bluuebunny/crossref_metadata_2025 huggingface dataset:
How Site‐Directed Mutagenesis Boosted Selectivity of a Promiscuous Enzyme
Authors: Nekvasilová Pavlína , Kulik Natalia , Rychlá Nikola , Pelantová Helena , Petrásková Lucie , Bosáková Zuzana , Cvačka Josef , Slámová Kristýna , Křen Vladimír , Bojarová Pavla
Published: August 2020

β‐N‐Acetylhexosaminidases (GH20; EC 3.2.1.52) are exo‐glycosidases with a dual activity for cleaving both N‐acetylglucosamine (GlcNAc) and N‐acetylgalactosamine (GalNAc) units from glycostructures. This substrate promiscuity is a hurdle in the selective synthesis of N‐acetylhexosamine oligosaccharides combining both GlcNAc and GalNAc units since there are hardly any GalNAc transferring enzymes available for synthetic applications. We present here site‐directed mutagenesis of a synthetically potent promiscuous β‐N‐acetylhexosaminidase from Talaromyces flavus (TfHex), which, as a wild type, exhibits a GalNAcase/GlcNAcase ratio of 1.2. On the basis of molecular modeling, we identified crucial amino acid residues responsible for its GalNAcase/GlcNAcase selectivity. Six site‐directed mutants were prepared, heterologously expressed in Pichia pastoris, purified, and kinetically characterized. As a result, novel engineered enzymes with an up to 7‐times higher selectivity for either GalNAc or GlcNAc substrates were obtained, preserving the favorable properties of the wild type TfHex, mainly its transglycosylation potential and tolerance to functional groups in the substrate molecule. The substrate selectivity and transglycosylation yield were further corroborated by reaction engineering. The new selective and synthetically capable enzymes were applied in the preparation of tailored N‐acetylhexosamines.

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Rhodium‐Catalysed Reductive Amination for the Synthesis of Tertiary Amines
Authors: Bianga Jonas , Kopplin Niklas , Hülsmann Jonas , Vogt Dieter , Seidensticker Thomas
Published: August 2020

A procedure for the synthesis of tertiary amines via reductive amination of aldehydes with molecular hydrogen as a reducing agent using homogeneous rhodium catalysis is presented. Using an amine to aldehyde ratio of 4/1 enabled the synthesis of tertiary amines from nine different aldehydes and nine different secondary amines with selectivities up to 99% and turnover frequencies (TOF) up to 7200 h−1. The reaction showed a high tolerance against alcohol and ester functions allowing the formation of multifunctional molecules. In addition, secondary amines can also be produced by this synthesis. For all compounds, activities were determined by hydrogen gas‐uptake. In order to increase the sustainability and efficiency of the procedure, a dosing strategy has been successfully developed. Using the determined reaction indicators enabled the stoichiometric use of aldehydes and amines without significant loss of selectivity.

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In Cellulo Protein Semi‐Synthesis from Endogenous and Exogenous Fragments Using the Ultra‐Fast Split Gp41‐1 Intein
Authors: Bhagawati Maniraj , Hoffmann Simon , Höffgen Katharina S. , Piehler Jacob , Busch Karin B. , Mootz Henning D.
Published: August 2020

Protein semi‐synthesis inside live cells from exogenous and endogenous parts offers unique possibilities for studying proteins in their native context. Split‐intein‐mediated protein trans‐splicing is predestined for such endeavors and has seen some successes, but a much larger variety of established split inteins and associated protocols is urgently needed. We characterized the association and splicing parameters of the Gp41‐1 split intein, which favorably revealed a nanomolar affinity between the intein fragments combined with the exceptionally fast splicing rate. Following bead‐loading of a chemically modified intein fragment precursor into live mammalian cells, we fluorescently labeled target proteins on their N‐ and C‐termini with short peptide tags, thus ensuring minimal perturbation of their structure and function. In combination with a nuclear‐entrapment strategy to minimize cytosolic fluorescence background, we applied our technique for super‐resolution imaging and single‐particle tracking of the outer mitochondrial protein Tom20 in HeLa cells.
Monochromophore‐Based Phosphorescence and Fluorescence from Pure Organic Assemblies for Ratiometric Hypoxia Detection
Authors: Liu Xiao‐Qin , Zhang Ke , Gao Jian‐Feng , Chen Yu‐Zhe , Tung Chen‐Ho , Wu Li‐Zhu
Published: August 2020

Hypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O2‐insensitive fluorophore and an O2‐sensitive phosphor in a polymer matrix, which require high cost and multi‐step synthesis of transition metal complexes. The two‐chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA‐UPy), bridged by a bis‐UPy‐functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (ΦP=7.7 %, τP=3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (Ksv=189.6 kPa−1) in aqueous solution as well as in living HeLa cells.
Molecular Supracence Resolving Eight Colors in 300‐nm Width: Unprecedented Spectral Resolution
Authors: Wan Wei , Li Alexander D. Q.
Published: August 2020

