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Recently, solution-processed quantum dot light-emitting diodes (QLEDs) have emerged as a promising candidate for next-generation lighting and display devices. However, when given a constant voltage or current, the QLEDs need a certain working time to reach their maximum brightness. Such positive aging challenge, dramatically reducing the response speed of the device and causing a luminescence delay, is urgent to be investigated and resolved. In the current work, we introduce a charge-storage layer architecture by inserting copper(I) thiocyanate (CuSCN) between the organic hole-injection layer and hole-transport layer. The extracted holes will be released during the next electrical signal stimulation to increase the efficiency of charge transport. As a result, the response speed of the QLEDs is improved by an order of magnitude. In addition, by inserting an inorganic CuSCN layer, the efficiency, lifetime, and environmental stability of red/green/blue full-color QLEDs are enhanced simultaneously. Moreover, this work provides a generic strategy for the fabrication of fast-response and high-efficiency full-color QLEDs without luminescence delay, which plays a critical role in the practical industrialization of QLEDs.

In conventional quantum dot light-emitting diodes (QLEDs), the organic charge transport materials are susceptible to erosion by water and oxygen, which would reduce the efficiency and lifetime of the devices. Herein, we modified the surface of the organic hole transport layer with an ultra-thin Al2O3 layer, which is deposited by using atomic layer deposition technique, to obtain the highly efficient and stable QLEDs. It is indicated that the ultra-thin Al2O3 interlayer plays a significant role in decreasing leakage current, suppressing exciton quenching and passivating the defects. The device with Al2O3 interface modification exhibits the maximum external quantum efficiency (EQE) of 20.8%, current efficiency (CE) of 21.6 cd A−1, and lifetime of 482000 h. In comparison with the control device, the EQE, CE and lifetime are improved by 31%, 32%, and 330%, respectively. The results indicate that the strategy of Al2O3 interface modification could provide an effective way for realizing highly efficiency QLED with long lifetime.

Background In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4–8 years with IPT. Methods IPT girls confirmed by GnRH stimulation test aged 4–8 years hospitalized from January 2015 to April 2018 at Shenzhen Children’s Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. Results Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p pp = 0.001) and DHEAS SDS (OR = 1.131, p = 0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n = 237), overweight (19.15%, n = 81) and obesity (24.82%, n = 105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ2 = 18.088, pp = 0.009) and DHEAS SDS (p = 0.003) affected BA advancement independent of BMI SDS. Conclusions Girls with IPT confirmed by GnRH stimulation test aged 4–8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Background and Aims Observational studies have suggested a bidirectional association between depression and inflammatory bowel disease [IBD], including Crohn’s disease [CD] and ulcerative colitis [UC]. However, it remains unclear whether the observed associations are causal due to the difficulties of determining sequential temporality. We investigated the association between depression and IBD by using bidirectional two-sample Mendelian randomization [MR]. Methods Independent genetic variants for depression and IBD were selected as instruments from published genome-wide association studies [GWAS] among individuals of predominantly European ancestry. Summary statistics for instrument–outcome associations were retrieved from three separate databases for both depression [Psychiatric Genomics Consortium, FinnGen and UK Biobank] and IBD [the largest GWAS meta-analysis, FinnGen and UK Biobank], respectively. MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger regression, and sensitivity analyses of Steiger filtering and MR PRESSO. From either direction, analyses were performed per outcome database and were subsequently meta-analysed using a fixed-effect model. Results Genetically predicted depression [per log-odds ratio increase] was associated with a higher risk of IBD; odds ratios [95% confidence interval] for IBD, CD and UC were 1.20 [1.05, 1.36], 1.29 [1.07, 1.56] and 1.22 [1.01, 1.47] in a combined sample size of 693 183 [36 507 IBD cases], 212 172 [13 714 CD cases] and 219 686 [15 691 UC cases] individuals, respectively. In contrast, no association was observed between genetically influenced IBD and depression in 534 635 individuals [71 466 depression cases]. Conclusions Our findings corroborated a causal association of depression on IBD, which may impact the clinical decision on the management of depression in patients with IBD. Though our results did not support a causal effect of IBD on depression, further investigations are needed to clarify the effect of IBD activity on depression [with different symptomology].

The central nervous system sends a neural impulse through an efferent nerve system toward muscles to drive movement. In an electronically artificial neural system, the electronic neural devices and interconnections prevent achieving highly connected and long-distance artificial impulse transmission and exhibit a narrow bandwidth. Here we design and demonstrate light-emitting memristors (LEMs) for the realization of an optoelectronic artificial efferent nerve, in which the LEM combines the functions of a light receiver, a light emitter, and an optoelectronic synapse in a single device. The optical signal from the pre-LEM (presynaptic membrane) acts as the input signal for the post-LEM (postsynaptic membrane), leading to one-to-many transmission, dynamic adjustable transmission, and light-trained synaptic plasticity, thus removing the physical limitation in artificially electronic neural systems. Furthermore, we construct an optoelectronic artificial efferent nerve with LEMs to control manipulators intelligently. These results promote the construction of an artificial optoelectronic nerve for further development of sensorimotor functionalities.

An ideal anti-counterfeiting technique has to be inexpensive, mass-producible, nondestructive, unclonable and convenient for authentication. Although many anti-counterfeiting technologies have been developed, very few of them fulfill all the above requirements. Here we report a non-destructive, inkjet-printable, artificial intelligence (AI)-decodable and unclonable security label. The stochastic pinning points at the three-phase contact line of the ink droplets is crucial for the successful inkjet printing of the unclonable security labels. Upon the solvent evaporation, the three-phase contact lines are pinned around the pinning points, where the quantum dots in the ink droplets deposited on, forming physically unclonable flower-like patterns. By utilizing the RGB emission quantum dots, full-color fluorescence security labels can be produced. A convenient and reliable AI-based authentication strategy is developed, allowing for the fast authentication of the covert, unclonable flower-like dot patterns with different sharpness, brightness, rotations, amplifications and the mixture of these parameters., Anti-counterfeiting technologies should ideally be unclonable, yet simple to fabricate and decode. Here, the authors develop an inkjet-printable and unclonable security label based on random patterning of quantum dot inks, and accompany it with an artificial intelligence decoding mechanism capable of authenticating the patterns.

