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Abstract Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4+T cells but not CD8+T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4+T cells in HCC immune surveillance.

This study investigates a class of two-dimensional, two-parameter squared discrete dynamical systems. It determines the conditions for local stability at the fixed points for these proposed systems. Theoretical and numerical analyses are conducted to examine the bifurcation behavior of the proposed systems. Conditions for the existence of Naimark–Sacker bifurcation, transcritical bifurcation, and flip bifurcation are derived using center manifold theorem and bifurcation theory. Results of the theoretical analyses are validated by numerical simulation studies. Numerical simulations also reveal the complex bifurcation behaviors exhibited by the proposed systems and their advantage in image encryption.

Risdiplam is a new drug for treating spinal muscular atrophy (SMA). However, pharmacovigilance analyses are necessary to objectively evaluate its safety-a crucial step in preventing severe adverse events (AEs). Accordingly, the primary objective of the current study was to examine the AEs associated with risdiplam use based on real-world data obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. More specifically, we examined incidents reported between the third quarter of 2020 and the second quarter of 2023. The imbalance of risdiplam-related AEs was evaluated by computing the reporting odds ratio. A total of 5,406,334 reports were thoroughly reviewed. By removing duplicate reports, we identified 1588 reports in which risdiplam was the main suspected drug whose use was accompanied by 3470 associated AEs. Among the included AEs, 703 were categorized as serious and 885 as non-serious. Risdiplam use induced AEs across 18 organ systems, resulting in 130 positive signals. Notably, we detected new AE signals, including cardiac arrest, nephrolithiasis, tachycardia, loss of libido, and elevated hepatic enzyme activities; however, no ophthalmologic toxicity was reported. Although these new adverse reaction signals associated with risdiplam have been defined, long-term clinical studies are needed to confirm these findings. Nevertheless, our findings provide a valuable reference for improving the clinical management of SMA.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. Methods Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. Results We found that ccRCC tissues had higher levels of CD8+ T cells, CD163− macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell–cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. Conclusion Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.

Inspired by the collective behaviors of active systems in nature, the collective behavior of micromotors has attracted more and more attention in recent years. However, little attention has been paid to the collective behavior of the immobilized micromotor, i.e., the micropump. In this paper, a unique pentacene-based micropump is reported, which demonstrates dynamic collective behavior activated by white light irradiation. The light irradiation may generate the photochemical reactions between pentacene and water, leading to the electroosmotic flow. As a result, this micropump is capable of pumping the surrounding solution inward along the substrate surface based on the electroosmosis mechanism. Intriguingly, the inward pumping causes the agglomeration of the tracer particles on the surface of the micropump. In addition, the aggregation can migrate following the change in the light irradiation position between two adjacent micropumps. Based on the aggregating and migrating behaviors of this pentacene-based micropump, we have achieved the conductivity restoration of the cracked circuit.

Context Puerarin (Pue) and tanshinone IIA (Tan IIA) are often used in combination in the treatment of cerebrovascular diseases.Objective To investigate the neuroprotective effect and synergic mechanism of Pue-Tan IIA on the treatment of ischaemic stroke (IS).Materials and methods IS was induced in rats by middle cerebral artery occlusion (MCAO). Rats were intraperitoneally injected with Pue (36 mg/kg), Tan IIA (7.2 mg/kg), or Pue-Tan IIA (36 and 7.2 mg/kg) for five times [30 min before ischaemia, immediately after reperfusion (0 h), 24, 48, and 72 h after reperfusion]. After administration, neurological function assessment and histological changes in the brain were performed. S-100β and NSE levels were measured to determine the severity of brain injury. Oxidative stress parameters and inflammatory mediators were measured. The proteins involved in Nrf2/ARE signalling pathway were determined by qRT-PCR and western blot.Results After administration, the neurological function scores, infarct volume, S-100β, and NSE levels were significantly reduced in MCAO rats, especially with Pue-Tan IIA treatment (p

In this study, we investigated the effects of modified aging treatments on the microstructures and hardness in a commercial 6016 Al alloy through hardness tests and transmission electron microscopy (TEM) observations. The results demonstrate that many fine needle-like β″ phases contribute to the high hardness of peak-aged (T6) alloys. Over-aging treatments lead to the precipitation of lath-like β′, β″/disordered, or B′/disordered composite phases. Moderate over-aging treatment results in the coarsening of grain boundary precipitates (GBPs) and widening of the precipitate-free zone (PFZ), while heavy over-aging treatment triggers the re-precipitation of Cu-containing GBPs and increases the number density of GBPs. A retrogression and re-aging (RRA) treatment precipitates β″, lath-like β′, and disordered phases, while a two-step aging (T78) treatment precipitates β″, B′, and disordered phases. Both the T78 and the RRA treatments lead to the coarsening of GBPs and the widening of PFZs. The decreased hardness during over-aging treatments is attributed to a combination of coarsening intragranular precipitates and/or wider PFZs. The T78 and RRA tempers achieve 95.5% and 94% of the hardness values of the T6 treatment, respectively. The hardness values of the RRA and T78 treated alloys are related to the finer nano-sized precipitates formed during the high temperature process. These precipitates can compensate for the loss of hardness caused by the increase in the widths of the PFZs and the coarsening of the matrix precipitates. The relationship between the hardness and microstructures such as PFZs and precipitates in the matrix during various heat treatments is elucidated.

