bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Yield Ti3C2Tx MXene–MoS2 Integrated Circuits
Authors: Xu Xiangming , Guo Tianchao , Hota Mrinal K. , Kim Hyunho , Zheng Dongxing , Liu Chen , Hedhili Mohamed Nejib , Alsaadi Rajeh S. , Zhang Xixiang , Alshareef Husam N.
Published: November 2021

It is very challenging to employ solution‐processed conducting films in large‐area ultrathin nanoelectronics. Here, spray‐coated Ti3C2Tx MXene films as metal contacts are successfully integrated into sub‐10 nm gate oxide 2D MoS2 transistor circuits. Ti3C2Tx films are spray coated on glass substrates followed by vacuum annealing. Compared to the as‐prepared sample, vacuum annealed films exhibit a higher conductivity (≈11 000 S cm−1) and a lower work function (≈4.5 eV). Besides, the annealed Ti3C2Tx film can be patterned through a standard cleanroom process without peeling off. The annealed Ti3C2Tx film shows a better band alignment for n‐type transport in MoS2 channel with small work function mismatch of 0.06 eV. The MoS2 film can be uniformly transferred on the patterned Ti3C2Tx surface and then readily processed through the cleanroom process. A large‐area array of Ti3C2Tx MXene–MoS2 transistors is fabricated using different dielectric thicknesses and semiconducting channel sizes. High yield and stable performance for these transistor arrays even with an 8 nm‐thick dielectric layer are demonstrated. Besides, several circuits are demonstrated, including rectifiers, negative‐channel metal–oxide–semiconductor (NMOS) inverters, and voltage‐shift NMOS inverters. Overall, this work indicates the tremendous potential for solution‐processed Ti3C2Tx MXene films in large‐area 2D nanoelectronics.
Preparation of fcc‐2H‐fcc Heterophase Pd@Ir Nanostructures for High‐Performance Electrochemical Hydrogen Evolution
Authors: Ge Yiyao , Wang Xixi , Chen Bo , Huang Zhiqi , Shi Zhenyu , Huang Biao , Liu Jiawei , Wang Gang , Chen Ye , Li Lujiang , Lu Shiyao , Luo Qinxin , Yun Qinbai , Zhang Hua
Published: November 2021

With the development of phase engineering of nanomaterials (PEN), construction of noble‐metal heterostructures with unconventional crystal phases, including heterophases, has been proposed as an attractive approach toward the rational design of highly efficient catalysts. However, it still remains challenging to realize the controlled preparation of such unconventional‐phase noble‐metal heterostructures and explore their crystal‐phase‐dependent applications. Here, various Pd@Ir core–shell nanostructures are synthesized with unconventional fcc‐2H‐fcc heterophase (2H: hexagonal close‐packed; fcc: face‐centered cubic) through a wet‐chemical seeded method. As a result, heterophase Pd66@Ir34 nanoparticles, Pd45@Ir55 multibranched nanodendrites, and Pd68@Ir22Co10 trimetallic nanoparticles are obtained via the phase‐selective epitaxial growth of fcc‐2H‐fcc‐heterophase Ir‐based nanostructures on 2H‐Pd seeds. Importantly, the heterophase Pd45@Ir55 nanodendrites exhibit excellent catalytic performance toward electrochemical hydrogen evolution reaction (HER) under acidic conditions. An overpotential of only 11.0 mV is required to achieve a current density of 10 mA cm−2 on Pd45@Ir55 nanodendrites, which is lower than those of the conventional fcc‐Pd47@Ir53 counterparts, commercial Ir/C and Pt/C. This work not only demonstrates an appealing route to synthesize novel heterophase nanomaterials for promising applications in the emerging field of PEN, but also highlights the significant role of the crystal phase in determining their catalytic properties.
Neuronal Induction of Bone‐Fat Imbalance through Osteocyte Neuropeptide Y
Authors: Zhang Yan , Chen Chun‐Yuan , Liu Yi‐Wei , Rao Shan‐Shan , Tan Yi‐Juan , Qian Yu‐Xuan , Xia Kun , Huang Jie , Liu Xi‐Xi , Hong Chun‐Gu , Yin Hao , Cao Jia , Feng Shi‐Kai , He Ze‐Hui , Li You‐You , Luo Zhong‐Wei , Wu Ben , Yan Zi‐Qi , Chen Tuan‐Hui , Chen Meng‐Lu , Wang Yi‐Yi , Wang Zhen‐Xing , Liu Zheng‐Zhao , Luo Ming‐Jie , Hu Xiong‐Ke , Jin Ling , Wan Teng‐Fei , Yue Tao , Tang Si‐Yuan , Xie Hui
Published: November 2021

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY.
Domain Wall Patterning and Giant Response Functions in Ferrimagnetic Spinels
Authors: Kish Lazar L. , Thaler Alex , Lee Minseong , Zakrzewski Alexander V. , Reig‐i‐Plessis Dalmau , Wolin Brian A. , Wang Xu , Littrell Kenneth C. , Budakian Raffi , Zhou Haidong , Gai Zheng , Frontzek Matthias D. , Zapf Vivien S. , Aczel Adam A. , DeBeer‐Schmitt Lisa , MacDougall Gregory J.
Published: November 2021

