bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver‐Target and Glucose‐Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization
Authors: Wang Aohua , Fan Weiwei , Yang Tiantian , He Shufang , Yang Yiwei , Yu Miaorong , Fan Li , Zhu Quanlei , Guo Shiyan , Zhu Chunliu , Gan Yong
Published: February 2020

Oral insulin therapy that targets the liver and further mimics glucose‐responsive secretion holds promise for correcting defects in glucose metabolism caused by peripheral delivery. This work describes the construction of polymersomes (Pep‐PMS), which are composed of glucose‐responsive polymers decorated with peptides that readily bind to the ganglioside‐monosialic acid (GM1) receptor in the intestinal epithelium. Pep‐PMS are efficiently transported across the intestinal epithelium through GM1‐mediated transcytosis, leading to their abundant accumulation in the liver. Moreover, Pep‐PMS can efficiently encapsulate insulin in euglycemia and release them in hyperglycemia. Under hyperglycemic conditions, the Pep‐PMS dissociate to release the encapsulated insulin in response to glucose oxidase (GOx)‐induced H2O2. Surprisingly, the postprandial blood glucose levels of diabetic rats treated with Pep‐PMS can be maintained even after being challenged by glucose administration. Hepatic glucose uptake and glycogen production are also elevated after treating diabetic rats with Pep‐PMS, which is similar to glucose utilization in normal rats. Oral delivery systems that target the liver and serve as a reservoir for glucose‐responsive insulin secretion may improve the therapeutic effect in people with diabetes.
A Novel Approach for Achieving High‐Efficiency Photoelectrochemical Water Oxidation in InGaN Nanorods Grown on Si System: MXene Nanosheets as Multifunctional Interfacial Modifier
Authors: Lin Jing , Yu Yuefeng , Zhang Zhijie , Gao Fangliang , Liu Sheng , Wang Wenliang , Li Guoqiang
Published: February 2020

MXene nanosheets with attractive electrical conductivity and tunable work function have been adopted as multifunctional interfacial modifier between InGaN nanorods and Si for photoelectrochemical water oxidation for the first time. Compared to bare InGaN/Si systems, MXene interfacial layers give rise to an ultralow onset potential of 75 mV versus reversible hydrogen electrode (RHE), which is the highest ever reported for InGaN‐ or Si‐based photoanodes by interfacial modification. Furthermore, the modified photoanode exhibits a significantly enhanced photocurrent density (7.27 mA cm−2) at 1.23 V versus RHE, which is about 10 times higher than that achieved with the InGaN/Si photoanode. The detailed mechanism demonstrates that the formed type‐II band alignment in InGaN/MXene heterojunction and an Ohmic junction at the MXene/Si interface make MXene an ideal electron‐migration channel to enhance charge separation and transfer process. This synergetic effect of MXene can significantly decrease the charge resistance at semiconductor/Si and semiconductor/electrolyte hetero‐interfaces, eventually resulting in the fast hole injection efficiency of 82% and superior stability against photocorrosion. This work not only provides valuable guidance for designing high‐efficiency photoelectrodes through the integration of multiscale and multifunctional materials, but also presents a novel strategy for achieving high‐performance artificial photosynthesis by introducing interfacial modifier.
A Highly Reversible, Dendrite‐Free Lithium Metal Anode Enabled by a Lithium‐Fluoride‐Enriched Interphase
Authors: Cui Chunyu , Yang Chongyin , Eidson Nico , Chen Ji , Han Fudong , Chen Long , Luo Chao , Wang Peng‐Fei , Fan Xiulin , Wang Chunsheng
Published: February 2020

Metallic lithium is the most competitive anode material for next‐generation lithium (Li)‐ion batteries. However, one of its major issues is Li dendrite growth and detachment, which not only causes safety issues, but also continuously consumes electrolyte and Li, leading to low coulombic efficiency (CE) and short cycle life for Li metal batteries. Herein, the Li dendrite growth of metallic lithium anode is suppressed by forming a lithium fluoride (LiF)‐enriched solid electrolyte interphase (SEI) through the lithiation of surface‐fluorinated mesocarbon microbeads (MCMB‐F) anodes. The robust LiF‐enriched SEI with high interfacial energy to Li metal effectively promotes planar growth of Li metal on the Li surface and meanwhile prevents its vertical penetration into the LiF‐enriched SEI from forming Li dendrites. At a discharge capacity of 1.2 mAh cm−2, a high CE of >99.2% for Li plating/stripping in FEC‐based electrolyte is achieved within 25 cycles. Coupling the pre‐lithiated MCMB‐F (Li@MCMB‐F) anode with a commercial LiFePO4 cathode at the positive/negative (P/N) capacity ratio of 1:1, the LiFePO4//Li@MCMB‐F cells can be charged/discharged at a high areal capacity of 2.4 mAh cm−2 for 110 times at a negligible capacity decay of 0.01% per cycle.
BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis
Authors: Chen Qiang , Lei Josh Haipeng , Bao Jiaolin , Wang Haitao , Hao Wenhui , Li Licen , Peng Cheng , Masuda Takaaki , Miao Kai , Xu Jun , Xu Xiaoling , Deng Chu‐Xia
Published: February 2020