In order to explore the hot deformation behaviors of the as-cast 7005 aluminum alloy, a number of hot tensile tests with four temperatures (100, 200, 300, and 400 °C) and three strain rates (0.001, 0.01, and 0.1 s−1) were performed. The Johnson–Cook model was used to express the relationship between stress, strain, strain rate, and temperature. Scanning electron microscopy (SEM), optical microscopy (OM), and transmission electron microscopy (TEM) were selected to reveal fracture features and microstructure evolution of the studied alloy. The results indicate that the flow stress level of the alloy reduces with increases in the deformation temperature and decreases in the strain rate. The established Johnson–Cook model can be employed to characterize the thermal flow behavior of the experimental alloy. The grains near the fracture surface were elongated, and a certain number of holes were found after deformation at 400 °C. The alloy exhibits obvious ductile fracture features. The dimple is deep with high quantity. Due to the plastic deformation, a high-density dislocation structure is found in the material. High-temperature conditions promote the annihilation of dislocation, and, as a result, the dislocation density decreases gradually with the increase in temperature. In addition, a certain number of precipitates were found in the alloy after high-temperature tension.

The hot tensile behavior of an extruded 6082 alloy sheet at varying temperatures and strain rates was investigated by a Gleeble3500 thermal simulation testing machine. The optical microscope (OM), scanning electron microscope (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) were applied to observe the microstructure evolution. It is found that the flow stress of the studied alloy declines with increasing deformation temperature. When deformed at high temperatures, the density of dislocation decreases obviously. In addition, precipitate coarsening occurs, resulting in a decrease in deformation resistance. The dimple number of the fracture samples increases with temperature and the size of the dimple becomes deeper, exhibiting an excellent plasticity. The 6082 sheet presents anisotropy of mechanical behavior at 300 °C, this can be attributed to the fibrous grain and the Brass component {011}. The anisotropic behavior seems to be slighter with an increase in temperature. No obvious anisotropic behavior was found when tensiled at 400 °C. Because it is easier to activate the slip system at elevated temperatures, meanwhile, the recrystallization begins to occur at 400 °C.

BackgroundAbnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD).MethodThe thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed.ResultsNo difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p

Summary: Owing to superior softness, wetness, responsiveness, and biocompatibility, bulk hydrogels are being intensively investigated for versatile functions in devices and machines including sensors, actuators, optics, and coatings. The one-dimensional (1D) hydrogel fibers possess the metrics from both the hydrogel materials and structural topology, endowing them with extraordinary mechanical, sensing, breathable and weavable properties. As no comprehensive review has been reported for this nascent field, this article aims to provide an overview of hydrogel fibers for soft electronics and actuators. We first introduce the basic properties and measurement methods of hydrogel fibers, including mechanical, electrical, adhesive, and biocompatible properties. Then, typical manufacturing methods for 1D hydrogel fibers and fibrous films are discussed. Next, the recent progress of wearable sensors (e.g., strain, temperature, pH, and humidity) and actuators made from hydrogel fibers is discussed. We conclude with future perspectives on next-generation hydrogel fibers and the remaining challenges. The development of hydrogel fibers will not only provide an unparalleled one-dimensional characteristic, but also translate fundamental understanding of hydrogels into new application boundaries.

The application of multidisciplinary techniques in the management of endocrine-related cancers is crucial for harnessing the advantages of multiple disciplines and their coordinated efforts in eliminating tumors. Due to the malignant characteristics of cancer cells, they possess the capacity to develop resistance to traditional treatments such as chemotherapy and radiotherapy. Nevertheless, despite diligent endeavors to enhance the prediction of outcomes, the overall survival rate for individuals afflicted with endocrine-related malignancy remains quite miserable. Hence, it is imperative to investigate innovative therapy strategies. The latest advancements in therapeutic tactics have offered novel approaches for the therapy of various endocrine tumors. This paper examines the advancements in nano-drug delivery techniques and the utilization of nanomaterials for precise cancer cures through targeted therapy. This review provides a thorough analysis of the potential of combined drug delivery strategies in the treatment of thyroid cancer, adrenal gland tumors, and pancreatic cancer. The objective of this study is to gain a deeper understanding of current therapeutic approaches, stimulate the development of new drug DDS, and improve the effectiveness of treatment for patients with these diseases. The intracellular uptake of pharmaceuticals into cancer cells can be significantly improved through the implantation of synthetic or natural substances into nanoparticles, resulting in a substantial reduction in the development of endocrine malignancies.

Abstract Aiming at the aggregation problem of online multi-attribute interactive ratings, a decision-making method based on Pythagorean Fuzzy Bonferroni mean with weighted interaction (PFWIBM) operator is developed by mining the advantages of ratings driven decision-making and the quantitative advantages of Pythagorean fuzzy sets on linguistic ratings. First, the shortcomings of existing operators in criterion interactive representation are analyzed, and the improved Bonferroni mean with weighted interaction and its dual operator are defined, which are used to aggregate the membership information and non-membership information under the Pythagorean fuzzy environment, respectively, and then the PFWIBM operator is constructed. Second, a generation method of interaction coefficients embedded in the PFWIBM operator is designed by combining expert knowledge and user ratings to overcome the limitations of the method of relying on subjective setting parameter values. Third, based on the proposed operator and the transformation relationship between Pythagorean fuzzy sets and linguistic ratings, an online multi-dimensional rating aggregation decision-making approach for solving product raking problems is developed. Finally, the proposed method is applied to a passenger car ranking example to show the feasibility of the method, and through some comparative analysis, the advantages of the proposed operator are clarified, and the influence of operator parameters on the decision-making results is analyzed.

