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Mesenchymal stem/stromal cells (MSCs) reside in the perivascular niche and modulate tissue/organ homeostasis; however, little is known about whether and how their localization and function are linked. Particularly, whether specific MSC subsets couple with and regulate specialized vessel subtypes is unclear. Here, we show that Gli1+ cells, which are a subpopulation of MSCs couple with and regulate a specialized form of vasculature. The specific capillaries, i.e., CD31hiEMCNhi type H vessels, are the preferable vascular subtype which Gli1+ cells are adjacent to in bone. Gli1+ cells are further identified to be phenotypically coupled with type H endothelium during bone growth and defect healing. Importantly, Gli1+ cell ablation inhibits type H vessel formation associated with suppressed bone generation and regeneration. Mechanistically, Gli1+ cells initiate angiogenesis through Gli and HIF-1α signaling. These findings suggest a morphological and functional framework of Gli1+ cells modulating coupled type H vasculature for tissue homeostasis and regenerative repair.

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target.

The purpose of this study was to investigate the relationship between the dental calcification stage (DCS) of the mandibular teeth and the cervical vertebral maturation stage (CVMS) in patients with unilateral complete cleft lip and palate (UCLP). One hundred sixty-two UCLP patients (100 males and 62 females) between 8–16 years old were included in this study. The DCS was estimated by the Demirjian method and was converted to the dental age (DA). The CVMS was evaluated by the Baccetti method. The DA of mandibular teeth on two sides of the cleft were analyzed using a t-test. Spearman correlation was used to study the association between CVMS and DCS. The correlation coefficient between the two sides of the cleft was then compared. The total DA was significantly smaller on the cleft side than on the noncleft side in males (p = 0.022). The Spearman rank correlation coefficient revealed a significant correlation between the DCS of each examined tooth and the CVMS (r = 0.627–0.793 in males and r = 0.806–0.899 in females). Additionally, the correlation of the two sides was not significantly different (p > 0.05). The DCS of the first premolar showed the strongest correlation with the CVMS. The results confirm the utility of the DCS on both sides of the mandible in male UCLP patients as a simple first-level diagnostic test to evaluate growth and development. The findings also indicate that both the DCS and the CVMS should be assessed if the maturity stage of a growing UCLP patient is relevant to clinical practice.

Processed walnuts including hot air-dried and roasted walnuts were prepared. Volatiles in raw and processed walnuts were analyzed using head-space solid phase microextraction combined with gas chromatography and mass spectrometry. Oxidative stability of hot air-dried walnuts in different antioxidants, with or without vacuum package was studied to find a proper package for oxidation stability of hot air-dried walnuts. The results showed that there were 14 volatiles in raw walnuts, 28 in hot air-dried walnuts and 38 in roasted walnuts. The changes of oil quality indices, total phenols, malondialdehyde and free radical scavenging activities during storage at 60 °C showed that the oil oxidation increased with storage time. The addition of antioxidants and vacuum package could slow down the oxidation. Vacuum aluminum foil package (14 × 20 cm) can delay the oil oxidation and extend the shelf life to ~ 230 days of hot air-dried walnuts at 20 °C. With added antioxidant this was extended to ~ 257 days. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13197-020-04305-9) contains supplementary material, which is available to authorized users.

In view of the fact that the existing methods are easy to be affected by nonlinear factors in the incident process of the light source, resulting in the received shock wave inconsistent with the reality and large calculation error, a two-color laser field imaging waveform simulation and enhancement method based on the Internet of things is proposed. According to the automatic transformation characteristics of augmented reality technology, the waveform simulation control process of two-color laser field imaging is constructed. The Gaussian distribution characteristics are used to analyze the target, the optical grid and double oscillation device are used to control the results, the spectrum Fourier transform is used to adjust the phase of the waveform, and finally the simulated modulated laser waveform is output. Through the comparison of laser waveform spectrum and peak value, the results show that this method is closest to the actual laser waveform, saves calculation time, and has good practical application effect.