The breast cancer susceptibility gene 1 (BRCA1) is a major tumor suppressor gene and is most frequently mutated in hereditary breast cancer. BRCA1 plays a critical role in many biological processes, especially maintaining genomic stability in the nucleus, yet its role in the cytoplasm remains elusive. Here, it is revealed that BRCA1 maintains a healthy mitochondrial network through regulating mitochondrial dynamics, including fission and fusion. BRCA1 deficiency causes dysfunctional mitochondrial dynamics through increased expression of mitofusin1/2. With mitochondrial stress, BRCA1 is recruited to the mitochondrial outer membrane, where it plays an essential role in maintaining a healthy mitochondrial network. Consequently, BRCA1 deficiency impairs stress‐induced mitophagy through blocking ataxia‐telangiectasia mutated (ATM)‐AMP‐activated protein kinase (AMPK)‐Dynamin‐related protein 1 (DRP1)‐mediated mitochondrial fission and triggers NLRP3 inflammasome activation, which creates a tumor‐associated microenvironment, thereby facilitating tumor proliferation and metastasis. It is further shown that inflammasome inhibition can prevent tumor recurrence and metastasis. This study uncovers an important role of BRCA1 in regulating mitophagy and suggests a therapeutic approach for fighting this deadly disease.
Large, Fast, and Bidirectional Bending of Slide‐Ring Polymer Materials
Authors: Kakizaki Shimpei , Shintake Jun , Iwatake Yasunori , Baba Kazumasa , Takeuchi Hiromitsu , Yamamoto Akio
Published: February 2020

The bending of slide‐ring materials (SRMs), polymer materials having ring‐shaped cross‐linking points providing deterioration tolerance and low hysteresis, is described. An SRM sheet exhibits a voltage‐controllable, extremely large, fast, and bidirectional bending deformation with shape memory functionality. A 50‐μm‐thick SRM sheet actuator exhibits an electrostatic actuation in two opposite directions and bending angle larger than 180° achieved within 0.4 s due to its shape memory effect. The memory effect remains for more than 250 min. As a potential application utilizing the bending of the SRM, a soft gripper is fabricated, which handles two objects placed opposite each other. This functionality is rarely achieved by a soft gripper composed of a single active material, which shows the characteristics of the SRM promising for the development of soft matter systems with novel functionalities and high performances.
Nickel‐Catalyzed α‐Carbonylalkylarylation of Vinylarenes: Expedient Access to γ,γ‐Diarylcarbonyl and Aryltetralone Derivatives
Authors: KC Shekhar , Dhungana Roshan K. , Khanal Namrata , Giri Ramesh
Published: February 2020

We report a Ni‐catalyzed regioselective α‐carbonylalkylarylation of vinylarenes with α‐halocarbonyl compounds and arylzinc reagents. The reaction works with primary, secondary, and tertiary α‐halocarbonyl molecules, and electronically varied arylzinc reagents. The reaction generates γ,γ‐diarylcarbonyl derivatives with α‐secondary, tertiary, and quaternary carbon centers. The products can be readily converted to aryltetralones, including a precursor to Zoloft, an antidepressant drug.
Pre‐targeted Imaging of Protease Activity through In Situ Assembly of Nanoparticles
Authors: Chen Zixin , Chen Min , Zhou Kaixiang , Rao Jianghong
Published: February 2020

The pre‐targeted imaging of enzyme activity has not been reported, likely owing to the lack of a mechanism to retain the injected substrate in the first step for subsequent labeling. Herein, we report the use of two bioorthogonal reactions—the condensation reaction of aromatic nitriles and aminothiols and the inverse‐electron demand Diels–Alder reaction between tetrazine and trans‐cyclooctene (TCO)—to develop a novel strategy for pre‐targeted imaging of the activity of proteases. The substrate probe (TCO‐C‐SNAT4) can be selectively activated by an enzyme target (e.g. caspase‐3/7), which triggers macrocyclization and subsequent in situ self‐assembly into nanoaggregates retained at the target site. The tetrazine‐imaging tag conjugate labels TCO in the nanoaggregates to generate selective signal retention for imaging in vitro, in cells, and in mice. Owing to the decoupling of enzyme activation and imaging tag immobilization, TCO‐C‐SNAT4 can be repeatedly injected to generate and accumulate more TCO‐nanoaggregates for click labeling.
Fluorosilicone resin as a high ultraviolet transmittance optical material
Authors: Ke Qining , Dai Zhipeng , Chen Xuhuang
Published: February 2020