The investigation of thermal deformation behavior plays a significant role in guaranteeing the overall performance of alloy materials. In this manuscript, a series of isothermal compression tests at different temperatures (300, 350, 400, and 450 °C) and strain rates (0.001, 0.01, 0.1, and 1 s−1) were conducted to study the thermal deformation behavior of 7075 aluminum alloy. Subsequently, processing maps at a strain from 0.4 to 1.39 were established according to the stress–strain data obtained from various deformation parameters. The microstructural evolution of the target alloy was observed with an optical microscope and transmission electron microscope. The results reveal the unstable regions are located at (360–450 °C, 0.04–1 s−1) and (300–315 °C, 0.01–0.22 s−1). Precipitation particles, pinned dislocations, and highly dislocated areas can be observed in the microstructure of the alloy in the unstable regions. This is a potential crack and defect formation point. The identified optimum processing parameters are located at (375–450 °C, 0.001–0.03 s−1), with a maximum dissipation efficiency of 0.6.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, pannus formation, and bone and cartilage damage. It has a high disability rate. The hypoxic microenvironment of RA joints can cause reactive oxygen species (ROS) accumulation and mitochondrial damage, which not only affect the metabolic processes of immune cells and pathological changes in fibroblastic synovial cells but also upregulate the expression of several inflammatory pathways, ultimately promoting inflammation. Additionally, ROS and mitochondrial damage are involved in angiogenesis and bone destruction, thereby accelerating RA progression. In this review, we highlighted the effects of ROS accumulation and mitochondrial damage on inflammatory response, angiogenesis, bone and cartilage damage in RA. Additionally, we summarized therapies that target ROS or mitochondria to relieve RA symptoms and discuss the gaps in research and existing controversies, hoping to provide new ideas for research in this area and insights for targeted drug development in RA.

In this paper, we study a generalized version of strongly reciprocally convex functions of higher order. Firstly, we prove some basic properties for addition, scalar multiplication, and composition of functions. Secondly, we establish Hermite-Hadamard and Fejér type inequalities for the generalized version of strongly reciprocally convex functions of higher order. We also include some fractional integral inequalities concerning with this class of functions. Our results have applications in optimization theory and can be considered extension/generalization of many existing results.

Water-saving agriculture (WSA) is often introduced as an effective strategy to reduce water infiltration and mitigate irrigation-induced landslide risks. The effects highly rely on smallholder farmers, who often would rather suffer from landslides than adapt. This study focused on farmers’ adoption intention of WSA in general and drip irrigation and drought-tolerant crop in specific, representing changes in technology and farming systems. An integrative theoretical model was developed based on the extended theory of planned behavior (TPB) with elements from the norm activation model and technology acceptance model. Hypotheses were tested using data from a questionnaire survey with 363 farmers in Loess Plateau, Northwest China. The results of structural equation modeling showed that the most crucial factor bolstering farmers’ adoption intention was subjective norm, regardless of different measures. Attitude was more influential than perceived behavior control in drip irrigation and vice versa in drought-tolerant crop adoption, indicating that attitude was more important in technology change and capacity played a crucial role in farming system shift. In addition, awareness of environmental consequences contributed positively to subjective norm and attitude, and perceived ease-of-use improved perceived behavior control. Most notably, the extended TPB model has more explanatory power than the classical one. By considering the moral and technical aspects, the extended model enhanced the comprehensiveness of explaining drivers of farmers’ WSA adoption intention under the irrigation-induced landslide risks. The findings shed light on future disaster risk management for China and other countries under the landslide risk.

Mesenchymal stem cells (MSCs) have been used to treat various diseases including Alzheimer’s disease and cancer. In particular, the immunomodulatory function of MSCs plays a major role in cancer therapy using stem cells. However, MSCs exert promotive and inhibitory effects on cancer. The immunomodulatory effects of MSCs in the tumor microenvironment (TME) are ambiguous, which is the primary reason for the different outcomes of MSCs therapies for tumors. This review discusses the use of MSCs in cancer immunotherapy and their immunomodulatory mechanisms in cancers.

Abstract Background Retinal degeneration is often accompanied by microglia-mediated neuroinflammation. Ferulic acid (FA), an active ingredient of traditional Chinese medicines (TCMs), has been reported to have anti-inflammatory effects. This study explores the impact of FA on microglia-mediated neuroinflammation and associated retinal degeneration in rd10 mice. Methods Rd10 mice received different concentrations of FA every day from postnatal day (P)4 to P24. On P25, the visual function of the mice was evaluated by electroretinogram, and retinae were collected for further investigation. Microglial activation and the expression of relevant cytokines in the retina were evaluated by qPCR, western blotting and immunofluorescence staining. Retinal structure was assessed by haematoxylin and eosin (HE) staining. Results Supplementation with 50 mg/kg FA provided optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as greater wave amplitude amplification on electroretinogram than untreated mice. FA suppressed microglial activation both in vivo and in vitro, and inhibited the expression of pro-inflammatory factors Tnfα, IL1β, and Ccl2 in the retinae of rd10 mice. Furthermore, FA suppressed the activation of STAT1 and subsequently inhibited IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions Attenuation of neuroinflammation by FA may be beneficial for retarding retinal degeneration.

Bulk amorphous alloys, as a material with broad application prospects, are highly expected in many cutting-edge applications. However, its plastic deformation relies on highly localized shear bands, resulting in brittle fracture characteristics of materials with low plastic strain as a whole. Therefore, strengthening and toughening of amorphous alloys is one of the key topics in the research of amorphous applications. In this paper, the effects of different isothermal annealing temperature on the microstructure and uniaxial compression properties of Cu _45 Zr _45 Ag _7 Al _3 amorphous alloy were studied by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results show that Cu _10 Zr _7 , AlCu _2 Zr, Cu _8 Zr _3 and Al _2 Zr phases precipitated successively from the amorphous alloy matrix with the increase of annealing temperature, and the fracture strength and plastic strain increased first and then decreased; At an isothermal annealing temperature of 741 K, the precipitated nanocrystalline Cu _10 Zr _7 phase can improve the fracture strength of the alloy; when the annealing temperature rises to 746 K, the strength of the alloy decreases slightly, but the plasticity increases; with the continuous increase of annealing temperature, the plasticity of the alloy decreases and the strength continues to increase; As the annealing temperature continues to increase, the fracture strength of the alloy decreases, exhibiting significant brittle fracture characteristics.