The manipulation of mesoscale domain wall phenomena has emerged as a powerful strategy for designing ferroelectric responses in functional devices, but its full potential is not yet realized in the field of magnetism. This work shows a direct connection between magnetic response functions in mechanically strained samples of Mn3O4 and MnV2O4 and stripe‐like patternings of the bulk magnetization which appear below known magnetostructural transitions. Building off previous magnetic force microscopy data, a small‐angle neutron scattering is used to show that these patterns represent distinctive magnetic phenomena which extend throughout the bulk of two separate materials, and further are controllable via applied magnetic field and mechanical stress. These results are unambiguously connected to the anomalously large magnetoelastic and magnetodielectric response functions reported for these materials, by performing susceptibility measurements on the same crystals and directly correlating local and macroscopic data.
Magnetically Aligned Ultrafine Cobalt Embedded 3D Porous Carbon Metamaterial by One‐Step Ultrafast Laser Direct Writing
Authors: Xu Jin , Wang Ruoxing , Jiang Haoqing , Liu Xingtao , An Licong , Jin Shengyu , Deng Biwei , Wu Wenzhuo , Cheng Gary J.
Published: November 2021

Spatial manipulation of nanoparticles (NPs) in a controlled manner is critical for the fabrication of 3D hybrid materials with unique functions. However, traditional fabrication methods such as electron‐beam lithography and stereolithography are usually costly and time‐consuming, precluding their production on a large scale. Herein, for the first time the ultrafast laser direct writing is combined with external magnetic field (MF) to massively produce graphene‐coated ultrafine cobalt nanoparticles supported on 3D porous carbon using metal–organic framework crystals as precursors (5 × 5 cm2 with 10 s). The MF‐confined picosecond laser scribing not only reduces the metal ions rapidly but also aligns the NPs in ultrafine and evenly distributed order (from 7.82 ± 2.37 to 3.80 ± 0.84 nm). ≈400% increment of N‐Q species within N compositionis also found as the result of the special MF‐induced laser plasma plume. (). The importance of MF is further exmined by electrochemical water‐splitting tests. Significant overpotential improvements of 90 and 150 mV for oxygen evolution reaction and hydrogen evolution reaction are observed, respectively, owing to the MF‐induced alignment of the NPs and controlled elemental compositions. This work provides a general bottom‐up approach for the synthesis of metamaterials with high outputs yet a simple setup.
Scalable Fabrication of Metallic Nanogaps at the Sub‐10 nm Level
Authors: Luo Sihai , Hoff Bård H. , Maier Stefan A. , de Mello John C.
Published: November 2021

Metallic nanogaps with metal–metal separations of less than 10 nm have many applications in nanoscale photonics and electronics. However, their fabrication remains a considerable challenge, especially for applications that require patterning of nanoscale features over macroscopic length‐scales. Here, some of the most promising techniques for nanogap fabrication are evaluated, covering established technologies such as photolithography, electron‐beam lithography (EBL), and focused ion beam (FIB) milling, plus a number of newer methods that use novel electrochemical and mechanical means to effect the patterning. The physical principles behind each method are reviewed and their strengths and limitations for nanogap patterning in terms of resolution, fidelity, speed, ease of implementation, versatility, and scalability to large substrate sizes are discussed.
Aptamer Probes Labeled with Lanthanide‐Doped Carbon Nanodots Permit Dual‐Modal Fluorescence and Mass Cytometric Imaging
Authors: Yu Youyi , Wang Xin , Jia Xiaolong , Feng Zijian , Zhang Lulu , Li Hongxia , He Jie , Shen Guangxia , Ding Xianting
Published: November 2021

High‐dimensional imaging mass cytometry (IMC) enables simultaneous quantification of over 35 biomarkers on one tissue section. However, its limited resolution and ultralow acquisition speed remain major issues for general clinical application. Meanwhile, conventional immunofluorescence microscopy (IFM) allows sub‐micrometer resolution and rapid identification of the region of interest (ROI), but only operates with low multiplicity. Herein, a series of lanthanide‐doped blue‐, green‐, and red‐fluorescent carbon nanodots (namely, B‐Cdots(Ln1), G‐Cdots(Ln2), and R‐Cdots(Ln3)) as fluorescence and mass dual‐modal tags are developed. Coupled with aptamers, B‐Cdots(159Tb)‐A10‐3.2, G‐Cdots(165Ho)‐AS1411, and R‐Cdots(169Tm)‐SYL3C dual‐functional aptamer probes, which are then multiplexed with commercially available Maxpar metal‐tagged antibodies for analyzing clinical formalin‐fixed, paraffin‐embedded (FFPE) prostatic adenocarcinoma (PaC) tissue, are further synthesized. The rapid identification of ROI with IFM using fluorescence signals and subsequent multiplexed detection of in situ ROI with IMC using the same tissue section is demonstrated. Dual‐modal probes save up to 90% IMC blind scanning time for a standard 3.5 mm × 3.5 mm overall image. Meanwhile, the IFM provides refined details and topological spatial distributions for the functional proteins at optical resolution, which compensates for the low resolution of the IMC imaging.
Direct hyperbilirubinemia and cholestasis in trisomy 13 and 18
Authors: Kepple Jeffrey W. , Peeples Eric S.
Published: November 2021

