bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual‐Crosslinked Dynamic Hydrogel Incorporating {Mo154} with pH and NIR Responsiveness for Chemo‐Photothermal Therapy
Authors: Guedes Gabriela , Wang Shiqi , Fontana Flavia , Figueiredo Patrícia , Lindén Jere , Correia Alexandra , Pinto Ricardo J. B. , Hietala Sami , Sousa Filipa L. , Santos Hélder A.
Published: August 2021

Polyoxometalates are an emerging class of molecular clusters, with well‐defined structures and chemical compositions that are produced through simple, low‐cost, and highly reproducible methods. In particular, the wheel‐shaped cluster {Mo154} is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self‐healing hydrogel of easy preparation and administration is developed, incorporating both {Mo154} and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N‐isopropylacrylamide) functionalized chitosan and {Mo154}. The gelation occurs within 60 s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self‐healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra‐red (NIR) radiation and pH changes. This stimuli‐responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo154}‐based systems, incorporated in self‐healing and injectable hydrogels for dual chemo‐photothermal therapy.
Ferroelectric Controlled Gas Adsorption in Doped Graphene/In2Se3Heterostructure
Authors: Wan Tsz Lok , Shang Jing , Gu Yuantong , Kou Liangzhi
Published: August 2021

Two‐dimensional materials are excellent candidates for effective gas detection due to the large surface‐volume ratio, however the controllability to adsorb/desorb the gas molecules for recycling use is still a big challenge. In this study, different from previous strategies to modulate gas adsorption behavior via strain and external electric field, a novel approach to achieve gas adsorption control via ferroelectric (FE) switching is proposed. From first principle simulations, it is found that gas molecule adsorptions on Fe and Mn doped defective graphene can be well controlled when it is placed on the surface of FE In2Se3. The adsorption energies and charge transfer can be significantly modulated when the polarization is reversed, due to the polarization dependent electron redistribution and band state shifts near the Fermi level. The hypothesis of the FE controlled gas adsorption is further supported by the adsorption variations under the electric field. These findings provide feasible approaches and design principles for the next generation gas sensors.
Self‐Powered Gyroscope Angle Sensor Based on Resistive Matching Effect of Triboelectric Nanogenerator
Authors: Xie Xinkai , Chen Yunfeng , Jiang Jinxing , Li Junyan , Yang Yanqin , Liu Yina , Yang Li , Tu Xin , Sun Xuhui , Zhao Chun , Sun Mingchao , Wen Zhen
Published: August 2021

Gyroscope is one of the most widely distributed and utilized motion sensors among Internet of Things sensing for sports health, artificial intelligence, military management, civil defense, etc. Preparing a thoroughly self‐powered gyroscope sensor based on triboelectric nanogenerator (TENG) with superior stability is of innovative research significance. In this work, a self‐powered gyroscope angle sensor (SGAS) based on resistive impedance matching effect of TENG is proposed to detect relative rotation angle, performing as an attitude indicator applied in the flight control system of the unmanned aerial vehicle. The ultrahigh sensitivity of 67.3 mV deg−1 and outstanding linearity between the output voltage and rotation angle are obtained. Moreover, an instantaneous response within 20 ms can be observed during the process when gradually increasing the rotation angle from 0° to 260°. By lighting up different light‐emitting diode patterns representing certain rotation angles, demonstrations on quantitative sensing alerts are also realized. The SGAS can operate without batteries or monitoring circuits, accompanied with excellent reliability and sensitivity, which is favorable for future automatic navigation control systems.
Growth and Structure of Strong Pockels Material Strontium Barium Niobate on SrTiO3and Si by Molecular Beam Epitaxy
Authors: Beskin Ilya M. , Kwon Sunah , Posadas Agham B. , Kim Moon J. , Demkov Alexander A.
Published: August 2021

Strontium barium niobate (SrxBa1–xNb2O6, referred to as SBN) is a material of interest for making efficient optical modulators due to its very high electro‐optic (EO or Pockels) coefficient. SBN is a ferroelectric with a Curie temperature that varies between 20 and 80 °C, depending on its Sr/Ba ratio. Structurally, it belongs to the tetragonal tungsten bronze family. The successful integration of SBN on Si in textured epitaxial form using molecular beam epitaxy via a SrTiO3(STO) buffer layer is reported. X‐ray diffraction and scanning transmission electron microscopy are used to analyze the crystalline quality, STO/SBN interface structure, and preferred orientations of the SBN film. Thin, highly oriented SBN films integrated on Si have potential applications in low power and small footprint integrated Si photonics.
Machine Learning Assisted Prediction of Cathode Materials for Zn‐Ion Batteries
Authors: Zhou Linming , Yao Archie Mingze , Wu Yongjun , Hu Ziyi , Huang Yuhui , Hong Zijian
Published: August 2021