Cervical cancer is a major cause of cancer death in women worldwide. Targeting human papillomavirus (HPV) viral oncoproteins E6 and E7 is a new strategy for cervical cancer immunotherapy and has been associated with resolution of HPV-induced lesions. How to efficiently induce T cell target killing of HPV infected cervical cancer is of great potential benefit for cervical cancer treatment. Fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for Toll-like receptor 4 (TLR4), and HPVE7 (EDA-E7) has been shown to efficiently induce dendritic cells maturation and trigger specific antitumor CD8+ T cells response in mice. In this study, we constructed EDA-E7 fusion protein of human origin and tested its function in dendritic cell maturation as well as antitumor T cell response. We found that EDA-E7 could be efficiently captured by human PBMC derived dendritic cells (DCs) in vitro and induce DCs maturation. Importantly, this effect could work in synergy with the TLR ligand anti-CD40 agonist, polyinosinic-polycytidylic acid [poly (I:C)], R848, and CpG2216. EDA-E7 matured DCs could activate T cells and trigger an anti-tumor response in vitro. Single cell RNA sequencing and T cell targeted killing assay confirmed the activation of T cells by EDA-E7 matured DCs. Therefore, therapeutic vaccination with EDA-E7 fusion protein maybe effective for human cervical carcinoma treatment.

Precocious puberty (PP) is one of the most common endocrine diseases in children, and the pathogenesis is currently unknown. Recent studies on the gut-brain axis have shown that there is a correlation between childhood endocrine diseases and the gut microbiota (GM). To explore the GM characteristics of children with different types of PP, we recruited 27 idiopathic central precocious puberty children (ICPP group), 18 peripheral precocious puberty children (PPP group), and 23 healthy children of the same age (HC group). Their stool samples were subjected to 16S rDNA sequencing. In this study, we found that the OTUs numbers, the annotated genera, and α-diversity of GM of the ICPP and PPP group were all significantly higher than that in the HC group (P

Designing energy efficient, flexible opto-electronic systems integrated with textiles remains a challenge. Here, the authors propose a solution-based blow-spinning technique for 3D flexible and stretchable metal oxide nanofiber networks for multimodal and monolithically integrated wearable electronics.

Spontaneous speech emotion recognition is a new and challenging research topic. In this paper, we propose a new method of spontaneous speech emotion recognition on the basis of binaural representations and deep convolutional neural networks (CNNs). The proposed method initially employs multiple CNNs to learn deep segment-level binaural representations such as Left-Right and Mid-Side pairs from the extracted image-like Mel-spectrograms. These CNNs are fine-tuned on target emotional speech datasets from a pre-trained image CNN model. Then, a new feature pooling strategy, called block-based temporal feature pooling, is proposed to aggregate the learned segment-level features for producing fixed-length utterance-level features. Based on the utterance-level features, linear support vector machines (SVM) is adopted for emotion classification. Finally, a two-stage score-level fusion strategy is used to integrate the obtained results from Left-Right and Mid-Side pairs. Extensive experiments on two challenging spontaneous emotional speech datasets, including the AFEW5.0 and BAUM-1s databases, demonstrate the effectiveness of our proposed method.

BackgroundWe performed a meta-analysis to evaluate the efficacy and safety of weekly long-acting growth hormone replacement therapy compared to daily growth hormone in children with short stature.MethodsA systematic literature search up to April 2021 was performed and 11 studies included 1,232 children with short stature treated with growth hormone replacement therapy at the start of the study; 737 of them were using weekly long-acting growth hormone replacement therapy and 495 were using daily growth hormone. They were reporting relationships between the efficacy and safety of long-acting growth hormone replacement therapy and daily growth hormone in children with short stature. We calculated the odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) to assess the efficacy and safety of weekly long-acting growth hormone replacement therapy compared to daily growth hormone in children with short stature using the dichotomous or continuous method with a random or fixed-effect model.ResultsLong-acting growth hormone replacement therapy had significantly lower height standard deviation scores chronological age (MD, −0.10; 95% CI, −0.13 to −0.08, p

Ichthyoplankton assemblages and their relationship with environmental variables are investigated in waters off the Pearl River Estuary in spring and autumn of 2019. Of 80 ichthyoplankton taxa identified using DNA barcode and morphological methods, 61 are identified to species. The most abundance families (Carangidae, Trichiuridae, Mullidae, and Scombridae) account for 61.34% of the horizontal total catch in spring, while Menidae and Carangidae are the most abundant families identified in autumn, accounting for 89.72% of the horizontal total catch. Cluster analysis identifies three species assemblages in spring, and four in autumn based on horizontal trawls. Relationships between assemblage structure and environmental variables (in situ and remote sensed) are determined by canonical correspondence analysis. Ichthyoplankton assemblage structure appears to be strongly influenced by sea level anomalies, salinity, water depth, temperature at 10 m depth, and distance from shore. We demonstrate the efficacy of using DNA barcode to identify ichthyoplankton, and suggest how these data can be used to protect fish spawning grounds in waters off the Pearl River Estuary.

