bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Growth of Bilayer‐MoS2 Films and MoS2‐Based Field‐Effect Transistor (FET) Performance Optimization
Authors: Fang Mingxu , Wang Fang , Han Yemei , Feng Yulin , Ren Tianling , Li Yue , Tang Dengxuan , Song Zhitang , Zhang Kailiang
Published: March 2018

The effect of hydrogen flow on MoS2 film synthesis via chemical vapor deposition is studied systematically. Large‐sized monolayer‐ and bilayer‐MoS2 triangles can be synthesized controllably at given temperatures. Optical microscopy, Raman spectroscopy, photoluminescence spectroscopy, and atomic force microscopy are used to characterize the number of layers, purity, and uniformity of the MoS2 triangle films. Moreover, the back‐gated field‐effect transistors (FETs) based on the monolayer‐ and bilayer‐MoS2 channels are fabricated using traditional micro‐nanoprocessing technology. Electrical behaviors are investigated and the bilayer‐MoS2 FETs show preferable performance with high mobility (≈21 cm2 V−1 s−1), on‐current (≈22 µA µm−1), and a small degradation in the on/off ratio (1.1 × 107). Finally, the semiconductive phase MoS2 (2H‐MoS2) is transformed to a metallic phase (1T‐MoS2) to reduce the resistance in metal‐MoS2 contact. The FET device with 1T‐MoS2 contact enhances mobility (≈45 cm2 V−1 s−1) and on‐current (≈50 µA µm−1) compared with the 2H‐MoS2 FETs. This work sheds light on the synthesis of variable‐layer MoS2 films and paves the way for further development regarding MoS2 film‐based devices.
Dimensional Crossover Transport Induced by Substitutional Atomic Doping in SnSe2
Authors: Lee Suyoun , Lee Young Tack , Park Seong Gon , Lee Kyu Hyoung , Kim Sung Wng , Hwang Do Kyung , Lee Kimoon
Published: March 2018

Substitutional atomic doping is one of the most convenient and precise routes to modulate semiconducting material properties. Although two‐dimensional (2D) layered transition metal dichalcogenides (TMDs) are of great interest as a prominent semiconducting material due to their unique physical/chemical properties, such a practical atomic doping is still rare, possibly due to the intrinsic localization nature of conduction paths based on d‐band states. Here, using single‐crystalline Cl‐doped SnSe2, the dimensional crossover in carrier transport accompanied by semiconductor‐to‐metal transition is reported. Nondoped SnSe2 shows semiconducting transport behavior dominated by 2D variable range hopping conduction, exhibiting relatively strong localization of carriers at low‐temperature regions. Moderately electron‐doped SnSe2 by substitution on Se with higher valent Cl exhibits superior electrical conductivity even than the heavily doped one owing to the higher electron mobility of the former (167 cm2 V−1 s−1 at 2 K). Combined with Raman spectra, temperature dependence of mobility clearly evidences the effective screening of homopolar optical mode phonon compared to typical TMD materials. Detailed characterizations with magnetoresistance behaviors finally demonstrate that the suppression of both homopolar optical mode phonon and carrier localization as retaining low‐dimensionality is key for high mobility conduction in electron‐doped SnSe2.
Morphology Control in Organic Solar Cells
Authors: Zhao Fuwen , Wang Chunru , Zhan Xiaowei
Published: March 2018

Organic solar cells (OSCs) can directly convert the sunlight into electrical energy and present some advantages, such as low cost, light weight, flexibility, semitransparency, and roll‐to‐roll large‐area fabrication. Due to the short diffusion length of exciton (≈10 nm) in organic semiconductor materials, the ideal nanoscale phase separation in the active layer is one of the crucial factors for achieving efficient exciton dissociation and charge transport. The morphology of the active layer is mainly determined by the nature of donors and acceptors (e.g., solubility, crystallinity, and miscibility), the film processing, the device configuration, and so on. In general, it is very hard to obtain ideal morphology in the as‐cast films. Therefore, it is usually essential to take measures to achieve the active layer with good molecular stacking, proper domain size, high domain purity, and suitable vertical phase separation. In this review, recent developments in morphology control and morphology characterization are summarized and analyzed. This review might help the community to decipher active layer morphology at multiple length scales and to achieve ideal morphology toward high‐performance OSCs.
What Makes a Good Solar Cell?
Authors: Kirchartz Thomas , Rau Uwe
Published: March 2018

Recent years have seen a substantial efficiency improvement for a variety of solar cell technologies as well as the rise of a new class of photovoltaic absorber materials, the metal‐halide perovskites. Conversion efficiencies that are coming closer and closer to the thermodynamic limits require a physical description of the corresponding solar cells that is compatible with those limits. This progress report summarizes recent work on the interdependence of basic material properties of semiconductor materials with their efficiency potential as photovoltaic absorbers. The connection of the classical Shockley–Queisser approach, with the band gap energy as the only parameter, to a more general radiative limit and to situations where nonradiative recombination dominates is discussed. The authors delineate a consistent loss analysis that enables a quantitative comparison between different solar cell technologies. In a next step, bulk material properties that influence the photovoltaic performance of a semiconductor like absorption coefficient, densities of states of the free carriers, or phonon energies are considered. It is shown that variations of these properties have a big influence on the optimized design of a solar cell but not necessarily on the achievable efficiency.
Donor–Acceptor–Acceptor's Molecules for Vacuum‐Deposited Organic Photovoltaics with Efficiency Exceeding 9%
Authors: Che Xiaozhou , Chung Chin‐Lung , Hsu Chou‐Chun , Liu Feng , Wong Ken‐Tsung , Forrest Stephen R.
Published: March 2018

