bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Pyridine–Pyridone Foldamer Channels as M2‐Like Artificial Proton Channels
Authors: Shen Jie , Ye Ruijuan , Liu Zhiwei , Zeng Huaqiang
Published: April 2022

Currently, completely abiotic channel systems that concurrently reproduce the high selectivity and high permeation rate of natural protein channels are rare. Here, we provide one such biomimetic channel system, i.e., a novel family of helically folded hybrid amide foldamers that can serve as powerful artificial proton channels to mimic key transport features of the exceptionally selective Matrix‐2 (M2) proton channels. Possessing an angstrom‐scale tubular pore 3 Å in diameter, these low water permeability artificial channels transport protons at a rate 1.22 and 11 times as fast as gramicidin A and M2 channels, respectively, with exceptionally high selectivity factors of 167.6, 122.7, and 81.5 over Cl−, Na+, and K+ ions. Based on the experimental and computational findings, we propose a novel proton transport mechanism where a proton may create a channel‐spanning water chain from two or more short water chains to facilitate its own transmembrane flux via the Grotthuss mechanism.
Molecular Iron Oxide Clusters Boost the Oxygen Reduction Reaction of Platinum Electrocatalysts at Near‐Neutral pH
Authors: Lv Jia‐Qi , Lang Zhong‐Ling , Fu Jia‐Qi , Lan Qiao , Liu Rongji , Zang Hong‐Ying , Li Yang‐Guang , Ye Ding‐Ding , Streb Carsten
Published: April 2022

The oxygen reduction reaction (ORR) is a key energy conversion process, which is critical for the efficient operation of fuel cells and metal–air batteries. Here, we report the significant enhancement of the ORR‐performance of commercial platinum‐on‐carbon electrocatalysts when operated in aqueous electrolyte solutions (pH 5.6), containing the polyoxoanion [Fe28(μ3‐O)8(L‐(−)‐tart)16(CH3COO)24]20−. Mechanistic studies provide initial insights into the performance‐improving role of the iron oxide cluster during ORR. Technological deployment of the system is demonstrated by incorporation into a direct formate microfluidic fuel cell (DFMFC), where major performance increases are observed when compared with reference electrolytes. The study provides the first examples of iron oxide clusters in electrochemical energy conversion and storage.
Discrete, Cationic Palladium(II)‐Oxo Clusters via f‐Metal Ion Incorporation and their Macrocyclic Host‐Guest Interactions with Sulfonatocalixarenes
Authors: Bhattacharya Saurav , Barba‐Bon Andrea , Zewdie Tsedenia A. , Müller Anja B. , Nisar Talha , Chmielnicka Anna , Rutkowska Iwona A. , Schürmann Christian J. , Wagner Veit , Kuhnert Nikolai , Kulesza Pawel J. , Nau Werner M. , Kortz Ulrich
Published: April 2022

We report on the discovery of the first two examples of cationic palladium(II)‐oxo clusters (POCs) containing f‐metal ions, [PdII6O12M8{(CH3)2AsO2}16(H2O)8]4+ (M=CeIV, ThIV), and their physicochemical characterization in the solid state, in solution and in the gas phase. The molecular structure of the two novel POCs comprises an octahedral {Pd6O12}12− core that is capped by eight MIV ions, resulting in a cationic, cubic assembly {Pd6O12MIV8}20+, which is coordinated by a total of 16 terminal dimethylarsinate and eight water ligands, resulting in the mixed PdII‐CeIV/ThIV oxo‐clusters [PdII6O12M8{(CH3)2AsO2}16(H2O)8]4+ (M=Ce, Pd6Ce8; Th, Pd6Th8). We have also studied the formation of host‐guest inclusion complexes of Pd6Ce8 and Pd6Th8 with anionic 4‐sulfocalix[n]arenes (n=4, 6, 8), resulting in the first examples of discrete, enthalpically‐driven supramolecular assemblies between large metal‐oxo clusters and calixarene‐based macrocycles. The POCs were also found to be useful as pre‐catalysts for electrocatalytic CO2‐reduction and HCOOH‐oxidation.
Long‐Lived Charge‐Transfer State in Spiro Compact Electron Donor–Acceptor Dyads Based on Pyromellitimide‐Derived Rhodamine: Charge Transfer Dynamics and Electron Spin Polarization
Authors: Chen Xi , Sukhanov Andrey A. , Yan Yuxin , Bese Damla , Bese Cagri , Zhao Jianzhang , Voronkova Violeta K. , Barbon Antonio , Yaglioglu Halime Gul
Published: April 2022

We observed a long‐lived charge transfer (CT) state in a novel orthogonal compact electron donor–acceptor dyads, with closed form of rhodamine (Rho) as electron donor and pyromellitimide (PI),or thionated PI, as electron acceptor. The two parts in the dyads are connected via a spiro quaternary carbon atom, thus the torsion between the donor and acceptor is completely inhibited, which is beneficial to reduce the reorganization energy and to exploit the Marcus inverted region effect to prolong the CT state lifetime. Femtosecond transient absorption spectra show that the charge separation is rather fast, while nanosecond transient absorption spectra confirmed the formation of long‐lived CT state (2.6 μs). Time‐resolved electron paramagnetic resonance (TREPR) spectra determined the spin multiplicity of the long living state and assigned it to a 3CT state. Replacement of an oxygen atom in the PI part with a sulfur atom favoring classical intersystem crossing processes, causes a consistently shortening of the lifetime of the 3CT state (0.29 μs).
A Hybrid Supramolecular Polymeric Nanomedicine for Cascade‐Amplified Synergetic Cancer Therapy
Authors: Yang Kai , Qi Shaolong , Yu Xinyang , Bai Bing , Zhang Xueyan , Mao Zhengwei , Huang Feihe , Yu Guocan
Published: April 2022