Objective: This study investigated the protective effects of dipeptidyl peptidase-4 inhibitor MK-626 on vascular endothelial function by regulating lncRNAs in hypertensive vasculature.Methods: Angiotensin Ⅱ (Ang Ⅱ)-loaded osmotic pumps were implanted in mice with or without MK-626 administration. GLP-1 levels in plasma were measured by ELISA. Aortic rings were suspended in myograph for tension measurement. Microarray was performed to analyze lncRNA and mRNA expression profiles. Protein expression and phosphorylation were examined by Western blot. The differentially expressed (DE)-genes were validated by qRT-PCR. The intracellular Ca2+ concentration was detected by laser confocal system.Results: MK-626 elevated plasma GLP-1 level, increased eNOS phosphorylation, improved endothelium-dependent relaxations, and reduced systolic blood pressure in Ang Ⅱ-induced hypertensive mice. Microarray revealed the dysregulations of 723 lncRNAs and 742 mRNAs were reversed by MK-626 in hypertensive mouse aortae. qRT-PCR validation showed that 13 DE-lncRNAs and eight dysregulated mRNAs in both hypertensive mouse aortae and mouse aortic endothelial cells (MAECs) were rescued by MK-626. Among them, four mRNAs (Cacna1C, Itgav, Itga8, and Npnt) were co-expressed with lncRNA ENSMUST00000155383. Cacna1C protein expression was reduced in the ECs but was elevated in smooth muscle cells from Ang Ⅱ-infused mice, which were both reversed by MK-626. Knockdown of lncRNA ENSMUST00000155383 suppressed the increased Cacna1c protein and mRNA expression, elevated Ca2+ level, and enhanced eNOS phosphorylation induced by MK-626 in the hypertensive mouse ECs.Conclusion: The dysregulations of lncRNA ENSMUST00000155383-associated genes might play crucial roles in hypertension-induced endothelial dysfunction through affecting calcium pathway. MK-626 might ameliorate endothelial dysfunction by upregulating lncRNA ENSMUST00000155383, enhancing Ca2+ concentration, and subsequently restoring eNOS activity in hypertension.

Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-κB/miR-155-5p/eNOS/NO/IκB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy.

One key challenging issues of facial expression recognition (FER) in video sequences is to extract discriminative spatiotemporal video features from facial expression images in video sequences. In this paper, we propose a new method of FER in video sequences via a hybrid deep learning model. The proposed method first employs two individual deep convolutional neural networks (CNNs), including a spatial CNN processing static facial images and a temporal CN network processing optical flow images, to separately learn high-level spatial and temporal features on the divided video segments. These two CNNs are fine-tuned on target video facial expression datasets from a pre-trained CNN model. Then, the obtained segment-level spatial and temporal features are integrated into a deep fusion network built with a deep belief network (DBN) model. This deep fusion network is used to jointly learn discriminative spatiotemporal features. Finally, an average pooling is performed on the learned DBN segment-level features in a video sequence, to produce a fixed-length global video feature representation. Based on the global video feature representations, a linear support vector machine (SVM) is employed for facial expression classification tasks. The extensive experiments on three public video-based facial expression datasets, i.e., BAUM-1s, RML, and MMI, show the effectiveness of our proposed method, outperforming the state-of-the-arts.

This study was performed to screen Lactobacillus and evaluate its inhibiting effects on Helicobacter pylori (Hp). Lactobacillus was isolated from fermented food in northeastern China. After identification and physiological characterization, the identified Lactobacillus was used to interact with Hp. The aggregation ability of Lactobacillus and Hp was determined. Moreover, the inhibiting effects of Lactobacillus on Hp urease enzyme activity and antioxidant ability were assessed. The results showed that four Lactobacillus strains including Lactobacillus sake, Lactobacillus plantarum, Lactobacillus rhamnosus and Lactobacillus brevis were isolated from fermented food in northeastern China. All four strains of Lactobacillus could inhibit Hp growth in different extent. The interaction with Hp was statistically analyzed with significant differences. The Lactobacillus isolated from fermented food in Northeast China, had an inhibitory effect on Hp growth. This study provided a foundation for development of probiotic preparations and exploring the inhibitory effect of Lactobacillus on Hp.

Abstract Background To investigate the effect of idiopathic epiretinal membrane (ERM) on the retinal-image quality and psychophysical contrast sensitivity function (CSF). Methods Forty-four subjects with diagnosis of idiopathic unilateral ERM were enrolled in this cross-sectional observational clinical study. The fellow unaffected eyes were set as the control group. For retinal-image quality assessment, an Optical Quality Analysis System (OQAS) based on double-pass technique was used to evaluate objective scatter index (OSI) and Strehl ratio. For visual performance, the CSF under photopic condition was measured. Results For retinal-image quality, the result of double-pass device revealed a significant lower Strehl ratio and larger OSI in the ERM eyes compared to the fellow eyes (all P

Background/Aims: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC). Methods: The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival. Results: LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4). Conclusion: IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.

ObjectiveThe current study investigated the mechanism underlying the therapeutic effects of berberine in the vasculature in hypertension.MethodsAngiotensin II (Ang II)-loaded osmotic pumps were implanted in C57BL/6J mice with or without berberine administration. Mouse aortae were suspended in myograph for force measurement. Microarray technology were performed to analyze expression profiles of lncRNAs and mRNAs in the aortae. These dysregulated expressions were then validated by qRT-PCR. LncRNA-mRNA co-expression network was constructed to reveal the specific relationships.ResultsAng Ⅱ resulted in a significant increase in the blood pressure of mice, which was suppressed by berberine. The impaired endothelium-dependent aortic relaxation was restored in hypertensive mice. Microarray data revealed that 578 lncRNAs and 554 mRNAs were up-regulated, while 320 lncRNAs and 377 mRNAs were down-regulated in the aortae by Ang Ⅱ; both were reversed by berberine treatment. qRT-PCR validation results of differentially expressed genes (14 lncRNAs and 6 mRNAs) were completely consistent with the microarray data. GO analysis showed that these verified differentially expressed genes were significantly enriched in terms of "cellular process", "biological regulation" and "regulation of biological process", whilst KEGG analysis identified vascular function-related pathways including cAMP signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway etc. Importantly, we observed that lncRNA ENSMUST00000144849, ENSMUST00000155383, and AK041185 were majorly expressed in endothelial cells.ConclusionThe present results suggest that the five lncRNAs ENSMUST00000144849, NR_028422, ENSMUST00000155383, AK041185, and uc.335+ might serve critical regulatory roles in hypertensive vasculature by targeting pivotal mRNAs and subsequently affecting vascular function-related pathways. Moreover, these lncRNAs were modulated by berberine, therefore providing the novel potential therapeutic targets of berberine in hypertension. Furthermore, lncRNA ENSMUST00000144849, ENSMUST00000155383, and AK041185 might be involved in the preservation of vascular endothelial cell function.

