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Iodinated X-ray contrast media (ICM) was frequently detected in the aqueous environment. In this work, the applicability of three graphene-based nanomaterials (graphene nanosheets (GNS), graphene oxide (GO), and reduced graphene oxide (rGO)) for the adsorptive removal of the six ICMs including iohexol, iopamidol, iomeprol, iopromide, iodixanol and ioversol from aqueous solution was firstly evaluated by batch adsorption method. Among the three graphene-based nanomaterials, the GNS displayed the best adsorption performances for the adsorption of the six ICMs. The maximum uptakes of the six ICMs by the GNS (161.5 mg g -1 for iohexol, 267.2 mg g -1 for iodixanol, 197.7 mg g -1 for iopromide, 197.0 mg g -1 for iopamidol, 109.6 mg g -1 for iomeprol, and 168.2 mg g -1 for ioversol) can rapidly achieved within 10 min and indicate no dependence on pH in the range of 4-9. The results obtained from the calculations of isotherms, kinetics and thermodynamic supported the occurrence of a chemisorption of the GNS for the six ICMs. The π-π interactions between benzene ring of the ICMs and the sp 2 -hybridized two-dimensional sheet of GNS were deemed the predominant adsorption mechanism., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All authors have reviewed and approved the submission of the manuscript. 1. Research Support for This Reported Work. Beyond the authors' primary affiliations, was additional support provided for this research since the time of its initial conception? This research received additional support from an organization beyond the authors' academic institutions. Organization Name: Education Department of Liaoning Province of China. What type of support did your research receive? (Check all that apply.) Financial support. Financial support by Basic Scientific Research Foundation of the Education Department of Liaoning Province of China (No. LJKZZ20220053). Who received the support? Author name. Hongtao Fan. Corresponding author 2. Relevant Support Outside This Reported Work. Within the last 3 years, do you or any of the authors have any personal financial interests or professional relationships related to the subject matter but not directly to this manuscript? No. 3. Any patents or copyrights licensed to the author(s) that are relevant to the work submitted for publication. No. 4. Anything else that may be perceived to have influenced the submitted work. No., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding of treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 blockade to map the evolution of local and systemic immunity of CRC patients. In tumors, we identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8 + T (Ttr-like) cells are closely related to treatment efficacy, and Tex cells show correlated proportion changes with multiple other tumor-enriched cell types following PD-1 blockade. In addition, we reveal the less-exhausted phenotype of blood-associated Ttr-like cells in tumors and find that their higher abundance suggests better treatment outcomes. Finally, a higher major histocompatibility complex (MHC) II-related signature in circulating CD8 + T cells at baseline is linked to superior responses. Our study provides insights into the spatiotemporal cellular dynamics following neoadjuvant PD-1 blockade in CRC., Competing Interests: Declaration of interests Z.Z. is a founder of Analytical Biosciences and a member of the advisory board of Cell., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To describe the clinical features of Chinese patients with hydroxychloroquine (HCQ)-induced pigmentation and analyze the potential risk factors associated with HCQ-induced pigmentation., Methods: A cross-sectional study was conducted over a duration of 7 months, during which patients who had received HCQ treatment for >6 months were included. Data was collected through a structured questionnaire that encompassed demographic and geographic characteristics, information on HCQ and concomitant medication usage, sun exposure characteristics, and hyperpigmentation-related characteristics. Univariate and multivariate analyses were employed to calculate the statistical association between HCQ-induced pigmentation and multiple variables., Results: Out of 316 patients, 83 (26.3%) patients presented hyperpigmentation during HCQ treatment. Hyperpigmentation presented after a median duration of HCQ treatment of 12 months (interquartile range, 6.0 months-30.0 months) with a median cumulative dose of 108 g of HCQ (interquartile range, 36-288 g). The most frequently affected sites of pigmentation were the face (60.2%), lower limbs (36.1%), and hands (20.5%). There was a linear decrease in the incidence of pigmentation with increasing daily sun exposure time (p= 0.030). In the multivariate analysis, variables (cumulative HCQ dose and daily sun exposure time) were included in the final models. The results revealed an independent correlation between HCQ-induced pigmentation and daily sun exposure exceeding 1 h (OR: 0.431; 95%CI: 0.208-0.892; p= 0.023)., Conclusions: The occurrence of HCQ-induced pigmentation is not uncommon, with an incidence rate of 26.3%. Daily sun exposure time exhibited a protective effect against HCQ-induced pigmentation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Although diffusion gradient in thin-film technique (DGT) has realized the in-situ sampling Sulfamethazine (SMT), the traditional DGT devices cannot be served as sensing devices but in-situ sampling devices. Here we report a recyclable surface enhanced Raman scattering (SERS) responsive DGT sensing device (recyclable SERS-DGT Sensing Device) capable of in-situ sensing of SMT in water. This is achieved by innovatively utilizing a recyclable SERS responsive liquid suspension of Au nanoparticles supported on g-C 3 N 4 (Au@g-C 3 N 4 NS) as DGT binding phase. Au@g-C 3 N 4 NS is synthesized via in-situ growth method and embed in DGT binding phase, which exhibits good SERS activity, aqueous stability recyclable and adsorption performance. The SERS-DGT Sensing Device is valid for measuring SMT under a wide range of conditions (i.e., deployment time 24∼180 h, concentrations range of 1.031∼761.9 ng mL -1 , pH 5∼9, ionic strength 0.0001∼0.05 mol L -1 NaCl, DOM concentrations 0∼100 mg L -1 , four recycles). Furthermore, substrate combined with DGT binding phase, can integrate the sampling, pretreatment and SERS detection of SMT, which can be recycled, improving the reliability and efficiency of environmental monitoring. In this article, recyclable SERS-DGT Sensing Device, a platform for recyclable in-situ sensing of antibiotics, holds great potential for environmental monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder characterized by progressive airflow limitation. This meta-analysis aims to evaluate the effectiveness of respiratory muscle training (RMT) on key pulmonary function parameters, inspiratory muscle strength and quality of life in patients with stable COPD., Methods: A comprehensive search was conducted in the databases including PubMed, Cochrane, Web of Science, Embase, and ClinicalTrials.gov, from their inception to June 12, 2023. Randomized controlled trials (RCTs) evaluating the impact of RMT on stable COPD were included for meta-analysis., Results: In total, 12 RCTs involving 453 participants were included in the meta-analysis. RMT demonstrated a significant increase in maximal inspiratory pressure (PImax, MD, 95% CI: 14.34, 8.17 to 20.51, P < 0.001) but not on maximal expiratory pressure (PEmax). No significant improvement was observed in 6-Min walk test (6MWT), dyspnea, forced expiratory volume in 1 s (FEV 1 ), forced vital capacity ratio (FVC) and quality of life between RMT and control groups. However, subgroup analysis revealed a significant negative effect of RMT alone on FEV 1 /FVC (MD, 95% CI: 2.59, -5.11 to -0.06, P = 0.04). When RMT was combined with other interventions, improvements in FEV1/FVC and FEV1 were found, although not statistically significant., Conclusion: RMT can effectively improve maximal inspiratory pressure in stable COPD patients, but the effect is slight in improving lung function, dyspnea and quality of life. It is recommended to combine with other treatment strategies to comprehensively improve the prognosis of COPD patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This article investigates the finite-time stability of a class of fractional-order bidirectional associative memory neural networks (FOBAMNNs) with multiple proportional and distributed delays. Different from the existing Gronwall integral inequality with single proportional delay ( N = 1 ), we establish the Gronwall integral inequality with multiple proportional delays for the first time in the case of N ≥ 2 . Since the existing fractional-order single-constant delay Gronwall inequality with two different orders cannot be directly applied to the stability analysis of the aforementioned system, initially, we skillfully develop a novel one with generalized fractional multiproportional delays' Gronwall inequalities of different orders. Furthermore, combined with the newly constructed generalized inequality, the stability criteria of FOBAMNNs with fractional orders and under weaker conditions, i.e., at most linear growth and linear growth conditions rather than the global Lipschitz condition, are given respectively. Finally, numerical experiments verify the effectiveness of the proposed method.