Monitoring multiple molecular probes simultaneously establishes their correlations and reveals the holistic mechanism. Current fluorescence imaging, however, is limited to about four colors because of typically circa 100‐nm spectral width. Herein, we show that molecular supracence imparts superior spectral resolution, resolving eight colors in 300‐nm width, about 37.5‐nm per color. A recently discovered light‐molecule interacting phenomenon, supracence only measures molecular emission above its excitation energy due to entanglement between atomic quantum system and electronic quantum system. As such, supracence takes advantage of sharp spectral edge of a single pathway and excitation specificity to produce narrow bands, whereas fluorescence has to deal with multiple pathways spilling out low‐energy long tail, that causes poor resolution. Thus, supracence enables myriad innovative molecular spectroscopy and microscopic imaging with profound impact broadly.
Enantioselective Crystallization of Chiral Inorganic Crystals of ϵ‐Zn(OH)2 with Amino Acids
Authors: Otis Gil , Nassir Molhm , Zutta Michael , Saady Abed , Ruthstein Sharon , Mastai Yitzhak
Published: August 2020

Many inorganic materials can form crystals, but little is known about their enantioselective crystallization. Herein, we report on the enantioselective crystallization of ϵ‐Zn(OH)2 (Wulfingite) chiral crystals by using amino acids. Crystals of ϵ‐Zn(OH)2 were crystallized from supersaturated sodium hydroxide and zinc nitrate aqueous solutions in the presence of l‐ or d‐arginine. All of the chiral measurements, such as selective chiral adsorption by circular dichroism (CD), chiral chromatography, and polarimetry measurements, clearly show chiral discrimination during the crystallization of ϵ‐Zn(OH)2. In addition, a new method has been developed for identifying chirality in crystals by using electron paramagnetic resonance (EPR). Although the values of chiral induction of the ϵ‐Zn(OH)2 crystals obtained are somewhat low, these values are still significant because they demonstrate that enantioselectivity during the crystallization of chiral inorganic crystals with chiral additives can be achieved. The method can be applied to many chiral inorganic systems. Understanding and controlling the crystallization of chiral inorganic crystals is important for gaining knowledge on the interaction of chiral molecules with inorganic surfaces. This knowledge can lead to an understanding of basic scientific questions such as the evolution of homochirality in biomolecules and the development of chiral inorganic crystals for a variety of purposes such as asymmetric catalysis and optical applications.
Wie weit wandert Energie in der DNA und verursacht Schäden? Nachweis des langreichweitigen Photoschadens in DNA
Authors: Kuhlmann Arthur , Bihr Larissa , Wagenknecht Hans‐Achim
Published: August 2020

Eine neue DNA‐Architektur ermöglicht zu untersuchen, wie weit Energie in DNA wandert und Cyclobutanpyrimidindimere (CPD) als Photoschäden, die Hautkrebs verursachen, bildet. Das Nucleosid des 3‐Methoxyxanthons erlaubt die ortsselektive Injektion von Lichtenergie in die DNA. Die designierte CPD‐Stelle, der die Phosphodiesterbindung fehlt, kann in definierten Distanzen platziert werden. Die CPD‐Bildung verbindet die beiden Oligonucleotide und erlaubt so die Analyse per Gelelektrophorese. Wir beobachteten eine sigmoidale Distanzabhängigkeit mit einem R0‐Wert von 25±3 Å. Unterhalb von R0 findet eine kurzreichweitige Energieübertragung mit geringer Distanzabhängigkeit statt, die charakteristisch für einen kohärenten Prozess ist. 5‐Methyl‐C als epigenetische Modifikation auf der 3′‐Seite erleichtert die CPD‐Bildung. Oberhalb von R0 findet eine inkohärente Energiewanderung über 30 A‐T‐Paare (105.4 Å) statt. Der Nachweis der CPD‐Bildung über eine derart lange Reichweite ist fundamental für unser Verständnis der DNA‐Photoschäden.
Selective Transfer Semihydrogenation of Alkynes with H2O (D2O) as the H (D) Source over a Pd‐P Cathode
Authors: Wu Yongmeng , Liu Cuibo , Wang Changhong , Lu Siyu , Zhang Bin
Published: August 2020

We reported a selective semihydrogenation (deuteration) of numerous terminal and internal alkynes using H2O (D2O) as the H (D) source over a Pd‐P alloy cathode at a lower potential. P‐doping caused the enhanced specific adsorption of alkynes and the promoted intrinsic activity for producing adsorbed atomic hydrogen (H*ads) from water electrolysis. The semihydrogenation of alkynes could be accomplished at a lower potential with up to 99 % selectivity and 78 % Faraday efficiency of alkene products, outperforming pure Pd and commercial Pd/C. This electrochemical semihydrogenation of alkynes might proceed via a H*ads addition pathway rather than a proton‐coupled electron transfer process. The decreased amount of H*ads at a lower potential and the more preferential adsorption of the Pd‐P to C≡C π bond than C=C moiety resulted in the excellent alkene selectivity. This method was capable of producing mono‐, di‐, and tri‐deuterated alkenes with up to 99 % deuterium incorporation.
Descriptor ΔGC‐O Enables the Quantitative Design of Spontaneously Blinking Rhodamines for Live‐Cell Super‐Resolution Imaging
Authors: Chi Weijie , Qiao Qinglong , Wang Chao , Zheng Jiazhu , Zhou Wei , Xu Ning , Wu Xia , Jiang Xiao , Tan Davin , Xu Zhaochao , Liu Xiaogang
Published: August 2020

