bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase
Authors: Battisti Umberto Maria , Gao Chunxia , Nilsson Oscar , Akladios Fady , Lulla Aleksei , Bogucka Agnieszka , Nain‐Perez Amalyn , Håversen Liliana , Kim Woonghee , Boren Jan , Hyvönen Marko , Uhlen Mathias , Mardinoglu Adil , Grøtli Morten 
Published: October 2022

AbstractEnzymes are effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Synthetic modulators of enzymes are useful tools for the study of enzymatic reactions and can provide starting points for the design of new drugs. Here, we report on the discovery of a class of biologically active compounds that covalently modifies lysine residues in human liver pyruvate kinase (PKL), leading to allosteric activation of the enzyme (EC50=0.29 μM). Surprisingly, the allosteric activation control point resides on the lysine residue K282 present in the catalytic site of PKL. These findings were confirmed by structural data, MS/MS experiments, and molecular modelling studies. Altogether, our study provides a molecular basis for the activation mechanism and establishes a framework for further development of human liver pyruvate kinase covalent activators.
Anthranilic Acid Accumulation in Saccharomyces cerevisiae Induced by Expression of a Nonribosomal Peptide Synthetase Gene from Paecilomyces cinnamomeus BCC 9616
Authors: Promsuk Gunlatida , Vuttipongchaikij Supachai , Prommarit Kamonchat , Suttangkakul Anongpat , Lazarus Colin M. , Wonnapinij Passorn , Wattana‐Amorn Pakorn 
Published: October 2022

AbstractHeterologous expression of nrps33, a nonribosomal peptide synthetase gene, from Paecilomyces cinnamomeus BCC 9616 in Saccharomyces cerevisiae unexpectedly resulted in the accumulation of anthranilic acid, an intermediate in tryptophan biosynthesis. Based on transcriptomic and real‐time quantitative polymerase chain reaction (RT‐qPCR) results, expression of nrps33 affected the transcription of tryptophan biosynthesis genes especially TRP1 which is also the selectable auxotrophic marker for the expression vector used in this work. The product of nrps33 could inhibit the activity of Trp4 involved in the conversion of anthranilate to N‐(5′‐phosphoribosyl)anthranilate and therefore caused the accumulation of anthranilic acid. This accumulation could in turn result in down‐regulation of downstream tryptophan biosynthesis genes. Anthranilic acid is typically produced by chemical synthesis and has been used as a substrate for synthesising bioactive compounds including commercial drugs; our results could provide a new biological platform for production of this compound.
A Comparative Study of Nitroxide‐Based Biradicals for Dynamic Nuclear Polarization in Cellular Environments
Authors: Ackermann Bryce E. , Lim Byung Joon , Elathram Nesreen , Narayanan Sirish , Debelouchina Galia T. 
Published: October 2022

AbstractDynamic nuclear polarization (DNP) is a powerful tool to enhance the NMR signals of molecules by transferring polarization from unpaired electron spins to nuclei through microwave irradiation. The resulting signal enhancements can enable the analysis of samples that have previously been intractable by NMR spectroscopy, including proteins, nucleic acids, and metabolites in cells. To carry out DNP, the sample is doped with a polarization agent, a biradical containing two nitroxide moieties. DNP applications in cells, however, present significant challenges as nitroxides are often susceptible to the reducing cellular environment. Here, we introduce a novel polarization agent, POPAPOL, that exhibits increased lifetimes under reducing conditions. We also compare its bioresistance and DNP performance with three popular, commercially available polarization agents. Our work indicates that pyrrolidine‐based nitroxides can outperform piperidine‐based nitroxides in cellular environments, and that future polarization agent designs must carefully balance DNP performance and stability for cellular applications.
Optical coherence tomography versus angiography and intravascular ultrasound to guide coronary stent implantation: A systematic review and meta‐analysis
Authors: Siddiqi Tariq Jamal , Khan Muhammad Shahzeb , Karimi Galougahi Keyvan , Shlofmitz Evan , Moses Jeffrey W. , Rao Sunil , West Nick E. J. , Wolff Eric , Hochler Jason , Chau Karen , Khalique Omar , Shlofmitz Richard A. , Jeremias Allen , Ali Ziad A. 
Published: October 2022