Although diffusion gradient in the thin-film technique (DGT) is highly regarded in environmental analysis, the traditional DGT devices cannot serve as sensing devices but in situ sampling devices. Here we report a surface enhanced Raman scattering (SERS) responsive DGT sensing device (SERS-DGT Sensor) capable of on-site determination of organic contaminants underwater. This is achieved by innovatively utilizing a SERS responsive liquid suspension of Au nanoparticles supported on graphene oxide (AuNPs@GO) as the DGT binding phase. Liquid suspension is synthesized via a combined secondary growth and molecular welding approach and used as DGT binding phase AuNPs@GO exhibit good SERS activity, aqueous stability, and adsorption performance. Based on the development time range of 24-144 h, the measurement of sulfadiazine (SMT) by SERS-DGT Sensor is evaluated in the concentration range of 0.3289-2631 ng mL -1 . The SERS-DGT sampler is valid for measuring SMT under a wide range of environmental conditions (i.e, pH 5-9, ionic strength 0.0001-0.05 mol L -1 NaCl, DOM concentrations 0-100 mg L -1 , the values of TC: SMT ≤ 20 and MNZ: SMT ≤ 20). SERS-DGT Sensor is applied to the practical test of SMT content in pig breeding wastewater, and compared with the grab sampling method, the results confirm that this novel hyphenated technique exhibits good accuracy and precision. The platform proves to be versatile by extending the method to the monitoring of rhodamine 6G, metronidazole, fluoxetine, and enrofloxacin. In this article, SERS-DGT Sensor, a platform for directly on-site sensing of organic DGT, holds great potential for in situ sampling and on-site sensing for a wide range of organics and provides a new idea for environmental monitoring.

A highly flexible stretchable thermoplastic polyurethane (TPU) composite loaded with a low-melting-point Ga 1 In 1 Sn 7 Bi 1 multiprincipal element alloy (LMPEA) was prepared, and its radiation shielding performance was evaluated. The fluid characteristic of LMPEA and the flexibility of TPU enable good interface compatibility. Ga 1 In 1 Sn 7 Bi 1 LMPEA consists of two eutectic structures, and the liquid gallium-rich phases are distributed at the boundary of the InBi intermetallic compound and Sn solid solution. In the low-photon energy range of 30-80 keV, LMPEA has a theoretical specific lead equivalent of 0.803 mmPb/mm and a theoretical weight reduction of 17.27% compared with lead. To evaluate the photon attenuation capability for the LMPEA/TPU composites, the Phy-X procedure and Monte Carlo simulations were used to determine the shielding parameters, such as the mass attenuation coefficient, linear attenuation coefficient, half-value layer, tenth-value layer, mean free path, effective atomic number, and fast neutron removal cross section. The attenuation performance test of X-ray protective materials measured the actual lead equivalent. At the same thickness, the LMPEA/TPU composite (66.667, 50.000 wt% LMPEA loading) has a higher measured lead equivalent than the in-service medical shielding materials, which meets the lead equivalent requirements of X-ray protective clothing. LMPEA/TPU composites are nontoxic, lightweight, and have excellent low-energy X-ray shielding ability, offering great potential for application in medical wearable materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Non-convex relaxation methods have been widely used in tensor recovery problems, compared with convex relaxation methods, and can achieve better recovery results. In this paper, a new non-convex function, Minimax Logarithmic Concave Penalty (MLCP) function, is proposed, and some of its intrinsic properties are analyzed, among which it is interesting to find that the Logarithmic function is an upper bound of the MLCP function. The proposed function is generalized to tensor cases, yielding tensor MLCP and weighted tensor Lγ -norm. Consider that its explicit solution cannot be obtained when applying it directly to the tensor recovery problem. Therefore, the corresponding equivalence theorems to solve the such problem are given, namely, tensor equivalent MLCP theorem and equivalent weighted tensor Lγ -norm theorem. In addition, we propose two EMLCP-based models for classic tensor recovery problems, namely low-rank tensor completion (LRTC) and tensor robust principal component analysis (TRPCA), and design proximal alternate linearization minimization (PALM) algorithms to solve them individually. Furthermore, based on the Kurdyka-Åasiwicz property, it is proved that the solution sequence of the proposed algorithm has a finite length and converges to the critical point globally. Finally, extensive experiments show that the proposed algorithm achieves good results, and it is confirmed that the MLCP function is indeed better than the Logarithmic function in the minimization problem, which is consistent with the analysis of theoretical properties.