Rechargeable Zn batteries with aqueous electrolytes have been considered as promising alternative energy storage technology, with various advantages such as low cost, high volumetric capacity, environmentally friendly, and high safety. However, a lack of reliable cathode materials has largely pledged their applications. Herein, a machine learning (ML)‐based approach to predict cathodes with high capacity (>100 mAh g−1) and high voltage (>0.5 V) is developed. Over ≈130 000 inorganic materials from the materials project database are screened and the crystal graph convolutional neural network based ML approach is applied with data from the AFLOW database, the combination of these two gives rise to ≈80 predicted cathode materials. Among them, ≈10 cathode materials have been experimentally discovered previously, which agrees remarkably well with experimental measurements, while ≈70 new promising candidates have been predicted for further experimental validations. The authors hope this study could spur further interests in ML‐based advanced theoretical tools for battery materials discovery.
Unusual Temperature Dependence of Bandgap in 2D Inorganic Lead‐Halide Perovskite Nanoplatelets
Authors: Yu Shaohua , Xu Jin , Shang Xiaoying , Ma En , Lin Fulin , Zheng Wei , Tu Datao , Li Renfu , Chen Xueyuan
Published: August 2021

Understanding the origin of temperature‐dependent bandgap in inorganic lead‐halide perovskites is essential and important for their applications in photovoltaics and optoelectronics. Herein, it is found that the temperature dependence of bandgap in CsPbBr3 perovskites is variable with material dimensionality. In contrast to the monotonous redshift ordinarily observed in bulk‐like CsPbBr3 nanocrystals (NCs), the bandgap of 2D CsPbBr3 nanoplatelets (NPLs) exhibits an initial blueshift then redshift trend with decreasing temperature (290–10 K). The Bose–Einstein two‐oscillator modeling manifests that the blueshift‐redshift crossover of bandgap in the NPLs is attributed to the significantly larger weight of contribution from electron‐optical phonon interaction to the bandgap renormalization in the NPLs than in the NCs. These new findings may gain deep insights into the origin of bandgap shift with temperature for both fundamentals and applications of perovskite semiconductor materials.
Neuron‐Inspired Steiner Tree Networks for 3D Low‐Density Metastructures
Authors: Yu Haoyi , Zhang Qiming , Cumming Benjamin P. , Goi Elena , Cole Jared H. , Luan Haitao , Chen Xi , Gu Min
Published: August 2021

Three‐dimensional (3D) micro‐and nanostructures have played an important role in topological photonics, microfluidics, acoustic, and mechanical engineering. Incorporating biomimetic geometries into the design of metastructures has created low‐density metamaterials with extraordinary physical and photonic properties. However, the use of surface‐based biomimetic geometries restricts the freedom to tune the relative density, mechanical strength, and topological phase. The Steiner tree method inspired by the feature of the shortest connection distance in biological neural networks is applied, to create 3D metastructures and, through two‐photon nanolithography, neuron‐inspired 3D structures with nanoscale features are successfully achieved. Two solutions are presented to the 3D Steiner tree problem: the Steiner tree networks (STNs) and the twisted Steiner tree networks (T‐STNs). STNs and T‐STNs possess a lower density than surface‐based metamaterials and that T‐STNs have Young's modulus enhanced by 20% than the STNs. Through the analysis of the space groups and symmetries, a topological nontrivial Dirac‐like conical dispersion in the T‐STNs is predicted, and the results are based on calculations with true predictive power and readily realizable from microwave to optical frequencies. The neuron‐inspired 3D metastructures opens a new space for designing low‐density metamaterials and topological photonics with extraordinary properties triggered by a twisting degree‐of‐freedom.
Tight Junction ZO Proteins Maintain Tissue Fluidity, Ensuring Efficient Collective Cell Migration
Authors: Skamrahl Mark , Pang Hongtao , Ferle Maximilian , Gottwald Jannis , Rübeling Angela , Maraspini Riccardo , Honigmann Alf , Oswald Tabea A. , Janshoff Andreas
Published: August 2021

Tight junctions (TJs) are essential components of epithelial tissues connecting neighboring cells to provide protective barriers. While their general function to seal compartments is well understood, their role in collective cell migration is largely unexplored. Here, the importance of the TJ zonula occludens (ZO) proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss (dKD) induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug‐of‐war emerges between two subpopulations of cells with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outward bulging apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding‐induced jamming and more small cells over time. Co‐cultures comprising wildtype and dKD cells migrate inefficiently due to phase separation based on differences in contractility rather than differential adhesion. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.
N2‐Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle
Authors: Cai Bolei , Lin Dan , Li Yan , Wang Le , Xie Jirong , Dai Taiqiang , Liu Fuwei , Tang Mingyue , Tian Lei , Yuan Yuan , Kong Liang , Shen Steve G. F.
Published: August 2021

The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin‐8 (IL‐8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL‐8, during which neutrophils are recruited to the implanted site and are N2‐polarized, which then secrete stromal cell‐derived factor‐1α (SDF‐1α) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF‐1/CXCR4 (C‐X‐C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'‐kinase (PI3K)/Akt pathway and β‐catenin‐mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil‐initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.
Ten Years of EWAS
Authors: Wei Siyu , Tao Junxian , Xu Jing , Chen Xingyu , Wang Zhaoyang , Zhang Nan , Zuo Lijiao , Jia Zhe , Chen Haiyan , Sun Hongmei , Yan Yubo , Zhang Mingming , Lv Hongchao , Kong Fanwu , Duan Lian , Ma Ye , Liao Mingzhi , Xu Liangde , Feng Rennan , Liu Guiyou , Project The EWAS , Jiang Yongshuai
Published: August 2021