With the development of high-speed railway, researchers pay much attention to the fatigue damage evaluation of critical components. For high-speed railway axles, surface scratches are defined as a main defect. The maximum scratch depth was detected carefully about 128 μm based on EA4T axles. To reveal the negative effect of surface scratches on fatigue performance of EA4T steel, rotating bending fatigue texts were carried out. The results indicated that the critical scratch depth (x0) of EA4T steel is about 10 μm. Less than 10 μm, surface scratch has no obvious effect on fatigue performance of EA4T steel. In addition, to evaluate the operation safety of scratch-affected axles, the geometry and loading type effects were considered. The fatigue limit curve of scratch-affected axles was estimated by Murakami equation. A fatigue estimation method of scratch-affected axles was proposed based on three-dimensional Kitagawa-Takahashi diagram that can be used in the maintenance and evaluation of damaged high-speed railway axles.

To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

An electronic synapse (e-synapse) based on memristive switching is a promising electronic element that emulates a biological synapse to realize neuromorphic computing. However, the complex resistive switching process it relies on hampers the reproducibility of its performance. Thus, achievement of a reproducible electronic synapse with a high rate of finished products has become a significant challenge in the development of an artificial intelligent circuit. Here, we demonstrate an ultrathin e-synapse having high yield (>95%), minimal performance variation, and extremely low power consumption based on an Al2O3/graphene quantum dots/Al2O3 sandwich structure that was fabricated using atomic layer deposition. The e-synapse showed both high device-to-device and cycle-to-cycle reproducibility with high stability, endurance, and switching uniformity, because the essential synaptic behaviors could be observed. This implementation of an e-synapse with an Al2O3/graphene quantum dots/Al2O3 structure should intensify motivation for engineering e-synapses for neuromorphic computing. Circuits that emulate the actions of biological synapses can be fabricated from devices known as quantum tunnel junctions. Fushan Li from China’s Fuzhou University, Tae Whan Kim from Korea’s Hanyang University, and colleagues produced an ‘e-synapse’ where a thin insulating film prevents electrons from moving through a circuit, except for a small number that jump across the barrier through quantum tunneling. When the researchers embedded graphene quantum dots in the film, they found that these nanoparticles switched the device between low and high resistance states by either trapping or releasing tunneling electrons. This allows the circuit to mimic certain functions of the brain; the gradual accumulation of electrons and their spontaneous release, for example, occurred on timeframes similar as seen in short-term memory loss. The team’s manufacturing scheme yielded devices with high stability and reproducibility. This article demonstrates an ultrathin e-synapse having high yield, minimal performance variation, and extremely low power consumption based on a Al2O3/graphene quantum dots/Al2O3 sandwich structure that was fabricated by using atomic layer deposition. It showed both high device-to-device and cycle-to-cycle reproducibility with high stability, endurance, and switching uniformity, because of which the essential synaptic behaviors could be observed. This implementation of an e-synapse with an Al2O3/graphene quantum dots/Al2O3 structure should intensify motivation for engineering e-synapses for neuromorphic computing.

Cancer is one of the leading causes of death worldwide. Recent advances in cellular therapy have demonstrated that this platform has the potential to give patients with certain cancers a second chance at life. Unlike chemical compounds and proteins, cells are living, self-replicating drugs that can be engineered to possess exquisite specificity. For example, T cells can be genetically modified to express chimeric antigen receptors (CARs), endowing them with the capacity to recognize and kill tumor cells and form a memory pool that is ready to strike back against persisting malignant cells. Anti-CD19 chimeric antigen receptor T cells (CART19s) have demonstrated a remarkable degree of clinical efficacy for certain malignancies. The process of developing CART19 essentially follows the conventional “one gene, one drug, one disease” paradigm derived from Paul Ehrlich’s “magic bullet” concept. With major players within the pharmaceutical industry joining forces to commercialize this new category of “living drugs,” it is useful to use CART19 as an example to examine the similarities and differences in its development, compared with that of a conventional drug. In this way, we can assimilate existing knowledge and identify the most effective approach for advancing similar strategies. This article reviews the use of biomarker-based assays to guide the optimization of CAR constructs, preclinical studies, and the evaluation of clinical efficacy; adverse effects (AEs); and CART19 cellular kinetics. Advanced technologies and computational tools that enable the discovery of optimal targets, novel CAR binding domains, and biomarkers predicting clinical response and AEs are also discussed. We believe that the success of CART19 will lead to the development of other engineered T cell therapies in the same manner that the discovery of arsphenamine initiated the era of synthetic pharmaceuticals. Keywords: Engineered T cell therapies, Chimeric antigen receptor, Drug development process, Biomarkers, CD19-specific chimeric antigen receptor, Anti-CD19 chimeric antigen receptor T cells

Although the Raman fiber amplifiers are attractive for their unique advantages and various Raman fiber amplifiers in continuous wave (CW) regime were built, there are a few fundamental limitations for short-pulsed Raman fiber amplifiers. In this paper, we present a theoretical and experimental study on a novel method termed picosecond (ps) coherent Raman fiber amplification, where the stimulated Raman scattering is employed to generate high-quality femtosecond pulses from narrowband ps pump pulses, with high conversion efficiency and compact construction. Detailed numerical simulation reveals the nonlinear dynamics of the ps-coherent Raman fiber amplification in an Yb-doped gain fiber. The spectral filtering effect induced by finite Raman gain bandwidth significantly improves the temporal quality of the generated Raman pulses, similar to the well-known Mamyshev regenerator. By employing this method in a 4.5 m Yb-doped polarization maintaining double-clad fiber, 67 nJ, 76 fs nearly transmission limited Raman pulses are generated from narrowband (

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov ; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn ). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients’ CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. Precis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts

An automatic segmentation of the diagnostically relevant focal area of X-ray angiography images was developed.A background suppression coding strategy was proposed based on the accurate segmentation results.Our segmentation method identifies the Regions of Interest with an average Dice Similarity Coefficient of 0.98 with respect to manual segmentation.The coding performance improvement reaches 34%, compared to the case of coding with no background suppression. Display Omitted X-ray angiography images are widely used to identify irregularities in the vascular system. Because of their high spatial resolution and the large amount of images generated daily, coding of X-ray angiography images is becoming essential. This paper proposes a diagnostically lossless coding method based on automatic segmentation of the focal area using ray-casting and α-shapes. The diagnostically relevant Region of Interest is first identified by exploiting the inherent symmetrical features of the image. The background is then suppressed and the resulting images are encoded using lossless and progressive lossy-to-lossless methods, including JPEG-LS, JPEG2000, H.264 and HEVC. Experiments on a large set of X-ray angiography images suggest that our method correctly identifies the Region of Interest. When compared to the case of coding with no background suppression, the method achieves average bit-stream reductions of nearly 34% and improvements on the reconstruction quality of up to 20 dB-SNR for progressive decoding.

