bluuebunny/crossref_metadata_2025 huggingface dataset:
A truncating NRIP1 variant in an Arabic family with congenital anomalies of the kidneys and urinary tract
Authors: Zheng Bixia , Wang Chunyan , Seltzsam Steve , Schneider Sophia , Schierbaum Luca , Wu Wilfred , Dai Rufeng , Connaughton Dervla M. , Nakayama Makiko , Mann Nina , Bauer Stuart B. , Awad Hazem S. , Eid Loai A. , Tasic Velibor , Shril Shirlee , Hildebrandt Friedhelm
Published: September 2021

Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of early‐onset chronic kidney disease. In a previous study, we identified a heterozygous truncating variant in nuclear receptor‐interacting protein 1 (NRIP1) as CAKUT causing via dysregulation of retinoic acid signaling. This large family remains the only family with NRIP1 variant reported so far. Here, we describe one additional CAKUT family with a truncating variant in NRIP1. By whole‐exome sequencing, we identified one heterozygous frameshift variant (p.Asn676Lysfs*27) in an isolated CAKUT patient with bilateral hydroureteronephrosis and right grade V vesicoureteral reflux (VUR) and in the affected father with left renal hypoplasia. The variant is present twice in a heterozygous state in the gnomAD database of 125,000 control individuals. We report the second CAKUT family with a truncating variant in NRIP1, confirming that loss‐of‐function mutations in NRIP1 are a novel monogenic cause of human autosomal dominant CAKUT.
Design of Persistent and Stable Porous Radical Polymers by Electronic Isolation Strategy
Authors: Su Yan , Chen Zhongxin , Tang Xiaohui , Xu Hong , Zhang Yujian , Gu Cheng
Published: September 2021

Conjugated organic radical polymers with stable radical features are difficult to design because the π conjugation in the polymer backbones makes the radicals readily delocalize and tend to undergo covalent bonding processes. In this work, we report an electronic isolation strategy to design stable porous radical polymers by homocoupling reaction from a meta‐position active monomer. The meta linkage ensures less conjugation in the polymer skeletons, localizes the resonant radicals, and prevents them from recombination. The resulting porous radical polymer exhibits exceptional radical characters with ultralow band gap of 0.68 eV, strong yet extended UV/Vis‐NIR absorption up to 1800 nm, and high spin density. The above features make the polymer very promising in the photothermal conversion with record‐high photothermal temperature increment of ≈∼240 °C and striking solar‐driven water evaporation efficiency of 96.8 %. Our results demonstrate the feasibility of electronic isolation of radicals for producing outstanding photothermal materials.
Atomic Cation‐Vacancy Engineering of NiFe‐Layered Double Hydroxides for Improved Activity and Stability towards the Oxygen Evolution Reaction
Authors: Peng Lishan , Yang Na , Yang Yuqi , Wang Qing , Xie Xiaoying , Sun‐Waterhouse Dongxiao , Shang Lu , Zhang Tierui , Waterhouse Geoffrey I. N.
Published: September 2021

NiFe‐layered double hydroxides (NiFe‐LDH) are among the most active catalysts developed to date for the oxygen evolution reaction (OER) in alkaline media, though their long‐term OER stability remains unsatisfactory. Herein, we reveal that the stability degradation of NiFe‐LDH catalysts during alkaline OER results from a decreased number of active sites and undesirable phase segregation to form NiOOH and FeOOH, with metal dissolution underpinning both of these deactivation mechanisms. Further, we demonstrate that the introduction of cation‐vacancies in the basal plane of NiFe LDH is an effective approach for achieving both high catalyst activity and stability during OER. The strengthened binding energy between the metals and oxygen in the LDH sheets, together with reduced lattice distortions, both realized by the rational introduction of cation vacancies, drastically mitigate metal dissolution from NiFe‐LDH under high oxidation potentials, resulting in the improved long‐term OER stability. In addition, the cation vacancies (especially M3+ vacancies) accelerate the evolution of surface γ‐(NiFe)OOH phases, thereby boosting the OER activity. The present study highlights that tailoring atomic cation‐vacancies is an important strategy for the development of active and stable OER electrocatalysts.
The Significance of Properly Reporting Turnover Frequency in Electrocatalysis Research
Authors: Anantharaj Sengeni , Karthik Pitchiah Esakki , Noda Suguru
Published: September 2021

For decades, turnover frequency (TOF) has served as an accurate descriptor of the intrinsic activity of a catalyst, including those in electrocatalytic reactions involving both fuel generation and fuel consumption. Unfortunately, in most of the recent reports in this area, TOF is often not properly reported or not reported at all, in contrast to the overpotentials at a benchmarking current density. The current density is significant in determining the apparent activity, but it is affected by catalyst‐centric parasitic reactions, electrolyte‐centric competing reactions, and capacitance. Luckily, a properly calculated TOF can precisely give the intrinsic activity free from these phenomena in electrocatalysis. In this Viewpoint we ask: 1) What makes the commonly used activity markers unsuitable for intrinsic activity determination? 2) How can TOF reflect the intrinsic activity? 3) Why is TOF still underused in electrocatalysis? 4) What methods are used in TOF determination? and 5) What is essential in the more accurate calculation of TOF? Finally, the significance of normalizing TOF by Faradaic efficiency (FE) is stressed and we give our views on the development of universal analytical tools to determine the exact number of active sites and real surface area for all kinds of materials.
Unexpected Reactions of α,β‐Unsaturated Fatty Acids Provide Insight into the Mechanisms of CYP152 Peroxygenases
Authors: Jiang Yuanyuan , Peng Wei , Li Zhong , You Cai , Zhao Yue , Tang Dandan , Wang Binju , Li Shengying
Published: September 2021