Supramolecular nanomedicines have shown great merits in cancer therapy, but their clinical translation is hampered by monotonous therapeutic modality and unsatisfactory antitumor performance. Herein, a hybrid supramolecular polymeric nanomedicine (SNPs) is developed based on β‐cyclodextrin/camptothecin (CPT) host−guest molecular recognition and iron‐carboxylate coordination. Iron ions stabilizingSNPscatalyze the conversion of intracellular hydrogen peroxide into highly toxic hydroxyl radical through a Fenton reaction, which further cleaves the thioketal linker of the supramolecular monomer to release potent CPT, thus amplifying the therapeutic efficacy by combining chemodynamic therapy and chemotherapy. The combination therapy stimulates antitumor immunity and promotes intratumoral infiltration of cytotoxic T lymphocytes by triggering immunogenic cell death. In synergy with PD‐L1 checkpoint blockade,SNPsenables enhanced immune therapy and a long‐term tumor remission.
Spotlight on mass spectrometric non‐target screening analysis: Advanced data processing methods recently communicated for extracting, prioritizing and quantifying features
Authors: Minkus Susanne , Bieber Stefan , Letzel Thomas
Published: April 2022

Non‐target screening of trace organic compounds complements routine monitoring of water bodies. So‐called features need to be extracted from the raw data that preferably represent a chemical compound. Relevant features need to be prioritized and further be interpreted, for instance by identifying them. Finally, quantitative data is required to assess the risks of a detected compound. This review presents recent and noteworthy contributions to the processing of non‐target screening (NTS) data, prioritization of features as well as (semi‐) quantitative methods that do not require analytical standards. The focus lies on environmental water samples measured by liquid chromatography, electrospray ionization and high‐resolution mass spectrometry. Examples for fully‐integrated data processing workflows are given with options for parameter optimization and choosing between different feature extraction algorithms to increase feature coverage. The regions of interest‐multivariate curve resolution method is reviewed which combines a data compression alternative with chemometric feature extraction. Furthermore, prioritization strategies based on a confined chemical space for annotation, guidance by targeted analysis and signal intensity are presented. Exploiting the retention time (RT) as diagnostic evidence for NTS investigations is highlighted by discussing RT indexing and prediction using quantitative structure‐retention relationship models. Finally, a seminal technology for quantitative NTS is discussed without the need for analytical standards based on predicting ionization efficiencies.
Stability, structure, and antioxidant activity of astaxanthin crystal from Haematococcus pluvialis
Authors: Zhang Xiaowei , Ren Xiangrui , Zhao Xiaoyan , Liu Hongkai , Wang Meng , Zhu Yunping
Published: April 2022

Crystallized anthaxanthin was prepared through the cleaning crystallization method and the stabilities during thermal, lighting, and pH treatment, and antioxidant activities in vitro were evaluated. The structural characterizations of astaxanthin crystal were verified by 1H, 13C NMR, and XRD analysis. The stability data showed that the astaxanthin crystal was more sensitive to heat, light, and pH compared to oleoresin. The sucrose had no outstanding influence on the astaxanthin crystal, while the stability of astaxanthin oleoresin slightly increased with the increase of sugar concentration. The XRD and nuclear magnetic resonance spectra elucidated that the astaxanthin crystal was all trans structure. The astaxanthin crystal showed the dominant 1,1′‐diphenyl‐2‐picrylhydrazyl (IC50 18.65 μmol L−1), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt˙+(21.1 μmol L−1), •OH (IC50 49.46 μmol L−1) and ferric reducing antioxidant power (IC50 81.60 μmol L−1) activities. The investigated results would be helpful for improving the development of astaxanthin crystal in food products.
Bis(2‐, 3‐, 4‐carboxyethylpyridinium) hexafluorosilicates as potential caries prophylactic agents
Authors: Gelmboldt Vladimir O. , Lytvynchuk Irina V. , Shyshkin Ivan O. , Khromagina Larysa N. , Fonari Marina S. , Kravtsov Victor Ch.
Published: April 2022

Interaction of 2‐, 3‐, 4‐carboxyethylpyridines (L1, L2, L3) with fluorosilicic acid results in the corresponding bis(pyridinium) hexafluorosilicates I–III, characterized by elemental analysis, IR, 1H, 19F nuclear magnetic resonance (NMR), and mass spectrometry, solubility data, and X‐ray crystallography. Crystallographic data: Fdd2, Z = 8, a = 28.610(2) Å, b = 18.8378(14) Å, c = 7.3236(5) Å (I); P‐1, Z = 1, a = 6.2712(4) Å, b = 7.1706(5) Å, c = 10.9721(7) Å, α = 102.514(6)°, β = 97.037(5)°, γ = 93.640(6)° (II); P21/c, Z = 2, a = 10.0345(6) Å, b = 9.8734(5) Å, c = 9.4704(6) Å, β = 94.347(6)° (III). The dominant intermolecular contacts from the Hirshfeld surface analysis are H…F/F…H, H…H, and H…O/O…H with percentages of 33.3%–34.5%, 26.4%–30.0%, and 16.0%–21.8%. The infrared spectra for I–III exhibit stretching vibrations ν(N+H) at 3300–3050 cm–1; stretching and deformation vibrations ν(SiF) and δ(SiF2) for [SiF6]2– anions are registered near 740 cm–1 and in the range of 480–440 cm–1. In the 19F NMR spectra of aqueous solutions of I–III, strong singlet signals of the [SiF6]2– anion were registered at δ(F) = −133.35 ppm (I), –131.43 ppm (II), –129.02 ppm (III) with two satellites due to the spin‐spin interaction 29Si–19F (J(29Si–19F) = 107.5 Hz (II), 107.6 Hz (III)). I–III reveal high solubility in water and dimethyl sulfoxide and very poor solubility in methanol and ethanol. All compounds demonstrate noticeable anticaries activity and absence of hepatotoxic effects, and bis(3‐carboxyethylpyridinium) hexafluorosilicate II displays the highest caries‐preventive efficacy, which significantly exceeds values for the reference preparations, NaF and (NH4)2[SiF6].
Bauhaus und Bauphysik – Eine bauphysikalische Untersuchung und Bewertung am Beispiel Haus Oud
Authors: Röseler Holger , Krause Pia , Eitle Adrian , Veres Eva , Leistner Philip
Published: April 2022