The scientific and reasonable evaluation of the carrying capacity of water resources is of guiding significance for solving the issues of water resource shortages and pollution control. It is also an important method for realizing the sustainable development of water resources. Aiming at an evaluation of the carrying capacity of water resources, an evaluation model based on the cloud model theory and evidential reasoning approach is studied. First, based on the existing indicators, a water resources evaluation index system based on the pressure-state-response (PSR) model is constructed, and a classification method of carrying capacity grade is designed. The cloud model theory is used to realize the transformation between the measured value of indicators and the degree of correlation. Second, to obtain the weight of the evaluation index, the weight method of the index weights model based on the entropy weight method and evidential reasoning approach is proposed. Then, the reliability distribution function of the evaluation index and the graded probability distribution of the carrying capacity of water resources are obtained by an evidential reasoning approach. Finally, the evaluation method of the carrying capacity of water resources is constructed, and specific steps are provided. The proposed method is applied to the evaluation of water resources carrying capacity for Hunan Province, which verifies the feasibility and effectiveness of the method proposed in the present study. This paper applies this method of the evaluation of the water resources carrying capacity of Hunan Province from 2010 to 2019. It is concluded that the water resources carrying capacity of Hunan Province belongs to III~V, which is between the critical state and the strong carrying capacity state. The carrying capacity of the province’s water resources is basically on the rise. This shows that the carrying capacity of water resources in Hunan Province is in good condition, and corresponding protective measures should be taken to continue the current state.

Sustainable supplier selection is the essential core of sustainable supply chain management, which can directly influence the manufacturer's performance and can enormously enhance the manufacturer's competitiveness in the international market. However, most of the previous studies concerning sustainable supplier selection have less focused on the reliability of the decision-makers judgments and the application of regret theory. To fill this gap, we presented an integrated sustainable supplier selection model based on regret theory and QUALItative FLEXible multiple criteria method (QUALIFLEX) under a 2-dimensional uncertain linguistic variable (2-DULV) environment. In the proposed model, 2-DULV including the reliability of evaluation information is employed to handle the uncertainty and vagueness of decision-makers judgments. A similarity-based method is used to derive the decision-makers' weight, and a maximizing deviation model is established to calculate the weights of evaluation criteria. Then an improved QUALIFLEX method based on regret theory is presented to obtain the ranking order of sustainable suppliers. The proposed approach integrates both the superiority of 2-DULV in effectively handling the uncertainty, vagueness, and reliability of evaluation information and the merit of regret theory in dealing with decision-maker's bounded rationality. Finally, a numerical example concerning an automobile manufacturer is provided to validate the effectiveness and feasibility of the presented model.

To provide the general information on corneal transplantation (CT) in China, China Cornea Society designed a questionnaire on CT from 2014 to 2018 and entrusted it to 31 committee members for implementation of the survey nationwide. This article presents the results of the survey and compares the indicators used in the survey and those in the annual statistical report released by the Eye Bank Association of America (EBAA). The number of corneal transplantations completed by the 64 hospitals from 2014 to 2018 was respectively 5377, 6394, 7595, 8270 and 8980, totally 36,616 (22,959 male and 13,657 female). The five largest hospitals by the number of corneal transplantations completed 15,994 surgeries in total, accounting for 43.68% of all the surgeries performed in the 64 hospitals. The most common indication for corneal transplantations was corneal leukoma (7683, 20.98%), followed by bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%) and corneal perforation (2839, 7.75%). The main surgical techniques were penetrating keratoplasty (PK) (19,896, 54.34%), anterior lamellar keratoplasty (ALK) (13,869, 37.88%). The proportion of PK decreased from 57.97% in 2014 to 52.88% in 2018 while the proportion of ALK increased from 36.04% in 2014 to 37.92% in 2018. The geographical distribution of keratoplasties performed in China is unbalanced. PK and ALK were the main techniques of CT and corneal leukoma, bacterial keratitis and corneal dystrophies were the main indications for CT in China.

Abstract Background Epstein-Barr virus (EBV) is widely found in nasopharyngeal carcinoma (NPC) tissue and associated with poor prognosis of patients. EBV nuclear antigen 1 (EBNA1) is expressed in all NPC tumors and plays multiple biological roles in both virus and host cells. Triptolide is a natural product extracted from Tripterygium and shows anti-cancer activities. The goal of this work was to illustrate the anti-cancer effect of triptolide and elucidate a novel anti-apoptotic mechanism of EBNA1 in NPC cells encountered with triptolide. Methods In the present study, a CCK-8 assay was used to analyze the proliferation of NPC cells treated with triptolide in a dose- and time-dependent ways. Effects of triptolide on NPC cell cycle and apoptosis were investigated by flow cytometric analysis. EBNA1 expression in mRNA and protein levels was determined by quantitative real-time PCR and Western blot, respectively. Results Our results showed that triptolide effectively inhibited proliferation of NPC cells. Triptolide arrested NPC cell cycles in S phase and induced apoptosis through a caspase-9-dependent apoptosis pathway. Low-dose of triptolide reduced the half-life of EBNA1 and significantly decreased EBNA1 expression by promoting the process of proteasome-ubiquitin pathway. Over-expression of EBNA1, which was independent from EBV genome, effectively attenuated the apoptosis induced by triptolide. In addition, triptolide significantly inhibited proliferations of tumors induced by EBV-positive cells in vivo. Furthermore, EBNA1 were expressed in all NPC biopsies of Chinese patients. Conclusions In summary, our study provides the evidence that triptolide induces EBNA1 degradation and stimulates NPC apoptosis through mitochondria apoptotic pathway. In addition, EBNA1 assists NPC cells to resist triptolide-induced apoptosis through inhibiting caspase-9-dependent apoptotic pathway.

