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Boolean query is an important method to achieve accurate data retrieval. The deeply study of Boolean query’s implementation strategy is conducive to flexible application of Boolean query, optimization of query expression and improvement of execution efficiency. Starting with the implementation strategy of Boolean query in Lucene framework, this paper studies the representation, execution sequence diagram, logical operation rules and sub-query merging algorithm. According to the implementation strategy, the simplification rules of complex Boolean query with depth of 2 are proposed, and their correctness is proved theoretically. Finally, the validity of these laws is verified by experimental simulation.

In this paper, stability for linear discrete switched descriptor system is studied by using the proportional plus derivative state feedback control. Firstly, the definition of normal and stable is extended from continuous descriptor systems to discrete descriptor systems. Secondly, some sufficient conditions are given to ensure that the closed-loop systems are normal and stable by designing state-dependent switching laws. Meanwhile, the expressions of proportional plus derivative state feedback controllers are given. A numerical simulation is given to show the validity of the obtained results.

As a kind of retrieval tool, the thesaurus plays an important role in the field of information retrieval. The compilation of thesaurus is beneficial to academic exchanges by scholars from different backgrounds. Based on the early survey, which discovers 423 Chinese thesauri and 126 English thesauri, this paper statistically analyzes the thesaurus from the publishing years, disciplinary fields, volume of words, organizations and semantic relations. The standards, the compiling techniques and the development of the indexing language are summarized respectively. All the above provides references for future work.

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen, particularly in immunocompromised patients due to their adverse antimicrobial susceptibility pattern. The objective of this article was to investigate the clinical impact of SM bacteremia on the 30-day mortality rate and identify the risk factors of the cause of mortality in patients with hematologic disorders. We retrospectively reviewed the clinical data in patients diagnosed with hematological disorders and SM bacteremia over an 8-year period from July 2010 to July 2018 at a 248-bed hematology department. We compared patients’ clinical characteristics and outcomes between the non-survivor and survivor groups. The overall incidence of SM bacteremia was 25.1 per 10,000 admissions. There were 59 patients (median age: 35 years; 57.6% males) included in the study with an overall SM bacteremia-related 30-day mortality of 44.1%. Multi-drug resistance was common. In vitro susceptibility is higher to ceftazidime (72.9%), ciprofloxacin (66.1%) and cefoperazone/sulbactam (59.3%). The risk factors identified in the univariate analysis were catheter re-implantation, accompanying polymicrobial infection, inadequate initial antimicrobial treatment, APACHE II score, temperature > 39 °C, septic shock, respiratory failure, and non-remission post treatment for primary diseases. Multivariate analysis further confirmed that inadequate initial antimicrobial treatment, respiratory failure, and non-remission after treatment for hematological diseases are independent risk factors associated with mortality (P = 0.001, 0.002 and 0.007, respectively). Our study suggests that SM bacteremia is highly associated with increased mortality in patients with hematologic diseases. Early detection, prompt comprehensive management including initiation of combined sensitive antibiotics, respiratory monitoring and support, platelet infusion, and strategies to improve patients’ remission status are recommended to improve the overall survival in patients with SM bacteremia.

This paper aims to study stability for discrete-time non-linear singular systems with switching actuators. A sufficient condition is addressed to ensure that non-linear closed-loop singular systems are input-to-state stable via average dwell time approach and the iterative relationship of discrete-time systems. In the stability criterion, we neither construct a certain Lyapunov function, nor design the specific structure of the control inputs. It is much easier to design each sub-controller of switching actuators via the proposed condition. Finally, a numerical example is provided to demonstrate the feasibility and effectiveness of the results obtained.

To the question of feature selection and multi-feature fusion in facial expression recognition, a novel fusion model is proposed in this paper based on evidence theory and local feature operator. First, the facial image is divided into several regions with significant recognition features, and the Local Binary Pattern (LBP) textural features of the regions are extracted. Then, the LBP histograms in the local regions are connected into a single histogram list, and Chi-square distance is used as the similarity measure to establish the guidelines for evidence synthesis. Finally, the Dempster-Shafer evidence inference theory (D-S evidence theory) is adopted to accomplish the feature vector fusion of all components and the class judgment of facial expression is performed. Experiment shows that the method is simple and effective, which has a high recognition rate and can improve the performance of the facial expression recognition system to some extent.

Donor killer immunoglobulin-like receptor (KIR) group B profiles (Bx) and homozygous of centromeric motif B (Cen-B/B) are the most preferable KIR gene content motifs for hematopoietic stem cell transplantation (HSCT). The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (regardless of number) were observed for standard-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients in this 4-year retrospective study. A total of 210 Chinese patients who underwent unrelated donor HSCT were investigated. Donor KIR profile Bx was associated with significantly improved overall survival (OS; P = .026) and relapse-free survival (RFS; P = .021) and reduced nonrelapse mortality (NRM; P = .017) in AML/MDS patients. A significantly lower survival rate was observed for transplants from Bx1 donors compared with Bx2, Bx3, and Bx4 donors for patients in first complete remission (n = 82; OS: P = .024; RFS: P = .021). Transplant from donors with Cen-B resulted in improved OS (HR = .256; 95% CI, .084 to .774; P = .016) and RFS (HR = .252; 95% CI, .084 to .758; P = .014) in AML/MDS patients at standard risk. However, this particular effect did not increase with a higher number of Cen-B motifs (cB/B versus cA/B; OS: P = .755; RFS: P = .768). No effect was observed on high-risk AML/MDS, acute lymphoblastic leukemia/non-Hodgkin lymphoma, and chronic myelogenous leukemia patients. Avoiding the selection of HSCT donors of KIR profile Bx1 is strongly advisable for standard-risk AML/MDS patients. The presence of the Cen-B motif rather than its number was more important in donor selection for the Chinese population.