Objective: A comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure., Design: We performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation., Results: Both IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell-cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores., Conclusion: Our study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies., Competing Interests: Competing interests: ZZ is a founder of Analytical Bioscience and an advisor for InnoCare. All financial interests are unrelated to this study. The remaining authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the effect of EGFR-TKI targeted therapy in patients with advanced non-small cell lung cancer (NSCLC)., Methods: Eighty-four cases of NSCLC were retrospectively assigned into an observation group (OG, n=42) and a control group (CG, n=42) according to the treatment methods. The CG received conventional chemotherapy, and the OG received icotinib hydrochloride EGFR-TKI targeted therapy. The clinical efficacy, cellular immunity, humoral immunity, quality of life, adverse reactions and survival time were compared between the two groups. Cox regression analysis was used to analyze the factors influencing the prognosis of advanced NSCLC., Results: The total response rate was substantially higher, and the incidence of adverse reactions was considerably lower in the OG than those in the CG (all P<0.05). The post-treatment SF-36 score was increased in both groups with significantly higher score in the OG than the CG (all P<0.001). The post-treatment CD4 + counts in both groups were notably lower than those of pre-treatment, and the count was lower in the CG than that in the OG (all P<0.001). The post-treatment CD8 + counts in both groups were notably higher after treatment than those of pre-treatment and was higher in the CG than that in the OG (all P<0.001). The post-treatment levels of IgM and IgA in both groups were declined compared with those of pre-treatment (P<0.001) with significantly lower levels in the OG than the CG (P<0.01). The 18-month mortality of the OG was significantly lower than that of the CG (P<0.05). Cox regression analysis showed that lesion diameter and differentiation degree of tumor cells were independent factors influencing the prognosis (P<0.05)., Conclusion: EGFR-TKI targeted therapy can relieve clinical symptoms, and improve immune function and quality of life of patients with advanced NSCLC, which is worthy of clinical application., Competing Interests: None., (AJTR Copyright © 2022.)

Background: Increased proliferation and impaired death of fibroblast-like synovial cells play an important role in the development of rheumatoid arthritis (RA). Survivin plays an important role in the prodromal stage and prognosis of RA and has been introduced as a biomarker of joint injury in RA patients. The purpose of this study was to explore whether propionate alleviates RA through miR-140-5p/survivin pathway., Methods: The synovial tissues of RA patients were collected to detect the expression levels of miR-140-5p and survivin; normal human fibroblast-like synovial cells (HLSs) and RA fibroblast-like synovial cells (RA-FLSs) were cultured and treated with 10 mM of sodium propionate (SP), then the expressions of miR-140-5p and survivin, cell viability and apoptosis were detected; collagen induced arthritis (CIA) rat model was constructed and treated with SP, then the tissue inflammation level and the expression levels of miR-140-5p and Survivin were detected., Results: The expression of miR-140-5p decreased in synovial tissues of RA patients and RA-FLSs cells, while the expression of survivin increased significantly in RA patients. SP promoted miR-140-5p expression and apoptosis in RA-FLSs cells and inhibited survivin expression and cell viability of RA-FLSs cells. In addition, miR-140-5p plays a protective role by targeting survivin. Importantly, in the CIA rat model, SP reduced joint inflammatory response, and the miR-140-5p inhibitor weakened the protective effect of SP., Conclusion: SP can alleviate RA by promoting the expression of miR-140-5p and inhibiting the excessive proliferation and death impairment of RA-FLSs cells induced by survivin.

3-Nitro-4-hydroxy-phenylarsonic acid (NHPA) as a veterinary drug can degraded into highly toxic inorganic arsenic and will be harmful to environment and food safety. Nanocomposites for the uptake of NHPA were obtained by efficiently immobilizing the nano-sized zirconium oxide onto hazelnut shell-based activated carbon using pyrolysis method. We found that the pyrolysis temperature played a crucial role in the adsorptive performances of the nanocomposites. The prepared nanocomposite at pyrolysis temperature of 600 °C with a mass ratio of ZrOCl 2 /activated carbon of 1:3 exhibited a fast adsorption equilibrium for NHPA within 5 min, excellent adsorption capacity of 825.7 mg g -1 and the higher adsorption capacity with the increase in temperature from 20 to 45 °C across a pH range of 4-6. 90% of the NHPA uptake was sustained in the NaNO 3 solution of 0.7 mol L -1 . The adsorption data were well simulated by the Langmuir and pseudo-second order equations. Thermodynamic parameters suggested that the uptake of the NHPA occurred spontaneously (ΔG 0 <0) with an endothermic characteristic (ΔH 0 >0). A synergetic effect of electrostatic attraction, As-O-Zr surface coordination and π-π interaction is the main adsorption mechanism of the nanocomposites for the removal of the NHPA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Polystyrene (PS) spheres were prepared through an emulsifier-free emulsion polymerization method, in which the reaction time, ionic strength, concentrations of copolymer were studied in detail. The resulting PS microspheres and Ag nanoparticles were used to construct a surface enhanced Raman scattering (SERS) substrate by a layer-by-layer assembly method. A relatively uniform distribution of PS/Ag in the films was obtained, and the multilayer substrate presented excellent SERS reproducibility and a tunable enhancement effect. The SERS substrate was used for detecting harmful pesticides (malachite green and dimetridazole) in food samples, with a limit of detection as low as 3.5 ppb. The obtained plasmonic composite has a promising future in the field of SERS sensing.

To achieve the goal of carbon neutrality, the demand for energy saving by the residential sector has witnessed a soaring increase. As a promising paradigm to monitor and manage residential loads, the existing studies on non-intrusive load monitoring (NILM) either lack the scalability of real-world cases or pay unaffordable attention to identification accuracy. This paper proposes a high accuracy, ultra-sparse sample, and real-time computation based NILM method for residential appliances. The method includes three steps: event detection, feature extraction and load identification. A wavelet decomposition based standard deviation multiple (WDSDM) is first proposed to empower event detection of appliances with complex starting processes. The results indicate a false detection rate of only one out of sixteen samples and a time consumption of only 0.77 s. In addition, an essential feature for NILM is introduced, namely the overshoot multiple (which facilitates an average identification improvement from 82.1% to 100% for similar appliances). Moreover, the combination of modified weighted K-nearest neighbors (KNN) and overshoot multiples achieves 100% appliance identification accuracy under a sampling frequency of 6.25 kHz with only one training sample. The proposed method sheds light on highly efficient, user friendly, scalable, and real-world implementable energy management systems in the expectable future.