Innervation and extracellular vesicle secretion co-exist in the local tissue microenvironment for message transfer, but whether they are interconnected to regulate organ homeostasis remains unknown. Sympatho-adrenergic activation is implicated in stress-induced depression and leads to bone loss, but the mechanisms and therapeutics are incompletely elucidated. Here, it is revealed that sympathetic neurostress through the β

Patients with persistent positive hepatitis B surface antigen (HBsAg), even with a low HBV-DNA load, have a higher risk of hepatocellular carcinoma (HCC) than those without HBV infection. Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms, this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA, and to explore underlying mechanisms.We screened out miR-203a, the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study.MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis. The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells. We demonstrated the function of miR-203a in inhibiting HCC cell proliferation, migration, clonogenic capacity, and tumor developmentHBsAg may promote the development of HCC and tumor stemness by inhibiting miR-203a, resulting in poor prognosis. miR-203a may serve as a crucial treatment target in HBsAg-positive HCC. More explicit mechanistic studies and animal experiments need to be conducted as a next step.

Deep metric learning methods aim to transform data features from original scattered space to a discriminative subspace in an end-to-end way, and they have shown promising results on wide applications. Triplet loss functions are the most popular models to tackle deep metric learning problem as they simultaneously enhance separability between different classes and compactness of each class in the embedded subspace. Therefore, effective triplets selection is crucial to the classification performance. However, most of these methods only focus on mining hard negative pairs, which refer to the nearest sample pairs of different classes, while fail to take subtle cluster structure of each class into consideration. To take such information into the metric learning model, a novel scheme based on subtype fuzzy clustering is proposed in this paper. By defining a new clustering degree, we conduct fuzzy clustering for each class to mine classification-oriented subtype structure. The new clustering degree is inversely proportional to the pairwise distance, thus, we can choose the positive pairs of the highest clustering degrees directly based on the farthest distances within each class. This new sampling approach avoids off-line clustering step, for which the network weights update procedure has to be temporarily paused. In other words, our method builds positive pairs without explicit clustering degree computation or off-line clustering. Our method inputs the selected positive pairs and negative pairs into the standard triplet loss to achieve network feature learning. Experimental results show competitive metric learning performance on three benchmark datasets.

PURPOSE To assess the potential role of amphiregulin as messenger molecule in ocular axial elongation. METHODS The experimental study included guinea pigs (total n = 78) (age: 3-4 weeks) which underwent bilateral lens-induced myopization and received 15 days later three intraocular injections in weekly intervals of amphiregulin antibody (doses:5 μg, 10 μg, 20 μg) into their right eyes, and three phosphate-buffered saline injections into their left eyes; and guinea pigs without lens-induced myopization and which received three unilateral intraocular injections of amphiregulin antibody (dose: 20 μg) or amphiregulin (doses: 1 ng; 10 ng; 20 ng) into their right eyes, and three phosphate-buffered saline injections into their left eyes. Seven days later, the animals were sacrificed. Intravitally, we performed biometry, and histology and immunohistochemistry post-mortem. RESULTS In animals with bilateral lens-induced myopization, the right eyes receiving amphiregulin antibody showed reduced axial elongation in a dose-dependent manner (dose: 5 μg: side difference: 0.14 ± 0.05 mm;10 μg: 0.22 ± 0.06 mm; 20 μg: 0.32 ± 0.06 mm; p

The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared β-Ga2O3:Cr3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga2O3) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods: I-TPGS/Ga2O3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga2O3/TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga2O3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga2O3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga2O3/TIG were finally evaluated using acute pneumonia mice. Results: It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga2O3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo. Additionally, targeted delivery of I-TPGS/Ga2O3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion: It is of great value to apply I-TPGS/Ga2O3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.

