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Additional file 1: Fig. S1. Verification of the consistency between fluorescence boundary and tumor boundary in intraoperative frozen section.

Leukemic stem cells (LSCs) and hematopoietic stem cells (HSCs) are both dependent on the hypoxic bone marrow (BM) microenvironment (also known as the BM niche). There is always fierce competition between the two types of cells, and the former exhibits a greater competitive advantage than the latter via multiple mechanisms. Under hypoxia, the dynamic balance between the generation and clearing of intracellular reactive oxygen species (ROS) is conducive to maintaining a quiescent state of cells. Quiescent LSCs can reside well in the BM niche, avoiding attack by chemotherapeutic agents, which is the cause of chemotherapeutic resistance and relapse in leukemia. HSCs acquire energy mainly through anaerobic glycolysis, whereas LSCs achieve energy metabolism largely through mitochondrial oxidative respiration. Mitochondria are the primary site of ROS generation. Thus, in theory, mitochondria-mediated respiration will cause an increase in ROS generation in LSCs and a higher intracellular oxidative stress level. The sensitivity of the cells to pro-oxidant drugs increases as well, which allows for the selective clearing of LSCs by pro-oxidative therapy. However, HSCs are also highly sensitive to changes in ROS levels, and the toxic effects of pro-oxidant drugs on HSCs poses a major challenge to pro-oxidative therapy in leukemia. Given the above facts, we reviewed studies on the oxidative resistance of LSCs and the oxidative damage to HSCs under pro-oxidative therapy. An in-depth investigation into the oxidative stress status and regulatory mechanisms of LSCs and HSCs in hypoxic environments will promote our understanding of the survival strategy employed by LSCs and the mechanism of the oxidative damage to HSCs in the BM niche, thus facilitating individualized treatment of leukemia patients and helping eliminate LSCs without disturbing normal hematopoietic cells.

Plant trials were carried out to compare multiphase flow using a conventional ladle shroud (CLS) and a trumpet-shaped ladle shroud (TLS) in a steelmaking tundish. Steel splashing, slag exposure, smoke and flame were recorded to investigate the fluid flow during both transient and steady casting. A large eddy simulation model was employed to visualize the flow structure and obtain detailed flow information. The results showed that the TLS outperformed the CLS in relieving steel splashing during ladle change due to the braking effect of the TLS on the jet. During steady casting, a relatively calm melt bath was achieved with less exposed steel using the TLS, which is attributed to the reduced turbulence in the tundish. An eccentric tundish open eye was observed using the CLS, which is related to the misaligned flow pattern when the slide gate is partially open.

The superficial inferior epigastric artery (SIEA) flap is widely used in the repair of large soft tissue defects of the extremities and in breast reconstruction. Because of the high fat content of the abdomen, it has been less used for glossectomy reconstruction. Here we present a series of seven patients who each underwent reconstruction with a thin SIEA flap after resection of the tongue. There were six men and one woman (mean age 48, range 24-66 years). All patients underwent preoperative computed tomographic (CT) angiography, and colour Doppler ultrasound (US) was used to select and map the most suitable SIEA. The flap was raised above the Scarpa's layer while adjusted the plane of dissection according to the specific needs for bulk in each case. All the flaps survived; one flap required a secondary anastomosis because of a venous anastomotic embolus. The size of flap used was 5.0cm×6.0cm - 7.0cm×9.0cm, and the flap was 0.8cm-1.4cm thick. The functional outcome was evaluated at 6 - 18 months follow up, when speech and swallowing were both good in all cases. The dissection above the pubic symphysis is an important refinement of the SIEA flap, and we conclude that the thin SIEA flap is a good choice for reconstruction after excision of cancer of the tongue.

