the undiluted fuel was smeared directly onto the dorsal skin of mice. Mice in negative and positive control groups were treated with acetone. After the last exposure, all the mice except those in negative control group were allergized by evenly smearing with 1% dinitrofluorobenzene (DNFB) solution on their dorsum. Five days after allergy, 1% DNFB solution was smeared onto right ear of all mice to stimulate the allergic reaction. Twenty-four hours after attack, the auricle swelling, spleen index and thymus index in corresponding mice were determined. In the first series of experiments, different dosages of RK were applied once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 1ml/kg.BW×1 and 2ml/kg.BW×1 group). In the second series of experiments, the certain and same dosage of RK was applied for different times, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 0.5mL/kg.BW×2, 0.5ml/kg.BW×3, 0.5ml/kg.BW×4 and 0.5mL/kg.BW×5 group). In the third series of experiments, the different dosages of RK were applied more than once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×5, 1ml/kg.BW×5 and 2ml/kg.BW×5 group). Lymphocyte proliferation experiment in vitrowas conducted to observe the persistent time of the cell-mediated immune suppression in mice by RK dermal exposure. The lymphocyte proliferation induced by concanavalin A (Con A) was analyzed by MTT assay, and T lymphocyte subsets (CD3+, CD4+ and CD8+) in peripheral blood and spleen lymphocyte cell cycle were analyzed by flow cytometry. Results RK dermal exposure (1ml/kg.BW×1) alleviated the ear edema, suppressed the spleen index elevation and thymus index reduction caused by DNFB sensitization in ICR mice, and the suppression effect increased with exposed dosage and time increasing. RK dermal exposure (1ml/kg.BW×1) suppressed ConAinduced spleen lymphocyte proliferation, and the effect persisted for 20d (P