In this work, we have searched for quasi-periodic oscillations (QPOs) in the 15 GHz light curve of the FSRQ PKS J0805--0111 monitored by the Owens Valley Radio Observatory (OVRO) 40 m telescope during the period from 2008 January 9 to 2019 May 9, using the weighted wavelet Z-transform (WWZ) and the Lomb-Scargle Periodogram (LSP) techniques. This is the first time to search for a periodic radio signal in the FSRQ PKS J0805–0111 by these two methods. Both methods consistently reveal a repeating signal with a periodicity of 3.38 ± 0.8 yr (>99.7% confidence level). In order to determine the significance of the periods, the false alarm probability method was applied, and a large number of Monte Carlo simulations were performed. As possible explanations, we discuss a number of scenarios including the thermal instability of thin disks scenario, the spiral jet scenario and the binary supermassive black hole scenario. We expect that the binary black hole scenario, where the QPO is caused by the precession of binary black holes, is the most likely explanation. FSRQ PKS J0805-0111 thus could be a good binary black hole candidate. In the binary black hole scenario, the distance between the primary black hole and the secondary black hole is about 1.71 × 1016 cm.

Background The modified polycystic ovary syndrome health-related quality-of-life questionnaire (MPCOSQ) is a 30-item instrument measuring quality-of-life in English-speaking patients with polycystic ovary syndrome (PCOS). We aimed to: 1) cross-culturally adapt the MPCOSQ into Chinese, and 2) assess the validity and reliability of the Chinese version of the MPCOSQ (Chi-MPCOSQ). Methods The MPCOSQ was translated using the forward-backward method, and its validity and reliability were assessed among 283 Chinese patients with PCOS. Internal consistency reliability and test-retest reliability were assessed by Cronbach’s α and intra-correlation coefficient (ICC), respectively. Construct validity was tested through exploratory factor analysis and confirmatory factor analysis. Discriminant validity was assessed by Mann-Whitney U test to compare the scores on the Chi-MPCOSQ between 283 women with PCOS and 93 women without PCOS. Results Exploratory factor analysis generated a 7-factor structure of the 30-item version of the Chi-MPCOSQ, which accounted for 77% of the overall variance. The Chi-MPCOSQ had high internal consistency (Cronbach’s α = 0.88) and good test-retest reliability (ICC = 0.89). Compared to PCOS patients, women without PCOS had consistently lower scores for every dimension of the Chi-MPCOSQ, demonstrating its good discriminant validity. Conclusion The Chi-MPCOSQ is a valid and reliable instrument for measuring quality-of-life among Chinese women with PCOS.

Summary Mesenchymal stem/stromal cells (MSCs) reside in the perivascular niche and modulate tissue/organ homeostasis; however, little is known about whether and how their localization and function are linked. Particularly, whether specific MSC subsets couple with and regulate specialized vessel subtypes is unclear. Here, we show that Gli1+ cells, which are a subpopulation of MSCs couple with and regulate a specialized form of vasculature. The specific capillaries, i.e., CD31hiEMCNhi type H vessels, are the preferable vascular subtype which Gli1+ cells are adjacent to in bone. Gli1+ cells are further identified to be phenotypically coupled with type H endothelium during bone growth and defect healing. Importantly, Gli1+ cell ablation inhibits type H vessel formation associated with suppressed bone generation and regeneration. Mechanistically, Gli1+ cells initiate angiogenesis through Gli and HIF-1α signaling. These findings suggest a morphological and functional framework of Gli1+ cells modulating coupled type H vasculature for tissue homeostasis and regenerative repair., Highlights • Gli1+ cells regulate the neighbored specialized vessels in bone • Upon bone defect Gli1+ cells emerge and induce type H vessel formation for healing • Gli1+ cell ablation reduces type H vessels associated with suppressed osteogenesis • Gli and HIF-1α signaling mediate Gli1+ cell regulation of endothelial angiogenesis, In this article, Jin and colleagues show that skeletal Gli1+ cells represent a subpopulation of MSCs characterized by perivascular location, which spatially and phenotypically couple with a neighbored specialized vessel subtype, i.e., type H vessels. Functionally, Gli1+ cell-mediated regulation of type H vessel formation is indispensable for bone growth and regeneration.