Three vacuum‐deposited donor–acceptor–acceptor (d–a–a') small molecule donors are studied with different side chains attached to an asymmetric heterotetracene donor block for use in high efficiency organic photovoltaics (OPVs). The donor with an isobutyl side chain yields the highest crystal packing density compared to molecules with 2‐ethylhexyl or n‐butyl chains, leading to the largest absorption coefficient and short circuit current in an OPV. It also exhibits a higher fill factor, consistent with its preferred out‐of‐plane molecular π–π stacking arrangement that facilitates charge transport in the direction perpendicular to the substrate. A power conversion efficiency of 9.3 ± 0.5% is achieved under 1 sun intensity, AM 1.5 G simulated solar illumination, which is significantly higher than 7.5 ± 0.4% of the other two molecules. These results indicate that side chain modification of d–a–a' small molecules offers an effective approach to control the crystal packing configuration, thereby improving the device performance.
Machine learning for crystal identification and discovery
Authors: Spellings Matthew , Glotzer Sharon C.
Published: March 2018

As computers get faster, researchers—not hardware or algorithms—become the bottleneck in scientific discovery. Computational study of colloidal self‐assembly is one area that is keenly affected: even after computers generate massive amounts of raw data, performing an exhaustive search to determine what (if any) ordered structures occur in a large parameter space of many simulations can be excruciating. We demonstrate how machine learning can be applied to discover interesting areas of parameter space in colloidal self‐assembly. We create numerical fingerprints—inspired by bond orientational order diagrams—of structures found in self‐assembly studies and use these descriptors to both find interesting regions in a phase diagram and identify characteristic local environments in simulations in an automated manner for simple and complex crystal structures. Utilizing these methods allows analysis to keep up with the data generation ability of modern high‐throughput computing environments. © 2018 American Institute of Chemical EngineersAIChE J, 64: 2198–2206, 2018
Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation
Authors: Nicolaï Niels , De Leersnyder Fien , Copot Dana , Stock Michiel , Ionescu Clara M. , Gernaey Krist V. , Nopens Ingmar , De Beer Thomas
Published: March 2018

Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (%w/w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25%w/w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. © 2018 American Institute of Chemical EngineersAIChE J, 64: 2500–2514, 2018
Influence of Different Moisture Contents on the Stability of Tocochromanols in Bulk Oils at 25 °C Storage
Authors: Jung Jinyeong , Yi BoRa , Kim Mi‐Ja , Lee JaeHwan
Published: March 2018

The stabilities of tocochromanols including α‐tocopherol, α‐tocotrienol, γ‐tocopherol, γ‐tocotrienol, and δ‐tocotrienol in grape seed oil, palm oil, or stripped soybean oil with added tocotrienol mixtures (SOTT) were determined under relative humidity (RH) 0, 32, 75, and 93% at 25 °C for 8 months of storage. Stability of tocochromanols was significantly influenced by the presence of moisture and other tocochromanols. Tocochromanol stability in grape seed oil was high at RH 75%, whereas palm oil had significantly lower tocochromanol content at RH 75% compared to those under other RH (p < 0.05). Tocochromanol stability in SOTT was high at RH 0%. δ‐Tocotrienol had the highest stability followed by α‐tocotrienol, γ‐tocotrienol, and α‐tocopherol in SOTT. Moisture content in palm oil was the lowest while that in SOTT was the highest at the same RH. Oxidative stability of palm oil was the highest followed by grape seed oil and SOTT based on conjugated dienoic acid content and p‐anisidine values. Moisture in oils affects the stability of tocochromanols and oxidative stability in vegetable oils.
Zero‐Trans Cake Shortening: Formulation and Characterization of Physicochemical, Rheological, and Textural Properties
Authors: Saghafi Zahra , Naeli Mohammad Hossein , Tabibiazar Mahnaz , Zargaraan Azizollaah
Published: March 2018

Cake shortening is an important ingredient that imparts taste and texture in the cake as the final product. Hydrogenated shortenings contain high amounts of trans fatty acids, which is considered a risk factor for obesity, cancers, and cardiovascular diseases. In this research, chemically interesterified blends of canola oil (CO) and palm stearin (PS) were recruited in order to formulate zero‐trans shortening, specifically for cake application. The optimization of shortening formulation was performed by Design‐Expert software, considering melting, congelation, textural, and rheological properties of cake shortening as responses. The formulated shortening in the weight ratio of 66.41:33.58 (PS:CO) (%, w/w) was analyzed and compared with two commercial cake shortenings in terms of fatty acid and triacylglycerol composition, slip melting point (SMP), solid fat content (SFC), and rheological and textural properties. The results showed that the formulated zero‐trans cake shortening with 0.2% trans, 47.2% saturated fatty acids, SMP of 40.9 °C, SFC of 10.51% at 37 °C, firmness of 1522.5 g, and linear viscoelastic range of 0.035% had the most acceptable criteria among cake‐shortening samples. The findings of this study offer insights into the relationship between shortening functionality and physicochemical properties and serve as a base for future studies on zero‐trans shortenings formulation.
Polyurethane‐incorporated chitosan/alginate core–shell nano‐particles for controlled oral insulin delivery
Authors: Bhattacharyya Aditi , Nasim Farhat , Mishra Roshnara , Bharti Ram P. , Kundu P.P.
Published: March 2018

