bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast‐Scan Cyclic Voltammetry (FSCV) Reveals Behaviorally Evoked Dopamine Release by Sugar Feeding in the Adult Drosophila Mushroom Body
Authors: Shin Mimi , Venton B. Jill
Published: August 2022

Drosophila melanogaster, the fruit fly, is an excellent model organism for studying dopaminergic mechanisms and simple behaviors, but methods to measure dopamine during behavior are needed. Here, we developed fast‐scan cyclic voltammetry (FSCV) to track in vivo dopamine during sugar feeding. First, we employed acetylcholine stimulation to evaluate the feasibility of in vivo measurements in an awake fly. Next, we tested sugar feeding by placing sucrose solution near the fly proboscis. In the mushroom body medial tip, 1 pmol acetylcholine and sugar feeding released 0.49±0.04 μM and 0.31±0.06 μM dopamine, respectively but sugar‐evoked release lasted longer than with acetylcholine. Administering the dopamine transporter inhibitor nisoxetine or D2 receptor antagonist flupentixol significantly increased sugar‐evoked dopamine. This study develops FSCV to measure behaviorally evoked release in fly, enabling Drosophila studies of neurochemical control of reward, learning, and memory behaviors.
Low‐Coordination Single Au Atoms on Ultrathin ZnIn2S4Nanosheets for Selective Photocatalytic CO2Reduction towards CH4
Authors: Si Shenghe , Shou Hongwei , Mao Yuyin , Bao Xiaolei , Zhai Guangyao , Song Kepeng , Wang Zeyan , Wang Peng , Liu Yuanyuan , Zheng Zhaoke , Dai Ying , Song Li , Huang Baibiao , Cheng Hefeng
Published: August 2022

Selective CO2photoreduction to hydrocarbon fuels such as CH4is promising and sustainable for carbon‐neutral future. However, lack of proper binding strengths with reaction intermediates makes it still a challenge for photocatalytic CO2methanation with both high activity and selectivity. Here, low‐coordination single Au atoms (Au1‐S2) on ultrathin ZnIn2S4nanosheets was synthesized by a complex‐exchange route, enabling exceptional photocatalytic CO2reduction performance. Under visible light irradiation, Au1/ZnIn2S4catalyst exhibits a CH4yield of 275 μmol g−1 h−1with a selectivity as high as 77 %. As revealed by detailed characterizations and density functional theory calculations, Au1/ZnIn2S4with Au1‐S2structure not only display fast carrier transfer to underpin its superior activity, but also greatly reduce the energy barrier for protonation of *CO and stabilize the *CH3intermediate, thereby leading to the selective CH4generation from CO2photoreduction.
Synthesis of Square Planar Cu4Clusters
Authors: Osei Manasseh Kusi , Mirzaei Saber , Bogetti Xiaowei , Castro Edison , Rahman Mohammad Azizur , Saxena Sunil , Hernández Sánchez Raúl
Published: August 2022

Template‐assisted synthesis of well‐defined polynuclear clusters remains a challenge for [M4] square planar topologies. Herein, we present a tetraamine scaffoldRL(NH2)4, where L is a rigidified resorcin[4]arene, to direct the formation ofC4‐symmetricRL(NH)4Cu4clusters with Cu−Cu distances around 2.7 Å, suggesting metal‐metal direct interactions are operative since the sum of copper's van der Waals radii is 2.8 Å. DFT calculations display HOMO to HOMO‐3 residing all within a 0.1 eV gap. These four orbitals display significant electron density contribution from the Cu centers suggesting a delocalized electronic structure. The one‐electron oxidized [Cu4]+species was probed by variable temperature X‐band continuous wave‐electron paramagnetic resonance (CW‐EPR), which displays a multiline spectrum at room temperature. This work presents a novel synthetic strategy for [M4] clusters and a new platform to investigate activation of small molecules.
Self‐Assembly of Macrocyclic Triangles into Helicity‐Opposite Nanotwists by Competitive Planar over Point Chirality
Authors: Shang Weili , Zhu Xuefeng , Jiang Yuqian , Cui Jie , Liu Kaiang , Li Tiesheng , Liu Minghua
Published: August 2022

While helix has elegant biomimetic structures and functionalities, it still remains a big question how the nanoscale helicity evolved from the molecular chiral building blocks across length scales. Herein, macrocyclic triangles composed of achiral edges and chiral vertices were rationally designed, in which the planar chirality emerged due to the restriction of edge rotation by intermolecular stackings and led to a unique chiral self‐assembly. In contrast to the solution systems where the chiroptical property is exclusively dominated by the point chiral vertices, the emerged planar chirality was found to control the chiral self‐assembly, resulting the nanotwist with the handedness determined by the planar chirality. Our work unveiled the self‐assembly behaviors of macrocyclic conformers for the first time and provided a deep understanding on the macrocyclic chirality evolution including the excited‐state chirality.
Differenzierte Peptid‐Multi‐Makrozyklisierungen an der Oberfläche eines helikalen Foldamer‐Templats
Authors: Dengler Sebastian , Douat Céline , Huc Ivan
Published: August 2022

