bluuebunny/crossref_metadata_2025 huggingface dataset:
Overlapping vulnerabilities in workers of the electronics recycling industry formal sector: A commentary
Authors: Ceballos Diana M. , Côté Daniel , Bakhiyi Bouchra , Flynn Michael A. , Zayed Joseph , Gravel Sabrina , Herrick Robert F. , Labrèche France
Published: September 2020

Vulnerabilities in workers performing electronics recycling (e‐recycling) in the informal sector worldwide have been well documented. However, the growing e‐recycling industry in the formal sector still brings many challenges to protect the health of workers and their environment. This commentary aims to draw attention to the overlooked vulnerabilities faced by the workers of the e‐recycling industry formal sector in high‐income countries and discuss the potential impact on health inequalities experienced by these workers. Expanding the definition of vulnerability, not limited to the biological susceptibility to chemical and physical exposures, the demographic characteristics of workers in the e‐recycling formal sector often reveal social groups known to be disadvantaged regarding occupational exposures and health effects, including young workers, immigrant or ethnic minorities, and workers with mental or physical health issues or disabilities. Overlapping structural vulnerabilities of the e‐recycling industry stem from its newness, its working conditions, its conditions of employment, and the sociodemographic characteristics of its workforce. This phenomenon in high‐income countries is not restricted to the e‐recycling industry alone. It is rather a symptom of more generalized macro socioeconomical phenomena. The present challenges are in line with the new gig and green economies and changes in the global market, and their consequences on the solid waste sector. Continued efforts to strengthen the inclusion of social aspects of health into the complex interaction of the structural vulnerabilities met by e‐recycling workers will be essential to anticipate and prevent health issues in this essential but still emerging workforce.
Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and brief review
Authors: Rizzi Susanna , Spagnoli Carlotta , Salerno Grazia Gabriella , Frattini Daniele , Caraffi Stefano Giuseppe , Trimarchi Gabriele , Moratti Claudio , Pascarella Rosario , Garavelli Livia , Fusco Carlo
Published: September 2020

The CAMK2B gene encodes the β‐subunit of calcium/calmodulin‐dependent protein kinase II (CAMK2), an enzyme that has crucial roles in synaptic plasticity, especially in hippocampal and cerebellar neurons. Heterozygous variants in CAMK2B cause a rare neurodevelopmental disorder, with 40% of the reported cases sharing the same variant: c.416C>T, p.(P139L). This case report describes a 22‐year‐old patient with this recurrent variant, who presents with severe intellectual disability, absence of language, hypotonia, microcephaly, dysmorphic features, epilepsy, behavioral abnormalities, motor stereotypies, optic atrophy, and progressive cerebellar atrophy. Notably, this patient is the oldest reported so far and allows us to better delineate the clinical phenotype associated with this variant, adding clinical aspects never described before, such as epilepsy, optic atrophy, scoliosis, and neuroradiological changes characterized by progressive cerebellar atrophy.
Pepsin exposure in a non‐acidic environment upregulates mucin 5AC (MUC5AC) expression via matrix metalloproteinase 9 (MMP9)/nuclear factor κB (NF‐κB) in human airway epithelial cells
Authors: Choi Yoon Seok , Na Hyung Gyun , Bae Chang Hoon , Song Si‐Youn , Kim Yong‐Dae
Published: September 2020

Background

Gastric reflux (GR) is a backflow of gastric content to the aerodigestive tract. GR was previously found to be associated with inflammatory airway diseases and a potential cause of airway remodeling. Chronic exposure to gastric content may induce damage from nose to lung, because digestive enzymes and acidity are toxic to airway epithelial cells. Recently, the toxicity of pepsin in a non‐acidic environment was found to increase proinflammatory cytokines and receptors in the epithelium of the aerodigestive tract. However, the effect of pepsin in non‐acidic conditions on mucin expression has not been investigated in human airway epithelial cells. The purpose of this study was to evaluate the effect of pepsin on mucin 5AC (MUC5AC) expression in upper and lower airway epithelial cells as an important potential factor of non‐acidic GR‐related airway inflammation.

Methods

In NCI‐H292 cells and human nasal epithelial cells (HNEpCs), the effects and signaling pathways of pepsin on MUC5AC expression were examined using reverse‐transcription polymerase chain reaction (RT‐PCR), real‐time PCR, enzyme immunoassay, zymography, Western blot, and immunofluorescence staining.

Results

Pepsin increased MUC5AC expression in non‐acidic condition of NCI‐H292 cells and HNEpCs. Further, pepsin activated matrix metalloproteinase 9 (MMP9) and phosphorylated nuclear factor κB (NF‐κB). Moreover, inhibitors of MMP9 and NF‐κB significantly attenuated pepsin‐induced MUC5AC expression, and the knockdown of NF‐κB by small interfering RNA (siRNA) significantly blocked pepsin‐induced MUC5AC expression in human airway epithelial cells.