Chitosan (CS) and polyurethane‐chitosan (PU‐CS) nano‐particles (NPs) were prepared for the core formation by complex coacervation method whereas alginate (ALG) and PU‐ALG were crosslinked by ionic gelation method to form the protective shell‐layer over the core. Effects of PU incorporation either within the core or shell or both were investigated by differentin vitroandin vivoparameters. Fourier transform infrared (FTIR) spectroscopy of different compositions of nano‐particles showed distinct characteristic peaks for CS, PU, and ALG, indicating their presence in variable ratios. Significance of polyurethane‐incorporated systems towards insulin encapsulation efficiency, swelling parameters, insulin release, andin vivopharmacological effect were also studied. Particle sizes, zeta potential, morphological analysis, mucoadhesion study, andin vivoacute toxicity studies of these core–shell nano‐particles were also performed. Bioavailability of insulin ranged from 9.04% to 11.6% for polyurethane‐incorporated chitosan‐alginate core–shell nano‐particle formulations which was significantly higher than the insulin bioavailability of basic CS/ALG core–shell nano‐particle system. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2018,135, 46365.
Quantitative Analysis of the Maturation of the Main and Accessory Olfactory Systems in Monotremes and Metatherians in Comparison to Rodents and Humans
Authors: Ashwell Ken William S. , Shulruf Boaz
Published: March 2018

We have used an unbiased statistical approach to compare the pace of development in the main and accessory olfactory systems in monotremes and metatherians with that in rodents and humans. We hypothesized that if metatherians and monotremes, which are born at small body size, use olfaction to locate the pouch and/or teat/milk field, then olfactory structures should reach structural maturity in metatherians and monotremes at a smaller size than eutherians like humans and rodents. The achievement of key structural milestones in the development of the main and accessory olfactory systems (11 and 7 milestones, respectively) was scored for 354 specimens and compared against a measure of general somatic growth (body length). We used a statistical approach adapted from Kaplan‐Meier analysis to determine median body length at which structural milestones were achieved, and to test the differences for statistical significance (Braslow statistic). The laboratory mouse achieved most main olfactory milestones at a smaller body size than all the metatherians and the monotremes, although the dasyurids (which are born at only 5.0 mm) and mouse achieved accessory olfactory milestones at similar body length. All other metatherians and monotremes reached olfactory milestones at body lengths similar to or larger than the laboratory rat. We therefore reject the hypothesis that metatherians and monotremes as a group exhibit advanced development of the olfactory pathways relative to body size. The findings suggest that, if olfaction is used by metatherians and monotremes at birth, it is achieved with only a rudimentary system without structurally mature central components. Anat Rec, 301:1258–1275, 2018. © 2018 Wiley Periodicals, Inc.
Differential Clinical Associations of Anti–Nuclear Matrix Protein 2 Autoantibodies in Patients With Idiopathic Inflammatory Myopathies
Authors: Yang Hanbo , Lu Xin , Peng Qinglin , Jiang Wei , Shi Jingli , Zhang Yamei , Chen He , Wang Guochun
Published: March 2018

Objective

To investigate the associations between anti–nuclear matrix protein 2 (anti–NXP‐2) autoantibody levels and disease activity as well as calcinosis severity in patients with idiopathic inflammatory myopathies (IIMs).

Methods

Serum levels of anti–NXP‐2 autoantibodies were determined in 709 patients with IIMs and also serially measured in the patients’ sera with an in‐house enzyme‐linked immunosorbent assay using MORC3 recombinant protein. Patients with anti–NXP‐2 autoantibodies were divided into 2 subgroups: those with and those without calcinosis. Associations of anti–NXP‐2 autoantibody levels with organ‐specific disease activity (using 10‐cm visual analog scale [VAS] scores), serum creatine kinase (CK) levels, and calcinosis severity were investigated in cross‐sectional and longitudinal analyses.

Results

A cross‐sectional analysis of 56 IIM patients with anti–NXP‐2 autoantibodies (38 without calcinosis and 18 with calcinosis) showed that in patients without calcinosis, the levels of anti–NXP‐2 autoantibodies were positively correlated with the physician's global assessment of disease activity and muscle VAS scores and serum CK levels, whereas no such association was found in patients with calcinosis. Results of the longitudinal study revealed strong correlations of anti–NXP‐2 antibody levels with the physician's global assessment and constitutional, cutaneous, gastrointestinal, and muscle VAS scores and serum CK levels in patients without calcinosis, but in patients with calcinosis, only a moderate correlation was observed between anti–NXP‐2 antibody levels and the physician's global VAS and constitutional VAS scores. Of note, in patients without calcinosis, anti–NXP‐2 autoantibodies were found to disappear during periods of clinical remission, but reappeared with disease relapse. No association between anti–NXP‐2 antibody levels and the severity of calcinosis was observed.