Ds-type inclusions during production are an important factor affecting the performance and quality of manufactured 10B21 steel. To minimize Ds-type inclusions in steel and improve the production qualification rate of steelmaking plants, a refining slag system optimization scheme was proposed based on the analysis of current inclusion evolution during the steelmaking process, and industrial tests were conducted to verify improvements resulting from application of the proposed scheme. The results showed that the composition of Ds inclusions in 10B21 steel are mainly CaO–Al2O3–MgO–CaS–TiN, which exists in the form of calcium–magnesium aluminate coated with titanium nitride and calcium sulfide. The main reason for the formation of Ds inclusions is the poor fluidity of the refining slag and its low capability to absorb inclusions. The poor coverage of the refining slag on the molten steel during refining can easily cause secondary oxidation of the molten steel. Thus, the formation and growth of Ds-type inclusions are aggravated after the calcium feeding line and soft blowing operation. Here, we propose to minimize Ds inclusions using our optimized refined slag system. The mass percentage of the optimized slag system is CaO: 55–60%, Al2O3: 20–35%, SiO2: 3–7%, MgO: 4–8%, (MnO + FeO) &lt, 1%, and the basicity is controlled within the range of 7–11. We observed that our optimized refining slag system has a significantly improved ability to remove inclusions, particularly Ds inclusions, which improves the qualification rate of 10B21 steel.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy originating from B- or T-lymphoid progenitor cells. Recent studies have shown that redox dysregulation caused by overproduction of reactive oxygen species (ROS) has an important role in the development and progression of leukemia. The application of pro-oxidant therapy, which targets redox dysregulation, has achieved satisfactory results in alleviating the conditions of and improving the survival rate for patients with ALL. However, drug resistance and side effects are two major challenges that must be addressed in pro-oxidant therapy. Oxidative stress can activate a variety of antioxidant mechanisms to help leukemia cells escape the damage caused by pro-oxidant drugs and develop drug resistance. Hematopoietic stem cells (HSCs) are extremely sensitive to oxidative stress due to their low levels of differentiation, and the use of pro-oxidant drugs inevitably causes damage to HSCs and may even cause severe bone marrow suppression. In this article, we reviewed research progress regarding the generation and regulation of ROS in normal HSCs and ALL cells as well as the impact of ROS on the biological behavior and fate of cells. An in-depth understanding of the regulatory mechanisms of redox homeostasis in normal and malignant HSCs is conducive to the formulation of rational targeted treatment plans to effectively reduce oxidative damage to normal HSCs while eradicating ALL cells.

As a clonal disease of hematopoietic stem cells (HSCs), the etiology and pathogenesis of leukemia is not fully understood. Recent studies suggest that cellular homeostasis plays an essential role in maintaining the function of HSCs because dysregulation of cellular homeostasis is one of the major factors underlying the malignant transformation of HSCs. Reactive oxygen species (ROS) and autophagy, key factors regulating cellular homeostasis, are commonly observed in the human body. Autophagy can be induced by ROS through a variety of signaling pathways, and conversely inhibits ROS-induced damage to cells and tissues. ROS and autophagy coordinate to maintain cellular homeostasis. Previous studies have demonstrated that both of ROS and autophagy play important roles in the development of leukemia and are closely involved in drug resistance in leukemia. Interference with cellular homeostasis by promoting programmed leukemia cell death via ROS and autophagy has been verified to be an efficient technique in the treatment of leukemia. However, the critical roles of ROS and autophagy in the development of leukemia are largely unknown. In this review, we summarize the roles of ROS and autophagy in the pathogenesis of leukemia, which may allow the identification of novel targets and drugs for the treatment of leukemia based on the regulation of HSCs homeostasis through ROS and autophagy.

Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot. In vitro, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels. In vivo, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.

Introduction: More than 42 million people are estimated to suffer from valvular heart disease (VHD) worldwide with a prevalence of 5.3% to 7.7% in the Chinese adult population. The purpose of this study was to examine the associations between symptoms, hope, self-management behaviors, and quality of life (QOL) for preoperative patients with symptomatic VHD in a rural area of China. Method: This was a descriptive comparative study that took place in Nanning, China, between January 2015 and March 2016. The sample was 128 preoperative patients with symptomatic VHD. Data were collected using the Symptom Distress Questionnaire, Herth Hope Index, Self-Management Scale, and Minnesota Living with Heart Failure Questionnaire. Results: Data from 122 patients were included in the final analysis. Mean scores of hope, self-management, and QOL were 36.71, 55.27, and 55.56. Worse total scores of symptom severity ( r = 0.57 to 0.69, p < .001) and self-management behaviors ( r = −0.22 to −0.25, p < .05) were associated with poorer QOL. Fatigue, loss of appetite, and self-management behaviors explained 49.90% variance of QOL ( p < .001). Discussion: Fatigue, loss of appetite, and self-management influenced QOL of patients with symptomatic VHD. Interventions aimed at strengthening self-management and relieving symptoms should be tailored for patients with symptomatic VHD base on their traditional animist belief and food culture in rural areas of China such as the Zhuang Autonomous Region.