Conclusion

These findings suggest that pepsin increased MUC5AC expression in non‐acidic conditions via the activation of MMP9 and NF‐κB in human airway epithelial cells.
Null Fluid Collapse in Rastall Theory of Gravity
Authors: Ziaie Amir Hadi , Tavakoli Yaser
Published: September 2020

A Vaidya spacetime is considered for gravitational collapse of a type II fluid in the context of the Rastall theory of gravity. For a linear equation of state for the fluid profiles, the conditions under which the dynamical evolution of the collapse can give rise to the formation of a naked singularity are examined. It is shown that depending on the model parameters, strong curvature, naked singularities would arise as exact solutions to the Rastall's field equations. The allowed values of these parameters satisfy certain conditions on the physical reliability, nakedness, and the curvature strength of the singularity. It turns out that Rastall gravity, in comparison to general relativity, provides a wider class of physically reasonable spacetimes that admit both locally and globally naked singularities.
A Polymorphic Azobenzene Cage for Energy‐Efficient and Highly Selective p‐Xylene Separation
Authors: Moosa Basem , Alimi Lukman O. , Shkurenko Aleksander , Fakim Aliyah , Bhatt Prashant M. , Zhang Gengwu , Eddaoudi Mohamed , Khashab Niveen M.
Published: September 2020

Developing the competence of molecular sorbents for energy‐saving applications, such as C8 separations, requires efficient, stable, scalable, and easily recyclable materials that can readily transition to commercial implementation. Herein, we report an azobenzene‐based cage for the selective separation of p‐xylene isomer across a range of C8 isomers in both vapor and liquid states with selectivity that is higher than the reported all‐organic sorbents. The crystal structure shows non‐porous cages that are separated by p‐xylene molecules through selective CH–π interactions between the azo bonds and the methyl hydrogen atoms of the xylene molecules. This cage is stable in solution and can be regenerated directly under vacuum to be used in multiple cycles. We envisage that this work will promote the investigation of the azo bond as well as guest‐induced crystal‐to‐crystal phase transition in non‐porous organic solids for energy‐intensive separations.
Supramolecular Assembly and Chirality of Synthetic Carbohydrate Materials
Authors: Gim Soeun , Fittolani Giulio , Nishiyama Yoshiharu , Seeberger Peter H. , Ogawa Yu , Delbianco Martina
Published: September 2020

Hierarchical carbohydrate architectures serve multiple roles in nature. Hardly any correlations between the carbohydrate chemical structures and the material properties are available due to the lack of standards and suitable analytic techniques. Therefore, designer carbohydrate materials remain highly unexplored, as compared to peptides and nucleic acids. A synthetic D‐glucose disaccharide, DD, was chosen as a model to explore carbohydrate materials. Microcrystal electron diffraction (MicroED), optimized for oligosaccharides, revealed that DD assembled into highly crystalline left‐handed helical fibers. The supramolecular architecture was correlated to the local crystal organization, allowing for the design of the enantiomeric right‐handed fibers, based on the L‐glucose disaccharide, LL, or flat lamellae, based on the racemic mixture. Tunable morphologies and mechanical properties suggest the potential of carbohydrate materials for nanotechnology applications.
Aminometallierung mit einem gemischten K/Li‐Amid: Eine Syntheseroute zu schwer zugänglichen Phenethylamin‐Derivaten
Authors: Hermann Andreas , Opper Ulrike , Voß Andreas , Brieger Lukas , Otte Felix , Unkelbach Christian , O'Shea Donal F. , Strohmann Carsten
Published: September 2020

Im Folgenden werden Erkenntnisse aus dem Vergleich von Aminometallierungs‐Reaktionen mit Lithiumamiden, Kaliumamiden und gemischten Lithium/Kaliumamiden vorgestellt. Durch eine Kombination von Einkristallröntgenstrukturanalysen, DFT‐Berechnungen und Abfangreaktionen von aminometallierten Zwischenprodukten werden die Vorteile einer hetero‐metallischen Strategie deutlich. Während Kaliumamide keine Reaktivität zeigen, ist die der Lithiumamide unkontrollierbar und eine Eliminierung kann nicht verhindert werden. Durch die synergistische Kombination beider Metalle wird jedoch eine ausreichend kontrollierbare Reaktivität erreicht. Die Aminometallierung mit Kalium führt zur Bildung von Alkylkalium‐Spezies, die im Vergleich zu ihren Lithium‐Kongeneren eine höhere Stabilität aufweisen und dadurch eine Isolierung sowie eine weitere Charakterisierung ermöglichen.
Metal Nanozyme with Ester Hydrolysis Activity in the Presence of Ammonia‐Borane and Its Use in a Sensitive Immunosensor
Authors: Nandhakumar Ponnusamy , Kim Gyeongho , Park Seonhwa , Kim Seonghye , Kim Suhkmann , Park Jin Kyoon , Lee Nam‐Sihk , Yoon Young Ho , Yang Haesik
Published: September 2020

Metal nanoparticle surfaces are used for peroxidase‐ and oxidase‐like nanozymes but not for esterase‐like nanozymes. It is challenging to obtain rapid catalytic hydrolysis on a metal surface and even more so without a catalytically labile substrate. Here, we report that metal nanoparticle surfaces rapidly catalyze non‐redox ester hydrolysis in the presence of redox H3N−BH3 (AB). Metal hydrides are readily generated on a Pt nanoparticle (PtNP) from AB, and as a result the PtNP becomes electron‐rich, which might assist nucleophilic attack of H2O on the carbonyl group of an ester. The nanozyme system based on PtNP, AB, and 4‐aminonaphthalene‐1‐yl acetate provides an electrochemical signal‐to‐background ratio much higher than natural enzymes, due to the rapid ester hydrolysis and redox cycling involving the hydrolysis product. The nanozyme system is applied in a sensitive electrochemical immunosensor for thyroid‐stimulating hormone detection. The calculated detection limit is approximately 0.3 pg mL−1, which indicates the high sensitivity of the immunosensor using the PtNP nanozyme.
Sequential Chiral Induction and Regulator‐Assisted Chiral Memory of Pillar[5]arenes
Authors: Fa Shixin , Egami Kouichi , Adachi Keisuke , Kato Kenichi , Ogoshi Tomoki
Published: September 2020