CYP152 peroxygenases catalyze decarboxylation and hydroxylation of fatty acids using H2O2 as cofactor. To understand the molecular basis for the chemo‐ and regioselectivity of these unique P450 enzymes, we analyze the activities of three CYP152 peroxygenases (OleTJE, P450SPα, P450BSβ) towards cis‐ and trans‐dodecenoic acids as substrate probes. The unexpected 6S‐hydroxylation of the trans‐isomer and 4R‐hydroxylation of the cis‐isomer by OleTJE, and molecular docking results suggest that the unprecedented selectivity is due to OleTJE’s preference of C2−C3 cis‐configuration. In addition to the common epoxide products, undecanal is the unexpected major product of P450SPα and P450BSβ regardless of the cis/trans‐configuration of substrates. The combined H218O2 tracing experiments, MD simulations, and QM/MM calculations unravel an unusual mechanism for Compound I‐mediated aldehyde formation in which the active site water derived from H2O2 activation is involved in the generation of a four‐membered ring lactone intermediate. These findings provide new insights into the unusual mechanisms of CYP152 peroxygenases.
Sn2PO4I: An Excellent Birefringent Material with Giant Optical Anisotropy in Non π‐Conjugated Phosphate
Authors: Guo Jingyu , Tudi Abudukadi , Han Shujuan , Yang Zhihua , Pan Shilie
Published: September 2021

Exploring non π‐conjugated phosphate birefringent crystal with a large birefringence has been a great challenge. Herein, based on the unique two‐dimensional layered structure in KBe2BO3F2 (KBBF), two new compounds, Sn2PO4I and Sn2BO3I, were designed and synthesized successfully, maintaining the layer structural feature and enhancing the optical anisotropy of crystals. In particular, the birefringence of Sn2PO4I is larger than or equal to 0.664 @546 nm, which is largest among the reported borates and phosphates, even surpassing commercial birefringent crystals YVO4 and TiO2. This work indicates that a breakthrough in birefringence of inorganic compound was achieved. Also, it provides a guiding idea for exploring large birefringence materials in the future.
Molten Salt Electrochemical Modulation of Iron–Carbon–Nitrogen for Lithium–Sulfur Batteries
Authors: Weng Wei , Xiao Juanxiu , Shen Yijun , Liang Xinxin , Lv Teng , Xiao Wei
Published: September 2021

Sulfur hosts with rationally designed chemistry to confine and convert lithium polysulfides are of prime importance for high‐performance lithium–sulfur batteries. A molten salt electrochemical modulation of iron–carbon–nitrogen is herein demonstrated as formation of hollow nitrogen‐doped carbon with grafted Fe3C nanoparticles (Fe3C@C@Fe3C), which is rationalized as an excellent sulfur host for lithium‐sulfur batteries. Fe3C over nitrogen‐doped carbon contributes to enhanced adsorption and catalytic conversion of lithium polysulfides. The sulfur‐loaded Fe3C@C@Fe3C electrodes hence show a high capacity, good cyclic stability, and enhanced rate performance. This work highlights the unique chemistry of metal carbides on facilitating adsorption–conversion process of lithium polysulfides, and also extends the scope of molten salt electrolysis to elaboration of energy materials.
Dynamic Control of Sacrificial Bond Transformation in the Fe−N−C Single‐Atom Catalyst for Molecular Oxygen Reduction
Authors: Yu Li , Li Yuchan , Ruan Yuefei
Published: September 2021

Atomically dispersed metal‐nitrogen sites show great prospect for the oxygen reduction reaction (ORR), whereas the unsatisfactory adsorption‐desorption behaviors of oxygenated intermediates on the metal centers impede improvement of the ORR performance. We propose a new conceptual strategy of introducing sacrificial bonds to remold the local coordination of Fe−Nx sites, via controlling the dynamic transformation of the Fe−S bonds in the Fe−N−C single‐atom catalyst. Spectroscopic and theoretical results reveal that the selective cleavage of the sacrificial Fe−S bonds induces the incorporation of the electron‐withdrawing oxidized sulfur on the Fe centers. The newly functionalized moieties endow the catalyst with superior ORR activity and remarkable stability, owing to the reduced electron localization around the Fe centers facilitating the desorption of ORR intermediates. These findings provide a unique perspective for precisely controlling the coordination structure of single‐atom materials to optimize their activity.
Ring Expansion Fluorination of Unactivated Cyclopropanes Mediated by a New Monofluoroiodane(III) Reagent
Authors: Ren Jing , Du Feng‐Huan , Jia Meng‐Cheng , Hu Ze‐Nan , Chen Ze , Zhang Chi
Published: September 2021

Herein, we report a new strategy for carbon−carbon bond scission and intramolecular ring expansion fluorination of unactivated cyclopropanes, which was accomplished with a new hypervalent fluoroiodane(III) reagent1. This novel method delivers medicinally relevant 4‐fully substituted fluoropiperidines in moderate to high yields with excellent regio‐ and diastereoselectivity. Reagent1, which has an N‐acetylbenziodazole framework, was readily synthesized via three steps in 76 % overall yield and was characterized by NMR spectroscopy and X‐ray crystallography. Owing to the presence of a secondary I⋅⋅⋅O bonding interaction between the λ3‐iodane atom and the carbonyl oxygen of the acetyl group of the N‐acetylbenziodazole framework,1has excellent stability and can be stored at ambient temperature for 6 months without any detectable decomposition. Density functional theory calculations and experimental studies showed that the reaction proceeds via a carbocation intermediate that readily combines with a fluoride ion to generate the product.
Modulating Tri‐Mode Emission for Single‐Component White Organic Afterglow
Authors: Jin Jibiao , Xue Peiran , Zhang Longyan , Jiang He , Wang Wuji , Yang Qingqing , Tao Ye , Zheng Chao , Chen Runfeng , Huang Wei
Published: September 2021