Background The purpose of this study was to analyze the association between the genetic polymorphism of genes (PAX6, SOSTDC1and FAM20B) and the susceptibility to mesiodens. Methods This study was carried out on 50 patients with mesiodens and 50 controls. The family history of each patient with mesiodens were recorded. Genomic DNA was extracted from saliva samples, and single nucleotide polymorphisms were detected in all exons and exon/intron boundaries of PAX6, SOSTDC1 and FAM20B using Sanger sequencing. The data were analyzed using pearson chi-square test with theoretical frequency ≥ 5. For theoretical frequency less than 5 but at least 1 (≤20% cell), the data were analyzed by continuity correction. For the rest, Fisher’s Exact test was used. A P-value

Morphea profunda (MP) is a variant of morphea that presents clinically as localized fibrotic plaques. Based on previous reports, there was no unified standard treatment for MP. Here we report a rare case of MP, which is the first report about treatment by hydroxychloroquine in combination with superficial X-ray. Compared with other regular therapeutic methods, this method not only produced a positive clinical effect in a short amount of time, but also caused fewer side effects.

Self-assembled structures of 2D materials with novel physical and chemical properties, such as the good electrical and optoelectrical performance in nanoscrolls, have attracted a lot of attention. However, high photoresponse speed as well as high responsivity cannot be achieved simultaneously in the nanoscrolls. Here, a photodiode consisting of single MoS

Transition metal dichalcogenides (TMDs) are a category of promising two-dimensional (2D) materials for the optoelectronic devices, and their unique characteristics include tunable band gap, nondangling bonds as well as compatibility to large-scale fabrication, for instance, chemical vapor deposition (CVD). MoS

The amplification sequences of FAM20B. (DOCX 22 kb)

The amplification sequences of SOSTDC1. (DOCX 13 kb)

Introduction: Acquired resistance to reversible EGFR tyrosine kinase inhibitors remains a significant obstacle, and acquired ERBB2 amplification is the most common “bypass” mechanism. For patients with sensitizing EGFR mutation who experience resistance via ERBB2 amplification, no targeted drug has been demonstrated to be effective. Patient concerns: A 56-year-old female nonsmoker suffered from left leg paralysis and low back pain. Imaging examination revealed a mass in the anterior segment of the right upper lobe lung and possible multiple metastases in the right hilar, mediastinal lymph nodes, bone metastases, and soft tissue invasion. Diagnosis: Transbronchial lung biopsy revealed a moderately differentiated adenocarcinoma (cT4N2M1c, stage IV). An EGFR exon 19 deletion was identified using amplification refractory mutation system. Interventions: After the patient was treated with gefitinib initiation (250 mg/d) for 15 months, the tumor progressed with ERBB2 amplification revealed by next-generation sequencing test. Then, the patient was started on afatinib (40 mg/d) plus bevacizumab (7.5 mg/kg every 3 weeks). Outcomes: The combination therapy of afatinib and bevacizumab in this patient was effective with some slight side effects. Computed tomography scans showed the tumor shrinkage and the pleural effusion disappeared in the right lung. The overall survival was 23.5 months. Conclusion: To date, there is no targeted therapy approved and demonstrated to be effective for non-small cell lung cancer patients with EGFR sensitizing mutations, and ERBB2 amplification. The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients.

