bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoglycaemic Activity of Extra Virgin Avocado (Persea americana) Oil and Extra Virgin Coconut (Cocos nucifera) Oil on Alloxan-induced Diabetic Rats
Authors: Offor Samuel J. , A. Tologbonse Adedayo , P. Iseh Uduak , E. Okoh Deborah , Akpan SifonObong
Published: January 2022

Diabetes mellitus is a chronic, metabolic disorder characterized by abnormal elevation of blood glucose levels (hyperglycaemia). Despite significant milestones achieved using conventional drugs in managing the disease, there are some drawbacks associated with their use such as drug resistance, adverse drug effects, high cost, and sometimes outright therapeutic failure. The urgent need to bridge this therapeutic lacuna calls for further exploration and investigation of other treatment options. This study therefore aims at evaluating the antidiabetic potentials of virgin avocado oil and virgin coconut oil in alloxan-induced diabetic rats. Animals were divided into 5 groups of five rats each. Group 1 (negative control) received 10 ml /kg/day of normal saline, group 2 (diabetic control) -10 ml/kg/day of normal saline; group 3 received extra virgin avocado oil (1 ml/250 g) body weight, group 4 received extra virgin coconut oil (2 ml/kg) bodyweight, and group 5 received 10 mg/kg/day of metformin. Treatments were administered orally for 15 days. Extra virgin avocado oil and extra virgin coconut oil respectively showed significant antidiabetic activities, and may be beneficial for management of diabetes mellitus.
Green Solvent‐Processed Hemi‐Isoindigo Polymers for Stable Temperature Sensors
Authors: Ngai Jenner H. L. , Polena John , Afzal Daniel , Gao Xiguang , Kapadia Mihir , Li Yuning
Published: January 2022

A series of donor‐acceptor polymers, namely PTEB, PMEB, PEEB, and PPEB, are designed and synthesized for temperature sensing. The polymers are composed of hemi‐isoindigo as the acceptor unit, 3,3″‐bis(dodecyloxy)‐2,2″‐bithiophene as the donor unit, and thiophene as the spacer unit. Carbamate solubilizing side chains are used to increase the solubility of the polymers in a green solvent anisole. Furthermore, the carbamate side chains can be thermally removed to form solvent‐resistant polymers PTNB, PMNB, PENB, and PPNB, respectively. The removal of carbamate side chains also helps to elevate the highest occupied molecular orbital energy level of the polymer, thereby promoting p‐doping. PMNB, PENB, and PPNB films are doped with 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F4TCNQ) and used for fabricating temperature sensors on flexible polyethylene terephthalate substrates. The sensors exhibit high temperature coefficient of resistance (TCR) of up to −1.92 (±0.125)% °C−1 at 20–60 °C. This is the highest TCR achieved to date for resistor‐type temperature sensors using a non‐composite single conductive polymer. High sensitivity, green solvent processability, and mechanical flexibility make these temperature sensors promising for use in low‐cost, ubiquitous applications.
Assembling Diverse Skyrmionic Phases in Fe3GeTe2 Monolayers
Authors: Xu Changsong , Li Xueyang , Chen Peng , Zhang Yun , Xiang Hongjun , Bellaiche Laurent
Published: January 2022

Skyrmionic magnetic states are promising in advanced spintronics. This topic is experiencing recent progress in 2D magnets, with, for example, a near 300 K Curie temperature observed in Fe3GeTe2. However, despite previous studies reporting skyrmions in Fe3GeTe2, such a system remains elusive, since it has been reported to host either Néel‐type or Bloch‐type textures, while a net Dzyaloshinskii–Moriya interaction (DMI) cannot occur in this compound for symmetry reasons. It is thus desirable to develop an accurate model to deeply understand Fe3GeTe2. Here, a newly developed method adopting spin invariants is applied to build a first‐principle‐based Hamiltonian, which predicts colorful topological defects assembled from the unit of Bloch lines, and reveals the critical role of specific forms of fourth‐order interactions in Fe3GeTe2. Rather than the DMI, it is the multiple fourth‐order interactions, with symmetry and spin–orbit couplings considered, that stabilize both Néel‐type and Bloch‐type skyrmions, as well as antiskyrmions, without any preference for clockwise versus counterclockwise spin rotation. This study also demonstrates that spin invariants can be used as a general approach to study complex magnetic interactions.
Highly Stable Artificial Synapses Based on Ferroelectric Tunnel Junctions for Neuromorphic Computing Applications
Authors: Song Sungmun , Ham Woori , Park Gyuil , Kho Wonwoo , Kim Jisoo , Hwang Hyunjoo , Kim Hyo‐Bae , Song Hyunsun , Ahn Ji‐Hoon , Ahn Seung‐Eon
Published: January 2022

Owing to the limited processing speed and power efficiency of the current computing method based on the von Neumann architecture, research on artificial synaptic devices for implementing neuromorphic computing capable of parallel computation is accelerating. The potential application of artificial synapses composed of ferroelectric tunnel junctions based on metal–hafnium zirconium oxide–metal structure for neuromorphic computing is investigated. Multiple resistance levels are implemented through partial polarization switching control, and synaptic plasticity is successfully imitated based on a high level of device stability and reproducibility. In addition, this device exhibits linear symmetric long‐term potentiation and long‐term depression using a highly variable pulse driving scheme. Finally, the artificial neural network applied with this synaptic device shows high classification accuracy (95.95%) for the Mixed National Institute of Standards and Technology handwritten digits.
Circular Subwavelength Photodetectors for 3D Space Exploration
Authors: Pan Qi , Sun Yali , Su Meng , Chen Sisi , Cai Zheren , Zhang Zeying , Zou Miaomiao , Chen Bingda , Mikhailova Julia V. , Zuev Dmitry , Song Yanlin
Published: January 2022

