bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermo‐Triggered In Situ Chitosan‐Based Gelation System for Repeated and Enhanced Sonodynamic Therapy Post a Single Injection
Authors: She Jialin , Zhou Xuanfang , Zhang Yaojia , Zhang Rui , Li Quguang , Zhu Wenju , Meng Zhouqi , Liu Zhuang
Published: November 2020

Sonodynamic therapy (SDT) by utilizing ultrasonic waves triggers the generation of reactive oxygen species (ROS) with the help of sonosensitizers to destruct deep‐seated tumors has attracted great attention. However, the efficacy of SDT may not be robust enough due to the insufficient oxygen supply within solid tumors. Additionally, repeated injections and treatments, which are often required to achieve the optimal therapeutic responses, may cause additional side effects and patient incompliance. Herein, a thermo‐triggered in situ hydrogel system is developed in which catalase (CAT) conjugated with sonosensitizer meso‐tetra (4‐carboxyphenyl) porphine (TCPP) is mixed into chitosan (CS) and beta‐glycerol phosphate disodium (GP) to form the precursor solution. After injection of the precursor solution into tumors, the in situ sol–gel transformation will occur as triggered by the body temperature, resulting in the localized tumor retention of TCPP‐CAT. The locally restrained TCPP‐CAT not only produces ROS under ultrasonic treatment, but also sustainably reverses the oxygen‐deficient status in solid tumors by triggering the O2 generation from the decomposition of endogenous H2O2, further promoting the efficacy of SDT. As a result, the repeated SDT after a single dose injection of such a hydrogel can offer robust treatment effects to effectively eradicate tumors.
Sprayable Thin and Robust Carbon Nanofiber Composite Coating for Extreme Jumping Dropwise Condensation Performance
Authors: Donati Matteo , Lam Cheuk Wing Edmond , Milionis Athanasios , Sharma Chander Shekhar , Tripathy Abinash , Zendeli Armend , Poulikakos Dimos
Published: November 2020

Condensation of water on metallic surfaces is critical for multiple energy conversion processes. Enhancement in condensation heat transfer efficiency often requires surface texturing and hydrophobicity, usually achieved through coatings, to maintain dropwise condensation. However, such surface treatments face conflicting challenges of minimal coating thermal resistance, enhanced coating durability, and scalable fabrication. This study presents a thin (≈2 µm) polytetrafluoroethylene–carbon nanofiber nanocomposite coating that meets these challenges and sustains coalescence‐induced jumping droplet condensation for extended periods under highly demanding condensation conditions. Coating durability is achieved through improved substrate adhesion by depositing a submicron thick aluminum primer layer. Carbon nanofibers in a polytetrafluoroethylene matrix increase coating thermal conductivity and promote spontaneous surface nanotexturing to achieve superhydrophobicity for condensate microdroplets. The coating material can be deposited through direct spraying, ensuring economical scalability and versatility for a wide range of substrates. No other coating is known for metallic surfaces that is able to sustain jumping dropwise condensation under shear of steam at 111 °C flowing at ≈3 m s−1 over the surface for 10 h and dropwise condensation for an additional 50 h. Up to ≈900% improvement in condensation heat transfer coefficient is achieved compared to conventional filmwise condensation.
Self‐Assembled Rolled‐Up Microcoils for nL Microfluidics NMR Spectroscopy
Authors: Lepucki Piotr , Egunov Aleksandr I. , Rosenkranz Marco , Huber Renato , Mirhajivarzaneh Alaleh , Karnaushenko Dmitry D. , Dioguardi Adam P. , Karnaushenko Daniil , Büchner Bernd , Schmidt Oliver G. , Grafe Hans‐Joachim
Published: November 2020

Several attempts are made to downscale nuclear magnetic resonance (NMR) spectroscopy systems and to enable high resolution chemical analysis of small sample quantities. However, miniaturization is nontrivial due to stringent demands on precise analyte sampling within the detector while performing local excitation of the sample and signal detection with a microsized coil. Imperfect coil geometry and inhomogeneities in the coil's surrounding environment have a detrimental impact on the signal quality, hampering further development of miniature NMR systems. To solve this challenge, a new type of monolithic wafer‐scale self‐assembled microcoils with a detection volume of 1.5 nL are integrated into a microfluidics circuit. The microcoils are fully encapsulated in polydimethylsiloxane (PDMS) allowing for simplified and precise supply of an analyte through the interior of the detector. Due to their construction, with the inner winding touching the analyte, the microcoils have an almost 100% filling factor. Magnetic field inhomogeneities are reduced through well‐defined microtubular architectures and susceptibility matched conductors. This approach results in a spectral linewidth of only 8 ppb with shimming and 22 ppb without shimming. The demonstrated methodology promotes the realization of next generation miniaturized analytical NMR systems for product monitoring, safety verification, medical testing, and material evaluation.
Hydrogel‐Based Diffractive Optical Elements (hDOEs) Using Rapid Digital Photopatterning
Authors: Xiong Zheng , Kunwar Puskal , Soman Pranav
Published: November 2020