Epigenome‐wide association study (EWAS) has been applied to analyze DNA methylation variation in complex diseases for a decade, and epigenome as a research target has gradually become a hot topic of current studies. The DNA methylation microarrays, next‐generation, and third‐generation sequencing technologies have prepared a high‐quality platform for EWAS. Here, the progress of EWAS research is reviewed, its contributions to clinical applications, and mainly describe the achievements of four typical diseases. Finally, the challenges encountered by EWAS and make bold predictions for its future development are presented.
Low‐Intensity Focused Ultrasound‐Responsive Ferrite‐Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics
Authors: Yao Jianting , Yang Zhuowen , Huang Liandi , Yang Chao , Wang Jianxin , Cao Yang , Hao Lan , Zhang Liang , Zhang Jingqi , Li Pan , Wang Zhigang , Sun Yang , Ran Haitao
Published: August 2021

Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium‐mediated sonodynamic therapy (DVDMS‐SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging‐guided SDT in plaque angiogenesis theranostics, termed PFP–HMME@PLGA/MnFe2O4–ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe2O4), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid‐glycolic acid (PLGA) shells and is conjugated to an anti‐VEGFR‐2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP‐mediated SDT promotes mitochondrial‐caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP‐mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP‐mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP‐mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.
Humanized Biomimetic Nanovesicles for Neuron Targeting
Authors: Zinger Assaf , Cvetkovic Caroline , Sushnitha Manuela , Naoi Tomoyuki , Baudo Gherardo , Anderson Morgan , Shetty Arya , Basu Nupur , Covello Jennifer , Tasciotti Ennio , Amit Moran , Xie Tongxin , Taraballi Francesca , Krencik Robert
Published: August 2021

Nanovesicles (NVs) are emerging as innovative, theranostic tools for cargo delivery. Recently, surface engineering of NVs with membrane proteins from specific cell types has been shown to improve the biocompatibility of NVs and enable the integration of functional attributes. However, this type of biomimetic approach has not yet been explored using human neural cells for applications within the nervous system. Here, this paper optimizes and validates the scalable and reproducible production of two types of neuron‐targeting NVs, each with a distinct lipid formulation backbone suited to potential therapeutic cargo, by integrating membrane proteins that are unbiasedly sourced from human pluripotent stem‐cell‐derived neurons. The results establish that both endogenous and genetically engineered cell‐derived proteins effectively transfer to NVs without disruption of their physicochemical properties. NVs with neuron‐derived membrane proteins exhibit enhanced neuronal association and uptake compared to bare NVs. Viability of 3D neural sphere cultures is not disrupted by treatment, which verifies the utility of organoid‐based approaches as NV testing platforms. Finally, these results confirm cellular association and uptake of the biomimetic humanized NVs to neurons within rodent cranial nerves. In summary, the customizable NVs reported here enable next‐generation functionalized theranostics aimed to promote neuroregeneration.
New Methods for the Functionalization of Polymer Matrices with Thiomolybdate Clusters Applied for Hydrogen Evolution Reaction Catalysis
Authors: Hannewald Nadine , Hniopek Julian , Heiland Magdalena , Zechel Stefan , Schmitt Michael , Streb Carsten , Popp Jürgen , Hager Martin D. , Schubert Ulrich S.
Published: August 2021

The embedding of molecular reactive species such as catalysts into polymers opens up new avenues for advanced composite design for energy technologies and beyond. Herein, two new approaches for the connection of molecular molybdenum sulfide clusters and synthetic polymers are presented. The approach one is based on the utilization of a molecular molybdenum sulfide cluster as a potential chain transfer agent in a free radical polymerization process. The second one is a postpolymerization functionalization of a thiol end‐functionalized polymer with a thiomolybdate cluster. Detailed characterization using Raman spectroscopy reveals the successful functionalization in the latter approach, whereas in the other one, a noncovalent interaction is suggested. Furthermore, visible light‐driven hydrogen evolution demonstrates that the molecular molybdenum sulfide cluster retains its catalytic activity after the combination with polymers.
Increasing Accuracy of In Vitro Cancer Models: Engineering Stromal Complexity into Tumor Organoid Platforms
Authors: Chakraborty Srija , DePalma Thomas J. , Skardal Aleksander
Published: August 2021

Cancer is a life‐threatening disease, and even upon successful treatment, recurrence often occurs. A wide variety of preclinical models exist to effectively study cancer and design more efficient treatments. However, a majority of cancer models cannot accurately recapitulate cancer as it exists in humans. Animal models physiologically differ from humans. In vitro models, such as organoids, allow construction with human‐based components, but most fail to accurately mimic the overall tumor microenvironment (TME), which is composed of stromal and immune cells, as well as a complex extracellular matrix (ECM). However, more recent versions of these in vitro tumor models are increasingly complex and include both engineered ECM and the bidirectional, biomolecular crosstalk between different stromal cell components, particularly fibroblasts which are key players in the TME. Therefore, studying these components gives a more detailed insight into how tumors develop, interface with surrounding stromal and tissue architecture, and respond to therapies. Herein, a range of in vitro tumor model form factors is described, and the role of fibroblasts and ECM in cancer is also discussed, with a focus on how their inclusion in bioengineered in vitro and ex vivo tumor models better recapitulate the physiological complexities of cancer.
Das erste Hochdruck‐Chromoxonitridoborat CrB4O6N – ein unerwartetes Bindeglied zur Chemie der Nitridosilikate
Authors: Fuchs Birgit , Johrendt Dirk , Bayarjargal Lkhamsuren , Huppertz Hubert
Published: August 2021