Conclusion

These findings indicate that anti–NXP‐2 autoantibodies serve as a useful marker for disease activity in patients with IIMs, especially in the absence of calcinosis. The differential associations observed between anti–NXP‐2 autoantibody levels and disease activity suggest that there may be a phenotypic difference between patients with and those without calcinosis.
Interfacial Materials for Anti‐Icing: Beyond Superhydrophobic Surfaces
Authors: Jin Shenglin , Liu Jie , Lv Jianyong , Wu Shuwang , Wang(s) Jianjun
Published: March 2018

The design and fabrication of interfacial materials for anti‐icing is of great importance, since undesired ice accumulation leads to serious economic, energy, and safety issues. Substantial progress on interfacial materials for the passive removal of ice has been achieved in the past three years. The present focus review critically summarizes and analyzes recent breakthroughs in interfacial materials for anti‐icing. In particular, we focus on the effect of surface textures on the timely removal of water droplets, the microscopic mechanism of ice formation, and the effect of an interfacial layer's properties on easy shedding of formed ice with a view towards designing high‐performance and durable interfacial materials for anti‐icing beyond superhydrophobic materials.
Efficient Synthesis of N‐Alkylated 4‐Pyridones by Copper‐Catalyzed Intermolecular Asymmetric Propargylic Amination
Authors: Shao Wen , Wang Ye , Yang Ze‐Peng , Zhang Xiao , You Shu‐Li
Published: March 2018

Copper‐catalyzed intermolecular asymmetric propargylic amination with 4‐hydroxypyridines has been realized for the first time. In the presence of Cu complex derived from Pybox ligand, the N‐propargylated 4‐pyridones were obtained under mild reaction conditions with up to 99 % yield and 95 % ee. The Pybox ligand bearing a 4‐F‐phenyl substituent plays a key role for the high enantioselectivity. The products can be easily transformed to the core structure of quinolizidine alkaloids.
Oxidative stress, as assayed by a single test, cannot be used as a diagnostic tool
Authors: Lichtenberg Dov , Pinchuk Ilya , Weber Daniela
Published: March 2018

The commonly used term “oxidative stress” (OS) is intuitively defined as an excess of pro‐oxidative compounds, over antioxidants. The redox status is homeostatically controlled because on one hand, pro‐oxidants are essential for normal body function, whereas, on the other hand, pro‐oxidants (and OS) are associated with many diseases due to the risk of oxidative damage. One reason “to monitor the OS” is to identify people under OS and treat people under high OS by antioxidants, because it is believed that people under OS benefit from antioxidant supplementation more than others. This approach led to the production of many assay kits, based on the concentrations of different biomarkers in body fluids. Unfortunately, this expensive approach (evaluated at about a half a billion dollars per year) yields very limited results because: (i) the effect of antioxidants on the OS is not that simple and (ii) OS cannot be quantitated in terms of a universal criterion and the method‐dependent OS yields different groups of people under OS. This conclusion gains strong support from analysis of the results of a previous study of the OS in more than 2000 participants, using many OS assays. The small overlapping between the “people under OS” as assayed by different biomarkers clearly shows that OS cannot be used as a diagnostic tool. © 2018 BioFactors, 44(3):222–223, 2018
Survival following liver transplantation for liver-only colorectal metastases compared with hepatocellular carcinoma
Authors: Dueland S , Foss A , Solheim J M , Hagness M , Line P-D
Published: March 2018

Background

Liver transplantation is considered the standard of care for patients with hepatocellular carcinoma (HCC) within the Milan criteria. Liver transplantation in patients with unresectable colorectal cancer with liver-only disease has been shown to be associated with a 5-year overall survival rate of 56 per cent, compared with 9 per cent in patients receiving standard palliative chemotherapy. The aim of the present study was to compare disease-free (DFS) and overall (OS) survival after liver transplantation in patients with HCC and those with colorectal metastases.

Methods

Data were collected from the SEcondary CAncer (SECA) study database and an institutional (national) database of patients undergoing liver transplantation for HCC; all liver-transplanted patients were included. Patients with colorectal metastases treated by liver transplantation were divided into high- and low-risk groups for mortality based on carcinoembryonic antigen levels, response to chemotherapy, largest lesion at time of transplantation and time from primary surgery to transplantation.

Results

Patients with colorectal metastases had a median of 8 lesions, compared with 1 in patients with HCC within the Milan criteria. DFS was shorter in both the high-risk and the low-risk colorectal cancer groups compared with that in patients with HCC. The 5-year OS rate in the low-risk colorectal cancer group was 75 per cent, compared with 76 per cent in patients with HCC within the Milan criteria. The 5-year OS rate in patients with HCC beyond the Milan criteria was 56 per cent.

Conclusion

The low-risk group of patients with colorectal cancer and unresectable liver-only disease had a 5-year OS rate following liver transplantation similar to that of patients with HCC with lesions within the Milan criteria.
Change in emotional self‐concept following socio‐cognitive training relates to structural plasticity of the prefrontal cortex
Authors: Lumma Anna‐Lena , Valk Sofie L. , Böckler Anne , Vrtička Pascal , Singer Tania
Published: March 2018

Introduction

Self‐referential processing is a key component of the emotional self‐concept. Previous studies have shown that emotional self‐referential processing is related to structure and function of cortical midline areas such as medial prefrontal cortex (mPFC), and that it can be altered on a behavioral level by specific mental training practices. However, it remains unknown how behavioral training‐related change in emotional self‐concept content relates to structural plasticity.