Während aktuell das Neue Europäische Bauhaus mit einer interdisziplinären Ausrichtung die zukünftige Gestaltung unserer Lebens‐ und Bauweisen in den Blickpunkt rückt, fielen vor wenigen Jahren zwei Jubiläen zusammen. 100 Jahre waren seit der Bauhaus‐Gründung vergangen und 90 Jahre seit der Gründung eines der ersten Forschungsinstitute mit dem Schwerpunkt Bauphysik. Natürlich trennt beide Institutionen nicht nur ein 10‐jähriger „Altersunterschied”. Mit dem historisch einzigartigen Bauhaus ist die anfangs sehr kleine Stuttgarter Gruppe bauphysikalischer Enthusiasten nicht zu vergleichen. Rückblickend lassen sich aber Ähnlichkeiten der Motive beider Initiativen konstatieren und es ist anzunehmen, dass beim „Neuen Bauen” von Anfang an auch Überlegungen in den Entwurfsprozess einflossen, die der Bauphysik zentrale Fragestellungen und wichtige Impulse mit auf den Weg gaben. Diese Beziehung zwischen Bauhaus und Bauphysik wird am Beispiel des Reihenhauses Oud in der Weißenhofsiedlung in Stuttgart untersucht.

Die Ergebnisse zeigen, dass die Bausubstanz im Reihenhaus Oud eine deutlich schlankere Konstruktion als Vergleichsbauten seiner Zeit aufwies. Die daraus resultierenden bauphysikalischen Auswirkungen, mit Fokus auf den Wärme‐, Feuchte‐ und Schallschutz, werden analysiert. In Summe stellte das Haus Oud einen wertvollen Beitrag zur Erforschung und Weiterentwicklung von kostengünstigen, innovativen Wohnformen dar und war prägend für zukünftige Bauprozesse bis in die Gegenwart.
Zur Theorie der Randles‐Sevčikschen Kathodenstrahl‐Polarographie
Authors: Matsuda Hiroaki , Ayabe Yuzo
Published: April 2022

Unter der Voraussetzung, daß die Elektrode nur einen potentialbestimmenden Vorgang enthält und die Diffusionsvorgänge durch die eindimensional einseitig unendlich ausgedehnte, ruhende Phase verlaufen, wird die theoretische Analyse der Stromspannungskurve der Randles‐Sevčikschen Kathodenstrahl‐Polarographie durchgeführt. Gemäß der Größe der Reaktionsgeschwindigkeit des Elektrodenvorganges beim Gleichgewichtspotential kG können die Stromspannungskurven in drei Fälle, nämlich in reversible, „quasi”︁‐reversible und irreversible Fälle, eingeteilt werden. Man erhält bei 25°C

1. den reversiblen Fall, wenn kG > 0,3 √ n v (cm · sec−1),

2. den „quasi”︁‐reversiblen Fall, wenn 0, 3 √ n v > kG > 2.10−5 √ n v (cm · sec−1),

3. den irreversiblen Fall, wenn kG < 2 · 10−5 √n v (cm · sec−1).

(n = Zahl der Elektronen, die bei dem Elektrodenvorgang aufgenommen bzw. abgegeben werden, v = Geschwindigkeit der Spannungsänderung.) Für jeden Fall wird die allgemeine Formel der Stromspannungskurve abgeleitet. Weiterhin ergeben sich auch die Ausdrücke für die Spitzenstromstärke, das Spitzenpotential und die Differenz zwischen dem Halbspitzen‐ und Spitzenpotential.

Zuletzt zeigt es sich, daß man den Durchtrittsfaktor und die Reaktionsgeschwindigkeit des Elektrodenvorganges aus den experimentellen Daten für diese drei charakteristischen Werte ermitteln kann. Als Beispiele werden für einige Ionen die Auswertungen durchgeführt.
Design, fabrication, and characterization of a multimodal reconfigurable bioreactor for bone tissue engineering
Authors: Montorsi Margherita , Genchi Giada G. , De Pasquale Daniele , De Simoni Giorgio , Sinibaldi Edoardo , Ciofani Gianni
Published: April 2022

In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio‐physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many stimulation systems into a single bioreactor led to the generation of several unimodal bioreactors, investigating one or at mostly two of the required biophysical stimuli. These systems miss the physiological mimicry of bone cells environment, and often produced contrasting results, thus making the knowledge of bone mechanotransduction fragmented and often inconsistent. To overcome this issue, in this study we developed a perfusion and electroactive‐vibrational reconfigurable stimulation bioreactor to investigate the differentiation of SaOS‐2 bone‐derived cells, hosting a piezoelectric nanocomposite membrane as cell culture substrate. This multimodal perfusion bioreactor is designed based on a numerical (finite element) model aimed at assessing the possibility to induce membrane nano‐scaled vibrations (with ~12 nm amplitude at a frequency of 939 kHz) during perfusion (featuring 1.46 dyn cm−2 wall shear stress), large enough for inducing a physiologically‐relevant electric output (in the order of 10 mV on average) on the membrane surface. This study explored the effects of different stimuli individually, enabling to switch on one stimulation at a time, and then to combine them to induce a faster bone matrix deposition rate. Biological results demonstrate that the multimodal configuration is the most effective in inducing SaOS‐2 cell differentiation, leading to 20‐fold higher collagen deposition compared to static cultures, and to 1.6‐ and 1.2‐fold higher deposition than the perfused‐ or vibrated‐only cultures. These promising results can provide tissue engineering scientists with a comprehensive and biomimetic stimulation platform for a better understanding of mechanotransduction phenomena beyond cells differentiation.
The lymphatic system throughout history: From hieroglyphic translations to state of the art radiological techniques
Authors: van Schaik Caroline J. , Boer Lucas L. , Draaisma Jos M. T. , van der Vleuten Carine J. M. , Janssen Jan Jaap , Fütterer Jurgen J. , Schultze Kool Leo J. , Klein Willemijn M.
Published: April 2022