Hydrogels, due to their optical transparency and biocompatibility, have emerged as an excellent alternative to conventional optical materials for biomedical applications. Advances in microfabrication techniques have helped convert conventional hydrogels into optically functional materials such as hydrogel‐based diffraction optical elements (hDOEs). However, key challenges related to device customization and ease/speed of fabrication need to be addressed to enable widespread utility and acceptance of hDOEs in the field. Here, rapid printing of customized hDOEs is reported on polyethylene glycol diacrylate (PEGDA) hydrogel using digital photopatterning; a novel method that combines simulated computer‐generated hologram (SCGH) and projection photolithography. To showcase the versatility of this approach, a range of hDOEs are demonstrated, including 1D/2D diffraction gratings, Dammann grating, Fresnel zone plate (FZP) lens, fork‐shaped grating, and computer‐generated hologram (CGH) of arbitrary pattern. Results demonstrate that printed hDOEs exhibit optical performance that is comparable with devices made with conventional materials. This versatile strategy can be potentially implemented with other photosensitive hydrogels to achieve user‐defined hDOEs in a time‐efficient and cost‐effective fashion.
Mn‐Substituted Tunnel‐Type Polyantimonic Acid Confined in a Multidimensional Integrated Architecture Enabling Superfast‐Charging Lithium‐Ion Battery Anodes
Authors: Wang Boya , Wei Yunhong , Fang Haoyu , Qiu Xiaoling , Zhang Qiaobao , Wu Hao , Wang Qian , Zhang Yun , Ji Xiaobo
Published: November 2020

Given the inherent features of open tunnel‐like pyrochlore crystal frameworks and pentavalent antimony species, polyantimonic acid (PAA) is an appealing conversion/alloying‐type anode material with fast solid‐phase ionic diffusion and multielectron reactions for lithium‐ion batteries. Yet, enhancing the electronic conductivity and structural stability are two key issues in exploiting high‐rate and long‐life PAA‐based electrodes. Herein, these challenges are addressed by engineering a novel multidimensional integrated architecture, which consists of 0D Mn‐substituted PAA nanocrystals embedded in 1D tubular graphene scrolls that are co‐assembled with 2D N‐doped graphene sheets. The integrated advantages of each subunit synergistically establish a robust and conductive 3D electrode framework with omnidirectional electron/ion transport network. Computational simulations combined with experiments reveal that the partial‐substitution of H3O+ by Mn2+ into the tunnel sites of PAA can regulate its electronic structure to narrow the bandgap with increased intrinsic electronic conductivity and reduce the Li+ diffusion barrier. All above merits enable improved reaction kinetics, adaptive volume expansion, and relieved dissolution of active Mn2+/Sb5+ species in the electrode materials, thus exhibiting ultrahigh rate capacity (238 mAh g−1 at 30.0 A g−1), superfast‐charging capability (fully charged with 56% initial capacity for ≈17 s at 80.0 A g−1) and durable cycling performance (over 1000 cycles).
Disability and sex/gender intersections in unmet workplace support needs: Findings from a large Canadian survey of workers
Authors: Jetha Arif , Gignac Monique A. M. , Ibrahim Selahadin , Martin Ginis Kathleen A.
Published: November 2020

Introduction

Individual attributes including disability and sex/gender have the potential to intersect and determine the likelihood of unmet workplace support needs. Our study compares unmet workplace support needs between workers with and without a disability, and according to disability type and sex/gender differences.

Methods

Workers with (n = 901) and without (n = 895) a disability were surveyed to examine their need and use of workplace supports including job accommodations, work modifications and health benefits. A multivariable logistic model was conducted to examine the relationship between disability status, disability type and sex/gender and unmet workplace support needs. The model included interaction terms between sex/gender × physical disability, sex/gender × nonphysical disability, and sex/gender × physical and nonphysical disability.

Results

Among participants with a disability, 24% had a physical disability, 20% had a nonphysical disability (e.g., cognitive, mental/emotional or sensory disability) and 56% had both physical and nonphysical disability. Over half of the respondents were women (56%). Results from the multivariable model showed that nondisabled women were more likely to report unmet workplace support needs when compared to nondisabled men (odds ratio [OR] = 1.54, 95% confidence interval [CI], 1.13–2.10). Findings also showed an intersection between the number and type of disability and sex/gender; women with both a physical and nonphysical disability had the greatest likelihood of reporting unmet workplace support needs when compared to nondisabled men (OR = 2.73; 95% CI, 1.83–4.08).

Conclusions

Being a woman and having one or more disabilities can determine unmet workplace support needs. Strategies to address workplace support needs should consider the intersection between disability and sex/gender differences.
Atomically Precise Preorganization of Open Metal Sites on Gold Nanoclusters with High Catalytic Performance
Authors: Yuan Shang‐Fu , Lei Zhen , Guan Zong‐Jie , Wang Quan‐Ming
Published: November 2020

Gold nanoclusters with surface open sites are crucial for practical applications in catalysis. We have developed a surface geometric mismatch strategy by using mixed ligands of different type of hindrance. When bulky phosphine Ph3P and planar dipyridyl amine (Hdpa) are simultaneously used, steric repulsion between the ligands will reduce the ligand coverage of gold clusters. A well‐defined access granted gold nanocluster [Au23(Ph3P)10(dpa)2Cl](SO3CF3)2 (Au23, dpa=dipyridylamido) has been successfully synthesized. Single crystal structural determination reveals that Au23 has eight uncoordinated gold atoms in the shape of a distorted bicapped triangular prism. The accessibility of the exposed Au atoms has been confirmed quantitatively by luminescent titration with 2‐naphthalenethiol. This cluster has excellent performance toward selective oxidation of benzyl alcohol to benzaldehyde and demonstrates excellent stability due to the protection of negatively charged multidentate ligand dpa.
Phenylpyridyl‐Fused Boroles: A Unique Coordination Mode and Weak B−N Coordination‐Induced Dual Fluorescence
Authors: He Jiang , Rauch Florian , Friedrich Alexandra , Krebs Johannes , Krummenacher Ivo , Bertermann Rüdiger , Nitsch Jörn , Braunschweig Holger , Finze Maik , Marder Todd B.
Published: November 2020