Achieving single‐component white organic afterglow remains a great challenge owing to the difficulties in simultaneously supporting long‐lived emissions from varied excited states of a molecule for complementary afterglow. Here, an extraordinary tri‐mode emission from the radiative decays of singlet (S1), triplet (T1), and stabilized triplet (T1*) excited states was proposed to afford white afterglow through modulating the singlet–triplet splitting energy (ΔEST) and exciton trapping depth (ETD). Low‐lying T1* for yellow afterglow was constructed by H‐aggregation engineering with large ETD and trace isomer doping, while high‐lying T1 and S1 for blue afterglow with thermally activated emission feature were realized by reducing ΔEST through donor–acceptor molecular design. Therefore, the single‐component white afterglow with high efficiency of 14.1 % and a lifetime of 0.61 s was achieved by rationally regulating the afterglow intensity ratios of complementary emissions from S1, T1, and T1*.
Anion–Anion Chemistry with Mass‐Selected Molecular Fragments on Surfaces
Authors: Yang Fangshun , Behrend K. Antonio , Knorke Harald , Rohdenburg Markus , Charvat Ales , Jenne Carsten , Abel Bernd , Warneke Jonas
Published: September 2021

While reactions between ions and neutral molecules in the gas phase have been studied extensively, reactions between molecular ions of same polarity remain relatively unexplored. Herein we show that reactions between fragment ions generated in the gas phase and molecular ions of the same polarity are possible by soft‐landing of both reagents on surfaces. The reactive [B12I11]1− anion was deposited on a surface layer built up by landing the generally unreactive [B12I12]2−. Ex‐situ analysis of the generated material shows that [B24I23]3− was formed. A computational study shows that the product is metastable in the gas phase, but a charge‐balanced environment of a grounded surface may stabilize the triply charged product, as suggested by model calculations. This opens new opportunities for the generation of highly charged clusters using unconventional building blocks from the gas phase.
Chemical and Enzymatic Synthesis of Sialylated Glycoforms of Human Erythropoietin
Authors: Hessefort Hendrik , Gross Angelina , Seeleithner Simone , Hessefort Markus , Kirsch Tanja , Perkams Lukas , Bundgaard Klaus Ole , Gottwald Karen , Rau David , Graf Christopher Günther Franz , Rozanski Elisabeth , Weidler Sascha , Unverzagt Carlo
Published: September 2021

Recombinant human erythropoietin (EPO) is the main therapeutic glycoprotein for the treatment of anemia in cancer and kidney patients. The in‐vivo activity of EPO is carbohydrate‐dependent with the number of sialic acid residues regulating its circulatory half‐life. EPO carries threeN‐glycans and thus obtaining pure glycoforms provides a major challenge. We have developed a robust and reproducible chemoenzymatic approach to glycoforms of EPO with and without sialic acids. EPO was assembled by sequential native chemical ligation of two peptide and three glycopeptide segments. The glycopeptides were obtained by pseudoproline‐assisted Lansbury aspartylation. Enzymatic introduction of the sialic acids was readily accomplished at the level of the glycopeptide segments but even more efficiently on the refolded glycoprotein. Biological recognition of the synthetic EPOs was shown by formation of 1:1 complexes with recombinant EPO receptor.
Single‐Phase Formation of Rh2O3 Nanoparticles on h‐BN Support for Highly Controlled Methane Partial Oxidation to Syngas
Authors: Kim Younhwa , Kang Sungsu , Kang Dohun , Lee Kyung Rok , Song Chyan Kyung , Sung Jongbaek , Kim Ji Soo , Lee Hyunjoo , Park Jungwon , Yi Jongheop
Published: September 2021

Single‐phase formation of active metal oxides on supports has been vigorously pursued in many catalytic applications to suppress undesired reactions and to determine direct structure‐property relationships. However, this is difficult to achieve in nanoscale range because the effect of non‐uniform metal‐support interfaces becomes dominant in the overall catalyst growth, leading to the nucleation of various metastable oxides. Herein, we develop a supported single‐phase corundum‐Rh2O3(I) nanocatalyst by utilizing controlled interaction between metal oxide and h‐BN support. Atomic‐resolution electron microscopy and first‐principle calculation reveal that single‐phase formation occurs via uniform and preferential attachment of Rh2O3(I) (110) seed planes on well‐defined h‐BN surface after decomposition of rhodium precursor. By utilizing the Rh/h‐BN catalyst in methane partial oxidation, syngas is successfully produced solely following the direct route with keeping a H2/CO ratio of 2, which makes it ideal for most downstream chemical processes.
Corroles: The Hitherto Elusive Parent Macrocycle and its Metal Complexes
Authors: Kumar Amit , Yadav Pinky , Majdoub Mahmoud , Saltsman Irena , Fridman Natalia , Kumar Sachin , Kumar Anil , Mahammed Atif , Gross Zeev
Published: September 2021