Detectors with the ability of 3D space exploration greatly promote sensing performance for artificial intelligence, automatic drive, etc. Current photodetectors for spatial angle detection are usually composed of planar stacked light‐sensing elements on the bulky 3D configuration. To meet the miniaturization and integration of intelligent systems, it is critical to break the obstacle between chip‐level architecture and spatial recognition function. Here, a chip‐level circular facade photodetector for 3D space exploration is demonstrated. The template used in the miniature solid‐shaping strategy guides the photosensitive materials patterning into 3D circular configuration, which divides the space into equal subdivisions. The multi‐directional light‐coupling interaction from the circular structure and the wider light–matter resonance from the self‐standing facade endow the 3D photodetectors with the capability of wide detection range (horizontal: 360°; vertical: 60°) and high detection accuracy (99.6%). Furthermore, this work provides a novel approach for 3D optoelectronics in intelligent systems.
Overcoming Electron Transfer Efficiency Bottlenecks for Hydrogen Production in Highly Crystalline Carbon Nitride‐Based Materials
Authors: Teixeira Ivo F. , Tarakina Nadezda V. , Silva Ingrid F. , López‐Salas Nieves , Savateev Aleksandr , Antonietti Markus
Published: January 2022

The hydrogen evolution reaction (HER) is a complex reaction involving many interdependent physicochemical steps. Highly ordered carbon nitride‐based materials, such as Na‐PHI and K‐PHI, display some of the highest activities for H2 evolution among the carbon nitride‐based materials, due to their electronic properties, but also the presence of cyanimide terminations, which favors the charge transfer for the Pt cocatalyst nanoparticles (NPs). For such highly optimized semiconductor structures, the necessity to control and improve other steps of the photocatalytic process becomes essential, in particular the poor electron transfer from the Pt NPs to the protons in solution over the Helmholtz or Stern layer. Taking highly ordered Na‐PHI as a test material, the influence of water‐dissolved alkali cations on the HER is systematically studied and it is experimentally verified that the electron transfer from the Pt NPs to the protons in solution limits the efficiency of heterogeneous carbon nitride‐based catalysts. This paper explains how hydrated alkali cations influence electron transfer and are able to boost the H2 evolution rate of the same Na‐PHI from 2401 up to 5330 µmol h−1 g−1 with an apparent quantum yield of 13% at 420 nm.
Differential Macrophage Responses to Gold Nanostars and Their Implication for Cancer Immunotherapy
Authors: Kenry  , Eschle Benjamin K. , Andreiuk Bohdan , Gokhale Prafulla C. , Mitragotri Samir
Published: January 2022

Gold nanostars (AuNSs) are actively explored for a range of theranostic and nanomedicine applications. While their biological applications are widely demonstrated, the fundamental interactions of these anisotropic nanomaterials with innate immune cells and their implication for cancer immunotherapy are less investigated. Specifically, it remains unclear how AuNSs interact with macrophages of different phenotypes and how these interactions influence the behavior of macrophages, especially their phagocytic and cancer modulating activities. Herein, the interactions between AuNSs of different shapes and macrophages of different phenotypes, including the naïve M0, pro‐inflammatory M1‐like, and anti‐inflammatory M2‐like phenotypes, are systematically interrogated. This study reveals that the morphology of AuNSs significantly impacts their interactions with macrophages. Macrophage viability, oxidative stress response, cytokine release, and phagocytotic ability depend on the macrophage phenotype as well as AuNS shape tip‐to‐core ratio. The selective response of macrophages toward AuNSs, particularly those of M1‐like phenotype, may be potentially leveraged for realizing cancer immunotherapy. Overall, it is anticipated that the findings of this study will further shape the understanding of the interactions between innate immune cells and Au nanomaterials and potentially open new opportunities for cancer therapy.
A Novel Metabolic Reprogramming Strategy for the Treatment of Diabetes‐Associated Breast Cancer
Authors: Hao Qiongyu , Huang Zhimin , Li Qun , Liu Dingxie , Wang Piwen , Wang Kun , Li Jieqing , Cao Wei , Deng Wenhong , Wu Ke , Su Rui , Liu Zhongmin , Vadgama Jay , Wu Yong
Published: January 2022

Diabetes is directly related to the risk of breast cancer (BC) occurrence and worsened BC prognosis. Currently, there are no specific treatments for diabetes‐associated BC. This paper aims to understand the fundamental mechanisms of diabetes‐induced BC progression and to develop personalized treatments. It reports a metabolic reprogramming strategy (MRS) that pharmaceutical induction of glucose import and glycolysis with metformin and NF‐κB inhibitor (NF‐κBi) while blocking the export of excessive lactate via inhibiting monocarboxylate transporter 4 (MCT4) leads to a metabolic crisis within the cancer cells. It demonstrates that the MRS shifts the metabolism of BC cells toward higher production of lactate, blocks lactate secretion, prompts intracellular acidification and induces significant cytotoxicity. Moreover, a novel MCT4 inhibitor CB‐2 has been identified by structure‐based virtual screening. A triple combination of metformin, CB‐2, and trabectedin, a drug that impedes NF‐κB signaling, strongly inhibits BC cells. Compared to normal glucose condition, MRS elicits more potent cancer cell‐killing effects under high glucose condition. Animal model studies show that diabetic conditions promote the proliferation and progression of BC xenografts in nude mice and that MRS treatment significantly inhibits HG‐induced BC progression. Therefore, inhibition of MCT4 combined with metformin/NF‐κBi is a promising cancer therapy, especially for diabetes‐associated BC.
A Prestressing Strategy Enabled Synergistic Energy‐Dissipation in Impact‐Resistant Nacre‐Like Structures
Authors: Wu Kaijin , Song Yonghui , Zhang Xiao , Zhang Shuaishuai , Zheng Zhijun , Gong Xinglong , He Linghui , Yao Hong‐Bin , Ni Yong
Published: January 2022