Outcomes for hematopoietic stem cell transplantation (HSCT) in various donor and recipient killer immunoglobulin-like receptor (KIR) genotypes have been studied extensively. The associations between KIR2DS4 and its variant KIR1D with outcomes of HSCT from a sibling-related HLA-matched donor with KIR haplotype A have not been explored, however. To study this, we genotyped donor–recipient pairs and divided 165 recipients of HSCT from a KIR gene haplotype A donor into 3 groups: 2DS4+/2DS4+ (2 intact KIR2DS4 alleles), 2DS4+/1D+ (heterozygous), and 1D+/1D+ (homozygous for the deletion variant KIR1D). No difference in the recovery of neutrophils and platelets among the 3 groups was observed. The cumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD) within day +100 was 28.94% in the 2DS4+/2DS4+ group, 14.11% in the 2DS4+/1D+ group, and 44.44% in the 1D+/1D+ group (P = .0159). Multivariate analysis identified 1D+/1D+ as an independent risk factor for aGVHD (hazard ratio [HR], 4.221; 95% confidence interval [CI], 1.470 to 12.124; P = .007). In contrast, the cumulative incidences of chronic GVHD, 3-year cumulative relapse, and treatment-related mortality did not differ significantly among the 3 groups. The rate of cytomegalovirus (CMV) reactivation was 46.96% in the 2DS4+/2DS4+ group, 20.16% in the 2DS4+/1D+ group, and 53.25% in the 1D+/1D+ group (P = .0017). Multivariate analysis identified 2DS4+/1D+ as an independent protective factor for CMV reactivation (HR, 0.268; 95% CI, 0.125 to 0.574; P = .001). Although overall survival (OS) did not differ among the groups in the first year, the 2DS4+/2DS4+ group had significantly better OS than the other groups after 1 year (P = .0361). In patients with advanced-stage disease, the 3-year probability of disease-free survival was 51.06% in the 2DS4+/2DS4+ group, 34.01% in the 2DS4+/1D+ group, and 0% in the 1D+/1D+ group (P = .0314). Collectively, our data suggest that the KIR 2DS4/1D allelic variance is associated with the outcome of sibling-related HLA-matched HSCT, and that donor subclassification of KIR 2DS4/1D alleles should be considered in this setting.

The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP–mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)–matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. Anti-HLA antibodies using the Luminex method was applied to 123, 117, and 106 serum samples collected before and 1 month and 3 months after transplantation. The presences of anti-HLA antibodies at the 3 time points were 37.4% (46 of 123), 40.2% (47 of 117), and 22.6% (24 of 106). Mismatch of HLA-DPB1 and/or DPA1 allele between patient-donor pairs was 83.6% (92 of 110). Patients with anti-HLA antibodies had delayed platelet recovery. The presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic graft-versus-host disease (GVHD), higher treatment-related mortality, and reduced overall survival (OS) and disease-free survival, especially in acute myeloid leukemia and myelodysplastic syndrome patients. Multivariate analysis showed that presence of anti-HLA antibodies before transplantation was a risk factor for GVHD and OS. Furthermore, HLA-DP loci–matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT.

Accurate regulation of innate immunity is necessary for the host to efficiently respond to invading pathogens and avoid excessive harmful immune pathology. Here we identified OTUD3 as an acetylation-dependent deubiquitinase that restricts innate antiviral immune signaling. OTUD3 deficiency in mice results in enhanced innate immunity, a diminished viral load, and morbidity. OTUD3 directly hydrolyzes lysine 63 (Lys63)-linked polyubiquitination of MAVS and thus shuts off innate antiviral immune response. Notably, the catalytic activity of OTUD3 relies on acetylation of its Lys129 residue. In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity. Importantly, acetyl-OTUD3 levels are inversely correlated with IFN-β expression in influenza patients. These findings establish OTUD3 as a repressor of MAVS and uncover a previously unknown regulatory mechanism by which the catalytic activity of OTUD3 is tightly controlled to ensure timely activation of antiviral defense.

Type I interferons (IFN-Is) are a family of cytokines that exert direct antiviral effects and regulate innate and adaptive immune responses through direct and indirect mechanisms. It is generally believed that IFN-Is repress tumor development via restricting tumor proliferation and inducing antitumor immune responses. However, recent emerging evidence suggests that IFN-Is play a dual role in antitumor immunity. That is, in the early stage of tumorigenesis, IFN-Is promote the antitumor immune response by enhancing antigen presentation in antigen-presenting cells and activating CD8+ T cells. However, in the late stage of tumor progression, persistent expression of IFN-Is induces the expression of immunosuppressive factors (PD-L1, IDO, and IL-10) on the surface of dendritic cells and other bone marrow cells and inhibits their antitumor immunity. This review outlines these dual functions of IFN-Is in antitumor immunity and elucidates the involved mechanisms, as well as their applications in tumor therapy.

