bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereoselective Synthesis of Atropisomeric Acridinium Salts by the Catalyst‐Controlled Cyclization of ortho‐Quinone Methide Iminiums
Authors: Wu Xingxing , Sparr Christof
Published: February 2022

Quinone methides are fundamental intermediates for a wide range of reactions in which catalyst stereocontrol is often achieved by hydrogen bonding. Herein, we describe the feasibility of an intramolecular Friedel–Crafts 6π electrocyclization through ortho‐quinone methide iminiums stereocontrolled by a contact ion pair. A disulfonimide catalyst activates racemic trichloroacetimidate substrates and imparts stereocontrol in the cyclization step, providing a new avenue for selective ortho‐quinone methide iminium functionalization. A highly stereospecific oxidation readily transforms the enantioenriched acridanes into rotationally restricted acridiniums. Upon ion exchange, the method selectively affords atropisomeric acridinium tetrafluoroborate salts in high yields and an enantioenrichment of up to 93 : 7 e.r. We envision that ion‐pairing catalysis over ortho‐quinone methide iminiums enables the selective synthesis of a diversity of heterocycles and aniline derivatives with distinct stereogenic units.
Experimental and theoretical study of novel amino‐functionalized P(V) coordination compounds suggested as inhibitor of MProof SARS‐COV‐2 by molecular docking study
Authors: Najarianzadeh Mobina , Tarahhomi Atekeh , Pishgo Samaneh , van der Lee Arie
Published: February 2022

Amino‐functionalized P(V) derivatives providing bothN‐ andO‐donor modes have attracted interest owing to their potential to form interesting coordination assemblies with applications such as biological drugs. Novel coordination modes of two‐ and four‐dentate tris (pyridin‐2‐yl)phosphoric triamide OP[NH‐2Py]3as ([Co(II){[O][NH‐2Py]P(O)[Ph]}2(DMF)2],1) and ([Cu(II)Cl{[NH‐2Py]2P(O)[N‐2Py]}].DMF,2) have been synthesized and structurally studied. The metal center environment is distorted octahedral for1and distorted square pyramidal for2. The crystal structure of a new complex of Cu(II)with a Cu[N]4[Cl]2environment ([Cu(II)Cl2(Pyrazole)4],3) is also investigated. An evaluation of the inhibitory effect against the coronavirus (Main Protease [MPro] of SARS‐CoV‐2) was carried out by a molecular docking study and illustrates that these compounds have a good interaction tendency with CoV‐2, where1has the best binding affinity with the biological target comparable with other SARS‐CoV‐2 drugs. Moreover, theoretical QTAIM and natural bond orbital (NBO) calculations are used to evaluate the metal‐oxygen/‐nitrogen bonds suggesting that they are mainly electrostatic in nature with a slight covalent contribution. A molecular packing analysis using Hirshfeld surface (HS) analysis shows that N—H … O (in1and2) and N—H … Cl (in3) hydrogen bonds are the dominant interactions that contribute to the crystal packing cohesion. The semi‐empirical PIXEL method indicates that the electrostatic and repulsion energy components in the structures of1and2and the dispersion and electrostatic components in that of3are the major contributors to the total lattice energy.
Synthesis, molecular docking, and biological evaluation of 5‐alkyl(aryl)‐2‐isobutylthiazole derivatives: As α‐amylase, α‐glucosidase, and protein kinase inhibitors
Authors: Khan Siraj , Buğday Nesrin , Rehman Asim Ur , Haq Ihsan Ul , Yaşar Sedat , Özdemir İsmail
Published: February 2022

A series of 18 biologically active C5‐arylated‐2‐isobutylthiazole derivatives that were synthesized by Pd‐NHC complexes [Pd(μ‐Cl)Cl (NHC)]2, NHC = SIXyl, 2), (LCl2Pd‐NHC, L = PPh3, 3), (LCl2Pd‐NHC, L = Py, 4), (LCl2Pd‐NHC, L = 3‐CHO‐Py, 5) catalyzed C‐H bond activation reactions. The catalytic activity of Pd‐NHC complexes was examined on the C‐H bond activation reaction of 2‐isobutylthiazole. All Pd‐NHC complexes were characterized by 1H nuclear magnetic resonance specroscopy (NMR), 13C NMR, fouirer transform infrared spektroscopy (FTIR), quadrupole‐time of flying‐liquit cromotagraphy/mass spektroscopy (Q‐TOF‐LC/MS), gas chromatography–mass spectrometry (GCMS), and melting point detection technique. The physicochemical properties, pharmacokinetics, and drug‐likeness were calculated by SwissADME. PkCSM database was used to calculate toxicities profile. All the products (6a–6s) were additionally assessed in vitro for their antidiabetic potential using α‐amylase and α‐glucosidase inhibitory activities. The protein kinase activity was performed to evaluate their anticancer activities. All the compounds possess drug‐like characters as they followed Lipinski's rule of five (RO5). Almost all the compounds showed no to fewer toxicities. In addition, other than the compounds, that is, 6a, 6b, 6c, 6m, 6n, 6p, and 6s, the rest of the compounds showed good α‐glucosidase inhibitory potential (IC50 7.17 ± 0.201 to 74.08 ± 0.244 μg/ml) when compared with acarbose standard (IC50 16.59 ± 0.135 μg/ml). All compounds had moderate to good inhibitory potential against the α‐amylase enzyme, with IC50 values ranging from 12.00 ± 0.289 to 76.15 ± 0.477 μg/ml. Eleven analogs (6e, 6f, 6g, 6h, 6j, 6k, 6l, 6n, 6o, 6p, and 6r) showed good to moderate activity. Seven analogs (6a, 6b, 6c, 6d, 6i, 6m, and 6s) showed no α‐amylase inhibitory activity. The protein kinase inhibition potential was determined for the first time, and the compounds 6d, 6e, 6f, 6h, 6k, 6p, and 6r depicted activity with the zone of inhibition in the range of 9 ± 1.3 to 19 ± 1.5 mm. The ligands and active site binding interactions of α‐glucosidase, α‐amylase, and protein kinase enzymes were also studied using molecular modeling.
Covalent organic framework‐supported Pd nanoparticles: An efficient and reusable heterogeneous catalyst for Suzuki–Miyaura coupling reactions
Authors: Jin Hao , Zhang Chi , Liu Pingwei , Ge Xin , Zhou Shaodong
Published: February 2022