BACKGROUND: The human papillomavirus (HPV) is emerging as an important risk factor in head and neck squamous cell carcinoma (HNSCC) patients. This has been observed particularly in the case of HPV16. The HPV16+ HNSCC subtype has distinct pathological, clinical, molecular, and prognostic characteristics. This study aimed to identify potential microRNAs (miRNAs) and their roles in HPV16+ HNSCC progression. METHOD: miRNA, mRNA and the clinical data of 519 HNSCC and 44 HNSCC-negative samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DEMs) in HPV16-related HNSCC tissues with prognostic value were selected. DEM levels were assessed based on clinicopathological parameters and overall survival (OS). Target genes were also predicted and functional analysis based on Gene Set Enrichment Analysis (GSEA) were then performed. RESULTS: In HPV16+ HNSCC tissues, miR-99a-3p and miR-4746-5p were significantly upregulated. In contrast, miR-411-5p was shown to be downregulated. miR-99a-3p(high)miR-411-5p(low)miR-4746-5p(high) expression could estimate improved OS and low frequent perineural invasion (PNI). Predicted target genes were enriched in cell growth, neuroepithelial cell differentiation, MAPK and FoxO signaling pathways. Epithelial mesenchymal transition (EMT) gene set and invasion related genes were downregulated in miR-99a-3p(high)miR-411-5p(low)miR-4746-5p(high) HNSCC patients. CONCLUSION: miR-99a-3p, miR-411-5p and miR-4746-5p might participate in HPV16+ HNSCC progression through EMT related pathways and affect prognosis.

The fracture of Cement Treated Base (CTB) is greatly influenced by its mesoscale structure and characteristics. The Discrete Element Method (DEM) was adopted to build a mesoscale Semicircular Bending (SCB) model of CTB. The DEM models were built based on two methods including the Digital Image Process (DIP) of actual aggregate distribution and randomization algorithm to generate aggregates. The mesoscale heterogeneity of the model consisted of aggregates, cement mortar, Interface Transition Zone (ITZ) and air voids. Analysis results showed that the DEM models based on both DIP and randomization with the Linear Parallel Bond Model (LPBM) presented satisfying results, compared with laboratory tests. It was found that the main cracks occurred along ITZ between mortar and aggregates. The gradation and distribution of aggregate, and air voids have all significant influence on the fracture resistance and the crack propagation of the CTB. The lime-ash treated material simulation results showed relatively higher fracture toughness over strength ratio.

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development.

Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients.In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α.

Transition metal dichalcogenides (TMDCs) are promising for future electronic and optoelectronic applications, such as field effect transistors (FETs), for their high carrier mobility with a thin layer, wide bandgap, and organic-like flexibility. However, background doping and unipolar electrical characteristics are commonly observed in TMDCs and their based FETs due to the naturally inevitable vacancy defects, which limit their application in electronics and optoelectronics systems. Here, taking MoS2 as an example, in a TMDC FET, ambipolar properties were achieved at room temperature by introducing an amorphous solid ionic conductor lithium tantalate (LiTaO3) as the gate dielectric, which could guarantee the modulation of the Fermi level in the MoS2 channel by the gate electric field. Based on the modulation mechanisms by the solid ionic conductor-gated electric field for the transformation of conduction mode, the three-terminal device exhibits a gate-controlled rectifying, that is, thyristor performance with a high rectification ratio over 300 obtained at a low gate voltage of 2 V. The present results show the great potential of TMDCs in future logic and other electronic device applications.

The steel corrosion induced by chloride penetration is a great threaten to concrete structures, in particular exposed to marine environments. Super absorbent polymer (SAP), as a water reservoir, is probably conducive to reinforced concrete suffered from steel corrosion in marine environments. Therefore, the influence of SAP on the chloride penetration and corrosion behavior of steel in concrete were investigated using concrete mixed with 0∼2 kg/m3 SAP. The results indicate that the permeability and chloride diffusion coefficient consistently rise up with increasing with SAP dosage. Furthermore, the higher SAP dosage results in an ascending free chloride content when subjected to tidal zone. However, when exposed to atmosphere zone, the effect of SAP can be neglected. Moreover, the corrosion current of the sample with SAP are larger than that without SAP, while more corrosion products can be observed in the sample with SAP. Since the stress and strain applied on concrete and internal steel bar of specimens with SAP are apparently smaller, the propagation of crack caused by steel corrosion is probably postponed. Thus, it can be roughly concluded that for concrete subjected to marine environment, adding SAP to concrete can delay the failure process of reinforced concrete to some extent and an optimized dosage of SAP is suggested to be 1 kg/m3.