Trisomy 13 and 18 are common chromosomal abnormalities that affect multiple organ systems. There is a paucity of published data, however, on the hepatic complications seen in these patient populations. One of the most common pathologic hepatobiliary issues seen in the newborn period is direct hyperbilirubinemia (DH). Thus, this study sought to estimate the incidence and evaluate possible etiologies of DH in neonates with trisomy 13 or 18. This retrospective cohort study included all infants admitted to our two neonatal intensive care units between 2012 and 2020 with the diagnosis of trisomy 13 or 18. DH is most commonly diagnosed as a direct bilirubin >1 mg/dl but a cutoff of >2 mg/dl is more specific for cholestasis, so both cutoffs were evaluated. Continuous data were compared using Fisher's exact test and categorical variables by the Mann–Whitney U test. Thirty‐five patients met inclusion: 13 with trisomy 13 and 22 with trisomy 18. DH of >2 mg/dl was seen in seven (53.8%) patients with trisomy 13 and five (22.7%) with trisomy 18. Using a cutoff of >1 mg/dl, the rate of trisomy 13 was unchanged, but the rate in trisomy 18 increased to 9/22 (40.9%). There was a trend toward more DH in trisomy 13 patients (p = 0.079) versus trisomy 18 and higher rates in infants who received total parenteral nutrition (TPN) (50.0 vs. 13.3%, p = 0.026). The presence of cardiac or ultrasound‐defined hepatobiliary abnormalities was not correlated with DH. Due to the high rates of DH in hospitalized neonates with trisomy 13 and 18, we recommend screening newborns with trisomy 13 or 18 for DH starting in the first week of life and continuing at least weekly until 4 weeks of life or until completion of TPN, whichever comes later. Future studies should further evaluate possible etiologies of DH in this population.
A biological approach to adult sex differences in skeletal indicators of childhood stress
Authors: O'Donnell Lexi , Hill Ethan C. , Anderson Amy S. , Edgar Heather Joy Hecht
Published: November 2021

Objectives

In previous work examining the etiology of cribra orbitalia (CO) and porotic hyperostosis (PH) in a contemporary juvenile mortality sample, we noted that males had higher odds of having CO lesions than females. Here, we examine potential reasons for this pattern in greater detail. Four non‐mutually exclusive mechanisms could explain the observed sex differences: (1) sex‐biased mortality; (2) sexual dimorphism in immune responses; (3) sexual dimorphism in bone turnover; or (4) sexual dimorphism in marrow conversion.

Subjects and methods

The sample consists of postmortem computed tomography scans and autopsy reports, field reports, and limited medical records of 488 individuals from New Mexico (203 females; 285 males) aged between 0.5 and 15 years. We used Kaplan–Meier survival analysis, predicted probabilities, and odds ratios to test each mechanism.

Results

Males do not have lower survival probabilities than females, and we find no indications of sex differences in immune response. Overall, males have a higher probability of having CO or PH lesions than females.

Conclusions

All results indicate that lesion formation in juveniles is influenced by some combination of sex differences in the pace of red–yellow conversion of the bone marrow and bone turnover. The preponderance of males with CO and PH likely speaks to the potential for heightened osteoblastic activity in males. We find no support for the hypotheses that sex biases in mortality or immune responses impacted lesion frequency in this sample. Sex differences in biological processes experienced by children may affect lesion formation and lesion expression in later life.
Metal‐Free Phosphorus‐Directed Borylation of C(sp2)−H Bonds
Authors: Sadek Omar , Le Gac Arnaud , Hidalgo Nereida , Mallet‐Ladeira Sonia , Miqueu Karinne , Bouhadir Ghenwa , Bourissou Didier
Published: November 2021

Spectacular progress has recently been achieved in transition metal‐catalyzed C−H borylation of phosphines as well as directed electrophilic C−H borylation. As shown here, P‐directed electrophilic borylation provides a new, straightforward, and efficient access to phosphine–boranes. It operates under metal‐free conditions and leverages simple, readily available substrates. It is applicable to a broad range of backbones (naphthyl, biphenyl, N‐phenylpyrrole, binaphthyl, benzyl, naphthylmethyl) and gives facile access to various substitution patterns at boron (by varying the boron electrophile or post‐derivatizing the borane moiety). NMR monitoring supports the involvement of P‐stabilized borenium cations as key intermediates. DFT calculations reveal the existence and stabilizing effect of π‐arene/boron interactions in the (biphenyl)(i‐Pr)2P→BBr2+ species.
Lewis‐Acidic PtIr Multipods Enable High‐Performance Li–O2 Batteries
Authors: Zhou Yin , Yin Kun , Gu Qianfeng , Tao Lu , Li Yiju , Tan Hao , Zhou Jinhui , Zhang Wenshu , Li Hongbo , Guo Shaojun
Published: November 2021

The sluggish oxygen reaction kinetics concomitant with the high overpotentials and parasitic reactions from cathodes and solvents is the major challenge in aprotic lithium‐oxygen (Li–O2) batteries. Herein, PtIr multipods with a low Lewis acidity of the Pt atoms are reported as an advanced cathode for improving overpotentials and stabilities. DFT calculations disclose that electrons have a strong disposition to transfer from Ir to Pt, since Pt has a higher electronegativity than Ir, resulting in a lower Lewis acidity of the Pt atoms than that on the pure Pt surface. The low Lewis acidity of Pt atoms on the PtIr surface entails a high electron density and a down‐shifting of the d‐band center, thereby weakening the binding energy towards intermediates (LiO2), which is the key in achieving low oxygen‐reduction‐reaction (ORR) and oxygen‐evolution‐reaction (OER) overpotentials. The Li–O2 cell based on PtIr electrodes exhibits a very low overall discharge/charge overpotential (0.44 V) and an excellent cycle life (180 cycles), outperforming the bulk of reported noble‐metal‐based cathodes.
Preparation and performance of polyether elastomer with a combination of polyurethane and polytriazole
Authors: Cong Kun , Liu Zhenhui , He Jiyu , Yang Rongjie
Published: November 2021