A Schiff base hollow covalent organic framework (COF) was used for anchoring Pd(II) to synthesize the Pd@COF‐TB nanocatalyst. Then, the as‐synthesized Pd@COF‐TB catalyst has been meticulously characterized using several methods. Thereafter, the catalytic performance of the Pd@COF‐TB species regarding Suzuki–Miyaura coupling reactions was examined, and the corresponding products were obtained with good to excellent yields. Besides, the Pd@COF‐TB catalyst could be recovered conveniently and reused at least eight times without obvious decrease in activity and selectivity. More importantly, the leaching of Pd during the reaction process could be negligible, which is crucially important when preparing bioactive species.
Expert Perspective: An Approach to Refractory Lupus Nephritis
Authors: Arora Swati , Rovin Brad H.
Published: February 2022

Systemic lupus erythematosus affects the kidneys in ~50% of all patients, and lupus nephritis (LN) is the most common manifestation of kidney involvement. Despite prompt diagnosis and treatment with aggressive immunosuppression, a significant proportion of LN patients do not respond to treatment and are considered to have refractory LN. Several factors other than drug resistance, such as nonadherence to treatment, undertreatment with conventional drugs, the effects of accumulated chronic damage, and genetic factors, may contribute to a poor response to treatment and should be considered. We define refractory LN as no change in (or worsening of) proteinuria and/or estimated glomerular filtration rate in response to 2 different standard‐of‐care induction regimens after 4–6 months in patients who are adherent to treatment. For patients who have LN that is truly refractory to standard of care, B cell–targeted therapy, specifically rituximab (RTX), is the most common next step. There is limited evidence available on alternative rescue therapies that may be used when there is no response to RTX. These include anti‐CD38, leflunomide, intravenous immunoglobulin, plasma exchange, autologous stem cell transplantation, chimeric antigen receptor T cell therapy, anticomplement therapy, and interleukin‐2 therapy.
A cocktail of protein engineering strategies: Breaking the enzyme bottleneck one by one for high UTP production in vitro
Authors: Li Zonglin , Sun Chuanqi , Lou Longwei , Li Zhimin
Published: February 2022

The pyrimidine metabolic pathway is tightly regulated in microorganisms, allowing limited success in metabolic engineering for the production of pathway‐related substances. Here, we constructed a four‐enzyme coupled system for the in vitro production of uridine triphosphate (UTP). The enzymes used include nucleoside kinase, uridylate kinase, nucleoside diphosphate kinase, and polyphosphate kinase for energy regeneration. All these enzymes are derived from extremophiles. To increase the total and unit time yield of the product, three enzymes other than polyphosphate kinase were modified separately by multiple protein engineering strategies. A nucleoside kinase variant with increased specific activity from 2.7 to 36.5 U/mg, a uridylate kinase variant (specific activity of 37.1 U/mg) with a 5.2‐fold increase in thermostability, and a nucleoside diphosphate kinase variant with a 2‐fold increase in a specific activity to over 900 U/mg were obtained, respectively. The reaction conditions of the coupled system were further optimized, and a two‐stage method was taken to avoid the problem of enzymatic pH adaptation mismatch. Under optimal conditions, this system can produce more than 65 mM UTP (31.5 g/L) in 3.0 h. The substrate conversion rate exceeded 98% and the maximum UTP productivity reached 40 mM/h.
Elucidating Instabilities Contributing to Capacity Fade in Bipyridine‐Based Materials for Non‐aqueous Flow Batteries
Authors: Kolesnichenko Claudina X. , Pratt Harry D. , Small Leo J. , Anderson Travis M.
Published: February 2022

Invited for this month's cover picture is the non‐aqueous redox flow battery team at Sandia National Laboratories. The cover picture shows a chemist modifying the anolyte side of the flow cell and renewable energy sources in the background. Read the full text of the Research Article at 10.1002/celc.202101490.
Hollow Capsule NiCo2NS Prepared by Self‐Sacrificing Template Method for High‐Efficiency Bifunctional Catalyst and Its Application in Zn‐Air Battery
Authors: Zhao Lingxue , Zhang Guanghui , Wang Bingqian , Li Guangda
Published: February 2022