Background In late December 2019, an outbreak of acute respiratory illness, coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. We aimed to study the epidemiology, clinical features and short-term outcomes of patients with COVID-19 in Wuhan, China. Methods We performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital, including 55 severe patients and 166 non-severe patients, from January 2, 2020 to February 10, 2020. Results Of the 221 patients with COVID-19, the median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU (intensive care unit) care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. Conclusions Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

In order to solve the problem of unsatisfactory accuracy of spectrum prediction in a network with multiple primary users, this paper proposes a cooperative spectrum prediction algorithm. The overlapping alliance game is introduced into spectrum prediction. The alliance structure with the highest accuracy of collaborative prediction is selected, and the result with the highest accuracy is obtained. In the experiment, three different collaborative prediction methods are compared and the effects of different parameter values on the simulation results are analysed. The results show that the proposed method has high prediction accuracy, adaptability and robustness.

Alzheimer's disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.

Background Agents promoting oligodendrocyte precursor cell differentiation have the potential to restore halted and/or delayed remyelination in patients with multiple sclerosis. However, few therapeutic targets have been identified. The objective of this study was to identify novel targets for promotion of remyelination and characterize their activity in vitro and in vivo. Methods A high-content screening assay with differentiation of primary rat oligodendrocyte precursor cells was used to screen GSK-proprietary annotated libraries for remyelination-promoting compounds. Compounds were further validated in vitro and in vivo models; clinical relevance of target was confirmed in human post-mortem brain sections from patients with MS. Results Of ~1000 compounds screened, 36 promoted oligodendrocyte precursor cell differentiation in a concentration-dependent manner; seven were histamine receptor-3 (H3R) antagonists. Inverse agonists of H3R but not neutral antagonists promoted oligodendrocyte precursor cell (OPC) differentiation. H3R was expressed throughout OPC differentiation; H3R expression was transiently upregulated on Days 3–5 and subsequently downregulated. H3R gene knockdown in OPCs increased the expression of differentiation markers and the number of mature oligodendrocytes. Overexpression of full-length H3R reduced differentiation marker expression and the number of mature cells. H3R inverse agonist GSK247246 reduced intracellular cyclic AMP (cAMP) and downstream cAMP response element-binding protein (CREB) phosphorylation in a dose-dependent manner. Histone deacetylase (HDAC-1) and Hes-5 were identified as key downstream targets of H3R during OPC differentiation. In the mouse cuprizone/rapamycin model of demyelination, systemic administration of brain-penetrable GSK247246 enhanced remyelination and subsequently protected axons. Finally, we detected high H3R expression in oligodendroglial cells from demyelination lesions in human samples of patients with MS, and validated a genetic association between an exonic single nucleotide polymorphism in HRH3 and susceptibility to multiple sclerosis. Conclusions From phenotypic screening to human genetics, we provide evidence for H3R as a novel therapeutic target to promote remyelination in patients with multiple sclerosis.

Receptor-interacting serine-threonine kinase 3 (RIPk3) is a key signaling molecule in the regulation of cell apoptosis and necroptosis, it plays an important role in the pathophysiological changes of many hematologic diseases. However, the regulatory role of RIPk3 in programmed cell death (PCD) is not fully known. In this study, bone marrow-specific RIPk3 gene knockout homozygotes (RIPk3-/- mice) were established by homologous recombination. The physiological index of peripheral blood, the morphology and structure of the bone marrow, the bone marrow nucleated cells (BMNCs), the hemopoietic stem cells (HSCs), interleukin-6 (IL-6) level and the colony formation capacity of bone marrow hematopoietic progenitor cells were compared between RIPk3-/- mice and wild-type mice. The results showed that, the cell death rate of BMNCs in RIPk3-/- mice was significantly higher than that in control mice, indicated that RIPk3 gene knockout may cause damage to bone marrow cells to some extent. However, the bone marrow had normal structure and morphology in the bone marrow-specific RIPk3-knockout mice, and there were not significantly different between the two mice in most of the blood physiological indicators, and colony yields of hemopoietic stem/progenitor cells. Further study found that the bone marrow IL-6 level of the RIPk3-/- mice increased significantly, besides, the number of BMNCs and HSCs in the bone marrow of the RIPk3-/- mice increased considerably as compared with the control mice. The findings implies that bone marrow RIPk3 gene knockout may lead to the increase of BMNCs cell death, however, increased secretion of hematopoietic cytokines such as IL-6 may promote the proliferation of hematopoietic stem/progenitor cells and thus maintain the stability of bone marrow hematopoiesis. This hypothesis and the detailed mechanisms remain to be further investigated.