The application of prestresses is a valuable strategy for enhancing the overall mechanical performances of structural materials. Residual stresses, acting as prestresses, exist naturally in biological structural materials, such as the nacre with the 3D “brick‐and‐mortar” arrangement. Although regulation of the tablets sliding has recently been demonstrated to be vital to improve toughness in synthetic nacre‐like structures, the effects of prestresses on the tablets‐sliding mechanism in these nacre‐like structures remain unclear. Here, by a combination of simulation, additive manufacturing, and drop tower testing the authors reveal that, at a critical prestress, synergistic effects between the prestress‐enhanced tablets sliding and prestress‐weakened structural integrality result in optimized impact resistance of nacre‐like structures. Furthermore, the prestressing strategy is easily implemented to a designed nacre‐inspired separator to enhance the impact resistance of lithium batteries. The findings demonstrate that the prestressing strategy combined with bioinspired architectures can be exploited for enhancing the impact resistance of engineering structural materials and energy storage devices.
Inflammation‐Triggered Supramolecular Nanoplatform for Local Dynamic Dependent Imaging‐Guided Therapy of Rheumatoid Arthritis
Authors: Li Luoyuan , Wang Xuelong , Gao Rongyao , Zhang Bei , Liu Yuxin , Zhou Jing , Fu Limin , Wang Jian
Published: January 2022

The aging of population has resulted in a significant increase in the prevalence of rheumatoid arthritis (RA), which is a persistent and recurrent synovial inflammation caused by abnormal immune activation. Herein, the authors designed an inflammation‐triggered disassembly (ITD) nanoplatform by a supramolecular assembly method, which controls the decomposition and drug release through changes in cytokine concentrations and redox potentials during the onset of arthritis, and its dual‐targeted synergistic effect on collagen‐induced arthritis (CIA) rats resulted in higher cell death rate and immunosuppressive rate. Meanwhile, they propose the local dynamic dependent imaging (LDDI) technology to diagnose the disease status, which may produce corresponding changes with the fluctuation of inflammatory activity and improve the accuracy of dual‐target therapy by monitoring the synovial changes through in situ photoactivation of the second near infrared light (NIR‐II). Very importantly, histological analysis shows that ITD strategy relieved joint destruction and cartilage degeneration and its clinical score is similar to that of the healthy group. Their work provides an effective strategy for the early diagnosis and treatment of acute and chronic inflammation diseases, which can interfere to abnormal immune activation, rather than affecting the normal function of immune system.
Correlation between Transient Response and Neuromorphic Behavior in Organic Electrochemical Transistors
Authors: Yamamoto Shunsuke , Polyravas Anastasios G. , Han Sanggil , Malliaras George G.
Published: January 2022

The factors controlling the neuromorphic response of organic electrochemical transistors (OECTs) are examined. In these devices, the gate voltage is used to supply the pre‐synaptic input, while the drain current is taken as the post‐synaptic output. The behavior of devices made from polymer blends of a mixed conductor (PEDOT:PSS) and an ion conductor (PSSNa) is analyzed. The experimental results highlight that the post‐synaptic response timescale depends on the size of ion in the electrolyte. Modeling shows that the neuromorphic response is controlled by the transient response of the ionic circuit of the OECT. These insights on device response time pave the way for a more rational design of OECT‐based neuromorphic devices.
Ultrafast and Highly Deformable Electromagnetic Hydrogel Actuators Assembled from Liquid Metal Gel Fiber
Authors: Tachibana Daiki , Murakami Koki , Kozaki Takashi , Matsuda Ryosuke , Isoda Yutaka , Nakamura Fumika , Isano Yuji , Ueno Kazuhide , Fuchiwaki Ohmi , Ota Hiroki
Published: January 2022

Hydrogel actuators are ultrasoft and pliable but achieving high driving speeds with large deformation and fine local controllability is difficult because the driving force originates from the external air pressure or heat, and the base material is fragile. Herein, hydrogel actuators that allow high‐speed driving and large deformation with high‐frequency local controllability while maintaining softness are fabricated based on liquid metal gel fibers as electrodes by using microfluidic technology. The Lorentz force produced by an electric current and a magnet is used for actuation control. An ultrafast response of 260.5 mm s−1 with high‐frequency controllability (6 Hz) and a large deformation of 172% with hydrogel actuation are observed. As proof of concept, moving stages, micromixers, and grippers exhibiting high speeds with high mechanical deformability while maintaining the inherent characteristics of hydrogel phases are demonstrated. Different hydrogels can be used with the proposed actuator architecture and fabrication scheme, enabling different functionalities.
One‐pot Synthesis of 3‐Aryliden‐2,3‐dihydro‐4‐quinolones from o‐Anilinopropargyl Alcohols via Aldol Condensation of In Situ Generated 2,3‐Dihydroquinolin‐4‐ones and Aryl Aldehydes
Authors: Pan Wanyong , Zhai Jiulong , Yang Hong , Li Tiantian , Lu Xiaolei , Wang Zhihai , Yin Yan
Published: January 2022