Abstract Background This study evaluates the macular function changes in patients with idiopathic macular epiretinal membrane (ERM) by multifocal electroretinography (mfERG) and their correlations with visual acuity and central macular thickness (CMT) by optical coherence tomography (OCT). Methods Twenty eyes of 20 patients with ERM underwent OCT and mfERG examinations. The response amplitude densities and implicit times of mfERG were compared to the control fellow eyes. Correlation analyses among visual acuity, central macular thickness and mfERG values in the central two concentric rings were performed. Results The mfERG P1 response amplitude densities in ring 1–2 and P1 implicit time in ring1 were significantly changed in epiretinal membrane eyes compared with controls (P

To study the effects of apigenin on dry eye disease (DED) in rats. Rats were divided into six groups: (I) normal control group, (II) DED control group, (III) vehicle control group, (IV) DED + apigenin 10 mg/kg, (V) DED + apigenin 20 mg/kg, and (VI) DED + apigenin 50 mg/kg. Schirmer test, tear film break-up time (BUT), and corneal fluorescein staining were used to evaluate the effects of apigenin on the ocular surface. The related inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological examination and inflammatory index were also performed. The results showed that administration of apigenin was shown a significant effect on the recovery of ocular surface function. Compared to the control group, apigenin treatment in DED rats significantly decreased the level of the tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6); however, the interleukin-10 (IL-10) level was increased. Histopathological examination further verified the anti-inflammatory effects of apigenin on DED rats. The results demonstrated that apigenin could protect DED rats via inhibition of inflammation, suggesting that it may have potential as a therapy for DED.

Among the seven tetraploid cotton species, little is known about transmission genetics and genome organization in Gossypium mustelinum, the species most distant from the source of most cultivated cotton, G. hirsutum. In this research, an F2 population was developed from an interspecific cross between G. hirsutum and G. mustelinum (HM). A genetic linkage map was constructed mainly using simple sequence repeat (SSRs) and restriction fragment length polymorphism (RFLP) DNA markers. The arrangements of most genetic loci along the HM chromosomes were identical to those of other tetraploid cotton species. However, both major and minor structural rearrangements were also observed, for which we propose a parsimony-based model for structural divergence of tetraploid cottons from common ancestors. Sequences of mapped markers were used for alignment with the 26 scaffolds of the G. hirsutum draft genome, and showed high consistency. Quantitative trait locus (QTL) mapping of fiber elongation in advanced backcross populations derived from the same parents demonstrated the value of the HM map. The HM map will serve as a valuable resource for QTL mapping and introgression of G. mustelinum alleles into G. hirsutum, and help clarify evolutionary relationships between the tetraploid cotton genomes.

Although numerous studies have shown that contact resistance depends significantly on roughness and fractal dimension, it remains elusive how they affect contact resistance between rough surfaces. The interface similarity index is first proposed to describe the similarity of the contact surfaces, which gives a good indication of the actual contact area between surfaces. We reveal that the surfaces’ similarity be an origin of contact resistance variation. The cyclic loading can increase the contact stiffness, and the contact stiffness increases with the increase of the interface similarity index. These findings explain the mechanism of surface roughness and fractal dimension on contact resistance, and also provide reference for the reliability design of the electrical connection.

Purpose Evidence shows that adenosine triphosphate (ATP) is involved in the transmission of multiple chronic pain via P2X7 receptor. This study was to investigate the P2X7 and microglial cells in the chronic prostatitis pain. Materials and Methods Rats were divided into control group and chronic prostatitis group (n = 24 per group). A chronic prostatitis animal model was established by injecting complete Freund's adjuvant (CFA) to the prostate of rats, and the thermal withdrawal latency (TWL) was detected on days 0, 4, 12 and 24 (n = 6 at each time point in each group). Animals were sacrificed and the pathological examination of the prostate, detection of mRNA expression of P2X7 and ionized calcium binding adaptor molecule 1 (IBA-1) and measurement of content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the dorsal horn of L5-S2 spinal cord were performed on days 0, 4, 12 and 24. In addition, the content of TNF-α and IL-1β in the dorsal horn of L5-S2 spinal cord was measured after intrathecal injection of inhibitors of microglial cells and/or P2X7 for 5 days. Results The chronic prostatitis was confirmed by pathological examination. The expression of P2X7 and IBA-1 and the content of TNF-α and IL-1β in rats with chronic prostatitis were significantly higher than those in the control group. On day 4, the expressions of pro-inflammatory cytokines became to increase, reaching a maximal level on day 12 and started to reduce on day 24, but remained higher than that in the control group. Following suppression of microglial cells and P2X7 receptor, the secretion of TNF-α and IL-1β was markedly reduced. Conclusion In chronic prostatitis pain, the microglial cells and P2X7 receptor are activated resulting in the increased expression of TNF-α and IL-1β in the L5-S2 spinal cord, which might attribute to the maintenance and intensification of pain in chronic prostatitis.