Exploring the application of high‐efficiency bifunctional oxygen catalysts to rechargeable zinc‐air batteries has been a research hotspot in recent years. We succeeded in obtaining NiCo2NS with a hollow capsule structure through the self‐sacrificing template method, which has a larger specific surface area and can provide more active sites for electrocatalysis relative to his solid. The introduction of S can change the valence distribution of N and the electronic structure of the M−N bond, so that NiCo2NS exhibits excellent performance in the overpotential and stability of the oxygen reduction and oxygen evolution reactions. It shows an overpotential of 154 mV at 10 mA cm−2 and a half‐wave potential of 0.76 V. When used as a bi‐functional catalyst in zinc‐air batteries, it exhibits good stability within 400 h. The flexible battery assembled by NiCo2NS also shows excellent performance, and can be cycled stably for 20 h. The current maintains good stability when it is bent at different angles during the cycle.
A Practical and High‐Affinity Fluorescent Probe for Butyrylcholinesterase: A Good Strategy for Binding Affinity Characterization
Authors: Wang Lei , Du Chenxi , Liu Hui , Qiu Weimin , Lu Xin , Hu Yanyu , Li Yueqing , Sun Tianyu , Chen Yao , Sun Haopeng
Published: February 2022

Comprehensive Summary

Butyrylcholinesterase (BChE) is regarded as a promising target for the treatment of Alzheimer's disease (AD), as its level significantly increases along with the progress of this disease. Therefore, the development of potent and high‐affinity small‐molecule BChE inhibitors may be a new strategy for the discovery of anti‐AD drugs. However, the current Ellman's method is unable to evaluate the affinity of compounds with BChE, and has a few deficiencies in drug development. Herein, the first small‐molecule fluorescence polarization (FP) probes for BChE were rationally designed based on a high affinity inhibitor. Studies indicated that probe F6 exhibited satisfactory fluorescence intensity and suitable fluorescent properties that were compatible with the filters in the FP system. Meanwhile, probe F6 exhibited potent binding affinity to BChE. It is feasible to be applied in detecting the affinity of non‐fluorescent compounds to BChE, which lays a solid foundation for the development of small‐molecule BChE inhibitors. At the same time, it also can be applied as a valuable chemical tool for better understanding the molecular biological mechanism of BChE.
Cephalotane‐Type Norditerpenoids from Cephalotaxus fortunei var. alpina
Authors: Ge Zhan‐Peng , Zhou Bin , Zimbres Flavia M. , Cassera Maria B. , Zhao Jin‐Xin , Yue Jian‐Min
Published: February 2022

Comprehensive Summary

A chemical investigation of the 95% EtOH extract of the seeds of Cephalotaxus fortunei var. alpina led to the isolation of nine new cephalotane‐type norditerpenoids, ceforalides A—I (1—9), and two known analogues (10 and 11). Compounds 1—8 belong to a rare class of A‐ring‐contracted cephalotane‐type norditerpenoids, of which compound 8 incorporates a unique tetrasubstituted 2,5‐cyclohexadienone A‐ring. Compound 9 is a rare 13,14‐seco‐17‐nor‐cephalotane‐type diterpenoid. Their structures were determined based on NMR, HRESIMS, ECD, and X‐ray diffraction analysis. Biological tests revealed compounds 10 and 11 displayed moderate antimalarial activity.
Aerobic Photocatalysis: Oxidation of Sulfides to Sulfoxides
Authors: Skolia Elpida , Gkizis Petros L. , Kokotos Chistoforos G.
Published: February 2022

Sulfoxides constitute one of the most important functional groups in organic chemistry found in numerous pharmaceuticals and natural products. Sulfoxides are usually obtained from the oxidation of the corresponding sulfides. Among various oxidants, oxygen or air are considered the greenest and most sustainable reagent. Photochemistry and photocatalysis is increasingly applied in new, as well as traditional, yet demanding, reaction, like the aerobic oxidation of sulfides to sulfoxides, since photocatalysis has provided the means to access them in mild and effective ways. In this review, we will summarize the photochemical protocols that have been developed for the oxidation of sulfides to sulfoxides, employing air or oxygen as the oxidant. The aim of this review is to present: i) a historical overview, ii) the key mechanistic studies and proposed mechanisms and iii) categorize the different catalytic systems in literature.
Sustainable and Efficient Low‐Energy Light Emitters: A Series of One‐Dimensional d10 Coinage Metal–Organic Chalcogenolates, [M(o‐SPhCO2H)]n
Authors: Veselska Oleksandra , Guillou Nathalie , Diaz‐Lopez Maria , Bordet Pierre , Ledoux Gilles , Lebègue Sébastien , Mesbah Adel , Fateeva Alexandra , Demessence Aude
Published: February 2022

A series of d10 coinage metal thiosalicylate coordination polymers (CPs) is reported. The 1D structures of the three CPs are formed by M3S3 fused hexagons for Cu and Ag compounds and interpenetrated helical chains for Au CP. Depending on the metal, solid‐state red and NIR emissive CPs are obtained with quantum yields up to 50 %, providing a great opportunity to replace the actual emissive critical raw materials.
An any‐unit‐to‐any‐unit method for hybrid‐structured voltage equalizer in series‐connected battery/super‐capacitor strings
Authors: Du Guangjian , Zhang Guidong , Yu Samson S. , Iu Herbert H. C. , Lin Weiqun , Le Weiping , Zhang Yun
Published: February 2022