A one‐pot conversion of o‐anilinopropargyl alcohols to 3‐aryliden‐2,3‐dihydro‐4‐quinolone derivatives with 20 mol% TfOH as the catalyst has been devised. The method may proceed through a sequential Meyer‐Schuster rearrangement of o‐anilinopropargyls/intramolecular conjugated addition/aldol condensation of in situ generated 2,3‐dihydroquinolin‐4‐ones and aldehydes. Finally, the subsequent additions succeeded between 3‐benzyliden‐2,3‐dihydro‐4‐quinolones and hydrazines to give fused multicycles. The reaction is metal‐ and ligand‐free, proceeds under mild conditions, gives high yields, and has a broad substrate scope, making it a valuable method for the construction of 3‐aryliden‐2,3‐dihydro‐4‐quinolone functionalized building blocks.
Comparison of serum neurodegenerative biomarkers among hospitalized COVID‐19 patients versus non‐COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia
Authors: Frontera Jennifer A. , Boutajangout Allal , Masurkar Arjun V. , Betensky Rebecca A. , Ge Yulin , Vedvyas Alok , Debure Ludovic , Moreira Andre , Lewis Ariane , Huang Joshua , Thawani Sujata , Balcer Laura , Galetta Steven , Wisniewski Thomas
Published: January 2022

Introduction

Neurological complications among hospitalized COVID‐19 patients may be associated with elevated neurodegenerative biomarkers.

Methods

Among hospitalized COVID‐19 patients without a history of dementia (N = 251), we compared serum total tau (t‐tau), phosphorylated tau‐181 (p‐tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy‐terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in‐hospital death versus survival, and discharge home versus other dispositions. COVID‐19 patient biomarker levels were also compared to non‐COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161).

Results

Admission t‐tau, p‐tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in‐hospital, while t‐tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non‐COVID controls with MCI or AD.

Discussion

Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID‐19 patients.
Nonequilibrium Charge Dynamics of Tomonaga–Luttinger Liquids in Quantum Hall Edge Channels
Authors: Fujisawa Toshimasa
Published: January 2022

Tomonaga–Luttinger liquids exhibit unique features that cannot be seen in ordinary Fermi liquids. Recent advancement in measurement techniques on 1D quantum Hall edge channels allows to reveal unique characteristics, such as spin‐charge separation and nonthermal metastable states. In this review, an overview of nonequilibrium dynamics in quantum‐Hall Tomonaga–Luttinger liquids is presented. After the introduction of a circuit model for collective excitations (bosons) in the system, transport eigenmodes in interaction‐ and disorder‐dominated regimes are discussed with time‐resolved charge measurements for the integer and fractional quantum Hall systems. Moreover, nonthermal steady states associated with the integrable model are studied with energy distribution functions obtained with a quantum dot spectrometer. These nontrivial dynamics can be extended to other 1D systems, including 2D topological insulators.
Shape Permanence in Diarylethene‐Functionalized Liquid‐Crystal Elastomers Facilitated by Thiol‐Anhydride Dynamic Chemistry
Authors: Hebner Tayler S. , Podgórski Maciej , Mavila Sudheendran , White Timothy J. , Bowman Christopher N.
Published: January 2022

Diarylethene‐functionalized liquid‐crystalline elastomers (DAE‐LCEs) containing thiol‐anhydride bonds were prepared and shown to undergo reversible, reprogrammable photoinduced actuation. Upon exposure to UV light, a monodomain DAE‐LCE generated 5.5 % strain. This photogenerated strain was demonstrated to be optically reversible over five cycles of alternating UV/Visible light exposure with minimal photochrome fatigue. The incorporation of thiol‐anhydride dynamic bonds allowed for retention of actuated states. Further, re‐programming of the nematic director was achieved by heating above the temperature for bond exchange to occur (70 °C) yet below the nematic‐to‐isotropic transition temperature (100 °C) such that order was maintained between mesogens. The observed thermal stability of each of the diarylethene isomers of over 72 h allowed for decoupling of photo‐induced processes and polymer network effects, showing that both polymer relaxation and back‐isomerization of the diarylethene contributed to LCE relaxation over a period of 12 hours after actuation unless bond exchange occurred.
Synthesis of doxorubicin‐loaded PBMA‐b‐POEGMA micelles and assessment of its anticancer activity against breast cancer cells (4T1)
Authors: Gharnas‐Ghamesh Hamideh , Masoumi Mojtaba , Erfani‐Moghadam Vahid
Published: January 2022

Doxorubicin (DOX) is a chemotherapy drug that possesses many side effects. This study aimed to synthesize PBMA‐b‐POEGMA [poly (butyl methacrylate)‐b‐poly (oligo ethylene glycol methacrylate)] diblock copolymer as a nanocarrier for loading of DOX, promoting anticancer efficacy of the drug, and decreasing its side effects. Hence, PBMA‐b‐POEGMA diblock copolymer was first synthesized by the RAFT method and then DOX encapsulated into the micellar nanocarrier. Self‐assembly behavior of copolymers and physicochemical/biological properties of nanocarriers were assessed. DLS and TEM images showed nanocarriers possessed spherical‐uniform structure with the mean size and polydispersity of 27 ± 1.34 nm and 0.13 ± 0.21 for blank‐micelles as well as, 45 ± 2.32 nm and 0.18 ± 0.18 for DOX‐loaded micelles, respectively. Synthesized micelles also provided high drug encapsulation efficiency (>80%) with a drug loading content of 4.53%. Moreover, the maximum released amount of drug was reported at 69%, with the Korsmeyer‐Peppas model, as a more suitable model to describe the release behavior of DOX from nanocarriers. Biologically, block copolymers were biocompatible against COS‐7 and 4T1 cell lines, in addition, free‐DOX showed higher cytotoxicity than DOX‐loaded micelles. Furthermore, 0.5 μg/mL concentration of drug‐loaded micelle led to growth inhibition of more than 60% of cancerous cells, during 48 h, so that higher level of cellular uptake of drug and apoptosis in 4T1 cells was induced by drug‐loaded micelles.
Übergangskonstruktionen aus UHPFRC für den Integralbrückenbau
Authors: Mayer Michael , Huß Michael , Kim Hoang Huy , Tue Nguyen Viet
Published: January 2022

