bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐Component C–H Bond Sulfonylation of Imidazoheterocycles by Visible‐Light Organophotoredox Catalysis
Authors: Breton‐Patient Chloé , Naud‐Martin Delphine , Mahuteau‐Betzer Florence , Piguel Sandrine
Published: January 2021

The first entirely visible‐light photoredox catalyzed sulfonylation of imidazoheterocycles has been developed. This transformation demonstrates an efficient C–H functionalization for the straightforward synthesis of novel C‐3 sulfonylated imidazoheterocycles from various imidazopyridines and diaryliodonium salts with different electronic and steric properties and easy to handle DABCO‐bis(sulfur dioxide). The reaction proceeds in moderate to good yields under mild conditions at room temperature using the inexpensive organophotocatalyst EosinY·Na2 and shows a high functional group tolerance (37 examples).
Photocaged and Mixed Photocaged Bioreversible‐Protected ATP Derivatives as Tools for the Controlled Release of ATP
Authors: Jeschik Nils , Schneider Tobias , Meier Chris
Published: January 2021

Adenosine triphosphate (ATP) is known as the universal energy source for cellular processes, in addition, ATP also plays an important role in inflammation and cell signaling. Extracellular ATP binds to purinergic receptors and initiates further immune responses. To investigate these processes in‐depth and to understand the complex mechanism of purinergic signaling, chemical tools are necessary. Here we present the synthesis of different photocaged ATP derivatives and the investigation of the light‐induced release of ATP depending on the different synthesized photocleavable protecting groups based on the 2‐nitrobenzyl moiety. Furthermore, we also present the synthesis of a mixed protected ATP‐derivative as an example for a novel class of lipophilically caged nucleoside triphosphates. This new type of compounds is protected with a highly lipophilic non‐toxic bio‐removable acyloxybenzyl group and a photocleavable group. This combination may allow both passive cell uptake and controlled release of ATP by irradiation with non‐harmful UV light.
Au(I)‐Catalyzed Hydration of 1‐Iodoalkynes Leading to α‐Iodoketones
Authors: Gómez‐Herrera Alberto , Hashim Ishfaq Ibni , Porré Marre , Nahra Fady , Cazin Catherine S. J.
Published: January 2021

A catalytic protocol for the Au(I)‐catalyzed hydration of 1‐iodoalkynes is disclosed. The use of Au(I)–NHC catalyst enabled the straightforward synthesis of a variety of α‐iodomethyl ketones in good to excellent yields. The utility of this simple method is further highlighted by showcasing iodination/hydration and hydration/oxidation sequential protocols leading to the construction of molecular complexity.
An Efficient Route to Symmetrical and Unsymmetrical Disulfide, Thioether, and Hydrocarbon Cyclophanes
Authors: Phan Ngoc‐Minh , Shear Trevor A. , Zakharov Lev N. , Johnson Darren W.
Published: January 2021

The union of metal‐directed self‐assembly, dynamic covalent chemistry, and sorting gives rise to 3 new unsymmetrical tetrameric disulfide macrocycles. Stepwise sulfur extrusion from the self‐assembled disulfides to, first, thioethers, and then to hydrocarbons by photochemically promoted routes, gives rise to a collection of 7 new thioether and hydrocarbon cyclophanes related to the venerable family of [n]paracyclophanes. These methods provide an efficient self‐assembly approach to the synthesis of hydrocarbon macrocycles (related to carbon “nanohoops”), a class of structures that are typically formed in lengthier, stepwise syntheses.
Intermediate Products of C60 High‐Temperature Chlorination – C60Cln (n = 8, 10, 14, 20, 24)
Authors: Tamm Nadezhda B. , Markov Vitaliy Yu. , Goryunkov Alexey A. , Troyanov Sergey I.
Published: January 2021

The products of high‐temperature (440 °C) chlorination of C60 with SbCl5 differ considerably from the products obtained at room temperature because high‐temperature allows for chlorine migration over the fullerene cage. Thus, one can expect to obtain the most favorable chlorination patterns for any C60Cln stoichiometry. We report the isolation and structural characterization of several chlorofullerenes, C2v‐C60Cl8, C1‐C60Cl10, and C1‐C60Cl14, which are intermediates to the more kinetically stable higher chlorides. Theoretical DFT calculations of formation energies verified the high thermodynamic stability of the isolated chlorides. Further chlorination produces Th‐C60Cl24 and, eventually, non‐IPR chlorides, 1805C60Cl24 and 1794C60Cl20. as a result of cage rearrangements. Also isolated is a product of the cage shrinkage, C58Cl20.
TBAF‐Catalyzed Tandem Synthesis of Triazolo[4,5‐c]quinolines at Ambient Temperature
Authors: Sun Nan , Yang Han , Zheng Kai , Jin Liqun , Hu Baoxiang , Shen Zhenlu , Hu Xinquan
Published: January 2021

A mild, efficient and metal‐free synthetic method for 1H‐[1,2,3]triazolo[4,5‐c]quinolines has been developed via intermolecular [3+2] cycloaddition of β‐(2‐aminoaryl)‐α,β‐ynones and TMS‐N3, followed by intramolecular dehydration annulation sequential reactions. With 5 mmol‐% of TBAF as catalyst, the reaction can smoothly proceed in DMF at ambient temperature to afford a wide range of functionalized 1H‐[1,2,3]triazolo[4,5‐c]quinolines in good to excellent yields.
A High‐Yielding Synthesis of EIDD‐2801 from Uridine**
Authors: Steiner Alexander , Znidar Desiree , Ötvös Sándor B. , Snead David R. , Dallinger Doris , Kappe C. Oliver
Published: January 2021