A comprehensive lymphatic system is indispensable for a well‐functioning body; it is integral to the immune system and is also interrelated with the digestive system and fluid homeostasis. The main difficulty in examining the lymphatic system is its fine‐meshed structure. This remains a challenge, leaving patients with uninterpreted symptoms and a dearth of potential therapies. We review the history of the lymphatic system up to the present with the aim of improving current knowledge. Several findings described throughout history have made fundamental contributions to elucidating the lymphatic system. The first contributions were made by the ancient Egyptians and the ancient Greeks. Vesalius obtained new insights by dissecting corpses. Thereafter, Ruysch (1638–1731) gained an understanding of lymphatic flow. In 1784, Mascagni published his illustration of the whole lymphatic network. The introduction of radiological lymphography revolutionized knowledge of the lymphatic system. Pedal lymphangiography was first described by Monteiro (1931) and Kinmonth (1952). Lymphoscintigraphy (nuclear medicine), magnetic resonance imaging, and near‐infrared fluorescence lymphography further improved visualization of the lymphatic system. The innovative dynamic contrast‐enhanced magnetic resonance lymphangiography (DCMRL) transformed understanding of the central lymphatic system, enabling central lymphatic flow disorders in patients to be diagnosed and even allowing for therapeutic planning. From the perspective of the history of lymph visualization, DCMRL has ample potential for identifying specific causes of debilitating symptoms in patients with central lymphatic system abnormalities and even allows for therapeutic planning.
The exon 12‐containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway
Authors: Wang Ling , Zhou Ying , Cao Canhui , Lin Shitong , Zhi Wenhua , Zhang Danya , Li Jie , Wei Rui , Jiang Guiying , Xu Hanjie , Wang Xueqian , Xi Ling , Wu Peng
Published: April 2022

LIM homeobox 6 (LHX6) has been reported to be downregulated and inhibits cell proliferation in various cancers. Alternative splicing of LHX6 leads to six annotated isoforms, which can be found in the NCBI database. However, the expression patterns and potential roles of these isoforms remain poorly characterized in cervical cancer. Here, we demonstrated that the LHX6 isoforms containing exon 12 (LHX6EX(+12) group) and isoforms lacking exon 12 (LHX6EX(–12) group) were differentially expressed in cervical tissue by qRT‐PCR. The mRNA expression level of LHX6EX(+12) group was higher than that of LHX6EX(−12) group in cervical cancer tissue. Knockdown of LHX6EX(+12) group and all LHX6 isoforms (LHX6All group) inhibited cell growth, increased cell apoptosis, and induced cell cycle arrest from G0/G1 phase to S phase in vitro. Consistently, overexpression of the LHX6EX(+12) group promoted cervical cancer cell proliferation in vitro. In contrast, no significant differences in cell proliferation were found between LHX6EX(−12) isoform knockdown group and its control. RNA‐sequencing suggested that the LHX6EX(+12) isoform group might exert its cancer‐promoting effects in cervical cancer via regulating MAPK signaling pathway. Downregulation of the LHX6EX(+12) group significantly suppressed the phosphorylation of MRK, ERK, JNK, and P38 at the protein level. We also identified some unique biological processes and signaling pathways in which each isoform group might be involved. In summary, our results indicated that LHX6EX(+12) isoform group was the dominant oncogenic type of LHX6 in cervical cancer, which may be a new biomarker and a potential precise therapeutic target for cervical cancer in the future.
Adiponectin and the risk of gastrointestinal cancers in East Asians: Mendelian randomization analysis
Authors: Jiang Hua , Hu Daojun , Wang Jun , Zhang Bo , He Chiyi , Ning Jiyu
Published: April 2022

Background

Adiponectin is an important adipocytokine and has been associated with the risks of gastrointestinal cancers (GICs). Mendelian randomization (MR) analysis is needed to assess the causal relationships between adiponectin and GICs.

Methods

We retrieved the summary data of genome‐wide association studies for adiponectin and six types of GICs in East Asians. A series of quality control steps were performed to select the eligible genetic instrumental tools. Horizontal pleiotropy and between‐SNP heterogeneity were tested to choose the primary MR method. We also conducted sensitivity analyses to test the robustness of the main findings.

Results

We detected neither heterogeneity nor horizontal pleiotropy for the eligible SNPs in all of the MR analyses. Inverse variance weighted (IVW) was therefore used as the primary method, and suggested that per 10% increase in log‐transformed adiponectin level was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.88, 95% CI 0.81, 0.96), whereas with an increased risk of hepatocellular carcinoma (OR = 1.26, 95% CI 1.09, 1.44) and of biliary tract cancer (OR = 1.54, 95% CI 1.12, 2.12). However, only the association between adiponectin and HCC risk was statistically significant after correction for multiple testing. No statistically significant association was detected between adiponectin and esophageal (OR = 1.05, 95% CI 0.89, 1.23), pancreatic (OR = 1.04, 95% CI 0.78, 1.37), and colorectal cancers (OR = 1.00, 95% CI 0.93, 1.07). Sensitivity analyses did not find contradictory results.