Polyether polyurethane elastomers prepared by polyisocyanate N100 and ethylene oxide‐tetrahydrofuran copolymer (PET) were compared to that polytriazole polyethylene oxide‐tetrahydrofuran (PTPET) elastomers prepared by alkynyl‐terminated polyethylene oxide‐tetrahydrofuran (ATPET) and glycidyl azide polymer (GAP) at a comparative molecular weight. The polyether polyurethane (PET‐N100) elastomers turned out to have better mechanical properties than that of PTPET/GAP elastomer. In order to explore the effectiveness of nitrogen‐enriched structures in the field of flame‐retardancy, PET‐N100 and PTPET/GAP elastomers were tested by cone calorimetry. The PET‐N100 elastomer exhibited an inferior performance of flame‐retardancy to that of PTPET/GAP elastomer. Therefore, a modification of the terminal hydroxyl group in GAP with 4,4′‐methylene‐bisphenyl‐isocyanate (MDI) and flame‐retardant diethyl bis(2‐hydroxyethyl) amino methyl phosphonate (DBMAP) was attempted and characterized by FT‐IR, NMR, and gel permeation chromatography. It was found that the synthesized GAP‐MDI‐DBAMP could serve as a novel curing agent for ATPET, which would endow the novel PTPET elastomer a combination of the advantageous properties, that is, the outstanding mechanical properties from PET‐N100 elastomer, favorable flame‐retardancy from PTPET/GAP elastomer and DBAMP. The thermogravimetry analysis/DTG, DSC, tensile strength test, and swelling analysis proved that PTPET/GAP‐MDI‐DBAMP elastomer had excellent thermal stability and mechanical strength.
Comparison of biomarker and chromatographic analytical approaches to pharmacokinetic study of sitagliptin
Authors: Kosman Vera M. , Karlina Marina V. , Faustova Natalia M. , Makarov Valery G. , Makarova Marina N.
Published: November 2021

The pharmacokinetic profiling of active compounds is necessary for drug development and application. Approaches to a pharmacokinetic study based on biological markers are alternatives to traditional approaches based on chromatographic methods. The aim of the study was to compare two analytical approaches to pharmacokinetics investigation for an example of sitagliptin in rabbits after one dose oral administration. The method for sitagliptin quantification in rabbit plasma samples based on a correlation between its concentration and dipeptidyl peptidase IV activity was proposed, validated, and applied. The high‐performance liquid chromatography (HPLC)‐ultraviolet (UV) method was also validated and applied for the same sample analysis. The plasma pharmacokinetics of sitagliptin after oral administration to the rabbits in one dose was characterized after two analytical assays. The close values of the main pharmacokinetic parameters were obtained after two approaches. The nontraditional approach based on correlation of special marker activity and active substance concentration appears to be more sensitive than HPLC‐UV. Thus, the sitagliptin concentrations determined by biomarker assay were higher than the lower limit of quantification (LLOQ) for a longer period (more timepoints) than after the HPLC‐UV assay. This feature may influence the values of some calculated concentration‐dependent (area under the curve [AUC]0‐t, etc.) and time‐dependent parameters (mean residence time [MRT], T1/2, etc.). The values of Tmax obtained by the two approaches were similar and adequate for oral drug administration that confirms the correctness of biomarker selection for pharmacokinetics assessment. The obtained results on the example of sitagliptin confirms that the biomarker approach is adequate and applicable for a pharmacokinetics study. Similar approaches may be effective for individual compounds and complex mixtures when it is difficult or impossible to analyze them traditionally by chromatographic methods.
Evaluating potential of tissue‐engineered cryogels and chondrocyte derived exosomes in articular cartilage repair
Authors: Nikhil Aman , Kumar Ashok
Published: November 2021

Treatment of articular cartilage injuries especially osteochondral tissue requires intervention of bioengineered scaffold. In this study, we investigated the potential of the tissue‐engineered cryogel scaffold fabricated using cryogelation technology. Two types of cryogels viz. chitosan‐gelatin‐chondroitin sulfate (CGC) for articular cartilage and nano‐hydroxyapatite‐gelatin (HG) for subchondral bone were fabricated. Further, novel bilayer cryogel designed using single process fabrication of two layers (CGC as top layer and HG as the lower layer) was designed to mimic osteochondral unit. CGC cryogel was tested for their biocompatibility using the enzymatically isolated chondrcoytes from goat articular cartilage while HG cryogel was tested using pre‐osteoblast cell line. Extracellular vesicles, specifically exosomes were isolated from the spent media of chondrocytes to validate their effect over cell proliferation and migration which are required for defect healing and infiltration respectively. These isolated exosomes were characterized and analyzed for confirming their size distribution profile and visualized morphologically using advanced microscopy techniques. For cartilage part, CGC cryogels were examined as delivery system for delivering exosomes at defect site, where 80% of release was observed in 72 h. Release of 18.7 µg chondroitin sulfate/mg cryogel was obtained in a period of one week from CGC cryogel (termed cryogel extract) which has chondroprotective effect. Further, effect of exosome concentration (10 and 20 µg/ml), CGC extract and combination of exosome and CGC extract (Exo‐Ex) were assessed over the chondrocytes. In addition, in vitro scratch wound assay was performed to analyse the migration capacity over the micro‐injury when treated with exosomes, cryogel extract and Exo‐Ex. The overall results thus answer key questions of therapeutic potential of chondrocyte exosomes, cryogel extract in addition to potential of CGC and HG cryogel for osteochondral repair.
Biomechanical behavior of mandible with posterior marginal resection using finite element analysis
Authors: Cheng Kang‐jie , Liu Yun‐feng , Wang Russell , Yuan Zi‐xi , Jiang Xian‐feng , Dong Xing‐tao
Published: November 2021