Corroles, macrocycles that owe their name to the cobalt‐chelating prosthetic group of vitamin B12 and share numerous features with the iron‐chelating porphyrin present in heme proteins/enzymes, constantly cross new boundaries ever since stable derivatives became easily accessible. Particularly important is the increasing utilization of corroles and the corresponding metal complexes for the benefit of mankind, in terms of new drug candidates for treating various diseases and as catalysts for sustainable energy relevant processes. One challenge is to gain access to the plain macrocycle, as to allow for full elucidation of the most fundamental properties of corroles. We have obtained the substituent‐free corrole by several surprising and conceptually different pathways. Selected features of the corresponding metal complexes are illuminated, for pointing towards unique phenomena that are anticipated to largely expand the horizon regarding their utilization for contemporary catalysis.
Aboriginal serrated and perforated shell artefacts from the Murray River, South Australia
Authors: ROBERTS AMY , WESTELL CRAIG , WILSON CHRISTOPHER , LANGLEY MICHELLE C. , MALLEE ABORIGINAL CORPORATION RIVER MURRAY AND , CORPORATION NGARRINDJERI ABORIGINAL
Published: September 2021

This article describes three freshwater mussel shell artefacts recently documented for the Murray River in South Australia. These finds more than double the known examples of such artefacts from this region. Two of the modified shells are perforated, with the other serrated. The finely serrated item is a rare artefact and we have not located any similar published examples in Australia, although international correlates exist. The function/s and cultural significance of the objects are also considered in this paper. Hypotheses for the perforated finds include ornamentation, tool stringing and fibre scraping. Ornamentation, idle tinkering and food utensil use are considered as possible intended functions for the serrated artefact. Given the age range of the objects reported here (c. 6181–517 cal BP), together with other finds in the Murray Darling Basin, we tentatively suggest that shells have been a material resource used continually in this region for a range of purposes. However, as argued by other researchers, we concur that there has probably been infrequent identification and reporting of such shell artefacts. This is considered particularly likely given that our finds were recovered from relatively small scale excavation/coring and surface sampling efforts. As such, this paper attempts to raise awareness of this form of material culture in archaeological sequences.
Synthesis and antischistosomal activity of linker‐ and thiophene‐modified biaryl alkyl carboxylic acid derivatives
Authors: Peter Ventura Alejandra M. , Haeberlein Simone , Konopka Leonie , Obermann Wiebke , Grünweller Arnold , Grevelding Christoph G. , Schlitzer Martin
Published: September 2021

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma and causes severe morbidity in infected patients. In 2018, 290.8 million people required treatment, and 200,000 deaths are reported per year. Treatment of this disease depends on a single drug, praziquantel (PZQ). However, in the past few years, reduced sensitivity of the parasites toward PZQ has been reported. Therefore, there is an urgent need for new drugs against this disease. In the past few years, we have focused on a new substance class called biaryl alkyl carboxylic acid derivatives, which showed promising antischistosomal activity in vitro. Structure–activity relationship (SAR) studies of the carboxylic acid moiety led to three promising carboxylic amides (morpholine, thiomorpholine, and methyl sulfonyl piperazine) with an antischistosomal activity down to 10 µM (morpholine derivative) and no cytotoxicity up to 100 µM. Here, we show our continued work on this substance class. We investigated, in extended SAR studies, whether modification of the linker and the thiophene ring could improve the antischistosomal activity. We found that the exchange of the alkyl linker by a pentadienyl or benzyl linker was tolerated and led to similar antischistosomal effects, whereas the exchange of the thiophene ring was not tolerated. Our data suggest that the thiophene ring is important for the antischistosomal activity of this compound class.
Gingival fenestration defect treated with gingivectomy and gingivoplasty: A case report with an 8‐year follow‐up
Authors: Kajimoto Natália de Campos , Buischi Yvonne de Paiva , Loomer Peter Michael , Pola Natália Marcumini , Nagata Maria José Hitomi , Bosco Alvaro Francisco
Published: September 2021

Introduction

Gingival fenestration (GF) is scarcely reported in the literature. We present a unique case of GF defect combined with gingivitis and altered passive eruption (APE).

Case Presentation

An 18‐year‐old female patient with gingivitis, APE, and GF in the mandibular left central incisor presented for periodontal treatment. The gingival lesion was successfully treated with basic periodontal therapy gingivectomy, and gingivoplasty and resulted in an excellent aesthetic long‐term outcome. This case report shows its 8‐year clinical follow‐up.

Conclusion

There are no earlier reports dealing with the use of gingivoplasty for the treatment of GF, as it is not the usual therapeutic intervention for these defects. Gingivoplasty proved to be effective in treating GF.

Why is this case new information?

Available literature on gingival fenestration defects does not describe gingivectomy and gingivoplasty as a treatment of choice.

Gingivectomy and gingivoplasty proved to be effective in treating gingival fenestration defects.

What are the keys to successful management of this case?

Proper diagnosis.

What are the primary limitations to success in this case?