Best management practices (BMPs) are an effective way to control water pollution. However, identification of the optimal distribution and cost-effect of BMPs provides a great challenge for watershed policy makers. In this paper, a semi-distributed, low-data, and robust watershed model, the Revised Generalized Watershed Loading Function (RGWLF), is improved by adding the pollutant attenuation process in the river channel and a bank filter strips reduction function. Three types of pollution control measures&mdash, point source wastewater treatment, bank filter strips, and converting farmland to forest&mdash, are considered, and the cost of each measure is determined. Furthermore, the RGWLF watershed model is coupled with a widely recognized multi-objective optimization algorithm, the non-dominated sorting genetic algorithm II (NSGAII), the combination of which is applied in the Luanhe watershed to search for spatial BMPs for dissolved nitrogen (DisN). Fifty scenarios were finally selected from numerous possibilities and the results indicate that, at a minimum cost of 9.09 &times, 107 yuan, the DisN load is 3.1 &times, 107 kg and, at a maximum cost of 1.77 &times, 108 yuan, the total dissolved nitrogen load is 1.31 &times, 107 kg, with the no-measures scenario, the DisN load is 4.05 &times, 107 kg. This BMP optimization model system could assist decision-makers in determining a scientifically comprehensive plan to realize cost-effective goals for the watershed.

This study aims to investigate the problem of finite-time $H_{\infty}$ control for continuous switched nonlinear systems. Firstly, we extend finite-time stability (FTS) and finite-time boundedness (FTB) to switched nonlinear systems. Secondly, in terms of the multiple Lyapunov functions and average dwell time (ADT) approach, some sufficient conditions are obtained to guarantee that the systems are finite-time bounded and satisfy a given $H_{\infty}$ performance. Finally, two examples are given to verify the feasibility and effectiveness of the obtained results.

In view of the current trend of the development of application-oriented colleges and universities, the problems existing in the teaching of Single Chip Microcomputer (SCM) are analyzed, and the project-based teaching mode is introduced. Then, the principle and specific implementation plan of the instructional design of the small project-based teaching are elucidated. With a small temperature measurement project as a detailed example, the specific implementation model of project-based teaching mode is explained, which organically combines the theoretical teaching with the practical teaching, thus the subjective learning initiative of the students is mobilized, and their awareness of innovation is developed. Practice has proved that this mode has achieved good results in practical teaching, which explores a new path for the teaching reform of the SCM course.

Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations. Clinical Trial Registration: NCT03148743.

With the development and application of next-generation sequencing (NGS) and target capture technology, the demand for an effective analysis method to accurately detect gene fusion from high-throughput data is growing. Hence, we developed a novel fusion gene analyzing method called single-end gene fusion (SEGF) by starting with single-end DNA-seq data. This approach takes raw sequencing data as input, and integrates the commonly used alignment approach basic local alignment search tool (BLAST) and short oligonucleotide analysis package (SOAP) with stringent passing filters to achieve successful fusion gene detection. To evaluate SEGF, we compared it with four other fusion gene discovery analysis methods by analyzing sequencing results of 23 standard DNA samples and DNA extracted from 286 lung cancer formalin fixed paraffin embedded (FFPE) samples. The results generated by SEGF indicated that it not only detected the fusion genes from standard samples and clinical samples, but also had the highest accuracy and sensitivity among the five compared methods. In addition, SEGF was capable of detecting complex gene fusion types from single-end NGS sequencing data compared with other methods. By using SEGF to acquire gene fusion information at DNA level, more useful information can be retrieved from the DNA panel or other DNA sequencing methods without generating RNA sequencing information to benefit clinical diagnosis or medication instruction. It was a timely and cost-effective measure with regard to research or diagnosis. Considering all the above, SEGF is a straightforward method without manipulating complicated arguments, providing a useful approach for the precise detection of gene fusion variation.

This paper is concerned with input and output strictly passive H-infinity control of switched linear systems. Based on the definition of input and output strictly passive, a sufficient condition is first derived by using multiple Lyapunov functions method, which can ensure that the autonomous system is asymptotically stable and satisfies H-infinity performance index. Next, the above result is extended to the controlled plant, and the sub-controller with explicit expression of each subsystem is given. Finally, two numerical examples are given to show the validity of the proposed approaches.

BACKGROUND There are very few studies investigating metabolic biomarkers to predict acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Metabolic models can provide a framework for analyzing the information-rich omics data sets in this setting. METHODS Four hundred and fifty-six samples from one hundred and fourteen consecutive patients who underwent HSCT from January 2012 to May 2014 were collected for this study. The changes in serum metabolite levels were investigated using a gas chromatography-mass spectrometry-based metabolomics approach and underwent statistical analysis. RESULTS Significant metabolic changes were observed on day 7. The stearic acid/palmitic acid (SA/PA) ratio was effective in the diagnosis of grade II-IV aGVHD. Multivariate analysis showed that patients with high SA/PA ratios on day 7 after HSCT were less likely to develop II-IV aGVHD than patients with low SA/PA ratios (odds ratio [OR] = 0.06, 95% CI 0.02-0.18, P < 0.001). After the adjustment for clinical characteristics, the SA/PA ratio had no significant effect on overall survival (hazard ratio [HR] = 1.95, 95% CI 0.92-4.14, P = 0.08), and patients in the high SA/PA ratio group were significantly more likely to relapse than those in the low ratio group (HR = 2.26, 95% CI 1.04-4.91, P = 0.04). CONCLUSION Our findings suggest that the SA/PA ratio on day 7 after HSCT is an excellent biomarker to predict both aGVHD and relapse. The serum SA/PA ratio measured on day 7 after transplantation may improve risk stratification for aGVHD and relapse after allogeneic stem cell transplantation. FUNDING National Natural Science Foundation of China (81470346, 81773361), Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Natural Science Foundation (BK20161204), Innovation Capability Development Project of Jiangsu Province (BM2015004), Jiangsu Medical Junior Talent Person award (QNRC2016707), and NIH (AI129582 and NS106170).