This study aims to characterize biomechanical behavior of various designs of posterior mandibular marginal resection under functional loadings using finite element method. The ultimate goal of this work is to provide clinically relevant information to prevent postoperative fracture and to stipulate prophylactic internal fixation for planning of marginal mandibulectomy. A 3D mandibular master model was reconstructed from cone beam computed tomography images. Different marginal resection models were created based on three design parameters, namely, defect curvilinear radius, anterior–posterior defect width and residual height of the mandibular body. Functional loadings from incisors (60 N) and contralateral first molar area (200 N) were applied to designed models and stress patterns were compared of five groups with curvilinear radius from 0 (conventional rectangular shape), 2.5, 3.5, 5, and 6 mm. Models with 25, 35 and 45 mm defect width mimic defects varied from canine to 3rd molar were tested. Residual height range from 10 to 4 mm was assessed. The results show high stresses predominated in the occlusal area and the posterior inferior border near the resection corner. The average maximum stress decreased by 29.8% (r = 2.5 mm), 51.9% (r = 3.5 mm), 54.4% (r = 5 mm), and 59.3% (r = 6 mm) compared to the baseline of r = 0 mm. The results from the combined defect width/residual height models demonstrate the increase of defect width and the decrease in residual height resulted in the increase of maximum stress. Our data also confirm that the factor of residual height supersedes defect width in terms of prevention of postoperative fracture when considering resection design.
Visible‐Light‐Induced Oxidative α‐Alkylation of Glycine Derivatives with Ethers under Metal‐Free Conditions
Authors: Song Yang , Zhang Hao , Guo Jiabao , Shao Yifei , Ding Yuzhou , Zhu Li , Yao Xiaoquan
Published: November 2021

In this work, a visible‐light‐induced oxidative α‐alkylation of glycine derivatives with ethers has been developed in the presence of catalytic Eosin Y. Under the blue light of a 3 W LED, a range of α‐etherized glycine derivatives, including α‐amino esters, α‐amino ketones and α‐amino amides, were achieved with good to excellent yields and functional group tolerance with tert‐butyl hydroperoxide (TBHP) as oxidant at ambient temperature. The operationally easy procedure provides an economical, metal‐free, and mild alternative for the synthesis of the α‐etherized glycine derivatives.
Single‐frequency ultrasonic extraction of bioactive chlorogenic acid from heilong48 soybean variety: Parametric optimization and comprehensive evaluation of physicochemical and bioactive properties
Authors: Akpabli‐Tsigbe Nelson Dzidzorgbe Kwaku , Ma Yongkun , Ekumah John‐Nelson , Osabutey Juliet , Hu Jie , Xu Manqing , Johnson Nana Adwoa Nkuma
Published: November 2021

Chlorogenic acid (CA), especially that found in soybean, is a rich bioactive compound but has received very little attention in research settings in past decades. Ultrasonic‐assisted extraction (UAE) could be an efficient method to increase CA release from soybean. Hence, this study aimed to optimize UAE parameters for CA extraction from heilong48 soybean (HS) variety with comprehensive physicochemical and bioactive properties evaluation. Optimization of ultrasound parameters with Box‐Behnken design (BBD) found frequency (20.0 kHz), power density (30.0 W/L), temperature (37.9℃), and time (28.0 min) as the significant optimized parameters, which gave CA yield of 5.007 ± 0.033 mg/g and DPPH of 93.197 ± 0.213 μmol AA eq/g dry sample and were higher than that of nonultrasound‐treated (raw) HS sample (CA yield, 1.627 ± 0.528 mg/g, and DPPH, 10.760 ± 0.207 μmol AA eq/g dry sample). A satisfactory model was obtained. SEM results confirmed the structural alterations of HS variety caused by the optimized UAE parameters. High TPC (4.726 ± 0.002 mg GAE/g), TPA (1.883 ± 0.005 mg GAE/g), and low TFC (0.040 ± 0.008 mg RE/g) were obtained. A positive linear correlation between antioxidant activity and TPC was established. Protein–phenolic interaction in HS variety was observed. The results proposed that polyphenols should be considered as a significant component of HS variety. Likewise, HS variety could be utilized for CA extraction.
European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children
Authors: de Ville de Goyet Jean , Baumann Ulrich , Karam Vincent , Adam René , Nadalin Silvio , Heaton Nigel , Reding Raymond , Branchereau Sophie , Mirza Darius , Klempnauer Jürgen L. , Fischer Lutz , Kalicinski Piotr , Colledan Michele , Lopez Santamaria Manuel , de Kleine Ruben H. , Chardot Christophe , Yilmaz Sezai , Kilic Murat , Boillot Olivier , di Francesco Fabrizio , Polak Wojciech G. , Verkade Henkjan J. ,   for the European Liver, Intestine Transplant Association
Published: November 2021

Background and Aims

The European Liver Transplant Registry (ELTR) has collected data on liver transplant procedures performed in Europe since 1968.