The Boolean Satisfiability problem (SAT) is a prototypical NP-complete problem, which has been widely studied due to its significant importance in both theory and applications. Stochastic local search (SLS) algorithms are among the most efficient approximate methods available for solving certain types of SAT instances. The quantitative configuration checking (QCC) heuristic is an effective approach for improving SLS algorithms on solving the SAT problem, resulting in an efficient SLS solver for SAT named Swqcc. In this paper, we focus on combining the QCC heuristic with an aspiration mechanism, and then design a new heuristic called QCCA. On the top of Swqcc, we utilize the QCCA heuristic to develop a new SLS solver dubbed AspiSAT. Through extensive experiments, the results illustrate that, on random 3-SAT instances, the performance of AspiSAT is much better than that of Swqcc and Sparrow, which is an influential and efficient SLS solver for SAT. In addition, we further enhance the original clause weighting schemes employed in Swqcc and AspiSAT, and thus obtain two new SLS solvers called Ptwqcc and AspiPT, respectively. The eperimental results present that both Ptwqcc and AspiPT outperform Swqcc and AspiSAT on random 5-SAT instances, indicating that both QCC and QCCA heuristics are able to cooperate effectively with different clause weighting schemes.

A solution-processed molybdenum oxide (MoOx) as the hole injection layer (HIL) by doctor-blade coating was developed to improve the efficiency and lifetime of red-emitting quantum-dot light-emitting diodes (QD-LEDs). It has been demonstrated that by adding isopropyl alcohol into the MoOx precursor during the doctor-blade coating process, the morphology, composition, and the surface electronic structure of the MoOx HIL could be tailored. A high-quality MoOx film with optimized charge injection was obtained, based on which all-solution-processed highly efficient red-emitting QD-LEDs were realized by using a low-cost doctor-blade coating technique under ambient conditions. The red QD-LEDs exhibited the maximum current efficiency and external quantum efficiency of 16 cd/A and 15.1%, respectively. Moreover, the lifetime of red devices initializing at 100 cd/m2 was 3236 h under ambient conditions, which is about twice as long as those with a conventional poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) H...

It remains unclear if the developmental trajectories of a specific inflammatory biomarker during the acute phase of ST-elevation myocardial infarction (STEMI) provide outcome prediction. By applying latent class growth modeling (LCGM), we identified three distinctive trajectories of CD14++CD16+ monocytes using serial flow cytometry assays from day 1 to day 7 of symptom onset in 96 de novo STEMI patients underwent primary percutaneous coronary intervention. Membership in the high-hump-shaped trajectory (16.8%) independently predicted adverse cardiovascular outcomes during a median follow-up of 2.5 years. Moreover, inclusion of CD14++CD16+ monocyte trajectories significantly improved area under the curve (AUC) when added to left ventricular ejection fraction-based prediction model (ΔAUC = 0.093, P = 0.013). Therefore, CD14++CD16+ monocyte trajectories during STEMI hospitalization are a novel risk factor for post-STEMI adverse outcomes. These results provide the first proof-of-principle evidence in support of the risk stratification role of LCGM-based longitudinal modeling of specific inflammatory markers during acute STEMI.

This study aimed to investigate the effects of targeted temperature management (TTM) modulation on traumatic brain injury (TBI) and the involved mechanisms using quantitative proteomics technology. SH-SY5Y and HT-22 cells were subjected to moderate stretch injury using the cell injury controller (CIC), followed by incubation at TTM (mild hypothermia, 32°C), or normothermia (37°C). The real-time morphological changes, cell cycle phase distribution, death, and cell viability were evaluated. Moderate TBI was produced by the controlled cortical impactor (CCI), and the effects of TTM on the neurological damage, neurodegeneration, cerebrovascular histopathology, and behavioral outcome were determined in vivo. Results showed that TTM treatment prevented TBI-induced neuronal necrosis in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, reduced cortical lesion volume and neuronal loss, attenuated cerebrovascular histopathological damage, brain edema, and improved behavioral outcome. Using an iTRAQ proteomics approach, proteins that were significantly associated with TTM in experimental TBI were identified. Importantly, changes in four candidate molecules (plasminogen [PLG], antithrombin III [AT III], fibrinogen gamma chain [FGG], transthyretin [TTR]) were verified using TBI rat brain tissues and TBI human cerebrospinal fluid (CSF) samples. This study is one of the first to investigate the neuroprotective effects of TTM on the proteome of human and experimental models of TBI, providing an overall landscape of the TBI brain proteome and a scientific foundation for further assessment of candidate molecules associated with TTM for the promotion of reparative strategies post-TBI.

The aim of this study was to assess the efficacy of platelet-rich plasma (PRP) in pain and self-report function of patients with knee osteoarthritis on the basis of comparisons with hyaluronic acid or placebo.Best-evidence synthesis of randomized controlled trials (RCTs) was conducted. Literature retrieval was limited to RCTs assessing the efficacy of PRP in knee osteoarthritis. Methodology evaluation and data extraction were based on Cochrane Collaboration guidelines. Meta-analyses were performed using mean difference or standardized mean difference as effect size.Ten RCTs were included and analyzed. Meta-analysis showed significant superiority of PRP in outcome scores when compared with hyaluronic acid (standardized mean difference = -0.85, P = 0.004, I = 93%), but no statistical difference was found in well-designed double-blind trials (standardized mean difference = -0.09, P = 0.38, I = 0%). Pooled standardized mean difference of trials comparing PRP with placebo directly was -2.13 (95% confidence interval = -3.29 to -0.98), and that of indirect comparison was -0.22 (95% confidence interval = -0.45 to -0.01).In relieving pain and improving self-report function, PRP showed no superiority over hyaluronic acid in well-designed double-blind trials, and beneficial effects of PRP in most trials probably resulted from insufficient blinding methods. However, PRP is still considered more effective than placebo on the basis of present evidence.