Dank der Bereitstellung von normativen Regelungen für den Entwurf und die Bemessung nimmt die Anzahl von Integralbrücken weltweit deutlich zu, sowohl durch Neubauten als auch durch die nachträgliche Integralisierung von bestehenden Bauwerken. Neben vielen Vorteilen bezüglich des Fahrkomforts und der Lebenszykluskosten stellt sich die Wechselwirkung im Übergangsbereich zwischen Bauwerk und Straße bei Integralbrücken deutlich komplexer dar als bei gewöhnlichen Brücken, insbesondere bei langen Bauwerken. Breite Risse im bituminösen Fahrbahnbelag konnten deshalb in diesem Bereich häufig beobachtet werden. Diese Risse beeinflussen nicht nur den Fahrkomfort, sondern auch die Dauerhaftigkeit maßgeblich. Um die Bauwerksverformung auf viele feine Risse zu verteilen, wurde am Institut für Betonbau der TU Graz eine neue Übergangskonstruktion aus UHPFRC entwickelt. Diese neuartige Lösung wurde mittlerweile bereits bei zwei Integralbrücken in Österreich mit Überbaulängen von 90 m (Fehring) und 103 m (Trautenfels) eingesetzt. Die ersten Ergebnisse aus dem installierten Monitoringsystem beim Bauwerk in Fehring bestätigen die Funktionsweise der neuen Konstruktion eindrucksvoll.
Effects of pyruvate on primary metabolism and product quality for a high‐density perfusion process
Authors: Caso Stefania , Aeby Mathieu , Jordan Martin , Guillot Raphael , Bielser Jean‐Marc
Published: January 2022

High volumetric productivities can be achieved when perfusion processes are operated at high cell densities. Yet it is fairly challenging to keep high cell density cultures in a steady state over an extended period. Aiming for robust processes, cultures were operated at a constant biomass specific perfusion rate (BSPR) in this study. The cell density was monitored with a capacitance probe and a continuous bleed maintained the targeted viable cell volume. Despite our tightly controlled BSPR, a gradual accumulation of ammonium and changes in cell diameter were observed during the production phase for three different monoclonal antibodies. Although a lot of efforts in media optimization have been made to reduce ammonium in fed‐batch process, less examples are known about how media components impact the cellular metabolism and thus the quality of monoclonal antibodies in continuous processes. In this study, we show that a continuous Na‐pyruvate feed (2 g/L/day) strongly reduced ammonium production and stabilized fucosylation, sialylation and high mannose content for three different mAbs.
Functionalized cryogel monoliths for fast and selective separation of nucleic acids directly from crude lysate
Authors: Shakya Akhilesh Kumar
Published: January 2022

The fast and selective separation of nucleic acids has been attractive recently because of their wide number of applications in the biomedical field such as the development of vaccines for infectious diseases, gene therapy, and diagnosis. Traditional approaches of nucleic acids separation are costlier, lengthy, and associated with possible denaturation because of the use of organic solvents in the elution step. Under this perspective, cryogels represent an attractive choice as a monolith stationary phase in column chromatography, which have proven efficient in recent chromatographic studies. Cryogels are the macroporous hydrogels with interconnecting properties between the pores. They allow the easy flow of large biomolecules with minimum mass transfer resistance. They are spongy in nature and possess good mechanical strength. Current article represents different developed functionalized cryogel monoliths for nucleic acids separation, their separation strategies, and challenges associated with further advancement in separation science.
LY395756 promotes NR2B expression via activation of AKT/CREB signaling in the juvenile methylazoxymethanol mice model of schizophrenia
Authors: Li Meng‐lin , Peng Yuan , An Ying , Li Guo‐yan , Lan Yue
Published: January 2022

Introduction

Synaptic N‐methyl‐d‐aspartate receptor subtype 2B(NR2B) is significantly reduced in prefrontal cortex (PFC) in the neurodevelopmental methylazoxymethanol (MAM) model of schizophrenia (SCZ). Recent research has shown that LY395756 can effectively restore NR2B levels and improve cognitive performance in juvenile MAM mice model. However, the underlying mechanisms of these beneficial effects remain unclear.

Materials and methods

Juvenile MAM mice model of SCZ is used in our study. Synaptic membrane protein levels were examined by western blotting under different treatment conditions. Interaction of cAMP‐response element binding protein (CREB) and the promoter of NR2B was detected by the chromatin immunoprecipitation (ChIP) assay. Further examination of signaling pathway that mediates NR2B expression was also investigated by western blotting.

Results

In the PFC of the juvenile MAM mice schizophrenia model, CREB was found to directly bind with the promoter of NR2B. LY395756 activated the phosphorylation of AKT. Phosphorylated AKT subsequently induced the phosphorylation of CREB, and the activated CREB promoted the expression of NR2B. Subsequent experiments showed that the dephosphorylation of CREB induced by protein phosphatase 1 (PP1) can inhibit NR2B levels. Taken together, these findings support that the AKT/CREB signaling pathway is essential for the promoting effect of LY395756 on synaptic NR2B in PFC in juvenile MAM mice SCZ model.