Gingival fenestration has been defined when the overlying gingiva is denuded, exposing the root to the oral cavity. However, in this case report, only the crown was exposed because the patient had altered passive eruption.
Trinuclear Cyanido‐Bridged [Cr2Fe] Complexes: To Be or not to Be a Single‐Molecule Magnet, a Matter of Straightness
Authors: Pichon Céline , Suaud Nicolas , Jubault Valentin , Duhayon Carine , Guihéry Nathalie , Sutter Jean‐Pascal
Published: September 2021

Trinuclear systems of formula [{Cr(LN3O2Ph)(CN)2}2M(H2LN3O2R)] (M=MnII and FeII, LN3O2R stands for pentadentate ligands) were prepared in order to assess the influence of the bending of the apical M−N≡C linkages on the magnetic anisotropy of the FeII derivatives and in turn on their Single‐Molecule Magnet (SMM) behaviors. The cyanido‐bridged [Cr2M] derivatives were obtained by assembling trans‐dicyanido CrIII complex [Cr(LN3O2Ph)(CN)2]− and divalent pentagonal bipyramid complexes [MII(H2LN3O2R)]2+ with various R substituents (R=NH2, cyclohexyl, S,S‐mandelic) imparting different steric demand to the central moiety of the complexes. A comparative examination of the structural and magnetic properties showed an obvious effect of the deviation from straightness of the M−N≡C alignment on the slow relaxation of the magnetization exhibited by the [Cr2Fe] complexes. Theoretical calculations have highlighted important effects of the bending of the apical C−N−Fe linkages on both the magnetic anisotropy of the FeII center and the exchange interactions with the CrIII units.
Studies on The Application of The Paternò‐Büchi Reaction to The Synthesis of Novel Fluorinated Scaffolds
Authors: Gomez Fernandez Mario Andrés , Lefebvre Corentin , Sudau Alexander , Genix Pierre , Vors Jean‐Pierre , Abe Manabu , Hoffmann Norbert
Published: September 2021

In the context of new scaffolds obtained by photochemical reactions, Paternò‐Büchi reactions between heteroaromatic, trifluoromethylphenyl ketone and electron rich alkenes to give oxetanes are described. A comprehensive study has then been carried out on the reaction of aromatic ketones with fluorinated alkenes. Depending on the substitution pattern at the oxetane ring, a metathesis reaction is described as a minor side process to give mono fluorinated alkenes. Overall, this last reaction corresponds to a photo‐Wittig reaction and yield amid isosteres. In order to explain the uncommon regioselectivity of the Paternò‐Büchi reaction with these alkenes, electrostatic‐potential derived charges (ESP) have been determined. In a second computational study, the relative stabilities of the typical 1,4‐diradical intermediates of the Paternò‐Büchi reaction have been determined. The results well explain the regioselectivity. Further transformations of the oxetanes or previous functionalization of the fluoroalkenes open perspectives for oxetanes as core structures for biologically active compounds.
Enantiodivergent One‐Pot Synthesis of Axially Chiral Biaryls Using Organocatalyst‐Mediated Enantioselective Domino Reaction and Central‐to‐Axial Chirality Conversion
Authors: Koshino Seitaro , Taniguchi Tohru , Monde Kenji , Kwon Eunsang , Hayashi Yujiro
Published: September 2021

Enantiodivergent one‐pot synthesis of biaryls was developed using a catalytic amount of a single chiral source. A domino organocatalyst‐mediated enantioselective Michael reaction and aldol condensation provided centrally chiral dihydronaphthalenes with excellent enantioselectivity, from which an enantiodivergent chirality conversion from central‐to‐axial chirality was achieved. Both enantiomers of biaryls were obtained with excellent enantioselectivity. All transformations can be conducted in a single reaction vessel. A plausible reaction mechanism for the enantiodivergence is proposed.
Multiscale conformational dynamics probed by time‐resolved circular dichroism from seconds to picoseconds
Authors: Hache François , Changenet Pascale
Published: September 2021

Time‐resolved circular dichroism has been developed for a few decades to investigate rapid conformational changes in (bio)molecules. In our group, we have come up with several experimental set‐ups allowing us to study pico‐nanosecond local phenomena in molecular systems as well as much slower effects occurring in proteins and DNA in the folding processes. After an overview of the worldwide realizations in this domain, we present emblematic experiments that we have carried out, spanning time domain from picoseconds to seconds.
A Step toward NRF2‐DNA Interaction Inhibitors by Fragment‐Based NMR Methods
Authors: Brüschweiler Sven , Fuchs Julian E. , Bader Gerd , McConnell Darryl B. , Konrat Robert , Mayer Moriz
Published: September 2021

The NRF2 transcription factor is a key regulator in cellular oxidative stress response, and acts as a tumor suppressor. Aberrant activation of NRF2 has been implicated in promoting chemo‐resistance, tumor growth, and metastasis by activating its downstream target genes. Hence, inhibition of NRF2 promises to be an attractive therapeutic strategy to suppress cell proliferation and enhance cell apoptosis in cancer. Direct targeting of NRF2 with small‐molecules to discover protein‐DNA interaction inhibitors is challenging as it is a largely intrinsically disordered protein. To discover molecules that bind to NRF2 at the DNA binding interface, we performed an NMR‐based fragment screen against its DNA‐binding domain. We discovered several weakly binding fragment hits that bind to a region overlapping with the DNA binding site. Using SAR by catalogue we developed an initial structure‐activity relationship for the most interesting initial hit series. By combining NMR chemical shift perturbations and data‐driven docking, binding poses which agreed with NMR information and the observed SAR were elucidated. The herein discovered NRF2 hits and proposed binding modes form the basis for future structure‐based optimization campaigns on this important but to date ‘undrugged’ cancer driver.
Dual Loading of Doxorubicin and Magnetic Iron Oxide into PLA‐TPGS Nanoparticles: Design, in vitro Drug Release Kinetics, and Biological Effects on Cancer Cells
Authors: Phan Ke Son , Ha Phuong Thu , Do Huu Nghi , Nguyen Trung Anh , Bui Thuc Quang , Pham Hong Nam , Le Mai Huong , Le Thi Thu Huong
Published: September 2021

The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)‐tocopheryl polyethylene glycol succinate (PLA‐TPGS) copolymer co‐loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA‐TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs.
Interplay of m6A and histone modifications contributes to temozolomide resistance in glioblastoma
Authors: Li Fuxi , Chen Siyun , Yu Jiaming , Gao Zhuoxing , Sun Zhangyi , Yi Yang , Long Teng , Zhang Chuanxia , Li Yuzhe , Pan Yimin , Qin Chaoying , Long Wenyong , Liu Qing , Zhao Wei
Published: September 2021

Background

Despite the development of new treatment protocols for glioblastoma (GBM), temozolomide (TMZ) resistance remains a primary hindrance. Previous studies, including our study, have shown that aberrant N6‐methyladenosine (m6A) modification is implicated in GBM pathobiology. However, the roles and precise mechanisms of m6A modification in the regulation of TMZ resistance in GBM remain unclear.