Introduction Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated promising efficacy in patients with relapsed and refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CART remains a major issue. Here, we analyzed the factors related to long-term efficacy, including overall survival (OS), leukemia-free survival (LFS) and cumulative relapse rate (CRR), following CAR-T therapy in 231 R/R B-ALL patients who achieved complete remission (CR) within one month after CAR T-cell therapy. Patients and Methods From April 2017 to March 2019, 254 patients with R/R B-ALL were enrolled onto one of five different clinical trials (NCT03173417; ChiCTR-ONC-17012829; NCT02546739; ChiCTR1800016541; and NCT03671460) at our center and received a second generation CD19+ CAR T-cell infusion. The median infused CAR T-cell dose was 3×105/kg (range: 0.2-10×105/kg). The CAR-T/T-cell ratio and the CD19+ B lymphocyte percentage in PBLC samples from 159 of the patients were analyzed using flow cytometry on day 0, 4, 7, 11, 14, 21, and 30 following CAR T-cell infusion. We performed single continuous variate factors analysis on the influence of the CAR-T/T-cell ratio and the percentage of CD19 + B-lymphocytes in day 30 post-infusion PBLC samples on the OS, LFS, and CRR. We also analyzed the impact of patient age, BM blast count, CAR-T-cell dose, and the interval time between CAR-T-cell therapy and consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) on OS and LFS. Results Among 254 patients, 231 cases achieved CR within one month after CART therapy. A total of 211 CR patients had long-term follow-up of more than 30 days with a median follow-up of 12 months (1 to 29 months). On day 30 post CAR T-cell infusion, the median CAR-T/T-cell ratio in PBLC samples was 0.51% (range: 0%-44.8%), with 59 of 169 patients (34.9%) having a CAR-T/T-cell ratio of ≥1% and 85 of 169 patients (50.3%) with a CAR-T/T-cell ratio of ≥0.5%. The median percentage of CD19+ B lymphocytes in PBLC on day 30 was 0.0% (range: 0.0%-9.4%), of which 157 of 169 patients (92.9%) had Using a single continuous variate factors analysis, we found that increasing BM blasts and percentage of CD19+ B-lymphocytes in PBLC samples on day 30 correlated with a worse OS and LFS (Table 1). BM blasts of ≥70% were statistically significantly correlated with a worse OS and LFS when compared to BM blasts of The remaining 184 patients in CR received a consolidation allo-HSCT after a median interval time of 67 days post CAR T-cell therapy (range: 30-334 days). Thirty-two of these patients (17%) relapsed with a median time to relapse of 221 days (57-490 days). The remaining 27 patients received CAR T-cell therapy only and 11 (41%) relapsed with a median time to relapse of 100 days (53-398 days). None of the four factors above had an influence on the CRR in either the bridging into allo-HSCT group or the CAR-T only group (Table 2). Conclusions Using a single continuous variate factors analysis, we found that a high BM blast count and the percentage of CD19+ B-lymphocytes in PBLC samples from R/R ALL patients on day 30 predicted a worse OS and LFS while age, the CAR-T/T-cell ratio on day 30, CAR-T cell dose, and the interval time between CAR-T cell infusion and allo-HSCT had no clear impact on long-term outcomes. Disclosures No relevant conflicts of interest to declare.

The performance of perovskite quantum dot light-emitting diodes (PeQLEDs) has been rapidly enhanced recently, but the devices are still stuck in the stage of using small-scale solution processes, such as spin-coating. In this work, we report the realization of high performance PeQLEDs by using inkjet printing technique. We demonstrate the preparation of a printable perovskite quantum dot ink by using a hybrid solvent consisting of high boiling solvent dodecane and low boiling solvent n-octane. A universal strategy for eliminating coffee rings during inkjet printing of perovskite inks is developed based on the modulation of ink formulation, and the stacking model of perovskite quantum dot in a pixel pit structure is proposed. The inkjet-printed PeLEDs exhibit a low turn-on voltage of 2.7 V, a brightness of 10992 cd/m2 at 6.6 V and a maximum current efficiency of 8.67 cd/A, which is by far the highest value reported for inkjet-printed PeLEDs. The results pave a way for future realization of high performance pixelated PeLED displays with inkjet printing technique.

We report on an all-normal-dispersion Yb-doped fiber laser with mode-locking mechanism based on nonlinear polarization rotation. The splitting and trapping of dissipative solitons (DSs) could be observed by inserting of a short section of polarization-maintaining fiber in cavity configuration as an in-line birefringence fiber filter. Two trapped orthogonal polarization DSs can travel with the same group velocity in the laser cavity. With the DSs trapping, the polarization sidebands are appeared in the spectrum. The trapping of DSs and sideband generation is numerically simulated as well.

Inkjet printing has been considered as a promising technique to achieve large-scale display panel with pixelated RGB quantum dots, to which the uniform quantum dots layer is of great importance. In this work, we exhibit our recent works of high-quality inkjet-printed red and green quantum dots (QDs) layer and fabrication of quantum dot light-emitting diodes (QLEDs) with normal architecture.

// Yingzi Qi 1, * , Feng Xu 1, * , Lingsheng Chen 1, 3 , Yanchang Li 1 , Zhongwei Xu 1 , Yao Zhang 1, 7 , Wei Wei 1 , Na Su 1 , Tao Zhang 1 , Fengxu Fan 1, 4 , Xing Wang 1 , Xue Qin 6 , Lingqiang Zhang 1 , Yinkun Liu 5 , Ping Xu 1, 2, 4 1 State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Institute of Radiation Medicine, Beijing 102206, China 2 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan 430072, China 3 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China 4 Anhui Medical University, Hefei 230032, China 5 Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 6 Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China 7 Institute of Microbiology, Chinese Academy of Science, Beijing 100101, China * These authors contributed equally to this work Correspondence to: Ping Xu, email: xuping@mail.ncpsb.org Yinkun Liu, email: liu.yinkun@zs-hospital.sh.cn Keywords: hepatocellular carcinoma (HCC), iTRAQ, filamin C (FLNC) Received: March 06, 2016 Accepted: September 02, 2016 Published: September 09, 2016 ABSTRACT Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection is one of the most life-threatening human cancers in China. However, the pathogenesis of HCC development is still unclear. Here, we systemically analyzed liver tissues from different stages of HCC patients through 8-plex Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approach. A total of 4,620 proteins were identified and 3,781 proteins were quantified. When T1, T2 and T3 tumor tissues were compared with T1 non-tumor cells, 330, 365 and 387 differentially expressed proteins were identified respectively. IPA (Ingenuity Pathway Analysis) analysis revealed that these differentially expressed proteins were involved in endothelial cancer, cell spreading, cell adhesion and cell movement of tumor cell lines pathway and so on. Further study showed that the filamin C (FLNC) protein was significantly overexpressed with the development of HCC, which might play an important role in HCC invasion and metastasis. These results were also confirmed with western blot (WB). The mRNA levels were significantly increased in 50 pairs of tumor and adjacent non-tumor tissues from TCGA database. The higher expression of FLNC in HCC might be a common phenomenon, thereby shedding new light on molecular mechanism and biomarker for the diagnosis purpose of HCC development.

