bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal NHC Palladium(II) Complex Containing CNN Pincer Skeleton and Its Application to Suzuki‐Miyaura Coupling of Aryl Chlorides in Water
Authors: Saini Vaishali , Madduluri Vimal Kumar , Pragya  , Rangan Krishnan , Khungar Bharti
Published: May 2023

The excellent catalytic activities of abnormal NHC carbene complexes, where the C2 position remains unaffected, and coordination occurs at the C4 or C5 position of the imidazolium ring, is still a fascinating but scarce area of research. This present work reports a palladium complex (LPdBr) bearing abnormal NHC with CNN pincer architecture. It is synthesized from imidazolium‐based quinoline ligand (LH) with Pd(OAc)2 via ‐NH and carbene deprotonation. The complex was fully characterized by NMR spectroscopy (1D and 2D) and high‐resolution mass spectrometry (HRMS). The structure and abnormal coordination modes of the complex are further confirmed with the help of single‐crystal X‐ray diffraction. The studies revealed the abnormal coordination mode in LPdBr where C5 carbon of the imidazolium ring participates in bonding, leaving the C2 position unaffected. The catalytic potential of complex LPdBr was investigated in the Pd‐catalyzed Suzuki‐Miyaura coupling of various aryl/heteroaryl chlorides with different aryl/naphthyl/phenanthryl boronic acids. The catalyst LPdBr successfully activated various less‐activated aryl chloride substrates. LPdBr also exhibited good catalytic activity at 1 mol% Pd loading under microwave irradiation and in green solvent water. The mechanism of the catalytic cycle is investigated and proposed by HRMS.
Facile Construction of Functionalized 4H‐Chromene Scaffolds via Sn(OTf)2‐Catalyzed C−H Functionalization/Cyclization Reaction and Ir‐Catalyzed Direct C−H Amidation
Authors: Qi Hongbo , He Junxia , Yuan Xingyu , Chen Shufeng
Published: May 2023

An efficient strategy for the construction of 4H‐chromene scaffolds from naphthols and conjugated diketones through a sequential Sn(OTf)2‐catalyzed Friedel–Crafts type C−H functionalization/cyclization process has been described. The Ir‐catalyzed C−H amination of these products could also be performed with the assistance of the carbonyl as a weak directing group, which produced a series of amino‐modified 4H‐chromene compounds in good yields.
Ultrasound evaluation of normal rhesus macaque fetal biometry and uteroplacental hemodynamics
Authors: D'Mello Rahul J. , Lo Jamie O. , Hagen Olivia L. , Castro Jenna N. , Graham Jason A. , Frias Antonio E. , Roberts Victoria H. J.
Published: May 2023

Nonhuman primates are important preclinical models for translational, reproductive, and developmental science. Clinical evaluation of human fetal development is performed using standard sonographic‐derived fetal biometry, assessments of amniotic fluid, and uteroplacental hemodynamics. These noninvasive in utero measurements provide important information regarding fetal growth and pregnancy well‐being. Abnormalities in fetal growth, amniotic fluid volume, or placental vascular function are associated with placental insufficiency and adverse perinatal outcomes including stillbirth. The fetal biometric parameters most commonly assessed are biparietal diameter, head circumference, abdominal circumference, and femur diaphysis length. Evaluation of amniotic fluid volume includes measuring the fluid in four quadrants of the uterus to generate an Amniotic Fluid Index. Measures of uteroplacental hemodynamics typically include doppler assessment of the umbilical artery and ductus venosus, but can also include interrogation of the uterine artery and umbilical vein. In this study, we compile prenatal ultrasound data of fetal biometry, amniotic fluid measurements, and uteroplacental hemodynamics obtained from pregnancy studies conducted at the Oregon National Primate Research Center. The data included are from control unperturbed pregnant animals who have not undergone in utero experimental manipulations. This is the first report of comprehensive sonographic measurements following standardized clinical obstetric protocols utilized in rhesus macaques. The outcome is a large, prenatal ultrasound resource to be used by laboratory animal researchers in future nonhuman primate pregnancy studies for antenatal assessment.
Rearrangements of Internally‐bridged Octaphyrin(1.1.1.1.1.1.1.1)s to Porphyrin Dimers
Authors: Nakai Akito , Tanaka Takayuki , Osuka Atsuhiro
Published: May 2023

Internally‐bridged octaphyrin(1.1.1.1.1.1.1.1) underwent a rearrangement to meso‐meso linked porphyrin dimer as a new metamorphosis. Extensive examination suggests that hydride‐addition is a key step for the rearrangements to afford thermodynamically more stable porphyrin framework. Further, β‐tetrabromo[36]octaphyrin was transformed to meso‐meso, β‐β, β‐β triply linked porphyrin dimer via a similar mechanism combined with Pd‐mediated reductive homocoupling.
Noncovalent Modulation of Chemoselectivity in the Gas Phase Leads to a Switchover in Reaction Type from Heterolytic to Homolytic to Electrocyclic Cleavage
Authors: Moorthy Suresh , Lambert Hugues , Mohan Neetha , Schwarzlose Thomas , Nau Werner M. , Kalenius Elina , Lee Tung‐Chun
Published: May 2023