Es wurden hybride Sequenzen synthetisiert, die Peptide mit einer Reihe von Cystein‐Resten und aromatische Foldamer‐Helices mit mehreren Chloracetamid‐Funktionen an ihrer Oberfläche umfassen. Solche Produkte können im Prinzip zahlreiche makromultizyklische Thioetherbrücken bilden, indem sie alle Cys‐Reste und alle Chloracetamidfunktionen intramolekular verbinden. Wir zeigen indes, dass die reaktiven Stellen auf der strukturell definierten Helix an solchen Positionen platziert werden können, so dass das Peptid selektiv reagiert, um eine Reihe unterschiedlicher Makrozyklen innerhalb meist eines bevorzugten Produkts zu bilden. Die Reaktionen wurden mittels HPLC überprüft und die Produkte mit zwei, drei oder vier Makrozyklen wurden mittels LC–MS und NMR identifiziert. Die Reihe selektiver Makrozyklisierungen definiert eine Art Reaktionspfad, bei dem ansonsten identische Reaktionsstellen aufgrund ihrer genauen Positionierung im Raum nacheinander beteiligt sind. Die Reaktionspfade lassen sich weitgehend auf der Grundlage struktureller Überlegungen und der Annahme, dass sich kleinere Makrozyklen schneller bilden, vorhersagen.
Challenges and Opportunities in Electrocatalytic CO2Reduction to Chemicals and Fuels
Authors: She Xiaojie , Wang Yifei , Xu Hui , Chi Edman Tsang Shik , Ping Lau Shu
Published: August 2022

The global temperature increase must be limited to below 1.5 °C to alleviate the worst effects of climate change. Electrocatalytic CO2reduction (ECO2R) to generate chemicals and feedstocks is considered one of the most promising technologies to cut CO2emission at an industrial level. However, despite decades of studies, advances at the laboratory scale have not yet led to high industrial deployment rates. This Review discusses practical challenges in the industrial chain that hamper the scaling‐up deployment of the ECO2R technology. Faradaic efficiencies (FEs) of about 100 % and current densities above 200 mA cm−2have been achieved for the ECO2R to CO/HCOOH, and the stability of the electrolysis system has been prolonged to 2000 h. For ECO2R to C2H4, the maximum FE is over 80 %, and the highest current density has reached the A cm−2level. Thus, it is believed that ECO2R may have reached the stage for scale‐up. We aim to provide insights that can accelerate the development of the ECO2R technology.
Fiber‐spinning Asymmetric Assembly for Janus‐structured Bifunctional Nanofiber Films towards All‐Weather Smart Textile
Authors: Xie An‐Quan , Zhu Liangliang , Liang Yunzheng , Mao Jian , Liu Yijiang , Chen Su
Published: August 2022

Given health threat by global warming and increased energy consumption in regulating body temperature, it is an urgent need to construct smart temperature‐regulating materials. Herein, a novel fiber‐spinning asymmetric chemical assembly (FACA) method is proposed to construct nanofiber materials with asymmetric photothermal properties. The silver nanowires (AgNWs) and poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) with opposite thermal radiation are assembled on reduced graphene oxide (rGO) film, imparting AgNW/rGO/PVDF‐HFP film with Janus structure that can realize the AgNWs side consistently keeps temperature of ca. 11 °C lower than the side of PVDF‐HFP nanofiber regardless of the irradiation directions under 1 sun, suggesting the adjustable photothermal regulation. Such photothermally selective hybrid nanofiber film provides great potential as fabrics to achieve all‐weather smart clothes, promoting controllable and comprehensive utilization of solar energy.
Pd supported on locust bean gum as reusable green catalyst for Heck and Sonogashira coupling reactions and 4‐nitroaniline reduction under ultrasound irradiation
Authors: Ben Romdhane Rabeb , Atoui Dhieb , Ketata Nahed , Dali Souad , Moussaoui Younes , Ben Salem Ridha
Published: August 2022

An easy and environmentally friendly method has been developed for locust bean gum extraction from carob seeds to be used as natural support of palladium. The reaction was carried out in water under ultrasonic irradiation for a short period of time (30 min). This catalyst was characterized by different analytical techniques such as ultraviolet–visible (UV‐vis), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy/energy dispersive X‐ray spectroscopy (SEM/EDX), elemental mapping analysis, and X‐ray diffraction (XRD). The catalytic activity of Pd supported by locust bean gum was studied in Heck and Sonogashira cross‐coupling reactions in different conditions under ultrasonic irradiation. Likewise, it was examined as green catalyst of 4‐nitroaniline reduction at room temperature in water. The reusability of the catalyst was verified for five consecutive cycles, where excellent yields were obtained.
Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis
Authors: Fan Luyun , Chen Junru , Pan Lili , Xin Xiaohong , Geng Bin , Yang Lirui , Wang Qian , Ma Wenjun , Lou Ying , Bian Jin , Cui Xiao , Li Jing , Wang Lu , Chen Zhenzhen , Wang Wenjie , Cui Changting , Li Shuangyue , Gao Qiannan , Song Qirui , Deng Yue , Fan Jiali , Yu Jiachen , Zhang Huimin , Li Yafeng , Cai Jun
Published: August 2022

Objective

Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune‐related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.