Osteoarthritis (OA), one of the most widespread musculoskeletal joint diseases among the aged, is characterized by the progressive loss of articular cartilage and continuous changes in subchondral bone. The exact pathogenesis of osteoarthritis is not completely clear. In this work, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) in combination with multivariate statistical analysis was applied to analyze the metabolic profiling of subchondral bone from 42 primary osteoarthritis patients. This paper described a modified two-step method for extracting the metabolites of subchondral bone from primary osteoarthritis patients. Finally, 68 metabolites were identified to be significantly changed in the sclerotic subchondral bone compared with the non-sclerotic subchondral bone. Taurine and hypotaurine metabolism and beta-alanine metabolism were probably relevant to the sclerosis of subchondral bone. Taurine, L-carnitine, and glycerophospholipids played a vital regulation role in the pathological process of sclerotic subchondral bone. In the sclerotic process, beta-alanine and L-carnitine might be related to the increase of energy consumption. In addition, our findings suggested that the intra-cellular environment of sclerotic subchondral bone might be more acidotic and hypoxic compared with the non-sclerotic subchondral bone. In conclusion, this study provided a new insight into the pathogenesis of subchondral bone sclerosis. Our results indicated that metabolomics could serve as a promising approach for elucidating the pathogenesis of subchondral bone sclerosis in primary osteoarthritis. Graphical Abstract Metabolic analysis of osteoarthritis subchondral bone.

Zinc oxide (ZnO) nanoparticles (NPs) are extensively adopted material to be used as efficient electron transport layer (ETL) in quantum dot light emitting diodes (QLEDs) due to their suitable properties of high electron mobility, good stability, and easy processability. However, because of the naturally high work function of ZnO NPs, the electrons can be spontaneously transferred at the quantum dot/ZnO interface. In addition, the enormous difference in electron and hole mobility can lead to interfacial exciton quenching and unbalanced charge injection. In this paper, the strategy of replacing the ZnO in QLEDs with Mg and polyvinylpyrrolidone (PVP) inorganic-organic hybrid co-doped ZnO NPs are introduced. The energy band structures of ZnO NPs are tailored by tuning the concentrations of Mg, resulting in a significant suppression of the spontaneous charge transfer at the quantum dot/ETL interface. Furthermore, the surface quenching sites and the electronic mobility of ETL were adjusted via PVP doping. The proposed method significantly enhances the current efficiency and external quantum efficiency to 16.16 cd/A and 15.45%, respectively, an improvement of about 2.5-fold compared to the devices with pure ZnO NPs.

Backgrounds Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has demonstrated 80-90% complete remission (CR) rate in R/R B-ALL; however, 10% to 20% of patients have no response and the potential etiology and risk factors remain unclear. Patients and Methods From Apr. 2017 to Mar. 2019, 254 patients with R/R B-ALL received treatment at our single center with a second-generation CD 19 CAR-T from 5 companies (NCT03173417; ChiCTR-ONC-17012829; NCT02546739; ChiCTR1800016541; and NCT03671460). The targeted median infused CAR-T cell dose was 3x105/kg. For all patients, screening was undertaken for 58 types of B-ALL related gene mutations and 49 congenital immune deficiency gene mutations using next generation sequencing (NGS) method. The patient and CAR-T product characteristics were analyzed to see if any factors affected the initial CR rate. Univariate analysis comparing CR rates between subgroups were carried out using chi-squared tests. Logistic regression model was adopted for multivariate analysis. Results On D30, 90.6% (230/254) patients achieved CR, and minimal residual disease (MRD)-negative CR was 89.4% (227/254). Univariate analysis (Table 1&2) showed a statistical difference in CR rate between females and males (84.54% vs. 94.27%, p=0.011). The CR rate of patients who received prior either CAR-T or blinatumomab treatment was lower than those who had not (50% vs. 91.53%, p=0.01). For the characteristic fusion genes, the CR rate in patients with MLL-AF4 was 80%, which was inferior to those with other or no fusion genes (P=0.041). For gene mutations, a lower CR rate was observed in patients with TP53 mutation compared to those with other or no mutations (72.73% vs. 92.11% vs. 94.39%, P=0.004). Presence of congenital immune deficiency gene mutations did not affect CR rate. Patients with >20% bone marrow (BM) blasts had a worse outcome than those with BM blasts≤20% (79.17% vs. 97.47%, p14 yr, patients with or without extramedullary disease (EMD), or patients receiving different chemotherapies between enrollment and CAR-T cells infusion on top of fludarabine and cyclophosphamide (FC) conditioning regimen. Cytokine release syndrome (CRS) and neurotoxicity had no effect on CR rate.There was a trend towards a lower CR rate in patients who received donor-derived CAR-T versus patient-derived CAR-T products (61.54% vs. 92.12%, p = 0.081). A lower CR rate was observed in patients who received CD28 costimulatory domain versus 4-1BB CAR-T products (77.27% vs. 91.70%, p=0.053). There was no difference in CR rate between patients infused with cell dose ≥3x105/kg vs. cell dose 2x104/kg. No CR difference was observed from different manufacturing companies. Moreover, 125/254 cases had available data for analysis on subsets of CAR-T cells including central memory T cells (Tcm), naive T cells and T memory stem cells (Tscm). Each group was divided into high- or low-level groups based on the median level. The CR rate was 92.19% vs. 88.52% in high and low Tcm groups, 92.31% vs. 88.33% in high or low naive group, and 89.80% vs.90.24% in high and low Tscm groups, respectively. No difference in CR between the groups were observed. Multivariate analysis was performed to investigate factors affecting achievement of CR (Table 3). Female group had lower odds of achieving CR after CAR-T therapy compared to male group [OR=0.232(95%CI 0.082-0.652)]. Compared to patients without TP53 mutation or only with other gene mutations, patients with TP53 mutation were more likely to have a low CR rate after CAR-T treatment [OR=4.511(95%CI 1.295-16.895)]. Patients with BM blast >20% had lower odds of achieving CR compared to those with BM blast ≤20% [OR=0.095 (95%CI 0.022-0.260)]. Treatment with CAR-T with CD28 as a costimulatory domain resulted lower odds of CR compared to treatment with CAR-T with 4-1BB [OR=7.141 (95%CI 1.722-29.612)]. Patients who developed severe neurotoxicity (grade 2-4) post CAR-T had higher odds of achieving CR compared to patients with grade 0-1 neurotoxicity [OR=34.796(95%CI 3.232-374.659)]. Conclusions In this analysis, we have observed that significant risk factors for not achieving CR after CD-19 CAR-T therapy include female gender, BM blasts more than 20%, a positive TP53 mutation, treatment with CD28 co-stimulatory domain vs 4-1BB CAR-T product, and mild as opposed to severe CAR-T related neurotoxicity. Disclosures No relevant conflicts of interest to declare.