Restoration of hazy image is an important issue in outdoor vision system. To accelerate the processing speed, a fast single image dehazing method is proposed based on the atmospheric scattering model and gray projection. In this method the transmission map is estimated roughly using minimum filtering which is based on dark channel prior and refined with fast average filtering. The gray projection method is adopted to obtain the atmospheric light. The subsection mechanism is designed to avoid the high light of sky region in recovered image, and Weber-Fechner Law is employed for color compensation in restored image. Our experimental results show that this algorithm can restore satisfied haze-free image, and keep the balance of quality and speed in real-time system.

Newly diagnosed acute myeloid leukemia (AML) failed to achieve complete remission after two courses of intensive chemotherapy. This was considered as primary refractory AML (PRR-AML), and still has a dismal prognosis. Allogeneic hematopoietic stem cell transplantation could be the only cure for these patients. However, the role of haploidentical hematopoietic stem cell transplantation (HID-HCT) for PRR-AML is still undetermined. We retrospectively analyzed the outcomes of 45 adult patients with PRR-AML who underwent HID-HCT, and compared it with the result of 53 patients who received HLA-matched related or unrelated donor transplantation (MD-HCT) during the same treatment period. The 3-year overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) rates in the HID-HCT group were 19.0, 16.5, 70.0, and 35.2%, respectively, but showed no significant differences from the results of MD-HCT. Multivariate analysis showed that complex karyotype with del(7) and time > 6 months from diagnosis to transplantation were associated with lower OS and LFS, and chronic GVHD demonstrated better OS and LFS in the entire cohort. Complex karyotype with del(7) was related with higher CIR and chronic GVHD with lower CIR. In conclusion, HID-HCT could be an alternative treatment strategy to improve the long-term survival in PRR-AML adult patients who have no HLA-matched donors.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is characterised by skin rash and multivisceral involvement. The liver is the organ most frequently affected and the degree of liver function impairment often correlates with the mortality rate of DRESS. We aimed to examine the expression of cytotoxic proteins, including soluble Fas ligand (sFasL), TNF-α, granulysin, perforin, and granzyme B in the sera and skin lesions of patients with DRESS and evaluate their clinical significance. Our cohort consisted of 21 patients with DRESS and control groups including 39 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 21 patients with maculopapular eruption, and 29 normal controls. Concentrations of cytotoxic proteins in the sera were measured using enzyme-linked immunosorbent assays. Tissue samples were also obtained from typical skin lesions, and immunohistochemical staining was conducted to assess the local expression of cytotoxic proteins. We found that sFasL and granzyme B were significantly overexpressed in the sera of DRESS patients compared to normal controls. Furthermore, the levels of sFasL, perforin, and granzyme B significantly correlated with the serum level of liver enzymes in DRESS patients. Immunohistochemical examination also showed overexpressed cytotoxic proteins in cutaneous DRESS lesions. Cytotoxic proteins may play a vital role in the pathogenesis of DRESS, and serum sFasL, perforin, and granzyme B may also be involved in liver function impairment in DRESS patients.

Lung cancer has very high mortality and glycyrrhizin was found to significantly inhibit the growth of lung cancer cells in vitro and tissues in mice. However, the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is still unclear. In this study, we first found that glycyrrhizin inhibited the growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration and invasion of lung cancer cells, which was suppressed by glycyrrhizin. Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. Therefore, this study revealed a potential mechanism by which glycyrrhizin can inhibit the progression of lung cancer.

Several studies have reported a significant role of high mobility group box protein 1 (HMGB1) in lung cancer. Nevertheless, there is a lack of knowledge regarding the expression of HMGB1 and its correlation with the clinicopathological features of lung cancer. In addition, the potential molecular mechanisms underlying the role of HMGB1 in lung cancer are still unknown. We therefore investigated the clinicopathological and prognostic significance as well as the potential role of HMGB1 in the development and progression of lung cancer. HMGB1 expression in the tumor tissues of the cohort correlated with clinicopathological features. Moreover, lung cell migration and invasion were significantly increased after treatment with HMGB1. The matrix metalloproteinase-2 (MMP-2) expression and activity were upregulated after treatment with HMGB1, while the upregulated expression of MMP-2 stimulated by HMGB1 in lung cancer cells was significantly reduced with the blockage of si-p65. These results indicated that HMGB1 expression was significantly associated with lung cancer progression. We also showed that HMGB1 promoted lung cancer invasion and metastasis by upregulating the expression and activity of MMP-2 in an NF-κB-dependent manner. Taken together, these data suggested that HMGB1 may be a potential prognosis and therapeutic marker for lung cancer.

DRESS is one of the most severe drug reactions. The aim of this retrospective study was to summarize the clinical presentation, genetic predisposition and prognostic factors of DRESS. A total of 52 patients with DRESS, who were inpatients at a medical referral centre in Shanghai, China, from January 2011 to December 2016, were analysed retrospectively. All the patients had skin eruption, 83% had liver involvement, and ≤10% had other organ involvement. Mean cost of hospitalization was US$5,511±3,050. The 3 most common causative agents were allopurinol (18/52; 35%), salazosulphapyridine (11/52; 21%) and carbamazepine (5/52; 10%). HLA-B*5801 and HLA-B*1302 were associated with allopurinol-induced DRESS. HLA-B*1301 was related to salazosulphapyridine-induced DRESS. The mortality rate was 6% (3/52). Epstein-Barr virus DNA was found in 10 patients (19%) and indicated a poor prognosis. Human herpes virus 6 DNA was detected in 17 patients (33%) and was associated with autoimmune sequelae. Due to its high medical cost and sometimes poor prognosis, prevention of DRESS should be a high priority.