In this study, hydrofluorosilicone oil with a cyclic structure () and tetramethyl‐tetravinylcyclotetrasiloxane () are synthesized through a hydrosilylation reaction with platinum as the catalyst to obtain high ultraviolet transmittance fluorosilicone. The curing process of fluorosilicone resin is monitored by Fourier transform infrared spectroscopy. The effects of differentAvalues (the molar ratio of Si─H to vinyl) on the curing process, mechanical properties, glass transition temperature, crosslinking density, hydrophobicity, and UV transmittance are studied. The results demonstrate that with the increase in theAvalue, the initial curing temperature and the temperature at the completion of curing decrease, the tensile strength initially increases and then decreases, and the glass transition temperature and crosslinking density increase. Furthermore, the contact‐angle and UV transmittance initially increase and subsequently decrease, the maximum contact‐angle is 107.61°, which shows good hydrophobicity, and the maximum UV transmittance at 351 nm reaches 93.66%.
Two Covalent Ultraviolet Nonlinear Optical Crystals
Authors: Liu Shuai , Song Gaomin , Ding Qingran , Li Yanqiang , Li Lina , Zhang Qian , Wang Yonggang , Lin Zheshuai , Luo Junhua , Zhao Sangen
Published: February 2020

Nonlinear optical (NLO) crystals are the vital components of laser science and technology, as they can convert lasers in common wavelengths into new wavelength bands for ultraviolet (UV), IR, and even terahertz laser output. Known UV NLO crystals mainly focus on crystals containing cations, but covalent crystals have rarely been reported. Here we report two covalent NLO crystals, B2O3 I and B2O3 II. According to the first‐principles calculations, B2O3 I and II have extremely short absorption edges of about 134 nm and 141 nm, large NLO coefficients of d22=1.38 pm/V and d24=0.702 pm/V, as well as sufficient birefringences of 0.037 and 0.031, respectively. Notably, the absorption edges are almost the shortest among NLO crystals. Meanwhile, the NLO coefficients are evidently larger than that of another well‐known covalent NLO crystal α‐SiO2 and are comparable to those of the commercial UV NLO crystal LiBO3 with Li+ cation. Furthermore, the birefringences are significantly larger than that of α‐SiO2, which are favorable to the phase matching for both crystals. These results reveal that B2O3 I and B2O3 II are excellent candidates for UV NLO applications. In‐depth calculations are carried out to reveal the origin of excellent NLO properties. These covalent crystals provide a new direction for the research of UV NLO crystals.
Switchable Optical Probes for Simultaneous Targeting of Multiple Anions
Authors: Dey Nilanjan , Bhattacharya Santanu
Published: February 2020

Traditional optical probes primarily work on the concept of one‐to‐one recognition strategy. Therefore, simultaneous detection of multiple anions is difficult using this kind of sensory systems. Similarly, designing of multi‐responsive array‐based materials is synthetically challenging as well as difficult to optimize. Thus, researchers across the globe became interested in developing single molecular probes, capable of detecting multiple anions (or anionic biomolecules) by simultaneously activating optically distinguishable output channels. Here, the modes of interaction largely depend on the structural features of the binding sites (cleft size, number of available coordination sites etc.), characteristics of the anions (ionic radius, hydration enthalpy, basicity, coordination number, pka of corresponding acids etc.) and the microenvironment around the probe molecules (micropolarity, viscosity, dielectric constant etc.) in the host matrix. In this review, we are mostly focusing on the structure‐activity relationships of such multiple anions sensing optical probes and their stimuli‐responsive properties.
A semi‐symbolic diagnoser for fault diagnosis of bounded labeled petri nets
Authors: Boussif Abderraouf , Ghazel Mohamed , Klai Kais
Published: February 2020

In this paper, we present a diagnoser‐based approach to deal with fault diagnosis of bounded labeled Petri nets. The approach consists in building a semi‐symbolic diagnoser to analyze diagnosability and perform online diagnosis. The contribution of this paper is twofold: (i) from the theoretical point of view, we provide new conditions for checking diagnosability based on a novel diagnoser variant that explicitly separates the normal reachable markings from the faulty ones, in each diagnoser node. This allows us to independently keep tracking the normal and the faulty diagnoser paths more efficiently. (ii) From the practical point of view and in order to reduce the memory required to build the diagnoser efficiently, we establish a semi‐symbolic encoding of the diagnoser state‐space. Such a representation deploys a symbolic encoding of the diagnoser nodes content, using Binary Decision Diagrams, while it keeps an explicit encoding of the observable transitions between the nodes. In addition, we provide an on‐the‐fly algorithm to simultaneously construct the diagnoser and analyze diagnosability. The effectiveness of the approach is illustrated through some experimentation performed on a Petri net benchmark.
Hepatic artery classification based on three-dimensional CT
Authors: Yan J , Feng H , Wang H , Yuan F , Yang C , Liang X , Chen W , Wang J
Published: February 2020

Background

Precise classification of the hepatic artery is helpful for preoperative surgical planning in hepatobiliary–pancreatic surgery. However, the anatomy of hepatic arteries is variable. This study investigated anatomical variation using three-dimensional visualization and evaluation (3DVE) to develop a nomenclature system.