In the gas phase, thermal activation of supramolecular assemblies such as host–guest complexes leads commonly to noncovalent dissociation into the individual components. Chemical reactions, for example of encapsulated guest molecules, are only found in exceptional cases. As observed by mass spectrometry, when 1‐amino‐methyl‐2,3‐diazabicyclo[2.2.2]oct‐2‐ene (DBOA) is complexed by the macrocycle β‐cyclodextrin, its protonated complex undergoes collision‐induced dissociation into its components, the conventional reaction pathway. Inside the macrocyclic cavity of cucurbit[7]uril (CB7), a competitive chemical reaction of monoprotonated DBOA takes place upon thermal activation, namely a stepwise homolytic covalent bond cleavage with the elimination of N2, while the doubly protonated CB7⋅DBOA complex undergoes an inner‐phase elimination of ethylene, a concerted, electrocyclic ring‐opening reaction. These chemical reaction pathways stand in contrast to the gas‐phase chemistry of uncomplexed monoprotonated DBOA, for which an elimination of NH3 predominates upon collision‐induced activation, as a heterolytic bond cleavage reaction. The combined results, which can be rationalized in terms of organic‐chemical reaction mechanisms and density‐function theoretical calculations, demonstrate that chemical reactions in the gas phase can be steered chemoselectively through noncovalent interactions.
Appealing sheath‐core spun high‐performance composite carbon molecular sieve membranes
Authors: Cao Yuhe , Liu Zhongyun , Qiu Wulin , Koros William J.
Published: May 2023

Carbon molecular sieve (CMS) membranes are attractive candidates to meet requirements for challenging gas separations. The added ability to maintain such intrinsic properties in an asymmetric morphology with a structure that we term a “Pseudo Wheel+Hub & Spoke” asymmetric form offers new opportunities. For CMS membrane, specifically, the structure provides both selective layer support and low flow resistance even for high feed pressures and fluxes in CO2 removal from natural gas. This capability is unavailable to even rigid glassy polymers due to the much higher modulus of CMS materials. Combining precursor asymmetric hollow fiber formation and optimized pyrolysis creates a defect free CMS proof‐of‐concept membrane for this application. Facile formation of the sheath‐core spun precursor with a 6FDA‐DAM sheath and Matrimid® core also avoids the need to seal defects before or after the carbonization of the precursors. The composite CMS membrane shows CO2/CH4 (50 : 50) mixed gas feed with an attractive CO2/CH4 selectivity of 64.3 and CO2 permeance of 232 GPU at 35 °C. A key additional benefit of the approach is reduction in use of the more costly high performance 6FDA‐DAM in a composite sheath‐core CMS membrane with the “Pseudo Wheel+Hub & Spoke” structure.
Lewis‐Säure‐katalysierte formale (3+2)‐Cycloaddition von Bicyclo[1.1.0]butanen mit Ketenen
Authors: Radhoff Niklas , Daniliuc Constantin G. , Studer Armido
Published: May 2023

Design, Synthese und Anwendung von Benzolbioisosteren haben in den letzten 20 Jahren viel Aufmerksamkeit erfahren. In jüngster Zeit haben sich Bicyclo[2.1.1]hexane als äußerst attraktive Bioisostere für ortho‐ und meta‐substituierte Benzole erwiesen. In diesem Artikel beschreiben wir eine milde, skalierbare und übergangsmetallfreie Methode zur Herstellung von hochsubstituierten Bicyclo[2.1.1]hexanen über eine Lewis‐Säure‐katalysierte (3+2)‐Cycloaddition von Bicyclo[1.1.0]butanketonen mit disubstituierten Ketenen. Die Reaktion zeigt eine hohe Toleranz gegenüber funktionellen Gruppen, wie die erfolgreiche Herstellung verschiedener 3‐Alkyl‐3‐Aryl‐ sowie 3,3‐Bisalkyl‐Bicyclo[2.1.1]hexan‐2‐onen belegt (26 Beispiele, bis zu 89 % Ausbeute). Die Folgechemie an der exozyklischen Ketonfunktion wird ebenfalls demonstriert.
Ru(bpy)32+‐Enabled Cell‐Surface Photocatalytic Proximity Labeling toward More Efficient Capture of Physically Interacting Cells
Authors: Qiu Shuang , Li Wannan , Deng Tao , Bi Angzhi , Yang Yang , Jiang Xi , Li Jie P.
Published: May 2023

Intercellular proximity labeling has emerged as a promising approach to enable the study of cell‐cell interactions (CCIs), but the efficiency of current platforms is limited. Here, we use Ru(bpy)32+ to construct an efficient photocatalytic proximity labeling (PPL) system on the cell surface that allows the highly discriminative CCI detection with spatiotemporal resolution. Through the mechanism study and quantitative characterization on living cells, we demonstrate that the singlet‐oxygen (1O2) mechanism is more efficient and specific than the single electron transfer (SET) mechanism in Ru‐mediated PPL. Ru(bpy)32+ catalysts with different cell‐anchoring moieties are prepared to facilitate the catalyst loading on primary cells. Finally, based on this system, we develop a “live” T cell receptor (TCR) multimer with TCR‐T cells that could sensitively identify and discriminate cells presenting antigens of different affinity, providing a powerful tool to better understand the heterogeneity of antigen presenting cells.
Palladium‐Catalyzed Hydrosilylation of Unactivated Alkenes and Conjugated Dienes with Tertiary Silanes Controlled by Hemilabile Hybrid P,O Ligand
Authors: Seo Sanghyup , Jung Joonho , Kim Hyunwoo
Published: May 2023