Perovskite quantum dots (PeQDs) have emerged as a new kind of nanomaterial in various applications, especially light-emitting diodes (LEDs). However, the synthesis of PeQDs is relatively complicated and the electron transport layer (ETL) is usually fabricated in a vacuum because of the dissolution of PeQDs films in organic solvents, which will increase the difficulty and cost in mass production. Here, a simple one-step “ultrasonic bath” treatment to synthesis PeQDs is adopted and applied into the PeQDs-LEDs. Meanwhile, an all-solution process is developed to fabricate PeQDs-LEDs based on the solvent engineering strategy. By using methyl acetate (MeOAc) as the solvent of ETL, the all-solution-processed PeQDs-LEDs exhibit bright luminance with the maximum current efficiency of 3.26 cd/A. This work is simple and easy to be scaled up, which will pave a new way to the low-cost all-solution processable PeQDs-LEDs.

The anterolateral ligament, a distinct structure connecting the lateral femoral epicondyle to the anterolateral proximal tibia, is gaining attention because of its possible function in ensuring internal rotational stability of the tibia. To study the prevalence and precise anatomical characteristics of the anterolateral ligament and its relationship to adjacent structures in a Chinese population, a total of 20 amputated knee specimens were collected. The anterolateral regions of the knees underwent detailed surgical dissection, followed by precise measurement of the anterolateral ligament and its adjacent structures. Histological analysis of the anterolateral ligament was performed using hematoxylin and eosin (H&E) staining. A thin soft tissue deep to the iliotibial band running obliquely across the lateral fibula ligament and connecting the lateral head of the gastrocnemius with the tibia, termed the 'gastrocnemius-tibial ligament' or superficial layer of the anterolateral ligament, was observed in 18 of the 20 specimens, corresponding to a prevalence of 90%. Furthermore, a well-defined anterolateral ligament deep to the gastrocnemius-tibial ligament and distinct from the lateral fibula ligament was found in all 20 knees (prevalence, 100%). The independent gastrocnemius-tibial ligament and anterolateral ligament had separate femoral originations at the lateral head of the gastrocnemius and the lateral femoral epicondyle, and the same osseous tibial insertion at the midpoint between Gerdy's tubercle and the most lateral aspect of the fibular head. H&E staining showed that both the anterolateral ligament and gastrocnemius-tibial ligament were ligaments consisting of collagenous bundles. In the Chinese Han population, the gastrocnemius-tibial ligament and anterolateral ligament may form a complex at the anterolateral aspect of the knee, which is likely involved in ensuring the internal rotational stability of the tibia.

A simple open-cavity laser is proposed for supercontinuum generation. Broadband supercontinuum covering the wavelength from 630 to 1700 nm with low multimode LD pump power (~ 1.7 W) is demonstrated. Giant nanosecond pulse generation can be realized by pumping a piece of Yb-doped double cladding fiber combined with two pieces of long passive fibers. There are no reflectors or modulators included in this laser. It is confirmed that the process of the passive self-Q-switch is mainly based on the stimulated Brillouin scattering effect. The peak power of the giant nanosecond pulses is high enough to generate supercontinuum with over 1000 nm bandwidth even in standard single-mode fiber, which makes this supercontinuum laser source low-cost and compact. Replacing the standard single-mode fiber with a piece of high nonlinear photonic crystal fiber, broader and flatter supercontinuum can be obtained because of the high nonlinear coefficient and the blue-shift of the zero-dispersion wavelength.

// Tengfei Zhang 1,2,* , Ling Cao 1,3,* , Jing Xie 4,* , Ni Shi 5 , Zhen Zhang 1,3 , Zhenzhen Luo 1,3 , Dongli Yue 1,3 , Zimeng Zhang 6 , Liping Wang 3 , Weidong Han 7 , Zhongwei Xu 8 , Hu Chen 9 and Yi Zhang 1,3,10,11 1 Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2 Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States 3 Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 4 Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia 5 Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States 6 Department of Immunology, Harvard Medical School, Boston, Massachusetts United States 7 Molecular & Immunological/Bio-Therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China 8 Department of Gastroenterology, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania, United States 9 Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science, Beijing, China 10 Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China 11 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China * These authors have contributed equally to this work Correspondence to: Yi Zhang, email: // Keywords : CD19, chimeric antigen receptor, B cell malignancies, meta analysis, efficiency Received : July 06, 2015 Accepted : August 20, 2015 Published : September 10, 2015 Abstract Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed ( p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.

Quantum dot light emitting diodes (QLEDs) are increasingly attractive owing to their compatibility with the inkjet printing process and potential application in low-cost large-area full-color pixelated display. The strategy for controlling the morphology of the quantum dot layer is definitely critical for realizing all-solution processed QLEDs with high performance, which certainly requires in-depth thinking regarding the design of ink composition and their optimization in the printing process. Herein, by carefully controlling the quantum dot ink composition and physicochemical properties, we demonstrate that the viscosity, contact angle, and the three-phase contact line moving would affect the final morphology of the quantum dot film formed by inkjet printing. We achieved coffee ring-free and low-roughness quantum dot film, and all-solution processed QLEDs with normal structure were fabricated for the first time. The devices have a low turn-on voltage of 2.0 V, a luminance of 12100 cd/m2 at the voltage o...