Background and objective Recombinant-activated factor VII (rVIIa) is a vitamin K-dependent glycoprotein that is an analog of the naturally occurring protease. It has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Gastrointestinal (GI) bleeding is a severe complication following hematopoietic stem cell transplantation (HSCT) in patients with thrombocytopenia, while hemostatic measures based on antifibrinolytic or transfusion therapy may not always be successful. The present study investigated the treatment with rFVIIa in severe GI bleeding among thrombocytopenia patients undergoing HSCT. Methods rFVIIa was given as a single dose of 60μg/kg in patients with GI bleeding following hematopoietic stem cell transplantation (HSCT). Results Among all patients enrolled, 12 (75%) of 16 patients obtained a response, of which 5 achieved a complete response and 7 achieved a partial response. The 4 remiaing patients (25%) had no response. Nine patients (56.3%) died in a follow-up of 90 days. No thromboembolic events wereassociated with the drug administration occurred. Conclusions Our study showed that rFVIIa may represent an additional therapeutic option in such cases.

Poly(lactide-co-glycolide) (PLGA)-based particles have been widely used as carriers of various kinds of drugs, which are sequestered by the cell membrane and degraded through endo-lysosome and auto-lysosomal pathways. Lysosome is the destination of endocytosis and autophagy, which is also an organelle for the cell to execute death. Here, we show that chloroquine (CQ) and ciprofloxacin (CPX) (LMP inducer reagents)-loaded PLGA hollow microspheres (HMs) could be delivered by passive targeting into endo-lysosome and auto-lysosome. Co-loading with NaHCO3 accelerates the release of CQ and CPX in the acid environment of endo-lysosome and auto-lysosome. Subsequently, the released CQ and CPX induce lysosomal membrane permeabilization (LMP), which leads to cancer cell death in three different manners: apoptosis, autophagic cell death and apoptosis with autophagosome. Moreover, we use rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR), to induce autophagy and inhibit cell growth. Rapamycin–NaHCO3-loaded HMs combined CQ–NaHCO3-loaded HMs could efficiently induce cancer cell death through apoptosis with autophagosome both in vitro and in vivo.

Dear Editor, Rearrangements involving mixed lineage leukemia (MLL) are common chromosome aberrations in infant, pediatric and adult acute leukemia, which are generally associated with poor prognosis. To date, more than 79 partner genes have been identified [1]. MLL fusion partners can be classified into four groups: nuclear proteins (MLLT3, MLLT10, and MLLT1), cytoplasmatic proteins (GAS7, SH3GL1, EPS15, and MLLT4), histone acetyltransferases (EP300, CREBBP), and the septin family (SEPT2, SEPT5, and SEPT6) [2]. In pediatric and adult AML, the most frequent fusion partners are represented by MLLT3-AF9 (9p22), MLLT10-AF10 (10p12), ELL (19p13.1), MLLT4-AF6 (6q27), and MLLT1-ENL (19p13.3) [1, 3]. However, as a partner gene, the SEPT5 gene has been reported in only five AML cases (Table 1). Here we present two cases of de novo AML with MLL-SEPT5 transcript. Chromosomal analysis revealed a karyotype of 46, XX/XY, t(11;22)(q23;q11.2). Reverse transcription polymerase chain reaction (RT-PCR) analysis indicated an MLL-SEPT5 fusion transcript. Sanger sequencing of the PCR product confirmed the fusion between MLL and SEPT5. Notably, a new fusion transcript between MLL exon 8 and SEPT5 intron 2 was detected in one of the patients. Patient 1 was a 21-yr-old man who presented with fever, oral ulcer, and tonsillitis. His hemoglobin level was 8.5 g/dL, white blood cell count was 35.45 ×10/L, and platelet count was 29×10/L. Bone marrow aspiration was hypercellular, containing 81% blasts. Immunophenotypic analysis showed that the blasts were positive for CD45, CD33, CD117, CD15, and HLADR, but negative for other markers. Cytogenetic studies revealed the karyotype of 46, XY, t(11;22)(q23;q11.2) [8]/46,XY [2]. Fluorescence in situ hybridization analysis using a MLL-specific probe showed a split in the MLL gene (Fig. 1). He received three courses of induction chemotherapy in our hospital followed by a mother-to-son haploidentical bone marrow transplantation. To date, he is in complete remission. To validate MLL-SEPT5 existence, we performed RT-PCR and direct DNA sequencing. Total RNA was extracted from the bone marrow cells using TRIzol reagent (Invitrogen, Paisley, UK) and chloroform. cDNA was obtained by RT-PCR using the M-MLV reverse transcriptase (Promega, Madison, WI, USA). The resulting cDNA was amplified by PCR using 2×Hieff PCR Master Mix (Yaeson, Shanghai, China) and the following primers: 5 -GCTCCACCCATCAAACCAAT-3 from exon 5 of MLL and 5 -TTCTTCTCAATGTCCACCGT-3 from exon 4 of SEPT5 (Fig. 2). PCR products were sequenced on both strands by using an Applied Biosystems ABI 3730 XL DNA analyzer (Thermo Fisher Scientific