Novel P,O‐type ligands, N‐disulfonyl bicyclic bridgehead phosphorus triamides, were synthesized and utilized in Pd‐catalyzed hydrosilylation involving tertiary silanes, unactivated alkenes, and conjugated dienes. The ligand displayed a remarkable level of reactivity for alkene hydrosilylation with tertiary silanes and its use resulted in a significant improvement in the regioselectivity of diene hydrosilylation towards 1,2‐hydrosilylation. X‐ray crystallographic analysis confirmed the bidentate nature of the ligand, with coordination of phosphorus and oxygen. Control experiments provided evidence for the formation of Pd0 species and the reversibility of Pd−H insertion in the reaction mechanism. Density functional theory (DFT) computations supported the importance of the hemilabile P,O ligand in stabilizing both the rate‐determining transition state of Pd−H insertion and the transition state of reductive elimination that determines the regioselectivity.
Lewis Acid Catalyzed Formal (3+2)‐Cycloaddition of Bicyclo[1.1.0]butanes with Ketenes
Authors: Radhoff Niklas , Daniliuc Constantin G. , Studer Armido
Published: May 2023

Design, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho‐ and meta‐substituted benzenes. Herein we report a mild, scalable and transition‐metal‐free protocol for the construction of highly substituted bicyclo[2.1.1]hexan‐2‐ones through Lewis acid catalyzed (3+2)‐cycloaddition of bicyclo[1.1.0]‐butane ketones with disubstituted ketenes. The reaction shows high functional group tolerance as documented by the successful preparation of various 3‐alkyl‐3‐aryl as well as 3,3‐bisalkyl bicyclo[2.1.1]hexan‐2‐ones (26 examples, up to 89 % yield). Postfunctionalization of the exocyclic ketone moiety is also demonstrated.
Gold‐Catalyzed Amine Cascade Addition to Diyne‐Ene: Enantioselective Synthesis of 1,2‐Dihydropyridines
Authors: Wei Jingwen , Xing Yangyang , Ye Xiaohan , Nguyen Bao , Wojtas Lukasz , Hong Xin , Shi Xiaodong
Published: May 2023

With the well‐documented chemical and biological applications, piperidine and pyridine are among the most important N‐heterocycles, and a new synthetic strategy, especially one with an alternative bond‐forming design, is of general interest. Using the gold‐catalyzed intermolecular condensation of amine and diyne‐ene, we report herein the first example of enantioselective 1,2‐dihydropyridine synthesis through a formal [3+2+1] fashion (up to 95 % yield, up to 99 % e.e.).
Isothermal curing analysis and properties of ultra heat‐resistant polyimide composites by DMA method
Authors: Xiong Xuhai , Li Wenqiang , Ren Rong , Wang Jing
Published: May 2023

The isothermal curing process of T700 carbon fiber/P450 polyimide prepreg is characterized by dynamic mechanical analysis method and the gelation points are analyzed by torsional braid analysis theory. The growth mechanisms of the mechanical property at different constant temperatures are investigated by the relative mechanical growth rate of storage modulus and the curing kinetics models are established. The theories of Flory and Hsich are used to calculate the activation energy during the curing reaction of prepreg. The results indicates that the gelation times which are detected by the method of torsional braid analysis at 300, 310, 330, and 350°C were 293.7, 213.8, 104.1, and 45.4 min, respectively. The activation energies of curing reaction are calculated by Flory theory and Hsich theory, they are 112.35 and 119.96 kJ/mol, respectively. The feasibly of curing system 300°C × 4 h + 330°C × 2 h + 350°C × 2 h + 370°C × 2 h is verified by the mechanical properties and the heat resistance of polyimide composite.
Experimental study of the topological flow transformations in an aerial vortex bioreactor with a floating washer
Authors: Naumov Igor V. , Gevorgiz Ruslan G. , Skripkin Sergey G. , Tintulova Maria V. , Tsoi Mikhail A. , Sharifullin Bulat R.
Published: May 2023

Background

Research into the flow structure in an aerial vortex bioreactor is relevant for developing the methods for growing cell cultures. Determining the optimal cultivation condition for a certain process is especially important in the case when such parameters of the medium as density and viscosity significantly change with the culture growth in the bioreactor.

Methods and results

The research of the flow dynamic was carried out in an 8.5 L universal aerial vortex bioreactor, with a washer freely floating on its surface and stabilizing the motion of the working fluid. The regularities of the vortex motion of the culture medium have been determined by Particle Image Velocimetry depending on its volume and the intensity of rotation of the activator, generating vortex motion in the air.

Conclusion

The observed vortex structure and its dynamics at increasing flow swirl intensity are established to coincide with the structure of a confined vortex flow in a cylindrical container with no washer for both single and two‐fluid configurations. This novel methodology of the flow optimization shows that an ascending swirling jet forms in the vicinity of the bioreactor axis, and a bubble‐like vortex breakdown forms in the axial region.
Establishment and application of a survival rate graph model based on biomarkers and imaging indexes after primary hepatocellular carcinoma resection
Authors: Xu Yue , Yao Xiaoqin , Li Jinmei , Zhang Guoyuan , Luo Guangcheng , Wang Qiang
Published: May 2023

Background

Primary liver cancer (PLC) is a highly malignant disease. This study developed an effective and convenient tool to evaluate survival times of patients after hepatectomy, which can provide a reference point for clinical decisions.

Methods

Clinical and laboratory data of 243 patients with PLC after hepatectomy were collected. Univariate cox regression analysis, Lasso regression analysis and multivariate cox regression analysis were used to determine the best prediction index. Multivariate cox regression analysis was used to construct a survival prediction model. A receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the model. The patients in this model were divided into was divided into high‐risk and low‐risk groups according to the optimal cut‐off value of the ROC curve for different prognostic years. Kaplan–Meier survival analysis and log‐rank test were used to analyse the survival differences between the two groups.