Methods

The origin and course of the hepatic artery were tracked and analysed by using three-dimensional visualization of CT images acquired between 2013 and 2017. The new classification and nomenclature system, named CRL, was developed based on the origins of the common, right and left hepatic arteries.

Results

Scans from 770 adults were evaluated. Preoperative 3DVE correlated better with surgical findings than the original CT images alone. Using the CRL classification system, hepatic arteries were divided into nine subtypes. Only 87·4–89·2 per cent of the hepatic arteries of 610 living-donor liver transplant donors were depicted in Michels', Hiatt's or Varotti's classification, compared with 100 per cent identified by the CRL classification. The CRL classification was validated against external data sets from previous studies, with 99·6–100·0 per cent of patients classified by the CRL system.

Conclusion

The CRL classification covers hepatic artery variants and may be used for planning liver surgery.
Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database
Authors: Kupstas A R , Hoskin T L , Day C N , Boughey J C , Habermann E B , Hieken T J
Published: February 2020

Background

Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort.

Methods

Patients with non-metastatic IBC treated in 2010–2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−), ER−/HER2− and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan–Meier curves and Cox proportional hazards regression to analyse overall survival.

Results

Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2− in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER−/HER2− in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2− (6·2 per cent), HER2+ (38·8 per cent), ER−/HER2− (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2− 64·9 per cent, HER2+ 74·0 per cent, ER−/HER2− 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER−/HER2− subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival.

Conclusion

Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.
Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A retrospective analysis
Authors: Berger Mathilde , Amini‐Adlé Mona , Maucort‐Boulch Delphine , Robinson Philip , Thomas Luc , Dalle Stéphane , Courand Pierre‐Yves
Published: February 2020

BRAF and MEKis have revolutionized the management of BRAFV600‐mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF‐D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF‐D in melanoma patients treated with BRAF and/or MEKis. Metastatic melanoma patients treated with BRAF and/or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (Lyon Sud University Hospital, Hospices Civils de Lyon). LVEF‐D was defined as a reduction in LVEF ≥10% from baseline to a value <55%; normalization was defined as a value ≥55%. Among the 88 patients included, 12 (13.6%) experienced a LVEF‐D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months (IQR [3‐21]). No patient previously treated with beta‐blockers (n = 12) experienced a LVEF‐D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow‐up did not find any predictive marker of LVEF‐D. All patients who benefited from a specific treatment of LVEF‐D had a normalization of LVEF at the end of follow‐up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta‐blockers than those who did not (P = .019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF‐D (P = .006) and the latter did not influence overall‐survival (P = .117) or progression‐free‐survival (P = .297). LVEF‐D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF‐D occurs.
The influencing factors and functions of DNA G‐quadruplexes
Authors: Yuan Wen‐Fang , Wan Lin‐Yan , Peng Hu , Zhong Yuan‐Mei , Cai Wen‐Li , Zhang Yan‐Qiong , Ai Wen‐Bing , Wu Jiang‐Feng
Published: February 2020

G‐quadruplexes form folded structures because of tandem repeats of guanine sequences in DNA or RNA. They adopt a variety of conformations, depending on many factors, including the type of loops and cations, the nucleotide strand number, and the main strand polarity of the G‐quadruplex. Meanwhile, the different conformations of G‐quadruplexes have certain influences on their biological functions, such as the inhibition of transcription, translation, and DNA replication. In addition, G‐quadruplex binding proteins also affect the structure and function of G‐quadruplexes. Some chemically synthesized G‐quadruplex sequences have been shown to have biological activities. For example, bimolecular G‐quadruplexes of AS1411 act as targets of exogenous drugs that inhibit the proliferation of malignant tumours. G‐quadruplexes are also used as vehicles to deliver nanoparticles. Thus, it is important to identify the factors that influence G‐quadruplex structures and maintain the stability of G‐quadruplexes. Herein, we mainly discuss the factors influencing G‐quadruplexes and the synthetic G‐quadruplex, AS1411.

Significance of the study

This review summarizes the factors that influence G‐quadruplexes and the functions of the synthetic G‐quadruplex, AS1411. It also discusses the use of G‐quadruplexes for drug delivery in tumour therapy.
Ionic Liquid Assisted Electrospinning of Porous LiFe0.4Mn0.6PO4/CNFs as Free‐Standing Cathodes with a Pseudocapacitive Contribution for High‐Performance Lithium‐Ion Batteries
Authors: Yang Jing , Tan Rou , Li Di , Ma Jianmin , Duan Xiaochuan
Published: February 2020