Approach and Results

Over a 50‐year period (1968–2017), clinical and laboratory data were collected from 133 transplant centers and analyzed retrospectively (16,641 liver transplants in 14,515 children). Data were analyzed according to three successive periods (A, before 2000; B, 2000–2009; and C, since 2010), studying donor and graft characteristics and graft outcome. The use of living donors steadily increased from A to C (A, n = 296 [7%]; B, n = 1131 [23%]; and C, n = 1985 [39%]; p = 0.0001). Overall, the 5‐year graft survival rate has improved from 65% in group A to 75% in group B (p < 0.0001) and to 79% in group C (B versus C, p < 0.0001). Graft half‐life was 31 years, overall; it was 41 years for children who survived the first year after transplant. The late annual graft loss rate in teenagers is higher than that in children aged <12 years and similar to that of young adults. No evidence for accelerated graft loss after age 18 years was found.

Conclusions

Pediatric liver transplantation has reached a high efficacy as a cure or treatment for severe liver disease in infants and children. Grafts that survived the first year had a half‐life similar to standard human half‐life. Transplantation before or after puberty may be the pivot‐point for lower long‐term outcome in children. Further studies are necessary to revisit some old concepts regarding transplant benefit (survival time) for small children, the role of recipient pathophysiology versus graft aging, and risk at transition to adult age.
Natural convection cooling process from two identical porous‐covering electronic components
Authors: Bouchair Rabah , Bourouis Abderrahim , Omara Abdeslam
Published: November 2021

In the present work, we focus to study numerically the natural convection cooling process from two identical electronic components located on the bottom wall of a two‐dimensional cavity. Each electronic component is covered by a porous medium with finite thickness. The conservation equations governing the problem are discretized using the finite volume method and the SIMPLER algorithm is used to handle the nonlinear character of conservation equations. Calculations were carried out for the following control parameters: the porous/fluid thermal conductivity ratio (1 ≤ RkP1 ≤ 100), the Darcy and Rayleigh numbers (10−1 ≤ Da ≤ 10−6, 103 ≤ Ra ≤ 106), the first porous‐cover thickness (0.05 ≤ e1 ≤ 0.3), and the separation distance between components (0.2 ≤ S ≤ 1) to highlight their influence on the cooling process. The results show that under specific values of the Darcy and Rayleigh numbers and in the limiting case of a high value of the porous/fluid thermal conductivity ratio (RkP1 = 100), a decrease in the maximum components temperature, up to 95%, is observed by increasing the porous‐cover thickness from 0.05 to 0.3. In addition, by increasing the permeability, the Rayleigh number or the separation distance, an improvement in the cooling process of the two components greater than or equal to 22% is achieved.
Effect and mechanism of circRNAs in tumor angiogenesis and clinical application
Authors: Zhao Luyang , Guo Yuying , Guo Yaxin , Ji Xiang , Fan Dandan , Chen Chen , Yuan Weitang , Sun Zhenqiang , Ji Zhenyu
Published: November 2021

Tumor blood vessels provide oxygen and necessary nutrients for the tumor, which provides the basis for tumor metastasis. Therefore, tumor angiogenesis plays a very important role in tumor growth and metastasis. In contrast to linear RNAs, circRNAs represent a type of closed‐loop RNA with diverse biological functions. At the same time, circRNAs have strong stability, timeliness, tissue specificity and disease specificity. With the rapid development of next‐generation sequencing and bioinformatics, there have been an increasing number of studies on circRNAs. At present, a large number of studies have reported that circRNAs regulate tumor growth, invasion, metastasis, tumor metabolism, tumor immunity and other biological functions. Increasing evidence has shown that circRNAs also play an important role in tumor angiogenesis. In this review, we briefly introduced tumor angiogenesis and circRNAs and outlined the main ways that circRNAs affect tumor angiogenesis from multiple aspects. Finally, we further explored the potential clinical application value of circRNAs in the context of tumor angiogenesis.
Amyloid‐β40 E22K fibril in familial Alzheimer's disease is more thermostable and susceptible to seeding
Authors: Lee Ming‐Che , Liao Yi‐Hung , Chen Shih‐Hui , Chen Yun‐Ru
Published: November 2021

Alzheimer's disease (AD) is the most prevalent and devastating neurodegenerative disease occurred in the elderly. One of the pathogenic hallmarks is senile plaques composed of amyloid‐β (Aβ) fibrils. Single mutations resided in Aβ were found in familial AD (FAD) patients that have early onset of the disease. The molecular details and properties of each FAD Aβ variants are still elusive. Here, we employed collective spectroscopic techniques to examine the properties of various Aβ40 fibrils. We generated fibrils of wild type (WT) and three FAD mutants on residue E22 including E22G, E22K, and E22Q. We monitored fibril formation by thioflavin T (ThT) assay, examined secondary structure by Fourier transform infrared and far‐UV circular dichroism spectroscopy, imaged fibril morphology by transmission electron microscopy, and evaluated ThT‐binding kinetics. In the thermal experiments, we found E22K fibrils resisted to high temperature and retained significant β‐sheet content than the others. E22K fibril seeds after high‐temperature treatment still possess the seeding property, whereas WT fibril seeds are disturbed after the treatment. Therefore, in this study we demonstrated the mutation at E22K increases the thermal stability and seeding function of amyloid fibrils.
Loperamide potentiates doxorubicin sensitivity in triple‐negative breast cancer cells by targeting MDR1 and JNK and suppressing mTOR and Bcl‐2: In vitro and molecular docking study
Authors: Elia Shenouda G. , Al‐Karmalawy Ahmed A. , Nasr Mohamed Y. , Elshal Mohamed F.
Published: November 2021