Methods

To address this issue, we examined the relationship between training‐induced change in participant's emotional self‐concept measured through emotional word use in the Twenty Statement Test and change in cortical thickness in the context of a large‐scale longitudinal mental training study called the ReSource Project.

Results

Based on prior behavioral findings showing increased emotional word use particularly after socio‐cognitive training targeting perspective‐taking capacities, this study extended these results by revealing that individual differences in the degree to which participants changed their emotional self‐concept after training was positively related to cortical thickness change in right mPFC extending to dorsolateral PFC (dlPFC). Furthermore, increased self‐related negative emotional word use after training was positively associated with cortical thickness change in left pars orbitalis and bilateral dlPFC.

Conclusions

Our findings reveal training‐related structural brain change in regions known to be involved in self‐referential processing and cognitive control, and could indicate a relationship between restructuring of the emotional self‐concept content as well as reappraisal of negative aspects and cortical thickness change. As such, our findings can guide the development of psychological interventions targeted to alter specific facets of the self‐concept.
Timing of chemotherapy‐induced neutropenia is a prognostic factor in patients with advanced gastric cancer undergoing first‐line chemotherapy with oxaliplatin and capecitabine: a retrospective study
Authors: Wang Yanrong , Chen Yang , Yin Hongyan , Gu Xiaobin , Shi Yan , Dai Guanghai
Published: March 2018

Chemotherapy‐induced neutropenia (CIN) has been shown to be associated with improved clinical outcomes in patients with various solid tumors. This study retrospectively assessed the association between timing of CIN and prognosis in 321 patients with advanced gastric cancer (AGC) who finished at least one cycle of chemotherapy with oxaliplatin and capecitabine (XELOX). Primary landmark analyses were restricted to 274 patients who received four cycles of chemotherapy and lived for more than 4 months. CIN was categorized as early‐onset and non‐early‐onset. The correlation between timing of CIN with survival was analyzed by the Kaplan‐Meier method and a Cox proportional hazards model. Relative to patients with non‐early‐onset CIN, those with early‐onset CIN had significantly longer times to disease progression (hazard ratio [HR] 0.574; 95% confidence interval [CI] 0.453–0.729, P < 0.001) and death (HR: 0.607; 95% CI: 0.478–0.770, P < 0.001), consistent with results from the landmark group. In conclusion, timing of CIN may be a potential prognostic biomarker in patients with AGC receiving first‐line chemotherapy with XELOX. Early‐onset CIN predicts better survival.
Physical activity across the lifespan and liver cancer incidence in the NIH‐AARP Diet and Health Study cohort
Authors: Arem Hannah , Loftfield Erikka , Saint‐Maurice Pedro F. , Freedman Neal D. , Matthews Charles E.
Published: March 2018

While liver cancer rates in the United States are increasing, 5‐year survival is only 17.6%, underscoring the importance of prevention. Physical activity has been associated with lower risk of developing liver cancer, but most studies assess physical activity only at a single point in time, often in midlife. We utilized physical activity data from 296,661 men and women in the NIH‐AARP Diet and Health Study cohort to test whether physical activity patterns over the life course could elucidate the importance of timing of physical activity on liver cancer risk. We used group modeling of longitudinal data to create physical activity trajectories using four time points across the life course from teenage years through middle age, identifying seven distinct trajectories. We then used Cox proportional hazards regression to assess the association between the physical activity trajectories and risk of hepatocellular carcinoma, the most common type of liver cancer. We found that, in adjusted analyses, compared to those with consistently low physical activity patterns, those who maintained activity levels over time had a 26–36% lower risk of liver cancer and those who increased physical activity over time had no associations with risk, while those who decreased activity over time had a nonsignificantly higher risk of liver cancer. Our results suggest that sustained physical activity is associated with lower risk of hepatocellular carcinoma, while increasing physical activity later in life may not yield the same benefit. Future research with larger sample sizes and more detailed data on dose and timing of physical activity may continue to yield insight into this association between physical activity and liver cancer risk.
Association between preoperative serum insulin levels and lymph node metastasis in endometrial cancer—a prospective cohort study
Authors: Mu Nan , Dong Mei , Liu Chunyan , Wang Xiuli , Cong Jianglin , Wang Liqian , Wang Xiaojie , Lakhani Ishan , Liu Xia , Hou Jianqing , Wang Shaoguang , Tse Gary
Published: March 2018