In pursuit of high‐performance cathode materials for lithium‐ion batteries with high energy and power densities, porous LiFe0.4Mn0.6PO4/CNF free‐standing electrodes have been successfully prepared through a facile ionic liquid (IL) assisted electrospinning method. Owing to the hierarchical porosity and N‐doped carbon layer derived from the ionic liquid, the resulting electrodes exhibited superior electrochemical performances with an improvement of conductivity and pseudocapacitive contribution, delivering a discharge capability of 162.7, 133.5, 114.5, and 102.6 mAh g−1 at the current rates of 0.1, 1, 5, and 10 C, respectively. It is highly expected that this facile IL‐assisted electrospinning method will lead to further developments for other phosphate‐based free‐standing electrodes, which offers a new route in designing polyanionic cathodes for high‐performance Li‐ion batteries.
Bifunctional Catalysts for Reversible Oxygen Evolution Reaction and Oxygen Reduction Reaction
Authors: Wu Xing , Tang Chongjian , Cheng Yi , Min Xiaobo , Jiang San Ping , Wang Shuangyin
Published: February 2020

Metal‐air batteries (MABs) and reversible fuel cells (RFCs) rely on the bifunctional oxygen catalysts for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). Finding efficient bifunctional oxygen catalysts is the ultimate goal and it has attracted a great deal of attention. The dilemma is that a good ORR catalyst is not necessarily efficient for OER, and vice versa. Thus, the development of a new type of bifunctional oxygen catalysts should ensure that the catalysts exhibit high activity for both OER and ORR. Composites with multicomponents for active centers supported on highly conductive matrices could be able to meet the challenges and offering new opportunities. In this Review, the evolution of bifunctional catalysts is summarized and discussed aiming to deliver high‐performance bifunctional catalysts with low overpotentials.
Nonclassical ammonium ions as intermediates in cinchona alkaloid rearrangements?
Authors: Lodewyk Michael W. , Tantillo Dean J.
Published: February 2020

The classical/nonclassical nature of cationic ammonium intermediates proposed to be involved in cinchona alkaloid solvolysis and related reactions is investigated. While these intermediates are found to possess highly distorted geometries in which the central nitrogen atom and three of the attached groups are essentially coplanar, we do not find evidence of a nonclassical bonding array. Instead, we find evidence that the intermediate resembles a classical, albeit strained, aziridinium structure, which is still able to account for experimental observations.
Borylation of Diazonium Salts by Highly Emissive and Crystalline Carbon Dots in Water
Authors: Lei Tao , Wei Si‐Meng , Feng Ke , Chen Bin , Tung Chen‐Ho , Wu Li‐Zhu
Published: February 2020

Efficient borylation reaction of diazonium salts in water is realized for the first time by using easily prepared, highly emissive and crystalline carbon dots. Electron‐donating and electron‐withdrawing groups on diazonium salts were well tolerated with moderate to good conversion efficiency. Compared with widely used metal complexes, organic dyes and quantum dots, the approach presented herein uses carbon dots, which are nontoxic and possess good biological and medicinal compatibility and high reactivity. Therefore, this approach presents a new prospective use for carbon dots in green chemistry.
Follicular regulatory T cells: a novel target for immunotherapy?
Authors: Huang Yao , Chen Zhe , Wang Hui , Ba Xin , Shen Pan , Lin Weiji , Wang Yu , Qin Kai , Huang Ying , Tu Shenghao
Published: February 2020

High‐affinity antibodies are produced during multiple processes in germinal centres (GCs), where follicular helper T (Tfh) cells interact closely with B cells to support B‐cell survival, differentiation and proliferation. Recent studies have revealed that a specialised subset of regulatory T cells, follicular regulatory T (Tfr) cells, especially fine‐tune Tfh cells and GC B cells, ultimately regulating GC reactions. Alterations in frequencies or function of Tfr cells may result in multiple autoantibody‐mediated or autoantibody‐associated diseases. This review discusses recent insights into the physiology and pathology of Tfr cells, with a special emphasis on their potential roles in human diseases. Discrepancies are common among studies, reflecting the limited understanding of Tfr cells. Further exploration of the mechanisms of Tfr cells in these diseases and thus targeting Tfr cells may help reinstate immune homeostasis and provide novel immunotherapy.
Assisted migration across fixed seed zones detects adaptation lags in two major North American tree species
Authors: Etterson Julie R. , Cornett Meredith W. , White Mark A. , Kavajecz Laura C.
Published: February 2020