Methods

To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.

Results

A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.

Conclusion

This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome–metagenome interface in TAK subtype prediction and pathogenesis are suggested.
Risk of Arrhythmia Among New Users of Hydroxychloroquine in Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population‐Based Study
Authors: Hoque M. Rashedul , Lu Leo , Daftarian Narsis , Esdaile John M. , Xie Hui , Aviña‐Zubieta J. Antonio
Published: August 2022

Objectives

We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE).

Methods

All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow‐up. We used cause‐specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes.

Results

We identified 11,518 propensity score–matched patients with RA or SLE in each group. Over the mean follow‐up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause‐specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89–1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83–1.04), 0.98 (95% CI 0.87–1.11), and 0.95 (95% CI 0.84–1.07), respectively.

Conclusion

Risk of any type of arrhythmia was not increased among new users of HCQ.
Enhanced Electrochemiluminescence of A Macrocyclic Tetradentate Chelate Pt(II) Molecule through Its Collisional Interactions with the Electrode
Authors: He Shuijian , Wang Xiang , Xiang Guiming , Lac Kevin , Wang Changshui , Wang Suning , Ding Zhifeng
Published: August 2022

A macrocyclic tetradentate chelate Pt(II) molecule (Pt1) served as an excellent luminophore in electrochemiluminescence (ECL) processes. The blue ECL of Pt1/S2O82− coreactant system in N,N’‐dimethylformamide was found to be 46 times higher than that of the Ru(bpy)2+/S2O82− system or 30 times higher than that of the 9,10‐diphenylanthracene/S2O82− system. The unprecedented high ECL quantum efficiencies were caused by the cyclic generation of monomer excited states through collisional interactions of Pt1 molecules with the electrode at an elevated frequency. The ECL is tunable from bright blue to pure white by simply changing the solvent from N,N’‐dimethylformamide to dichloromethane. The white ECL of Pt(II) molecule was reported for the first time and the mechanism was proposed to be the simultaneous emissions from the monomer excited state (blue) and excimer (red).
Survival prediction by Bayesian network modeling for pseudomyxoma peritonei after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy
Authors: Zhao Xin , Li Xinbao , Lin Yulin , Ma Ru , Zhang Ying , Xu Dazhao , Li Yan
Published: August 2022

Objectives

To establish a survival prognostic model for pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) based on Bayesian network (BN).

Methods

453 PMP patients were included from the database at our center. The dataset was divided into a training set to establish BN model and a testing set to perform internal validation at a ratio of 8:2. From the training set, univariate and multivariate analyses were performed to identify independent prognostic factors for BN model construction. The confusion matrix, receiver operating characteristic (ROC) curve and the area under curve (AUC) were used to evaluate the performance of the BN model.

Results

The univariate and multivariate analyses identified 7 independent prognostic factors: gender, previous operation history, histological grading, lymphatic metastasis, peritoneal cancer index, completeness of cytoreduction and splenectomy (all p < 0.05). Based on independent factors, the BN model of training set was established. After internal validation, the accuracy and AUC of the BN model were 70.3% and 73.5%, respectively.

Conclusion

The BN model provides a reasonable level of predictive performance for PMP patients undergoing CRS + HIPEC.
Valeridoids G – Q, Eleven seco‐Iridoids from Valeriana jatamansi and Their Bioactivites
Authors: Quan Li‐Qiu , Wang Yun , Tang Jian‐Xian , Zhou Yan , Liao Cai‐Cen , Liu Dan , Zhao Xu‐Dong , Li Rong‐Tao , Li Hong‐Mei
Published: August 2022

Eleven new seco‐iridoids, valeridoids G‐Q (1–6 and 8–12), along with four known products, 9‐epi‐valtral C (7), desacylbaldrinal (13), 11‐methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR‐ESI‐MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C3 epimers, whose ether bonds between C‐1 and C‐3 opened, and new ether bonds formed between C‐3 and C‐6. Valeridoid Q belonged to the C‐1 degradation of seco‐iridoids. As a result, 9‐epi‐valtral C displayed significant inhibition on Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus argenteus, Shigella flexneri and Klebsiella pneumoniae, and valeridoid Q exhibited the most significant inhibition against Salmonella enteritidis. 9‐Epi‐valtral C and baldrinal selectively inhibited the growth of human glioma stem cells. Valeridoid Q exhibited significant anti‐influenza activity, while valeridoid O inhibited nitric oxide production.
SARS‐CoV‐2 Papain‐Like Protease: Structure, Function and Inhibition
Authors: Ullrich Sven , Nitsche Christoph
Published: August 2022