AbstractBackgroundOptical coherence tomography (OCT) is an adjunct to angiography‐guided coronary stent placement. However, in the absence of dedicated, appropriately powered randomized controlled trials, the impact of OCT on clinical outcomes is unclear.ObjectiveTo conduct a systematic review and meta‐analysis of all available studies comparing OCT‐guided versus angiography‐guided and intravascular ultrasound (IVUS)‐guided coronary stent implantation.MethodsMEDLINE and Cochrane Central were queried from their inception through July 2022 for all studies that sought to compare OCT‐guided percutaneous coronary intervention (PCI) to angiography‐guided and IVUS‐guided PCI. The primary endpoint was minimal stent area (MSA) compared between modalities. Clinical endpoints of interest were all‐cause and cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis (ST). Risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were pooled using a random‐effects model.ResultsThirteen studies (8 randomized control trials and 5 observational studies) enrolling 6312 participants were included. OCT was associated with a strong trend toward increased MSA compared to angiography (MD = 0.36, p = 0.06). OCT‐guided PCI was also associated with a reduction in the incidence of all‐cause mortality [RR = 0.59, 95% CI (0.35, 0.97), p = 0.04] and cardiovascular mortality [RR = 0.41, 95% CI (0.21, 0.80), p = 0.009] compared with angiography‐guided PCI. Point estimates favored OCT relative to angiography in MACE [RR = 0.75, 95% CI (0.47, 1.20), p = 0.22] and MI [RR = 0.75, 95% CI (0.53, 1.07), p = 0.12]. No differences were detected in ST [RR = 0.71, 95% CI (0.21, 2.44), p = 0.58], TLR [RR = 0.71, 95% CI (0.17, 3.05), p = 0.65], or TVR rates [RR = 0.89, 95% CI (0.46, 1.73), p = 0.73]. Compared with IVUS guidance, OCT guidance was associated with a nonsignificant reduction in the MSA (MD = −0.16, p = 0.27). The rates of all‐cause and cardiovascular mortality, MACE, MI, TLR, TVR, or ST were similar between OCT‐guided and IVUS‐guided PCI.ConclusionsOCT‐guided PCI was associated with reduced all‐cause and cardiovascular mortality compared to angiography‐guided PCI. These results should be considered hypothesis generating as the mechanisms for the improved outcomes were unclear as no differences were detected in the rates of TLR, TVR, or ST. OCT‐ and IVUS‐guided PCI resulted in similar post‐PCI outcomes.
Pemphigus vegetans misdiagnosed as condylomata acuminata: A case report
Authors: Siadat Amir Hossein , Moeine Reza , Iraji Fariba , Galehdari Hamid , Shahriarirad Reza 
Published: October 2022

AbstractPemphigus vegetans is a rare variant of pemphigus vulgaris, characterized by vegetating lesions primarily in the flexures. A 41‐year‐old male patient presented with pemphigus vegetans highly mimicking condylomata acuminata, which led to mistreatment. Careful analysis of clinical and laboratory findings enabled us to reach a correct diagnosis and successful treatment.
Asymmetric acidic/alkaline N2 electrofixation accelerated by high‐entropy metal–organic framework derivatives
Authors: Sun Yuntong , Wu Wenqiang , Yu Lei , Xu Shuaishuai , Zhang Yuxiang , Yu Licheng , Xia Baokai , Ding Shan , Li Ming , Jiang LiLi , Duan Jingjing , Zhu Junwu , Chen Sheng 
Published: October 2022