Boreal forests are experiencing dramatic climate change, having warmed 1.0°–1.9°C over the last century. Yet forest regeneration practices are often still dictated by a fixed seed zone framework, in which seeds are both harvested from and planted into predefined areas. Our goal was to determine whether seedlings sourced from southern seed zones in MinnesotaUSAare already better adapted to northerly seed zones because of climate change. Bur oak (Quercus macrocarpa) and northern red oak (Quercus rubra) seedlings from two seed zones (i.e., tree ecotypes) were planted into 16 sites in two northern seed zones and measured for 3 yr. Our hypotheses were threefold: (1) tree species with more southern geographic distributions would thrive in northern forests where climate has already warmed substantially, (2) southern ecotypes of these species would have higher survival and growth than the northern ecotype in northern environments, and (3) natural selection would favor seedlings that expressed phenotypic and phenological traits characteristic of trees sourced from the more southern seed zone. For both species, survival was high (>93%), and southern ecotypes expressed traits consistent with our climate adaptation hypotheses. Ecotypic differences were especially evident for red oak; the southern ecotype had had higher survival, lower specific leaf area (SLA), faster height and diameter growth, and extended leaf phenology relative to the northern ecotype. Bur oak results were weaker, but the southern ecotype also had earlier budburst and lowerSLAthan the northern ecotype. Models based on the fixed seed zones failed to explain seedling performance as well as those with continuous predictors (e.g., climate and geographical position), suggesting that plant adaptations within current seed zone delineations do align with changing climate conditions. Adding support for this conclusion, natural selection favored traits expressed by the more southern tree ecotypes. Collectively, these results suggest that state seed sourcing guidelines should be reexamined to permit plantings across seed zones, a form of assisted migration. More extensive experiments (i.e., provenance trails) are necessary to make species‐specific seed transfer guidelines that account for climate trends while also considering the precise geographic origin of seed sources.
Nightly selection of resting sites and group behavior reveal antipredator strategies in giraffe
Authors: Burger Anna Lena , Fennessy Julian , Fennessy Stephanie , Dierkes Paul W.
Published: February 2020

This study presents the first findings on nocturnal behavior patterns of wild Angolan giraffe. We characterized their nocturnal behavior and analyzed the influence of ecological factors such as group size, season, and habitat use. Giraffe were observed using night vision systems and thermal imaging cameras on Okapuka Ranch, Namibia. A total of 77 giraffe were observed during 24 nights over two distinct periods—July–August 2016 (dry season) and February–March 2017 (wet season). Photoperiod had a marked influence on their activity and moving behavior. At dusk, giraffe reduced the time spent moving and increasingly lay down and slept at the onset of darkness. Body postures that likely correspond to rapid eye movement (REM) sleep posture (RSP) were observed 15.8 ± 18.3 min after giraffe sat down. Season had a significant effect with longer RSP phases during the dry season (dry: 155.2 ± 191.1 s, n = 79; wet: 85.8 ± 94.9 s, n = 73). Further analyses of the influence of social behavior patterns did not show an effect of group size on RSP lengths. When a group of giraffe spent time at a specific resting site, several individuals were alert (vigilant) while other group members sat down or took up RSP. Simultaneous RSP events within a group were rarely observed. Resting sites were characterized by single trees or sparse bushes on open areas allowing for good visibility in a relatively sheltered location.
Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients
Authors: Bergh Niklas , Gude Einar , Bartfay Sven‐Erik , K Andreassen Arne , Arora Satish , Dahlberg Pia , Dellgren Göran , Gullestad Lars , Gustafsson Finn , Karason Kristjan , Rådegran Göran , Bollano Entela , Andersson Bert
Published: February 2020

Aims

Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)‐based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow‐up after HTx in a sub‐study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI‐based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise.

Methods and results

Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre‐HTx to the first follow‐up at 7–11 weeks post‐HTx and thereafter remained unchanged up to 3 years of follow‐up. During follow‐up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post‐capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≥ 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7–11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy‐proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy‐proven treated acute rejections were not associated with altered haemodynamics.

Conclusions

De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy‐proven treated rejections.
A Self‐tuning Robust Control System for nonlinear real‐time hybrid simulation
Authors: Maghareh Amin , Dyke Shirley J. , Silva Christian E.
Published: February 2020

In a real‐time hybrid simulation, a transfer system is used to enforce the interface interaction between computational and physical substructures. A model‐based, multilayer nonlinear control system is developed to accommodate extensive performance variations and uncertainties in a physical substructure. The aim of this work is to extend the application of real‐time hybrid simulation to investigating failure, nonlinearity, and nonstationary behavior. This Self‐tuning Robust Control System (SRCSys) consists of two layers: robustness and adaptation. The robustness layer synthesizes a nonlinear control law such that the closed‐loop dynamics perform as intended under a broad range of parametric and nonparametric uncertainties. Sliding mode control is employed as the control scheme in this layer. Then, the adaptation layer reduces uncertainties at run time through slow and controlled learning of the control plant. The tracking performance of the SRCSys is evaluated in two experiments that have highly uncertain physical specimens.
Residual learning based CNN for breast cancer histopathological image classification
Authors: Gour Mahesh , Jain Sweta , Sunil Kumar T.
Published: February 2020