Conclusions

Our investigation has identified a novel mechanism by which LY395756 increases NR2B expression in juvenile MAM mice SCZ model. The AKT/CREB signaling pathway warrants further research as a potential direction for clinical treatment of SCZ.
A real‐world study of dacomitinib in later‐line settings for advanced non‐small cell lung cancer patients harboring EGFR mutations
Authors: Li Hong‐Shuai , Zhang Jin‐Yao , Yan Xiang , Xu Hai‐Yan , Hao Xue‐Zhi , Xing Pu‐Yuan , Wang Yan
Published: January 2022

Objective

Dacomitinib has been approved for the first‐line treatment of non‐small cell lung cancer (NSCLC) carrying classical epidermal growth factor receptor (EGFR) mutations; however, real‐world data on its later‐line application are lacking.

Materials and methods

Patients’ data were retrospectively collected from the Chinese National Cancer Center and the PLA hospital between August 2019 and August 2021. Kaplan‐Meier method and Log‐rank test were utilized to assess progression‐free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analysis was conducted to determine prognostic indicators.

Results

In total, 56 NSCLC patients harboring EGFR mutations treated with later‐line single dacomitinib or combinatory dacomitinib were enrolled. A total of 53 patients (94.6%) had treatment‐related adverse events; eight patients (14.3%) had grade 3 or 4 events. Among 49 evaluable patients, 26.5% (13 patients) had a confirmed partial response and 73.5% (36 patients) had disease control; the median duration of follow‐up was 9.6 months (95% confidence interval [CI], 8.4–10.8 months), the median progression‐free survival was 5.4 months (95% CI, 3.5–7.3 months), and the half‐year, 1‐year, and 2‐year OS rate were 79.2%, 70.6%, and 64.1%, respectively. Univariate analysis suggested that smoking, line of dacomitinib, and interval between last EGFR‐tyrosine kinase inhibitor (TKI) and dacomitinib were associated with PFS and OS; chemotherapy between last EGFR‐TKI and dacomitinib, and EGFR‐TKI generation followed by dacomitinib were respectively associated with PFS and OS; multivariate analysis indicated chemotherapy between last EGFR‐TKI and dacomitinib negatively affect PFS, and smoking and third‐generation EGFR‐TKI followed by dacomitinib negatively affect OS.

Conclusions

This real‐world study has shown that dacomitinib is active and well‐tolerated in NSCLC patients harboring different EGFR mutations in later‐line settings, even for those with brain metastases. Patients who benefited more from the first TKI were more likely to benefit from dacomitinib, and earlier application of dacomitinib after front‐line TKI resistance may be considered.
The clinicopathological and molecular characteristics of resected EGFR‐mutant lung adenocarcinoma
Authors: Zhou Wensheng , Liu Zhichao , Wang Yanan , Zhang Yanwei , Qian Fangfei , Lu Jun , Wang Huimin , Gu Ping , Hu Minjuan , Chen Ya , Yang Zhengyu , Zhao Ruiying , Lou Yuqing , Han Baohui , Zhang Wei
Published: January 2022

Background

Epidermal growth factor receptor (EGFR) mutations were frequently found with concomitant genetic alterations in lung adenocarcinoma (LUAD). This study aimed to investigate the profile of concomitant alterations of EGFR‐mutant LUAD ≤3 cm in size and its prognostic effect on recurrence.

Methods

From January 2018 to December 2018, patients with resected LUAD ≤3 cm in size in Shanghai Chest Hospital were identified. All patients underwent capture‐based targeted next‐generation sequencing (NGS) with a panel of 68 lung cancer‐related genes and were found with EGFR mutation. Clinicopathological and molecular characteristics and recurrence‐free survival (RFS) were analyzed.

Results

A total of 637 patients were enrolled in this study. The top three frequent co‐mutational genes were TP53 (179 of 637, 28.1%), PIK3CA (27 of 637, 4.2%), and ATM (22 of 637, 3.5%). The most common amplified genes were EGFR (37 of 637, 5.8%), followed by CDK4 (37 of 637, 5.8%) and MYC (12 of 637, 2.0%). Only TP53 mutation and EGFR amplification were adverse prognostic factors for RFS (all p < 0.001) in univariate analysis. Multivariable analysis further demonstrated that TP53 mutation and EGFR amplification were independent risk factors for RFS [(hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.07–4.00, p = 0.030; HR 3.09, 95% CI 1.49–6.40, p = 0.002, respectively].

Conclusions

Concomitant TP53 mutation and EGFR amplification were poor prognostic factors for RFS in patients with EGFR‐mutant resected LUAD. Our findings provide valuable understanding of the impact of concurrent alterations and implication for better implementation of precision therapy for patients.
Essential Oils of Six Achillea Species: Chemical Profiles, Antimicrobial Potential and Toxicity toward Crustaceans
Authors: Stojanović Jelena P. , Stojanović Gordana S. , Stojanović‐Radić Zorica Z. , Zlatković Bojan K. , Ickovski Jovana D. , Zlatanović Ivana G. , Jovanović Snežana Č. , Mitić Zorica S.
Published: January 2022