Conclusion

High level of adiponectin may have a causal effect on and can serve as a biomarker for the carcinogenesis of gastric cancer, hepatocellular carcinoma, and biliary tract cancer.
Multiple symptomatic giant coronary aneurysms
Authors: Vukomanovic Damir , Unzek Samuel , Reichert William , Mookadam Farouk
Published: April 2022

We describe a rare case of coronary artery aneurysms due to Kawasaki disease in an elderly patient. Our case presents multiple giant coronary artery aneurysms affecting the left coronary system which is less common compared with right coronary aneurysms. Giant coronary artery aneurysms are uncommon; even more rare is their association with ischemic symptoms, and treatment can be challenging. We describe a case of symptomatic multiple coronary artery aneurysms with symptom relief after coronary artery bypass grafting in an elderly patient.
Single‐Entity Electrochemical Detection of As‐Prepared Metallic and Dielectric Nanoparticle Stochastic Impacts in a Phosphonium Ionic Liquid
Authors: Ahmadinasab Nazanin , Stockmann Talia Jane
Published: April 2022

Nanoparticles (NPs) are of considerable interest, owing to their enhanced catalytic activity and optical properties. Ionic liquids (ILs) are employed as a medium to prepare small (<20 nm in diameter) and relatively low dispersity (typically, ±1–2 nm) NPs. While ensemble techniques (e. g., UV/Vis) can provide a great deal of information, increasingly, single‐entity electrochemistry (SEE) has been used to provide physical insight into individual NP catalysis and dynamics. Herein, Pt NP impact current spikes for particles prepared in the IL phase and based on electrocatalytic amplification (ECA) of the borohydride oxidation reaction (BOR) were recorded during i‐t measurements. Additionally, direct oxidative LiBH4 nanocrystal (NC) impact signals were observed herein for the first time. By quantifying the charge transferred during the stochastic collision events, the radius of the NCs (rNC) was calculated (∼5.5 nm) and compares favorably with TEM images. Critically, small additions (1 % v/v) of a molecular, polar organic solvent (tetrahydrofuran, THF) disrupt the ILs supramolecular fluidic nature, which enhances NC impact frequency and the aggregation of Pt NPs.
Taming of the DIBAL Promoted Debenzylation of α‐Cyclodextrin. Kinetics, Substituent Effects and Efficient Synthesis of Lings Tetrol**
Authors: Bols Mikael , Friis Victor
Published: April 2022

The kinetics of the reaction of perbenzyl α‐cyclodextrin was studied varying the concentration of DIBAL and substrate, and the temperature. The initial debenzylation was found to be 1st order in substrate and follow the relationship 0.0675+0.179[DIBAL]2 with respect to the concentration of DIBAL. The second and the third debenzylation which led to the 3A,6A,6D‐triol (Lings triol) were both found to be 1st order in substrate concentration and zero order in DIBAL concentration. Longer reaction times with DIBAL in high concentration gave further debenzylation to comparatively complex mixtures containing the 2B,3A,6A,6D‐tetrol and the 3A,6A,6C,6D‐tetrol. In contrast reaction at 0.1 M DIBAL gave the symmetrical 3A,6A,3D,6D‐tetrol (Lings tetrol) in 60 % yield. The effect of chlorine or methyl substitution of the phenyl groups of perbenzyl α‐cyclodextrin was also investigated. Per 4‐chlorobenzyl slowed down the reaction with DIBAL, while 4‐methylbenzyl increased the reaction rate, but still gave the corresponding 6 A‐monool or 6A,6D‐diol products. A Hammett reaction constant of −4.9 was found for the first debenzylation showing a high degree of positive charge in the transition state. The per(2,4‐dichlorobenzyl)‐α‐cyclodextrin‐derivative was completely resistant to DIBAL, however upon addition of trimethyl aluminium this derivative also reacted to give the 6A,6D‐diol product.
Boosting Electrocatalytic Oxygen Evolution over Ce−Co9S8 Core–Shell Nanoneedle Arrays by Electronic and Architectural Dual Engineering
Authors: Liu Kun , Zhu Zhuoya , Jiang Mengqi , Li Liangcheng , Ding Linfei , Li Meng , Sun Dongmei , Yang Gaixiu , Fu Gengtao , Tang Yawen
Published: April 2022

An dual electronic and architectural engineering strategy is a good way to rationally design earth‐abundant and highly efficient electrocatalysts of the oxygen evolution reaction (OER) for sustainable hydrogen‐based energy devices. Here, a Ce‐doped Co9S8 core–shell nanoneedle array (Ce−Co9S8@CC) supported on a carbon cloth has been designed and developed to accelerate the sluggish kinetics of the OER. Profiting from valance alternative Ce doping, a fine core–shell structure and vertically aligned nanoneedle arrayed architecture, Ce−Co9S8@CC integrates modulated electronic structure, highly exposed active sites, and multidimensional mass diffusion channels; together, these afford a favorable catalyzed OER. Ce−Co9S8@CC exhibits remarkable performance in the OER in an alkaline medium, where the overpotential requires only 242 mV to deliver a current density of 10 mA cm−2 for the OER; this is 70 mV superior to that of Ce‐free Co9S8 catalyst and other counterparts. Good stability and impressive selectivity (nearly 100 % Faradic efficiency) are also demonstrated. When integrated into a two‐electrode OER//HER electrolyzer, the as‐prepared Ce−Co9S8@CC displays a low operation potential of 1.54 V at 10 mA cm−2 and long‐term stability, thus demonstrating great potential for economical water electrolysis.
Homologous recombination deficiency is inversely correlated with microsatellite instability and identifies immunologically cold tumors in most cancer types
Authors: Budczies Jan , Kluck Klaus , Beck Susanne , Ourailidis Iordanis , Allgäuer Michael , Menzel Michael , Kazdal Daniel , Perkhofer Lukas , Kleger Alexander , Schirmacher Peter , Seufferlein Thomas , Stenzinger Albrecht
Published: April 2022