In this study, three high-efficient green light iridium(iii) complexes were designed and synthesized, wherein 2-methyl-8-(2-pyridine) benzofuran [2,3- B ] pyridine (MPBFP) is the main ligand and three β-diketone derivatives, namely 3,7-diethyl-4,6-nondiazone (detd), 2,2,6,6-tetramethyl-3,5-heptyldione (tmd) and acetylacetone (acac), are ancillary ligands. The thermal stabilities, electrochemical properties, and electroluminescence (EL) performance of these three complexes, namely (MPBFP) 2 Ir(detd), (MPBFP) 2 Ir(tmd) and (MPBFP) 2 Ir(acac), were investigated. The results show that the absorption peaks of the three complexes range from 260 to 340 nm, and the maximum emission wavelengths are 537 nm, 544 nm and 540 nm, respectively. The LUMO level is -2.18 eV, -2.20 eV, -2.21 eV, and the HOMO level is -5.30 eV, -5.25 eV, and -5.25 eV, respectively. The thermal decomposition temperatures of each of the three compounds are 359 °C, 389 °C and 410 °C respectively, with a weight loss of 5%. Green phosphorescent electroluminescent devices were prepared with the structure of ITO/HAT-CN/TAPC/TCTA/TCTA:X/Bepp2/LiF/Al, and the three complexes were dispersed in the organic light-emitting layer as the guest material X. The maximum external quantum efficiency of the devices is 17.2%, 16.7%, and 16.5%, respectively. The maximum brightness is 57 328 cd m -2 , 69 267 cd m -2 and 69 267 cd m -2 , respectively. With respect to the EL properties, (MPBFP) 2 Ir(detd) is the best performer among the three complexes. The different performances exhibited by these complexes were discussed from the view point of substituent effect on the β-diketone ligands., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Several randomized controlled trials (RCTs) have compared the treatment of acute lung injury (ALI) with omega-3 fatty, yet the results remained inconsistent. Therefore, we attempted this meta-analysis to analyze the role of omega-3 fatty in the treatment of ALI patients., Methods: We searched PubMed databases from inception date to October 31, 2019, for RCTs that compared the treatment of ALI with or without omega-3 fatty. Two authors independently screened the studies and extracted data from the published articles. Summary mean differences (MD) with 95% confidence intervals (CI) were calculated for each outcome by fixed- or random-effects model., Results: Six RCTs with a total of 277 patients were identified, of whom 142 patients with omega-3 fatty acid treatment and 135 patients without omega-3 fatty treatment. Omega-3 fatty treatments significantly improve the PaO 2 (MD = 13.82, 95% CI 8.55-19.09), PaO 2 /FiO 2 (MD = 33.47, 95% CI 24.22-42.72), total protein (MD = 2.02, 95% CI 0.43-3.62) in ALI patients, and omega-3 fatty acid treatments reduced the duration of mechanical ventilation (MD = - 1.72, 95% CI - 2.84 to - 0.60) and intensive care unit stay (MD = - 1.29, 95% CI - 2.14 to - 0.43) in ALI patients., Conclusions: Omega-3 fatty can effectively improve the respiratory function and promote the recovery of ALI patients. Future studies focused on the long-term efficacy and safety of omega-3 fatty use for ALI are needed.

The Coats-Redfern method is commonly used to calculate the activation energy of the thermal degradation from a single non-isothermal thermogravimetric curve since its first proposal in 1964. This paper represents the accurate expressions, sound derivation process and proper usage of the Coats-Redfern equations, based on the critique into the Coats-Redfern's original article, Djalal Trache's incorrect comments on Reza Arjmandi et al.'s article, and the flaw in Reza Arjmandi et al.'s work per se., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Flexible plasmonic Surface-enhanced Raman scattering (SERS) substrates were fabricated using cellulose textile fibers, in which the textile fibers were recycled from waste paper in an eco-friendly way. The Glycidyltrimethylammonium chloride (GTAC) with positive charges was grafted onto the surface of the cellulose textile fibers through cationization. Plasmonic silver nanoparticles (Ag NPs) with negative charges were decorated onto the cellulose textile fibers via electrostatic interactions. After cationization, the variation range of the diameter of the cellulose textile fibers was significantly increased because part of the cellulose was dissolved under alkaline condition, leading to more 'hot spots' for SERS during the shrinking process. The cellulose textile fiber-Ag NPs nanocomposite was employed for monitoring bisphenol A (BPA) in water and soft drink by SERS and the sensitivity of BPA detection achieved 50 ppb. The recovery values of BPA in soda water samples were from 96% to 105%. These results illustrate that the cellulose textile fiber-Ag NPs nanocomposite can be used as flexible, high sensitivity SERS substrates for detecting harmful ingredients in food or environment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, Mn-doped MgAl-layered double hydroxides (LDHs) were successfully synthesized for efficient removal arsenate from aqueous solution. The structure and composition of Mn-doped MgAl-LDHs intercalated by different ions such as CO 3 2- , Cl - , or NO 3 - were investigated. The characterizations of XRD, ATR FT-IR, SEM, TG-DTA, and N 2 adsorption-desorption presented that the Mn-doped MgAl-LDHs (donated as Mn-LDHs) have very similar physical morphologies and properties to the MgAl-Cl-LDHs (donated as Mg-LDHs). However, the Mn-LDHs exhibits more preferable arsenate adsorption than Mg-LDHs. The As(V) removal kinetics data of Mn-LDHs is followed pseudo-second-order expression. The adsorption capacity of As(V) on Mn-LDHs via Langmuir isotherm model was 166.94 mg g -1 . The results of XPS revealed that the enhanced removal mechanism can be attributed to surface complexation of As(V) with Mn on the surface of Mn-LDHs. These results prove that Mn-doped LDHs can be considered as a potential material for adsorption As(V) from wastewater.