Using 4‐phenylpyridine or 2‐phenylpyridine in place of biphenyl, two electron‐poor phenylpyridyl‐fused boroles, [TipPBB1]4 and TipPBB2 were prepared. [TipPBB1]4 adopts a unique coordination mode and forms a tetramer with a cavity in both the solid state and solution. The boron center of TipPBB2 is 4‐coordinate in the solid state but the system dissociates in solution, leading to 3‐coordinate borole species. Compared to its borafluorene analogues, the electron‐accepting ability of TipPBB2 is largely enhanced by the pyridyl group. TipPBB2 exhibits dual fluorescence in solution due to an equilibrium between free TipPBB2 and a weak intermolecular coordination adduct with a second molecule. This equilibrium was further investigated by low‐temperature NMR spectroscopy and photophysical studies. Theoretical studies indicate that the highest occupied molecular orbital (HOMO) of TipPBB2 localizes at the Tip group, in contrast to its borafluorene derivatives, wherein the HOMOs are localized on the borafluorene cores.
Catalytic Synthesis of Potassium Acyltrifluoroborates (KATs) from Boronic Acids and the Thioimidate KAT Transfer Reagent
Authors: Schuhmacher Anne , Ryan Sarah J. , Bode Jeffrey W.
Published: November 2020

We report the synthesis of potassium acyltrifluoroborates (KATs) by a palladium‐catalyzed cross‐coupling of boronic acids and the thioimidate KAT transfer reagent. The combination of widely available aryl‐ and vinylboronic acids with commercially available thioimidate 1 using catalytic PdII and a CuII additive enables the preparation of KATs in high yields and with good functional group tolerance. This formal insertion of CO into organoboronic acids can also be applied to boronic acid pinacol esters and potassium organotrifluoroborates using a slightly modified procedure. The cross‐coupling can be telescoped into the one‐pot synthesis of amides and α‐aminotrifluoroborates by exploiting the unique chemistry of KATs and their trifluoroborate iminium (TIM) derivatives.
Renormalized Flory‐Huggins lattice model of physicochemical kinetics and dynamic complexity in self‐healing double‐network hydrogel
Authors: Xing Ziyu , Lu Haibao , Hossain Mokarram
Published: November 2020

Self‐healing capability offers great designability on mechanical properties of double‐network (DN) hydrogel. However, the thermodynamics understanding behind such physicochemical transitions and self‐healing behaviors are yet to be explored properly. This study describes a renormalized Flory‐Huggins lattice model for DN hydrogels, of which the physicochemical kinetics and dynamic complexity are resulted from stress‐induced bond scission and macromolecule rearrangement. Based on the Flory‐Huggins lattice model and Gaussian distribution theory, an extended free‐energy model was formulated by the steric repulsive free‐energy function. Afterwards, the function was used to identify the working mechanisms and thermodynamics in self‐healing DN hydrogels with ultra‐high mechanical strength. Finally, the effectiveness of model was demonstrated by applying it to predict the mechanical behaviors of DN hydrogels, where the analytical results showed good agreements with experiment data.
Performance enhancement of nanofiltration membranes via surface modification with a novel acylation reagent
Authors: Qin Yitian , Zhang Zhao , Kang Guodong , Zhu Zhihao , Yu Haijun , Cao Yiming
Published: November 2020

Acyl chloride monomers have been serving as the dominant acylation reagent for preparing thin‐film composite (TFC) nanofiltration (NF) membranes over the past few decades. Herein, a novel acylation reagent (trimellitic anhydride, TMA) was exploited in conjunction with trimesoyl chloride (TMC) to undergo interfacial polymerization with piperazine (PIP) on the polysulfone substrate membranes. The introduction of TMA enabled the deeper diffusion of PIP monomers into the organic phase, resulting in the creation of novel circular‐shaped protuberances on the top surface of the polyamide layer and the significant increase in the effective membrane area. Besides, abundant in‐situ carboxylic groups were generated in the polyamide layer, conducive to both the surface hydrophilicity and negative charge density. Consequently, with an addition of 0.03 wt% TMA, pure water flux reached up to 15.3 L m−2 hour−1 bar−1, almost 2.2 times that of the pristine membrane, and high rejection of Na2SO4 (97.3%) was maintained, evincing the superior desalination performance of the TMA‐modified membranes. The interaction mechanism between TMA, TMC, and PIP was described in detail. Furthermore, the TMA‐modified membranes exhibited a stable separation performance over the long‐running process.
Process economics evaluation of cell‐free synthesis for the commercial manufacture of antibody drug conjugates
Authors: Stamatis Christos , Farid Suzanne S.
Published: November 2020