Chirality transfer is widely observed in life processes, and many artificial chiral transfer systems have been developed. In these systems, chiral information is transferred from chiral inducers to chiral acceptors by a direct chiral induction process and a direct chiral memorization process. We have developed ternary nondirect chiral transfer systems based on pillar[5]arenes, in which a third factor was introduced as a regulator. The planar chirality of an acceptor was induced and memorized by a chiral inducer with precise control by a regulator. In the chiral induction period, the feed sequence of the chiral inducer and regulator affected the chiral induction behavior of the chiral acceptor. The chiral memory ability of the acceptor was substantially improved by the combined action of the chiral inducer and regulator.
Hyperfluorescence Imaging of Kidney Cancer Enabled by Renal Secretion Pathway Dependent Efflux Transport
Authors: Du Bujie , Chong Yue , Jiang Xingya , Yu Mengxiao , Lo U‐Gling , Dang Andrew , Chen Yu‐An , Li Siqing , Hernandez Elizabeth , Lin Jason C. , Hsieh Jer‐Tsong , Zheng Jie
Published: September 2020

Renal tubular secretion is an active efflux pathway for the kidneys to remove molecules but has yet to be used to enhance kidney cancer targeting. We report indocyanine green (ICG) conjugated with a 2100 Da PEG molecule (ICG‐PEG45) as a renal‐tubule‐secreted near‐infrared‐emitting fluorophore for hyperfluorescence imaging of kidney cancers, which cannot be achieved with hepatobiliary‐ and glomerular‐clearable ICG. This pathway‐dependent targeting of kidney cancer arises from the fact that the secretion pathway enables ICG‐PEG45 to be effectively effluxed out of normal proximal tubules through P‐glycoprotein transporter while being retained in cancerous kidney tissues with low P‐glycoprotein expression. Tuning elimination pathways and utilizing different efflux kinetics of medical agents in normal and diseased tissues could be a new strategy for tackling challenges in disease diagnosis and treatments that cannot be addressed with passive and ligand‐receptor‐mediated active targeting.
Metal Halide Regulated Photophysical Tuning of Zero‐Dimensional Organic Metal Halide Hybrids: From Efficient Phosphorescence to Ultralong Afterglow
Authors: Xu Liang‐Jin , Plaviak Anna , Lin Xinsong , Worku Michael , He Qingquan , Chaaban Maya , Kim Bumjoon J. , Ma Biwu
Published: September 2020

The photophysical tuning is reported for a series of tetraphenylphosphonium (TPP) metal halide hybrids containing distinct metal halides, TPP2MXn (MXn=SbCl5, MnCl4, ZnCl4, ZnCl2Br2, ZnBr4), from efficient phosphorescence to ultralong afterglow. The afterglow properties of TPP+ cations could be suspended for the hybrids containing low band gap emissive metal halide species, such as SbCl52− and MnCl42−, but significantly enhanced for the hybrids containing wide band gap non‐emissive ZnCl42−. Structural and photophysical studies reveal that the enhanced afterglow is attributed to stronger π–π stacking and intermolecular electronic coupling between TPP+ cations in TPP2ZnCl4 than in the pristine organic ionic compound TPPCl. Moreover, the afterglow in TPP2ZnX4 can be tuned by controlling the halide composition, with the change from Cl to Br resulting in a shorter afterglow due to the heavy atom effect.
Ein neues, mechanisch verzahntes [Pd2L4] Käfigmotiv durch Dimerisierung von zwei Peptid‐basierten Lemniskaten
Authors: Schulte Thorben R. , Holstein Julian J. , Schneider Laura , Adam Abdulselam , Haberhauer Gebhard , Clever Guido H.
Published: September 2020

Die meisten metallo‐supramolekularen Verbindungen mit niedriger Nuklearität nehmen einfache Topologien an, wobei Brückenliganden benachbarte Metallzentren direkt verbinden. Hier steuern wir ein neues Strukturmotiv zur Familie der Wirtsverbindungen mit niedriger Anzahl von Metallzentren (zwei) bei, das aus einem Paar doppelt verzahnter, achtförmiger Untereinheiten besteht, die auch als “Lemniskate” bezeichnet werden. Jedes Metall wird durch zwei chirale, zweizähnige Liganden chelatisiert, die aus einem peptidischen, Naturprodukt‐ähnlichen Makrocyclus bestehen, der zwei Pyridyl‐funktionalisierte Arme trägt. Ergebnisse von DFT‐Rechnungen deuten darauf hin, dass die Dimerisierung der mononuklearen Hälften durch eine Kombination aus 1) Coulomb‐Wechselwirkung mit dem zentralen Anion, 2) π‐π‐Stapelung zwischen verschlungenen Ligandarmen und 3) dispersiven Wechselwirkungen zwischen dem inneren Kern, eingebettet in eine Hülle aus Kavitand‐artigen Makrocyclen, getrieben wird. Die resultierende, käfigartige Struktur wurde über NMR‐, MS‐ und Einkristallröntgenstrukturanalysen charakterisiert. Das mechanisch gebundene System unterstreicht den Umfang der strukturellen Vielfalt, die durch metallvermittelte Selbstassemblierung aus nur wenigen Bestandteilen zugänglich ist.
Template‐Directed Quantitative One‐Pot Synthesis of Homochiral Helical Receptors Enabling Enantioselective Binding
Authors: Kim Kyung Mog , Song Geunmoo , Lee Seungwon , Jeon Hae‐Geun , Chae Woojeong , Jeong Kyu‐Sung
Published: September 2020