Following the publication of this article, we realized that the joint first author's name had been printed incorrectly in the journal: This was mispelled as "Lingqing Chen". The corrected name (Lingqiang Chen) is featured here. We regret any inconvenience this has caused, and thank the Editor for allowing us the opportunity to publish a Corrigendum. [the original article was published in the Molecular Medicine Reports 16: 3208‑3216, 2017; DOI: 10.3892/mmr.2017.7028].

Lu2O3:RE3+ (RE3+ = Eu3+, Tb3+, Ho3+) nanoparticles have been successfully synthesized by a facile homogeneous precipitation method with subsequent sintering process. The crystal structure, morphology and luminescence properties of the as-prepared samples have been characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), photoluminescence (PL) and cathodoluminescence (CL) spectra. Upon ultraviolet (UV) and low-voltage electron beam excitation, Lu2O3:RE3+ (RE3+ = Eu3+, Tb3+, Ho3+) nanoparticles show strong red (Eu3+,5D0 → 7F2), green (Tb3+,5D4 → 7F5), and green (Ho3+,5S2 → 5I8) emissions. They exhibit a good advantage of multicolor emissions in the visible region, and endow these kinds of materials with potential application in many fields, such as light display systems, optoelectronic devices and biological imaging.

Osteoarthritis (OA) is a multifactorial disease characterized by degeneration of the articular cartilage due to genetic and epigenetic components. The pathogenesis of OA is complex and the mechanism of chondrocyte homeostatic regulation remains to be fully elucidated. Previous studies have demonstrated that microRNAs (miRNAs/miR) contribute to cartilage dysfunction. However, the functional role of miR‑98 in interleukin‑1β (IL‑1β)‑induced chondrocyte apoptosis in OA cartilage remains to be investigated. The present study aimed to identify and characterize the expression profile of miR‑98 and apoptosis‑associated proteins in healthy and OA chondrocytes, and western blot analysis and TUNEL staining were used to evaluate the role of miR‑98 in the regulation of chondrocyte apoptosis. The present study demonstrated that miR‑98 expression was increased in OA chondrocytes in response to IL‑1β stimulation, and the expression levels of apoptosis-associated proteins, including Fas cell surface death receptor, caspase‑3, caspase‑8 and B‑cell lymphoma‑2 (Bcl‑2)-associated X protein, were also increased in IL‑1β‑stimulated chondrocytes. In addition, it was revealed that upregulation of miR‑98 was accompanied by reduced expression of Bcl‑2 following exposure to IL‑1β. IL‑1β‑induced downregulation of Bcl‑2 was associated with miR‑98‑mediated translational repression. Transfection of OA chondrocytes with a miR‑98 inhibitor had an inhibitory effect on IL‑1β‑induced cell apoptosis, increased cell proliferation and upregulated Bcl‑2 expression. It is possible that miR‑98 inhibited IL‑1β‑induced chondrocyte apoptosis by modulating Bcl‑2 expression levels. The findings of the present study indicated that the effects of miR‑98 on chondrocyte apoptosis were induced by regulation of Bcl‑2 expression. In addition, the present study confirmed that miR‑98 targeted the 3'‑untranslated region of Bcl‑2. In conclusion, miRNA‑coordinated regulation of apoptosis‑associated protein expression has been identified in OA chondrocytes following IL‑1β induction.

Mg-Al layered double hydroxides (LDHs) adsorbent was synthesized in situ on γ-Al 2 O 3 for the removal of Cr(VI) from aqueous solution. The material was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electronic microscopy and thermogravimetry and differential thermal analysis. Compared to the LDHs powder, the calcined LDHs sorbent prepared in situ on γ-Al 2 O 3 had higher specific surface area and was easy to recover and reuse. The adsorptive capacity for removing Cr(VI) from aqueous solution was resulting from the memory effect of LDHs based on the XRD results. Both the pseudo-second-order kinetic model and the Langmuir model fit the experimental data well. Furthermore, the adsorbent exhibits excellent sorption-regeneration performances.

Altered expression of miRNA-98 (miR-98) has been reported in osteoarthritis (OA) patients, while its role and underlying mechanisms remain elusive. In the present study, a rat model of OA was established using modified Hulth method, and the expression level of miR-98 and its effect on cartilage degradation and cell apoptosis in OA rats were examined. The results showed that up-regulated miR-98 was observed in OA rats, and knockdown of miR-98 in OA rats resulted in an inhibitory effect on cartilage degradation and chondrocyte apoptosis. Then the potential apoptosis associated genes regulated by miR-98 were screened and examined in cartilage tissues. The target gene of miR-98 was validated by luciferase reporter assay. The data showed that the increased miR-98 was accompanied with a reduced expression of Bcl-2 at both mRNA and protein levels. Furthermore, the silencing of miR-98 in OA rats prevented the down-regulation of Bcl-2 in cartilage tissues. Finally, the luciferase reporter assay validated that Bcl-2 was the target gene of miR-98. In this study, we found that miR-98 might promote chondrocyte apoptosis and cartilage degradation by down-regulating Bcl-2 expression in the pathogenesis of OA, suggesting that miR-98 can be a potential target for the treatment of OA., (© The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluated the possibility of sampling dissolved orthophosphate using the diffusive gradient in thin films (DGT) technique with a phosphate ion-imprinted polymer (PIP)-based adsorbent and assessed the effect of biofilm on the DGT measurement. The composition of biofilm formed on the DGT surface was analyzed, and the effect of biofouling on the diffusion coefficient of the analyte was investigated. The corrected diffusion coefficient for the biofouled DGT was estimated and used for the calculation of the DGT equation. PIP-binding gels had a higher adsorption affinity for orthophosphate than for the other anions, indicating its selectivity for orthophosphate. The concentrations predicted via DGT agreed well with the concentrations determined in the bulk solutions. Sampling of orthophosphate using PIP-DGT was consistent over a pH range of 3-9 and ionic strength range of 0.01-10 000 μM. Other P compounds cannot be measured using the PIP-DGT technique. The diffusion coefficient of the orthophosphate linearly decreased with increasing thickness of the biofilm. This sampling method performed predictably in freshwater when the biofilm was not formed or when value for the biofilm interference was reduced by using the corrected diffusion coefficient.