Biopsy is one of the most commonly used modality to identify breast cancer in women, where tissue is removed and studied by the pathologist under the microscope to look for abnormalities in tissue. This technique can be time‐consuming, error‐prone, and provides variable results depending on the expertise level of the pathologist. An automated and efficient approach not only aids in the diagnosis of breast cancer but also reduces human effort. In this paper, we develop an automated approach for the diagnosis of breast cancer tumors using histopathological images. In the proposed approach, we design a residual learning‐based 152‐layered convolutional neural network, named as ResHist for breast cancer histopathological image classification. ResHist model learns rich and discriminative features from the histopathological images and classifies histopathological images into benign and malignant classes. In addition, to enhance the performance of the developed model, we design a data augmentation technique, which is based on stain normalization, image patches generation, and affine transformation. The performance of the proposed approach is evaluated on publicly available BreaKHis dataset. The proposed ResHist model achieves an accuracy of 84.34% and an F1‐score of 90.49% for the classification of histopathological images. Also, this approach achieves an accuracy of 92.52% and F1‐score of 93.45% when data augmentation is employed. The proposed approach outperforms the existing methodologies in the classification of benign and malignant histopathological images. Furthermore, our experimental results demonstrate the superiority of our approach over the pre‐trained networks, namely AlexNet, VGG16, VGG19, GoogleNet, Inception‐v3, ResNet50, and ResNet152 for the classification of histopathological images.
Prevalence and predictors of expulsion in home‐based child care settings
Authors: Hooper Alison , Schweiker Claire
Published: February 2020

This study explored the prevalence of expulsion in home‐based child care (HBCC) settings using a nationally representative sample of HBCC providers from the National Survey of Early Care and Education. In addition to prevalence, enrollment and provider characteristics that predicted expulsion were examined. Although there is increasing awareness of the prevalence of early childhood suspension and expulsion in early care and education settings and the negative effects it has on children's development, few studies have included or focused on HBCC, where many children receive care. This study highlights that many home‐based providers, especially listed providers, report that they expelled at least one child within the last year. Significant predictors of expulsion emerged, including enrollment characteristics such as caring for children with disabilities, enrolling more children, and caring for children unrelated to the provider. Provider characteristics, including years of experience, provider education, and provider age, also predicted provider report of expulsion. These results provide insight as to possible strategies that may be effective in reducing expulsion rates in this caregiving context.
Exploring corporate governance research in accounting journals through latent semantic and topic analyses
Authors: Zengul Ferhat D. , Byrd James D. , Oner Nurettin , Edmonds Mark , Savage Arline
Published: February 2020

The literature on corporate governance (CG) has been expanding at an unprecedented rate since major corporate scandals surfaced, such as Enron, WorldCom, and HealthSouth. Corresponding with accounting's important role in CG, accounting scholars increasingly have investigated CG in recent years, so the body of literature is growing. Although previous attempts have been made to summarize extant literature on CG via reviews, none of these attempts has utilized recent developments in text analyses and natural language processing. This study uses latent semantic and topic analyses to address this research gap by analysing abstracts from 1,399 articles in all accounting journals that the Australian Business Deans Council (ABDC) has rated A and A*. The ABDC journal list is widely recognized as a journal‐quality indicator across many universities worldwide. The analyses revealed 10 distinct research topics on CG in the ABDC's top accounting journals. The results presented include the five most representative articles for each topic, as distinguished by topic scores. This study carries important practice and policy implications, as it reveals major research streams and exhibits how researchers respond to various CG problems.
Blockchain for tracking serial numbers in money exchanges
Authors: Mohamed Kareem , Aziz Amr , Mohamed Belal , Abdel‐Hakeem Khaled , Mostafa Mostafa , Atia Ayman
Published: February 2020

Money exchange is one of the most common day‐to‐day activities performed by humans in the daily market. This paper presents an approach to money tracking through a blockchain. The proposed approach consists of three main components: serial number localization, serial number recognition, and a blockchain to store all transactions and ownership transfers. The approach was tested with a total of 110 banknotes of different currency types and achieved an average accuracy of 91.17%. We conducted a user study in real‐time with 21 users, and the mean accuracy across all users was 86.42%. Each user gave us feedback on the proposed approach, and most of them welcomed the idea.
DHPAC, a novel microtubule depolymerizing agent, suppresses angiogenesis and vasculogenic mimicry formation of human non‐small cell lung cancer
Authors: Gong Fu‐Lian , Wang Lei , Yu Lu‐Gang , Dang Yi‐Fan , Jiang Xiao‐Ning , Zhao Lin , Guo Xiu‐Li
Published: February 2020