To assess the dimensions of Brucke’s muscle, as the longitudinal portion, and of Muller’s muscle and Iwanoff’s muscle combined as circular and radial/reticular portions of the ciliary muscle. The histomorphometric study included human globes that had been enucleated due to an ocular tumor or end-stage glaucoma. After immunohistochemical staining of the ciliary muscles, the histology slides were examined under a light microscope applying a digitized image analysis system. The study included 55 globes [axial length 25.6 ± 3.0 mm (range 21.0 mm–36.0 mm)] from 55 patients [mean age, 33.7 ± 18.3 years (range:1–66 years)]. Length of Brucke’s muscle (mean 3.40 ± 0.76 mm) increased with longer axial length (P

Purpose To compare the benefits and harms of radiofrequency ablation (RFA) and hepatic resection (HR) and to test the consistency of currently available evidence. Materials and Methods PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared the effects of HR and RFA for Barcelona Clinic Liver Cancer very early or early stage hepatocellular carcinoma (HCC). The primary outcome was overall survival, and secondary outcomes were recurrence rate, complication rate, and hospitalization duration. A random- or fixed-effects model according to the level of heterogeneity was applied. The meta-analysis was performed by using software, and trial sequential analysis (TSA) was performed. Results Five trials examining 742 patients were included in this study (sizes of trials: 161, 230, 168, 120, and 63 patients). The meta-analysis showed that RFA and HR had similar overall survival at 1 year (relative risk [RR], 1.39; 95% confidence interval [CI]: 0.36, 5.33; P = .63) and 3 years (RR, 1.40; 95% CI: 0.75, 2.62; P = .29), whereas RFA resulted in decreased overall survival compared with HR at 5 years (RR: 1.91; 95% CI: 1.32, 2.79; P = .001). The TSA showed that more trials were needed to control random errors. The incidence of overall recurrence was markedly higher and the hospitalization duration was significantly shorter in the RFA group than in the HR group, which was confirmed by TSA. Complications may have been less frequent in the RFA group, but TSA showed that additional trials were necessary to confirm this conclusion. Conclusion The indication for RFA as a primary treatment for patients who are eligible for HR with early stage HCC is unclear, and additional well-designed RCTs are needed. © RSNA, 2017 Online supplemental material is available for this article.

Background The main causes of intracerebral hemorrhage differ between young adults and older adults. Data regarding potential targets for early intervention in young adult patients with intracerebral hemorrhage are lacking. Methods We retrospectively analysed data for 196 young adult patients with intracerebral hemorrhage who were admitted to Tianjin Huanhu Hospital and died within 30 days of admission between June 2005 and June 2015. The Kaplan–Meier method was used to calculate survival rate, and the log-rank test was used to determine survival rate significance. A Cox proportional hazards regression model was used for univariate and multivariate analyses. Results Univariate analysis revealed a statistically significant association of age, disturbance of consciousness, National Institutes of Health Stroke Scale and Glasgow Coma Scale scores, seizure occurrence, infratentorial hemorrhage, intraventricular extension, hernia, glucose level, white blood cell count, albumin level, creatinine level, uric acid level, and surgical treatment with early mortality (P Conclusions Our results suggest that young adult patients who exhibit infratentorial hemorrhage and intraventricular extension in the early stages of intracerebral hemorrhage onset exhibit an increased risk of early mortality.