Results

Tumour size, portal vein thrombosis, distant metastasis, alpha‐fetoprotein and protein induced by vitamin K absence or antagonist‐II levels were independent risk factors for overall survival (OS) after PLC surgery. The area under the concentration‐time curve for 2‐, 3‐ and 4‐year survival of patients was 0.710, 0.825 and 0.919, respectively, with a good calibration of the Hosmer–Lemeshow test (p > 0.05) and net benefit. The mortality rates in patients with 2, 3 and 4 years of survival were 70.59%, 67.83% and 66.67% for the high‐risk group and 21.84%, 22.50% and 22.67% for the low‐risk group, respectively. The mortality rate of the high‐risk group was significantly higher than that of the low‐risk group (p < 0.05).

Conclusion

The OS model of prognosis after PLC surgery constructed in this study can be used to predict the 2‐, 3‐ and 4‐year survival prognoses of patients, and patients with different prognosis years can be re‐stratified so that they achieve more accurate and personalised assessment, thereby providing a reference point for clinical decision‐making.
Extended Scope and Understanding of Zinc‐Dependent Alcohol Dehydrogenases for Reduction of Cyclic α‐Diketones
Authors: Stark Frances , Hoffmann Aaron , Ihle Nadine , Loderer Christoph , Ansorge‐Schumacher Marion B.
Published: May 2023

Alcohol dehydrogenases (ADH) are important tools for generating chiral α‐hydroxyketones. Previously, only the ADH of Thauera aromatica was known to convert cyclic α‐diketones with appropriate preference. Here, we extend the spectrum of suitable enzymes by three alcohol dehydrogenases from Citrifermentans bemidjiense (CibADH), Deferrisoma camini (DecADH), and Thauera phenylacetica (ThpADH). Of these, DecADH is characterized by very high thermostability; CibADH and ThpADH convert α‐halogenated cyclohexanones with increased activity. Otherwise, however, the substrate spectrum of all four ADHs is highly conserved. Structural considerations led to the conclusion that conversion of diketones requires not only the expansion of the active site into a large binding pocket, but also the circumferential modification of almost all amino acid residues that form the first shell of the binding pocket. The constellation appears to be overall highly specific for the relative positioning of the carbonyl functions and the size of the C‐ring.
[2+4] Cycloaddition Product of an Amidinate Substituted Dialumene with Toluene
Authors: Kumar Arun , Yadav Komal , Graw Nico , Pandey Madhusudan K. , Herbst‐Irmer Regine , Lourderaj Upakarasamy , Stalke Dietmar , Roesky Herbert W.
Published: May 2023

Reduction of LAlI2(L=PhC(NiPr2C6H3)2) with two equivalents of KC8in toluene affords the [2+4]cycloaddition product of a dialumene with toluene. The mechanism for the formation of product complex was investigated using density functional theory (DFT) methods.
Shape‐Morphing Liquid‐Crystal polymers
Authors: Zhang Dachuan , Yuan Chenrui , Zhou Yang , Wu Si
Published: May 2023

Liquid‐crystal polymers are a type of representative material combining the order‐disorder transition of liquid crystals and the superior properties of polymers. The phase transition from the liquid‐crystal phase to the isotropic state of mesogens causes large, controllable, and reversible deformation of polymers; thus, liquid‐crystal polymers have emerged as one of the most valuable candidates for shape‐morphing materials. Therefore, this review will focus on the recent development of shape‐morphing liquid‐crystal polymers, including the modes of energy conversions, material design strategies and further applications. In the main, novel material design methods and a wide range of application of shape‐morphing liquid‐crystal polymers are discussed.
Divergent Synthesis of Stachyurin and Casuarinin Focusing on C‐Glycosidic Bond Reactivity
Authors: Kusuki Reina , Murakami Kei , Katsuta Ryo , Ishigami Ken , Wakamori Shinnosuke
Published: May 2023

Stachyurin and casuarinin are ellagitannins, a class of polyphenols that exhibit various biological activities that have an impact on human health. Casuarinin is a stachyurin stereoisomer. These compounds contain the characteristic C‐glycosidic bond between the open‐chain d‐glucose and the phenol aromatic ring. Therefore, chemical elucidation of the C‐glycosidic bond reactivity is required to exploit their multiple bioactivities. This study developed a method for the divergent synthesis of stachyurin and casuarinin via the α‐selective C‐glycosylation as well as the β‐selective introduction of the oxygen functional group, focusing on structural specificity. The proposed method applies to the syntheses of stachyurin and casuarinin analogues, thereby facilitating the utilisation of their beneficial bioactivities.
Push‐Pull Bridged Distyrylbenzene with Highly Bright Solid‐State Red‐Orange Aggregation‐Induced Emission
Authors: Shimomura Yoshimichi , Konishi Gen‐ichi
Published: May 2023

Multiple emission colors in solid‐state organic fluorophores with the same main skeleton are essential for improving the performance of light‐emitting devices/materials. Specifically, emission in the red/near‐infrared region is of great importance in the biological field. Previously, we developed di‐bridged‐distyrylbenzeneDBDB[7]with high‐brightness solid‐state blue and aggregation‐induced emissions (AIE) by introducing the bridging structures of a seven‐membered ring into the vinylene groups of distyrylbenzene (DSB). Herein, we synthesizeMNDBDMeODB[7](1), which features substituted methoxy and malononitrile groups as donor and acceptor groups, respectively, inDBDB[7]. In solvents more polar than THF,MNDSDMeOB(3), which has the same main skeleton as1but without bridges, shows no emission in the solid state, whereas1exhibits highly bright red‐orange emission in the solid state owing to the suppression of intermolecular electronic interactions by the bridges and the AIE property. We also synthesizeMNDSD(EHO)B(2) in which the methoxy groups of3are replaced by ethylhexyloxy groups, thus disrupting the crystallinity of the molecule.2exhibits positive fluorescence solvatochromism and has a high fluorescence quantum yield in the solid state as a red‐emittingDSBderivative. The solid‐state emission properties of1and2will improve the applicability ofDSBs and functionalities of light‐emitting devices/materials.
Image‐Based Flow Regime Recognition in Aerated Stirred Tanks Using Deep Transfer Learning
Authors: Khaydarov Valentin , Becker Marc Philipp , Urbas Leon
Published: May 2023