A simple reordering of the reaction sequence allowed the improved synthesis of EIDD‐2801, an antiviral drug with promising activity against the SARS‐CoV‐2 virus, starting from uridine. Compared to the original route, the yield was enhanced from 17 % to 61 %, and fewer isolation/purification steps were needed. In addition, a continuous flow procedure for the final acetonide deprotection was developed, which proved to be favorable toward selectivity and reproducibility.
Synthesis, Self‐Assembly, and Nucleic Acid Recognition of an Acylhydrazone‐Conjugated Cationic Tetraphenylethene Ligand
Authors: Coste Maëva , Kotras Clément , Bessin Yannick , Gervais Virginie , Dellemme David , Leclercq Maxime , Fossépré Mathieu , Richeter Sébastien , Clément Sébastien , Surin Mathieu , Ulrich Sébastien
Published: January 2021

Supramolecular polymers are of interest in the pursuit of multivalent nucleic acids recognition. However, their formation often relies on non‐covalent forces that are also at play in the interaction with nucleic acids. In this work, we designed a novel compound (TPE‐Gir) combining a tetraphenylethene aromatic core tethered to four quaternary ammoniums through acylhydrazone spacers, and we investigated in detail its self‐assembly and interaction with different types of nucleic acids. The spectroscopic analyses indicate the self‐assembly of regular fluorescent nanoparticles (observed by DLS and TEM) in the absence of nucleic acids, the strong propensity to intercalate into single‐stranded DNA, the ability to bind into the minor groove of double‐stranded DNA, and the selective binding to G‐quadruplex (G4) structures by fitting within a wide G4‐groove. Those recognition events are quantified by isothermal titration calorimetry and the proposed binding models are supported by docking simulations.
Department of Chemistry, IIT Bombay: In Pursuit of Excellence
Authors: Datta Anindya
Published: January 2021

Prof. Anindya Datta introduces the Department of Chemistry at IIT Bombay and reviews its achievements and future goals.
Novel, Chiral, and Enantiopure C2‐Symmetric Thioureas Promote Asymmetric Protio‐Pictet‐Spengler Reactions by Anion‐Binding Catalysis
Authors: Retini Michele , Bartoccini Francesca , Zappia Giovanni , Piersanti Giovanni
Published: January 2021

Although anion‐binding processes are well‐known for their crucial role in molecular recognition, they have only recently been utilized for catalysis. Herein, a new class of chiral, enantiopure C2‐symmetrical thioureas that, in combination with 4‐methoxybenzoic acid, promotes the enantioselective protio‐Pictet‐Spengler reaction to provide unprotected tetrahydro‐β‐carbolines in good yields (40–93 %) and moderate‐to‐high enantioselectivities (34–95 % ee) in one step from tryptamine and aldehyde derivatives is described. The formation of a chiral catalyst‐anion complex was explored by1H NMR.
Non‐Canonical Reactivity of Gold Carbene with Alkyne: An Overview of the Mechanistic Premise
Authors: Sancheti Shashank P. , Patil Nitin T.
Published: January 2021

The unique nature of gold carbene and its synchronous counterpart gold‐stabilized carbocation, is mainly responsible for the non‐canonical reactivity profile that it demonstrates in comparison to any other transition metal carbene. Being an important subset to this class, reactions of gold carbene with alkyne sponsor products far more diverse than cyclopropenation as canonically expected in case of other transition metal carbenes. These gold‐catalyzed reactions have largely been proposed to follow either a [1,n]‐carbene transfer process or an alternate pathway involving a direct interception of the β‐gold vinyl cation with a nucleophile at the cationic carbon. Despite of a clear distinction in structure, bonding and energy of a vinyl gold carbene and β‐gold vinyl cation; they have been found to exhibit identical reactivities like cyclopropenation, C(sp2)–H insertion, etc. making it extremely difficult to “experimentally” investigate and validate a mechanistic pathway. It is because of lack of conclusive experimental evidence, in addition to the limited number of detailed computational studies, that multiple pathways have been proposed simultaneously to rationalize the product formation. As an effort to shed light on the mechanisms of these reactions, herein, documentation of these reactions with a focus on their mechanistic premise has been presented.
A Novel and Practical Continuous Flow Chemical Synthesis of Cannabidiol (CBD) and its CBDV and CBDB Analogues
Authors: Chiurchiù Elena , Sampaolesi Susanna , Allegrini Pietro , Ciceri Daniele , Ballini Roberto , Palmieri Alessandro
Published: January 2021

Cannabidiol is one of the main non‐psychoactive cannabinoids present in Cannabis sativa and, in the last decade, it is gaining great interest among the scientific community for its pharmaceutical, nutraceutical, and cosmetic applications. Herein, we report the first continuous flow chemical synthesis of cannabidiol (CBD) and its analogues cannabidivarin (CBDV) and cannabidibutol (CBDB). This approach permits to synthesize products in very good yields (55–59 %), limiting the formation of psychoactive and illegal cannabinoids such as tetrahydrocannabinol (THC).
Stereoselective Synthesis of (2S,6R)‐Diamino‐(5R,7)‐dihydroxy‐heptanoic Acid (DADH): An Unusual Amino Acid from Streptomyces sp. SANK 60404
Authors: Okamura Hironori , Yasuno Yoko , Nakayama Atsushi , Takikawa Hirosato , Shinada Tetsuro
Published: January 2021