Herein, we reported a simple, fast, and quantitative theoretical descriptor ΔGC‐O that allows accurate predictions of a wide range of spontaneously blinking rhodamines. ΔGC‐O denotes the Gibbs free energy differences between the closed and open forms of rhodamines and has a good linear relationship with experimental pKcycl values. This correlation affords an effective guide for the quantitative designs of spontaneously blinking rhodamines and eliminates trial‐and‐error. We have validated the predictive power of ΔGC‐O via the development of two spontaneously blinking rhodamines of different colors and enhanced brightness. We also demonstrated their super‐resolution imaging utilities in dynamic live‐cell imaging. We expect that ΔGC‐O will greatly facilitate the efficient creations of spontaneously blinking fluorophores and aid the advancements of super‐resolution bioimaging techniques.
A Photoconductive X‐ray Detector with a High Figure of Merit Based on an Open‐Framework Chalcogenide Semiconductor
Authors: Wu Sijie , Liang Chengyu , Zhang Jiaxu , Wu Zhou , Wang Xiao‐Li , Zhou Rui , Wang Yaxing , Wang Shuao , Li Dong‐Sheng , Wu Tao
Published: August 2020

A wide range of tunability in the physical parameters of a semiconductor used for X‐ray detection is desirable to achieve targeted performance optimization. However, in a dense‐phase semiconductor, fine‐tuning one parameter often leads to unwanted changes in other parameters. Herein, the intrinsic openness in an open‐framework semiconductor has been confirmed, for the first time, to be a key structural factor that weakens the mutual exclusivity of the adjustable physical parameters owing to a non‐linear control mechanism. The controllable doping of S in a zeolitic In–Se host results in an optimal balance between resistivity, band gap, and carrier mobility, which finally results in an excellent X‐ray detector with a high figure of merit for the mobility–lifetime product (7.12×10−4 cm2 V−1); this value is superior to that of a commercial α‐Se detector. The current strategy of choosing open‐framework semiconductor materials opens a new window for targeting high‐performance X‐ray detection.
A Simple Biosystem for the High‐Yielding Cascade Conversion of Racemic Alcohols to Enantiopure Amines
Authors: Tian Kaiyuan , Li Zhi
Published: August 2020

The amination of racemic alcohols to produce enantiopure amines is an important green chemistry reaction for pharmaceutical manufacturing, requiring simple and efficient solutions. Herein, we report the development of a cascade biotransformation to aminate racemic alcohols. This cascade utilizes an ambidextrous alcohol dehydrogenase (ADH) to oxidize a racemic alcohol, an enantioselective transaminase (TA) to convert the ketone intermediate to chiral amine, and isopropylamine to recycle PMP and NAD+ cofactors via the reversed cascade reactions. The concept was proven by using an ambidextrous CpSADH‐W286A engineered from (S)‐enantioselective CpSADH as the first example of evolving ambidextrous ADHs, an enantioselective BmTA, and isopropylamine. A biosystem containing isopropylamine and E. coli (CpSADH‐W286A/BmTA) expressing the two enzymes was developed for the amination of racemic alcohols to produce eight useful and high‐value (S)‐amines in 72–99 % yield and 98–99 % ee, providing with a simple and practical solution to this type of reaction.
Optimization of cinnamaldehyde microcapsule wall materials by experimental and quantitative methods
Authors: Li Mengting , Li Changgui , Zhou You , Tian Hua , Deng Qiaoyuan , Liu Haifang , Zhu Li , Yin Xueqiong
Published: August 2020

Microencapsulation is a widely‐investigated technique used for the unstable material preservation since the wall materials prevent the core materials from loss and deterioration. To improve the stability of cinnamaldehyde (CAL), different microcapsule wall systems are fabricated by spray‐drying, and then characterized by experimental methods to determine the most suitable wall materials. Surface morphology, encapsulation efficiency, effective loading capacity, as well as moisture absorption property are evaluated, and the results suggest that a three‐matrix system of methyl cellulose (MC)/sodium alginate (SA)/MC or MC/carboxymethyl chitosan (CMC)/SA wall formulation is more suitable for CAL microencapsulation. Moreover, a novel quantitative method is also proposed to verify the most stable wall material microencapsulation. The quantitative results show that the highest activation energy (53.00 ± 2.24 kJ/mol) is observed for the MC/CMC/SA‐encapsulated CAL microcapsule. Taken together, the results suggest that MC/CMC/SA wall formulation shows excellent barrier properties and is superior to other wall materials in preventing microencapsulated CAL deterioration. This study will be efficient in designing an ideal capsule for CAL microencapsulation.
Understanding Indonesia's role in the ‘ASEAN Outlook on the Indo‐Pacific’: A role theory approach
Authors: Agastia I Gusti Bagus Dharma
Published: August 2020

Following other regional powers, Indonesia announced its own interpretation of the Indo‐Pacific concept in 2018. Considering Indonesia's strategic position in the Indo‐Pacific, does this announcement indicate the prospects of a more active Indonesian role in the region? This article examines Indonesia's national role conception regarding the Indo‐Pacific concept. Drawing from the literature on role theory, particularly on role conception and role location, and by analysing foreign policy narratives espoused by dominant actors in the Indo‐Pacific region, this article finds Indonesia's articulation of the Indo‐Pacific concept as an example of role location within the new Indo‐Pacific structure, particularly in locating Indonesia's ‘middle power’ role. Dominant actors in the Indo‐Pacific have generally accepted Indonesia's Indo‐Pacific concept, which shows that Indonesia has managed to live up to expectations befitting of a middle power through its enactment of ‘regional leader’ and ‘bridge‐builder’ roles.
Synthesis and biological evaluation of substituted pyrrolidines and pyrroles as potential anticancer agents
Authors: Ji Jiali , Sajjad Farrukh , You Qun , Xing Dong , Fan Hui , Reddy Alavala G. K. , Hu Wenhao , Dong Suzhen
Published: August 2020