Continuous improvements of cell‐free synthesis (CFS) systems have generated interest in adopting the technology for the manufacture of biologics. This paper provides an evaluation of the manufacturing cost‐effectiveness of CFS for the commercial production of antibody‐drug conjugates (ADCs). The evaluation was performed using an advanced techno‐economic engine (TEE) built in Python. The TEE is programmed in an object‐oriented environment capable of simulating a plethora of process flowsheets and predicting size and cost metrics for the process and the facility. A case study was formulated to compare the economics of whole bioprocesses based on either a CFS system or a mammalian cell system (CHO) for the manufacture of an ADC at a range of product demands. The analysis demonstrated the potential of CFS for the commercial manufacture of biologics and identified key cost drivers related to the system. The CFS system showed an approximately 80% increase in the cost of goods compared to CHO with a significant cost attributed to the in‐house manufacture of the bacterial cell extract, necessary for the CFS reaction step in the process. A sensitivity and target analysis highlighted the need for further process improvements especially in the titer for the CFS process to become more competitive against well‐established systems.
Inhibitory effects of astilbin, neoastilbin and isoastilbin on human cytochrome CYP3A4 and 2D6 activities
Authors: Shi Yurui , Xie Jing , Chen Rongda , Liu Guiming , Tao Yanzhou , Fan Yangyang , Wang Xiaolin , Li Li , Xu Jiaming
Published: November 2020

Astilbin, neoastilbin and isoastilbin are three flavonoid isomers from Smilacis glabrae Roxb. (S. glabrae). Several studies have shown that consumption of flavonoids can increase the risk of food/drug–drug interaction by affecting the activities of human cytochrome CYP3A4 and 2D6. In the present study, an ultrahigh‐performance liquid chromatography and triple quadrupole mass spectrometry method was developed for the determination of the interaction between three flavonoid isomers and two CYPs. Under the optimized reaction conditions, the Km values were 18.9 and 36.4 μM and the Vmax values were 0.02 and 0.20 μM/min for CYP3A4 and 2D6 in vitro, respectively. Astilbin showed the strongest inhibition on CYP3A4, followed by isoastilbin and neoastilbin with IC50 values of 2.63, 3.03 and 6.51 μM. Neoastilbin showed the strongest inhibition on CYP2D6, followed by isoastilbin and astilbin, with IC50 values of 1.48, 11.87 and 14.16 μM, respectively. The three isomers showed reversible inhibition on both enzymes. Neoastilbin and astilbin were noncompetitive type for CYP3A4 and 2D6, isoastilbin was a mixture and noncompetitive type for CYP3A4 and 2D6, respectively. Our study suggests that the three isomers may increase the risk of food/drug–drug interactions by affecting the activities of CYP3A4 and 2D6.
β‐Cyclodextrin Encapsulation of Synthetic AHLs: Drug Delivery Implications and Quorum‐Quenching Exploits
Authors: Ziegler Eric W. , Brown Alan B. , Nesnas Nasri , Chouinard Christopher D. , Mehta Anil K. , Palmer Andrew G.
Published: November 2020

Many bacteria, such as Pseudomonas aeruginosa, regulate phenotypic switching in a population density‐dependent manner through a phenomenon known as quorum sensing (QS). For Gram‐negative bacteria, QS relies on the synthesis, transmission, and perception of low‐molecular‐weight signal molecules that are predominantly N‐acyl‐l‐homoserine lactones (AHLs). Efforts to disrupt AHL‐mediated QS have largely focused on the development of synthetic AHL analogues (SAHLAs) that are structurally similar to native AHLs. However, like AHLs, these molecules tend to be hydrophobic and are poorly soluble under aqueous conditions. Water‐soluble macrocycles, such as cyclodextrins (CDs), that encapsulate hydrophobic guests have long been used by both the agricultural and pharmaceutical industries to overcome the solubility issues associated with hydrophobic compounds of interest. Conveniently, CDs have also demonstrated anti‐AHL‐mediated QS effects. Here, using fluorescence spectroscopy, NMR spectrometry, and mass spectrometry, we evaluate the affinity of SAHLAs, as well as their hydrolysis products, for β‐CD inclusion. We also evaluated the ability of these complexes to inhibit wild‐type P. aeruginosa virulence in a Caenorhabditis elegans host infection study, for the first time. Our efforts confirm the potential of β‐CDs for the improved delivery of SAHLAs at the host/microbial interface, expanding the utility of this approach as a strategy for probing and controlling QS.
Severe cryoglobulinemia with cerebral infarction successfully treated with steroid and rituximab: A case report
Authors: Yagi Naoko , Yoshimura Takuro , Nakamae Hirohisa , Hayashi Daisuke , Tanaka Yasuyuki , Ichikawa Yoshitaka , Hino Masayuki
Published: November 2020

We report the case of severe cryoglobulinemia with cerebral infarction and ischemic cardiac disease successfully treated with steroid and rituximab.
Surgical repair of large pulmonary artery to left atrium fistula
Authors: Hussain Alaa , Younis Muhamed , Srour Samir , Saleh Mohamed , Ismael Mohammed
Published: November 2020

We report a successful surgical closure of a rught pulmonary artery to left atrium fistula (RPALAF) with secondary atrial septal defect (ASD) in a 3.5 years old girl. These fistulae are rare cause of cyanosis and require early diagnosis and treatment to prevent the serious complications of them.
Roles of Enhancement of C−H Activation and Diminution of C−O Formation Within M1‐Phase Pores in Propane Selective Oxidation
Authors: Liu Yilang , Twombly Adam , Dang Yanliu , Mirich Anne , Suib Steven L. , Deshlahra Prashant
Published: November 2020