Stereoselective synthesis of (2S,6R)‐diamino‐(5R,7)‐dihydroxy‐heptanoic acid (DADH), a biosynthetic precursor of vazabitide A, isolated from Streptomyces sp. SANK 60404 was achieved for the first time. Three stereogenic centers of DADH were constructed by the chemical manipulation on Garner's aldehyde as a chiral source and DuPHOS‐Rh‐catalyzed asymmetric hydrogenation of a dehydroamino acid ester. The synthetic advantage of the present method was demonstrated by the flexible synthesis of the DADH stereoisomers from Garner's aldehyde.
Klyflaccilins B‐T, Polyoxgenated Eunicellins from the Soft Coral Klyxum flaccidum
Authors: Li Geng , Sun Li‐Li , Dickschat Jeroen S. , Guo Yue‐Wei
Published: January 2021

Nineteen polyoxygenated eunicellin diterpenoids, named klyflaccilins B‐T (1–19), were isolated from the South China Sea soft coral Klyxum flaccidum. Their structures were established by extensive spectroscopic analysis and for several of the isolated compounds the absolute configurations were determined by X‐ray diffraction analysis.
The Electrochemiluminescent Immunosensors for Point‐of‐Care Testing of Methamphetamine Using a Portable Meter
Authors: Tan Rong , Shen Yi , Li Dongning , Yang Ya , Tu Yifeng
Published: January 2021

The crowd of methamphetamine (METH) abuse has obviously increased during past decades, their physical and mental health are seriously jeopardized. It compelled growing worry worldwide so that there is an anxious requirement to develop the accurate, sensitive, rapid, and convenient detection techniques to tackle the problem. In regard to this matter, we reported two sensors for METH with synergistical alliance of sensitive electrochemiluminescence (ECL) quantification and specifically immune recognition. These sensors are applicable for point‐of‐care testing when equipped a portable ECL meter with outstanding performance, makes the feasibility of on‐spot analysis. The dual‐way analysis of immunosensors can be carried on, both exhibit unprecedented sensitivity toward METH. Here, AuNPs functioned indium tin oxide (ITO) coated polyethylene terephthalate (PET) is used as the basal electrode, providing excellent ECL background and supporting the sensing matrix. The real sample identification demonstrated the practicability and accuracy which met the requirement of forensic judgement and clinical treatment. This work provides a viable methodology and technology for a rapid and reliable analysis of hard drug abuser's samples.
Electrokinetic actuation of an uncharged polarizable dielectric droplet in charged hydrogel medium
Authors: Barman Sirsendu Sekhar , Bhattacharyya Somnath , Dutta Prashanta
Published: January 2021

Electrokinetic transport of an uncharged nonconducting microsized liquid droplet in a charged hydrogel medium is studied. Dielectric polarization of the liquid drop under the action of an externally imposed electric field induces a non‐homogeneous charge density at the droplet surface. The interactions of the induced surface charge of the droplet with the immobile charges of the hydrogel medium generates an electric force to the droplet, which actuates the drop through the charged hydrogel medium. A numerical study based on the first principle of electrokinetics is adopted. Dependence of the droplet velocity on its dielectric permittivity, bulk ionic concentration, and immobile charge density of the gel is analyzed. The surface conduction is significant in presence of charged gel, which creates a concentration polarization. The impact of the counterion saturation in the Debye layer due to the dielectric decrement of the medium is addressed. The modified Nernst–Planck equation for ion transport and the Poisson equation for the electric field is considered to take into account the dielectric polarization. A quadrupolar vortex around the uncharged droplet is observed when the gel medium is considered to be uncharged, which is similar to the induced charge electroosmosis around an uncharged dielectric colloid in free‐solution. We find that the induced charge electrokinetic mechanism creates a strong recirculation of liquid within the droplet and the translational velocity of the droplet strongly depends on its size for the dielectric droplet embedded in a charged gel medium.
Engineered Nanoscale Single‐Metal‐Oxides Catalytic Thin Films for High‐Performance Water Oxidation
Authors: Babar Noor‐Ul‐Ain , Khan Majad , Joya Khurram Saleem
Published: January 2021

Surface assembling of nanoscale materials for electrocatalysis is imperative to progress water splitting. There is a dire need to develop cost‐effective and easily accessible methods to make metal oxides, aiming to execute the oxygen evolution reaction (OER) at low overpotential and high stability for long‐term activity. Thin‐film metal oxides for water oxidation are prepared via aerosol‐assisted chemical vapor deposition (AACVD) on simple substrates as shown here. Catalytic films (CFs) of CoOx, NiOx, CuOx, and FeOx are phase pure oxides, smooth, and of nanoparticulate type, and are highly crystalline. Water oxidation catalysis is initiated at low onset potentials and achieves 10 mA cm−2 just at the potentials of 250–330 mV in 1.0 m KOH solution. All catalysts present impressive kinetics behavior for boosting OER activity, signifying their inherent potential for propelling water oxidation at lower energy demands. Excitingly, stable current densities remain sustained during prolonged period water catalysis. Promising behavior of the ultrafine CFs is attributed to the exploitation of the elegant synthetic strategy under controlled conditions to realize a high redox potential and cyclic M2+/3+ couple activation with sustainable catalytic active sites. Nanoscale and porous features of the highly pure and crystalline films further promote the electrocatalytic process and remain intact even after long‐term catalytic investigations.
Design of Metals Sulfides with Carbon Materials for Supercapacitor Applications: A Review
Authors: Iqbal Muhammad Faisal , Ashiq Muhammad Naeem , Zhang Meng
Published: January 2021