Endometrial cancer is a common gynecological malignancy in developed countries. Insulin has been identified as a risk factor for endometrial cancer. However, whether insulin levels are related to the risk of lymph node metastasis (LNM) in endometrial cancer is unknown. We conducted a prospective cohort study in a regional hospital to examine the relationships between insulin levels and risk of LNM in premenopausal and postmenopausal women. A total of 668 patients were recruited. Of these, 206 were premenopausal (mean age: 42.01 ± 10.17) and 462 were postmenopausal (mean age: 62.13 ± 13.85). The incidence of LNM in both premenopausal and postmenopausal groups was comparable at 7% and 8%, respectively. In premenopausal women, multivariate logistic regression demonstrated that insulin levels (OR: 2.11, 95% CI: 1.48–2.85, P < 0.05) were significant predictors of LNM risk. In the same group, insulin levels remained significant predictors of LNM risk (cut‐off: 10.48 μIU/mL) when adjusted for body mass index (BMI) (OR: 3.51, 95% CI: 1.42–5.98; P < 0.05) or for waist‐to‐hip ratio (WHR) (OR: 1.87, 95% CI: 1.08–2.66; P < 0.05). Similarly, in postmenopausal women, multivariate logistic regression showed that insulin levels (OR: 1.99, 95% CI: 1.30–2.89; P < 0.05) also significantly predicted LNM risk. This relationship was maintained even after adjustment for BMI (cut‐off: 7.40 μIU/mL, OR: 1.99, 95% CI: 1.01–3.12, P < 0.05) or for WHR (cut‐off: 10.15 μIU/mL, OR: 1.61, 95% CI: 1.04–2.35; P < 0.05). Insulin levels are significantly associated with LNM risk in both premenopausal and postmenopausal women with endometrial cancer. Further prospective studies are needed to examine a potential causal relationship and determine whether its use can offer incremental value for risk stratification in this patient population.
Polymorphism rs2682818 in miR‐618 is associated with colorectal cancer susceptibility in a Han Chinese population
Authors: Chen Yuetong , Du Mulong , Chen Wei , Zhu Lingjun , Wu Congye , Zhang Zhengdong , Wang Meilin , Chu Haiyan , Gu Dongying , Chen Jinfei
Published: March 2018

MicroRNAs (miRNAs), endogenous small noncoding RNAs (ncRNAs), play crucial roles in cancer development. Many studies have demonstrated that miRNAs can serve as diagnostic and therapeutic biomarkers for malignancies. Additionally, single nucleotide polymorphisms (SNPs) located in miRNA functional regions have been reported to be involved in cancer susceptibility. In this study, we investigated the associations between SNPs located in miRNA functional regions and colorectal cancer (CRC) susceptibility. We systematically screened all candidate miRNAs and their SNPs and then evaluated the relationships between the SNPs and CRC susceptibility in a Han Chinese population including 878 patients with CRC and 884 controls. Genotyping was performed by TaqMan assay. After comprehensively screening the miRNAs and SNPs, we elected to evaluate the association between SNP rs2682818 in miR‐618 and CRC susceptibility. We found that the AA and AC/AA genotypes of rs2682818 were associated with a decreased risk of CRC compared with the CC genotype (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37–0.79 for AA vs. CC in codominant model; OR = 0.82, 95% CI = 0.68–0.99 for AC/AA vs. CC in dominant model). However, we obtained no statically significant results in our subgroup analyses. SNP rs2682818 in miR‐618 has potential as a biomarker for individuals with high CRC susceptibility. Our findings need to be verified in studies including larger samples. Moreover, molecular functional studies of miR‐681 must be performed to confirm its relationship with CRC.
Traditional Chinese Medicine CFF‐1 induced cell growth inhibition, autophagy, and apoptosis via inhibiting EGFR‐related pathways in prostate cancer
Authors: Wu Zhaomeng , Zhu Qingyi , Yin Yingying , Kang Dan , Cao Runyi , Tian Qian , Zhang Yu , Lu Shan , Liu Ping
Published: March 2018

Traditional Chinese medicine (TCM) has a combined therapeutic result in cancer treatment by integrating holistic and local therapeutical effects, by which TCM can enhance the curative effect and reduce the side effect. In this study, we analyzed the effect of CFF‐1 (alcohol extract from an anticancer compound Chinese medicine) on prostate cancer (PCa) cell lines and studied in detail the mechanism of cell death induced by CFF‐1 in vitro and in vivo. From our data, we found for the first time that CFF‐1 obviously arrested cell cycle in G1 phase, decreased cell viability and then increased nuclear rupture in a dose‐dependent manner and finally resulted in apoptosis in prostate cancer cells. In molecular level, our data showed that CFF‐1 induced inhibition of EGFR auto‐phosphorylation and inactivation of EGFR. Disruption of EGFR activity in turn suppressed downstream PI3K/AKT and Raf/Erk signal pathways, resulted in the decrease of p‐FOXO1 (Ser256) and regulated the expression of apoptosis‐related and cycle‐related genes. Moreover, CFF‐1 markedly induced cell autophagy through inhibiting PI3K/AKT/mTOR pathway and then up‐regulating Beclin‐1 and LC‐3II and down‐regulating phosphorylation of p70S6K. In vivo, CFF‐1‐treated group exhibited a significant decrease in tumor volume compared with the negative control group in subcutaneous xenograft tumor in nude mice via inhibiting EGFR‐related signal pathways. Thus, bio‐functions of Chinese medicine CFF‐1 in inducing PCa cell growth inhibition, autophagy, and apoptosis suggested that CFF‐1 had the clinical potential to treat patients with prostate cancer.
Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy
Authors: Liao Rui , Peng Cong , Li Ming , Li De‐Wei , Jiang Ning , Li Pei‐Zhi , Ding Xiong , Wu Qiao , Du Cheng‐You , Gong Jian‐Ping
Published: March 2018

In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence‐free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including α‐fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C‐indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram‐predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.
Nutlin‐3a as a novel anticancer agent for adrenocortical carcinoma with CTNNB1 mutation
Authors: Hui Wen , Liu Shenghua , Zheng Jie , Fang Zujun , Ding Qiang , Feng Chenchen
Published: March 2018