Methods

m6A individual‐nucleotide‐resolution cross‐linking and immunoprecipitation sequencing (miCLIP‐seq) was performed to identify m6A modification of transcripts in TMZ‐resistant and ‐sensitive tumors. To explore the role of METTL3 in TMZ resistance, TMZ‐resistant GBM cells were transfected with METTL3 shRNA or overexpression lentivirus and then assessed by cell viability, tumor sphere formation, and apoptosis assays. An intracranial GBM xenograft model was developed to verify the effect of METTL3 depletion during TMZ treatment in vivo. ATAC‐seq, ChIP‐qPCR, and dual‐luciferase reporter assays were carried out to verify the role of SOX4/EZH2 in the modulation of METTL3 expression upon TMZ treatment.

Results

We demonstrated that TMZ treatment upregulated the expression of the m6A methyltransferase METTL3, thereby increasing m6A modification of histone modification‐related gene transcripts. METTL3 is required to maintain the features of GBM stem cells. When combined with TMZ, METTL3 silencing suppressed orthotopic TMZ‐resistant xenograft growth in a cooperative manner. Mechanistically, TMZ induced a SOX4‐mediated increase in chromatin accessibility at the METTL3 locus by promoting H3K27ac levels and recruiting RNA polymerase II. Moreover, METTL3 depletion affected the deposition of m6A on histone modification‐related gene transcripts, such as EZH2, leading to nonsense‐mediated mRNA decay. We revealed an important role of EZH2 in the regulation of METTL3 expression, which was via an H3K27me3 modification‐independent manner.

Conclusions

Our findings uncover the fundamental mechanisms underlying the interplay of m6A RNA modification and histone modification in TMZ resistance and emphasize the therapeutic potential of targeting the SOX4/EZH2/METTL3 axis in the treatment of TMZ‐resistant GBM.
Physical layer secure key generation with nonlinear preprocessing of RSS for power constraint wireless networks
Authors: Sharma Ravindra , Upadhyay Raksha
Published: September 2021

There has been growing attention in physical layer security (PLS) techniques for wireless networks. PLS techniques are based on physical layer characteristics and are less computationally complex than traditional cryptographic approaches, which work on higher layers of networks. Physical layer key generation (PLKG) is one of the prominent key based PLS techniques that exploits reciprocity and randomness of wireless fading channel to establish secure communication between two transceivers. PLKG system consists of five stages as RSS measurement, its preprocessing, quantization and encoding, key reconciliation, and privacy amplification. Each stage has a substantial role in deciding the performance of PLKG system, but RSS preprocessing offers wide scope in performance improvement for the system. In this work, we propose PLKG system using a new class of preprocessing technique first time, which is nonlinear. We formulated the problem uniquely and considered two nonlinear techniques: nonlinear preprocessing using expander (NLPE) and nonlinear preprocessing using compressor (NLPC). We analyzed the performance of system using NLPE and NLPC and found NLPE is most suitable. Performance of the system is evaluated in terms of bit disagreement rate (BDR) and randomness of keys. Results show that NLPE performs extremely well, as compared with linear approach and without preprocessing approach, especially at low signal to noise ratio (SNR) range. Emerging wireless networks such as internet of things (IoT), centralized radio access network (CRAN), wireless sensor network (WSN), and so forth are being operated at lower transmission power with lightweight hardware. Hence, for such type of power constraint networks, proposed PLKG system with NLPE can be proven a perfect security solution.
Variation in parasite resistance of Arctic charr, Salvelinus alpinus, between and within sympatric morphs
Authors: Karvonen Anssi , Beck Samantha V. , Skúlason Skúli , Kristjánsson Bjarni K. , Leblanc Camille A.
Published: September 2021

Genetic variation in resistance against parasite infections is a predominant feature in host–parasite systems. However, mechanisms maintaining genetic polymorphism in resistance in natural host populations are generally poorly known. We explored whether differences in natural infection pressure between resource‐based morphs of Arctic charr (Salvelinus alpinus) have resulted in differentiation in resistance profiles. We experimentally exposed offspring of two morphs from Lake Þingvallavatn (Iceland), the pelagic planktivorous charr (“murta”) and the large benthivorous charr (“kuðungableikja”), to their common parasite, eye fluke Diplostomum baeri, infecting the eye humor. We found that there were no differences in resistance between the morphs, but clear differences among families within each morph. Moreover, we found suggestive evidence of resistance of offspring within families being positively correlated with the parasite load of the father, but not with that of the mother. Our results suggest that the inherited basis of parasite resistance in this system is likely to be related to variation among host individuals within each morph rather than ecological factors driving divergent resistance profiles at morph level. Overall, this may have implications for evolution of resistance through processes such as sexual selection.
EPR, Magnetic, and Computational Characterization of Linear and Zigzag Ladder‐type Chains of Exchange Coupled Cu(II) Complexes with Picolinic and Dipicolinic Acid Ligands
Authors: Pérez Ana L. , Kemmerer Axel , Baggio Ricardo , Ramos Carlos A. , Dalosto Sergio D. , Passeggi Mario C. G. , Rizzi Alberto C. , Brondino Carlos D.
Published: September 2021