Template‐directed synthesis and dynamic covalent chemistry were implemented to achieve quantitative one‐pot syntheses of homochiral helical cavities inside aromatic foldamers. One‐handed helical receptors P‐1, M‐1, P‐2 and M‐2 were assembled from their precursors in the presence of appropriate templates (d‐ and l‐tartaric acid, and d‐ and l‐sorbitol, respectively) via three sequential steps in one pot: imine‐linked chain elongation, template‐induced folding and [4+2] cycloaddition between helical turns. These helical receptors were proven to enantioselectively bind chiral guests used as the templates, and the differences between the association constants of enantiomeric guests were up to more than two orders of magnitude. The structures and binding modes of the receptors were fully characterized by single‐crystal X‐ray crystallography and 1H NMR spectroscopy.
Tuning Gate‐Opening of a Flexible Metal–Organic Framework for Ternary Gas Sieving Separation
Authors: Dong Qiubing , Zhang Xin , Liu Shuang , Lin Rui‐Biao , Guo Yanan , Ma Yunsheng , Yonezu Akira , Krishna Rajamani , Liu Gongpin , Duan Jingui , Matsuda Ryotaro , Jin Wanqin , Chen Banglin
Published: September 2020

In comparison with the fast development of binary mixture separations, ternary mixture separations are significantly more difficult and have rarely been realized by a single material. Herein, a new strategy of tuning the gate‐opening pressure of flexible MOFs is developed to tackle such a challenge. As demonstrated by a flexible framework NTU‐65, the gate‐opening pressure of ethylene (C2H4), acetylene (C2H2), and carbon dioxide (CO2) can be regulated by temperature. Therefore, efficient sieving separation of this ternary mixture was realized. Under optimized temperature, NTU‐65 adsorbed a large amount of C2H2and CO2through gate‐opening and only negligible amount of C2H4. Breakthrough experiments demonstrated that this material can simultaneously capture C2H2and CO2, yielding polymer‐grade (>99.99 %) C2H4from single breakthrough separation.
Manipulating Light‐Induced Dynamic Macro‐Movement and Static Photonic Properties within 1D Isostructural Hydrogen‐Bonded Molecular Cocrystals
Authors: Li Shuzhen , Lu Bo , Fang Xiaoyu , Yan Dongpeng
Published: September 2020

Smart molecular crystals with light‐driven mechanical responses have received interest owing to their potential uses in molecular machines, artificial muscles, and biomimetics. However, challenges remain in control over both the dynamic photo‐mechanical behaviors and static photonic properties of molecular crystals based on the same molecule. Herein, we show the construction of isostructural co‐crystals allows their light‐induced cracking and jumping behaviors (photosalient effect) to be controlled. Hydrogen‐bonded co‐crystals from 4‐(1‐naphthylvinyl)pyridine (NVP) with co‐formers (tetrafluoro‐4‐hydroxybenzoic acid (THA) and tetrafluorobenzoic acid (TA)) crystallize as isostructural crystals, but have different static and dynamic photo‐mechanical behaviors. These differences are due to alternations in the orientation ofNVPand hydrogen‐bonding modes of the co‐formers. After light activation, the 1DNVP‐TAcrystal splits and shears off within 1 s. ForNVP‐THA, its photostability and high quantum yield give novel photonic properties, including low optical waveguide loss, highly polarized anisotropy, and efficient up‐conversion fluorescence.
Asymmetric Dearomatization of Indole by Palladium/PC‐Phos‐Catalyzed Dynamic Kinetic Transformation
Authors: Chu Haoke , Cheng Jie , Yang Junfeng , Guo Yin‐Long , Zhang Junliang
Published: September 2020

A palladium‐catalyzed intermolecular dynamic kinetic asymmetric dearomatization of 3‐arylindoles with internal alkynes was developed with the use of achiral Xantphos and chiral sulfinamide phosphine ligand (PC‐Phos) as the co‐ligands. This method could deliver various spiro[indene‐1,3′‐indole] compounds in good yields (up to 95 % yield) with up to 98 % ee. The salient features of the transformation include the use of readily available substrates, ease of scale‐up and the versatile functionalization of the products. The mechanistic experiments gave some insights on active intermediates.
Recent advances in the iron‐catalysed multicomponent reactions
Authors: Saranya Salim , Aneeja Thaipparambil , Neetha Mohan , Anilkumar Gopinathan
Published: September 2020

Iron‐catalysed reactions are widely used in organic synthesis owing to its benefits over other metals. Among the important organic reactions, multicomponent reactions play a significant role due to its greener aspects like high atom economy, minimal amount of by‐product, economic feasibility etc. For the past few years, iron‐catalysed multicomponent reactions have attracted the attention of several chemists which lead to the invention of some fine chemistry. The majority of iron‐catalysed multicomponent reactions results in the synthesis of heterocyclic compounds having biologically active natural products, pharmaceutical etc. These developments in the iron‐catalysed multicomponent reactions are the focus of this review. This is the first review in this topic which covers the literature up to 2020, and it encompasses the different methods for the synthesis of acyclic, carbocyclic and heterocyclic compounds.
Robust analytical proportional‐integral‐derivative tuning rules for regulation of air pressure in supply manifold of proton exchange membrane fuel cell
Authors: Kareem Ghousiya Begum , Ganesan Balasubramanian
Published: September 2020