Adrenocortical carcinoma (ACC) is a rare malignancy, and CTNNB1 is frequently mutated in ACC. Our study aims to screen for effective agents with antineoplastic activity against ACC with CTNNB1 mutation. In‐silico screening of the Genomics of Drug Sensitivity in Cancer (GDSC) database was conducted. Drug sensitivity in cells with CTNNB1 mutation was analyzed and further in vitro and in vivo studies were performed using the compound. Only one compound, Nutlin‐3a, an MDM2 inhibitor, was significantly sensitive in 18 cancer cells with CTNNB1 mutation. Further analysis of the 18 cells revealed no significant efficacy between cells with both CTNNB1 and TP53 mutations indicating concomitant TP53 mutation did not impact on drug efficacy. We verified that Nutlin‐3a inhibited cellular proliferation in ACC cell line NCI‐H295R which harbored CTNNB1 mutation but not in SW13 cells which did not. Nutlin‐3a induced cell apoptosis and G1 cell‐cycle arrest in NCI‐H295R cells. Nutlin‐3a also decreased cellular migration and inhibited epithelial‐to‐mesenchymal transition (EMT) process in terms of EMT index. Nutlin‐3a resulted in decreased β‐catenin level independent of p53 level in NCI‐H295R but not SW13 cells. We also evaluated the effect of Nutlin‐3a on hormonal secretion of NCI‐H295R cells and found it resulted in decreased levels of cortisol, androgen, and progesterone. Nutlin‐3a treatment inhibited ACC tumor growth with no observed toxicity in mice in vivo. Our study has revealed that Nutlin‐3a potently inhibits ACC with CTNNB1 mutation. How p53/MDM2 axis coordinates with Wnt/beta‐Catenin signaling in ACC warrants further study.
Excessive risk of second primary cancers in young‐onset colorectal cancer survivors
Authors: He Xingkang , Wu Wenrui , Ding Yu'e , Li Yue , Si Jianmin , Sun Leimin
Published: March 2018

With an increasing trend of patients with young‐onset colorectal cancer (CRC), risks of second primary cancers (SPCs) among them become a concerning issue. We aimed to define the detailed risk and site‐distributed patterns of SPCs in young CRC individuals (age ≤50). A population‐based cohort were identified from the Surveillance, Epidemiology, and End Results database between 1973 and 2013. Standardized incidence ratios (SIRs) and absolute excess risk (AER) were calculated to assess the risk for SPCs compared with the general population. A total of 44,106 patients, including 3245 (7.4%) the young and 40,861 (92.6%) the old, developed 50,679 secondary malignancies subsequently. With increased age, the risk of secondary cancers gradually decreased. A significant 44% excess risk of SPCs was observed in the young (SIR = 1.44, AER = 34.23), while a slightly increased risk was noted in the old (SIR = 1.02, AER = 4.29). For young survivors, the small intestine (SIR = 8.49), bile ducts (SIR = 3.77), corpus, and uterus (SIR = 2.45) were the most common sites of SPCs. Significantly, excess SIRs in the young were persisted regardless of other factors. For the young, secondary cancer‐related deaths were responsible for 51.2% of overall deaths and secondary stomach, liver and bile, pancreas cancers were top three causes. An excessive risk of SPCs existed in young CRC survivors, and this trend was consistent among different subgroups. We hope our findings may inform future targeted screening strategies among young‐onset CRC survivors.
Dual Maleimide Tagging for Relative and Absolute Quantitation of Cysteine‐Containing Peptides by MALDI‐TOF MS
Authors: Ouyang Fuzhong , Zhao Zhihao , Gao Ruifang , Shi Rui , Wu Enhui , Lv Rui , Xu Guoqiang , Liu Jian
Published: March 2018

A dual maleimide (DuMal) tagging method has been developed for both relative and absolute quantitation of cysteine‐containing peptides (CCPs) in combination with MALDI‐TOF mass spectrometry. A pair of maleimides with minimal differences in their chemical structures, N‐methylmaleimide and Nethylmaleimide, have been chosen to allow for the rapid (≈minutes) tagging of CCPs in the Michael addition reaction with high efficiency. It has been validated that the DuMal tagging technique is sensitive and reliable in the quantitative analysis of CCPs. Absolute quantitation of CCPs can be achieved with a detection limit as low as 7.3 nm. Relative quantitation of CCPs can be performed in various sample mixtures with consistent results (coefficient of variation <5 %). The DuMal tagging technique provides a sensitive and accurate approach for the quantitation of biomolecules containing thiol reactive sites; thus it is promising for protein detection, disease diagnosis, and biomarker discovery associated with post‐translational modifications of cysteines.
An RNA‐Cleaving Catalytic DNA Accelerated by Freezing
Authors: Yu Tianmeng , Zhou Wenhu , Liu Juewen
Published: March 2018