Supercapacitors are very exclusive among energy‐storage devices for the wearable and portable industry. Due to simplicity, abundance occurrence, good electrical conductivity, and rich redox states, metal sulfides have a significant impact in supercapacitor applications in the present decade. Sulfur is the anion, associated with metal cations, and provides substantial tunable electrochemical, electrical, physical, and chemical properties in metal sulfides. In addition, carbonaceous materials enhance the electrochemical characteristics of metal sulfides synergistically for supercapacitors. Fast and scalable synthesis and fabrication of the supercapacitor cell with low‐cost metal sulfides and heterostructures should be developed to achieve the potential applications of these hybrid glorious materials. Herein, the significant and critical discussion of metal sulfides synthesis and their hybrid with carbon electrode structures for supercapacitor applications is disclosed. The realistic synthesis of metal sulfides, basic charge storage phenomena to elaborate the electrode nature, electrochemical properties including a single electrode, and asymmetric and symmetric cells are demonstrated for comparative purposes. The market values and application of supercapacitors are also elaborated. Herein, a better understanding to fresh readers about metal sulfide hybrid electrode structures for supercapacitors is provided.
Late‐Quaternary miliolite (biogenic carbonate) deposits and their implications for sea‐level fluctuations and climatic variability
Authors: Durga Prasad A. , Bhattacharya Falguni , Chauhan Gaurav , Balaji D. , Thakkar M.G. , Rao Y. Srinivasa
Published: January 2021

The western coast of India (Kachchh) has ubiquitous preservations of Quaternary carbonate deposits popularly known as “miliolites”. Field‐based detail documentation of the nature and distribution of miliolites supported by sedimentology and scanning electron microscopy (SEM) microtextural studies indicates that the miliolites were primarily deposited by wind as aeolinites and are termed “primary miliolites (PM)”. These were subsequently fluvially eroded and deposited and such deposits are termed “secondary miliolites (SM)”. The PM are dated between 28 ka to 16 ka largely clustering around the Last Glacial Maxima (LGM). In comparison, the fluvially reworked SM occurs as valley‐fill deposits and were deposited episodically during 23 ka to 10 ka before present. Climatically, the deposition of PMs suggests enhanced aridity whereas SMs represent episodic strengthening of the Indian Summer Monsoon (ISM). The bedding attitudes of the PMs indicate that they were deposited predominantly by the northeasterly winds whereas the presence of the deflation lag deposits suggests downwind migration of sands during the equilibrium condition (reduced sediment supply). The aeolian parameters (based on the grain size and wind velocities) for PMs indicate high shear velocity (~23 to 48 cm−1) and high transport rate (< 0.1 to 0.2 g/cm s). The short average flying distance implies that the biogenic sands were transported in multiple pulses (from coast to inland) at rates varying from ~200 m/h to ~1 km/h. Comparing our data with related occurrences along the biologically productive coasts in the mid‐latitudinal belt indicates that the regional/global aridity during the lowered sea level was responsible for inland occurrences of aeolinites, particularly during the LGM. The strengthened northeast monsoon winds during the LGM was conducive to upwelling and production of biogenic carbonates along the coasts. The subsequent reworking of the aeolinites were mainly the results of local variability in precipitation.
Where will widening occur in an outwash braidplain? A new approach to detecting controls on fluvial lateral erosion in a glacierized catchment (north‐western Spitsbergen, Svalbard)
Authors: Weckwerth Piotr , Sobota Ireneusz , Greń Katarzyna
Published: January 2021

The dynamics of fluvial system evolution depend on fluvial processes and their driving forces associated with climatic variations, which affect changes in the morphology of river channels and floodplains. Neither channel slope and morphology, nor the properties of fluvial sediment have previously been considered as determinants of active braidplain widening on outwash plains (formed from valley/alpine glaciers and confined by pre‐existing topography) in the High Arctic region and in the forefields of retreating glaciers. Factors determining widening of braidplain activity of the Waldemar River outwash (north‐western Spitsbergen, Svalbard) were analysed on the basis of geomorphological, sedimentological, glaciological and meteorological research, and indicate significant multiple correlations between meltwater discharge, precipitation, braidplain width, morphology of the braided channel and the textural features of braidplain deposits. The capability of multivariate adaptive regression splines to detect these relationships was described, and threshold values were identified. The results indicate that the rate of active braidplain widening is proportional to the meltwater outflow in proglacial rivers, which can decrease despite a growing rate of glacial ablation. A proposed model enables us to predict zones of braidplain prone to widening activity in the High Arctic (humid) outwash fans and plains as well as fans developed in arid intermountain basins. The necessary conditions to activate braidplain widening processes were (1) spatial changes in the outwash feeding system due to glacier terminus retreat and (2) crossing the thresholds in passive factors (S and d50) controlling lateral erosion intensity. As a result, the braidplain reached a new dynamic equilibrium, in which high‐magnitude–low‐frequency extreme meltwater discharges were of particular importance in terms of braidplain dynamics and are the dominant controls on the pattern of distributary channels.
Experimental study of density effect and natural convection in a latent heat storage unit with paraffin wax and air
Authors: Lanka Sandeep Raj , Bandaru Durga Prasad , Sane Sreenivasulu
Published: January 2021