The slow balancing speed of switched‐capacitor (SC)‐based equalizers makes this structure difficult to apply in series‐connected battery strings. In order to reduce the number of energy conversion processes and achieve leapfrog transmission of energy, a hybrid‐structured voltage equalizer (HSVE) is developed in this work for battery strings to achieve high‐speed any‐unit‐to‐any‐unit (AU2AU) equalization, in which each unit can also achieve internal balance in any arbitrary imbalance status. Compared to the conventional equalizers using complex monitoring and control strategy, the proposed equalizer does not need any cell monitoring circuits—all MOSFETs are triggered by a pair of complementary pulse signals with a fixed switching frequency and constant duty ratio, and electricity can automatically and directly exchange among all battery cells. Hardware experiments on super‐capacitors and Li‐ion batteries are conducted in this study, which prove the feasibility of the proposed voltage equalizer. The proposed battery management strategy will have wide applications in modern battery‐related industries such as electric vehicles (EVs).
Observation of a black‐cheeked waxbill (Brunhilda charmosyna) cleaning a Kirk’s dik‐dik (Madoqua kirkii)
Authors: Nyaguthii Brendah , Njoroge Peter , Farine Damien R.
Published: February 2022

The vast majority of interspecific interactions are competitive or exploitative. Yet, some positive interspecies interactions exist, where one (commensalism) or both (mutualism) species benefit. One such interaction is cleaning mutualisms, whereby a cleaner removes parasites from a client. In this note, we document the novel observation of a black‐cheeked waxbill (Brunhilda charmosyna) appearing to clean a Kirk's dik‐dik (Madoqua kirkii), at the Mpala Research Centre in Laikipia County, Kenya. The purported cleaning took place for over one minute and is notable firstly for the dik‐dik remaining still for the duration of cleaning and secondly for involving two species that are much smaller than those traditionally involved in bird–mammal cleaning interactions. Unfortunately, no further cleaning events were subsequently observed, raising questions about whether this record was opportunistic or a regular occurrence. Future observations may reveal whether this behavior is widespread and whether it involves other small passerines.
Beyond the encounter: Predicting multi‐predator risk to elk (Cervus canadensis) in summer using predator scats
Authors: MacAulay Kara M. , Spilker Eric G. , Berg Jodi E. , Hebblewhite Mark , Merrill Evelyn H.
Published: February 2022

There is growing evidence that prey perceive the risk of predation and alter their behavior in response, resulting in changes in spatial distribution and potential fitness consequences. Previous approaches to mapping predation risk across a landscape quantify predator space use to estimate potential predator‐prey encounters, yet this approach does not account for successful predator attack resulting in prey mortality. An exception is a prey kill site that reflects an encounter resulting in mortality, but obtaining information on kill sites is expensive and requires time to accumulate adequate sample sizes.

We illustrate an alternative approach using predator scat locations and their contents to quantify spatial predation risk for elk (Cervus canadensis) from multiple predators in the Rocky Mountains of Alberta, Canada. We surveyed over 1300 km to detect scats of bears (Ursus arctos/U. americanus), cougars (Puma concolor), coyotes (Canis latrans), and wolves (C. lupus). To derive spatial predation risk, we combined predictions of scat‐based resource selection functions (RSFs) weighted by predator abundance with predictions that a predator‐specific scat in a location contained elk. We evaluated the scat‐based predictions of predation risk by correlating them to predictions based on elk kill sites. We also compared scat‐based predation risk on summer ranges of elk following three migratory tactics for consistency with telemetry‐based metrics of predation risk and cause‐specific mortality of elk.

We found a strong correlation between the scat‐based approach presented here and predation risk predicted by kill sites and (r = .98, p < .001). Elk migrating east of the Ya Ha Tinda winter range were exposed to the highest predation risk from cougars, resident elk summering on the Ya Ha Tinda winter range were exposed to the highest predation risk from wolves and coyotes, and elk migrating west to summer in Banff National Park were exposed to highest risk of encountering bears, but it was less likely to find elk in bear scats than in other areas. These patterns were consistent with previous estimates of spatial risk based on telemetry of collared predators and recent cause‐specific mortality patterns in elk.

A scat‐based approach can provide a cost‐efficient alternative to kill sites of quantifying broad‐scale, spatial patterns in risk of predation for prey particularly in multiple predator species systems.
Genetic variation in sodium glucose co‐transporter 1 and cardiac structure and function at middle age
Authors: Bavishi Aakash , Colangelo Laura A. , Rasmussen‐Torvik Laura J. , Lima Joao A.C. , Nannini Drew R. , Vaduganathan Muthiah , Pandey Ambarish , Lloyd‐Jones Donald M. , Shah Sanjiv J. , Patel Ravi B.
Published: February 2022

Aims

The effects of inhibition of sodium glucose cotransporter (SGLT)‐1, as opposed to SGLT2, on cardiovascular structure and function are not well known. We assessed the associations of a missense genetic variant of SGLT1 with cardiac structure and function.

Methods and results

We evaluated associations of a functionally modifying variant of SLC5A1 (rs17683011 [p.Asn51Ser]), the gene that encodes SGLT1, with cardiac structure and function on echocardiography among middle‐aged adults in the Coronary Artery Risk Development in Young Adults Study. Of 1904 participants (55.3 ± 3.5 years, 57% female, 34% Black), 166 (13%) White participants and 18 (3%) Black participants had at least one copy of rs17683011. There were no significant differences in age, sex, body mass index, glucose, or diabetes status by the presence of the rs17683011 variant. In Black participants, the presence of at least one copy of the rs17683011 variant was significantly associated with better GLS compared with those without a copy of the variant after covariate adjustment (−15.8 ± 0.7% vs. −14.0 ± 0.1%, P = 0.02). Although the direction of effect was consistent, the association between the presence of at least one copy of rs17683011 and GLS was not statistically significant in White participants (−15.1 ± 0.2% vs. −14.8 ± 0.1%, P = 0.16). There were no significant associations between rs17683011 and other measures of LV structure, systolic function, or diastolic function.