AbstractHigh‐entropy materials are composed of five or more metal elements with equimolar or near‐equimolar concentrations within one crystal structure, which offer remarkable structural properties for many applications. Despite previously reported entropy‐driven stabilization mechanisms, many high‐entropy materials still tend to decompose to produce a variety of derivatives under operating conditions. In this study, we use transition‐metal (Ni, Co, Ni, Zn, V)‐based high‐entropy metal–organic frameworks (HE‐MOFs) as the precursors to produce different derivatives under acidic/alkaline treatment. We have shown that HE‐MOFs and derivatives have shown favorable kinetics for N2 electrofixation in different pH electrolytes, specifically cathodic nitrogen reduction reaction in acidic media and anodic oxygen evolution reaction in alkaline media. To buffer the pH mismatch, we have further constructed an asymmetric acidic/alkaline device prototype by using bipolar membranes. As expected, the prototype showed remarkable activities, with an NH3 yield rate of 42.76 μg h−1 mg−1, and Faradaic efficiency of 14.75% and energy efficiency of 2.59%, which are 14.4 and 4.4 times larger than those of its symmetric acidic and alkaline counterparts, respectively.
Interactive Bioconjugation at N‐Terminal Cysteines by Using O‐Salicylaldehyde Esters towards Dual Site‐Selective Functionalization
Authors: Silva Maria J. S. A. , Cavadas Rafaela A. N. , Faustino Hélio , Veiros Luís F. , Gois Pedro M. P. 
Published: October 2022

AbstractN‐terminal Cys modification has been intensively studied to produce homogeneous bioconjugates essentially through two modes of reaction: reversible modification with the equilibrium shifted towards the formation of the desired conjugate or stable and irreversible conjugates. Herein, we report a new method of N‐terminal cysteine modification using O‐salicylaldehyde esters (OSAEs) through fast conjugation and irreversible deconjugation. These reagents can rapidly react with N‐terminal Cys at low‐micromolar concentration to form thiazolidines with subsequent hydrolysis of the ester moiety to the phenolic derivative. These phenolic thiazolidines can be hydrolyzed at acidic pH (≈4.5) to recover the intact N‐terminal Cys. Bioconjugation reactions using OSAEs offer controlled reversibility to as act as a protecting group for N‐terminal cysteines, allowing the modification of in‐chain residues without perturbing the N‐terminal Cys, which can then be deprotected and used as a conjugation site.
Oxidative Desymmetrization Enables the Concise Synthesis of a trans‐Cyclooctene Linker for Bioorthogonal Bond Cleavage
Authors: Kuba Walter , Sohr Barbara , Keppel Patrick , Svatunek Dennis , Humhal Viktoria , Stöger Berthold , Goldeck Marion , Carlson Jonathan C. T. , Mikula Hannes 
Published: October 2022

AbstractModified trans‐cyclooctenes (TCO) are capable of highly efficient molecular manipulations in biological environments, driven by the bioorthogonal reaction with tetrazines (Tz). The development of click‐cleavable TCO has fueled the field of in vivo chemistry and enabled the design of therapeutic strategies that have already started to enter the clinic. A key element for most of these approaches is the implementation of a cleavable TCO linker. So far, only one member of this class has been developed, a compound that requires a high synthetic effort, mainly to fulfill the multilayered demands on its chemical structure. To tackle this limitation, we developed a dioxolane‐fused cleavable TCO linker (dcTCO) that can be prepared in only five steps by applying an oxidative desymmetrization to achieve diastereoselective introduction of the required functionalities. Based on investigation of the structure, reaction kinetics, stability, and hydrophilicity of dcTCO, we demonstrate its bioorthogonal application in the design of a caged prodrug that can be activated by in‐situ Tz‐triggered cleavage to achieve a remarkable >1000‐fold increase in cytotoxicity.
Iron‐Catalyzed Borylation of Propargylic Acetates for the Synthesis of Multisubstituted Allenylboronates
Authors: Bermejo‐López Aitor , Kong Wei‐Jun , Tortajada Pedro J. , Posevins Daniels , Martín‐Matute Belén , Bäckvall Jan‐E. 
Published: October 2022