Experimental analysis is carried out on tube in tube type heat exchanger. The phase change material (PCM) is melted under the influence of high‐temperature air as HTF. PCM density effect is presented with the temperature change in axial and radial positions. During charging, the lower elevation temperature curve's intersection with the higher elevation's temperature curves is identified. The earliest intersection is found at 20 minutes with 51°C. The late intersection is found at 62 minutes and 75°C. Natural convection jump phenomenon is also spotted. Each temperature curve in middle and outer radial positions is classified into three categories (before the jump, during the jump, and after the jump). Natural convection jumps are found in the range of 2.667 to 8.5°C/minute. The density effect and natural convection jump are found to be insignificant during discharging.
Immigration counter-acts local micro-evolution of a major fitness component: Migration-selection balance in free-living song sparrows
Authors: Reid Jane M. , Arcese Peter , Nietlisbach Pirmin , Wolak Matthew E. , Muff Stefanie , Dickel Lisa , Keller Lukas F.
Published: January 2021

Ongoing adaptive evolution, and resulting “evolutionary rescue” of declining populations, requires additive genetic variation in fitness. Such variation can be increased by gene flow resulting from immigration, potentially facilitating evolution. But, gene flow could in fact constrain rather than facilitate local adaptive evolution if immigrants have low additive genetic values for local fitness. Local migration-selection balance and micro-evolutionary stasis could then result. However, key quantitative genetic effects of natural immigration, comprising the degrees to which gene flow increases the total local additive genetic variance yet counteracts local adaptive evolutionary change, have not been explicitly quantified in wild populations. Key implications of gene flow for population and evolutionary dynamics consequently remain unclear. Our quantitative genetic analyses of long-term data from free-living song sparrows (Melospiza melodia) show that mean breeding value for local juvenile survival to adulthood, a major component of fitness, increased across cohorts more than expected solely due to drift. Such micro-evolutionary change should be expected given nonzero additive genetic variance and consistent directional selection. However, this evolutionary increase was counteracted by negative additive genetic effects of recent immigrants, which increased total additive genetic variance but prevented a net directional evolutionary increase in total additive genetic value. These analyses imply an approximate quantitative genetic migration-selection balance in a major fitness component, and hence demonstrate a key mechanism by which substantial additive genetic variation can be maintained yet decoupled from local adaptive evolutionary change.
Brown seaweed Cystoseiraschiffneri as a promising source of sulfated fucans: Seasonal variability of structural, chemical, and antioxidant properties
Authors: Benslima Abdelkarim , Sellimi Sabrine , Hamdi Marwa , Nasri Rim , Jridi Mourad , Cot Didier , Li Suming , Nasri Moncef , Zouari Nacim
Published: January 2021

A fucoidan, sulfated polysaccharide, was extracted from the brown seaweed Cystoseira schiffneri during 4 harvest periods (December, April, July, and September) and studied for its structural and chemical properties. The Cystoseira schiffneri fucoidan (CSF) showed important variation in sulfate content ranging from 7.8% in December to 34.8% in July. This was confirmed by Fourier transform infrared and nuclear magnetic resonance spectroscopies showing characteristic signals of sulfated polysaccharides. Molecular mass of the CSF varied as a function of season from 3,745 in December to 26,390 Da in July. Gas chromatography–mass spectroscopy showed that CSF fractions were “mannogalactofucans” composed mainly of mannose, fucose, and galactose with low levels of other monosaccharides. Moreover, interesting in vitro antioxidant activities that depend on the harvest season were noted for CSF. Thus, the present work might contribute to establish criteria for extracting bioactive fucoidans from an endemic Tunisian seaweed C. schiffneri.
Dental radiation dosimetric maps from intensity‐modulated radiation therapy planning for head and neck cancers
Authors: Polce Simran , Gogineni Emile , Antone Jeffrey , Ghaly Maged , Keith Frank Douglas , Segal Joshua D. , Parashar Bhupesh
Published: January 2021

Background

The purpose of this study was to create dental radiation maps to calculate the mean dose to individual teeth, maxilla and mandible using intensity‐modulated radiation therapy (IMRT).

Methods

Eighteen common clinical settings were chosen. Radiation plans were extracted, and each tooth was contoured at its junction with the gingiva and labeled based on the Universal/American numbering system.

Results

All patients were treated with prescribed doses of 50–70 Gy in 1.66–2 Gy/fraction. Patients receiving mean doses >50 Gy to the teeth, mandible, and maxilla included those with advanced tumors of the oral cavity and gross lymphadenopathy of level 1b.

Conclusion

We believe this to be the first study generating dosimetric maps of estimated doses to each tooth and each third of the mandible and the maxilla for common examples of head and neck cancer faced by radiation oncologists. Adoption of these dental maps may help improve clinical workflow efficiency.
Multiple coordinated cellular dynamics mediate CA1 map plasticity
Authors: Mizuta Kotaro , Nakai Junichi , Hayashi Yasunori , Sato Masaaki
Published: January 2021

In the hippocampus, spatial and nonspatial information are jointly represented as a neural map in which locations associated with salient features are over‐represented by increased densities of relevant place cells. Although we recently demonstrated that experience‐dependent establishment of these disproportionate maps is governed by selective stabilization of salient place cells following their conversion from non‐place cells, the underlying mechanism for pre‐established map reorganization remained to be understood. To this end, we investigated the changes in CA1 functional cellular maps imaged using two‐photon calcium imaging in mice performing a reward‐rearrangement task in virtual reality. Mice were pre‐trained on a virtual linear track with a visual landmark and a reward in two distinct locations. Then, they were re‐trained on the same track with the exception that the location of reward was shifted to match the landmark location. We found that, in contrast to de novo map formation, robust map reorganization occurred through parallel coordination of new place field formation, lateral shifting of existing place fields, and selective stabilization of place fields encoding salient locations. Our findings demonstrate that intricate interplay between multiple forms of cellular dynamics enables rapid updating of information stored in hippocampal maps.
Factors associated with secondary traumatic stress and burnout in neonatal care staff: A cross‐sectional survey study
Authors: Scott Zoe , O'Curry Sara , Mastroyannopoulou Kiki
Published: January 2021

Introduction

High rates of secondary traumatic stress and burnout have been found across nursing populations. However, few studies have focused on neonatal staff.