Conclusions

The rs17683011 variant, a functionally modifying variant of the SGLT1 gene, was associated with higher GLS among middle‐age adults. These exploratory findings require further validation and suggest that SGLT1 inhibition may have beneficial effects upon LV systolic function.
Right atrial pressure represents cumulative cardiac burden in heart failure with preserved ejection fraction
Authors: Nagata Reika , Harada Tomonari , Omote Kazunori , Iwano Hiroyuki , Yoshida Kotaro , Kato Toshimitsu , Kurosawa Koji , Nagai Toshiyuki , Anzai Toshihisa , Obokata Masaru
Published: February 2022

Aims

Right‐sided filling pressure is elevated in some patients with heart failure (HF) and preserved ejection fraction (HFpEF). We hypothesized that right atrial pressure (RAP) would represent the cumulative burden of abnormalities in the left heart, pulmonary vasculature, and the right heart.

Methods and results

Echocardiography was performed in 399 patients with HFpEF. RAP was estimated from inferior vena cava morphology and its respiratory change [estimated right atrial pressure (eRAP)], and patients were divided according to eRAP (3 or ≥8 mmHg). Patients with higher eRAP displayed more severe abnormalities in LV diastolic function as well as right heart structure and function than those with normal eRAP. Cardiac deaths or HF hospitalization occurred in 84 patients over a median follow‐up of 19.0 months (interquartile range 6.7–36.9). The presence of higher eRAP was independently associated with an increased risk of the composite outcome (adjusted hazard ratio 2.20 vs. normal eRAP group, 95% confidence interval 1.34–3.62, P = 0.002). Kaplan–Meier curves separating the patients into four groups based on eRAP and E/e' ratio showed that event‐free survival varied among the groups, providing an incremental prognostic value of eRAP over E/e' ratio. The classification and regression tree analysis demonstrated that eRAP was the strongest predictor of the outcome followed by right ventricular dimension, E/e' ratio, and estimated right ventricular systolic pressure, stratifying the patients into four risk groups (incident rate 8.8–72.2%).

Conclusions

These data may provide new insights into the prognostic role of RAP in the complex pathophysiology of HFpEF and suggest the utility of eRAP for the risk stratification in patients with HFpEF.
Mirror‐Image Magnetic Circularly Polarized Luminescence from Perovskite (M+Pb2+Br3, M+=Cs+ and Amidinium) Quantum Dots
Authors: Amasaki Ryo , Kitahara Maho , Kimoto Takahiro , Fujiki Michiya , Imai Yoshitane
Published: February 2022

Ambidextrous magnetic circularly polarized luminescence (MCPL) and redshift in photoluminescence (PL) spectra are observed from two types of achiral soluble diamagnetic perovskite‐Pb‐quantum dots in toluene solution at room temperature, when subjected to external north‐up and south‐up magnetic fields of 1.7 T. The magnitude of the MCPL, gMCPL, is in the order of |gMCPL|=10−3 within a wavelength range of 480–580 nm. The wavelength and the sign of the MCPL spectra can be controlled by the types of perovskite constituent atom and the direction of the magnetic field, respectively.
Carbonic Anhydrase Inhibitors Featuring a Porphyrin Scaffold: Synthesis, Optical and Biological Properties
Authors: Merabti Amina , Roger Maxime , Nguyen Christophe , Nocentini Alessio , Gerbier Philippe , Richeter Sébastien , Gary‐Bobo Magali , Supuran Claudiu T. , Clément Sébastien , Winum Jean‐Yves
Published: February 2022

The synthesis, characterization and study of optical properties of innovative tetrafunctionalized zinc(II) porphyrins with carbonic anhydrase (CA) inhibitors in sulfonamide and coumarin series are described. The synthetic methodology relies on the preparation of the porphyrin core by condensation of azido triethyleneglycol functionalized benzaldehyde derivative with pyrrole followed by its metalation and inhibitors couplingviaHuisgen click‐reaction. The tetrafunctionalized zinc(II) porphyrin with coumarin moieties showed selective inhibition against tumour‐associated hCA IX and hCA XIIversusthe cytosolic off‐targets hCA I and hCA II. This compound was able to accumulate on cell membrane and to impair pancreas cancer cells (Capan‐1) proliferation in normoxic conditions with LC50of 4.5 μM. Moreover, its optical properties revealed efficient photosensitizing properties, leading to cancer cells death under light irradiation, making this compound a suitable candidate for photodynamic therapy.
Thermal Performance of Reverse‐Layered Air‐Cooled Cylindrical Lithium Battery Pack Integrated with Staggered Battery Arrangement and Spoiler
Authors: Zhang Furen , Zhu Yilin , Ge Zhe
Published: February 2022