A series of polysubstituted pyrrolidines obtained via ruthenium‐catalyzed cascade cyclization of diazo pyruvates and anilines as well as their corresponding pyrrole analogs obtained via dehydration were evaluated for their antiproliferation activities. Pyrrolidines 3h and 3k showed good proliferation inhibitory effects toward 10 cancer cell lines with IC50 values ranging from 2.9 to 16 μM. Furthermore, pyrrolidine 3k induced cell cycle arrest at the G0/G1 phase and time‐ and dose‐dependent cellular apoptosis in both HCT116 and HL60 cells, suggesting that this type of pyrrolidine structure might be a good candidate for future anticancer therapies.
Reprogramming of antibiotics to combat antimicrobial resistance
Authors: Dubey Kashyap K. , Indu  , Sharma Manisha
Published: August 2020

This review outlines a literature‐based approach with illustrative examples of drug repurposing (one molecule, multiple targets), which will be useful in tackling the problem of antimicrobial resistance (AMR). Globally, the demands for new drugs have increased due to multidrug‐resistant pathogens and emerging viruses. Keeping these facts in view, drug repurposing started for utilization of a drug in a different way from a preexisting drug, which reduces the time and cost of development of a new drug. Repurposing increases the potency of a drug and reduces its toxicity level, as it is required in lower amounts, supporting the utilization of the drug as a new therapeutic option. This will be further explored to highlight the application in AMR.
Real‐time monitoring of quality attributes by in‐line Fourier transform infrared spectroscopic sensors at ultrafiltration and diafiltration of bioprocess
Authors: Wasalathanthri Dhanuka P. , Feroz Hasin , Puri Neha , Hung Jessica , Lane Gregory , Holstein Melissa , Chemmalil Letha , Both Douglas , Ghose Sanchayita , Ding Julia , Li Zheng Jian
Published: August 2020

Technologies capable of monitoring product quality attributes and process parameters in real time are becoming popular due to the endorsement of regulatory agencies and also to support the agile development of biotherapeutic pipelines. The utility of vibrational spectroscopic techniques such as Fourier transform mid‐infrared (Mid‐IR) and multivariate data analysis (MVDA) models allows the prediction of multiple critical attributes simultaneously in real time. This study reports the use of Mid‐IR and MVDA model sensors for monitoring of multiple attributes (excipients and protein concentrations) in real time (measurement frequency of every 40 s) at ultrafiltration and diafiltration (UF/DF) unit operation of biologics manufacturing. The platform features integration of fiber optic Mid‐IR probe sensors to UF/DF set up at the bulk solution and through a flow cell at the retentate line followed by automated Mid‐IR data piping into a process monitoring software platform with pre‐loaded partial least square regression (PLS) chemometric models. Data visualization infrastructure is also built‐in to the platform so that upon automated PLS prediction of excipients and protein concentrations, the results were projected in a graphical or numerical format in real time. The Mid‐IR predicted concentrations of excipients and protein show excellent correlation with the offline measurements by traditional analytical methods. Absolute percent difference values between Mid‐IR predicted results and offline reference assay results were ≤5% across all the excipients and the protein of interest; which shows a great promise as a reliable process analytical technology tool.
Extremely Low‐Frequency Electromagnetic Field Altered PPARγ and CCL2 Levels and Suppressed CD44+/CD24− Breast Cancer Cells Characteristics
Authors: Oh In‐Rok , Raymundo Bernardo , Jung Sung A , Kim Hyun Jung , Park Jung‐Keug , Kim Chan‐Wha
Published: August 2020

Extremely low‐frequency electromagnetic fields (ELF‐EMFs) (1–300 Hz) have been found to have practical applications in biological research. A case in point is the effect of ELF‐EMF on the regulation of cell fate. In this study, we investigated the correlation between ELF‐EMF stimulation of PPARγ to the stemness, tumorigenicity, and invasiveness of breast cancer stem cells in vitro. The CD44+/CD24− subpopulation of the breast CSCs was isolated from the MDA‐MB‐231 breast cancer cell line. The CSCs were then exposed to ELF‐EMF and further assays were carried out. ELF‐EMF increased the expression of PPARγ and other critical proteins leading to cell cycle arrest and reduced stemness as evidenced by decreased expression of stemness genes and reduced proliferation rate in ELF‐EMF‐exposed CSCs compared to that in nonexposed CSCs. There was a decrease in the tumor‐forming and invasion ability of CSCs that were exposed to ELF‐EMFs.
“Designer babies?!” A CRISPR‐based learning module for undergraduates built around the CCR5 gene
Authors: Pieczynski Jay N. , Kee Hooi Lynn
Published: August 2020