Propane and propene oxidations on M1 phase MoVTeNb mixed oxide catalysts exhibit relatively high selectivity to acrolein and acrylic acid. We probe the ability of the reactant molecules to access the catalytic sites inside the heptagonal pores of these oxides and analyze elementary steps that limit selectivity. Measured propane/cyclohexane activation rate ratios on MoVTeNbO are nearly an order of magnitude higher than non‐microporous VOx/SiO2, which suggests significant contribution of M1 phase pores to propane activation because both molecules react via homologous rate‐limiting C−H activation. Density functional theory suggests that desired C3H8 dehydrogenation and C3H6 allylic oxidation to acrolein and acrylic acid are limited by C−H activation steps, while less valuable oxygenates form via steps limited by C−O bond formation. Calculated activation barriers for C−O formation are invariably higher than C−H activation when these activations occur inside the pores, suggesting that reactions restricted within the pores are highly selective to desired products. These results demonstrate the role of pore confinement and a framework to assess selectivity limitation in hydrocarbon oxidations involving a complex network of sequential and parallel steps.
Manganese Oxide as an Inorganic Catalyst for the Oxygen Evolution Reaction Studied by X‐Ray Photoelectron and Operando Raman Spectroscopy
Authors: Radinger Hannes , Connor Paula , Stark Robert , Jaegermann Wolfram , Kaiser Bernhard
Published: November 2020

Manganese oxide (MnOx) is considered a promising material for the oxygen evolution reaction (OER) to replace noble metal catalysts in water splitting. The improvement of MnOx requires mechanistic and kinetic knowledge of the four‐electron transfer steps of the OER. X‐ray photoelectron spectroscopy, a widely used tool to characterize the electronic structure of thin films, is used in combination with surface‐enhanced Raman spectroscopy to gain a deeper knowledge of the different mixed MnOx types and their respective change in chemical composition. Using Raman spectroscopy during electrochemical measurements, all samples were found to reveal Birnessite‐type MnO2 motifs in alkaline media at an applied potential. Their activity correlates with two shifting Raman active modes, one of them being assigned to the formation of MnIII species, and one to the expansion of layers of MnO6 octahedra. A special activation treatment leads independent of the starting material to a highly amorphous mixed‐valence oxide, which shows the highest OER activity.
How Metallic Impurities in Carbon Cathodes Affect the Electrochemistry of Aluminum Batteries
Authors: Smajic Jasmin , Simoes Filipa R. Fernandes , Costa Pedro M. F. J.
Published: November 2020

As a promising electrochemical energy storage system, rechargeable aluminum batteries face critical challenges in their quest for commercial viability. While the design of suitable cathodes has attracted much attention, their chemical composition and purity has been less of a concern. This is especially true for carbon cathodes, where the presence of metallic impurities is often overlooked. Herein, we demonstrate the influence that transition metals exert on the electrochemistry of carbon nanotube cathodes for non‐aqueous aluminum batteries. In the presence of chloroaluminate electrolytes, these synthesis by‐products originate inflated capacities, increased self‐discharge and misleading electrochemical signatures, among others. Thus, our findings affirm the need for strict control of the composition and purity of materials (and components) used in non‐aqueous aluminum batteries.
Study of Polyoxometalates as Electrode Materials for Lithium‐Ion Batteries: Thermal Stability Paves the Way to Improved Cycle Stability
Authors: Bosch Georg‐Maximilian , Sarapulova Angelina , Dsoke Sonia
Published: November 2020

Polyoxometallates (POMs) are ideal candidates for energy storage because of their multi‐electron transfer. (n‐Bu4N)3PW12O40 (TBA‐PW) and Cs3PW12O40 (Cs‐PW), prepared by proton‐exchange with tetrabutylammonium (TBA+) and cesium (Cs+) from H3PW12O40, suffer from serious capacity fading, owing to the contained crystal water. The presence of water in POMs is well known, but its effect on electrochemical performance is not reported yet. In contrast to TBA‐PW, Cs‐PW has a higher thermal stability and can be treated at 600 °C, which allows the complete water removal (Cs‐PW‐600). Cs‐PW‐600 has a 15‐times better cycling performance than the one dried at 120 °C. Different pressures were applied to optimize the electrode fabrication. Samples treated at 8 tons show a three‐times better rate capability with respect to the unpressed sample, with 42.8 % retention of the capacity at 200 mA g−1. Cs‐PW‐600 can be seen as an example for further investigations on POMs as electrode materials.
Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity
Authors: Frei Angelo , King A. Paden , Lowe Gabrielle J. , Cain Amy K. , Short Francesca L. , Dinh Hue , Elliott Alysha G. , Zuegg Johannes , Wilson Justin J. , Blaskovich Mark A. T.
Published: November 2020

Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug‐resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it is reasonable to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad‐spectrum antifungal activity. Some of these complexes show minimum inhibitory concentrations (MIC) in the low micro‐ to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report the first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg kg−1 are tolerated without adverse effects, paving the way for further in vivo studies of these complexes.
Cephalosporin Prodrug Inhibitors Overcome Metallo‐β‐Lactamase Driven Antibiotic Resistance
Authors: van Haren Matthijs J. , Tehrani Kamaleddin H. M. E. , Kotsogianni Ioli , Wade Nicola , Brüchle Nora C. , Mashayekhi Vida , Martin Nathaniel I.
Published: November 2020