In order to improve the cooling performance of the reverse layered air‐cooled cylindrical lithium‐ion battery pack, a structure optimization design scheme integrated with a staggered battery arrangement and longitudinal spoiler was proposed. Based on the computational fluid dynamics (CFD) method, the cooling performance of an air‐cooled battery thermal management system (BTMS) was studied, and the reliability of CFD calculation results was verified by the forced air cooling experiment of the battery pack. Firstly, the effect of a staggered arrangement of batteries on the cooling performance of the battery pack was explored. The results revealed that the hybrid staggered arrangement of the batteries greatly improved the heat dissipation performance of the cooling system. Compared with the initial condition, the maximum temperature (Tmax) and maximum temperature difference (ΔTmax) were reduced by 12.73 °C (24.96%) and 7.7 °C (87.8%), respectively. However, the problems of high temperature of batteries and poor temperature uniformity of the battery pack still existed. Secondly, the cooling performance of BTMS was further improved by constructing the structure integrated with hybrid staggered arrangement and longitudinal spoilers. The results respectively revealed that Tmax and ΔTmax were decreased by 13.06 °C (25.6%) and 8.45 °C (96.35%). Finally, the influences of the length, thickness, and number of spoilers were discussed.
Transport and Electrochemical Properties of NaxFe1–yMnyO2‐Cathode Materials for Na‐Ion batteries. Experimental and Theoretical Studies
Authors: Walczak Katarzyna , Redel Katarzyna , Idczak Rafał , Konieczny Robert , Idczak Karolina , Tran Vinh Hung , Plewa Anna , Ziąbka Magdalena , Rybski Michał , Tobola Janusz , Molenda Janina
Published: February 2022

Herein, Na
x
Fe1–y
Mn
y
O2 (y = 0.4, 0.5, 0.6, 0.7, and 0.8) oxides, which are a potential cathode materials group for Na‐ion batteries, are presented. Samples are prepared by solid‐state synthesis and crystallized in P2‐type structure (P63/mmc). Mössbauer spectroscopy studies revealed that in pristine and deintercalated samples the whole iron occurs at a high‐spin Fe3+ state. Electrochemical impedance spectroscopy measurements exhibited the thermally activated electrical conductivity of Na0.67Fe1–y
Mn
y
O2 with relatively high activation energies (≈0.4 eV). Obtained results are supported by the electronic structure calculations (KKR‐CPA method), which indicates that total density of states at the Fermi level increases with manganese content in the sample. Electrochemical properties of Na|Na+|Na
x
Fe1–y
Mn
y
O2 test cells and the specific charge/discharge capacities analysis confirmed that only the manganese ions in Na
x
Fe1–y
Mn
y
O2 are active in electrochemical processes and higher content of manganese results in obtaining higher specific capacities (≈150 mAh g−1 for y = 0.8 under C/10 current load).
Artificial habitat structures for animal conservation: design and implementation, risks and opportunities
Authors: Watchorn Darcy J , Cowan Mitchell A , Driscoll Don A , Nimmo Dale G , Ashman Kita R , Garkaklis Mark J , Wilson Barbara A , Doherty Tim S
Published: February 2022

Habitat loss and degradation, and their interaction with other threats, are driving declines in animal populations worldwide. One potential approach for mitigating these threats is to create artificial habitat structures as substitutes for lost or degraded natural structures. Here, we provide – to the best of our knowledge – the first general definition of artificial habitat structures and synthesize important considerations for their effective use. We show that such structures represent a versatile conservation tool that has been trialed in a variety of contexts globally, albeit with varying degrees of success. The design of these structures must be well informed by the drivers of natural habitat selection, and their use should be part of an experimental framework to enable evaluation and refinement. We highlight possible ecological risks associated with the use of artificial habitat structures and urge that they not be exploited as inappropriate biodiversity offsets or for greenwashing. Looking forward, cross‐disciplinary collaborations will facilitate the development of sophisticated and effective structures to assist animal conservation in this era of rapid global change.
Premature Mortality Observations among Alaska’s Pacific Salmon During Record Heat and Drought in 2019
Authors: Biela Vanessa R. , Sergeant Christopher J , Carey Michael P , Liller Zachary , Russell Charles , Quinn-Davidson Stephanie , Rand Peter S , Westley Peter A.H , Zimmerman Christian E
Published: February 2022

Widespread mortality of Pacific salmon Oncorhynchus spp. returning to spawn in Alaska coincided with record-breaking air temperatures and prolonged drought in summer 2019. Extreme environmental conditions are expected to happen more frequently with rapid climate change and challenge the notion that Alaska could indefinitely provide abundant, cool freshwater habitat for Pacific salmon. A total of 110 geographically widespread opportunistic observations of premature mortality (carcasses) were collected from a variety of sources. Premature mortalities were documented for Pink Salmon Oncorhynchus gorbuscha, Sockeye Salmon O. nerka, Chum Salmon O. keta, Chinook Salmon O. tshawytscha, and Coho Salmon O. kisutch. Additionally, observations of Pink Salmon returning to spawn in Prince William Sound streams in 2019, obtained from systematic aerial surveys conducted annually, revealed low migration success in 87% of rain-driven streams (n = 30), 52% of snow-driven streams (n = 65), and only 18% of glacier-driven streams (n = 11). Salmon mortality observations were consistent with death due to heat stress resulting from high water temperatures or drought caused hypoxia and stranding. Developing a better understanding of how broad-scale climate patterns manifest at the stream scale can help us determine whether a major shift in Pacific salmon productivity is underway and inform fisheries management plans to better mitigate future risks.
Active tectonics in the upper reaches of the Yellow River from Lagan Gorge to Liujia Gorge, northwestern China: Insights from geomorphic indices
Authors: Ji Yiqi , Su Shengrui , Huang Qiangbing
Published: February 2022