The aim of the present study was to review the effectiveness of psychological and/or educational interventions for reducing psoriasis severity and improving psychological and quality of life (QOL) outcomes in psoriasis. Sixteen papers met the inclusion criteria. Overall, the effectiveness of the existing interventions from this narrative synthesis is positive, especially in psychological and QOL outcomes. Of the 16 included studies, only five were randomized controlled trials (RCTs). The strength of the evidence to support the effectiveness of the existing interventions was limited due to methodological weakness in the included studies. The review concludes that further research is needed to examine the effectiveness of psychological and/or educational interventions for individuals with psoriasis, including a greater number of RCTs in order to increase the methodological validity of intervention studies. Also, future research needs to be conducted to establish which interventions are most effective for specific sub-populations who may best profit from psycho-educational interventions.

Cigarette smoking is an important risk factor for chronic obstructive pulmonary disease (COPD), yet its pathogenic mechanisms are not yet fully understood. Endothelial dysfunction is known to be involved in the pathogenesis of COPD. A detailed understanding of the mechanism involved in its progression would have a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cells (HPMECs). Overexpression of SIRT4 significantly inhibits CSE-induced mononuclear cell adhesion to HPMECs. Consistently, we found that overexpression of SIRT4 attenuates the induction of vascular cell adhesion molecule 1 (VCAM-1) and E-selectin. Importantly, SIRT4 was found to negatively regulate CSE-induced NF-κB activation via inhibiting the degradation of IκBα. Moreover, we also found that proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, the downstream target genes of NF-κB, are also inhibited by overexpression of SIRT4. These results suggest that SIRT4 protects HPMECs exposed to CSE stress via a mechanism that may involve the NF-κB pathway. Strategies based on the enhancement of SIRT4 may prove to be beneficial in the treatment of cigarette smoking caused COPD.

Self-assembled structures of 2D materials with novel physical and chemical properties, such as the good electrical and optoelectrical performance in nanoscrolls, have attracted a lot of attention. However, high photoresponse speed as well as high responsivity cannot be achieved simultaneously in the nanoscrolls. Here, a photodiode consisting of single MoS2 nanoscrolls and a p-type WSe2 is demonstrated and shows excellent photovoltaic characteristics with a large open-circuit voltage of 0.18 V and high current intensity. Benefiting from the heterostructure, the dark current is suppressed resulting in an increased ratio of photocurrent to dark current (two orders of magnitude higher than the single MoS2 nanoscroll device). Furthermore, it yields high responsivity of 0.3 A W-1 (corresponding high external quantum efficiency of ≈75%) and fast response time of 5 ms, simultaneously. The response speed is increased by three orders of magnitude over the single MoS2 nanoscroll device. In addition, broadband photoresponse up to near-infrared could be achieved. This atomically thin WSe2 /MoS2 nanoscroll integration not only overcomes the disadvantage of MoS2 nanoscrolls, but also demonstrates a single nanoscroll-based heterostructure with high performance, promising its potential in the future optoelectronic applications.

Laboratory experiments exploring the interaction between molten steel, slag and lining refractory were performed. The transient erosion and reaction over time were investigated, and the transient change of the reaction layer and inclusions generated in the molten steel were evaluated using optical microscopy and SEM-EDS. Without slag addition before remelting, the FeO from reoxidation entered the space between the lining refractory and the steel and strengthened the erosion of the lining refractory. Several layers were found from the steel to the original lining refractory layer: steel phase, FeO layer, a FeO-rich lining layer and an Original Lining (OL)-rich lining layer. The thickness of the reaction layer increased nearly linearly with the reaction time at an erosion rate of 4.2 µm/min. With slag addition before remelting, the reaction layer between the steel and the original lining materials included several sub-layers: a gap, a slag layer, an FeO-rich lining layer and an Original Lining (OL)-rich lining layer. The thickness of the reaction layer nearly linearly increased with the reaction time and with an erosion rate of 5.7 µm/min. Slags were entrained into the steel occasionally.