Homologous recombination deficiency (HRD) leads to DNA double‐strand breaks and can be exploited by the use of poly (ADP‐ribose) polymerase (PARP) inhibitors to induce synthetic lethality. Extending the original therapeutic concept, the role of HRD is currently being investigated in clinical trials testing immune checkpoint blockers alone or in combination with PARP inhibitors, but the relationship between HRD and immune cell context in cancer is incompletely understood. We analyzed the association between immune cell composition, gene expression, and HRD in 9,041 tumors of 32 solid cancer types from The Cancer Genome Atlas (TCGA). The numbers of genomic scars were quantified by the HRD sum score (HRDsum) including loss of heterozygosity, large‐scale state transitions, and telomeric allelic imbalance. The T‐cell inflamed gene expression profile correlated weakly, but significantly positively, with HRDsum across cancer types (ρ = 0.17). Within individual cancer types, a significantly positive correlation was observed only in breast cancer, ovarian cancer, and four other cancer types, but not in the remaining 26 cancer types. HRDsum and tumor mutational burden (TMB) correlated significantly positively across cancer types (ρ = 0.42) and within 18 cancer types. HRDsum and a proliferation metagene correlated significantly positively across cancer types (ρ = 0.52) and within 20 cancer types. Mismatch repair deficiency and HRD as well as proofreading deficiency showed a high level of exclusivity. High HRD scores were associated with an immunologically activated tumor microenvironment only in a minority of cancer types. Our data favor the combination of genetic markers, complex genomic markers (including HRDsum and TMB), and other molecular markers (including proliferation scores) for a precise and comprehensive read‐out of the tumor biology and an individually tailored treatment.
A Patent Review on FDA‐Approved Antibody‐Drug Conjugates, Their Linkers and Drug Payloads
Authors: Chia C. S. Brian
Published: April 2022

Antibody‐drug conjugates (ADCs) have emerged as a promising class of biologics since the first approval of Gemtuzumab ozogamicin in 2000. Compared to small molecule drugs, ADCs are structurally much more complex as they comprise of an antibody conjugated to cytotoxic payloads by specially‐designed linkers. Correspondingly, the ADC patent landscape is also much more complex. This review collates and discusses the patents protecting ADCs approved by the FDA up to 31 December 2021, with particular emphasis on their linker and cytotoxin payload technologies.
Engineered Exosomes as a Photosensitizer Delivery Platform for Cancer Photodynamic Therapy
Authors: Dao Anyi , Kushwaha Rajesh , Kumar Ashish , Huang Huaiyi , Banerjee Samya
Published: April 2022

Photodynamic therapy (PDT), a non‐/minimally invasive cancer treatment method, has the advantages of low side effects, high selectivity, and low drug resistance. It is currently a popular cancer treatment method. However, given the shortcomings of photosensitizers such as poor photostability, poor water solubility, and short half‐life in vivo when used alone, the development of photosensitizer nano‐delivery platforms has always been a research hotspot to overcome these shortcomings. In the human body, various types of cells generally release bilayer extracellular vesicles known as exosomes. Compared with traditional materials, exosomes are currently an ideal drug delivery platform due to their homology, low immunogenicity, easy modification, high biocompatibility, and natural carrying capacity. Therefore, in this concept, we focus on the research status and prospects of engineered exosome‐based photosensitizer nano‐delivery platforms in cancer PDT.
Providing assurance and scrutability on shared data and machine learning models with verifiable credentials
Authors: Barclay Iain , Preece Alun , Taylor Ian , Radha Swapna Krishnakumar , Nabrzyski Jarek
Published: April 2022

Adopting shared data resources requires scientists to place trust in the originators of the data. When shared data is later used in the development of artificial intelligence (AI) systems or machine learning (ML) models, the trust lineage extends to the users of the system, typically practitioners in fields such as healthcare and finance. Practitioners rely on AI developers to have used relevant, trustworthy data, but may have limited insight and recourse. This article introduces a software architecture and implementation of a system based on design patterns from the field of self‐sovereign identity. Scientists can issue signed credentials attesting to qualities of their data resources. Data contributions to ML models are recorded in a bill of materials (BOM), which is stored with the model as a verifiable credential. The BOM provides a traceable record of the supply chain for an AI system, which facilitates on‐going scrutiny of the qualities of the contributing components. The verified BOM, and its linkage to certified data qualities, is used in the AI scrutineer, a web‐based tool designed to offer practitioners insight into ML model constituents and highlight any problems with adopted datasets, should they be found to have biased data or be otherwise discredited.
A social hybrid recommendation system using LSTM and CNN
Authors: Daneshvar Hirad , Ravanmehr Reza
Published: April 2022

With the ever‐increasing use of Internet and social networks that generate a vast amount of information, there is a serious need for recommendation systems. In this article, we propose a recommender system utilizing deep neural networks that simultaneously considers both the users' ratings to the movies and the visual features of the movie poster and trailer. For this purpose, a hybrid movie recommender system, RSLCNet, has been developed using CNN and LSTM architectures. The proposed system considers the dynamics of users' interests in the collaborative filtering engine using the LSTM network that receives user‐rating sequences. In the content‐based filtering engine, utilizing CNN, the visual features of movie posters and trailers are extracted, and along with the actors and the directors, similar movies are recommended to the user. Moreover, each user's social influence is calculated employing the social information available on the user's Twitter account and used in the average movie rating to improve the effectiveness of the content‐based filtering part. The required datasets have been collected from MovieTweetings, Mise‐en‐scène, and OMDB. The evaluation results show that the accuracy and effectiveness of the proposed approach have been improved in terms of MAE and RMSE compared to the best available methods.
Analyzing Spatial Transcriptomics Data Using Giotto
Authors: Del Rossi Natalie , Chen Jiaji G. , Yuan Guo‐Cheng , Dries Ruben
Published: April 2022

Spatial transcriptomic technologies have been developed rapidly in recent years. The addition of spatial context to expression data holds the potential to revolutionize many fields in biology. However, the lack of computational tools remains a bottleneck that is preventing the broader utilization of these technologies. Recently, we have developed Giotto as a comprehensive, generally applicable, and user‐friendly toolbox for spatial transcriptomic data analysis and visualization. Giotto implements a rich set of algorithms to enable robust spatial data analysis. To help users get familiar with the Giotto environment and apply it effectively in analyzing new datasets, we will describe the detailed protocols for applying Giotto without any advanced programming skills. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Getting Giotto set up for use