CrB4O6N kristallisiert in der nicht‐zentrosymmetrischen Raumgruppe P63mc (Nr. 186) mit den Gitterparametern a=5.1036(1), c=8.3519(3) Å und einem Volumen von 188,40(1) Å3. Synthetisiert durch ein Hochdruck‐/Hochtemperaturexperiment bei 7 GPa und 1673 K, repräsentiert die Phase das erste Hochdruck‐Oxonitridoborat. Strukturell zeigen sich sternförmige Einheiten bestehend aus vier BO3N‐Tetraedern, die in Analogie zu den homeotypen Nitridosilikaten MYbSi4N7 (M=Sr, Ba, Eu) durch ein gemeinsames vierfach koordiniertes Stickstoffatom miteinander verknüpft sind. Diese Einheiten bilden ein Netzwerk aus, in dessen Kanälen die Cr3+‐Ionen liegen. Im Gegensatz zu den trigonal‐planaren B(O/N)3‐Einheiten in allen anderen bekannten Oxonitridoboraten zeigt CrB4O6N erstmals tetraedrische Baueinheiten. Die strukturellen Zusammenhänge sowie die Ergebnisse der spektroskopischen Messungen und theoretischen Rechnungen am Chromoxonitridoborat werden im Folgenden erörtert.
Creating safe schools by building safe relationships
Authors: Eppler‐Wolff Nancy , Martin Anne
Published: August 2021

Jonathan Cohen outlines three types of goals for schools to pursue—systemic improvement goals, instructional improvement goals, and relational improvement goals—but states that it is impractical to expect schools to address all three at once. This study argues that it is in fact essential that relational improvement goals be pursued concomitantly with systemic and instructional improvement goals in order for the latter to succeed. Several foundational psychoanalytic precepts used to build the patient–therapist alliance apply well to building relationships with stakeholders within a school context, ranging from students and parents to teachers and leaders. We present our own experience implementing the School‐Based Mental Health Collaboration (SBMHC) in a handful of public elementary schools in high‐poverty neighborhoods in New York City. This program relies on classroom consultants who spend a half day a week in an assigned classroom co‐teaching a social–emotional learning (SEL) curriculum; consulting with teachers about students, classroom management, and the integration of SEL into the classroom culture; and referring children for community‐based services. SBMHC staff take a mentalizing stance of nonjudgmental curiosity about the meaning and function of stakeholders' behaviors, while encouraging stakeholders to do the same with each other. This approach builds strong relationships in which stakeholders can reflect safely and thoughtfully about their own behaviors and that of their students. We find that it is within this “holding environment” that school stakeholders are best poised to undertake the difficult attitudinal and behavioral changes necessary to promote school safety.
Red Bean Pod Derived Heterostructure Carbon Decorated with Hollow Mixed Transition Metals as a Bifunctional Catalyst in Zn‐Air Batteries
Authors: Mahbub Muhammad Adib Abdillah , Adios Celfi Gustine , Xu Michael , Prakoso Bagas , LeBeau James M. , Sumboja Afriyanti
Published: August 2021

Design and synthesis of low‐cost and efficient bifunctional catalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in Zn‐air batteries are essential and challenging. We report a facile method to synthesize heterostructure carbon consisting of graphitic and amorphous carbon derived from the agricultural waste of red bean pods. The heterostructure carbon possesses a large surface area of 625.5 m2 g−1, showing ORR onset potential of 0.89 V vs. RHE and OER overpotential of 470 mV at 5 mA cm−2. Introducing hollow FeCo nanoparticles and nitrogen dopant improves the bifunctional catalytic activity of the carbon, delivering ORR onset potential of 0.93 V vs. RHE and OER overpotential of 360 mV. Electron energy‐loss spectroscopy (EELS) O K‐edge map suggests the presence of localized oxygen on the FeCo nanoparticles, suggesting the oxidation of the nanoparticles. Zn‐air battery with these carbon‐based catalysts exhibits a peak power density as high as 116.2 mW cm−2 and stable cycling performance over 210 discharge/charge cycles. This work contributes to the advancement of bifunctional oxygen electrocatalysts while converting agricultural waste into value‐added material.
Determining the optimal PD‐1/PD‐L1 inhibitors for the first‐line treatment of non‐small‐cell lung cancer with high‐level PD‐L1 expression in China
Authors: Teng Meng‐Meng , Chen Si‐Ying , Yang Bo , Wang Yan , Han Rui‐Ying , An Meng‐Na , Dong Ya‐lin , You Hai‐Sheng
Published: August 2021

Background and Objective

The programmed death 1 and ligand (PD‐1/PD‐L1) inhibitors have significantly altered therapeutic perspectives on non‐small‐cell lung cancer (NSCLC). However, their efficacy and safety are unknown since direct clinical trials have not yet been performed on them. It is also necessary to determine the economics of PD‐1/PD‐L1 inhibitors due to their high cost. The aim was to evaluate the efficacy, safety, and cost‐effectiveness of PD‐1/PD‐L1 inhibitor monotherapy for advanced NSCLC patients in China with high PD‐L1 expression as first‐line treatment.