Glioma, with varying malignancy grades and histological subtypes, is the most common primary brain tumor in adults. Long noncoding RNAs (lncRNAs) are non-protein-coding transcripts and have been proven to play an important role in tumorigenesis. Our study aims to elucidate the combined effect of lncRNA maternally expressed gene 3 (MEG3) and microRNA-19a (miR-19a) in human glioma U87 and U251 cell lines. Real-time PCR revealed that MEG3 was downregulated and miR-19a was upregulated in malignant glioma tissues and cell lines. Bioinformatics analyses (TargetScan, miRanda, and starBase V2.0) showed that phosphatase and tensin homolog (PTEN) is a target of miR-19a with complementary binding sites in the 3′-UTR. As expected, luciferase results verified the putative target site and also revealed the complementary binding between miR-19a and MEG3. miR-19a represses the expression of PTEN and promotes glioma cell proliferation, migration, and invasion. However, MEG3 could directly bind to miR-19a and effectively act as a competing endogenous RNA (ceRNA) for miR-19a to suppress tumorigenesis. Our study is the first to demonstrate that lncRNA MEG3 suppresses glioma cell proliferation, migration, and invasion by acting as a ceRNA of miR-19a, which provides a novel insight about the pathogenesis of glioma.

Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored. Here, HCC cells underwent heat treatment and were cultured under hypoxic conditions to mimic the aforementioned situation, and morphological changes were observed in the surviving cells. Compared with their parental cells, hypoxic HCC cells showed changes that include enhanced invasive, metastatic, and chemoresistant abilities as well as mesenchymal characteristics. There was also a higher percentage of stem-like cells. However, either improving the hypoxic microenvironment or silencing hypoxia inducible factor (HIF)-1α signaling significantly reduced the invasive, metastatic, and chemoresistant potential and reversed the epithelial-mesenchymal transition to varying degrees. Together, these results indicated that a sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF-1α signaling might be effective strategies for patients who experience insufficient RFA therapy.

To investigate the symmetry of nasal maxillary complex in the three-dimensional directions of patients with unilateral complete cleft lip and palate(UCLP) at the stage of mixed dentition.Craniofacial cone-beam CT(CBCT) images of 20 UCLP patients at the stage of mixed dentition were selected. Three-dimensional reconstruction of bone tissue was carried out by Mimics software, nasal root point and 32 markers with the same name of the healthy side and the cleft side of the nasal maxillary complex were traced, three-dimensional reference planes were set up, then the distances between the points to the three-dimensional planes were measured respectively. SPSS 22.0 software package was used to analyze the data.In the horizontal direction, compared with the non-cleft side, the width of the cleft side of the maxilla at INM and SPC was smaller, the width of maxilla at LPA and SPr was larger, the differences were statistically significant (P0.05). In the sagittal direction, compared with the non-cleft side, the depth of LPA, Maz and SPr at the cleft side was larger, the depth of SPM and SPC was smaller, the differences were statistically significant (P0.05).In the vertical direction, the positions of LPA, INM and Maz at the cleft side was lower than the non-cleft side, SPC and SPr were higher, the differences were statistically significant(P0.05). The remaining points had no significant difference (P0.05).The nasal maxillary complex of UCLP patients at the stage of mixed dentition is asymmetric in three directions. The asymmetric locations were mainly located in the nasal cavity and alveolar bone. No obvious asymmetry is found in the orbital region and the maxillary region far from the cleft.

In this paper, the stability of networked control systems with channel noise, bandwidth, packet dropouts and delay constraints are studied. The stability of networked control system is analyzed by frequency domain method. The performance of a communication network is reflected by time delay, noise, packet dropouts and network bandwidth. By frequency domain analysis and spectrum decomposition technique, the minimum SNR expression of stable networked control systems is obtained. In addition, the minimum value of system stability is determined by the time delay, packet dropouts, bandwidth of the communication network, and the locations of unstable poles and non-minimum phase zeros of the given model. The final results show the relationship between the stability of the networked control systems, the structural characteristics of the given model (such as the position of non-minimum phase zero and unstable poles) and the parameters of the communication network (delay, packet dropouts and bandwidth). Finally, the effectiveness of the proposed method is illustrated by a numerical example.