Objective: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases., Methods: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment. Paired synovial (n=3, RA, PsA) and skin biopsies (n=5, Ps) were also collected. Gene expression was analyzed by microarrays., Results: 26 out of 31 subjects responded to IFX. The transcriptional response of CD14+ cells to IFX was unique for the three diseases, with little overlap (<25%) in significantly changed gene lists (with PsA having the largest number of changed genes). In Ps, altered gene expression was more pronounced in lesional skin (relative to paired, healthy skin) compared to blood (relative to healthy controls). Marked suppression of up-regulated genes in affected skin was noted 2 weeks after therapy but the expression patterns differed from uninvolved skin. Divergent patterns of expression were noted between the blood cells and skin or synovial tissues in individual patients. Functions that promote cell differentiation, proliferation and apoptosis in all three diseases were enriched. RA was enriched in functions in CD14- cells, PsA in CD14+ cells and Ps in both CD14+ and CD14- cells, however, the specific functions showed little overlap in the 3 disorders., Conclusion: Divergent patterns of altered gene expression are observed in RA, PsA and Ps patients in blood cells and target organs in IFX responders. Differential gene expression profiles in the blood do not correlate with those in target organs.

For the first time, a diffusive gradients in thin films (DGT) device using molecularly imprinted polymer (MIP) as the binding agent and nylon membrane (NM) as the diffusive layer (NM-MIP-DGT) has been developed for sampling 4-chlorophenol (4-CP) in water. The MIP was prepared by precipitation polymerization with methacrylic acid as monomer and ethyleneglycoldimethacrylate as cross-linker. The diffusion coefficient of 4-CP through NM was obtained to be 0.788±0.040 μ cm(2) s(-1) by diffusion cell method. The ratio was 1.01±0.05 (mean±standard deviation) for the concentration of 4-CP sampled by NM-MIP-DGT and analyzed by HPLC method to the total concentration of 4-CP in the synthetic solution where free 4-CP species dominated. The results showed that NM-MIP-DGT could sample 4-CP in synthetic solution accurately. The performance of NM-MIP-DGT for sampling 4-CP was independent of pH in the range of 3-7 and ionic strength in the range of 0.0001-0.1 mol L(-1) NaCl solution. The concentration of free form of 4-CP sampled by NM-MIP-DGT decreased with the increasing concentration of dissolved organic carbon in different water samples due to the electrostatic interaction of natural organic compounds with 4-CP. 1.8 mg L(-1) of the free form of 4-CP was determined by HPLC which was sampled by NM-MIP-DGT in an intermediate untreated industrial effluent. The NM-MIP-DGT can be a potential passive tool for sampling the free form of 4-CP in water., (Copyright © 2014. Published by Elsevier B.V.)

ZnO nanostructures were manipulated, via a low-temperature solution process, from pure nanorod arrays to complex nanostructures of microflowers on nanorod arrays with adjusted quantities of flowers. We proposed the mechanism of local dissolution-driven growth to rationally discuss the novel growth process. These nanostructures were used as photoanodes in dye-sensitized solar cells. Compared to pure nanorod arrays, the nanorod array-microflower hierarchical structures improved the power conversion efficiency from 0.41% to 0.92%, corresponding to a 124% efficiency increase. The enhancement of the efficiency was mainly ascribed to the synergistic effect of the enhanced surface area for higher dye loading and the improved light harvesting from efficient light scattering. Present results provide a promising route to improve the capability of light-harvesting for ZnO nanorod array-based DSSCs.

Background: Technical improvements have decreased sequencing costs and, as a result, the size and number of genomic datasets have increased rapidly. Because of the lower cost, large amounts of sequence data are now being produced by small to midsize research groups. Crossbow is a software tool that can detect single nucleotide polymorphisms (SNPs) in whole-genome sequencing (WGS) data from a single subject; however, Crossbow has a number of limitations when applied to multiple subjects from large-scale WGS projects. The data storage and CPU resources that are required for large-scale whole genome sequencing data analyses are too large for many core facilities and individual laboratories to provide. To help meet these challenges, we have developed Rainbow, a cloud-based software package that can assist in the automation of large-scale WGS data analyses., Results: Here, we evaluated the performance of Rainbow by analyzing 44 different whole-genome-sequenced subjects. Rainbow has the capacity to process genomic data from more than 500 subjects in two weeks using cloud computing provided by the Amazon Web Service. The time includes the import and export of the data using Amazon Import/Export service. The average cost of processing a single sample in the cloud was less than 120 US dollars. Compared with Crossbow, the main improvements incorporated into Rainbow include the ability: (1) to handle BAM as well as FASTQ input files; (2) to split large sequence files for better load balance downstream; (3) to log the running metrics in data processing and monitoring multiple Amazon Elastic Compute Cloud (EC2) instances; and (4) to merge SOAPsnp outputs for multiple individuals into a single file to facilitate downstream genome-wide association studies., Conclusions: Rainbow is a scalable, cost-effective, and open-source tool for large-scale WGS data analysis. For human WGS data sequenced by either the Illumina HiSeq 2000 or HiSeq 2500 platforms, Rainbow can be used straight out of the box. Rainbow is available for third-party implementation and use, and can be downloaded from http://s3.amazonaws.com/jnj&#95;rainbow/index.html.

Objective: To evaluate associations between biomarkers and radiographic progression in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) treated with MTX or golimumab, a tumor necrosis factor inhibitor (with or without MTX)., Methods: Serum samples from 152 MTX-naive adults with active RA who received placebo + MTX (n = 37) or golimumab (combined 50 mg + MTX or 100 mg ± MTX; n = 115) were analyzed for selected markers of inflammation and bone/cartilage turnover. One hundred patients were randomly selected for additional protein profiling using multianalyte profiles (HumanMap v1.6, Rules Based Medicine). Radiographs at baseline, Week 28, and Week 52 were scored using van der Heijde-Sharp (vdH-S) methodology. Correlations were assessed between biomarker levels (baseline and change at Week 4) and joint space narrowing, erosion, and total vdH-S scores (changes at Weeks 28 and 52). Statistical significance was defined as a correlation coefficient with an absolute value ≥ 0.3 and p < 0.05., Results: Biomarker correlations with changes in vdH-S scores at Week 28 and/or 52 were observed predominantly in the placebo + MTX group and rarely in the combined golimumab treatment group. Changes in epidermal growth factor (EGF) and CD40 ligand (CD40L) at Week 4 were positively correlated with changes in total vdH-S scores at Weeks 28 and 52 in the placebo + MTX group., Conclusion: These preliminary findings indicate that EGF and CD40L may have utility in monitoring MTX-treated patients with RA who are more likely to have radiographic progression as measured by increases in vdH-S scores.