Several studies have reported a significant role of high mobility group box protein 1 (HMGB1) in lung cancer. Nevertheless, there is a lack of knowledge regarding the expression of HMGB1 and its correlation with the clinicopathological features of lung cancer. In addition, the potential molecular mechanisms underlying the role of HMGB1 in lung cancer are still unknown. We therefore investigated the clinicopathological and prognostic significance as well as the potential role of HMGB1 in the development and progression of lung cancer. HMGB1 expression in the tumor tissues of the cohort correlated with clinicopathological features. Moreover, lung cell migration and invasion were significantly increased after treatment with HMGB1. The matrix metalloproteinase-2 (MMP-2) expression and activity were upregulated after treatment with HMGB1, while the upregulated expression of MMP-2 stimulated by HMGB1 in lung cancer cells was significantly reduced with the blockage of si-p65. These results indicated that HMGB1 expression was significantly associated with lung cancer progression. We also showed that HMGB1 promoted lung cancer invasion and metastasis by upregulating the expression and activity of MMP-2 in an NF-κB-dependent manner. Taken together, these data suggested that HMGB1 may be a potential prognosis and therapeutic marker for lung cancer.

Natural killer (NK) cells are one group of innate lymphocytes that are important for host defense against malignancy and viruses. MicroRNAs (miRNAs) play a critical role in regulating responses of immune cells including NK cells. Accumulating evidence suggests that miR-146a is involved in the regulation of immune responses. However, the mechanism by which miR-146a regulates NK cell function is largely unknown. In the current study, we found that miR-146a intrinsically regulated NK cell function. Forced overexpression of miR-146a decreased IFN-γ production, whereas downregulation of miR-146a by anti-miR-146a significantly enhanced IFN-γ production in the human NK-92 cell line and primary human NK cells upon stimulation with IL-12 or co-stimulation with IL-12 and IL-18. Mechanistically, miR-146a regulated IFN-γ production via NF-κB, as evidenced in NK-92 cells, by downregulation of NF-κB p65 phosphorylation when miR-146a was overexpressed but upregulation of NF-κB p65 phosphorylation when anti-miR-146a was overexpressed. miR-146a directly targeted IRAK1 and TRAF6, the upstream signaling components of the NF-κB signaling pathway. This direct targeting mechanism confirmed the above gain- and loss-of-function approaches. However, the potent IFN-γ-producing subset, CD56bright NK cells, expressed higher levels of miR-146a than the lesser IFN-γ-producing subset, CD56dim NK cells. We also observed that co-stimulation of IL-12 and IL-18 significantly increased miR-146a expression in bulk NK cells and in the CD56bright subset in a time-dependent manner, correlating with augmented IFN-γ production. These data suggest that miR-146a plays a negative role in IFN-γ production by human NK cells and this miRNA may be critical in preventing NK cells from being super activated and overproducing IFN-γ.

T-cell immunoglobulin and mucin domain-containing molecule3 (Tim-3) represents a novel mechanism of T-cell dysfunction and exhaustion. Tim-3 has also been identified in various solid tumors. However, the role of Tim-3 expression on blast cells in acute myeloid leukemia (AML) is not well understood. In this study, we aimed to explore the role of Tim-3 in patients with de novo AML, and the correlation between Tim-3 and clinicopathological prognosis. The study cohort consisted of 76 patients with de novo non-M3 AML. These patients' bone marrow samples were collected and then bone marrow mononuclear cells (BMCs) were isolated for flow cytometry to detect Tim-3 expression on blasts. According to FAB type, 76 diagnosed AML patients included in this study were: M0 (n=2), M1 (n=16), M2 (n=20), M4 (n=20), M5 (n=16), and M6 (n=2). A positive expression (>20%) of Tim-3 was found in 87% (66/76) of patients with AML. The average percentage of Tim-3(+) blasts in these AML patients was 58.26 ± 29.23%. Moreover, the frequency of Tim-3 high expression was higher in M4 patients than that in other AML patients according to FAB type (P=0.004). Tim-3 high expression was also closely associated with inv(16) (P=0.01) and C/EBPA mutation (P=0.03). The mutations of the following six genes, i.e., FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, were independent of the Tim-3 expression. Additionally, it is more likely to find higher levels of Tim-3 in the low-risk group than in the intermediate- and high-risk groups (P=0.02). The expression of Tim-3 was positively correlated with CD13 (r=0.36, P=0.001), CD34 (r=0.41, P=0.000), and CD7 (r=0.27, P=0.02) in AML patients. AML patients with high Tim-3 expression achieved significantly high complete remission (CR) rate (P=0.01), while their Tim-3 expression significantly decreased after CR (P=0.01). Blockade of Tim-3 expression on AML blasts significantly reduced the Idarubicin (IDA)-mediated suppression of cell growth and reduction of cell apoptosis in vitro. Collectively, our study suggests that high Tim-3 expression on AML blasts could enhances chemotherapy sensitivity.

Tri(4-iodo-2,3,5,6-tetrachlorophenyl)methane (2) is reported as a general building block for the synthesis of various π-conjugated polychlorotriphenylmethyl (PTM) radicals. Three push-pull-type triphenylamine-substituted PTM radicals with different substitution patterns were prepared and all exhibited intense inter-valence charge-transfer bands and large two-photon absorption (TPA) cross sections. Moreover, increase of solvent polarity also resulted in improved TPA response. The charge-transfer character of the relevant excited states provoked the efficient photo-generation of charges, anions in the PTM and cations in the amine arms, driven by the amphoteric redox character and the small coupling between donor and acceptor.

A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.