We report magnetic, EPR, and computational studies on two representative examples of structurally well‐characterized one dimension (1D) molecular systems: the copper complexes catena‐[bis(μ‐pyridine‐2‐carboxylato)‐copper dihydrate] and catena‐[(μ2‐pyridine‐2,6‐dicarboxylato)‐diaqua‐copper(II)], hereafter 1 and 2, respectively. Experimental and theoretical results confirmed that the structural chains in both compounds behave as magnetic chains in which the copper ions are weakly coupled by isotropic exchange. Magnetic susceptibility measurements of 1 suggested that the copper ions are antiferromagnetically coupled whereas EPR measurements suggested ferromagnetic coupling at temperature above 100 K which becomes antiferromagnetic at low temperatures. Computational calculations would indicate that the ferromagnetic‐antiferromagnetic change may be due to dCu−Oap shortening on lowering temperature temperature (a fact that was observed experimentally by XRD at low temperatures), which redistributes the small Cu(II) unpaired spin density delocalized on the apical ligand to copper. The 1D magnetic behavior of the zigzag ladder chain of 2 is less detectable than that of the single chain of 1. Magnetic susceptibility measurements in conjunction with computational calculations showed that the pathways that give rise to the 1D ladder transmit ferromagnetic exchange interactions with different strengths, with the stronger interaction being transmitted along the rungs. The role of the weaker exchange interactions transmitted along the rails on the magnetic dimensionality of 2 is analyzed.
Efficient Conversion of Biomass Derived Levulinic Acid to γ‐Valerolactone Using Hydrosilylation
Authors: Garg Nitish K. , Schmalz Veronika , Johnson Magnus T. , Wendt Ola F.
Published: September 2021

Converting biomass into value‐added chemicals is of significant interest and we report an efficient hydrosilylation to convert levulinic acid to γ‐valerolactone using cost‐effective silanes such as PMHS and TMDS with B(C6F5)3 as catalyst. This metal free methodology works at room temperature reaching TONs and TOFs up to 16000 and 2000 h−1. Insights into the reaction mechanism are reported.
Monitoring of Intracellular Vesicles in Cultured Neurons at Different Growth Stages Using Intracellular Vesicle Electrochemical Cytometry
Authors: Zhang Yueyue , Liu Jiangbo , Jing Xinxin , Li Fan , Mao Xiuhai , Li Min
Published: September 2021

The exploration of intracellular vesicles plays crucial roles for neuronal activity assessment. Neurons at different growth stages may possess distinct neuronal activity, including vesicular content and release kinetics. Here, we monitored the vesicular content and its release kinetics in neurons at different growth stages by intracellular vesicle electrochemical cytometry. We found that the neurotransmitters content of vesicles changed to be increased and the vesicle release process became longer as the neurons grew. Further, we demonstrated that the vesicular adsorption and rupture modes changed from the dominant simple event to simple and complex event coexisting mode. We speculate that this work provides a new strategy for the neuronal activity assessment or real‐ time cell activity analysis.
Provisional posttraumatic stress disorder is associated with greater severity of eating disorder and comorbid symptoms in adolescents treated in residential care
Authors: Brewerton Timothy D. , Gavidia Ismael , Suro Giulia , Perlman Molly M. , Genet Jessica , Bunnell Douglas W.
Published: September 2021

Objective

Past traumatic events, subsequent posttraumatic stress disorder (PTSD) and related psychiatric comorbidities are commonly associated with eating disorders (EDs) in adults but remain understudied in adolescents.

Methods

Adolescent participants (mean [SD] age = 15.1 ± 1.5 years, 96.5% female) with EDs entering residential treatment (n = 647) at six sites in the United States completed validated self‐report assessments of ED, PTSD, major depression, anxiety disorders and quality of life. Provisional DSM‐5 PTSD diagnoses (PTSD+) were made via the Childhood Trauma Questionnaire, admission interviews and the PTSD Symptom Checklist for DSM‐5.

Results

PTSD+ occurred in 35.4% of participants, and those with ED‐PTSD+ had significantly higher scores on all assessments (p ≤ 0.001), including measures of ED psychopathology, major depression, anxiety disorders and quality of life, as well as significantly higher rates of all forms of childhood trauma. Those with PTSD+ also exhibited a significantly higher percent median body mass index for age and sex and a lower propensity toward anorexia nervosa, restricting type.

Conclusions

Results confirm that adolescent patients in residential treatment with ED‐PTSD+ are more symptomatic and have worse quality of life than their ED counterparts without PTSD. Integrated treatment approaches that effectively address ED‐PTSD+ are greatly needed in ED programs that treat adolescents.
NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
Authors: Xu Na , Lu Yi , Yao Xinmiao , Zhao Rui , Li Zhebin , Li Jialei , Zhang Yinglei , Li Bo , Zhou Ye , Shen Huifang , Wang Liqun , Chen Kaixin , Yang Li , Lu Shuwen
Published: September 2021