This is the first comparative study on antimicrobial activity of essential oils (EOs) of six Achillea species (A. crithmifolia, A. distans, A. grandifolia, A. millefolium, A. nobilis, and A. lingulata) against ATCC and clinical microbial strains isolated from human swabs and on their toxicological potential on crustaceans. Oxygenated monoterpenes represented the major compound class in all six EOs, ranging from around 50 % (A. millefolium, A. nobilis, and A. lingulata) up to over 80 % (A. crithmifolia and A. grandifolia). Specific phytochemical profiles of the major volatiles were determined for each species. Still, borneol was the dominant compound in EOs of three yarrow species: A. distans, A. lingulata, and A. millefolium. Other major compounds were 1,8‐cineole in A. crithmifolia, camphor in A. grandifolia, and artemisia ketone in A. nobilis EO. Antimicrobial activities of EOs were examined by a microdilution method revealing inhibitory action against all 15 studied strains in the range of 0.07–20.00 mg/mL (MICs). High toxicity (LC50 <100 μg/mL) in Artemia salina acute toxicity bioassay was a shared characteristic, appearing in five out of six tested EOs, i. e., those isolated from A. lingulata, A. millefolium, A. distans, A. nobilis, and A. grandifolia. In both types of biological tests, A. lingulata EO has shown the highest and A. crithmifolia EO the lowest potential. The strongest activities, recorded for EO of A. lingulata, which was the only studied species from the section Anthemoideae, may be explained by its somewhat unusual chemical composition. According to the obtained results, the second dominant compound of this EO is γ‐palmitolactone, which may be a significant agent regarding the antimicrobial activity and toxicity to crustaceans, either on its own or in union with other components, and it may be a suitable topic for further research.
Case report: Schizophrenia and hypertrophic osteoarthropathy, a rare syndrome hiding a life‐threatening condition
Authors: Baklouti Emna , Karoui Mehdi , Kammoun Rania , Ellouze Faten
Published: January 2022

Schizophrenia is associated to somatic disorders especially cardio‐vascular and auto‐immune. Through this case report, we describe an association with hypertrophic osteoarthropathy (HPO). For this patient, it was a paraneoplastic syndrome secondary to lung cancer. This syndrome is rare but important to recognize since it could hide a life‐threatening condition.
Ordered Mesoporous Carbon‐supported Morphologically‐controlled Nano‐Gold: Role of Support as well as the Shape and Size of Gold Nanoparticles on the Selective Oxidation of Glycerol
Authors: Murthy Palle Ramana , Selvam Parasuraman
Published: January 2022

Glyceric acid is one of the important intermediates of glycerol oxidation. However, it is extremely difficult to achieve high glyceric acid selectively as the reaction follows a complex pathway with the formation of a variety of undesired products. In this context, periodic mesoporous carbon‐supported gold catalysts show promise for selective formation of the targeted product. Therefore, in this investigation, an effort has made to study the effect of particle size and shape of a series of carbon supported with varied sized/shaped gold catalysts on the liquid‐phase oxidation of glycerol. Further, the role played by the surface of gold‐nanoparticles has prompted us to investigate in detail the isotropic (nanocube/nanosphere) and anisotropic (nanoslabs/nanorods) gold supported onto both activated/amorphous carbon (Au/AC) and ordered mesoporous carbon (Au/CMK‐3) towards glycerol oxidation. It was observed that the CMK‐3 supported gold nanocube exhibited the highest yield towards glyceric acid with an excellent stability in terms of recyclability/reusability.
Correlations between Outside Temperature and Energy Consumption of Biogas Upgrading Plants
Authors: Meier Karlheinz
Published: January 2022

The aim of this research was to prove or refute the existence of a correlation between outside temperature and the energy consumption of large biomethane injecting plants. To this end, data of four biomethane plants in Germany from March 1, 2019 to February 28, 2021 were gathered and correlated. To rule out different factors, the data were gathered as daily production sums and daily averages. It was found that no correlation exists and that this was consistent for all four plants.
Cobalt‐Catalyzed Intermolecular Hydroamination of Unactivated Alkenes Using NFSI as Nitrogen Source
Authors: Sun Peng‐Wei , Zhang Ze , Wang Xinyao , Li Linshan , Li Yuxin , Li Zhengming
Published: January 2022

Comprehensive Summary

Cheap metal (Fe, Mn, and Co)‐catalyzed hydroamination of alkenes has been an attractive method for synthesis of amines because of biocompatibility of metal, excellent Markovnikov selectivity and chemoselectivity. However, most reports are limited to unsaturated nitrogen sources (nitric oxide, azos, azides, cyano, etc.), for which aminated products are very limited. Notably, while used widely for fluorinating reaction, N‐fluorobenzenesulfonimide (NFSI) as amine source for hydroamination has seldom been reported. Here we developed a cobalt‐catalyzed intermolecular hydroamination of unactivated alkenes using NFSI as nitrogen source under mild conditions. The reaction exhibits excellent chemo‐ and regio‐selectivity with no hydrofluorination or linear‐selectivity products. Notably, the reaction proceeded with excellent yield even though the amount of Co(salen) catalyst was reduced to 0.2 mol%. Recently, a similar work was also reported by Zhang and coworkers (ref. 19).
Configuration approach for personalized travel mashup
Authors: Boulakbech Marwa , Messai Nizar , Sam Yacine , Devogele Thomas
Published: January 2022

Nowadays, we live in an interconnected ecosystem of heterogeneous services which are available anytime and anywhere. Although these services can be used individually, their combined usage provides end‐users with real added value. Nevertheless, existing mashup solutions are not fully targeted to end‐users. Indeed, these solutions require technical knowledge to deal with the technological heterogeneity in which they are offered. The key limitation of current mashup solutions is their general‐purpose nature, which privileges expressive power over intuitiveness. As the reason for mashups was the desire of end‐users to build applications responding to their situational needs, we propose a domain‐specific mashup approach that “speaks the language of the user.” The article presents (1) a domain‐specific visual language that allows end‐users to easily build mashup‐based compositions, (2) a mashup schema which is a gateway between service implementations and end‐users, providing a high‐level description in order to hide technological issues when including services in composition; and (3) a configuration module that executes the travel mashup query and generates a personalized trip planning. The results of a user study confirm that domain‐specific mashup tools lower the entry barrier to mashup development.
Teen substance use showed record declines in 2021: MTF
Authors: Knopf Alison
Published: January 2022