Emerging variants of SARS‐CoV‐2 and potential novel epidemic coronaviruses underline the importance of investigating various viral proteins as potential drug targets. The papain‐like protease of coronaviruses has been less explored than other viral proteins; however, its substantive role in viral replication and impact on the host immune response make it a suitable target to study. This review article focuses on the structure and function of the papain‐like protease (PLpro) of SARS‐CoV‐2, including variants of concern, and compares it to those of other coronaviruses, such as SARS‐CoV‐1 and MERS‐CoV. The protease's recognition motif is mirrored in ubiquitin and ISG15, which are involved in the antiviral immune response. Inhibitors, including GRL0617 derivatives, and their prospects as potential future antiviral agents are also discussed.
Towards Non‐stick Silk: Tuning the Hydrophobicity of Silk Fibroin Protein
Authors: Fountain Julia N. , Hawker Morgan J. , Hartle Lauren , Wu Junqi , Montanari Vittorio , Sahoo Jugal Kishore , Davis Luke M. , Kaplan David L. , Kumar Krishna
Published: August 2022

Silk fibroin protein is a biomaterial with excellent biocompatibility and low immunogenicity. These properties have catapulted the material as a leader for extensive use in stents, catheters, and wound dressings. Modulation of hydrophobicity of silk fibroin protein to further expand the scope and utility however has been elusive. We report that installing perfluorocarbon chains on the surface of silk fibroin transforms this water‐soluble protein into a remarkably hydrophobic polymer that can be solvent‐cast. A clear relationship emerged between fluorine content of the modified silk and film hydrophobicity. Water contact angles of the most decorated silk fibroin protein exceeded that of Teflon®. We further show that water uptake in prefabricated silk bars is dramatically reduced, extending their lifetimes, and maintaining mechanical integrity. These results highlight the power of chemistry under moderate conditions to install unnatural groups onto the silk fibroin surface and will enable further exploration into applications of this versatile biomaterial.
Extending the Structure‐Activity Relationship of Disorazole C1: Exchanging the Oxazole Ring by Thiazole and Influence of Chiral Centers within the Disorazole Core on Cytotoxicity
Authors: Lizzadro Luca , Spieß Oliver , Collisi Wera , Stadler Marc , Schinzer Dieter
Published: August 2022

The synthesis of novel disorazole C1 analogues is described and their biological activity as cytotoxic compounds is reported. Based on our convergent entry to the disorazole core we present a flexible and robust strategy to construct a variety of interesting new analogues. In particular, two regions of the molecules were examined for structural modification: 1. Replacement of the heterocyclic moiety by an exchange of the oxazole ring by a thiazole; and 2. Evaluation of the influence of the absolute configuration of the chiral centers of the molecule. Predicated on our flexible strategy we were able to construct all analogues in an efficient way and could perform an exciting SAR (structure‐activity‐relationship) study to obtain insight in the cytotoxic activity influenced by the chiral centers of the disorazole core.
Leishmania amazonensis from distinct clinical forms/hosts has polymorphisms in Lipophosphoglycans, displays variations in immunomodulatory properties and, susceptibility to antileishmanial drugs
Authors: Rêgo Felipe D. , Cardoso Camila d. A. , Moreira Paulo Otávio L. , Nogueira Paula M. , Araújo Márcio S. , Borges Valéria Matos , Laurenti Márcia D. , Bartholomeu Daniella C. , Reis Alexandre B. , Monte‐Neto Rubens L. d. , Soares Rodrigo P.
Published: August 2022

Lipophosphoglycan (LPG), the major Leishmania glycoconjugate, induces pro‐inflammatory/immunosuppressive innate immune responses. Here, we evaluated functional/biochemical LPG properties from six Leishmania amazonensis strains from different hosts/clinical forms. LPGs from three strains (GV02, BA276, and LV79) had higher pro‐inflammatory profiles for most of the mediators, including tumor necrosis factor alpha and interleukin 6. For this reason, glycoconjugates from all strains were biochemically characterized and had polymorphisms in their repeat units. They consisted of three types: type I, repeat units devoid of side chains; type II, containing galactosylated side chains; and type III, containing glucosylated side chains. No relationship was observed between LPG type and the pro‐inflammatory properties. Finally, to evaluate the susceptibility against antileishmanial agents, two strains with high (GV02, BA276) and one with low (BA336) pro‐inflammatory activity were selected for chemotherapeutic tests in THP‐1 cells. All analyzed strains were susceptible to amphotericin B (AmB) but displayed various responses against miltefosine (MIL) and glucantime (GLU). The GV02 strain (canine visceral leishmaniasis) had the highest IC50 for MIL (3.34 μM), whereas diffuse leishmaniasis strains (BA276 and BA336) had a higher IC50 for GLU (6.87–12.19 mM). The highest IC50 against MIL shown by the GV02 strain has an impact on clinical management. Miltefosine is the only drug approved for dog treatment in Brazil. Further studies into drug susceptibility of L. amazonensis strains are warranted, especially in areas where dog infection by this species overlaps with those caused by Leishmania infantum.
DPCPX induces Bim‐dependent apoptosis in nasopharyngeal carcinoma cells
Authors: Pan Suming , Zhang Xiangguo , Guo Yugan , Li Yin
Published: August 2022