Monitoring of flow regimes in aerated stirred tanks is important to ensure energy efficiency and product quality. The use of deep learning models for the recognition of flow regimes shows promising results. However, such models require a large amount of data for training. The aim of this paper is to apply the deep transfer learning approach to address this challenge. We compare various pre‐trained models with the differential learning rate and 2‐step transfer learning approaches to analyse the resultant model performance. We also investigate the effect of the dataset size on the classification accuracy.
Pharmacokinetics and Pharmacodynamics of Lansoprazole/Sodium Bicarbonate Immediate‐release Capsules in Healthy Chinese Subjects: An Open, Randomized, Controlled, Crossover, Single‐, and Multiple‐dose Trial
Authors: Yu Lixiu , Zhai Xuejia , Wu Sanlan , Cao Peng , Deng Yahui , Yang Quancheng , Zhang Qilin , Wu Jiancai , Deng Yue , Liu Qiaoling , Zhang Yu
Published: May 2023

Proton pump inhibitors (PPIs) differ in onset of action and bioavailability. This trial was conducted to investigate the pharmacokinetics and pharmacodynamics of an immediate‐release capsule formulation containing lansoprazole 30 mg and sodium bicarbonate 1100 mg (T preparation) in healthy Chinese subjects. This was an open, single‐center, randomized, single and multiple oral doses, and two‐period crossover study in 30 healthy subjects. After single‐ and multiple‐dose oral administration, blood samples were obtained and lansoprazole concentration in serum was measured for pharmacokinetic analysis. Meanwhile, the intragastric pH was monitored continuously to evaluate the pharmacodynamics of the investigational drugs. The Tmax of the T preparation was 0.5 hours, while the Tmax of the R preparation was 1.5 hours after multiple doses, which indicated that the absorption speed of the T preparation was significantly faster than that of the R preparation. The same characteristics also existed after single‐dose administration. The area under the curve (AUC)ss of the T preparation was bio‐equivalent to that of the R preparation under steady state. The time percentage of intragastric pH > 4.0 for the T preparation was higher than that of the R preparation after 1 hour for both single‐ and multiple‐dose. It suggested compared with R preparation, the time percentage of intragastric pH > 4.0 met the criteria for superiority after 1 hour administration for the T preparation. In addition, no serious adverse events occurred in this study. Across this study, the T preparation was better than the R preparation at improving drug absorption and increasing intragastric pH, and had a favorable safety profile.
Catalytic Deactivation and Regeneration of Nickel Microparticles in a Home‐Built Microchannel‐Coupled Millireactor: Substrate Specificity and Multiphase Flow Dependency
Authors: Jaiswal Pooja , Yogeshwar Prerna , Guha Biswas Koushik , Panda Debashis
Published: May 2023

Substrate‐assisted product desorption often proposed in heterogeneous catalysis (nanozymes) denounces the catalytic deactivation of these catalysts. On the contrary, the catalytic deactivation of rigid heterogeneous catalyst becomes noticeable in a continuous flow reactor. Surprisingly, it has been addressed inadequately and in an isolated manner. In this study, we have developed a cost‐effective non‐lithographic method for the fabrication of a PDMS‐based microchannel‐coupled‐millreactor. Immobilized nickel particles are resistant to leaching in the flow process. During continuous operation, millireactors show a strong catalytic activity for reduction of resazurin and p‐nitrophenol with a conversion rate of almost 100 %. Catalytic poisoning is ubiquitous and gets gradually prominent whereas complete catalytic deactivation of magnetic Ni‐microparticles is found to be an instantaneous process. Relatively large‐sized resorufin binds predominantly to the surface and thereby blocks the access of the substrate to the Ni‐particles. The dissociations of product molecules ‐ resorufin and p‐aminophenol are the rate‐limiting steps that caused the abrupt deactivation of Ni‐microparticle. The kinetic mechanism of heterogeneous derived from the Langmuir‐Hinshelwood mechanism satisfactorily explains the catalytic poisoning and deactivation of nickel microparticles. This study sheds light on the intricacies of catalytic activity and poisoning of magnetic nickel microparticles.
Anti‐Tumoural [NHC(thiolato)] Gold(I) Complexes Derived from HIF‐1α Inhibitor AC1‐004 Target the Mitochondrial Redox System and Show Antiangiogenic Effects in vivo
Authors: Schleser Sebastian W. , Köhler Leonhard H. F. , Riethmüller Florian , Reich Sebastian , Fertig Robin , Schlotte Luca , Seib Jonathan , Goller Alexander , Begemann Gerrit , Kempe Rhett , Schobert Rainer
Published: May 2023