After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cell alloreactivity in HLA cells of recipients is regulated by killer immunoglobulin-like receptors (KIRs) on donor NK cells. The effect of KIRs on HSCT outcomes is controversial, particularly in those undergoing HLA-identical sibling HSCT. In this study, effects of KIR and HLA genotypes on the HSCT outcome were investigated in a 5-year retrospective study comprising 219 patient-donor pairs undergoing HLA-identical sibling HSCT for myeloid and lymphoid malignancies. We found that 39.7% (87 of 219) of these pairs, which were KIR mismatched, had better overall survival (OS) and reduced grade III to IV acute graft-versus-host disease (aGVHD), especially in acute myeloid leukemia (AML) patients. Bx1 donor KIR genotype with haplotype B on a telomeric region was a risk factor for the OS and relapse-free survival (RFS). Donor centromeric (c) and telomeric (t) KIR haplotype analysis showed that donor KIR cB-tA/tB was associated with improved OS and RFS compared with cA-tA or cA-tB. Furthermore, donor KIR B haplotype of the centromeric motifs (Cen-B) was an independent beneficial factor in improving OS and RFS and in protecting from relapse after HSCT. In AML patients, the occurrence of aGVHD was significantly lower in HLA-C1 group compared with that in HLA-C2 group, although such effect was not observed in patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Our results suggest that KIR could impact outcome and donor KIR haplotype with Cen-B confer significant survival benefits to HLA-identical sibling HSCT.

T-cell metabolism is a promising target for controlling aGVHD. By using GC-MS technique, we previously identified that serum stearic acid/palmitic acid ratio on day 7 was an excellent biomarker to predict aGVHD after allo-HSCT, suggesting an important role of saturated fatty acid intake in the pathogenesis of aGVHD. However, the mechanism remains unknown. By using mouse aGVHD model, here we found that high stearic acid diet (HSAD), but not palmitic acid diet, significantly aggravated aGVHD, and its promoting role was mediated by gut microbiota. 16S rRNA sequencing identified Akkermansia muciniphila (Akk) was obviously increased in HSAD recipient. Add back Akk in WT mice ameliorated aGVHD-related mortality. Furthermore, depleting CD4 T cells significantly rescued HSAD induced aGVHD mortality, whereas depleting CD8 T cells could not. In addition, HSAD recipients of RORgt−/− allografts had improved survival compared with recipients of WT allografts, indicating that Th17 cells were involved in HSAD induced aGVHD. Meanwhile, we found that Th17 cells were significantly increased in aGVHD target tissues in HSAD recipients. Functional studies showed that stearic acid could promote Akk growth in vitro, and extracts from Akk significantly promoted Th17 cells differentiation in vitro, suggesting that Akk increased the proportion of Th17 cells, thereby exacerbating aGVHD.

The role of Th17 cells and Th17-associated cytokines in the development of acute graft-versus-host disease (aGVHD) in clinical allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is not well established. In the current study, a cohort of 69 allo-HSCT patients was examined for the percentages of Th17 and FoxP3+ Treg cells and the expressions of RORγt and FoxP3 in peripheral blood mononuclear cells (PBMCs). The Th17 percentage and RORγt expression were significantly higher, whereas Treg percentage and FoxP3 expression were significantly lower in severe aGVHD (grade 3 to 4) and mild aGVHD (grade 1 to 2) patients than in patients without aGVHD (grade 0) and healthy donors. We then investigated the expressions of Th17-associated cytokines, including TGF-β, IL-6, IL-1β, IL-17, IL-21, IL-22, IL-23, as well as IL-23R in the PBMCs of patients after allo-HSCT. The expressions of IL-17 and IL-22 in CD4+ T cells were also examined. The results showed that the expressions of IL-6, IL-1β, IL-17, IL-21, IL-23, and IL-23R were all increased, whereas IL-22 expression was decreased in aGVHD patients. The changes were also correlated with the severity of aGVHD. We also investigated the dynamic changes of Th17/Treg cells and Th17-associated cytokines in patients during the onset and resolution of aGVHD. The results demonstrated a reciprocal relationship between Treg and Th17 cells. Th17-associated cytokine expressions, namely IL-17 and IL-23, were closely related to the occurrence and resolution of aGVHD. We conclude that the dynamic balance between the Th17 and FoxP3+ Treg cells and the changes of Th17-associated cytokines could be the indicators of the disease progression and promising candidates of prognostic biomarkers of aGVHD.

Hazy images hinder image understanding in many applications such as autonomous vehicle. In this paper, we propose an efficient method to improve image quality of hazy images. Our method estimates the transmission function based on a linear model that allows efficient computation and employs quadtree to search for a region that best represents the scatter of airlight. Experiments were conducted using publicly available images. It is demonstrated that our proposed method achieved comparable results to the state-of-the-art ones. In the estimation of sunlight radiance, the quadtree that integrates local brightness and gradient as well as spatial constraint provide a robust means to identify region of sky. Most significantly, our proposed method greatly improved the efficiency. When dealing with moderate and large size image, the improvement could be more than thirty-fold.

With the development of economic globalization, the international economic integration of the contemporary, English I, the most widely used language in the world, whose as position and value are more and more important. As a main function of communication language, English plays an important role in our daily life, study and work. Under this new background, the requires raised by English also is changing that we not only get good exam achievement, more words , the grammar, but also can communicate, namely, listening and saying. This also means that the educational institutions that teach us to learn English, especially the colleges and universities are put forward new challenges, but, there are many flaws in teaching students English which makes us unable to meet the demands of our society and unable to adapt to the requirement of internationalization and globalization.so , This article has analyzed the current college English teaching mode, found out the loopholes, and put forward the corresponding improvement measures.