The core aim of this manuscript is to recommend analytical tuning rules to regulate and control the air supply pressure moving from the supply manifold (SM) to the electrode (cathode) of proton exchange membrane fuel cell (PEMFC). This is done to have an optimal oxygen excess ratio in the fuel cell for enhanced energy generation. The higher order dynamics of PEMFC is approximated to be non‐integer first‐order stable plus time delay model. A simple proportional ‐integral/proportional‐integral‐derivative (PI/PID) control scheme is designed for a specific maximum sensitivity (Ms) using analytical tuning rules. This, in turn, enhances its dynamic performance by regulating the SM pressure. The proposed integer order PI/PID control technique is compared with the other fractional order IMC‐PI control techniques that are recently published. The simulation results obtained prove that the proposed tuning rules provide a good response compared with fractional order controllers and thereby maintaining the SM pressure. The robustness of the novel controller is analyzed by introducing perturbations and noise to the dynamic model. The tuning rules proposed are applicable for two maximum sensitivity values of 1.4 and 2 as a measure of robustness. To measure system performance, few time domain metrics and integral absolute error (IAE), integral square error (ISE), and TV metrics are used. For both the Ms values, the proposed techniques provide stable and improved responses.
The long shadow of violence: The impact of exposure to intimate partner violence in infancy and early childhood
Authors: Mueller Isabelle , Tronick Ed
Published: September 2020

Early exposure to adversities, such as witnessing intimate partner violence (IPV) can have long‐lasting impact on infants behavioral, emotional, and neurological development. Yet, research so far has focused on how IPV affects the well‐being of women or on the retrospective effects in older children. The first 2 years of life are characterized by rapid development of brain and behavior, making infants even more vulnerable than women or older children to the detrimental effects of exposure to violence. The goal of this review is to summarize the scientific findings on the effects of IPV on infant brain maturation and related socioemotional development. We describe effects of violence on attachment, symptoms of trauma in infants, and possible pathways involved in how IPV exposure may affect maturation of brain regions related to emotional regulation. We relate affected brain structures to development of stress reactivity (amygdala), memory (hippocampus), the processing of witnessed events itself (auditory and visual cortex), and how these consequences relate to potential subsequent psychopathology.
Hiding in Plain Sight‐ancient Chinese anatomy
Authors: Shaw Vivien , Diogo Rui , Winder Isabelle Catherine
Published: September 2020

For thousands of years, scientists have studied human anatomy by dissecting bodies. Our knowledge of their findings is limited, however, both by the subsequent loss of many of the oldest texts, and by a tendency toward a Eurocentric perspective in medicine. As a discipline, anatomy tends to be much more familiar with ancient Greek texts than with those from India, China, or Persia. Here, we show that the Mawangdui medical texts, entombed in the Mawangdui burial site in Changsha, China 168 BCE, are the oldest surviving anatomical atlas in the world. These medical texts both predate and inform the later acupuncture texts which have been the foundation for acupuncture practice in the subsequent two millennia. The skills necessary to interpret them are diverse, requiring the researcher firstly to read the original Chinese, and secondly to perform the anatomical investigations that allow a re‐viewing of the structures that the texts refer to. Acupuncture meridians are considered to be esoteric in nature, but these texts are clearly descriptions of the physical body. As such, they represent a previously hidden chapter in the history of anatomy, and a new perspective on acupuncture.
In vitro inhibitory effects of some acetophenone derivatives on some metabolic enzymes and molecular docking
Authors: Taslimi Parham
Published: September 2020

In this study, the acetophenone derivatives 1–6 were found to be effective inhibitor molecules for α‐glycosidase, human carbonic anhydrases I and II (hCA I/II), and acetylcholinesterase (AChE), with Ki values in the range of 167.98 ± 25.06 to 304.36 ± 65.45 µM for α‐glycosidase, 555.76 ± 56.07 to 1,043.66 ± 98.78 µM for hCA I, 598.63 ± 90.04 to 945.76 ± 74.50 µM for hCA II, and 71.34 ± 11.25 to 143.75 ± 31.27 µM for AChE, and IC50 values of 73.65–101.13 µM for tyrosinase. In the last step, molecular docking calculations were performed to compare the biological activities of molecules with their docking scores in these enzymes. The interactions of the studied molecules against human α‐galactosidase (PDB ID: 1R47), hCA I (PDB ID: 3LXE), human AChE (PDB ID: 4M0E), hCA II (PDB ID: 5AML), and human tyrosinase (PDB ID: 5M8Q) were examined to compare the biological activity values. The ADME/T analysis (adsorption, distribution, metabolism, and discharge) was then performed for the future use of these molecules as drugs.
Improvements in Fatigue Lag Behind Disease Remission in Early Rheumatoid Arthritis: Results From the Canadian Early Arthritis Cohort
Authors: Holdren Melissa , Schieir Orit , Bartlett Susan J. , Bessette Louis , Boire Gilles , Hazlewood Glen , Hitchon Carol A. , Keystone Edward , Tin Diane , Thorne Carter , Bykerk Vivian P. , Pope Janet E. ,   the Canadian Early Arthritis Cohort investigators
Published: September 2020

Objective

To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA).

Methods

Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11‐point numerical rating scale (NRS) for up to 5 years of follow‐up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3‐months of cohort entry were compared.