Methods

From the PubMed, Cochrane, and Web of Science databases, we retrieved survival, progression, and safety data on PD‐1/PD‐L1 inhibitor monotherapy for advanced NSCLC patients. A network meta‐analysis (NMA) was performed to consider PD‐1/PD‐L1 inhibitors in efficacy and safety. A Markov model with a full‐lifetime horizon was adopted. Clinical and utility data were collected through the trial. The cost per quality‐adjusted life year (QALY) was as incremental cost‐effectiveness ratio (ICER). Sensitivity analyses were performed.

Results

This study included five phase III clinical trials using four drugs: nivolumab, pembrolizumab, atezolizumab, and durvalumab. The NMA demonstrated that the four drugs had similar efficacy and safety, while pembrolizumab and atezolizumab were better for than for nivolumab (hazard ratio (HR) = 0.66, 95% confidence intervals (CIs): 0.46–0.95 and HR = 0.59, 95%CI: 0.37–0.94) in progression‐free survival (PFS), and the risk of a severe adverse event was higher for atezolizumab than for nivolumab and pembrolizumab. Compared with nivolumab, durvalumab, pembrolizumab, and atezolizumab had QALY of 0.19, 0.38, and 0.53, respectively, which induced ICERs of $ 197,028.8/QALY, $ 111,859.0/QALY, and $ 76,182.3/QALY, respectively.

Conclusion

The efficacy and safety are similar among types of PD‐1/PD‐L1‐inhibitor monotherapy. The cost‐effectiveness of nivolumab appears optimal, but the other PD‐1/PD‐L1 inhibitors are not as cost‐effective for the first‐line treatment of advanced NSCLC in China.
Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer
Authors: Szlosarek Peter W. , Wimalasingham Akhila G. , Phillips Melissa M. , Hall Peter E. , Chan Pui Ying , Conibear John , Lim Louise , Rashid Sukaina , Steele Jeremy , Wells Paula , Shiu Chiung‐Fang , Kuo Chih‐Ling , Feng Xiaoxing , Johnston Amanda , Bomalaski John , Ellis Stephen , Grantham Marianne , Sheaff Michael
Published: August 2021

Introduction

We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient non‐squamous non‐small cell lung cancer (NSCLC) via a phase 1 dose‐expansion trial with exploratory biomarker analysis.

Methods

Sixty‐seven chemonaïve patients with advanced non‐squamous NSCLC were screened, enrolling 21 ASS1‐deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36 mg/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry.

Results

ADIPemCis was well‐tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n = 18/21; 95% CI 63.7%–97%), with a partial response rate of 47.6% (n = 10/21; 95% CI 25.7%–70.2%). The median progression‐free and overall survivals were 4.2 (95% CI 2.9–4.8) and 7.2 (95% CI 5.1–18.4) months, respectively. Two PD‐L1‐expressing (≥1%) patients are alive following subsequent pembrolizumab immunotherapy (9.5%). Tumoral ASS1 deficiency enriched for p53 (64.7%) mutations, and numerically worse median overall survival as compared to ASS1‐proficient disease (10.2 months; n = 29). There was no apparent increase in KRAS mutations (35.3%) and PD‐L1 (<1%) expression (55.6%). Re‐expression of tumoral ASS1 was detected in one patient at progression (n = 1/3).

Conclusions

ADIPemCis was safe and highly active in patients with ASS1‐deficient non‐squamous NSCLC, however, survival was poor overall. ASS1 loss was co‐associated with p53 mutations. Therapies incorporating pegargiminase merit further evaluation in ASS1‐deficient and treatment‐refractory NSCLC.
Isolation of the canine inhibin βB subunit gene and characterization of signalling mediated by canine inhibin βB
Authors: Sakota Shotaro , Shimokawa Fumie , Funaba Masayuki , Murakami Masaru
Published: August 2021

Activin B, a homodimer of the inhibin βB subunit, acts as a regulator of gonadal function and as an adipokine. To clarify the role of activin B in dogs, we characterized the canine inhibin βB gene and signalling pathways regulated by the canine inhibin βB. Using 5′‐ and 3′‐rapid amplification of cDNA end (RACE) and RT‐PCR on RNA isolated from the ovary of dogs, we identified short and long forms of the inhibin βB gene. Immunoreactive inhibin βB molecules were detected at ~25 and ~14 kDa under nonreducing and reducing conditions, respectively, in culture supernatants from HEK293 cells transfected with a plasmid containing the long form of the inhibin βB gene, indicating activin B production and secretion. Similar to human and murine activin B, the canine activin B‐stimulated transcriptions of reporter genes, CAGA‐luc and Hepcidin‐luc, regulated by the canonical activin/transforming growth factor‐β (TGF‐β) and bone morphogenetic protein (BMP) pathway, respectively. Activin B‐induced CAGA‐luc transcription was not detected in ALK7‐deficient MDCK canine‐derived cells; however, the forced expression of ALK7 resulted in the activin B‐dependent expression in MDCK cells. Unexpectedly, the activin B‐induced activation of the BMP pathway was partially blocked by the inhibition of endogenous activin/TGF‐β receptor activity. The present study identified an experimentally isolated long form of the canine inhibin βB gene producing activin B that transactivates BMP‐ and activin/TGF‐β‐regulated gene expression.
The contribution of psychological assessment to systemic racism
Authors: Walters Anne S.
Published: August 2021