A series of oxazole substrates and some analogues are successfully transformed to the synthetically and biologically important derivatives bearing a cyclopropane ring.

Toll like receptors (TLRs) are the major agents for innate immunity that recognize invading microbial products and regulate the growth of normal and malignant human B lymphocytes. Multiple myeloma (MM) is a clonal plasma cell malignancy, though the regulatory role of TLRs in MM plasma cells has been reported, the molecular mechanism remains unclear. We first compared the transcripts of TLR1 to TLR10 in MM patients and healthy donors and found that TLR2, -4 and -9 transcripts were higher in bone marrow mononuclear cells (BMMCs) from patients than those from donors; in addition the expression of TLR4 and TLR9 were higher in MM cells than normal cells as demonstrated by flow cytometric analyses. The ligands of these two TLRs were capable to promote the growth of MM cells and protect them from serum-deprivation-induced apoptosis but not normal plasma cells, which could be attenuated with anti-IL6 neutralizing antibodies or blockage of NF-kappaB activities. Further investigation demonstrated that these TLR ligands could trigger the nuclear translocation of NF-kappaB p65 and the activated NF-kappaB was sufficient to increase the expression of IL6 transcript in MM cells. These data suggested that activated NF-kappaB signalling probably plays a crucial role for the ligands of TLR4 and TLR9 to promote the growth and survival of MM cells partially through IL6 autocrine.

After analysing the problems observed in the sensor technology course at Weifang University, some methods to improve students' learning initiatives are proposed based on training students' comprehensive engineering abilities. These methods include updating the teaching content, adjusting the theory and experimental teaching methods, and modifying the evaluation rules. Reforms include reducing theoretical contents, adding the practicability circuits and new sensor contents; using a combination of methods in classroom teaching based on the small-projects teaching method, modular teaching method, and on-site teaching method; adding the comprehensive experiment and design experiment in the practical teaching, which develops design and operating capabilities independently; transforming the evaluation system from traditional theoretical achievement to a synthesis of practical achievement, daily achievement, and theoretical achievement, causing students to shift from passive to active learning. These curriculum reforms have greatly stimulated students' interest in learning and achieved good teaching results.

Approaches to develop hybrid rice (Oryza sativa L.) with super high yield involve the improvement of plant type, the exploitation of intersubspecific heterosis, the pyramiding of heterosis genes in different rice ecotypes, and the utilization of favorable genes from distant relatives. Three main plant types have been suggested in the literature for improving hybrid rice yield: (i) heavy panicle type, (ii) super high yielding plant type, and (iii) super high yielding ideotype. Recently, intersubspecific heterosis has been partially exploited with three strategies: (i) developing parental lines of indica-japonica intermediate type with favorable genes from both parents, (ii) introgressing intersubspecific gene with the help of wide compatibility and thermosensitive genic male sterility (TGMS) genes, and (iii) breeding pro-indica japonica lines. It is also possible to pyramid different heterosis genes from various rice ecotypes through molecular marker aided reciprocal recurrent selection. The identification of yield enhancing genes from wild rice, the construction of autoregulated senescence delaying gene, and the cloning of key enzymes related to C4 pathway have been accomplished using molecular biotechnology. By introducing these genes into the parents of the hybrid rice, the heterosis of the hybrid rice can be dramatically improved.

Water-lubricated rubber bearings are one of the most appropriate bearings for underwater use. Because of the configuration and special application environment, numerical simulation is difficult with FEM software and relevant report is rare. The water lubrication is especially interesting in terms of cost and convenience. As a result of capital cost of water-lubricated rubber bearing and time consuming experiment, the numerical approach with FEM prevails. But owning to the petty gap where lubrication fluid is bounded in, the modeling is very difficult. Three dimensional free modal and stress distribution of the bearing are analyzed in numerical simulating with FEM software. The present work of analyzing model is further worthwhile as the model can give yield results according to experiments. The modal and harmonic analyzing results can be used directly in material design and also the improvement of structure.

This paper aims to study the H∞ control problem for a class of uncertain switched descriptor systems. First of all, the definition of quadratically normal and quadratically stable (QNQS) is introduced for switched descriptor systems. Next, adopting switching proportional plus derivative state feedback (SPDSF) and multiple Lyapunov functions methods, some sufficient conditions are obtained to guarantee the closed-loop systems QNQS and satisfy H∞ performance. Meanwhile the switching strategies are also designed. Finally, two numerical examples are given to illustrate the effectiveness of the proposed methods.

Background aims Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics. Methods We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism. Results After 7 days of culture, compared with those cultured with cytokines alone (3.25 ± 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 ± 0.61 ( P = 0.003) and 4.06 ± 0.43 ( P = 0.025)–fold, respectively. Direct cell-to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38− cells than stroma-free culture (156.17 ± 21.32 versus 79.12 ± 19.77–fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% ± 11.0% versus 16.0% ± 14.3%; P = 0.750). EPCs highly expressed interleukin 6 ( IL6 ) and angiopoietin 1 ( ANGPT1 ), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo . Discussion These data demonstrated that EPCs improve the CD34+ population but do not compromise the repopulating efficacy of the amplified HSPCs, possibly via cytokine secretion and Wnt signaling pathway activation.

Many 1,3‐azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three‐membered rings is retained in the products. Thus, the cyclopropyl–halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway. MOE (Min. of Education, S’pore) Accepted version

A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.