CRISPR‐cas technology is being incorporated into undergraduate biology curriculum through lab experiences to immerse students in modern technology that is rapidly changing the landscape of science, medicine and agriculture. We developed and implemented an educational module that introduces students to CRISPR‐cas technology in a Genetic course and an Advanced Genetics course. Our primary teaching objective was to immerse students in the design, strategy, conceptual modeling, and application of CRISPR‐cas technology using the current research claim of the modification of the CCR5 gene in twin girls. This also allowed us to engage students in an open conversation about the bioethical implications of heritable germline and non‐heritable somatic genomic editing. We assessed student‐learning outcomes and conclude that this learning module is an effective strategy for teaching undergraduates the fundamentals and application of CRISPR‐cas gene editing technology and can be adapted to other genes and diseases that are currently being treated with CRISPR‐cas technology.
Clinicopathological characteristics and survival of spinal cord astrocytomas
Authors: Zhang Yao‐Wu , Chai Rui‐Chao , Cao Ren , Jiang Wen‐Ju , Liu Wei‐Hao , Xu Yu‐Lun , Yang Jun , Wang Yong‐Zhi , Jia Wen‐Qing
Published: August 2020

Background

Due to their rarity, the clinicopathological characteristics and prognostic factors of spinal cord gliomas are still unclear. Here, we aimed to clarify these issues in a cohort of 108 spinal cord astrocytomas.

Methods

We characterized the clinicopathological characteristics, including 2016 World Health Organization (WHO) grade, age, sex, location, segment length, resection, pre‐ and postsurgery, Modified McCormick Scale (MMS), radio‐ and chemotherapy, and Ki‐67 and H3 K27M mutations, in 108 spinal cord astrocytomas through heatmaps. The Cox regression analysis and Kaplan‐Meier curves were used to study the prognostic value of these clinicopathological features.

Results

There are a total 38 H3 K27M‐mutant tumors, including 31 cases with histological grade II/III tumors. The age of low‐grade astrocytoma patients (WHO grade I/II, n = 54) was significantly younger (27.0 vs 35.5 years, P = .001) than those with high‐grade tumors (WHO grade III/IV, n = 54). All patients underwent surgical resection with neurophysiological monitoring, and the surgery did not result in significant changes in MMS. The presurgery MMS was associated with overall survival in the high‐grade subgroup (P = .008) but not in the low‐grade subgroup (P = .312). While, the high content of resection improved the survival of only patients with low‐grade astrocytomas (P = .016) but not those with high‐grade astrocytomas (P = .475). Both the low‐grade and high‐grade astrocytomas had no obvious benefit from neither adjuvant chemotherapy nor radiotherapy (all P > .05).

Conclusions

We characterized the clinicopathological characteristics and their prognostic values in 108 spinal cord astrocytomas, which could help with evidence‐based management of spinal cord astrocytomas.
Confront the challenges of 2020 with community support
Authors: Sutton Halley
Published: August 2020

The Campus Security Report Advisory Board spoke, via Zoom call, about several of the issues facing campus security officers today, including how the COVID‐19 pandemic has impacted roles on campus, concerns about the upcoming fall semester, and how protests on campus might impact relations with students. On the call were David Miles, University Director of Public Safety at Fairleigh Dickinson University; Lara Fox, Director of Clery Compliance at Northern Arizona University; Stanley Skipworth, Director of Campus Safety at Claremont Colleges; Ed Book, Chief of Police & Emergency Management at Santa Fe College; and Jeff Kedrowski, Principal at FOG Advisors, Security Management Consultants.
Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum‐Targeting Copper(II) Complex
Authors: Kaur Pooja , Johnson Alice , Northcote‐Smith Joshua , Lu Chunxin , Suntharalingam Kogularamanan
Published: August 2020

Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4, capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub‐micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC‐potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC‐enriched HMLER‐shEcad spheroid formation and viability over non‐tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage‐associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells.
Efficacy of drug‐coated balloon angioplasty after directional coronary atherectomy for coronary bifurcation lesions (DCA/DCB registry)
Authors: Kitani Shunsuke , Igarashi Yasumi , Tsuchikane Etsuo , Nakamura Shigeru , Seino Yoshitane , Habara Maoto , Takeda Yoshihiro , Shimoji Kenichiro , Yasaka Yoshinori , Kijima Mikihiro
Published: August 2020

Objectives

To evaluate the efficacy and safety of additional drug‐coated balloon (DCB) angioplasty after directional coronary atherectomy (DCA) for coronary bifurcation lesions.

Background

The optimal therapy for bifurcation lesions has not been established, even in the drug‐eluting stent era. DCA possibly prevents plaque and carina shift in bifurcation lesions by plaque debulking; however, the efficacy of combined DCA and DCB (DCA/DCB) for bifurcation lesions remains unclear.

Methods

This multicenter registry retrospectively recruited patients with bifurcation lesions who underwent DCA/DCB and follow‐up angiogram at 6–15 months. The primary endpoint was the 12‐month target vessel failure (TVF) rate. The secondary endpoints were procedure‐related major complications, major cardiovascular events at 12 months, restenosis at 12 months, target lesion revascularization (TLR) at 12 months, and target vessel revascularization (TVR) at 12 months.

Results

We enrolled 129 patients from 16 Japanese centers. One hundred and four lesions (80.6%) were located around the left main trunk bifurcations. No side branch compromise was found intraoperatively. Restenosis was observed in three patients (2.3%) at 12 months. TLR occurred in four patients (3.1%): 3 (2.3%) in the main vessel and 1 (0.8%) in the ostium of the side branch at 12 months. TVF incidence at 12 months was slightly higher in 14 patients (10.9%), and only two patients (1.6%) had symptomatic TVR. One patient (0.8%) had non‐target vessel‐related myocardial infarction.