Angiogenesis and vasculogenic mimicry (VM) are the main causes of tumor metastasis and recurrence. In this study, we investigated the antiangiogenesis and anti‐VM formation of a novel microtubule depolymerizing agent, DHPAC, as well as combretastatin A4 (CA4, a combretastatin derivate) in non‐small‐cell lung cancer (NSCLC), subsequently elucidating the underlying mechanisms. In human umbilical vein endothelial cells (HUVECs), DHPAC could enter cells and inhibit proliferation, migration, and angiogenesis in the presence and absence of conditioned medium from H1299 cells. Interestingly, the inhibition was enhanced under the stimulation of the conditioned medium. Under hypoxia or normoxia, DHPAC suppressed signal transducer and activator of transcription 3 phosphorylation and reduced vascular endothelial growth factor (VEGF) expression and secretion from HUVECs, thus impeding the activation of the downstream signal transduction pathway of VEGF/VEGFR2. However, JNK inhibitors reversed the inhibitory effect of DHPAC on the angiogenesis, suggesting that DHPAC regulated angiogenesis through activating JNK. In H1299 cells, DHPAC could inhibit proliferation, migration, invasion, and the formation of VM. In addition, DHPAC inhibited the phosphorylation of FAK and AKT and decreased the expressions of VEGF, matrix metalloproteinase 2 (MMP2), MMP9 and Laminin 5, suggesting that DHPAC inhibited VM formation via the FAK/AKT signaling pathway. In addition, CA4 showed a similar effect as DHPAC against angiogenesis and VM formation. These new findings support the use of microtubule destabilizing agents as a promising strategy for cancer therapy.
A missense variant remote from the active site impairs stability of human phosphoglucomutase 1
Authors: Stiers Kyle M. , Hansen Reed P. , Daghlas Bana A. , Mason Kelly N. , Zhu Jian‐She , Jakeman David L. , Beamer Lesa J.
Published: February 2020

Missense variants of human phosphoglucomutase 1 (PGM1) cause the inherited metabolic disease known as PGM1 deficiency. This condition is categorised as both a glycogen storage disease and a congenital disorder of glycosylation. Approximately 20 missense variants of PGM1 are linked to PGM1 deficiency, and biochemical studies have suggested that they fall into two general categories: those affecting the active site and catalytic efficiency, and those that appear to impair protein folding and/or stability. In this study, we characterise a novel variant of Arg422, a residue distal from the active site of PGM1 and the site of a previously identified disease‐related variant (Arg422Trp). In prior studies, the R422W variant was found to produce insoluble protein in a recombinant expression system, precluding further in vitro characterisation. Here we investigate an alternative variant of this residue, Arg422Gln, which is amenable to experimental characterisation presumably due to its more conservative physicochemical substitution. Biochemical, crystallographic, and computational studies of R422Q establish that this variant causes only minor changes in catalytic efficiency and 3D structure, but is nonetheless dramatically reduced in stability. Unexpectedly, binding of a substrate analog is found to further destabilise the protein, in contrast to its stabilising effect on wild‐type PGM1 and several other missense variants. This work establishes Arg422 as a lynchpin residue for the stability of PGM1 and supports the impairment of protein stability as a pathomechanism for variants that cause PGM1 deficiency.

Synopsis

Biochemical and structural studies of a missense variant far from the active site of human PGM1 identify a residue with a key role in enzyme stability.
Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer
Authors: Cavalli Giulio , Dagna Lorenzo , Biavasco Riccardo , Villa Antonello , Doglioni Claudio , Ferrero Elisabetta , Ferrarini Marina
Published: February 2020

Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by infiltration of multiple tissues by CD68+ foamy Mϕs (or ‘histiocytes’). Clinical manifestations arise from mass-forming lesions or from tissue and systemic inflammation. ECD histiocytes harbor oncogenic mutations along the MAPK-kinase signaling pathway (BRAFV600E in more than half of the patients), and secrete abundant pro-inflammatory cytokines and chemokines. Based on these features, ECD is considered an inflammatory myeloid neoplasm, and is accordingly managed with targeted kinase inhibitors or immunosuppressive and cytokine-blocking agents. Evidence is emerging that maladaptive metabolic changes, particularly up-regulated glycolysis, represent an additional, mutation-driven feature of ECD histiocytes, which sustains deregulated and protracted pro-inflammatory activation and cytokine production. Besides translational relevance to the management of ECD patients and to the development of new therapeutic approaches, recognition of ECD as a natural human model of chronic, maladaptive Mϕ activation instructs the understanding of Mϕ dysfunction in other chronic inflammatory conditions.
Earwax: A potentially useful medium to identify inborn errors of metabolism?
Authors: Krywawych Stefan , Cleary Maureen , McSweeney Mel , Heales Simon
Published: February 2020

Earwax was investigated as a source to identify patients' different inborn errors of metabolism (IEMs). Acylcarnitines, amino acids, and guanidino metabolites were measured from 28 treated patients with 11 different metabolic disorders including 3 organic acidaemias, 2 fatty acid oxidation defects, 6 amino acid disorders, and 1 peroxisomal abnormality. On the basis of the ratio of different acylcarnitine species relative to free carnitine, isovaleric acidaemia, methylmalonic acidaemia, and long‐chain hydroxyacylCoA dehydrogenase deficiency could be discriminated from the other disorders. For amino acids, neither creatinine nor alternative amino acid proved suitable reference standards against which results could be expressed. However, argininosuccinate and alloisoleucine were present in significantly elevated concentrations in two patients with argininosuccinate lyase deficiency and two patients with branched‐chain ketoacid dehydrogenase deficiency. This study has raised the potential of earwax for investigation of IEMs and may also have role in postmortem investigations. In view of its limited invasiveness, earwax also may have a role as a material to monitor treatment responses and compliance in patients with IEMs.