Results

Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56–0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C‐reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow‐up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow‐up. Maximal improvements in fatigue lagged behind remission by 6 months.

Conclusion

Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3‐months was associated with short‐term and long‐term benefits in fatigue over time.
Direct Introduction of Sulfonamide Groups into Quinoxalin‐2(1H)‐ones by Cu‐Catalyzed C3‐H Functionalization
Authors: Tan Yushi , Liu Boyan , Han Ya‐Ping , Zhang Yuecheng , Zhang Hong‐Yu , Zhao Jiquan
Published: September 2020

Direct sulfonamidation of quinoxalin‐2(1H)‐one derivatives has been developed using a readily available Cu salt as the catalyst and inexpensive ammonium persulfate as the oxidant in moderate conditions. Owing to the feature of handy operation and good functional group tolerance, this method provides a convenient and efficient access to curative 3‐sulfonamidated quinoxalin‐2(1H)‐one scaffolds.
Untersuchung, Analyse und Bewertung von Dünenerosionen an der deutschen Ostseeküste
Authors: Saathoff Fokke , Kaehler Christian , Fürst Sebastian
Published: September 2020

An der Ostseeküste Mecklenburg‐Vorpommerns und Schleswig‐Holsteins wird die Küstenlinie häufig durch Landesküstenschutzdünen geschützt. Im aktuellen Bericht des IPCC werden für die Zukunft ein deutlicher Anstieg des Meeresspiegels und eine Zunahme von Sturmfluten prognostiziert. Dünenbauwerke sind von dieser Entwicklung direkt betroffen. Im BMBF‐Forschungsprojekt PADO untersuchten Wissenschaftler der Professur Geotechnik und Küstenwasserbau (Universität Rostock) zusammen mit verschiedenen Partnern, wie Dünen im Ernstfall in Längsrichtung versagen, wie Polderflächen durch eine Dünenbresche geflutet werden und wie sie sich nach Absinken der Hochwasserwelle wieder entleeren. Für die Untersuchung der Dünendynamik bei Hochwasserereignissen wurde ein großmaßstäbliches Dünenbauwerk an der Ostseeküste in Rostock‐Warnemünde errichtet. Durch eine umfangreiche Instrumentierung des Bauwerks und ein neu entwickeltes innovatives Messsystem konnten alle relevanten Prozesse im Hochwasserfall erfasst werden. Die so gewonnenen Daten dienen u. a. als Grundlage für die Kalibrierung numerischer Modelle, weiterführende Untersuchungen zur Hydrologie im Hinterland und zur umwelt‐ und sozioökonomischen Bewertung der möglichen Auswirkungen. Mit den Ergebnissen des Projekts konnten neue relevante Erkenntnisse zur Dünendynamik generiert und die Bemessungsansätze für Dünen und kombinierte Küstenschutzsysteme mit Dünen und Deichen weiterentwickelt werden.
Bioactive calcium silicate glass synthesized from sustainable biomass wastes
Authors: Punj Shivani , Singh Kulvir
Published: September 2020

Biomass wastes of corn, sugarcane, and eggshells were used as resources to synthesize calcium silicate glass by applying the melt quench technique. The glasses were characterized by different experimental techniques to check their suitability as bioproducts. The in vitro bioactive properties of the glasses were evaluated in simulated body fluid (SBF). As confirmed by X‐ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy, a carbonated amorphous hydroxyapatite layer was formed on the surface of the glass. The ions released from the glasses into SBF were analyzed by microwave plasma atomic emission spectroscopy. The dissolution rate of the glass increased with increasing proportion of eggshell powder in it. The Ca/P molar ratio for all the glasses was in the range of 1.78 to 4.1. These bioactive glasses formed carbonated amorphous hydroxyapatite, which can be used to enhance the osteointegration rate in the human body. Bio‐food wastes are a sustainable, environment‐friendly and cost‐effective source for the synthesis of different types of bioproducts. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Restoration and Modification of Magnetosome Biosynthesis by Internal Gene Acquisition in a Magnetotactic Bacterium
Authors: Arakaki Atsushi , Goto Mayu , Maruyama Mina , Yoda Takuto , Tanaka Masayoshi , Yamagishi Ayana , Yoshikuni Yasuo , Matsunaga Tadashi
Published: September 2020

Integration of a large‐sized DNA fragment into a chromosome is an important strategy for characterization of cellular functions in microorganisms. Magnetotactic bacteria synthesize intracellular organelles comprising membrane‐bound single crystalline magnetite, also referred to as magnetosomes. Magnetosomes have gained interest in both scientific and engineering sectors as they can be utilized as a material for biomedical and nanotechnological applications. Although genetic engineering of magnetosome biosynthesis mechanism has been investigated, the current method requires cumbersome gene preparation processes. Here, the chromosomal integration of a plasmid containing ≈27 magnetosome genes (≈26 kbp region) in a non‐magnetic mutant of Magnetospirillum magneticum AMB‐1 using a broad‐host‐range plasmid is shown. The genome sequencing of gene‐complemented strains reveals the chromosomal integration of the plasmid with magnetosome genes at a specific site, most likely by catalysis of an endogenous transposase. Magnetosome production is successfully enhanced by integrating a variation of magnetosome gene operons in the chromosome. This chromosomal integration mechanism will allow the design of functional magnetosomes de novo and M. magneticum AMB‐1 may be used as a chassis for the designed magnetosome production.
Design and evaluation of a continuous semipartition bioreactor for in situ liquid‐liquid extractive fermentation
Authors: Teke George M. , Pott Robert W. M.
Published: September 2020