Conclusions

Our data suggested that DCA/DCB provided good clinical outcomes and minimal side branch damage and could be an optimal non‐stent percutaneous coronary intervention strategy for bifurcation lesions.
Oral findings and craniofacial morphology in a patient with Schwartz‐Jampel syndrome and severe obstructive sleep apnea: A case report
Authors: Pibulniyom Mevadee , Pungchanchaikul Patimaporn , Assawakawintip Thanate , Peanchitlertkajorn Supakit
Published: August 2020

We reported dental and craniofacial characteristics of an SJS patient with severe OSA. Not only does the syndrome cause skeletal abnormalities and myotonia, but it also affects the craniofacial development resulting in a severe constriction of maxillary arch and bimaxillary retrognathia which may increase a risk to develop pediatric OSA.
Recent Advances in Heterogeneous Catalysis for Ammonia Synthesis
Authors: Marakatti Vijaykumar S. , Gaigneaux Eric M.
Published: August 2020

Even after a century, ammonia (NH3) synthesis from nitrogen and hydrogen through Haber‐Bosch process is still energy intensive. Even with recently introduced second generation Ru based catalysts with superior performance over commercial Fe based catalysts, there is still place for upgrading with new approach using advanced materials in catalyst formulation. The alkali and alkaline metal promoted Ru supported carbon and metal oxide catalyst attracted attention at initial stage and extensively studied for NH3 synthesis in the 20th century. Until recently, advanced materials such as electrides, hydrides, nitrides, oxides and oxy‐hydrides‐nitrides studied as support and active component of catalyst fascinated much attention, with milder reaction conditions for NH3 synthesis. These materials with unique properties of reversible storage of electrons, hydrides, nitrides and oxygen vacancies enrich electron density on Ru catalyst and cleave N≡N bond with very low activation energy (<60 kJ/mol). The mechanistic understanding of these materials leads to the fact that activation N≡N bond is no more rate‐determining step (RDS). Instead, formation of N−H bond is RDS, pushing towards an innovative research directions and scientific basis for development of new catalysts. Enormous maturation of experimental and theoretical methods with improved precession over worldwide research effort helped in gaining a fundamental understanding of these materials in NH3 synthesis. The most of Ru supported on these advanced materials were better in performance compared to benchmark Cs−Ru/MgO and Ru/AC catalysts in NH3 synthesis. Insights on these materials and their mechanism are covered in this review, which digs towards finding a realistic catalyst for NH3 synthesis.
2D PbS Nanosheets with Zigzag Edges for Efficient CO2 Photoconversion
Authors: Zhu Zezhou , Qu Yunteng , Wang Zhiyuan , Zhou Fangyao , Zhao Changming , Lin Yue , Li Liqiang , Yao Yagang , Wu Yuen
Published: August 2020

The rational design of transition‐metal sulfide with two‐dimensional (2D) structure and tunable edges on the nanoscale can effectively improve their activity for variously catalytic reactions. Herein, the 2D PbS nanosheets with abundant zigzag edges (e‐PbS NS), which exhibited an excellent performance for CO2 photoconversion to CO, were constructed. The zigzag edges on the PbS NS are beneficial for exposing more active sites and promoting charge separation, thereby accelerating the kinetics process of CO2 photoreduction. This study provides a strategy to regulate structure with effective edge sites for the CO2 reduction.
Suzuki Cross‐Coupling Reaction with Genetically Encoded Fluorosulfates for Fluorogenic Protein Labeling
Authors: Zhao Qian , Guo Guoying , Zhu Weiwei , Zhu Liping , Da Yifan , Han Ying , Xu Hongjiao , Wu Shuohan , Cheng Yaping , Zhou Yani , Cai Xiaoqing , Jiang Xianxing
Published: August 2020

A palladium‐catalyzed cross‐coupling reaction with aryl halide functionalities has recently emerged as a valuable tool for protein modification. Herein, a new fluorogenic modification methodology for proteins, with genetically encoded fluorosulfate‐l‐tyrosine, which exhibits high efficiency and biocompatibility in bacterial cells as well as in aqueous medium, is described. Furthermore, the cross‐coupling of 4‐cyanophenylboronic acid on green fluorescent protein was shown to possess a unique fluorogenic property, which could open up the possibility of a responsive “off/on” switch with great potential to enable spectroscopic imaging of proteins with minimal background noise. Taken together, a convenient and efficient catalytic system has been developed that may provide broad utilities in protein visualization and live‐cell imaging.
Heavy‐Atom Tunneling in Semibullvalenes: How Driving Force, Substituents, and Environment Influence the Tunneling Rates
Authors: Schleif Tim , Tatchen Jörg , Rowen Julien F. , Beyer Frederike , Sanchez‐Garcia Elsa , Sander Wolfram
Published: August 2020

Invited for the cover of this issue are the groups of Elsa Sanchez‐Garcia and Wolfram Sander at the Universität Duisburg‐Essen and the Ruhr‐Universität Bochum. The image depicts the ideas skillfully visualized by Markus Henkel on the shift in equilibrium induced by isotopic labelling. Read the full text of the article at 10.1002/chem.202001202.
Total Synthesis of Dictyodendrins A–F by the Gold‐Catalyzed Cascade Cyclization of Conjugated Diyne with Pyrrole
Authors: Matsuoka Junpei , Inuki Shinsuke , Matsuda Yuka , Miyamoto Yoichi , Otani Mayumi , Oka Masahiro , Oishi Shinya , Ohno Hiroaki
Published: August 2020