ADORA1 promotes tumor growth and development in multiple cancers. DPCPX (a selective adenosine A1 receptor antagonist), a specific ADORA1 antagonist, has shown antitumor effects in many cancer types. Nevertheless, the function of DPCPX in nasopharyngeal carcinoma (NPC) still remains to be unraveled. In this study, we investigated the functional role of DPCPX on NPC cells. We found that DPCPX promotes NPC cells growth inhibition. DPCPX induced Bim‐dependent apoptosis in NPC cells irrespective of p53 status via the FoxO3a pathway following PI3K/AKT inhibition. Furthermore, DPCPX enhanced the antitumor effect of cisplatin, 5‐FU and Paclitaxel in NPC. Xenograft experiment revealed that deficiency of Bim in vivo stalls apoptosis and antitumor activity of DPCPX. In conclusion, the PI3K/AKT/FoxO3a/Bim axis plays a critical role in the anticancer effects of DPCPX in NPC.
Orbital atherectomy of calcified coronary ostial lesions
Authors: Chambers Jeffrey W. , Martinsen Brad J. , Sturm Robert C. , Mandair Divneet , Valle Javier A. , Waldo Stephen W. , Guzzetta Francesca , Armstrong Ehrin J.
Published: August 2022

Objectives

To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions.

Background

Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long‐term outcome data.

Methods

Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high‐volume PCI centers. Kaplan–Meier analysis was utilized to assess the primary endpoints of 30‐day, 1‐year, and 2‐year freedom‐from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST).

Results

A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30‐day, 1‐year, and 2‐year, a high FF‐MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively.

Conclusions

This study represents the largest real‐world experience of coronary OA use in heavily calcified ostial lesions with long‐term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.
Cu3(HHTP)2 c‐MOF/ZnO Ultrafast Ultraviolet Photodetector for Wearable Optoelectronics
Authors: Kang Chenxu , Ahsan Iqbal Muhammad , Zhang Suyun , Weng Xiaoliang , Sun Yuting , Qi Lu , Tang Wei , Ruan Shuangchen , Zeng Yu‐Jia
Published: August 2022

Two‐dimensional conductive metal–organic frameworks (2D c‐MOFs) are a family of highly tunable and electrically conducting materials that can be utilized in optoelectronics. A major issue of 2D c‐MOFs for photodetection is their poor charge separation and recombination dynamics upon illumination. This study demonstrates a Cu3(HHTP)2/ZnO type‐II heterojunction ultraviolet (UV) photodetector fabricated by layer‐by‐layer (LbL) deposition, in which the charge separation of photogenerated carriers is enhanced. At optimized MOF layer cycles, the device achieves a responsivity of 78.2 A/W and detectivity of 3.8×109 Jones at 1 V. Particularly, the device can be operated in the self‐powered mode with an ultrafast response time of 70 μs, which is the record value for MOF‐based photodetectors. In addition, even after 1000‐time bending of 180°, the flexible device maintains stable performance. This flexible MOF‐based UV photodetector with anti‐fatigue and anti‐bending properties provides strong implication to wearable optoelectronics.
Leveraging Metal and Ligand Reactive Sites for One Pot Reactions: Ligand‐Centered Borenium Ions for Tandem Catalysis with Palladium
Authors: Skaria Manisha , Culpepper Johnathan D. , Daly Scott R.
Published: August 2022

Tandem catalysts that perform two different organic transformations in a single pot are highly desirable because they enable rapid and efficient assembly of simple organic building blocks into more complex molecules. Many examples of tandem catalysis rely on metal‐catalyzed reactions involving one or more metal complexes. Remarkably, despite surging interest in the development of chemically reactive (i. e., non‐innocent) ligands, there are few examples of metal complexes that leverage ligand‐centered reactivity to perform catalytic reactions in tandem with separate catalytic reactions at the metal. Here we report how multifunctional Pd complexes with triaminoborane‐derived diphosphorus ligands, called TBDPhos, appear to facilitate borenium‐catalyzed cycloaddition reactions at the ligand, and Pd‐catalyzed Stille and Suzuki cross‐coupling reactions at the metal. Both transformations can be accessed in one pot to afford rare examples of tandem catalysis using separate metal and ligand catalysis sites in a single complex.
A Lewis Acid Stabilized Ketenimine in an Unusual Variant of the Electrophilic Aromatic Substitution
Authors: Surkau Jonas , Bläsing Kevin , Bresien Jonas , Michalik Dirk , Villinger Alexander , Schulz Axel
Published: August 2022