Objective

The objectives of this article are to explore the prevalence and severity of secondary traumatic stress (STS) and burnout in neonatal staff, and identify risk factors and protective factors for STS and burnout within this population with the aim of informing future staff support.

Methods

A quantitative, cross‐sectional study using a survey design was conducted; 246 neonatal staff reported measures of STS, burnout, self‐compassion and satisfaction with ward climate.

Results

Neonatal staff reported high rates of moderate–severe STS and burnout. STS and burnout were negatively associated with self‐compassion and satisfaction with ward climate, suggesting them to be protective factors against STS and burnout. STS was found to be a risk factor for burnout and vice versa.

Conclusion

Interventions that increase understanding of STS and burnout, nurture self‐compassion, provide support and enhance stress management could help mitigate the impact of STS and burnout amongst neonatal staff.
Rspo1–LGR4 axis in BMSCs protects bone against radiation‐induced injury through the mTOR‐dependent autophagy pathway
Authors: Chen Xiaodan , Chen Lingling , Tan Jiali , Zhang Liping , Xia Juan , Cheng Bin , Zhang Weizhen
Published: January 2021

While mesenchymal stem cells (MSCs) have been widely used to repair radiation‐induced bone damage, the molecular mechanism underlying the effects of MSCs in the maintenance of bone homeostasis under radiation stress remains largely unknown. In this study, the role and mechanisms of R‐spondin 1 (Rspo1)–leucine‐rich repeat‐containing G protein‐coupled receptor 4 (LGR4) axis on the initiation of self‐defense of bone mesenchymal stem cells (BMSCs) and maintenance of bone homeostasis under radiation stress were investigated. Interestingly, radiation increased levels of Rspo1 and LGR4 in BMSCs. siRNA knockdown of Rspo1 or LGR4 aggravated radiation‐induced impairment of self‐renewal ability and osteogenic differentiation potential of BMSCs. However, exogenous Rspo1 significantly attenuated radiation‐induced depletion of BMSCs, and promoted the lineage shift towards osteoblasts. This alteration was associated with the reversal of mammalian target of rapamycin (mTOR) activation and autophagy decrement. Pharmacological and genetic blockade of autophagy attenuated the radio‐protective effects of Rspo1, rendering BMSCs more vulnerable to radiation‐induced injury. Then bone radiation injury was induced in C57BL6J mice to further determine the radio‐protective effects of Rspo1. In mice, administration of Rspo1 recombinant protein alleviated radiation‐induced bone loss. Our results uncover that Rspo1–LGR4–mTOR–autophagy axis are key mechanisms by which BMSCs initiate self‐defense against radiation and maintain bone homeostasis. Targeting Rspo1–LGR4 may provide a novel strategy for the intervention of radiation‐induced bone damage.
The role of autophagy in bone homeostasis
Authors: Guo Yi‐Fan , Su Tian , Yang Mi , Li Chang‐jun , Guo Qi , Xiao Ye , Huang Yan , Liu Ya , Luo Xiang‐Hang
Published: January 2021

Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.
TGF‐β/Alk5 signaling prevents osteoarthritis initiation via regulating the senescence of articular cartilage stem cells
Authors: Tan Qiaoyan , Wang Quan , Kuang Liang , Zhang Jinfan , Peng Xiuqin , Liang Sen , Liu Mi , Chen Hangang , Chen Shuai , Luo Xiaoqing , Qi Huabing , Li Can , Luo Fengtao , Huang Shuo , Ni Zhenhong , Jin Min , Su Nan , Yang Jing , Yang Peng , Chen Bo , Chen Liang , Du Xiaolan , Xie Yangli , Chen Lin
Published: January 2021

Osteoarthritis (OA) is the most common joint disease. The surface of joint cartilage is a defensive and first affected structure of articular cartilage (AC) during the pathogenesis of OA. Alk5 signaling is critical for maintaining AC homeostasis, however, the role and underlying mechanism for the involvement of Alk5 signaling in the phenotypes of articular cartilage stem cells (ACSCs) at the surface of AC is still unclear. The role of Alk5 in OA development was explored using an ACSCs‐specific Alk5‐deficient (cKO) mouse model. Alterations in cartilage structure were evaluated histologically. Senescence was detected by SA‐β‐gal, while reactive oxygen species (ROS), MitoTracker, and LysoTracker staining were used to detect changes related to senescence. In addition, mice were injected intra‐articularly with ganciclovir to limit the detrimental roles of senescent cells (SnCs). Alk5 cKO mice showed a decreased number of the slow‐cell cycle cells and less lubricant secretion at the surface accompanied with drastically accelerated cartilage degeneration under ageing and surgically induced OA conditions. Further studies showed that Alk5 deficient ACSCs exhibited senescence‐like manifestations including decreased proliferation and differentiation, more SA‐β‐gal‐positive cells and ROS production, as well as significantly swollen mitochondria and lysosome breakdown. We further found that local limitation of the detrimental roles of SnCs can attenuate the development of posttraumatic OA. Taken together, our findings suggest that Alk5 signaling acts as an important regulator of the SnCs in the superficial layer during AC maintenance and OA initiation.
Cadherin‐11 deficiency mitigates high‐fat diet‐induced inflammatory atrial remodeling and vulnerability to atrial fibrillation
Authors: Fang Guojian , Cao Wei , Chen Long , Song Shuai , Li Yingze , Yuan Jiali , Fei Yudong , Ge Zhuowang , Chen Yuhan , Zhou Lei , Xiao Ying , Wan Yi , Wang Yuepeng , Wang Qunshan
Published: January 2021