Invited for the cover of this issue is Hiroaki Ohno and co‐workers at Kyoto University and National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN). The image depicts gold catalysis which promotes the domino reaction to push the switch for the diversity‐directed total synthesis. Read the full text of the article at 10.1002/chem.202001950.
C(1)‐Phenethyl Derivatives of [closo‐1‐CB11H12]− and [closo‐1‐CB9H10]− Anions: Difunctional Building Blocks for Molecular Materials
Authors: Jakubowski Rafał , Pietrzak Anna , Friedli Andrienne C. , Kaszyński Piotr
Published: August 2020

C(1)‐vinylation of [closo‐1‐CB9H10]− (A) and [closo‐1‐CB11H12]− (B) with 4‐benzyloxystyryl iodide followed by hydrogenation of the double bond and reductive deprotection of the phenol functionality led to C(1)‐(4‐hydroxyphenethyl) derivatives. The phenol functionality was protected as the acetate. The esters were then treated with PhI(OAc)2 and the resulting isomers were separated kinetically (for derivatives of anion A) or by chromatography (for derivatives of anion B) giving the difunctionalized building blocks in overall yields of 9 % and 50 %, respectively. A similar series of reactions was performed starting with anions A and B and 4‐methoxystyryl bromide and iodide. Significant differences in the reactivity of derivatives of the two carborane anions were rationalized with DFT computational results. Application of the difunctionalized carboranes as building blocks was demonstrated through preparation of two ionic liquid crystals. The extensive synthetic work is accompanied by single crystal XRD analysis of six derivatives.
Non‐Coordinated Phenolate Anions and Their Application in SF6 Activation
Authors: Weitkamp Robin F. , Neumann Beate , Stammler Hans‐Georg , Hoge Berthold
Published: August 2020

The reaction of the strong monophosphazene base with the weakly acidic phenol leads to the formation of a phenol–phenolate anion with a moderately strong hydrogen bond. Application of the more powerful tetraphosphazene base (Schwesinger base) renders the isolation of the corresponding salt with a free phenolate anion possible. This compound represents the first species featuring the free phenolate anion [H5C6‐O]−. The deprotonation of phenol derivatives with tetraphosphazene bases represents a great way for the clean preparation of salts featuring free phenolate anions and in addition allows the selective syntheses of hydrogen bonded phenol‐phenolate salts. This work presents a phosphazenium phenolate salt with a redox potential of −0.72 V and its capability for the selective activation of the chemically inert greenhouse gas SF6. The performed two‐electron reduction of SF6 leads to phosphazenium pentafluorosulfanide ([SF5]−) and fluoride salts.
Life Cycle Assessment of Steel Mill Gas‐Based Methanol Production within the Carbon2Chem® Project
Authors: Thonemann Nils , Maga Daniel
Published: August 2020

Within the Carbon2Chem® project, new processes have been developed to valorize steel mill gases by producing methanol. This article compares the global warming impact of integrated steel and methanol production to the stand‐alone production of steel and methanol. In order to generate mass and energy balances of the cross‐industrial network, several simulation approaches were conducted, and two power sources investigated. In the case of a power mix in 2030, the conventional production of steel and methanol is favorable, and in the case of wind power, the integrated production of steel and methanol shows greater benefit. If an electricity mix with a carbon intensity of less than 0.23 kgCO2‐eq.kWh−1 electricity is used, the integrated production of steel and methanol has a lower global warming impact than stand‐alone steel and methanol production.
Combination of Refractometry and Densimetry – A Promising Option for Fast Raw Methanol Analysis
Authors: Martens Marla , Hadrich Max J. , Nestler Florian , Ouda Mohamed , Schaadt Achim
Published: August 2020

Besides water, raw methanol produced from steel mill gases within the Carbon2Chem® project contains dissolved carbon dioxide. Refractometry and densimetry were investigated as analysis methods to analyze raw methanol samples quickly and reliably. To verify existing calibration curves, a set of standard solutions from pure chemicals was produced. Experimental results differed significantly from published refractive index data, especially in the range of high methanol weight fractions, which are of particular interest for the Carbon2Chem® project.
Druggability Assessment for Selected Serine Proteases in a Pharmaceutical Industry Setting
Authors: Wehrhan Leon , Hillisch Alexander , Mundt Stefan , Tersteegen Adrian , Meier Katharina
Published: August 2020

Target druggability assessment is an integral part of the early target characterization and selection process in pharmaceutical industry. Here, we investigate a set of five different serine proteases from the blood coagulation cascade. The aim of this study is twofold. Firstly, leveraging the wealth of available in‐house high‐throughput screening (HTS) data, we analyze HTS hit rates and discuss their predictive value for the development of small molecule (SMOL) candidates. Purely structure‐activity relationship (SAR) based druggability ratings are compared with computational protein‐structure based druggability assessments. Secondly, we evaluate the impact of using conformational ensembles from molecular dynamics (MD) simulations instead of single static crystal structures as basis for computational druggability assessments. Based on this study, we recommend incorporating molecular dynamics routinely into the early target characterization process, especially if only a single X‐ray structure is available.
Exploiting historical data: Pruning autotuning spaces and estimating the number of tuning steps
Authors: Oľha Jaroslav , Hozzová Jana , Fousek Jan , Filipovič Jiří
Published: August 2020