AbstractA novel iron‐catalyzed borylation of propargylic acetates leading to allenylboronates has been developed. The method allows the preparation of a variety of di‐, tri‐ and tetrasubstituted allenylboronates at room temperature with good functional group compatibility. Stereochemical studies show that an anti‐SN2’ displacement of acetate by boron occurs; this also allows transfer of chirality to yield enantiomerically enriched allenylboronates. The synthetic utility of this protocol was further substantiated by transformations of the obtained allenylboronates including oxidation and propargylation.
Preparation of Perovskite Solar Cells in the Air: Degradation Mechanism and Prospects on Large‐Area Fabrication†
Authors: Guo Shuaishuai , Liu Kaikai , Rao Li , Hu Xiaotian , Chen Yiwang 
Published: October 2022

Comprehensive SummaryThe preparation of perovskite solar cells (PSCs) in the air environment has attracted the attention of numerous experimenters due to its low preparation cost and the possibility of commercialization. Although the power conversion efficiency (PCE) of PSCs has increased rapidly and exceeded 25%, which is comparable to commercial polysilicon solar cells, most certified or reported high‐efficiency perovskite solar cells are still confined to glove boxes or relatively small active areas in the air environment due to moisture, oxygen, high temperature, and ultraviolet (UV) factors. In this review, the factors that lead to perovskite degradation are reviewed, and the appropriate strategies for manufacturing high‐efficiency and stable perovskite solar cells under environmental conditions are summarized to help the technology be commercialized for high‐quality, stable, and large‐area perovskite thin films in the air.
A generalized single‐index linear threshold model for identifying treatment‐sensitive subsets based on multiple covariates and longitudinal measurements
Authors: Ge Xinyi , Peng Yingwei , Tu Dongsheng 
Published: October 2022

AbstractIdentification of a subset of patients who may be sensitive to a specific treatment is an important step towards personalized medicine. We consider the case where the effect of a treatment is assessed by longitudinal measurements, which may be continuous or categorical, such as quality of life scores assessed over the duration of a clinical trial. We assume that multiple baseline covariates, such as age and expression levels of genes, are available, and propose a generalized single‐index linear threshold model to identify the treatment‐sensitive subset and assess the treatment‐by‐subset interaction after combining these covariates. Because the model involves an indicator function with unknown parameters, conventional procedures are difficult to apply for inferences of the parameters in the model. We define smoothed generalized estimating equations and propose an inference procedure based on these equations with an efficient spectral algorithm to find their solutions. The proposed procedure is evaluated through simulation studies and an application to the analysis of data from a randomized clinical trial in advanced pancreatic cancer.
Antiplasmodial and Antimalarial Activity of 3,5‐Diarylidenetetrahydro‐2H‐pyran‐4(3H)‐ones via Inhibition of Plasmodium falciparum Pyridoxal Synthase
Authors: Moorthy Hariharan , Yadav Mamta , Tamang Nitesh , Mavileti Sai Kiran , Singla Labhini , Choudhury Angshuman Roy , Sahal Dinkar , Golakoti Nageswara Rao 
Published: October 2022

AbstractA series of 22 different 3,5‐diarylidenetetrahydro‐2H‐pyran‐4(3H)‐ones (DATPs) were synthesized, characterized, and screened for their in vitro antiplasmodial activities against chloroquine (CQ)‐sensitive Pf3D7, CQ‐resistant PfINDO, and artemisinin‐resistant PfMRA‐1240 strains of Plasmodium falciparum. DATP 19 (3,5‐bis(4‐hydroxy‐3,5‐dimethoxybenzylidene)tetrahydro‐2H‐pyran‐4(3H)‐one) was found to be the most potent (IC50 1.07 μM) against PfMRA‐1240, whereas 21 (3,5‐bis(3,4,5‐trimethoxybenzylidene)tetrahydro‐2H‐pyran‐4(3H)‐one) showed IC50 values of 1.72 and 1.44 μM against Pf3D7 and PfINDO, respectively. Resistance indices (RI) as low as 0.2 to 0.5 for 10 (3,5‐bis(4‐nitrobenzylidene)tetrahydro‐2H‐pyran‐4(3H)‐one) and 20 (3,5‐bis(3‐nitrobenzylidene)tetrahydro‐2H‐pyran‐4(3H)‐one), and <1 for most other DATPs reveals their greater potency against resistant strains than the sensitive one. The single‐crystal XRD data for DATP 21 are reported. In silico support was obtained through docking studies. Killing all three strains within 4–8 h, these DATPs showed rapid kill kinetics toward the trophozoite stage. Furthermore, DATP 18 (3,5‐bis(quinolin‐4‐ylmethylene)tetrahydro‐2H‐pyran‐4(3H)‐one) inhibited PfPdx1 enzyme activity with IC50 20.34 μM, which is about twofold lower than that (IC50 43 μM) for an already known inhibitor 4PEHz. At an oral dose of 300 mg/kg body weight, DATPs 19 and 21 were found to be nontoxic to mice, and at 100 mg/kg body weight, DATP 19 was found to suppress parasitaemia, which led to an increase in median survival time by three days relative to untreated control mice in a malaria curative study.
Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages
Authors: Noce Beatrice , Di Bello Elisabetta , Zwergel Clemens , Fioravanti Rossella , Valente Sergio , Rotili Dante , Masotti Andrea , Salik Zeya Ansari Mohammad , Trisciuoglio Daniela , Chakrabarti Alokta , Romier Christophe , Robaa Dina , Sippl Wolfgang , Jung Manfred , Häberli Cécile , Keiser Jennifer , Mai Antonello 
Published: October 2022