As we continue our journey toward a more just and inclusive society, it is critical to examine contributions of our typical practices in psychology and psychiatry to systemic racism. To this end, psychologists have long been aware that our standards of assessment are potentially problematic when applied to BIPOC populations and there is long‐standing caution as part of our training about the potential lack of racially and ethnically diverse norms for many forms of assessment. At least some of the time, we can find alternatives that minimize bias, and we can educate others about the potential misuses when we cannot. Is this enough? How else can we be more active in challenging misuses of IQ and educational assessment that contribute to disparities in education and achievement for our children?
Progress of the Catalytic Deactivation of H‐ZSM‐5 Zeolite in Glycerol Dehydration
Authors: Catuzo Gabriel L. , Possato Luiz G. , Sad María Eugenia , Padró Cristina , Martins Leandro
Published: August 2021

Glycerol conversion into value‐added chemicals has received much attention due to the prospect of increasing the biodiesel industry‘s profitability. The dehydration of glycerol is one of the most explored reactions in the valorization of glycerol, and the zeolite H‐ZSM‐5 is one of the furthermost used structures. In this study, several characterization techniques were used to investigate the detailed aging of coke in spent H‐ZSM‐5 zeolites after their use in the gas‐phase glycerol dehydration to produce acrolein. The carbonaceous deposits formed almost totally in the first minutes of the reaction. They rapidly got trapped inside the pores, hampering the accessibility to active sites and the zeolite‘s full catalytic action. Two types of coke were formed during the reaction: polyglycols, on the external surface, and aromatics, inside the pores, representing the majority (∼98 wt.%) of the carbonaceous compounds. Besides, aromatic compounds age over time, becoming bulkier and more deficient in hydrogen. We also found a correlation between the amount of coke, its size, accessibility to the acid active sites, and changes in crystallographic parameters of the zeolite with the presence of coke.
Adsorption of Brilliant Blue and Malachite Green by Nano‐graphene Exfoliated from Waste Batteries
Authors: Karunanithi Bogeshwaran , Kannaiyan Sathish Kumar , Balakrishnan Karunanithi , Muralidharan Srividhya , Gopi Gowri
Published: August 2021

Waste graphite rods from waste batteries, acting as a source of graphite, were electrochemically exfoliated to synthesize graphene. Mesoporous graphene with a pore size of 14.81 Å and a surface area of 710.396 m2g−1 was chosen for adsorptive studies involving toxic dyes, Brilliant Blue (BB) and Malachite Green (MG), by varying the graphene dosage, contact period, temperature, pH, and the concentration of the dye solution. The maximum adsorption capacities reported were 120 mg gBB−1 and 342 mg gMG−1, with dye removal rates of BB and MG greater than 99 and 98 %, respectively. Adsorption occurred as multilayer, following the Freundlich isotherm model, and the pseudo‐second‐order kinetic model fitted best, indicating chemisorption. Thermodynamic studies reveal an exothermic, spontaneous, and chemical adsorption.
One‐Pot Synthesis of Tensile‐Strained PdRuCu Icosahedra toward Electrochemical Hydrogenation of Alkene
Authors: Zhu Kaili , Xu Xudong , Xu Mengqiu , Deng Ping , Wu Wenbo , Ye Wei , Weng Zihui , Su Yue , Wang Huijie , Xiao Fei , Fang Zeping , Gao Peng
Published: August 2021

Electrochemical hydrogenation (ECH) uses electricity to drive proton (H+) reduction for hydrogenation, which can greatly reduce energy supply and environmental pollution, representing an ideal alternative to traditional thermal hydrogenation. In this work, we put forward tensile‐strained PdRuCu alloy to promote ECH. Tensile strain promotes the adsorption of C=C by changing the d‐band center. Meanwhile, alloying Ru and Cu into Pd lattice facilitates hydrogenation by weakening Pd−H bonding. Therefore, PdRuCu icosahedra display excellent ECH performance of 2‐methyl‐3‐buten‐2‐ol (MBE) with specific activity of 227.4 μmolMBE nm−2 min−1 at −0.3 V versus reversible hydrogen electrode (RHE), about 16.1 and 10.5 times higher than that of commercial Pd/C and Ru/C, respectively. In addition, PdRuCu icosahedra was excellent in the scaling up of substrate concentration combined with anisyl alcohol oxidation to produce high‐value added anisaldehyde at anode. This work provides a guideline for the rational design of highly active and durable metallic catalyst in ECH.
Amylopectin graft copolymers for oil sands tailings treatment
Authors: Davey Stepheney , Soares João B. P.
Published: August 2021