The drainage basin of the upper reaches of the Yellow River from Lagan Gorge to Liujia Gorge, which spans Gonghe, Guide, Jianzha, Xunhua and Linxia basins, is located in the transition zone between the Qinghai–Tibet Plateau and the Loess Plateau, northwestern China. Its evolution is controlled by the northeastward growth and uplift of the Qinghai–Tibet Plateau. To characterize and quantify the response of surface processes to deep geological mechanisms and to investigate the types of Late Cenozoic tectonic deformation in the study area and the relationship with large geological hazards, we analysed various geomorphological indicators, combined with field observations and the estimated incision rates and established a reasonable tectonic deformation model. The results demonstrate that the variations in the geomorphic indices are highly consistent with active tectonics. Higher hypsometric integral (HI), higher normalized stream length‐gradient index (SLK), higher basin asymmetry factor (AF), higher drainage basin shape (BS) and lower ratios of valley floor width to valley height (VF) indicate higher tectonic uplift rate in the Jianzha‐Xunhua basins compared to other basins where there are many giant landslides. These giant landslides occurring there can probably be correlated with the vigorous tectonic activity, thus generating a great significance in geological hazard prevention and control along the upper Yellow River.
Chidamide with PEL regimen (prednisone, etoposide, lenalidomide) for elderly or frail patients with relapsed/refractory diffuse large B‐Cell lymphoma ‐results of a single center, retrospective cohort in China
Authors: Wang Yawen , Xue Hongwei , Song Wei , Xiao Shuxin , Jing Fanjing , Dong Tieying , Wang Lili
Published: February 2022

Treatment for relapsed/refractory Diffuse Large B‐Cell Lymphoma (R/R DLBCL) is evolving rapidly due to the emergence of novel drugs, of which histone deacetylase inhibitors (HDACis) are an important example. This study showed efficacy in patients with R/R DLBCL after failure of conventional therapies. We conducted a single‐center, retrospective study of 34 frail or elderly R/R DLBCL patients who had been treated off‐label with chidamide‐containing regimens from 2018 to 2020. X2 or Fisher test were used to compare response rate and Kaplan‐Meier method was used to perform the survival analyses which compared with log‐rank test between different groups. The test standard was p < 0.05. In total, 34 patients with R/R DLBCL received CPEL+/‐R for at least 1 cycle were included. Most of them were refractory patients (n = 28,82.4%). The interim objective response rate (ORR) was 73.5% (32.4% complete remission [CR]), and the ultimate ORR was 50.0% (35.3% CR). After a median follow‐up of 13.1 months, the median progression‐free survival (PFS) was 10.5 months (95%CI 6.4–14.6) and the median overall survival (OS) was 19.3 months (95%CI 11.8–26.9). The 1 year expected PFS and OS rate was 43.0% and 73.7%, respectively. The most common grade 3/4 hematologic adverse events (AEs) were neutropenia (n = 11,32.3%) and anemia (n = 4, 11.8%) 0.23.5% (8/34) of all patients experienced grade 3/4 nonhematologic AEs. No treatment‐related deaths were observed. The study showed chidamide‐included regimen could be an option for R/R DLBCL patients ineligible for intensive chemotherapies. Current data showed favorable efficiency and moderate safety profile. Further study is warranted for better illustration of efficacy and usage in combination therapies.
Cubic B‐splines method for Hall and ion slip impacts on unsteady MHD rotating flow past a vertical moving porous plate
Authors: Kumar S. Abhilash Anand , Ibrahim S. Md.
Published: February 2022

The heat and mass transfer of unsteady magnetohydrodynamic (MHD) flow of Newtonian fluid with Hall current and ion‐slip currents due to vast possible engineering applications is very important in areas like power generators, MHD accelerators, refrigeration coils, electric transformers, and heating elements. A quality‐based research on Hall and ion‐slip consequences on the rotating unsteady MHD flow past an infinite perpendicular moving absorbent plate have not been performed. Therefore, the Hall and ion‐slip consequences on rotating unsteady MHD flow past an infinite perpendicular moving absorbent plate have not been performed. The similarity transformations are engaged to transfer the governing partial differential equations within favor of the scheme of nonlinear ordinary differential equations and elucidated numerically making use of cubic B‐splines collocation mechanism. The influences of felicitous parameters on basic equations are remarked on through graphical profiles. Even though the computational estimations of frictional forces, Nusselt number, and Sherwood number for various parameters are distributed in tabular format and exchanged of views comparatively.
Cellular osmoregulation of the ark clam (Anadara kagoshimensis) hemocytes to hyposmotic media
Authors: Kladchenko Ekaterina S. , Andreyeva Aleksandra Y. , Mindukshev Igor V. , Gambaryan Stepan
Published: February 2022

Many bivalve species are considered to be euryhaline organisms due to effective adaptation to fluctuations of environmental salinity. Cellular mechanisms responsible for tolerance to salinity changes remain unclear for bivalves despite this question being critically important for commercially cultured species frequently introduced into regions differing from natural habitat by salinity regime. In the present work laser diffraction method was used for the analysis of volume changes in hemoglobin‐containing ark clam (Anadara kagoshimensis) hemocytes following hyposmotic stimulation. Hemocytes responded to hyposmotic shock (decrease of media osmolarity from 461 to 216 mОsm/L) by a rapid swelling up to 171.5 ± 15.2% of control level. At normal osmotic conditions (osmolarity 461 mOsm/L), hemocyte mean cellular volume (MCV) was 354.0 ± 24.4 fl and maximum MCV of hyposmotically swollen cells prior lysis was 555.5 ± 57.4 fl (at the osmolarity 194 mOsm/L). Ark clam hemocytes demonstrated volume recovery response following hyposmotic swelling. Regulatory volume decrease (RVD) reaction did not depend on hemoglobin confirmation status. Final MCV of swollen hemocytes at the end of experimental period of RVD in oxygenated and deoxygenated suspensions did not significantly differ.
Does the thermal mismatch hypothesis predict disease outcomes in different morphs of a terrestrial salamander?
Authors: Venesky Matthew D. , DeMarchi Joseph , Hickerson Cari , Anthony Carl D.
Published: February 2022