Atrial fibrillation (AF) is the most common cardiac arrhythmia nowadays. The occurrence of AF is closely associated with obesity. Cadherin‐11 (Cad‐11), as a member of the cadherin family, can make a contribution to diet‐induced obesity and it will be informative to know whether Cad‐11 exerts its effects on atrial remodeling and AF vulnerability in a diet‐induced obesity model. In this study, we demonstrated that the expression of Cad‐11 was significantly upregulated in the left atrium of AF patients with obesity and mice following 16 weeks of high‐fat diet (HFD) feeding. Further confirmed that Cad‐11 could regulate the activity of atrial fibroblasts by participating in inducing proinflammatory cytokines production. At animal levels, we found that although there was a lack of statistical difference in body weight, Cad‐11−/− mice could markedly improve impaired glucose tolerance and hyperlipidemia. Adverse atrial structural remodeling, including atrial enlargement, inflammation, and fibrosis provoked by HFD feeding were mitigated in Cad‐11−/− mice. Mechanistically, Cad‐11 activated mitogen‐activated protein kinases and nuclear factor‐κB for interleukin‐6 production in atrial fibroblasts that may contribute to the atrial fibrosis process in obesity‐related AF, suggesting Cad‐11 might be a new therapeutic target for obesity‐related AF.
Gold digging: Searching for gut microbiota that enhances antitumor immunity
Authors: Hou Fengyi , Pan Zhiyuan , Yang Ruifu , Zhi Fachao , Bi Yujing
Published: January 2021

Programmed cell death protein‐1/programmed cell death‐ligand 1 and cytotoxic T‐lymphocyte antigen‐4 are two immune checkpoint inhibitors (ICIs), exhibiting significant antitumor effects on multiple types of cancers in clinical practice. However, only some patients respond to ICI agents, which limits their widespread application. Recent findings revealed that the gut microbiota is relevant to host health through the modulation of host physical and immune functions. Therefore, the modulation of gut microbiota to achieve the desired taxa may be a potential strategy to improve the efficacy of immunotherapies. In this review, we classified the relative microbes according to their taxonomic information and aimed to clarify their modulatory functions and potent effects on ICI immunotherapy by focusing on recent trials investigating the relationships between the gut microbiota and ICIs.
Hepatocyte size fractionation allows dissection of human liver zonation
Authors: Ölander Magnus , Wegler Christine , Flörkemeier Inken , Treyer Andrea , Handin Niklas , Pedersen Jenny M. , Vildhede Anna , Mateus André , LeCluyse Edward L. , Urdzik Jozef , Artursson Per
Published: January 2021

Human hepatocytes show marked differences in cell size, gene expression, and function throughout the liver lobules, an arrangement termed liver zonation. However, it is not clear if these zonal size differences, and the associated phenotypic differences, are retained in isolated human hepatocytes, the “gold standard” for in vitro studies of human liver function. Here, we therefore explored size differences among isolated human hepatocytes and investigated whether separation by size can be used to study liver zonation in vitro. We used counterflow centrifugal elutriation to separate cells into different size fractions and analyzed them with label‐free quantitative proteomics, which revealed an enrichment of 151 and 758 proteins (out of 5163) in small and large hepatocytes, respectively. Further analysis showed that protein abundances in different hepatocyte size fractions recapitulated the in vivo expression patterns of previously described zonal markers and biological processes. We also found that the expression of zone‐specific cytochrome P450 enzymes correlated with their metabolic activity in the different fractions. In summary, our results show that differences in hepatocyte size matches zonal expression patterns, and that our size fractionation approach can be used to study zone‐specific liver functions in vitro.
Exosomes from donor‐derived adipose mesenchymal stem cells prolong the survival of vascularized composite allografts
Authors: Chen Zhizhao , Xue Shuai , Zhang Sheng , Cheng Ke , Ye Qifa
Published: January 2021

Donor‐derived adipose‐derived mesenchymal stem cells (ADMSCs) dampen the alloimmune response and exosomes are reported to have biological activity similar to their parent cells. Here, we investigated the roles of exosomes from donor‐derived ADMSCs (ADMSC‐exo) in vascularized composite allotransplantation (VCA). Brown Norway‐to‐Lewis rat hindlimb transplantations were intravenously treated with either exosome from donor‐derived ADMSCs or phosphate‐buffered saline, combined with a short course of immunosuppression. We established that the treatment with ADMSC‐exo prolongs the survival time of VCA grafts. Skin and muscle samples from ADMSC‐exo‐treated animals showed no histological signs of rejection, but samples from controls showed rejection of degree III. Comparing to the control group, a significant increase of donor cell chimerism, Tr1 and Treg, while a decrease of CD4+ T and Th1 cells were observed in the ADMSC‐exo‐treated group. Our findings imply that ADMSC‐exo may be a valuable and safe treatment for extending VCA graft survival.
Long‐term monitoring of two snake species reveals immune–endocrine interactions and the importance of ecological context
Authors: Spence Austin R. , French Susannah S. , Hopkins Gareth R. , Durso Andrew M. , Hudson Spencer B. , Smith Geoffrey D. , Neuman‐Lee Lorin A.
Published: January 2021