Non-traumatic osteonecrosis of the femoral head (NTONFH) is a progressive disease, always leading to hip dysfunction if no early intervention was applied. The difficulty for early diagnosis of NTONFH is due to the slight symptoms at early stages as well as the high cost for screening patients by using magnetic resonance imaging. The aim was to detect biomarkers of early-stage NTONFH, which was beneficial to the exploration of a cost-effective approach for the early diagnose of the disease. Metabolomic approaches were employed in this study to detect biomarkers of early-stage NTONFH (22 patients, 23 controls), based on the platform of ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and the uses of multivariate statistic analysis, putative metabolite identification, metabolic pathway analysis and biomarker analysis. In total, 33 serum metabolites were found altered between NTONFH group and control group. In addition, glycerophospholipid metabolism and pyruvate metabolism were highly associated with the disease. The combination of LysoPC (18:3), l-tyrosine and l-leucine proved to have a high diagnostic value for early-stage NTONFH. Our findings may contribute to the protocol for early diagnosis of NTONFH and further elucidate the underlying mechanisms of the disease.

Objective: This study was aimed to evaluate the efficacy of preemptive analgesia (PA) by using celecoxib combined with low-dose tramadol/acetaminophen (tramadol/APAP) in treating post-operative pain of patients undergoing unilateral total knee arthroplasty (TKA). Methods: A total of 132 patients scheduled for TKA were included in this study. Three-day pre-operative medication was administrated in PA group with subsequent effective intra- and post-operative multimodal analgesia, while control patients received multimodal analgesia without PA. Visual analog scale (VAS) was utilized to assess the pain intensity at rest and during movement. VAS scores of participants were recorded 3 days before surgery, 1 day, 3 days, 1 week, 3 weeks, 6 weeks, 3 months, 6 months, and 12 months postoperatively. Moreover, the length of hospital stay, expense of hospitalization, C-reactive protein (CRP) values during hospitalization, and complications during medication were also recorded. Results: PA showed superiority over control at 3 weeks (P = 0.013) and 6 weeks (P = 0.046) in resting pain, and 1 week (P = 0.015), 3 weeks (P = 0.003), 6 weeks (P = 0.003) and 3 months (P = 0.012) postoperatively in movement pain. There was no statistically significant difference in the length of hospital stay, total expense, CRP values, as well as complications. Conclusions: Based on satisfactory intra- and post-operative analgesia, PA by 3-day administration of celecoxib and low-dose tramadol/APAP might be an effective and safe therapy regarding patients undergoing TKA in terms of alleviating post-operative pain.

// Zhongwei Xu 1, 7 , Linghui Zhai 1 , Tailong Yi 1, 4 , Huiying Gao 1 , Fengxu Fan 1, 4 , Yanchang Li 1 , Youliang Wang 2 , Ning Li 1 , Xiaohua Xing 1 , Na Su 1 , Feilin Wu 1 , Lei Chang 1 , Xiuli Chen 6 , Erhei Dai 6 , Chao Zhao 5 , Xiao Yang 2 , Chunping Cui 1 , Ping Xu 1, 3, 4 1 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Engineering Research Center for Protein Drugs, National Center for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing, 102206, P.R. China 2 Beijing Institute of Bioengineering, Beijing, 100071, P. R. China 3 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430072, P. R. China 4 Anhui Medical University, Hefei, 230032, China 5 Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, and Research Center on Aging and Medicine, Fudan University, Shanghai, 200032, China 6 The Fifth Hospital of Shijiazhuang City, Shijiazhuang, 050021, China 7 Central Laboratory, Logistics University of Chinese People’s Armed Police Force, Tianjin, 300309, China Correspondence to: Ping Xu, email: xuping@mail.ncpsb.org Keywords: HBx, SILAM, CDC42, CFL1, ADFP Received: March 10, 2016 Accepted: September 13, 2016 Published: September 30, 2016 ABSTRACT Hepatitis B virus X protein (HBx) participates in the occurrence and development processes of hepatocellular carcinoma (HCC) as a multifunctional regulation factor. However, the underlying molecular mechanism remains obscure. Here, we describe the use of p21 HBx/+ mouse and SILAM (Stable Isotope Labeling in Mammals) strategy to define the pathological mechanisms for the occurrence and development of HBx induced liver cancer. We systematically compared a series of proteome samples from regular mice, 12- and 24-month old p21 HBx/+ mice representing the inflammation and HCC stages of liver disease respectively and their nontransgenic wild-type (WT) littermates. Totally we identified 22 and 97 differentially expressed proteins out of a total of 2473 quantified proteins. Bioinformatics analysis suggested that the lipid metabolism and CDC42-induced cytoskeleton remodeling pathways were strongly activated by the HBx transgene. Interestingly, the protein-protein interaction MS study revealed that HBx directly interacted with multiple proteins in these two pathways. The same effect of up-regulation of cytoskeleton and lipid metabolism related proteins, including CDC42, CFL1, PPARγ and ADFP, was also observed in the Huh-7 cells transfected with HBx. More importantly, CFL1 and ADFP were specifically accumulated in HBV-associated HCC (HBV-HCC) patient samples, and their expression levels were positively correlated with the severity of HBV-related liver disease. These results provide evidence that HBx induces the dysregulation of cytoskeleton remodeling and lipid metabolism and leads to the occurrence and development of liver cancer. The CFL1 and ADFP might be served as potential biomarkers for prognosis and diagnosis of HBV-HCC.

The severity and/or progression of osteonecrosis of the femoral head (ONFH) are commonly assessed by radiography, nuclear magnetic resonance image which aren’t invariably correlated to severity of disease and may be disturbed by other factors. Consequently, exploring the novel biochemical signatures of ONFH may be beneficial for diagnosing and understanding this disease. In this work, a bone trabecula metabolomics was undertaken to determine the expression pattern of low molecular mass metabolites in patients of femoral head necrosis based on the ultra-performance liquid chromatography/time-of-flight tandem mass spectrometry (UPLC/TOF MS/MS). Histological study showed that necrotic bone was characterized by necrosis, fibrosis and lacuna, but adjacent “normal” bone was pathologically normal. Principal component analysis in combination with orthogonal partial least-squares discrimination analysis was used to find out changed metabolites. MS/MS was used to speculate the corresponding molecule. Both osteonecrotic bone trabecula (ONBT) and adjacent “normal” bone trabecula (ANBT) showed higher levels of amino acids, such as proline, arginine, glutamine, dipeptides and lower levels of antioxidants. Most disrupted lipids, such as fatty acid esters, glycerophospholipids, sphingolipids, were found in osteonecrotic zone. The area under the receiver operating characteristic curve of combinational biomarkers (d-arginine, l-proline, l-carnitine, inosine) in ONBT and ANBT was 0.996 and 0.950, respectively. Our findings might provide a significant insight to understand the metabolic mechanism and diagnosis biomarkers of ONFH in the future.