The increasing prevalence of metallo‐β‐lactamase (MBL)‐expressing bacteria presents a worrying trend in antibiotic resistance. MBLs rely on active site zinc ions for their hydrolytic activity and the pursuit of MBL‐inhibitors has therefore involved the investigation of zinc chelators. To ensure that such chelators specifically target MBLs, a series of cephalosporin prodrugs of two potent zinc‐binders: dipicolinic acid (DPA) and 8‐thioquinoline (8‐TQ) was prepared. Although both DPA and 8‐TQ bind free zinc very tightly (Kd values in the low nm range), the corresponding cephalosporin conjugates do not. The cephalosporin conjugates are efficiently hydrolyzed by MBLs to release DPA or 8‐TQ, as confirmed by using both NMR and LC‐MS studies. Notably, the cephalosporin prodrugs of DPA and 8‐TQ show potent inhibitory activity against NDM, VIM, and IMP classes of MBLs and display potent synergy with meropenem against MBL‐expressing clinical isolates of K. pneumoniae and E. coli.
Chemical product design integrating MCDA: Performance prediction and human preferences modelling
Authors: Suárez Palacios Oscar Yesid , Narváez Rincón Paulo César , Camargo Mauricio , Corriou Jean‐Pierre , Fonteix Christian
Published: November 2020

Computation‐based techniques and modelling of human knowledge and preferences by using multi‐criteria decision aid (MCDA) methods are integrated in a multi‐scale and multi‐disciplinary approach for the chemical product and process design. The proposed methodology has four main stages: (a) construction of a molecular model for predicting product performance, (b) validation of product performance, (c) selection of alternatives integrating preferences of manufacturers and consumers, and (d) process optimization implementing MCDA methods. The methodology is oriented to find new products that can replace components of formulations, whose performance is already known. It was applied to an exploratory study about the use of glycerol as raw material to produce plasticizers for polyvinyl chloride (PVC), replacing 2‐ethylhexyl phthalate (DEHP). The results of the case study and the proposed process design offer promising prospects regarding their application in other chemical products.
Explicit Treatment of Non‐Michaelis‐Menten and Atypical Kinetics in Early Drug Discovery**
Authors: Srinivasan Bharath
Published: November 2020

Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential to sustain life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were mostly tested and implemented for cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more‐complex systems (for instance, multiprotein complexes, oligomeric assemblies, membrane proteins and post‐translationally modified proteins), the initial axioms defined by Michaelis‐Menten (MM) kinetics are rendered inadequate, and the development of a new kind of kinetic analysis to study these systems is required. This review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug‐discovery for such systems, to enable effective screening and characterisation of small‐molecule inhibitors with desirable physiological outcomes.
Synthesis and Structure‐Activity Relationship of Xenocoumacin 1 and Analogues as Inhibitors of Ribosomal Protein Synthesis
Authors: Zumbrunn Cornelia , Krüsi Daniela , Stamm Christina , Caspers Patrick , Ritz Daniel , Rueedi Georg
Published: November 2020

Ribosomal protein synthesis is an important target in antibacterial drug discovery. Numerous natural products have served as starting points for the development of antibiotics. We report here the total synthesis of xenocoumacin 1, a natural product that binds to 16S ribosomal RNA at a highly conserved region, as well as analogues thereof. Preliminary structure–activity relationship studies were aimed at understanding and modulating the selectivity between eukaryotic and prokaryotic ribosomes. Modifications were mainly tolerated in the aromatic region. Whole‐cell activity against Gram‐negative bacteria is limited by efflux and penetration, as demonstrated in genetically modified strains of E. coli. Analogues with high selectivity for eukaryotic ribosomes were identified, but it was not possible to obtain inhibitors selective for bacterial protein synthesis. Achieving high selectivity (albeit not the desired one) was thus possible despite the high homology between eukaryotic and prokaryotic ribosomes in the binding region.
Color vision assessment‐1: Visual signals that affect the results of the Farnsworth D‐15 test
Authors: Evans Benjamin E. W. , Rodriguez‐Carmona Marisa , Barbur John L.
Published: November 2020

The Farnsworth D‐15 test (D‐15) is commonly used to screen for moderate to severe congenital color vision deficiency. The aim of this study was to establish reliable D‐15 statistics for normal, deutan and protan subjects, and to investigate the different visual signals one can use to carry out the test, even in dichromats and rod monochromats. Six hundred and seventy‐four subjects were examined using the D‐15, the Colour Assessment and Diagnosis test and the Nagel anomaloscope. A rod monochromat and five dichromats were tested using the standard D‐15 protocol before the caps were separated into two groups and subjects were asked to repeat the task. D‐15 spectral radiance data, measured under D65 illumination, were used to estimate differences in photoreceptor excitations for each of the caps. When no crossings and up to two adjacent transpositions on the D‐15 results diagram are accepted as a pass, 100% of normal trichromats, 54% of deutans and 43% of protans pass the D‐15. A rod monochromat and two protanopes and deuteranopes were able to complete the D‐15 when the caps were separated into two groups, despite severe loss or even complete absence of color vision. When up to two adjacent transpositions are accepted 50% of color deficient subjects, some with severe red/green loss, pass the D‐15. While the D‐15 is normally used to screen for moderate to severe color deficiency, subjects with severe loss can still use combined, residual red/green, yellow/blue and luminance signals to pass.
Color vision assessment‐3. An efficient, two‐step, color assessment protocol
Authors: Barbur John L. , Rodriguez‐Carmona Marisa , Evans Benjamin E. W.
Published: November 2020