During early embryonic development, bone morphogenetic protein (BMP) signaling is essential for neural/non-neural cell fate decisions. BMP signaling inhibits precocious neural differentiation and allows for proper differentiation of mesoderm, endoderm, and epidermis. However, the mechanisms underlying the BMP pathway-mediated cell fate decision remain largely unknown. Here, we show that the expression of Ovol2, which encodes an evolutionarily conserved zinc finger transcription factor, is down-regulated during neural differentiation of mouse embryonic stem cells. Knockdown of Ovol2 in embryonic stem cells facilitates neural conversion and inhibits mesendodermal differentiation, whereas Ovol2 overexpression gives rise to the opposite phenotype. Moreover, Ovol2 knockdown partially rescues the neural inhibition and mesendodermal induction by BMP4. Mechanistic studies further show that BMP4 directly regulates Ovol2 expression through the binding of Smad1/5/8 to the second intron of the Ovol2 gene. In the chick embryo, cOvol2 expression is specifically excluded from neural territory and is up-regulated by BMP4. In addition, ectopic expression of cOvol2 in the prospective neural plate represses the expression of the definitive neural plate marker cSox2. Taken together, these results indicate that Ovol2 acts downstream of the BMP pathway in the cell fate decision between neuroectoderm and mesendoderm to ensure proper germ layer development.

Slag entrainment in a continuous casting mold is one of the major causes of macro nonmetallic inclusions in continuous casting steel products. Stabilizing the level fluctuation is an important factor to improve steel quality. A new type of submerged entry nozzle (SEN) named self-braking SEN was designed. In the current study, water modeling experiments were performed to study the effect of self-braking SEN on level fluctuation in a continuous casting slab mold. The level position and the root mean square value of level fluctuation were analyzed through the online detection data. The results showed that the flow in the mold was more symmetrical and the tracer dispersion was more uniform. Moreover, the meniscus was also more uniform than the conventional nozzle with the self-braking SEN, especially at high casting speed.

Researches on the relation of a loaded mechanical energy to the damaged banana maturation and its quality evolution has significance to its storage, but there are few researches at present. This paper studied on the effect of the loaded energy on banana to its internal maturation substance evolution and stored quality with time, including the change of maximum impact stress, re-enduring impact energy. The results showed there existed a significant correlation between energy transformation and increment of maturity substance in the damaged banana. Also, there existed a significant association between energy transformation and increment of maturity substance in the damaged banana in its storage time, and appeared a trends that the mechanical energy being transferred into fruit internal energy increased its maturity substance and decreased its stored quality, but individual maturity difference had less effect. Thus, decreasing the energy and the substance transformation in damage area are the important means of extending the physiology life of fruits, which is an urgent problem to be solved in their field of processing and storage at present.

Functional and inclusion dependency discovery is important to knowledge discovery, database semantics analysis, database design, and data quality assessment. Motivated by the importance of dependency discovery, this paper reviews the methods for functional dependency, conditional functional dependency, approximate functional dependency, and inclusion dependency discovery in relational databases and a method for discovering XML functional dependencies. Refereed/Peer-reviewed

To replace nickel-based stainless steel, a nitrogen-bearing stainless steel was produced to lower the production cost stemming from the shortage of nickel recourses. Thermodynamic model to calculate the saturated nitrogen content in the stainless steel was developed and the model was validated by experimental measurements performed with a high temperature induction furnace. Nitrogen gas under constant pressure was injected into the molten steel with a top lance. Thus, the nitrogen was transferred to the molten stainless steel. The effects of chemical composition, temperature, superficial active elements and nitrogen flow rate on the transfer of nitrogen to the steel were investigated and discussed. The results showed that the dissolution rate of nitrogen in the molten steel increases with a higher temperature and larger nitrogen flow rate but decreases significantly with an increase in the content of surface-active elements. Alloying elements such as chromium and manganese having a negative interaction coefficient can increase the dissolution of nitrogen in the molten steel. It was also proposed that the primary factor affecting the final saturated nitrogen content is temperature rather than the dissolved oxygen content.