AC1‐004 is a potent inhibitor of the hypoxia‐inducible factor alpha (HIF‐1α) pathway, essential for tumour growth, angiogenesis and metastasis. We modelled a series of gold(I) complexes on AC1‐004, retaining its 5‐carboalkoxybenzimidazole as an NHC ligand while replacing its 2‐aryloxymethyl residue with modified thiolato gold(I) fragments. The intention was to augment a potential HIF‐1α inhibition by conducive effects typical of NHC gold complexes, such as an inhibition of tumoural thioredoxin reductase (TrxR), an increase in reactive oxygen species (ROS), and cytotoxic and antiangiogenic effects. We report on the synthesis and biological effects of twelve such N,N’‐dialkylbenzimidazol‐2‐ylidene gold(I) complexes, obtained in average yields of 65 % for the thiophenolato and 45 % for the novel 4‐(adamant‐2‐yl)benzenethiol complexes. The structure of one complex was validated via single‐crystal X‐ray diffraction. Structure‐activity relationships (SAR) were derived by variation of the N‐substituents (Me, Et, iPr, pentyl, Bn) and the thiolato ligand. Their cytotoxicity against various human cancer cell lines of different entities reached IC50 values in the single‐digit micromolar range. The complexes were also assayed for the induction of tumour cell apoptosis (activation of caspase‐3/7), TrxR inhibition and antiangiogenic effects in zebrafish. Cyclopropene‐bearing congeners were employed in click reactions to examine the subcellular accumulation of the complexes.
Optimization of Large‐Scale Adeno‐Associated Virus (AAV) Production
Authors: Bilal Alina S. , Parker Sarah N. , Murray Victoria B. , MacDonnell Lauren F. , Thuerauf Donna J. , Glembotski Christopher C. , Blackwood Erik A.
Published: May 2023

Genetic manipulation in vivo is a critical method for mechanistically understanding gene function in disease and physiological processes. To facilitate this, embryonic transgenesis in popular animal models like mice has been developed. Compared to the longer, expensive methods of transgenesis, viral vectors, such as adeno‐associated virus (AAV), have grown increasingly in popularity due to their relatively low cost and ease of production, translating to an overall greater versatility as a biological tool. In this article, we describe protocols for AAV production and purification for efficient transduction in vivo. Importantly, our method differs from others in application of a streamlined, more cost‐effective approach. From this method, as many as 2 × 1013 genome‐containing viral particles (vp), or 200 units, can be produced within 3 to 4 weeks, with a minimal cost of $1800 to $2000 for supplies and reagents and <15 hr of personnel time per week. A unit here is defined as 1 × 1011 vp, our standard dose of AAV per animal, injected via tail vein. Therefore, our method provides production and purification of AAV in quantities capable of transducing up to 200 animals. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: AAV production

Basic Protocol 2: AAV purification
Identification of potential targets against SARS‐CoV‐2 of antiviral drugs based on photoaffinity probes
Authors: Ma Yuexiang , Wang Jin , Pan Xiaoyan , Zhang Jie , Shan Yuanyuan
Published: May 2023

Facing the sudden outbreak of coronavirus disease 2019 (COVID‐19), it is extremely urgent to develop effective antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Drug repurposing is a promising strategy for the treatment of COVID‐19. To identify the precise target protein of marketed medicines, we initiate a chemical biological program to identify precise target of potential antivirus drugs. In this study, two types of recombinant human coronavirus SARS‐CoV‐2 RdRp protein capturing probes with various photoaffinity labeling units were designed and synthesized based on the structure of FDA‐approved drugs stavudine, remdesivir, acyclovir, and aladenosine. Fortunately, it was found that one novel photoaffinity probe, RD‐1, could diaplayed good affinity with SARS‐CoV‐2 RdRp around the residue ARG_553. In addition, RD‐1 probe also exhibited potent inhibitory activity against 3CLpro protease. Taken together, our findings will elucidate the structural basis for the efficacy of marketed drugs, and explore a rapid and efficient strategy of drug repurposing based on the identification of new targets. Moreover, these results could also provide a scientific basis for the clinical application of marketed drugs.
New pyrrole derivatives as DNA gyrase and 14α‐demethylase inhibitors: Design, synthesis, antimicrobial evaluation, and molecular docking
Authors: Hilmy Khaled M. H. , Kishk Fawzya N. M. , Shahen Esmat B. A. , Sobh Eman A. , Hawata Mohamed A.
Published: May 2023

An efficient one‐pot reaction utilizing readily available chemical reagents was used to prepare novel 2‐amino‐1,5‐diaryl‐1H‐pyrrole‐3‐carbonitrile derivatives and the structures of these compounds were validated by spectroscopic data and elemental analyses. All the synthetic compounds were evaluated for their antimicrobial activities (MZI assay). The tested compounds proved high activities on Staphylococcus aureus (Gram‐positive bacteria) and Candida albicans (Pathogenic fungi). However, they did not show any activity on Escherichia coli (Gram‐negative bacteria). The most effective compounds in MZI assay 7c, 9a, 9b, 11a, and 11b were selected to determine their MIC on S. aureus and C. albicans. Furthermore, DNA gyrase and 14‐α demethylase inhibitory assays were performed to study the inhibitory activities of 7c, 9a, 9b, 11a, and 11b. The results illustrated that compound 9b was the most DNA gyrase inhibitor (IC50 of 0.0236 ± 0.45 µM, which was 1.3‐ fold higher than gentamicin reference IC50 values of 0.0323 ± 0.81 µM). In addition, compound 9b demonstrated the highest 14‐α demethylase inhibitory effect with IC50 of 0.0013 ± 0.02 µM, compared to ketoconazole (IC50 of 0.0008 ± 0.03 µM) and fluconazole (IC50 of 0.00073 ± 0.01 µM), as antifungal reference drugs. Lastly, docking studies were performed to rationalize the dual inhibitory activities of the highly active compounds on both DNA gyrase and 14‐α demethylase enzymes.
A pilot randomized controlled trial of transdiagnostic network‐informed personalized treatment for eating disorders versus enhanced cognitive behavioral therapy
Authors: Butler Rachel M. , Ortiz Anna Marie L. , Pennesi Jamie‐Lee , Crumby Emma K. , Cusack Claire E. , Levinson Cheri A.
Published: May 2023

Objective

Eating disorders (EDs) are serious mental illnesses with high mortality and relapse rates and carry significant societal and personal costs. Nevertheless, there are few evidence‐based treatments available. One aspect that makes treatment difficult is the high heterogeneity in symptom presentation. This heterogeneity makes it challenging for clinicians to identify pertinent treatment targets. Personalized treatment based on idiographic models may be well‐suited to address this heterogeneity, and, in turn, presumably improve treatment outcomes.