The oil sands industry has contributed to the Canadian economy for over 50 years. Challenges have arisen, however, due to worldwide concerns regarding the long‐term environmental impact of waste by‐products generated in the bitumen extraction process from oil sands. Reclaiming legacy tailings and reducing the number of ponds are two of these challenges. This article describes the synthesis and characterization of amylopectin‐graft‐hydrolyzed‐poly(methyl acrylate) copolymers with different graft lengths and densities, and how they can be used to treat oil sands tailings. Flocculation and dewatering results depend strongly on how the hydrophobic amylopectin backbones are combined with the hydrophilic hydrolyzed poly(methyl acrylate) grafts. These hybrid polymers, combining a natural backbone with synthetic grafts, seem to be an attractive alternative to treat oil sands and probably other mineral ore tailings.
Catalytic Hydrogen Transfer Reactions
Authors: Zhu Shou‐Fei
Published: August 2021

Our recently studies on three types of reactions with hydrogen transfer as a key step, including catalytic asymmetric proton transfer reactions using “chiral proton transfer shuttle”, catalytic B—H bond insertion containing a hydrogen atom transfer, and iron‐catalyzed hydrosilylation reactions containing hydride transfer were briefly introduced.

What is the most favorite and original chemistry developed in your research group?

The discovery of B—H bond insertion reaction.

How do you get into this specific field? Could you please share some experiences with our readers?

The reaction of B—H bond insertion was a serendipitous result during we pursuing the other carbene insertion reactions. My lesson on this project is that the discovery may come from bold hypothesis, cautious verification, and appropriate evaluation on unexpected results.

How do you supervise your students?

Try my best to stimulate their enthusiasm for innovation, provide them strongest supports, and explore unknown with them as a partner.

What is the most important personality for scientific research?

Passion for self‐actualization and curiosity.

How do you keep balance between research and family?

Travel with my family regularly and try to share my research progresses with them.
Persistent human bocavirus 1 infection and tonsillar immune responses
Authors: Ivaska Lotta E. , Silvoniemi Antti , Palomares Oscar , Turunen Riitta , Waris Matti , Mikola Emilia , Puhakka Tuomo , Söderlund‐Venermo Maria , Akdis Mübeccel , Akdis Cezmi A. , Jartti Tuomas
Published: August 2021

Background

Persistent human bocavirus 1 (HBoV1) infection is a common finding in patients suffering from chronic tonsillar disease. However, the associations between HBoV1 infection and specific immune reactions are not completely known. We aimed to compare in vivo expression of T‐cell cytokines, transcription factors, and type I/III interferons in human tonsils between HBoV1‐positive and ‐negative tonsillectomy patients.

Methods

Tonsil tissue samples, nasopharyngeal aspirate (NPA), and serum samples were obtained from 143 immunocompetent adult and child tonsillectomy patients. HBoV1 and 14 other respiratory viruses were detected in NPAs and tonsil tissues by polymerase chain reaction (PCR). Serology and semi‐quantitative PCR were used for diagnosing HBoV1 infections. Expression of 14 cytokines and transcription factors (IFN‐α, IFN‐β, IFN‐γ, IL‐10, IL‐13, IL‐17, IL‐28, IL‐29, IL‐37, TGF‐β, FOXP3, GATA3, RORC2, Tbet) was analyzed by quantitative reverse‐transcription (RT)‐PCR in tonsil tissues.

Results

HBoV1 was detected by PCR in NPA and tonsils from 25 (17%) study patients. Serology results indicated prior nonacute infections in 81% of cases. Tonsillar cytokine responses were affected by HBoV1 infection. The suppression of two transcription factors, RORC2 and FOXP3, was associated with HBoV1 infection (p < 0.05). Furthermore, intratonsillar HBoV1‐DNA loads correlated negatively with IFN‐λ family cytokines and IL‐13.

Conclusions

Our study shows distinctively decreased T‐helper17 and T‐regulatory type immune responses in local lymphoid tissue in HBoV1‐positive tonsillectomy patients. HBoV1 may act as a suppressive immune modulator.
Luminance contrast detection is optimized for the large‐scale luminance texture of the surround
Authors: Hayasaka Misaki , Nagai Takehiro , Yamauchi Yasuki , Sato Tomoharu , Kuriki Ichiro
Published: August 2021

Contrast sensitivity functions (CSFs) have been typically measured under persistent adaptation to a uniform background. However, this is an unusual situation, considering that visual scenes in our daily lives are typically filled by objects of various luminance levels in a wide dynamic range. We investigated the interactions between the luminance range of textured adapting background and test luminance (luminance of an immediate surround) to see how the contrast sensitivities adapt to background luminance distributions. The background was a random array of one‐dimensional lines, which had a maximum luminance range of approximately 1:520 000, and the test stimulus was a Gabor patch presented on an immediate uniform surround with various luminance levels. The carrier orientation of the Gabor patch was orthogonal to that of the background lines. In the results, the sensitivity was highest near the mean of background luminance, and the luminance range with the highest sensitivity became wider (i.e., the selectivity of sensitivity optimization weakened) as the background luminance range became larger. This sensitivity optimization was significant mainly in the lower spatial frequency. These results indicate that the overall contrast sensitivity is adjusted to the luminance range of the visual scene and the sensitivity optimization is more flexible in relatively lower spatial frequency.
An advanced hybrid algorithm for nonlinear function optimization with real world applications
Authors: Verma Pooja , Parouha Raghav Prasad
Published: August 2021