Electrophilic aromatic substitution (EAS) can provide a straightforward approach to the efficient synthesis of functionalized complex aromatic molecules. In general, Lewis acids serve as a beneficial stimulus for the formation of a Wheland complex, the intermediate in the classical SEAr mechanism of EAS, which is responsible for H/E (E=electrophile) substitution under formal H+ elimination. Herein, we report an unusual variant of EAS, in which a complex molecule such as the tricyanomethane, HC(CN)3, is activated with a strong Lewis acid (B(C6F5)3) to the point where it can finally be used in an EAS. However, the Lewis acid here causes the isomerization of the tricyanomethane to the ketenimine, HN=C=C(CN)2, which in turn directly attacks the aromatic species in the EAS, with simultaneous proton migration of the aromatic proton to the imino group, so that no elimination occurs that is otherwise observed in the SEAr mechanism. By this method, it is possible to build up amino‐malononitrile‐substituted aromatic compounds in one step.
Templated Generation of a Bcl‐xL Inhibitor by Isomer‐Free SPAAC Based on Azacyclonon‐5‐yne
Authors: Brauer Juliane , Mötzing Marina , Gröst Corinna , Hoffmann Ralf , Berg Thorsten
Published: August 2022

High‐affinity inhibitors of large protein–protein interactions often have a high molecular weight, which compromises their cell permeability and oral bioavailability. We recently presented isomer‐free, strain‐promoted azide‐alkyne cycloaddition (iSPAAC) as a method by which to generate large, chemically uniform bioactive molecules inside living cells from two smaller components with higher cell permeability. Here, we present the synthesis of Fmoc‐protected azacyclonon‐5‐yne (Fmoc‐ACN) as the first cyclononyne suitable for iSPAAC. ACN facilitated the structure‐guided development of a single‐digit micromolar triazole inhibitor of the protein–protein interaction domain of the antiapoptotic protein Bcl‐xL. Inhibitor formation in aqueous buffer at 37 °C, templated by the target protein Bcl‐xL, proceeded 2800 times faster than the reaction between Fmoc‐ACN and benzyl azide under standard conditions in acetonitrile. Our data demonstrate the utility of cyclononynes for iSPAAC and their potential for achieving vastly accelerated templated reactions in aqueous environments.
Enantioselective Approach for Expanding the Three‐Dimensional Space of Tetrahydroquinoline to Develop BET Bromodomain Inhibitors**
Authors: Lespinasse Marie‐Ange , Wei Kaiyao , Perrin Justine , Winkler Matthias , Hamaidia Sieme , Leroy Alexis , Macek Jilkova Zuzana , Philouze Christian , Marche Patrice N. , Petosa Carlo , Govin Jérôme , Emadali Anouk , Wong Yung‐Sing
Published: August 2022

The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline‐catalyzed Mannich reaction followed by the addition of BF3 ⋅ OEt2, which generates a highly electrophilic aza‐ortho‐quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one‐pot process provides access for the first time to tetrahydroquinolines with acis‐2,3 andtrans‐3,4 configuration. As proof of concept, we demonstrate that a three‐step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2‐selective BET bromodomain inhibitor with anti‐inflammatory effect.
On the fluidization of cohesive powders: Differences and similarities between micro‐ and nano‐sized particle gas–solid fluidization
Authors: Kamphorst Rens , Wu Kaiqiao , Salameh Samir , Meesters Gabrie M. H. , van Ommen J. Ruud
Published: August 2022

The fluidization of cohesive powders has been extensively researched over the years. When looking at literature on the fluidization of cohesive particles, one will often find papers concerned with only micro‐ or only nano‐sized powders. It is, however, unclear whether they should be treated differently at all. In this paper, we look at differences and similarities between cohesive powders across the size range of several nanometres to 10s of micrometres. Classification of fluidization behaviour based on particle size was found to be troublesome since cohesive powders form agglomerates and using the properties of these agglomerates introduces new problems. When looking at inter‐particle forces, it is found that van der Waals forces dominate across the entire size range that is considered. Furthermore, when looking into agglomeration and modelling thereof, it was found that there is a fundamental difference between the size ranges in the way they agglomerate. Where the transition between the types of agglomeration is located is, however, unknown. Finally, how models are made and agglomerate sizes are measured is currently insufficient to accurately predict or measure their sizes consistently.
Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review
Authors: Jagpal Parbir K. , Alshareef Saad , Marriott John F. , Krishna Mamidipudi Thirumala
Published: August 2022

Background

Multiple drug allergy and multiple drug intolerance syndrome (MDAS/MDIS) labels are an impediment to clinical care and knowledge regarding these conditions is limited. This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco‐economics of MDAS and MDIS.

Methods

Systematic literature search across 11 databases (01 January 2000–06 November 2020) for MDIS, MDAS and related terminology. Studies were reviewed for quality of evidence and risk of bias by employing Critical Appraisal Skills Programme cohort study checklist. A narrative synthesis approach facilitated by systematic textual descriptions, tabulation and thematic analysis was adopted.

Results

There was heterogeneity in terminology and methodology. Few studies applied standard drug allergy diagnostic methods. There is some evidence to suggest that multiple drug hypersensitivity syndrome (MDHS; i.e., confirmed allergies in MDAS) is a distinct clinical entity. Prevalence of MDIS and MDAS labels in unselected & selected populations varied between 2.1%–6.4% & 4.9%–90% and 1.2% & 0%–36% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co‐morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non‐steroidal anti‐inflammatory drugs. No studies relating to clinical impact and pharmaco‐economics were found.