Multidrug resistance (MDR) is the leading cause of treatment failure in triple‐negative breast cancer (TNBC) patients treated with doxorubicin (DXR). We aimed to investigate the potential of the antidiarrheal drug Loperamide (LPR) in sensitizing TNBC cells to DXR and elucidate the underlying molecular mechanisms. Therefore, we examined the effects of DXR alone or in combination with LPR on MDA‐MD‐231 cells viability using MTT assay, cell cycle, and apoptosis by flow cytometry, and the expression of the MDR‐related genes (MDR1 and JNK1) and cell cycle/survival genes (p21, mTOR, and Bcl‐2) by quantitative reverse transcription polymerase chain reaction. Results showed that adding LPR to DXR potentiated its antiproliferation effect and reduced its IC50 by twofolds compared with DXR alone. The value of the combination index of LPR/DXR was <1 indicating a synergistic effect. Combined DXR/LPR treatment also caused G1 arrest and potentiated apoptosis more than DXR‐single treatment. At the molecular levels, LPR/DXR treatment downregulated the mRNA of MDR1 (1.35‐folds), JNK1 (2.5‐folds), mTOR (6.6‐folds), Bcl‐2 (9.5‐folds); while upregulated p21 gene (8‐folds) compared with DXR alone. Molecular docking analyses found LPR antagonizes MDR1 and JNK1 proteins, and hence supports the in vitro studies. In conclusion, the results confirmed the potential of LPR in sensitizing TNBCs to DXR by targeting MDR1 and JNK1 and suppressing Bcl‐2 and mTOR genes, while upregulating the cell cycle inhibitor gene p21. Additionally, LPR could be repurposed to reduce the therapeutic doses of DXR as indicated by the dose reduction index (DRI) and subsequently decrease its side effects.
Biphasic effect of mechanical stress on lymphocyte activation
Authors: Yassouf Mhd Yousuf , Zhang Xu , Huang Zisheng , Zhai Da , Sekiya Reiko , Kawabata Tsuyoshi , Li Tao‐Sheng
Published: November 2021

Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C‐Jun, and increased the expression of early activation marker CD69 in resting CD8+ cells. Interestingly, 50 mmHg mechanical stressing induced the nuclear localization of NFAT1; but conversely decreased C‐Jun and inhibited the expression of CD69 in lymphocytes under lipopolysaccharide or phorbol 12‐myristate 13‐acetate/ionomycin stimulation. Additionally, we observed similar changes trends when comparing RNA‐seq data of hypertensive and normotensive COVID‐19 patients. Our results indicate a biphasic effect of mechanical stress on lymphocyte activation, which provides insight into the variety of immune responses in pathologies involving elevated mechanical stress.
Synthesis and biological evaluation of novel 1,3,4‐oxadiazole derivatives as anticancer agents and potential EGFR inhibitors
Authors: Osmaniye Derya , Görgülü Şennur , Sağlık Begüm Nurpelin , Levent Serkan , Özkay Yusuf , Kaplancıklı Zafer Asım
Published: November 2021

EGFR (epidermal growth factor receptor) tyrosine kinases are frequently used in recent years, especially in small cell lung cancer. As with all other anticancer drugs, problems such as high side‐effect profiles and resistance to anticancer drugs call for new antiproliferative compounds. In the light of the above information, novel quinoxalin‐oxadiazole derivatives were synthesized as EGFR inhibitors in this study. Synthesis of compounds (3a–3j) was performed according to the literature methods. Their structures were elucidated by 1H‐NMR, 13C‐NMR, and HRMS spectroscopic methods. Structure elucidation was performed for compound 3e using 2D NMR technique. MTT test was performed to assess the cell proliferation effects of the different compounds on lung and mammary cell lines (A549, MCF7). In addition, obtained compounds (3a–3j) were screened against healthy CCD19‐Lu cell line (human lung fibroblast normal cells) to determine selectivity of the cytotoxic activities. Among the tested compounds, 3e and 3j showed significant cytotoxic activity against A549 cancer cell. Moreover, compound 3g and 3h displayed good activity. And the compounds 3e and 3j performed significant EGFR inhibition. Interaction modes of the compounds 3e, 3j were investigated against EGFR tyrosine kinase by means of docking studies. As a result of the studies, the importance of the quinoxaline ring and the NO2 substituent has been understood. In future studies, it is planned to make modifications by keeping these two structures constant. The activity can be contributed by using other heterocyclic rings instead of the oxadizaole ring.
Investigation of Effects of Gadolinium‐Based Contrast Agents on Uterine Contractility Using Isolated Rat Myometrium
Authors: Dinç Gülseren , Salihoğlu Arif K. , Ozgoren Burak , Akkaya Selçuk , Ayar Ahmet
Published: November 2021

Background

Despite concerns about safety, gadolinium‐based contrast agents (GBCAs) are still used for abdominal and pelvic imaging during pregnancy. Researchers have mainly focused on teratogenicity, while very little is known about their possible direct effects on uterine contractility, yet free gadolinium potentially impacts contractility through interaction with calcium channels.

Purpose

To investigate possible effects of selected GBCAs (namely gadoteridol, gadoversetamide, gadobutrol, gadoterate meglumine, and gadoxetic acid) on the contractility of rat myometrium.

Study Type

In vitro organ bath study.

Animal Model

Myometria were isolated from adult (10–12 weeks old) Sprague Dawley rats, both pregnant (N = 8) and nonpregnant (N = 36).

Field Strength/Sequence

NA.

Assessment

Myometrial strips were suspended in tissue bath containing physiological saline and isometric contractions were recorded. GBCAs were added to the tissue bath cumulatively, and their effects on contractility parameters (quantified by amplitude, frequency, and area under contractility curve [AUC]) were evaluated by 10‐minute intervals.