This article presents an advanced hybrid algorithm (haDEPSO) for nonlinear constrained function optimization problem. It consists of the advised advanced differential evolution, that is, aDE (wherein a novel mutation, crossover, and selection strategy is introduced, to avoid premature convergence) and particle swarm optimization, namely, aPSO (in which novel gradually varying parameters is utilized, to escape stagnation). The proposedhaDEPSO achieve better results as aDE and aPSO provides diverse convergence characteristic to the solution space. Moreover, inhaDEPSO distinct population is merged with other in a predefined way, to balance between exploration and exploitation. Efficiency of the proposed hybridhaDEPSO along with its integrating component aDE and aPSO are inspected on IEEE CEC'2006 constrained benchmark functions and IEEE CEC'2011 real world problems. According to the comparison results, the proposed methods achieved better results than traditional DE and PSO with their hybrids as well as over many state‐of‐the‐art algorithms.
Investigation of Factors Associated With Immunogenicity Labeling Updates and Characteristics of Biologics License Applications
Authors: Jiang Ai‐Lei , Breder Christopher D. , Chang Lin‐Chau
Published: August 2021

Immunogenicity, the potential to elicit an antidrug immune response, is a critical concern in developing biological products, but its consequences are difficult to predict with animal studies. The aims of the present study are to investigate the evolution of immunogenicity information in labeling and to identify attributes associated with immunogenicity labeling updates. Biologics License Applications (BLAs) approved by the Center for Drug Evaluation and Research, US Food and Drug Administration between 2008 and 2017 were studied. A majority of BLAs described the incidence/prevalence of antidrug antibodies (ADAs) (94.9%) and neutralizing antibodies (NAbs) (68.4%) in their original labeling documents. However, less than one third of the BLAs mentioned the impact of ADAs/NAbs in the original (20.3%) and most recent (29.1%) labeling documents. BLAs with a priority review status (57.4% vs. 33.3%), orphan designation (61.5% vs. 34.2%), or a mention of ADA impact in the latest label (69.6% vs. 38.9%) had higher percentages of applications with postmarketing requirements (PMRs) directly related to immunogenicity concerns in comparison with applications without those characteristics. Among the BLAs with updated immunogenicity information, the mean time to the first update was 1,077 days, while that for BLAs with accelerated approval was shorter (709.1 ± 492.2 days vs. 1173.8 ± 661.8 days). The results suggest that there is a substantial amount of critical information lacking in the original labeling documents and an overdependence on PMRs for more evidence. Additional efforts should be made to investigate the impact of ADAs to provide timely information for improved patient care.
Effect of Intralipid infusion on peripheral blood T cells and plasma cytokines in women undergoing assisted reproduction treatment
Authors: Foyle Kerrie L , Sharkey David J , Moldenhauer Lachlan M , Green Ella S , Wilson Jasmine J , Roccisano Cassandra J , Hull M Louise , Tremellen Kelton P , Robertson Sarah A
Published: August 2021

Objectives

Intravenous infusion of Intralipid is an adjunct therapy in assisted reproduction treatment (ART) when immune‐associated infertility is suspected. Here, we evaluated the effect of Intralipid infusion on regulatory T cells (Treg cells), effector T cells and plasma cytokines in peripheral blood of women undertaking IVF.

Methods

This prospective, observational pilot study assessed Intralipid infusion in 14 women exhibiting recurrent implantation failure, a clinical sign of immune‐associated infertility. Peripheral blood was collected immediately prior to and 7 days after intravenous administration of Intralipid. Plasma cytokines were measured by Luminex, and T‐cell subsets were analysed by flow cytometry.

Results

A small increase in conventional CD8+ T cells occurred after Intralipid infusion, but no change was seen in CD4+ Treg cells, or naïve, memory or effector memory T cells. Proliferation marker Ki67, transcription factors Tbet and RORγt, and markers of suppressive capacity CTLA4 and HLA‐DR were unchanged. Dimensionality‐reduction analysis using the tSNE algorithm confirmed no phenotype shift within Treg cells or other T cells. Intralipid infusion increased plasma CCL2, CCL3, CXCL8, GM‐CSF, G‐CSF, IL‐6, IL‐21, TNF and VEGF.

Conclusion

Intralipid infusion elicited elevated pro‐inflammatory cytokines, and a minor increase in CD8+ T cells, but no change in pro‐tolerogenic Treg cells. Notwithstanding the limitation of no placebo control, the results do not support Intralipid as a candidate intervention to attenuate the Treg cell response in women undergoing ART. Future placebo‐controlled studies are needed to confirm the potential efficacy and clinical significance of Intralipid in attenuating cytokine induction and circulating CD8+ T cells.