Aggressive natural killer cell leukemia (ANKL) is a fatal hematological neoplasm characterized by a fulminating clinical course and extremely high mortality. Current diagnosis of this disease is not effective during the early stages and it is easily misdiagnosed as other NK cell disorders. We retrospectively analyzed the clinical characteristics and flow cytometric immunophenotype of 47 patients with ANKL. Patients with extranodal NK/T cell lymphoma, nasal type (ENKTL) and chronic lymphoproliferative disorder of NK cell (CLPD-NK), who were diagnosed during the same time period were used for comparisons. Abnormal NK cells in ANKL were found to have a distinctiveCD56bright/CD16dim immunophenotype and markedly increased Ki-67 expression, whereas CD57 negativity and reduced expression of killer immunoglobulin-like receptor (KIR), CD161, CD7, CD8 and perforin were exhibited compared with other NK cell proliferative disorders (p

Most present studies on the acoustic emission signals of rotating machinery are experiment-oriented, while few of them involve on-spot applications. In this study, a method of redundant second generation wavelet transform based on the principle of interpolated subdivision was developed. With this method, subdivision was not needed during the decomposition. The lengths of approximation signals and detail signals were the same as those of original ones, so the data volume was twice that of original signals; besides, the data redundancy characteristic also guaranteed the excellent analysis effect of the method. The analysis of the acoustic emission data from the faults of on-spot low-speed heavy-duty gears validated the redundant second generation wavelet transform in the processing and denoising of acoustic emission signals. Furthermore, the analysis illustrated that the acoustic emission testing could be used in the fault diagnosis of on-spot low-speed heavy-duty gears and could be a significant supplement to vibration testing diagnosis.

MSCs (mesenchymal stem cells) are a stem cell source that can be easily obtained from bone marrow. Despite the increasing importance of the pig as a large animal model, little is known about foetal pMSCs (porcine MSCs). In this study, we observed the gene expression of pluripotent markers in foetal pMSCs and the capacity of pMSCs to differentiate into adipocytes, osteocytes and neural-like cells using quantitative RT–PCR (reverse transcription–PCR), normal histological staining and immunohistochemistry. Foetal pMSCs have either a spindle or a flattened shape, and flow cytometry revealed the expression of the MSC-related proteins CD44 and CD105 (endoglin) but not CD34 and CD45. pMSCs express pluripotent markers such as Oct4 (octamer-binding transcription factor 4) and Nanog at the protein and mRNA levels. qRT-PCR (quantitative real-time PCR) analyses revealed that pMSCs expressed nestin [for NSCs (neural stem cells)]. Immunocytochemical and RT–PCR data showed that 29% and 23% of pMSCs expressed MAP2 (microtubule-associated protein 2) for neurons and β-tubulin III (Tuj1) for immature neurons, respectively, after induction of neural differentiation. These findings demonstrate the plasticity of pMSCs and their potential for use in cellular replacement therapy for neural diseases.

Purpose. To summarize the experience in treating patients with genitoplasty due to disorders of sex development in China. Methods. The operative procedures, gender of rearing, surgical outcome, and psychosocial and family adjustments of 262 patients were reviewed retrospectively. Results. At initial diagnosis, the mean age was years (range: 2–38 years). There were 96 children, 133 adolescents, and 33 adults. Follow-up was done every 6 months. Patients with female sex assignment had no urinary incontinence or voiding difficulty. Five patients underwent the second surgery (3%); vaginal dilation was performed in 35 patients with postoperative vaginal stenosis; 12 patients (7.4%) were unsatisfactory with the outcome. For patients with male sex assignment, the median length of penis was 2.2 cm in prepubertal patients, 4.2 cm in pubertal patients, and 5.0 cm in adults; 39 patients developed postvoid dribbling (39%); 21 patients underwent a second surgery (21%); urethral dilation was done in 28 patients (28%) due to urethral stricture; 38 patients were unsatisfactory with the outcome (38%). In addition, 136 patients (83%) with female sex assignment and 54 (54%) with male sex assignment had favorable psychosocial adjustment. Conclusions. Patients with male sex assignment have more surgical complications and difficulties in psychosocial adjustment as compared to those with female sex assignment.

DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC) and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC.

To make a biped robot walk stably at various speeds, a novel switch control approach is proposed to make the gaits switch smoothly between different walking speeds. The switch controller is designed based on the Lyapunov stability theory and the sufficient condition is given to make the closed-loop system stable. This controller can allow the robot to reach the stable gaits corresponding to the various speeds and improve the robustness of switch process. Potential energy compensation control has been studied in the dynamic model of a passive dynamic walking robot with knees. The functional relationship between the initial states and the walking speed is obtained. Numerical simulations are provided to verify the effectiveness of the control strategy.

Both adoptive immunotherapy and gene therapy hold a great promise for treatment of malignancies. However, these strategies exhibit limited anti-tumor activity, when they are used alone. In this study, we explore whether combination of cytokine-induced killer (CIK) adoptive immunotherapy with oncolytic adenovirus-mediated transfer of human interleukin-12 (hIL-12) gene induce the enhanced antitumor potency. Our results showed that oncolytic adenovirus carrying hIL-12 (AdCN205-IL12) could produce high levels of hIL-12 in liver cancer cells, as compared with replication-defective adenovirus expressing hIL-12 (Ad-IL12). AdCN205-IL12 could specifically induce cytotoxocity to liver cancer cells. Combination of CIK cells with AdCN205-IL12 could induce higher antitumor activity to liver cancer cells in vitro than that induced by either CIK or AdCN205-IL12 alone, or combination of CIK and control vector AdCN205-GFP. Furthermore, treatment of the established liver tumors with the combined therapy of CIK cells and AdCN205-IL12 resulted in tumor regression and long-term survival. High level expression of hIL-12 in tumor tissues could increase traffic of CIK cells to tumor tissues and enhance their antitumor activities. Our study provides a novel strategy for the therapy of cancer by the combination of CIK adoptive immunotherapy with oncolytic adenovirus-mediated transfer of immune stimulatory molecule hIL-12.