Basic Protocol 2: Pre‐processing

Basic Protocol 3: Clustering and cell‐type identification

Basic Protocol 4: Cell‐type enrichment and deconvolution analyses

Basic Protocol 5: Spatial structure analysis tools

Basic Protocol 6: Spatial domain detection by using a hidden Markov random field model

Support Protocol 1: Spatial proximity–associated cell‐cell interactions

Support Protocol 2: Assembly of a registered 3D Giotto object from 2D slices
Atomically Dispersed Cu Sites on Dual‐Mesoporous N‐Doped Carbon for Efficient Ammonia Electrosynthesis from Nitrate
Authors: Xu Mengqiu , Xie Qifan , Duan Delong , Zhang Ye , Zhou Yuhu , Zhou Haiqiao , Li Xiaoyu , Wang Yao , Gao Peng , Ye Wei
Published: April 2022

The industrial Haber‐Bosch process for ammonia synthesis is extremely important in modern society. However, it is energy intensive and leads to severe pollution, which has motivated eco‐friendly NH3 synthesis research. Electroreduction of contaminant nitrate ions back to NH3 is an effective complement but is still limited by low NH3 yields and nitrate‐to‐NH3 selectivities. In this study, the electrochemical nitrate reduction reaction (NTRR) is carried out over a single‐atom Cu catalyst. Atomically dispersed Cu sites anchored on dual‐mesoporous N‐doped carbon framework display excellent NTRR performance with NH3 production rate of 13.8 mol
 gcat−1 h−1 and NO3−‐to‐NH3 faradaic efficiency (FE) of 95.5 % at −1.0 V. Cu−N−C catalyst can sustain continuous 120 h NTRR test in the simulated NH3 synthesis scenarios with large current density (about 200 mA cm−2) and amplified volume of NO3− solution (9 times). Theoretical calculations reveal that atomically dispersed Cu1−N4 sites reduce the energy barrier of potential‐determining step in NTRR and promote the decomposition of primary intermediate in NO3−‐to‐N2 process. These findings provide a guideline for the rational design of highly active, selective and durable electrocatalysts for the NTRR.
BSCL2/Seipin deficiency in hearts causes cardiac energy deficit and dysfunction via inducing excessive lipid catabolism
Authors: Zhou Hongyi , Li Jie , Su Huabo , Li Ji , Lydic Todd A. , Young Martin E , Chen Weiqin
Published: April 2022

Background

Heart failure (HF) is one of the leading causes of death worldwide and is associated with cardiac metabolic perturbations. Human Type 2 Berardinelli‐Seip Congenital Lipodystrophy (BSCL2) disease is caused by mutations in the BSCL2 gene. Global lipodystrophic Bscl2−/− mice exhibit hypertrophic cardiomyopathy with reduced cardiac steatosis. Whether BSCL2 plays a direct role in regulating cardiac substrate metabolism and/or contractile function remains unknown.

Methods

We generated mice with cardiomyocyte‐specific deletion of Bscl2 (Bscl2cKO) and studied their cardiac substrate utilisation, bioenergetics, lipidomics and contractile function under baseline or after either a treatment regimen using fatty acid oxidation (FAO) inhibitor trimetazidine (TMZ) or a prevention regimen with high‐fat diet (HFD) feeding. Mice with partial ATGL deletion and cardiac‐specific deletion of Bscl2 were also generated followed by cardiac phenotyping.

Results

Different from hypertrophic cardiomyopathy in Bscl2−/− mice, mice with cardiac‐specific deletion of Bscl2 developed systolic dysfunction with dilation. Myocardial BSCL2 deletion led to elevated ATGL expression and FAO along with reduced cardiac lipid contents. Cardiac dysfunction in Bscl2cKO mice was independent of mitochondrial dysfunction and oxidative stress, but associated with decreased metabolic reserve and ATP levels. Importantly, cardiac dysfunction in Bscl2cKO mice could be partially reversed by FAO inhibitor TMZ, or prevented by genetic abolishment of one ATGL allele or HFD feeding. Lipidomic analysis further identified markedly reduced glycerolipids, glycerophospholipids, NEFA and acylcarnitines in Bscl2cKO hearts, which were partially normalised by TMZ or HFD.

Conclusions

We identified a new form of cardiac dysfunction with excessive lipid utilisation which ultimately causes cardiac substrate depletion and bioenergetics failure. Our findings also uncover a crucial role of BSCL2 in controlling cardiac lipid catabolism and contractile function and provide novel insights into metabolically treating energy‐starved HF using FAO inhibitor or HFD.
CD155/SRC complex promotes hepatocellular carcinoma progression via inhibiting the p38 MAPK signalling pathway and correlates with poor prognosis
Authors: Jin An‐Li , Zhang Chun‐Yan , Zheng Wen‐Jing , Xian Jing‐Rong , Yang Wen‐Jing , Liu Te , Chen Wei , Li Tong , Wang Bei‐Li , Pan Bai‐Shen , Li Qian , Cheng Jian‐Wen , Wang Peng‐Xiang , Hu Bo , Zhou Jian , Fan Jia , Yang Xin‐Rong , Guo Wei
Published: April 2022

Background

Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor prognosis. As a cell adhesion molecule, poliovirus receptor (PVR/CD155) is abnormally overexpressed in tumour cells, and related to tumour proliferation and invasion. However, the potential role and mechanism of CD155 have not yet been elucidated in HCC.

Methods

Immunohistochemistry, RT‐PCR and Western blot assays were used to determine CD155 expression in HCC cell lines and tissues. Cell Counting Kit‐8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration and invasion. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cox regression and Kaplan–Meier analyses were performed to explore the clinical significance of CD155. The role of CD155 in vivo was evaluated by establishing liver orthotropic xenograft mice model. RNA sequencing, bioinformatics analysis and co‐immunoprecipitation assay were used to explore the downstream signalling pathway of CD155.