Background: Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue., Objective: We sought to explore the role of the T-helper (Th)1 and Th17 pathways in sarcoidosis., Methods: We used molecular profiling and gene expression analysis to analyze the Th1 and Th17 pathways and other immune-mediated pathways in CS. Molecular profiles were obtained from sarcoidosis skin lesions (lesional skin [LS]), unaffected skin from patients with CS (non-LS), and the skin of healthy control subjects. Whole blood was collected to compare the molecular profile of sarcoidosis skin lesions and whole blood., Results: Twenty participants were enrolled: 15 with active CS and 5 healthy volunteers. Microarray analyses comparing non-LS and healthy volunteer skin with LS showed several thousand genes differentially expressed (≥2-fold change false discovery rate, P < .01). Targeted selections of genes associated with Th1 and Th17 phenotypes showed a strong Th1 profile of sarcoidosis and expression of interleukin (IL)-23 and IL-23R with limited expression of other Th17 pathway genes. IL-21 and signal transducer and activator of transcription 3 (STAT3) were also dysregulated in skin and whole blood, providing additional evidence for involvement of the IL-12 pathway and potential activation of the Th17 pathway., Limitations: Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally., Conclusion: These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

The analysis of whole blood samples by flow cytometry for pharmacodynamic and biomarker assessments in clinical studies has been limited by the necessity to test these samples within a short time frame after blood collection. In most clinical studies, blood specimens are shipped to a centralized testing facility; it is critical to demonstrate specimen stability over a period of time which will encompass the time elapsed between specimen collection and testing. A possible solution to overcome this limitation is the use of a fixative to preserve the cell surface antigen stability in whole blood. We examined the stability of markers for T lymphocytes (CD3, CD4, CD8, CD45RA, and CD45RO), B lymphocytes (CD19), NK cells (CD16+CD56), activation (CD25 and HLA-DR), chemokine receptors (CCR5 and CXCR3) and skin homing (CLA) in fixed blood over 7 days and used this information to select the markers for global clinical studies. These assays with selected markers were further validated using fit-for-purpose approach (Lee et al., 2006) and to set the sample acceptability criteria for use in clinical sample testing. Most of the markers examined were stable when collected in Cyto-Chex® BCT for one week with the exception of the activation markers on T cells., (Published by Elsevier B.V.)

A technique for the selective measurement of diffusive gradients in thin-films (DGT) for free Cu2+ ions was developed using a 0.030 M solution of polyvinyl alcohol (PVA) as the liquid binding phase with the liquid-type DGT devices (PVA DGT). The PVA DGT had a substantial binding capacity at pH 5.6 - 8.6 and concentrations of competitive Na+ up to 0.7 M. The measurements of PVA DGT and cupric ion selective electrode (Cu-ISE) for free Cu2+ in synthetic river water (recovery = 97.51 +/- 2.58% for PVA DGT and recovery = 98.25 +/- 1.46% for Cu-ISE), in spiked river water (recovery = 24.99 +/- 3.55% for PVA DGT and recovery = 26.32 +/- 3.33% for Cu-ISE) and in spiked industrial wastewater (recovery = 4.21 +/- 3.13% for PVA DGT and recovery = 5.10 +/- 2.78% for Cu-ISE) were equivalent. The results showed that PVA DGT could measure selectively the free Cu2+ ion concentrations in water samples.

Background: MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC samples of different stages, and four matched normal colon tissue samples. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis., Results: The expression analysis of clinical CRC samples identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical samples. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context., Conclusion: MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in CRC provide a basis for understanding the functional role of miRNAs in cancer.

An aqueous solution containing sodium polyacrylate (PA, 0.0030M) was used in diffusive gradients in thin-films technique (DGT) to measure DGT-labile Cu(2+) and Cd(2+) concentrations. The DGT devices (PA DGT) were validated in four types of solutions, including synthetic river waters containing metal ions with or without complexing EDTA, natural river water (Hun River, Shenyang, China) spiked with Cu(2+) and Cd(2+), and an industrial wastewater (Shenyang, China). Results showed that only free metal ions were measured by PA DGT, recovery=98.79% for Cu(2+) and recovery=97.80% for Cd(2+) in solutions containing only free metal ions, recovery=51.02% for Cu(2+) and recovery=51.92% for Cd(2+) in solution with metal/EDTA molar ratio of 2:1 and recovery=0 in solutions with metal/EDTA molar ratio of 1:1 and 1:2. These indicated that the complexes of Cu-EDTA and Cd-EDTA were DGT-inert or not DGT-labile. The DGT performance in spiked river water (recovery=8.47% for Cu(2+) and recovery=27.48% for Cd(2+)) and in industrial wastewater (recovery=14.16% for Cd(2+)) were also investigated. Conditional stability constants (logK) of PA-Cu and PA-Cd complexes were determined as 6.98 and 5.61, respectively, indicating strong interaction between PA and the metals.

Non-small cell lung cancer (NSCLC), which is comprised mainly of adenocarcinoma and squamous cell carcinoma (SCC), is the cause of 80% of all lung cancer deaths in the United States. NSCLC is also associated with a high rate of relapse after clinical treatment and, therefore, requires robust prognostic markers to better manage therapy options. The aim of this study was to identify microRNA (miRNA) expression profiles in SCC of the lung that would better predict prognosis. Total RNA from 61 SCC samples and 10 matched normal lung samples was processed for small RNA species and profiled on MirVana miRNA Bioarrays (version 2, Ambion). We identified 15 miRNAs that were differentially expressed between normal lung and SCC, including members of the miR-17-92 cluster and its paralogues. We also identified miRNAs, including miR-155 and let-7, which had previously been shown to have prognostic value in adenocarcinoma. Based on cross-fold validation analyses, miR-146b alone was found to have the strongest prediction accuracy for stratifying prognostic groups at approximately 78%. The miRNA signatures were superior in predicting overall survival than a previously described 50-gene prognostic signature. Whereas there was no overlap between the mRNAs targeted by the prognostic miRNAs and the 50-gene expression signature, there was a significant overlap in the corresponding biological pathways, including fibroblast growth factor and interleukin-6 signaling. Our data indicate that miRNAs may have greater clinical utility in predicting the prognosis of patients with squamous cell lung carcinomas than mRNA-based signatures.