Doxorubicin (DOX) is an anthracycline antibiotic used in the clinical treatment of cancer, but its use is limited due to its cardiotoxic effects. Therefore, it is necessary to explore natural compounds that are effective in protecting against the cardiotoxicity caused by DOX. Neutral Morchella conica polysaccharides‐2 (NMCP‐2) is a natural polysaccharide with antioxidant activity that was isolated and purified from Morchella conica in our laboratory's previous study. This study aimed to investigate the possible protective effect of NMCP‐2 on DOX‐induced cardiotoxicity and the potential underlying mechanisms. The model of DOX‐induced H9C2 cells and the model of DOX‐induced mice were used in this study. In in vitro studies of H9C2 myocardial cells, NMCP‐2 effectively increased the activity of H9C2 cells, reducing the levels of lactate dehydrogenase (LDH). In the mouse model of DOX‐induced chronic cardiotoxicity, NMCP‐2 significantly reduced the cardiac index, reduced the release of serum cardiac enzymes, and improved the pathology of murine myocardial tissues, thereby alleviating DOX‐induced cardiotoxicity. Further mechanism studies showed that pretreatment with NMCP‐2 counteracted the oxidative stress induced by DOX, as indicated by increasing superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) activities, and malondialdehyde (MDA) production decreased. In addition, we observed NMCP‐2 inhibited the activation of the mitochondrial apoptosis pathway and regulated the disordered expression of Bcl‐2 and Bax in the myocardial tissues of DOX‐treated mice. These findings indicated that NMCP‐2, a natural bioactive compound, could potentially be used as a food supplement to reduce the cardiotoxicity caused by DOX.
Lottery and bubble stocks and the cross‐section of option‐implied tail risks
Authors: Agarwalla Sobhesh Kumar , Saurav Sumit , Varma Jayanth R.
Published: September 2021

The options smile provides forward‐looking information about the risk at the center of the distribution (ATM‐IV) and at the tails (Skew). We investigate the cross‐sectional determinants of the options smile using indices that capture firm fundamental risks, heterogeneity in belief, lottery characteristics, and bubble characteristics. We find that at‐the‐money (ATM) volatility is explained mainly by historical risks and predicted future risks measured using accounting‐based risk measures and firm characteristics. However, the cross‐sectional variation in the skew is driven by risk premia and by buying and selling pressure, which is influenced by heterogeneity in belief and the underlying's lottery‐like and bubble‐like characteristics.
Neural mechanisms of pain processing differ between endurance athletes and nonathletes: A functional connectivity magnetic resonance imaging study
Authors: Geisler Maria , Ritter Alexander , Herbsleb Marco , Bär Karl‐Jürgen , Weiss Thomas
Published: September 2021

Pain perception and the ability to modulate arising pain vary tremendously between individuals. It has been shown that endurance athletes possess higher pain tolerance thresholds and a greater effect of conditioned pain modulation than nonathletes, both indicating a more efficient system of endogenous pain inhibition. The aim of the present study was to focus on the neural mechanisms of pain processing in endurance athletes that have not been investigated yet. Therefore, we analyzed the pain processing of 18 male athletes and 19 healthy male nonathletes using functional magnetic resonance imaging. We found lower pain ratings in endurance athletes compared to nonathletes to physically identical painful stimulation. Furthermore, brain activations of athletes versus nonathletes during painful heat stimulation revealed reduced activation in several brain regions that are typically activated by nociceptive stimulation. This included the thalamus, primary and secondary somatosensory cortex, insula, anterior cingulate cortex, midcingulate cortex, dorsolateral prefrontal cortex, and brain stem (BS). Functional connectivity analyses revealed stronger network during painful heat stimulation in athletes between the analyzed brain regions except for connections with the BS that showed reduced functional connectivity in athletes. Post hoc correlation analyses revealed associations of the subject's fitness level and the brain activation strengths, subject's fitness level and functional connectivity, and brain activation strengths and functional connectivity. Together, our results demonstrate for the first time that endurance athletes do not only differ in behavioral variables compared to nonathletes, but also in the neural processing of pain elicited by noxious heat.
Methoxycyclization of 1,5‐Enynes by Coinage Metal Catalysts: Is Gold Always Superior?
Authors: Wodrich Matthew D. , Corminboeuf Clémence
Published: September 2021

Au(I) catalysts promote the intramolecular cycloisomerization of 1,n‐enynes, as well as facilitate reactions with alcohols, characteristics that have led to their wide‐spread in the synthesis of complex natural products. Literature reports of Cu and Ag species catalyzing the same or similar reactions are much less common. Here, we utilize molecular volcano plots to assess the activity of 45 coinage metal phosphine/phosphite catalysts possessing a variety of stereoelectronic properties for the methoxycyclization reaction of a prototypical 1,5‐enyne. Our analysis reveals that the intrinsic properties of gold allow it to be coupled with a wide range of ligands, all of which exhibit high catalytic activity. On the other hand, the coupling of silver and copper with more traditional phosphines, such as triphenylphosphine, leads to catalysts with diminished catalytic ability. The activity of Ag and Cu species, however, can be enhanced by appending ligands with strong π‐accepting character, which shifts these species closer to the volcano peak.
The dynamic interdependence in the demand of primary and emergency secondary care: A hidden Markov approach
Authors: Laudicella Mauro , Li Donni Paolo
Published: September 2021

This paper develops an extension of the class of finite mixture models for longitudinal count data to the bivariate case by using a hidden Markov chain approach. The model allows for disentangling unobservable time‐varying heterogeneity from the dynamic effect of utilisation of primary and secondary care and measuring their potential substitution effect. Three points of supports adequately describe the distribution of the latent states suggesting the existence of three profiles of low, medium and high users who shows persistency in their behaviour, but not permanence as some switch to their neighbour's profile.