AbstractSchistosoma mansoni HDAC8 is a reliable target to fight schistosomiasis, and several inhibitors have been reported in the literature up to now. Nevertheless, only a few displayed selectivity over the human deacetylases and some exhibited very low or no activity against parasite larvae and/or adult worms. We report here the in vitro enzyme and biological activity of a small library of HDAC inhibitors from our lab, in many cases exhibiting submicromolar/nanomolar potency against smHDAC8 and diverse degrees of selectivity over hHDAC1 and/or hHDAC6. Such compounds were tested against schistosomula, and a selection of them against the adult forms of S. mansoni, to detect their effect on viability. Some of them showed the highest viability reduction for the larval stage with IC50 values around 1 μM and/or displayed ∼40–50 % activity in adult worms at 10 μM, joined to moderate to no toxicity in human fibroblast MRC‐5 cells.
Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression
Authors: Lutgendorf Susan K. , Thaker Premal H. , Goodheart Michael J. , Arevalo Jesusa M. G. , Chowdhury Mamur A. , Noble Alyssa E. , Dahmoush Laila , Slavich George M. , Penedo Frank J. , Sood Anil K. , Cole Steven W. 
Published: October 2022

AbstractBackgroundBiobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.MethodsExosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease‐free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed‐effects linear models to determine whether the progression‐predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms).ResultsAn RNA‐based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates.ConclusionThese data identified a novel exosome‐derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.
An optimized ticket manager based energy‐aware multipath routing protocol design for IoT based wireless sensor networks
Authors: Roberts Michaelraj Kingston , Thangavel Jayapratha 
Published: October 2022

SummaryRecently, wireless sensor networks (WSNs) and Internet of Things (IoTs) have emanated as an indispensable assets that play a critical role in revolutionizing the field of data communication. Owing to the evolution of communication standards, research trends in IoT based wireless sensor networks have been rapidly progressing toward achieving effective data routing with a prolonged network lifetime and minimized energy consumption. In this article, an optimized ticket manager based energy‐aware multipath routing protocol (TMERP) is proposed. The proposed protocol design comprises three important functional entities: ticket manager (TM), routing planner (RP), and backup node (BN). The TM is responsible for controlling and monitoring all the constraints related to networking. Then, the RP minimizes the overall complexity of the optimal resource allocation by avoiding an end‐to‐end delay. Finally, the BN facilitates efficient data routing through the optimal selection of routing paths using the node trust evaluation and backup process to minimize data loss. Hence, the proposed multipath routing system has a distinct advantage in enhancing the network lifetime constraint with minimal energy consumption owing to the collective performance of its functional entities. The simulation results of the experimental studies show that the proposed protocol design achieved an improved performance in terms of network energy, throughput, and network operational lifetime by 39.3%, 47.9%, and 10.5%, respectively when compared with similar existing protocols.