Autotuning, the practice of automatic tuning of applications to provide performance portability, has received increased attention in the research community, especially in high performance computing. Ensuring high performance on a variety of hardware usually means modifications to the code, often via different values of a selected set of parameters, such as tiling size, loop unrolling factor, or data layout. However, the search space of all possible combinations of these parameters can be large, which can result in cases where the benefits of autotuning are outweighed by its cost, especially with dynamic tuning. Therefore, estimating the tuning time in advance or shortening the tuning time is very important in dynamic tuning applications. We have found that certain properties of tuning spaces do not vary much when hardware is changed. In this article, we demonstrate that it is possible to use historical data to reliably predict the number of tuning steps that is necessary to find a well‐performing configuration and to reduce the size of the tuning space. We evaluate our hypotheses on a number of HPC benchmarks written in CUDA and OpenCL, using several different generations of GPUs and CPUs.
Photoswitching Molecular Junctions: Platforms and Electrical Properties
Authors: Kim Youngsang
Published: August 2020

Remarkable advances in technology have enabled the manipulation of individual molecules and the creation of molecular electronic devices utilizing single and ensemble molecules. Maturing the field of molecular electronics has led to the development of functional molecular devices, especially photoswitching or photochromic molecular junctions, which switch electronic properties under external light irradiation. This review introduces and summarizes the platforms for investigating the charge transport in single and ensemble photoswitching molecular junctions as well as the electronic properties of diverse photoswitching molecules such as diarylethene, azobenzene, dihydropyrene, and spiropyran. Furthermore, the article discusses the remaining challenges and the direction for moving forward in this area for future photoswitching molecular devices.
Development of High‐Drug‐Loading Nanoparticles
Authors: Liu Yun , Yang Guangze , Jin Song , Xu Letao , Zhao Chun‐Xia
Published: August 2020

Formulating drugs into nanoparticles offers many attractive advantages over free drugs including improved bioavailability, minimized toxic side effects, enhanced drug delivery, feasibility of incorporating other functions such as controlled release, imaging agents for imaging, targeting delivery, and loading more than one drug for combination therapies. One of the key parameters is drug loading, which is defined as the mass ratio of drug to drug‐loaded nanoparticles. Currently, most nanoparticle systems have relatively low drug loading (<10 wt%), and developing methods to increase drug loading remains a challenge. This Minireview presents an overview of recent research on developing nanoparticles with high drug loading (>10 wt%) from the perspective of synthesis strategies, including post‐loading, co‐loading, and pre‐loading. Based on these three different strategies, various nanoparticle systems with different materials and drugs are summarized and discussed in terms of their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stabilities, and their applications in drug delivery. The advantages and disadvantages of these strategies are presented with an objective of providing useful design rules for future development of high‐drug‐loading nanoparticles.
Novel Arylazo‐1,2,5‐oxadiazole Photoswitches: Synthesis, Photoisomerization and Nitric Oxide Releasing Properties
Authors: Zhilin Egor S. , Polkovnichenko Michael S. , Ananyev Ivan V. , Fershtat Leonid L. , Makhova Nina N.
Published: August 2020

A series of novel molecular photoswitches incorporating an aryldiazenyl moiety linked to a 1,2,5‐oxadiazole (furazan) or 1,2,5‐oxadiazole 2‐oxide (furoxan) subunit was synthesized by a simple and step‐economic chemical route. Upon visible light irradiation, (E)‐arylazo‐1,2,5‐oxadiazoles underwent photoisomerization to the corresponding (Z)‐isomers which are stable under ambient conditions. Structural factors affecting the photoswitching ability were also revealed. Synthesized photoswitches exhibited good performance due to the absence of fatigue or decomposition over at least ten cycles under air in a temperature range of 20–60 °C. NO donor properties of the synthesized arylazofuroxans were also evaluated in vitro and it was found that (Z)‐arylazofuroxans released significantly larger amounts of NO than the corresponding (E)‐isomers, which suggests strong potential of these molecular photoswitches in photopharmacology and other biomedical applications.
Rotational properties of annulus dusty plasma in a strong magnetic field
Authors: Choudhary Mangilal , Bergert Roman , Moritz Sandra , Mitic Slobodan , Thoma Markus H.
Published: August 2020

The collective dynamics of an annulus dusty plasma formed between a co‐centric conducting (non‐conducting) disk and ring configuration is studied in a strongly magnetized radiofrequency (rf) discharge. A superconducting electromagnet is used to introduce a homogeneous magnetic field to the dusty plasma medium. In the absence of the magnetic field, the dust grains exhibit thermal motion around their equilibrium position. The dust grains start to rotate in the anticlockwise direction with increasing magnetic field (B > 0.02 T), and the constant value of the angular frequency at various strengths of the magnetic field confirms the rigid body rotation. The angular frequency of dust grains linearly increases up to a threshold magnetic field (B > 0.6 T) and after that its value remains nearly constant in a certain range of magnetic field. Further increase in magnetic field (B > 1 T) lowers the angular frequency. Low value of the angular frequency is expected by reducing the width of the annulus dusty plasma or the input rf power. The azimuthal ion drag force due to the magnetic field is assumed to be the energy source which drives the rotational motion. The resultant radial electric field in the presence of a magnetic field determines the direction of rotation. The variation of floating (plasma) potential across the annular region at given magnetic field explains the rotational properties of the annulus dusty plasma in the presence of a magnetic field.