According to the Monitoring the Future (MTF) survey released by the National Institute on Drug Abuse (NIDA) last year, the percentage of adolescents reporting substance use decreased significantly in 2021.
A new Approach for the Voltammetric Sensing of the Phytoestrogen Genistein at a Non‐modified Boron‐doped Diamond Electrode
Authors: Barzani Hemn A. H. , Saadi Ali Hoshyar , Şahin Cihat , Kıran Musa , Yardım Yavuz
Published: January 2022

An effective electrochemical sensor was constructed using an unmodified boron‐doped diamond electrode for determination of genistein by square‐wave voltammetry. Cyclic voltammetric investigations of genistein with HClO4 solution indicated that irreversible behavior, adsorption‐controlled and well‐defined two oxidation peaks at about +0.92 (PA1) & +1.27 V (PA2). pH, as well as supporting electrolytes, are important in genistein oxidations. Quantification analyses of genistein were conducted using its two oxidation peaks. Using optimized experiments as well as instrumental conditions, the current response with genistein was proportionately linear in the concentrations range of 0.1 to 50.0 μg mL−1 (3.7×10−7−1.9×10−4 mol L−1), by the detection limit of 0.023 μg mL−1 (8.5×10−8 mol L−1) for PA1 and 0.028 μg mL−1 (1.1×10−7 mol L−1) for PA2 in 0.1 mol L−1 HClO4 solution (in the open circuit condition at 30 s accumulation time). Ultimately, the developed method was effectively applied to detect genistein in model human urine samples by using its second oxidation peak (PA2).
Intelligent electric vehicles charging coupled demand response of isolated microgrid
Authors: Niharika  , Mukherjee Vivekananda
Published: January 2022

In recent times, the shrinkage of fossil fuel reserves and increase in greenhouse emissions have compelled to switch to suitable eco‐friendly solutions. Electric vehicles (EVs), being one such solution, have been the center of attraction for the industries as well as the researchers. This paper deals with the inclusion of plug‐in EVs (PEVs) in isolated microgrid (I‐MG). An intelligent demand‐side management approach has been proposed for co‐ordination of the power generation from distributed generators, battery energy storage systems (BESSs), and other forms of distributed energy resources (DERs) to fulfill the daily load demand as well as energy demand of EVs. Medium voltage I‐MG integrated with DERs, BESSs and PEVs has been used for the study and the analysis has been done to justify the need for smart charging of PEVs in an I‐MG. The proposed technique combines smart charging and demand response which simplifies the consumer’s concerns and provides a cost‐effective solution.
Compositional and Sr‐Nd isotopic features of the Xiejiayao ophiolite in the North Qilian Orogenic Belt, NW China: Implications for the petrogenesis and tectonic setting
Authors: Zhao Cong , Zhao Jing , Ni Shijun , Chen Youliang , Huang Luyu
Published: January 2022

The ophiolites along the North Qilian Orogenic Belt are considered to be fragments of ancient oceanic crusts and lithospheric mantle of the Palaeozoic North Qilian Ocean (a branch of the Proto‐Tethys). Compared with other ophiolites in this belt, the genesis of the Xiejiayao ophiolite has been poorly studied so far, making it difficult to understand the tectonic evolution of the ocean. In this study, we present new compositional and Sr‐Nd isotopic analyses of basaltic rocks from the Xiejiayao ophiolite to shed light on its petrogenesis and geodynamic background. These oceanic basalts are characterized by flat REE patterns, low elemental ratios of high‐field‐strength elements (e.g., La/Sm, Sm/Yb, La/Yb, Gd/Yb, [Th/Yb]PM) and abundant spinels, implying that they were generated via partial melting in the spinel stability field of the mantle. Their positive εNd(t) values (6.1–8.4), high Zr/Nb (43.65–79.40) as well as low Nb/Ta (10.91–15.09), Zr/Hf (34.64–39.28), and Nb/Yb (0.41–0.59) ratios further reflect that the ancient mantle had already become depleted to some extent before the onset of the Palaeozoic ocean. Additionally, basalts share many geochemical similarities (e.g., Zr, Y, Ti, and V) with both mid‐ocean ridge and island arc basalts. This supports the strong likelihood of origin in a back‐arc basin close to the suprasubduction zone for the ophiolite. Therefore, accompanied by the northward subduction of the oceanic lithosphere during the early Palaeozoic, a large‐scale back‐arc basin developed progressively in response to the back‐arc expansion. The Xiejiayao basaltic magmas were generated in the back‐arc basin via partial melting of the depleted mantle and their source was probably mixed with subducted melts/fluids from the dehydration and melting of oceanic slabs and sediments.
Biosimilar competition: Early learning
Authors: Frank Richard G. , Shahzad Mahnum , Kesselheim Aaron S. , Feldman William
Published: January 2022

Biologics accounted for roughly $145 billion in spending in 2018. They are also the fastest growing segment of the pharmaceutical industry. The Biological Price Competition and Innovation Act (BPCIA) of 2010 created an abbreviated pathway for biosimilar products to promote price competition in the market for biological drugs. There was great anticipation that the BPCIA would lead to a moderation in drug prices driven by market competition. The observed levels of competition and the accompanying savings have not reached those expected levels. We investigate the early impacts of biosimilar competition on the use and pricing of biological products. We focus especially on the ways in which altered market structures stemming from the implementation of the BPCIA have affected the prices for biological products subject to biosimilar competition. We do so by studying seven products that have recently faced biosimilar competition. We estimate fixed effects and Instrumental Variables models to estimate the impact of market competition on prices. Our results indicate that in the range of one to three entrants each additional marketed product results in a reduction in weighted average market prices of between 5.4% and 7% points. These are the result of a combination of reductions in originator prices and shifting in demand to biosimilar products.