Methods

In the current randomized controlled trial, participants will be randomly assigned to either 20 sessions of enhanced cognitive behavioral therapy (CBT‐E) or transdiagnostic network‐informed personalized treatment for EDs (T‐NIPT‐ED). Assessment of ED symptoms, clinical impairment, and quality of life will occur at pre‐, mid‐, posttreatment, and 1‐month follow‐up.

Results

We will examine the acceptability and feasibility of T‐NIPT‐ED compared to CBT‐E. We also will test the initial clinical efficacy of T‐NIPT‐ED versus CBT‐E on clinical outcomes (i.e., ED symptoms and quality of life). Finally, we will test if the network‐identified precision targets are the mechanisms of change.

Discussion

Ultimately, this research may inform the development and dissemination of evidence‐based personalized treatments for EDs and serve as an exemplar for personalized treatment development across the broader field of psychiatry.

Public Significance

Current evidence‐based treatments for eating disorders result in low rates of recovery, especially for adults with AN. Our study aims to test the feasibility, acceptability, and clinical efficacy of a data‐driven, individualized approach to ED treatment, network‐informed personalized treatment, compared to the current evidence‐based treatment for EDs, Enhanced CBT. Findings have the potential to improve treatment outcomes for EDs by identifying and targeting core symptoms maintaining EDs.
Pd‐Catalysed Diastereoselective Synthesis of aza‐Spirocyclic P‐Stereogenic Phosphine Oxides
Authors: Zhang Bin , Zhang Xiao‐Ming , Zhang Qing‐Wei
Published: May 2023

Phosphine oxides and spirocyclic compounds are privileged molecules widely employed in a variety of catalytic transformations either as chiral ligands for metals or bifunctional organocatalysts. Herein, we developed a Pd‐catalysed cross‐coupling reaction to synthesize spirocyclic amino‐phosphine oxides with a P‐stereogenic centre which could serve as potential P*(O), N‐ligands or organocatalysis.
Feasibility of diffusion‐tensor and correlated diffusion imaging for studying white‐matter microstructural abnormalities: Application in COVID‐19
Authors: Teller Nick , Chad Jordan A. , Wong Alexander , Gunraj Hayden , Ji Xiang , Goubran Maged , Gilboa Asaf , Roudaia Eugenie , Sekuler Allison , Churchill Nathan , Schweizer Tom , Gao Fuqiang , Masellis Mario , Lam Benjamin , Heyn Chris , Cheng Ivy , Fowler Robert , Black Sandra E. , MacIntosh Bradley J. , Graham Simon J. , Chen J. Jean
Published: May 2023

There has been growing attention on the effect of COVID‐19 on white‐matter microstructure, especially among those that self‐isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single‐shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single‐shell‐compatible diffusion MRI modeling methods are compared for detecting the effect of COVID‐19, including diffusion‐tensor imaging, diffusion‐tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self‐isolated patients at the study initiation and 3‐month follow‐up, along with age‐ and sex‐matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single‐shell methods to demonstrate COVID‐19‐related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID‐19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID‐19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID‐19 related white‐matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b‐values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3‐month follow‐up, likely due to the limited size of the follow‐up cohort. To summarize, correlated diffusion imaging is shown to be a viable single‐shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID‐19 patients, suggesting the two regions react differently to viral infection.
Photobiomodulation increases uprighting tooth movement and modulates IL‐1β expression during orthodontically bone remodeling
Authors: Murakami‐Malaquias‐Silva Felipe , Perim Rosa Ellen , Malavazzi Tainá Caroline Santos , Silva Tamiris , de Santana Sarmento Dmitry José , Garcez Aguinaldo Silva , Fernandes Marcella Ueda R. , Tortamano Andre , Ramalho Karen Muller , Motta Lara Jansiski , Fernandes Kristianne Porta Santos , Bussadori Sandra Kalil , Mesquita‐Ferrari Raquel Agnelli , Horliana Anna Carolina Ratto Tempestini
Published: May 2023

This study investigated the effects of photobiomodulation (PBM) in acceleration of orthodontic movement of inferior molar uprighting movement. Thirty‐four individuals, with indication of molar uprighting movement for oral rehabilitation, were randomly divided in two groups: verticalization + PBM (808 nm, 100 mW, 1 J per point, 10 points and 25 J/cm2) or verticalization + PBM simulation. Elastomeric chain ligatures were changed every 30 days for 3 months. FBM was performed immediately, 24 h, 72 h, 1 and 2 months after activation. The primary outcome was the amount of uprighting movement. Secondary outcomes were pain, amount of medication, OHIP‐14 questionnaire, and cytokine IL‐1β. PBM group increase uprighting movement when compared to control after 3 months and modulate IL‐1β expression. For pain control, the amount of medication and OHIP‐14 no difference were found. This study suggests that PBM accelerates tooth movement during molar uprighting, due to modulation of IL‐1β during bone remodeling.
Valley morphology and Quaternary seismic stratigraphy of the Manicouagan impact crater lake (Eastern Canada)
Authors: Lenz Kai‐Frederik , Gebhardt Andrea Catalina , Lajeunesse Patrick , Lohrberg Arne , Gross Felix , Krastel Sebastian
Published: May 2023