Statistical Tests

Normality data, checked by Shapiro–Wilk test, were transformed by arcsine when needed. One‐ or two‐way analysis of variance was performed, where appropriate, followed by Student–Newman–Keuls test. A P value of <0.05 was considered statistically significant.

Results

All of the assayed GBCAs elicited some alterations in the myometrial contractility in a concentration‐dependent manner. Gadoterate meglumine, gadoxetic acid, and gadoversetamide caused a concentration‐dependent significant attenuation in AUC (oxytocin‐induced, from 100% during control period to 45.1 ± 9.0% (nonpregnant) and 59.9 ± 8.5% (pregnant), for 90 μM gadoterate meglumine; respectively), and frequency of the spontaneous and oxytocin‐induced contractions. Gadobutrol and gadoteridol at highest dose significantly attenuated mean AUC and frequency of oxytocin‐induced contractions of nonpregnant myometrium.

Data Conclusion

Results from this in vitro study indicate that GBCAs elicit modulation of myometrial contractions at clinically relevant concentrations. These effects may account, at least partially, for the known potential side effects (rare cases of miscarriages and elective abortion) of these agents.

Level of Evidence

1

Technical Efficacy

Stage 5
Nanobioremediation of heavy metals: Perspectives and challenges
Authors:   Sunanda , Misra Modhurima , Ghosh Sachan Shashwati
Published: November 2021

Sustainable agriculture and humanity's civilization rest upon valuable natural resources such as earth and water, which have gone maximal exploitation and have been deteriorated by human activities. Heavy metals are natural components and one of the major pollutants of our environment, with a high atomic number and five times the density of water. The conventional physicochemical treatments for metal removal being cost‐intensive, have naturally paved the way for bioremediation, which is an attractive and economical alternative. Over the last few years, bionanotechnology has emerged as a useful tool in the remediation of heavy metals. The elimination of heavy metals continues to be a burning issue in research, and nanomaterials provide a particular affinity as well as high surface area for heavy metal adsorption. A chemically engineered nanoparticle can be expensive and also requires the use of toxic agents which may be undesirable for the environment. To cut the cost and produce clean, ecofriendly nanoparticles, biogenic synthesis of nanoparticles can be accomplished with the help of different microorganisms as well as plants, which can be further exploited for heavy metal remediation.
Evolution of South China Sea and East Asian monsoon from spring to summer by the progression of daily weather types
Authors: Qian Jian‐Hua , Lu Mong‐Ming , Sui Chung‐Hsiung
Published: November 2021

The monsoon development in the early rainy season in East Asia is analysed by the evolution of daily weather types (WTs). The WTs are classified by a k‐means clustering analysis based on 850 hPa winds from April 1 to July 31 in the 40‐year period of 1979–2018. Five WTs are identified, typifying the progression of weather regimes in the monsoonal evolution. WTs 1 and 2, with easterly winds in the South China Sea (SCS), occurs mostly in April and early May, corresponding to typical WTs before the SCS monsoon onset. In WT3, winds in the SCS turns westerly, and a rain band emerges in South China, extending east‐northeastward to the Pacific Ocean south of Japan, which signifies the May–June Mei‐yu in South China. Then, with the rain band moved to Yangtze River Valley (YRV) in WT4, this WT corresponds to the June–July Mei‐Yu in central and eastern China along the YRV. Finally, WT5 occurs more frequently towards the end of July, and corresponds to the post‐Mei‐Yu WT, indicating the ending of the early summer rainfall season in East Asia. The evolution of the WTs is gradual but intermittent, representing the weather‐within‐climate information. Each WT likely persists to itself. But WT1 and WT2 also progress to each other. The long persistence of WT3 and WT4 up to several weeks indicates the quasi‐stationary Mei‐Yu in South China and the YRV, respectively. The year‐to‐year variability of the WTs is also evident in the WTs. The El Niño–Southern Oscillation (ENSO) impact on the precipitation in the East Asian region is analysed for three types of ENSO: Eastern Pacific, Central Pacific, and mixed El Niño and La Niña. The seasonal mean precipitation anomalies can be interpreted by the frequencies of the daily WTs under different ENSO conditions.
Didaktik: Kugeln, Bilder oder Augmented Reality?
Authors: Przywarra Tobias , Risch Björn
Published: November 2021

Im Chemieunterricht gilt der Übergang von der makroskopischen auf die (sub)mikroskopische Ebene als Schlüsselstelle. Anschauungsmodelle unterstützen diese Reise ins Diskontinuum. Doch welche Modelltypen eignen sich dazu, Experimente auf der Teilchenebene zu deuten? Ein Vergleich an einem Versuch zu Lösevorgängen.
A case of cholesteatoma in a medieval Hispano‐Mudejar population (13th–14th centuries ad)
Authors: Dorado Enrique , Aso José , Sebastián Cristina , Ramírez Ildefonso , Carrillo Manuel F. , Murillo‐González Jorge
Published: November 2021

The case presented includes a left temporal bone from an individual exhumed from the Hispano‐Mudejar necropolis in Uceda (Guadalajara, Spain) dated between the 13th and 14th centuries bc. External examination and computed tomography images show lesions in the external acoustic canal, in the form of diffuse widening, suggestive of a cholesteatoma originating in this canal, with invasion of the middle ear through the tympanic membrane. The difficulties with examining the internal elements of the ear are discussed, which causes the underestimation of these diseases in paleopathology studies.