The EtNa DNAzyme was isolated during the isopropanol precipitation step of an in vitro selection effort. Although inactive with the intended cofactor, its RNA cleavage activity was observed under a few conditions. With Na+, EtNa was highly active in ∼50 % ethanol, whereas in water, it was highly active with Ca2+. In this work, we showed that the EtNa DNAzyme was accelerated by freezing in water in the presence of Na+. The apparent Kd value reached 6.2 mm Na+ under the frozen condition, over 20 times tighter than that in water at room temperature. With 10 mm Na+, EtNa had a cleavage rate of 0.12 h−1 after freezing at −20 °C. This effect was unique to EtNa, as all other tested DNAzymes were inhibited by freezing except for the Na+‐specific NaA43. Freezing also inhibited EtNa if Ca2+ was used. We attributed this to the concentrations of EtNa and Na+ in the micropockets between ice crystals, but divalent metals might misfold DNA. Overall, we have systematically studied the effect of freezing on the RNA‐cleavage activity of DNAzymes. The DNAzyme sequence and the metal ion species are both crucial to determine the effect of freezing.
Hyperbilirubinemia following lenalidomide administration
Authors: Azmy Veronica , Neparidze Natalia
Published: March 2018

Key Clinical Message

Asymptomatic hyperbilirubinemia in a patient with no underlying liver disease or renal impairment while on lenalidomide therapy may be attributable to the unmasking of previously undiagnosed Gilbert's syndrome, as previously shown in the literature. The hyperbilirubinemia should resolve after discontinuation of the drug.
Synthesis of Oxazolidinones and Derivatives through Three‐Component Fixation of Carbon Dioxide
Authors: Mei Congmin , Zhao Yibo , Chen Qianwei , Cao Changsheng , Pang Guangsheng , Shi Yanhui
Published: March 2018

An effective three‐component fixation of atmospheric CO2 with readily available 1,2‐dichloroethane and aromatic amine toward oxazolidinones catalyzed by in situ NHC was developed. The reaction occurred in good to excellent yields with good generality and wide functional group tolerance, including challenging steric hindered substituted‐dichloroethane (e.g. 1,2‐dichloropropane and 2,3‐dichlorobutane). The catalytic system is not sensitive to air and moisture, and high yield of oxazolidinone was achieved even with about 0.3 atm of pressure of carbon dioxide. The mechanistic study suggests that the reaction catalyze by in situ NHC via NHC‐CO2 adduct, 1‐butyl‐3‐methylimidazolium‐2‐carboxylate as intermediate and aminochloride involves in reaction pathways. The catalyst can be recycled for at least 3 times without obvious loss of catalytic activity. The protocol is also effective to prepare six‐membered 3‐aryl‐1,3‐oxazinan‐2‐one and even seven‐membered 3‐aryl‐1,3‐oxazepan‐2‐one, when 1,3‐dichloropropane and 1,4‐dichlorobutane was employed.
Streptavidin–Enzyme Linked Aggregates for the One‐Step Assembly and Purification of Enzyme Cascades
Authors: Mallin Hendrik , Ward Thomas R.
Published: March 2018

Herein, we report enzyme aggregates assembled around covalently cross‐linked streptavidin tetramers. The streptavidin oligomeric matrix (SavMatrix) is produced by using SpyTag/SpyCatch technology and binds tightly to fusion proteins bearing a streptavidin‐binding peptide (SBP). Fusing the SBPs to different enzymes leads to precipitation of the streptavidin–enzyme aggregates upon mixing the complementary components. This straightforward strategy can be applied to crude cell‐free extracts, allowing the one‐step assembly and purification of catalytically active aggregates. Enzyme cascade assemblies can be produced upon adding different SBP‐fused enzymes to the SavMatrix. The reaction rate for lactate dehydrogenase (LDH) is improved tenfold (compared with the soluble enzyme) upon precipitation with the SavMatrix from crude cell‐free extracts. Additionally, the kinetic parameters are improved. A cascade combining a transaminase with LDH for the synthesis of enantiopure amines from prochiral ketones displays nearly threefold rate enhancement for the synthesis of (R)‐α‐methylbenzylamine compared with the free enzymes in solution.
Bioinspired Reduced Graphene Oxide/Polyacrylonitrile‐Based Carbon Fibers/CoFe2O4 Nanocomposite for Flexible Supercapacitors with High Strength and Capacitance
Authors: Song Kun , Wang Xin , Wang Jun , Zhang Bin , Zuo Chunling
Published: March 2018

For the first time, zero‐dimensional (0D) CoFe2O4 nanoparticles, one‐dimensional (1D) polyacrylonitrile‐based carbon fibers (PBCF), and two‐dimensional (2D) reduced graphene oxide (RGO) nanosheets were used as building blocks to create an integrated ternary nanocomposite paper with a nacre‐like microstructure for flexible supercapacitors. Inspired by the “mortar‐brick” toughening mechanism of nacre, hydrogen and covalent bonding were further introduced into the bioinspired paper with 0D CoFe2O4, 1D PBCF, and 2D RGO to realize increased mechanical properties through the synergistic toughening effects of the interfacial interactions of hydrogen and covalent bonding. These collaboratively lead to enhanced mechanical properties such as high tensile strength, exceptional toughness, and eminent electrical conductivity. When used as a free‐standing flexible electrode, the bioinspired interconnected 3D network exhibits an outstanding volumetric capacity of 240 F ⋅ cm−3 at 10 mV ⋅ s−1 and an excellent cycle life of 2000 cycles for a flexible symmetric supercapacitor device (SSCD). Remarkably, the fabricated flexible SSCD can be cycled reversibly in the voltage range of −1 to 0 V and shows a maximum energy density of 33.33 mW ⋅ h cm−3, suggesting great potential for practical applications in flexible energy storage devices.