Color vision tests and multi‐test protocols in current use often fail to detect small changes in red/green (RG) and yellow/blue (YB) color vision due to poor sensitivity. The tests also have low specificity. In this study, we examine how improved understanding of within‐ and inter‐subject variability in RG and YB color vision and accurate assessment of the differences in color thresholds between the least‐sensitive, age‐matched normal trichromats, and the least‐affected deutans and protans can be used to design an efficient color vision screener (CVS) test. To achieve this objective, we examined two extensive data sets from earlier studies and carried out new experiments to provide better estimates of within‐subject variability in color thresholds and to validate the CVS test. The data sets provide essential information on inter‐subject variability, the effects of normal aging on RG and YB thresholds, and the spread in RG color thresholds in deutan and protan subjects. A statistical model was developed to optimize the parameters of the CVS test and to predict the limits of what can be achieved in color assessment. The efficiency and repeatability of the CVS test were then assessed in 84 subjects. The results match model predictions and reveal close to 100% test efficiency. The test takes between 140 and 160 seconds to complete and has close to 100% repeatability. An efficient, “two‐step” protocol based on the initial use of the CVS test followed by full color assessment in only those who fail the CVS test is also described.
Location‐based social network recommendations with computational intelligence‐based similarity computation and user check‐in behavior
Authors: Elangovan Rajalakshmi , Vairavasundaram Subramaniyaswamy , Varadarajan Vijayakumar , Ravi Logesh
Published: November 2020

Location recommending frameworks plays a very significant role in suggesting the users with new places to visit especially when users are visiting unfamiliar areas. Most of the existing recommender systems do not consider the fact that different users have different behavior while checking in. Some approaches do not consider the essential factors while providing recommendations. These systems lack adaptability and hence they provide poor recommendations. An adaptive approach to provide users with a personalized recommendation has been proposed in this paper. We have considered three features namely, user activeness feature, user similarity feature, and the spatial feature. In addition to this, we have also considered the location popularity for a given timeslot. We have divided the users into inactive and active based on the degree of activeness on social networks using fuzzy c‐means clustering. We have provided two strategies based on the activeness of the user. A two‐dimensional Gaussian kernel density estimation strategy is used for the active user. A one‐dimensional power‐law function strategy is used for inactive users. Moreover, we have integrated the time‐based popularity of the location and probability estimation based on the similarity between the users. To evaluate the proposed model, we have used a large‐scale Foursquare dataset.
The Sulfo‐Click Reaction and Dual Labeling of Nucleosides
Authors: Clavé Guillaume , Vasseur Jean‐Jacques , Smietana Michael
Published: November 2020

This article contains detailed synthetic procedures for the implementation of the sulfo‐click reaction to nucleoside derivatives. First, 3′‐O‐TBDMS‐protected nucleosides are converted to their corresponding 4′‐thioacid derivatives in three steps. Then, various conjugates are synthetized via a biocompatible and chemoselective coupling procedure using sulfonyl azide partners. Finally, to illustrate the potential of the sulfo‐click reaction, a nucleoside bearing two orthogonal azido groups is synthesized and engaged in one‐pot dual labeling through a sulfo‐click/copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) cascade. The high efficiency of the sulfo‐click reaction as applied to nucleosides opens up new possibilities in the context of bioconjugation. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: General protocol for the synthesis of 4′‐thioacid‐nucleoside derivatives

Basic Protocol 2: Implementation of the sulfo‐click reaction

Basic Protocol 3: Synthesis of 3′‐azido‐4′‐(carboxamido)ethane‐sulfonyl azide‐3′‐deoxythymidine

Basic Protocol 4: Detailed synthetic procedure for one‐pot double‐click conjugations
BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s reveal distinct pathophysiologic features and impact on clinical outcomes in melanoma patients
Authors: Sosa Cuevas Eleonora , Ouaguia Laurissa , Mouret Stephane , Charles Julie , De Fraipont Florence , Manches Olivier , Valladeau‐Guilemond Jenny , Bendriss‐Vermare Nathalie , Chaperot Laurence , Aspord Caroline
Published: November 2020

Objectives

Dendritic cells play a pivotal but still enigmatic role in the control of tumor development. Composed of specialised subsets (cDC1s, cDC2s, pDCs), DCs are critical in triggering and shaping antitumor immune responses. Yet, tumors exploit plasticity of DCs to subvert their functions and escape from immune control. This challenging controversy prompted us to explore the pathophysiological role of cDCs and pDCs in melanoma, where their precise and coordinated involvement remains to be deciphered.

Methods

We investigated in melanoma patients the phenotypic and functional features of circulating and tumor‐infiltrating BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s and assessed their clinical impact.