Conclusion

There is considerable burden of MDAS and MDIS labels. Data needs cautious interpretation as majority of studies described involved unverified labels. Despite this limitation and heterogeneity of studies, there is some evidence to suggest that MDHS is a distinct clinical entity. Well‐designed multi‐centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.
Interdisciplinary intervention for the management of nonmedical opioid use among patients with cancer pain
Authors: Arthur Joseph A. , Edwards Tonya , Lu Zhanni , Tang Michael , Amaram‐Davila Jaya , Reddy Akhila , Hui David , Yennurajalingam Sriram , Anderson Aimee E. , Jennings Kristofer , Reddy Suresh , Bruera Eduardo
Published: August 2022

Background

Few studies have assessed interventions aimed at managing nonmedical opioid use (NMOU) behavior among patients with cancer. The authors developed the Compassionate High‐Alert Team (CHAT) intervention to manage patients receiving opioids for cancer pain who demonstrate NMOU behavior. The objective of this study was to determine the change in frequency of NMOU behaviors, pain intensity, and opioid requirements among those who received the intervention.

Methods

A total of 130 patients receiving opioids for cancer pain that had documented evidence of NMOU and received the CHAT intervention were reviewed. Demographic and clinical information such as NMOU behaviors, pain scores, and morphine equivalent daily dose at baseline, 3, and 6 months post‐intervention was obtained.

Results

NMOU behaviors significantly decreased from a median (interquartile range) of 2 (1–3) at baseline to 0 (0–1) at both 3 and 6 months post‐intervention (p < .001). A total of 45 of 75 (60%) and 31 of 50 (62%) of CHAT recipients achieved complete response to the intervention at 3 and 6 months, respectively. Higher baseline number of NMOU behaviors was independently associated with patient response to the intervention (odds ratio [OR], 1.97; 95% confidence interval [CI],1.09–4.28, p = .049 at 3 months; OR, 2.5; 95% CI, 1.20–6.47, p = .03 at 6 months). The median pain score decreased from 7 at baseline to 6 at both 3 and 6 months (p = .01). Morphine equivalent daily dose did not significantly change during that same period (143 mg/day vs. 139 mg/day, p = .13).

Conclusions

Most patients who received the CHAT intervention improved in their NMOU behaviors and pain intensity scores 3 and 6 months post‐intervention. These preliminary findings support the efficacy of CHAT in managing patients receiving opioids for cancer pain who demonstrate NMOU behavior.
Comparison of the performance of different learning algorithms in leaf feature extraction and recognition using convolution neural network
Authors: Kayhan Gökhan
Published: August 2022

Plant identification with computer systems has been developed with image processing tools and has helped researchers to identify unknown plant species with high accuracy. In this study, the leaves of five different plants were classified according to their shapes using deep learning. A database was created with leaf images of mint, echinacea, St. John's wort, melissa, and thyme plants. Images in this database were classified with a convolution neural network (CNN). For this classification, 70% training and 30% testing were randomly selected in the database. The parameters of the CNN layer consist of a set of learnable filters. In the CNN, 10 kernel matrices with stride [1 1] were used. A rectified linear unit was chosen as the activation function. Maximum pooling was performed using a filter with stride [2 2]. In this classification, five fully connected layers were created. Using CNN, the performance of different learning algorithms was compared. It was observed that CNN achieved more successful results than traditional attribute methods.
Simultaneous Broadband Suppression of Homonuclear and Heteronuclear Couplings in 1H NMR Spectroscopy
Authors: Mycroft Coral , Nilsson Mathias , Morris Gareth A. , Castañar Laura
Published: August 2022

The 1H NMR analysis of species containing NMR‐active heteronuclei can be difficult due to signal overlap caused by the combined effects of homonuclear and heteronuclear scalar (J) couplings. Here, a general pure shift method is presented for obtaining ultra‐high resolution 1H NMR spectra where spectral overlap is drastically reduced by suppressing both homonuclear and heteronuclear J‐couplings, giving one single signal per 1H chemical environment. Its usefulness is demonstrated in the analysis of fluorine‐ and phosphorus‐containing compounds of pharmaceutical and biochemical interest.
Semimechanistic Physiologically‐Based Pharmacokinetic/Pharmacodynamic Model Informing Epcoritamab Dose Selection for Patients With B‐Cell Lymphomas
Authors: Li Tommy , Hiemstra Ida H. , Chiu Christopher , Oliveri Roberto S. , Elliott Brian , DeMarco Dena , Salcedo Theodora , Egerod Frederikke Lihme , Sasser Kate , Ahmadi Tahamtan , Gupta Manish
Published: August 2022