Extractive fermentation (or in situ product removal (ISPR)) is an operational method used to combat product inhibition in fermentations. To achieve ISPR, different separation techniques, modes of operation and physical reactor configurations have been proposed. However, the relative paucity of industrial application necessitates continued investigation into reactor systems. This article outlines a bioreactor designed to facilitate in situ product extraction and recovery, through adapting the reaction volume to include a settler and solvent extraction and recycle section. This semipartition bioreactor is proposed as a new mode of operation for continuous liquid‐liquid extractive fermentation. The design is demonstrated as a modified bench‐top fermentation vessel, initially analysed in terms of fluid dynamic studies, in a model two‐liquid phase system. A continuous abiotic simulation of lactic acid (LA) fermentation is then demonstrated. The results show that mixing in the main reaction vessel is unaffected by the inserted settling zone, and that the size of the settling tube effects the maximum volumetric removal rate. In these tests the largest settling tube gave a potential continuous volumetric removal rate of 7.63 ml/min; sufficiently large to allow for continuous product extraction even in a highly productive fermentation. To demonstrate the applicability of the developed reactor, an abiotic simulation of a LA fermentation was performed. LA was added to reactor continuously at a rate of 33ml/h, while continuous in situ extraction removed the LA using 15% trioctylamine in oleyl alcohol. The reactor showed stable LA concentration of 1 g/L, with the balance of the LA successfully extracted and recovered using back extraction. This study demonstrates a potentially useful physical configuration for continuous in situ extraction.
Metabolic profiling of aromatic compounds in cerebrospinal fluid of neurosurgical patients using microextraction by packed sorbent and liquid–liquid extraction with gas chromatography–mass spectrometry analysis
Authors: Pautova Alisa K. , Khesina Zoya B. , Litvinova Tatiana N. , Revelsky Alexander I. , Beloborodova Natalia V.
Published: September 2020

A new approach to the quantitative analysis of aromatic metabolites in cerebrospinal fluid samples of neurosurgical patients based on microextraction by packed sorbent coupled with derivatization and GC–MS was developed. Analytical characteristics such as recoveries (40–90%), limit of detection (0.1–0.3 μm) and limit of quantitation (0.4–0.7 μm) values, accuracy (<±20%), precision (<20%) and linear correlations (R2 ≥ 0.99) over a 0.4–10 μm range of concentrations demonstrated that microextraction by packed sorbent provides results for the quantitative analysis of target compounds comparable with those for liquid–liquid extraction. Similar results were achieved using 40 μl of sample for microextraction by packed sorbent instead of 200 μl for liquid–liquid extraction. Benzoic, 3‐phenylpropionic, 3‐phenyllactic, 4‐hydroxybenzoic, 2‐(4‐hydroxyphenyl)acetic, homovanillic and 3‐(4‐hydroxyphenyl)lactic acids were found in cerebrospinal fluid samples (n = 138) of neurosurgical patients in lower concentrations than in serum samples (n = 110) of critically ill patients. Analysis of the cerebrospinal fluid and serum samples taken at the same time from neurosurgical patients (n = 5) revealed similar results for patients without infection and multidirectional results for patients with central nervous system infection. Our preliminary results demonstrate the necessity of further evaluating the aromatic compound profile in cerebrospinal fluid for its subsequent verification for potential diagnostic markers.
Metabolomics analysis of multidrug resistance in colorectal cancer cell and multidrug resistance reversal effect of verapamil
Authors: Wang Xinying , Wang Zihan , Wang Kaili , Gao Ming , Zhang Hang , Xu Xia
Published: September 2020

Multidrug resistance remains a huge challenge in the chemotherapy of cancer and numerous studies have reported that P‐glycoprotein is the most common mechanism of multidrug resistance. Verapamil has been shown to be able to reverse development of multidrug resistance mediated by P‐glycoprotein. However, the mechanism of action for verapamil in reversing multidrug resistance at the metabolic level has been rarely reported. In this research, we report the reversal effect of verapamil on multidrug resistance and its mechanisms of action using metabolomics. The results show that the P‐glycoprotein‐mediated chemotherapy drug resistance was significantly reversed by verapamil in resistant SW620/Ad300 cells. In‐depth studies demonstrated that verapamil at reversal concentration had no effect on the P‐glycoprotein expression level, but increased intramolecular accumulation of paclitaxel in SW620/Ad300 cells. Metabolomics revealed that the multidrug resistance of SW620/Ad300 cells was related to changes in glycerophospholipid metabolism, sphingolipid metabolism and citric acid cycle, and verapamil could antagonize the multidrug resistance by reversing the above‐mentioned glycerophospholipid metabolism and sphingolipid metabolism. This research shows the multidrug resistance reversal mechanism of verapamil at the metabolic level, which helps in understanding the exact multidrug resistance mechanism of verapamil and might be potentially useful to find new multidrug resistance reversal agents.

The combination of verapamil (VRP) and paclitaxel (PTX) yielded synergistic effects.

VRP had no effect on the expression of P‐gp, but increased intramolecular accumulation of PTX.