Results

Principal component analyses (PCA) based on phenotypic or functional parameters of DC subsets revealed intra‐group clustering, highlighting specific features of DCs in blood and tumor infiltrate of patients compared to healthy donors. DC subsets exhibited perturbed frequencies in the circulation and actively infiltrated the tumor site, while harbouring a higher activation status. Whereas cDC2s and pDCs displayed an altered functionality in response to TLR triggering, circulating and tumor‐infiltrating cDC1s preserved potent competences associated with improved prognosis. Notably, the proportion of circulating cDC1s predicted the clinical outcome of melanoma patients.

Conclusion

Such understanding uncovers critical and distinct impact of each DC subset on clinical outcomes and unveils fine‐tuning of interconnections between DCs in melanoma. Elucidating the mechanisms of DC subversion by tumors could help designing new therapeutic strategies exploiting the potentialities of these powerful immune players and their cross‐talks, while counteracting their skewing by tumors, to achieve immune control and clinical success.
A population of CD4hiCD38hi T cells correlates with disease severity in patients with acute malaria
Authors: Apte Simon H , Minigo Gabriela , Groves Penny L , Spargo Jessie C , Plebanski Magdalena , Grigg Matthew J , Kenangalem Enny , Burel Julie G , Loughland Jessica R , Flanagan Katie L , Piera Kim A , William Timothy , Price Ric N , Woodberry Tonia , Barber Bridget E , Anstey Nicholas M , Doolan Denise L
Published: November 2020

Objective

CD4+ T cells are critical mediators of immunity to Plasmodium spp. infection, but their characteristics during malarial episodes and immunopathology in naturally infected adults are poorly defined. Flow cytometric analysis of PBMCs from patients with either P. falciparum or P. knowlesi malaria revealed a pronounced population of CD4+ T cells co‐expressing very high levels of CD4 and CD38 we have termed CD4hiCD38hi T cells. We set out to gain insight into the function of these novel cells.

Methods

CD4+ T cells from 18 patients with P. falciparum or P. knowlesi malaria were assessed by flow cytometry and sorted into populations of CD4hiCD38hi or CD4norm T cells. Gene expression in the sorted populations was assessed by qPCR and NanoString.

Results

CD4hiCD38hi T cells expressed high levels of CD4 mRNA and canonical type 1 regulatory T‐cell (TR1) genes including IL10, IFNG, LAG3 and HAVCR2 (TIM3), and other genes with relevance to cell migration and immunomodulation. These cells increased in proportion to malaria disease severity and were absent after parasite clearance with antimalarials.

Conclusion

In naturally infected adults with acute malaria, a prominent population of type 1 regulatory T cells arises that can be defined by high co‐expression of CD4 and CD38 (CD4hiCD38hi) and that correlates with disease severity in patients with falciparum malaria. This study provides fundamental insights into T‐cell biology, including the first evidence that CD4 expression is modulated at the mRNA level. These findings have important implications for understanding the balance between immunity and immunopathology during malaria.
A bronchial mucous gland adenoma harboring GNAS R201C mutation
Authors: Kojima Ryuji , Morimoto Junichi , Ishida Yasuo , Sugano Isamu , Yamazaki Kazuto
Published: November 2020

We present a case of bronchial mucous gland adenoma (MGA) and discuss the results of its cytomorphological and cytogenetic examination serving as a basis for the differential diagnosis. To our best knowledge, this is a first report that demonstrate a GNAS gene (R201C) mutation in mucous gland adenoma, which may play an important role in MGA tumorigenesis, as is the case in other mucinous‐type epithelial neoplasms of various organs.
Detrital input quantification in lacustrine petroleum systems: An example of the pre‐salt source rocks from the Lower Congo Basin (Congo)
Authors: Behar Françoise , Delhaye‐Prat Vincent , Garel Sylvain
Published: November 2020

This study describes an integrated workflow designed to quantify detrital input into lacustrine deposits in terms of regional extent and total organic carbon content. This workflow includes (a) organic geochemical data such as Rock Eval and palynofacies and (b) palaeogeographical maps. This workflow was applied to the immature Barremian source rocks from the Lower Congo Basin because of a large available data set describing a complex sedimentary record. From palynofacies analysis, it was demonstrated that lacustrine organic matter corresponds to a hydrogen index higher than 600 mg/g C whereas detrital input corresponds to a hydrogen index lower than 300 mg/g C. The range seen in the hydrogen index of between 300 and 600 mg/g C corresponds to mixtures of organic matter. The correlation between the hydrogen index and detrital content was then applied to 50 wells which allowed the extent of detrital input to be mapped at local and regional scales. The geochemical data were plotted on high‐resolution palaeogeographic maps for four stratigraphic intervals, BA2, BA2‐BA3, BA3‐PN and BA3‐PI. Results confirm the periodic presence of lacustrine turbiditic systems allowing strong detrital inputs into the palaeolake under the tropical palaeoclimate, especially in the BA2‐BA3 and BA3‐PI intervals. These inputs of continental‐derived organic material degrade the quality and richness of the lacustrine source rock leading to a decrease of the initial hydrogen index values. These detrital influxes were related to coastal rivers whereas, in the deepest parts of the basin, the autochthonous organic matter is well‐preserved and not diluted, which allowed the deposition of exceptional source rocks especially during the BA2 and BA2‐BA3 intervals. All of these geochemical diagnostics are consistent with available palaeogeographic maps. This study demonstrated the importance of integrating geochemical data into the palaeo‐reconstruction of the source rock depositional environment. It enables palaeogeographic maps to be constrained in terms of both detrital input and preservation at both regional and local scales for a given source rock.