Lakes in formerly glaciated regions can provide valuable paleoclimate archives. Lake Manicouagan (Manikuakan, according to Innu toponymy), formed in the basin of the ~214‐Ma Manicouagan impact crater of eastern Québec, is a key area for reconstructing long‐term environmental change, as it was directly affected by the Pleistocene glaciations and the waxing and waning of the Laurentide Ice Sheet. Here, we present high‐resolution seismic data revealing an overdeepened bedrock valley filled with a sedimentary sequence. We assess its potential to serve as a paleoclimate archive. The varying shape of the overdeepened valley indicates complex erosional processes. A lower narrow V‐shaped gorge is indicative of either pressurized subglacial meltwater or pre‐Quaternary fluvial erosion, or a combination of both. Three scenarios are discussed regarding deposition of the sedimentary sequence: (i) deposition only during and after retreat of the last glacial episode; (ii) deposition during multiple glacial–interglacial cycles; and (iii) deposition mainly during a subglacial lake stage. We suggest subglacial followed by proglacial sedimentation as the most probable scenario for deposition of the sedimentary succession. We recommend considering the sediments of Lake Manicouagan as a paleoclimate archive reaching back at least to 7.5 ka, but the lake also probably contains sediments deposited before the last deglacial period.
Infection reporting in patients undergoing irreversible electroporation of locally advanced pancreatic cancer
Authors: Filson Anthony , Martin Robert C. G.
Published: May 2023

Background

Intraoperative bile cultures (IOBCs) taken during pancreatic surgery are commonly performed and there has been limited evidence that a positive IOBC could aid in perioperative adverse event (AE) management. Therefore, this study aims to describe infection management in patients undergoing irreversible electroporation (IRE).

Methods

An Institutional Review Board (IRB)‐approved prospective database was utilized from 8/2016 to 6/2022, with 127 pancreatic adenocarcinoma patients included.

Results

A total of 28 patients that underwent IRE also had a simultaneous positive IOBC and the remaining 99 patients that underwent IRE had negative IOBC. A total of 11(39%) of the patients with a positive IOBC had AE's, and 38 (38%) of the patients with negative IOBC had AE's. Both groups had similar rates of AEs leading to new hospitalization and prolonged hospitalizations. Overall, there was no correlation between a positive IOBC and a patient developing an AE.

Conclusions

The findings of this study provide insights that improve the infectious management of patients undergoing IRE.
The local Borg–Marchenko uniqueness theorem of matrix‐valued Dirac‐type operators for coefficients locally smooth at the right endpoint
Authors: Wei Guangsheng , Zhang Zhongfang
Published: May 2023

We provide an expression of the Weyl–Titchmarsh matrix associated with a self‐adjoint matrix‐valued Dirac‐type operator defined on [0, b) for . As a concrete application of it, we establish asymptotics of the difference of two Weyl–Titchmarsh matrices corresponding to two Dirac‐type operators , with a.e. on [0, a], in with , when the are sufficiently smooth in a right neighborhood of the point a and their right derivatives at a coincide up to a certain order. In addition to this, we also provide new proofs of the local Borg–Marchenko theorem and asymptotic high‐energy expansion of Weyl–Titchmarsh matrices associated with Dirac‐type operators.
Simply connected Voisin manifolds of dimension four
Authors: Wang Linsheng
Published: May 2023

Voisin constructed a series of examples of simply connected compact Kähler manifolds of even dimension, which do not have the rational homotopy type of a complex projective manifold starting from dimension six. In this note, we prove that Voisin's examples of dimension four also do not have the rational homotopy type of a complex projective manifold. Oguiso constructed simply connected compact Kähler manifolds starting from dimension four, which cannot deform to a complex projective manifold under a small deformation. We also prove that Oguiso's examples do not have the rational homotopy type of a complex projective manifold.
Photochromic Polyurethane Coatings with Cross‐Linked Structure and Self‐Healing Behavior Based on the FRET Effect
Authors: Liu Yayuan , Tian Fuyue , Hu Jing , Ning Nanying , Yu Bing , Tian Ming
Published: May 2023

Intelligent fluorescent coatings have received widespread attention in the encryption technique field such as anti‐counterfeit, while the traditional fluorescent coatings are easy to be damaged by external force. In this study, the fluorescent and self‐healing anti‐counterfeit coatings are prepared after rational molecular design. Two polymers containing fluorescent groups, including polyurethane containing the anthracene (AN) side group and polyimide containing the naphthalenediimide (NDI) structure are synthesized to realize multiple color changes with fluorescence through simply blending. Due to the overlapping fluorescence spectra of the groups, enabling the fluorescence resonance energy transfer effect (FRET), the coating with different group ratios exhibits tunable fluorescence under the same excitation light, providing diverse patterns. Moreover, due to the reversible photo‐crosslinking and thermal de‐dimerization properties of anthracene, the recording, erasure, and rewriting of the surface pattern can be realized, and the fluorescent anti‐counterfeit coatings exhibit excellent self‐healing properties after cross‐linking due to the FRET effect, which solves the problem of poor healing and ensures the stability and integrity. The fluorescent coating with cross‐linked structure and self‐healing behavior based on the FRET effect greatly expands the functional applications of traditional polyurethane materials.