VRP antagonized the MDR by regulating glycerophospholipid metabolism and sphingolipid metabolism.
For green or not for green? The effect of cooperation goals and type on environmental performance
Authors: Calza Francesco , Parmentola Adele , Tutore Ilaria
Published: September 2020

Although many scholars have demonstrated that companies engaged in collaborations achieve better environmental performance than other companies, existing studies have not analyzed in depth whether this effect changes considering the characteristics of cooperation. Our paper aims to explore whether collaboration with other companies always has a positive effect on environmental performance or whether it depends on cooperation goals, collaboration type, or company size. Empirical analysis based on a sample of 773 European companies demonstrated that an external source of knowledge is an important way to foster firms' environmental proactivity, especially when environmental goals are shared at the basis of collaboration. Second, we verified that companies involved in JVs with environmental goals achieve greater environmental performance than companies that use M&As to acquire external knowledge. Finally, we demonstrated that it is more important for small companies to be involved in environmental collaboration than larger ones.
Solid–fluid separation in the gravitational field: Courseware generation using computational fluid dynamics simulation
Authors: Almeida Natalia Pazin , Canhadas Maynara Cipriano , Albertini Madeleine Rocio Medrano Castillo , Santos Kassia Graciele dos , Vieira Neto José Luiz
Published: September 2020

The growth of the Brazilian economy has resulted in an increased demand for engineers and the expansion of Brazilian Universities. As for the teaching of unit operations, a lack of interactive and illustrative courseware was observed. The modeling and simulation tools are excellent alternatives to predict the particle and fluid dynamics and have been used in the design and optimization of industry equipment, providing information in areas where it is difficult to acquire experimental measurements. This paper shows simulations using the computational fluid dynamics technique of the exercises presented in a course on solid–fluid separation in the gravitational field, such as sand chambers, dust chamber, horizontal and vertical elutriators. The effect of size, shape, and density of particles on the collection efficiency was evaluated. Figures and videos generated in this study will facilitate students' understanding of the phenomena involved in the particle collection inside those separation devices.
Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China
Authors: Gao Wen , Jian Yuan , Du Juan , Li Xiaozhe , Zhou Huixing , Zhang Zhiyao , Yang Guangzhong , Wang Guorong , Tian Ying , Li Yanchen , Wu Yin , Fu Weijun , Li Juan , Chen Wenming
Published: September 2020

Background

Autologous stem cell transplantation (ASCT) has been recommended as a standard approach for young multiple myeloma (MM) patients for decades, even in the era of novel agents. Gain of chromosome 1q21 is a common cytogenetic abnormality in MM, while its clinical prognostic value is still controversial.

Methods

In this multicenter study, we retrospectively analyzed 1q21 gain in 446 newly diagnosed MM patients who received at least one ASCT from three large myeloma centers in China.

Results

Of the all 446 patients, 1q21 gain was an adverse predictor of progression‐free survival (PFS) (34 vs 56 months, P = .005) and overall survival (OS) (69 vs 100 months, P = .002). Gain of 1q21 was more likely to coexist with t(4;14), t(14;16), and del(13q). Nevertheless, isolated 1q21 gain still exhibited unfavorable effects on PFS (35 vs 66 months, P = .045) and OS (61 vs 100 months, P = .026). The coexistence of 1q21 gain and high‐risk cytogenetics (HRCs) [del(17p), t(4;14),and/or t(14;16)] showed poor prognosis on both PFS and OS, while no additional adverse effect could be identified when compared with HRCs alone. Moreover, when coexisting with t(11;14), patients with 1q21 gain showed a comparable survival to those without 1q21 gain. For patients treated with novel induction regimens followed by ASCT, 1q21 gain also conferred an inferior prognosis. Multivariate analysis further confirmed 1q21 gain could independently predict shorter PFS and OS.

Conclusion

In conclusion, 1q21 gain is an adverse prognostic factor for MM patients received ASCT.
Effectiveness of chemotherapy after anti‐PD‐1 blockade failure for relapsed and refractory Hodgkin lymphoma
Authors: Casadei Beatrice , Argnani Lisa , Morigi Alice , Lolli Ginevra , Broccoli Alessandro , Pellegrini Cinzia , Nanni Laura , Stefoni Vittorio , Coppola Paolo E. , Carella Matteo , Cavo Michele , Zinzani Pier Luigi
Published: September 2020

Programmed death‐1 (PD1) blockade is an efficient and safe therapeutic option in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, a substantial proportion of patients’ progresses or loses the response to anti‐PD1 treatment. We retrospectively investigated the effectiveness of salvage chemotherapies (CHT) for unsatisfactory response to anti‐PD1, in 25 R/R cHL patients. Twenty‐three patients (92%) were refractory to the last treatment before anti‐PD1. After a median of 14 cycles (range 3‐52), 68% (17/25) of patients had unsatisfactory responses to anti‐PD1 therapy, whereas 6 had a partial response (PR) and 2 patients achieved complete response (CR), with an overall response rate (ORR) of 32%. After a median time of 1.5 months, 15 patients received a single agent treatment and 10 had a multi‐agents regimen, due to the failure of PD1 blockade. The ORR was 60% (8 CR and 7 PR). Seven patients (3 in PR and 4 in CR) underwent a consolidation strategy with stem cell transplantation. Median progression‐free survival (PFS) with salvage treatment was reached at 19.1 months, while median PFS after anti‐PD1 has been reached at 8.2 months. After a median follow‐up of 32.4 months, 6 patients died while 13 are still in CR. The median overall estimated from the start of CHT was not reached. The efficacy of treatment following anti‐PD1 is not yet established, especially in lymphoma patients. To note, in our series, a subset of heavily pre‐treated and chemo‐refractory patients increased response rates to and survival with CHT given after exposure to immune‐checkpoint inhibitors.