We report on a mode-locked Yb-doped fiber laser with a semiconductor saturable absorber mirror. Without the bandpass filter or the fiber grating in laser cavity, the tunable single wavelength and dual-wavelength pulses could still be obtained.

Over 1000 nm supercontinuum was obtained in a simple open cavity pulsed laser. Nanosecond pulses generation can be realized without any reflectors or modulators based on the stimulated Brillouin scattering effect.

With the continuous increase in the size and complexity of a real-time computer system, the use of formal verification methods in software development is also on the rise. The traditional formal verification method is not fully applicable to the development of actual system life cycle. Therefore, this paper presents a new real-time system verification method, It take the deadlock timed Bu chi ⋅⋅ automata as the medium, and translate the timed temporal logic into timed communicating sequential process language. The tock event is also joined, which can be directly used for the detection of refinement tool FDR. The method verifies the situation of deadlock. To establish the link between the conventional model checking and refinement model checking can well combine the advantages of both and improve system security and reliability. Keywords; refinement relation; formal verification; real-time system; safety

We report on a passively Q-switched Yb-doped all-fiber (YDF) ring laser based on stimulated Brillouin scattering (SBS) feedback in a 20-m single-mode fiber (SMF). The Q-switched pulses are generated from the Stokes pulses of SBS and amplified in the YDF. The 10-ns self-Q-switched pulses with ∼1 kW maximum peak power are obtained. The repetition frequency of the pulse train is tuned from 4 to 12.6 kHz by changing the pump power in the experiment. A bandpass filter inserted in the laser cavity was used to suppress the time jitter of the Q-switched pulses.

The aim of this study was to evaluate the efficacy of supplementary fixation in hip arthroplasty with the use of Kirschner-wires and tension band for geriatric patients suffering unstable intertrochanteric osteoporotic fractures. A total of 103 patients aged more than 75 years were recruited

X-ray angiography (angio) images are widely used to identify irregularities in the vascular system. Because of their high spatial resolution and the increasing amount of X-ray angio images generated, compression of these images is becoming paramount. In this paper, we propose a diagnostically lossless compression method based on automatic segmentation using ray-casting and α-shapes. The diagnostically relevant Region of Interest is separated from the background by exploiting the inherent symmetrical features of the image. The background-suppressed images are then losslessly encoded using DICOM-compliant lossless compression methods. Experimental results suggest that the proposed method correctly identifies the Region of Interest in X-ray angio images with an average segmentation accuracy of 98.4% and achieves more than 2 bits per pixel improvement on compression performance as compared to lossless compression with no background suppression.

Summary form only given. X-ray angiographic (angio) images are widely used for identifying irregularities in the vascular system. Because of their high spatial resolution and the increasingly amount of X-ray angio images generated, compression of these images is becoming increasingly appealing. In this paper, we introduce a diagnostically lossless compression scheme for X-ray angio images. The coding scheme relies on a novel method based on ray casting and a-shapes for distinguishing the clinically relevant Region of Interest from the background. The background is then suppressed to increase data redundancy, allowing to achieve a higher coding performance. Experimental results suggest that the proposed scheme correctly identifies the Region of Interest in X-ray angio images and achieves more than 2 bits per pixel reduction in average as compared to the case of compression with no background suppression. Results are reported here for 20 out of 25 images compressed using various lossless compression methods.

Cognitive radio technology is a promising technology to solve the inefficiency problem of the usage of spectrum, and with the help of the cooperative communication technology, the system can obtain more performance. This paper proposes a cooperative communication strategy based on physical-layer network coding (PNC) to work out the difficulty that the primary cannot communicate, which the secondary user can also access the spectrum. Meanwhile, we also discuss the power allocation scheme and relay selection strategy to maximum the system capacity. With amplify forward (AF), the secondary forwards the signal after orthogonal zing the single of the primary user and the secondary user. Simulation results showed that, with the cooperation of the secondary user, the primary user can communicates efficiently, the secondary user transmits availably as well. The system achieves the best performance by the power allocation scheme and relay selection strategy.

While there has been much attention paid to the applications of Modeling and Simulation (M&S) for safety critical system testbed lately, little has been done to address related technology areas that enable M&S to be more easily constructed.Model Composabilty is the ability to compose component across a variety of application domains. This contribution discusses basic researches for a port-based object (PBO) approach to integrated M&S of testbed. We give the formal description of PBO with the safety property and describe the method of composable design based on PBO, and then illustrate this approach by a simple example.

In this paper, we propose a method for modeling and analysis of fault detection in real-time systems. This approach is based on the model of time petri net (TPN), which derives from the timing analysis of the TPN models with guarded transitions. With the reachability analysis of each mark of TPN model, some finite length of test sequences are generated through computing the shortest path from the initial mark to each leaf node. Then we carry out input in the proper time intervals and check out whether the system satisfies the requirements for real time and the functions of software that according to the output results. This approach is well illustrated by means of modeling and analysis of a safety-critical system: Interlock Logic System.

In most problems of first-order rule learning, rule space is usually structured by thetas-subsumption operator. But in first-order rule space, thetas-subsumption is a quasi-ordering. If the number of coved training examples is used as the criterion for ranking candidates of hypothesis, there is a equivalent-class problem when searching along the quasi-ordering. Rules in an equivalent-class can't be distinguished according to their fitness function values. In another aspect, it makes the search to prefer longer rules, and would reduce the system efficiency and readability of learned rules. To solve these problems, in this paper, a new fitness function based on binding is presented. The contrast experiment has been done to show the effect of the new fitness function in guiding the search through first-order rule space

This paper proposes a new approach of human face recognition using partial least square (PLS) and covering algorithm. PLS constructs the component so that the correlation between the class variable and themselves maximized. Covering Algorithm is a kind of neural network method. The approach first processes the image with wavelet transform, and then eliminates the redundant features with PLS. It reduces the dimension of image by extracting the principal features. Finally, classifies the image by covering algorithm.

In this paper we propose a new black-box testing approach on how to select test cases to overcome the shortcoming that some conventional black-box testing methods lack precise testing adequacy measures to measure the quality of testing and direct the testing process and thoroughly test safety-critical software. The method is based on two key ideas: (1) specification classifying, and (2) controlled objects covering. By using the method, several kinds of computer interlocking safety software have been successfully tested and the testing results show that the method is efficient.

A novel approach for testing the effectiveness, efficiency, safety and relative appropriateness of Computer Interlocking Software (CIS)-a kind of safety-critical software is presented with a software platform developed to support this approach. A brief description of the proposed approach is also included.