While there is huge promise in monitoring physiological parameters in free‐living organisms, we also find high amounts of variability over time and space. This variation requires us to capitalize on long‐term physiological monitoring to adequately address questions of population health, conservation status, or evolutionary trends as long‐term sampling can examine ecoimmunological and endocrine interactions in wild populations while accounting for the variation that often makes ecophysiological field studies difficult to compare. In this study, we tested how immune efficacy and endocrinology interact while accounting for ecological context and environmental conditions in two snake species. Specifically, we measured bacterial killing ability, steroid hormones, and morphological characteristics in multiple populations of the Western Terrestrial Gartersnake (Thamnophis elegans) and Common Gartersnake (T. sirtalis) for multiple seasons over 6 years. Leveraging this long‐term dataset, we tested how a broad immune measure and endocrine endpoints interact while accounting for individual traits, sampling date, and environmental conditions. Across both species, we found bacterial killing ability to be directly related to corticosterone (CORT) and temperature and greater overall in the spring compared to the fall. We found CORT and testosterone yielded relationships with individual sex, sampling temperature, and time of year. Wild populations can exhibit high amounts of variation in commonly collected physiological endpoints, highlighting the complexity and difficulty inherent in interpreting single endpoints without taking ecological and environmental conditions into account. Our study emphasizes the importance of reporting the environmental conditions under which the sampling occurred to allow for better contextualization and comparison between studies.
lncRNA MCM3AP‐AS1 inhibits the progression of colorectal cancer via the miR‐19a‐3p/FOXF2 axis
Authors: Dai Wenxin , Zeng Wangyuan , Lee Dongwon
Published: January 2021

Background

Long non‐coding RNA MCM3AP antisense RNA 1 (lncRNA MCM3AP‐AS1) has a regulatory role in the development of diverse malignancies, whereas its role and mechanism in colorectal cancer (CRC) is not yet clear.

Methods

The relative expression of MCM3AP‐AS1, miR‐19a‐3p and forkhead box F2 (FOXF2) mRNA in 53 cases of CRC and its adjacent normal tissues, human normal colonic mucosal cells (FHC cells) and CRC cell lines was examined by a quantitative real‐time polymerase chain reaction, and the changes of cell multiplication and migration were examined by the cell counting kit‐8 method, EdU test, and scratch‐healing test, respectively. Bioinformatics, dual‐luciferase reporter gene assay and a RNA immunoprecipitation experiment were adopted to predict and verify the relationship between MCM3AP‐AS1 and miR‐19a‐3p; bioinformatics and dual‐luciferase reporter gene assay were adopted to predict and verify the relationship between miR‐19a‐3p and FOXF2. Western blotting was executed to examine the effects of MCM3AP‐AS1 overexpression or knockdown on FOXF2 protein expression.

Results

MCM3AP‐AS1 expression was down‐modulated in CRC, and its dysregulation was linked to unfavorable pathological characteristics. MCM3AP‐AS1 significantly impeded the multiplication and migration of CRC cells. MCM3AP‐AS1 was recognized as a molecular sponge to suppress miR‐19a‐3p expression, and FOXF2 was a target gene of miR‐19a‐3p. MCM3AP‐AS1 positively modulated FOXF2 expression, and its biological effect was dependent the on miR‐19a‐3p/FOXF2 axis.

Conclusions

MCM3AP‐AS1 can inhibit CRC promoting by modulating the miR‐19a‐3p/FOXF2 axis.
Long non‐coding RNA SNHG8 promotes prostate cancer progression through repressing miR‐384 and up‐regulating HOXB7
Authors: Shi Zhenfeng , Zhang Hao , Jie Situ , Yang Xiaojian , Huang Qunxiong , Mao Yunhua , Zhang Yan
Published: January 2021

Background

Multiple long non‐coding RNAs (lncRNAs) have been demonstrated to function as vital regulators in the progression of prostate cancer (PCa). In the present study, we aimed to probe the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in PCa progression.

Methods

A quantitative real‐time polymerase chain reaction and western blotting were utilized to measure SNHG8, microRNA‐384 (miR‐384) and homeobox B7 (HOXB7) expression. Call‐couting kit‐8 and bromodeoxyuridine experiments were employed to evaluate PCa cell proliferation. Transwell experiments were performed to detect PCa cell migration and invasion. Dual‐luciferase reporter experiments and RNA immunoprecipitation experiments were conducted to determine the targeting relationships among miR‐384, SNHG8 and HOXB7.

Results

SNHG8 was up‐regulated in PCa tissues and cells. Silencing of SNHG8 suppressed the proliferation, migration and invasion of PCa cells. SNHG8 functioned as a molecular sponge to repress miR‐384. The effects of SNHG8 knockdown on PCa cell proliferation, migration and invasion were counteracted by miR‐384 inhibition. HOXB7 was confirmed to be a target gene of miR‐384. SNHG8 knockdown repressed HOXB7 expression via targeting miR‐384.

Conclusions

SNHG8 promotes PCa cell proliferation, migration and invasion via decoying miR‐384 and up‐regulating HOXB7.