At present, there is no method available to predict response to farnesyltransferase inhibitors (FTIs). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1/APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy using a "leave one out" cross validation (LOOCV; 96%). RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair. The utility of this classifier for predicting response to tipifarnib was validated in an independent set of 58 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (154 vs 56 days; P < .001), which was independent of other covariates, including a previously described prognostic gene expression classifier. Therefore, these data indicate that a 2-gene expression assay may have utility in categorizing a population of patients with AML who are more likely to respond to tipifarnib.

Peripheral blood may be the most feasible tissue source in clinical assessment of differences in gene expression between diseases and drug treatments due to accessibility. Yet, gene expression profiling from blood remains a challenge. Blood is a complicated biological system consisting of a variety of cell types at different stages of development. In addition, blood is also one of the most variable tissue types for gene expression analysis. The success of a blood microarray study depends on the choice of cell isolation method and preparation technique. In this review, we give a brief overview of the current status of using blood as a source for expression profiling and discuss potential applications of this method in the practices of clinical research.

The combination of zirconocene-mediated coupling of silylated alkynes with a protonation-desilylation or bromination-desilylation process afforded otherwise unavailable butadiene derivatives. When (E,E)-2,3-dialkyl-1,4-bis(trimethylsilyl)-1,3-butadienes were treated with 3 equiv of Br(2) in CH(2)Cl(2), (E)-2,3-dialkyl-1,1,4,4-tetrabromo-2-butenes were obtained in excellent yields with perfect stereoselectivity.

We performed a comparative genomic sequence analysis between human and mouse for 24 imprinted genes on human chromosomes 1, 6, 7, 11, 13, 14, 15, 18, 19, and 20. The MEME program was used to search for motifs within conserved sequences among the imprinted genes and we then used the MAST program to analyze for the presence or absence of motifs in the imprinted genes and 128 nonimprinted genes. Our analysis identified 15 motifs that were significantly enriched in the imprinted genes. We generated a logistic regression model by combining multiple motifs as input variables and the 24 imprinted genes and the 128 nonimprinted genes as a training set. The accuracy, sensitivity, and specificity of our model were 98, 92, and 99%, respectively. The model was further validated by an open test on 12 additional imprinted genes. The motifs identified in this study are novel imprinting signatures, which should improve our understanding of genomic imprinting and the role of genomic imprinting in human diseases.

Interleukin-12 (IL-12) is an immunoregulatory cytokine that plays an essential role in cell-mediated immunity. It is known to induce T cell apoptosis in in vivo systems such as graft-versus-host disease (GVHD) and experimental autoimmune uveitis (EAU). However, the role of IL-12 in T cell apoptosis in the absence of antigenic stimulation has not been clearly defined. This study was conducted to investigate whether IL-12, in the absence of an antigen, is able to induce T cell apoptosis, and also, which signalling pathways utilized by IL-12 are involved in this process. Our data clearly showed that IL-12 in the absence of an antigen induces apoptosis in T cells. Flow cytometry and ELISA showed FasL up-regulation and increased IFN-gamma synthesis in IL-12 treated T cells, while Fas and TNF-R1 showed little change. Semi-quantitative RT-PCR demonstrated that IL-12 was able to up-regulate TNF-alpha and FasL mRNA expression. Furthermore, IL-12 induced apoptosis was associated with caspase-3, caspase-2, caspase-7, DNA fragmentation factor 45 (DFF45) and Fas associated death domain (FADD) whereas TNF receptor associated death domain (TRADD) and receptor interacting protein (RIP) were not. Inhibition of Janus tyrosine kinase (JAK) was able to suppress IL-12 induced T cell apoptosis. Anti-FasL antibody was able to block IL-12 induced T cell apoptosis. In conclusion, our findings suggest that IL-12 is able to induce T cell apoptosis in the absence of an antigen. In addition, the present data suggest that this process is FasL mediated and caspase-3 dependent. Furthermore, JAK was shown to be involved in this process. These results may have significant implications in the understanding of IL-12 mediated T cell apoptosis., (Copyright 2002 Elsevier Science Ltd.)

In order to explore the role of p15(INK4B) gene with highly methylated CpG island in the pathogenesis of leukemia, the expression levels of p15(INK4B) gene was detected in patients with AML and CML. Methylation-specific PCR (MSP) assay was employed in the experiments. The methylation incidence was 83.9% (26/31) in AML and 0% (0/28) in CML. The results showed that methylation of p15(INK4B) gene was the one of the major ways for inactivation of the gene, and the methylation could be appeared in clinical development of the disease and patients condition worsened. Methylation of p15(INK4B) did not occur and its function probably is normal in CML.

To study the action, characteristics and expression of high methylation of p15(INK4B) and p16(INK4A) genes in multiple myeloma (MM), the sensitive methylation specific PCR method was employed to detect the hypermethylation of p15(INK4B) and p16(INK4A) in 24 patients with MM. Results showed that the methylation incidence of p15(INK4B) and p16(INK4A) genes were 70.8% (17/24) and 58.3% (14/24) in the MM patients, with the products of 148 bp and 150 bp fragments, respectively. The methylation of p15(INK4B) and p16(INK4A) genes were simultaneously happened in MM patients of plasmocytoma type with two cases at II phase and two cases at III phase. The simultaneous non-methylation of p15(INK4B) and p16(INK4A) genes were founded in five cases of MM patients, all of the tumor cells were of small plasmocyte type with mature differention. Conclusion suggested that there were high incidence of methylation of p15(INK4B) and p16(INK4A) genes in patients with MM. Hypermethylation can be detected in the early stage of disease, which was associated with its progress. It indicated a bad prognosis when methylation happended simultaneously in the two genes. Methylation of p15(INK4B) and p16(INK4A) genes may be related to the pathogeny of MM.