Epcoritamab is a CD3xCD20 bispecific antibody (bsAb) that induces T‐cell–mediated cytotoxicity against CD20‐positive B cells. Target engagement and crosslinking of CD3 and CD20 (trimer formation) leads to activation and expansion of T cells and killing of malignant B cells. The primary objective of the dose‐escalation part of the phase I/II trial of epcoritamab was to determine the maximum tolerated dose, recommended phase II dose (RP2D), or both. For bsAbs, high target saturation can negatively affect trimer formation. The unique properties and mechanisms of action of bsAbs require novel pharmacokinetic (PK) modeling methods to predict clinical activity and inform RP2D selection. Traditional PK/pharmacodynamic (PD) modeling approaches are inappropriate because they may not adequately predict exposure–response relationships. We developed a semimechanistic, physiologically‐based PK/PD model to quantitatively describe biodistribution, trimer formation, and tumor response using preclinical, clinical PK, biomarker, tumor, and response data from the dose‐escalation part of the phase I/II trial. Clinical trial simulations were performed to predict trimer formation and tumor response in patients with diffuse large B‐cell lymphoma (DLBCL) or follicular lymphoma (FL). Model‐predicted trimer formation plateaued at doses of 48 to 96 mg. Simulation results suggest that the 48‐mg dose may achieve optimal response rates in DLBCL and FL. Exposure–safety analyses showed a flat relationship between epcoritamab exposure and risk of cytokine release syndrome in the dose range evaluated. This novel PK/PD modeling approach guided selection of 48 mg as the RP2D and provides a framework that may be applied to other CD3 bsAbs.
Production of Eukaryotic Glycoproteins for Structural and Functional Studies Using Expi293F Cells
Authors: Greven Jessica A. , Brett Tom J.
Published: August 2022

Milligram quantities of pure proteins are required for structural, functional, and pharmaceutical screening studies. These requirements can be challenging for a majority of important therapeutic targets that are secreted glycoproteins, receptors, membrane proteins, or large cytosolic complexes. Here, we present protocols for producing and purifying large amounts of secreted glycoproteins using the mammalian cell‐based Expi293F system via large‐scale transient transfection. This system can be easily adapted for the production of membrane proteins and large cytosolic complexes. The method can be utilized to quickly evaluate numerous expression constructs to identify optimal expressers. Use of mammalian cells ensures proper post‐translational modifications, including disulfide bonds and glycosylation, that can be important for accurate functional studies. In addition, minor modifications can be introduced to produce labeled or deglycosylated proteins for structural studies by X‐ray crystallography, nuclear magnetic resonance, or cryo‐electron microscopy. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Production of milligram quantities of plasmid DNA for large‐scale transient transfection

Basic Protocol 2: Large‐scale culture and transient transfection of Expi293F cells

Basic Protocol 3: Purification of hexahistidine‐tagged proteins from medium
Different temporal trends in vascular plant and bryophyte communities along elevational gradients over four decades
Authors: Becker‐Scarpitta Antoine , Auberson‐Lavoie Diane , Aussenac Raphael , Vellend Mark
Published: August 2022

Despite many studies showing biodiversity responses to warming, the generality of such responses across taxonomic groups remains unclear. Very few studies have tested for evidence of bryophyte community responses to warming, even though bryophytes are major contributors to diversity and functioning in many ecosystems. Here, we report an empirical study comparing long‐term change in bryophyte and vascular plant communities in two sites with contrasting long‐term warming trends, using “legacy” botanical records as a baseline for comparison with contemporary resurveys. We hypothesized that ecological changes would be greater in sites with a stronger warming trend and that vascular plant communities, with narrower climatic niches, would be more sensitive than bryophyte communities to climate warming. For each taxonomic group in each site, we quantified the magnitude of changes in species' distributions along the elevation gradient, species richness, and community composition. We found contrasted temporal changes in bryophyte vs. vascular plant communities, which only partially supported the warming hypothesis. In the area with a stronger warming trend, we found a significant increase in local diversity and dissimilarity (β‐diversity) for vascular plants, but not for bryophytes. Presence–absence data did not provide sufficient power to detect elevational shifts in species distributions. The patterns observed for bryophytes are in accordance with recent literature showing that local diversity can remain unchanged despite strong changes in composition. Regardless of whether one taxon is systematically more or less sensitive to environmental change than another, our results suggest that vascular plants cannot be used as a surrogate for bryophytes in terms of predicting the nature and magnitude of responses to warming. Thus, to assess overall biodiversity responses to global change, abundance data from different taxonomic groups and different community properties need to be synthesized.
Molting phenology of a lacustrine ringed seal, Pusa hispida saimensis
Authors: Niemi Marja , Nykänen Milaja , Biard Vincent , Kurkilahti Mika , Kunnasranta Mervi
Published: August 2022

The timing and effect of a range of environmental variables on the annual molt of ringed seals (Pusa hispida saimensis) in Lake Saimaa were studied in 2013–2019. Molting patterns were investigated by mixed models run on photoidentification data collected by camera trapping and digital camera surveys. Photoperiod was the predominant environmental variable affecting the molt but molting of females was also linked to air temperature and ice thickness. The cumulative proportion of molting seals peaked around the 18th–20th May, when day length reached 18 h. The main molting season, when most of the seals were hauled out at the same time, lasted on average for 16 days with considerable inter‐annual differences in the duration (range 11–22 days). The results provide important baseline information on Saimaa ringed seal molt. Continued monitoring is important as the molt is an energetically demanding period for the seals, and any changes in molting behavior may indicate changes in habitat or in environmental conditions.