Results

CD155 was upregulated in HCC tissues and represented a promising prognostic indicator for HCC patients (n = 189) undergoing curative resection. High CD155 expression enhanced cell proliferation, migration and invasion, and contributed to cell survival in HCC. CD155 overexpression also induced epithelial–mesenchymal transition in HCC cells. CD155 function in HCC involved SRC/p38 MAPK signalling pathway. CD155 interacted with SRC homology‐2 domain of SRC and promoted SRC activation, further inhibiting the downstream p38 MAPK signalling pathway in HCC.

Conclusions

CD155 promotes HCC progression via the SRC/p38 MAPK signalling pathway. CD155 may represent a predictor for poor postsurgery prognosis in HCC patients.
A Highly Fluorescent σ‐Bonded Platinum(II) Diketopyrrolopyrrole Complex
Authors: Kamioka Misaki , Wang Yitong , Mori Shigeki , Furuta Hiroyuki , Shimizu Soji
Published: April 2022

A σ‐bonded platinum(II) diketopyrrolopyrrole (Pt‐DPP) complex was synthesized from a reaction of p‐pinacolatoborylphenyl‐substituted DPP with dichloro(1,5‐cyclooctadiene)platinum(II), followed by a ligand exchange reaction with triphenylphosphine. The Pt‐DPP complex is highly fluorescent not only in solution but also in the solid state. From the comparison of the emission properties with those of N‐benzyl‐DPPs bearing phenyl and p‐bromophenyl substituents, the intense emission of the Pt‐DPP complex is ascribed to the DPP‐centered fluorescence. In the solid state, aggregation‐caused quenching is mitigated by the well‐segregated molecular packing due to the bulky triphenylphosphine ligands. The facile synthesis and unique fluorescence properties of the Pt‐DPP complex are beneficial for creating DPP‐based functional chromophores.
Exploring the Research Progress about the Applications of Cyclodextrins and Nanomaterials in Electroanalysis
Authors: Fritea Luminiţa , Tertiş Mihaela , Cristea Cecilia , Săndulescu Robert
Published: April 2022

Cyclodextrins and nanomaterials are widely used in the achievement of powerful platforms in supramolecular chemistry and nanotechnology. The relatively hydrophobic internal cavity of the CDs selectively retains molecules having the proper geometry, while the hydrophilic exterior allows CDs to improve the dispersibility and molecular recognition. The nanomaterials provide higher surface area, good conductivity, and electrocatalytic effect. The use of nanomaterials and CDs in electrochemical sensors’ design allows the development of a large variety of devices, explaining the increasing number of papers in the last years that are discussed in this review.
Upscaling ground‐based structural glaciological investigations via satellite remote sensing to larger‐scale ice masses: Bylot Island, Canadian Arctic
Authors: Jennings Stephen J. A. , Hambrey Michael J. , Moorman Brian J. , Holt Tom O. , Glasser Neil F.
Published: April 2022

Using satellite remote sensing, this study aims to assess the validity of upscaling ground‐based structural observations of small valley glaciers, to larger‐scale ice masses that are too vast or inaccessible for field‐study or ground‐truthing. Focusing on four adjacent valley glaciers on Bylot Island, Nunavut, Arctic Canada, we establish that ground‐based structural observations from two smaller (Stagnation and Fountain Glaciers) can be used to interpret the structures visible in optical satellite imagery in two much larger glaciers (Aktineq and Sermilik Glaciers). All the glaciers investigated have prominent longitudinal lineations, which are interpreted from ground observations to be longitudinal foliation. Other structures that were identified include primary stratification, crevasses, crevasse traces, and thrust‐faults. Strong longitudinal foliation is concentrated at flow‐unit boundaries, with differential ablation of ice facies commonly resulting in a ridge‐and‐furrow supraglacial topography that controls supraglacial streams and debris concentrations. Consequently, areas of strong foliation appear darker than areas of weak foliation in satellite imagery. As coarser resolution imagery is utilized to map large‐scale ice masses, sub‐pixel structural information is lost. Individual lineations mapped in coarser resolution imagery therefore probably comprise groups of clustered foliation at the sub‐pixel scale. Lateral narrowing measurements and calculated one‐dimensional strain across zones of longitudinal foliation are assessed as a tool for identifying large‐scale surface strain patterns, in particular large‐scale pure shear regimes. These one‐dimensional strain measurements suggest that flow‐unit boundaries are areas that undergo considerable cumulative strains. The upscaling approach used here can be applied to the largest ice masses, notably the Antarctic Ice Sheet.
Heterogenously‐expressed chitosanase combining a green ball milling method for enzymatic degradation
Authors: Su Haipeng , Sun Jianan , Guo Chaoran , Jia Zhenrong , Mao Xiangzhao
Published: April 2022

Chitooligosaccharides (COSs) and d‐glucosamine (GlcN), the most valuable biomolecules due to their various physiological functions, can be available inexpensively from chitosan by bio‐enzymatic degradation, in which chitosanases play a key role. On the other hand, pretreatment of chitosan is the necessary procedure in the bioproduction by enzymatic hydrolysis. Therefore, the green and efficient pretreatment strategy as well as superior enzyme activity are the most critical aspects in scaled up production. This study investigated environmentally friendly and efficient enzymatic hydrolysis of powdery chitosan (PC) pretreated by ball‐milling. First, heterologous expression yielded OUC‐CsnPT, a glycoside hydrolase family 46 chitosanase with a predominant specific activity of 5346.56 U/mg at pH 6.0°C and 45°C. The endo‐type chitosanase OUC‐CsnPT hydrolyzed chitosan to produce GlcN and chitobiose [(GlcN)2]. Then, ball‐milling was employed to pretreat PC to promote chitosanase OUC‐CsnPT hydrolysis, and the effectiveness was characterized by scanning electron microscope, X‐ray diffraction, and FTIR‐attenuated total reflection. Through the development of the novel route, the yield of COSs and GlcN for ball‐milling powdery chitosan increased by 10.8‐folds with a concentration of 14.5 μmol/ml. Hence, this technique presents a promising strategy suited to be a straightforward and environmentally friendly option for oligosaccharides production, broadening the theoretical basis for PC biodegradation.