Many aspects of ectotherm physiology are temperature‐dependent. The immune system of temperate‐dwelling ectothermic host species is no exception and their immune function is often downregulated in cold temperatures. Likewise, species of ectothermic pathogens experience temperature‐mediated effects on rates of transmission and/or virulence. Although seemingly straightforward, predicting the outcomes of ectothermic host−pathogen interactions is quite challenging. A recent hypothesis termed the thermal mismatch hypothesis posits that cool‐adapted host species should be most susceptible to pathogen infection during warm temperature periods whereas warm‐adapted host species should be most susceptible to pathogens during periods of cool temperatures. We explore this hypothesis using two ecologically and physiologically differentiated color morphs of the Eastern Red‐backed Salamander (Plethodon cinereus) and a pathogenic chytrid fungus (Batrachochytrium dendrobatidis; hereafter “Bd”) using a fully factorial laboratory experiment. At cool temperatures, unstriped salamanders (i.e., those that are tolerant of warm temperatures) had a significantly higher probability of Bd infection compared with cool‐tolerant striped salamanders, consistent with the thermal mismatch hypothesis. However, we found no support for this hypothesis when salamanders were exposed to Bd at warm temperatures: the probability of Bd infection in the cool‐tolerant striped salamanders was nearly identical in both cool and warm temperatures, opposite the predictions of the thermal mismatch hypothesis. Our results are most consistent with the fact that Bd grows poorly at warm temperatures. Alternatively, our data could indicate that the two color morphs do not differ in their tolerance to warm temperatures but that striped salamanders are more tolerant to cool temperatures than unstriped salamanders.
Gadolinium Retention in the Brain of Mother and Pup Mouse: Effect of Pregnancy and Repeated Administration of Gadolinium‐Based Contrast Agents
Authors: Yao Xiang , Zhang Haoran , Shi Dafa , Li Yanfei , Guo Qiu , Yu Ziyang , Wang Siyuan , Ren Ke
Published: February 2022

Background

The association of repeated administration of gadolinium‐based contrast agents (GBCAs) with the gadolinium (Gd) retention in the brains of mother and fetus remains unclear.

Purpose

To investigate the effects of pregnancy and repeated administration of GBCAs on Gd retention in the brains of mother and pup mice.

Study type

Cross‐sectional cohort toxicity study.

Animal Model

From gestational days 16–19, pregnant (n = 48) BALB/c mice.

Field Strength

A 9.4 T and fast spin echo sequence.

Assessment

Half of the mother mice (n = 24) were killed at postnatal day 1 (P1) for inductively coupled plasma mass spectrometry (ICP‐MS) and transmission electron microscopy (TEM). Besides the ICP‐MS and TEM, four pups were randomly selected from each mother and killed at P1 for ultraperformance liquid chromatography mass spectrometry (UPLC‐MS) and Nissl staining.

Statistical Tests

One‐way analysis of variance and unpaired t‐test.

Results

In the group of gadodiamide, retention of Gd in the brains of pregnant mice was significantly lower than that of nonpregnant mice in the area of the deep cerebellar nuclei (DCN) (10.35 ± 2.16 nmol/g vs. 18.74 ± 3.65 nmol/g). Retention of Gd in the DCN of pups whose mothers were administered gadoterate meglumine was significantly lower than that of pups whose mothers were administered gadodiamide (0.21 ± 0.09 nmol/g vs. 6.15 ± 3.21 nmol/g) at P1. In mice treated with gadodiamide, most of the retained Gd in the brain tissue was insoluble (19.5% ± 9.5% of the recovered amount corresponded to the intact complex in the DCN).

Data Conclusion

In different brain areas of the mother and pup mice, the retention of Gd after gadoterate meglumine administration was lower than that of gadodiamide and gadopentetate dimeglumine administration, and almost all the detected Gd in pups' brains was intact soluble GBCAs.

Evidence Level

1

Technical Efficacy

Stage 2
Hallucinogenic drugs and their potential for treating fear‐related disorders: Through the lens of fear extinction
Authors: Glavonic Emilija , Mitic Milos , Adzic Miroslav
Published: February 2022

Fear‐related disorders, mainly phobias and post‐traumatic stress disorder, are highly prevalent, debilitating disorders that pose a significant public health problem. They are characterized by aberrant processing of aversive experiences and dysregulated fear extinction, leading to excessive expression of fear and diminished quality of life. The gold standard for treating fear‐related disorders is extinction‐based exposure therapy (ET), shown to be ineffective for up to 35% of subjects. Moreover, ET combined with traditional pharmacological treatments for fear‐related disorders, such as selective serotonin reuptake inhibitors, offers no further advantage to patients. This prompted the search for ways to improve ET outcomes, with current research focused on pharmacological agents that can augment ET by strengthening fear extinction learning. Hallucinogenic drugs promote reprocessing of fear‐imbued memories and induce positive mood and openness, relieving anxiety and enabling the necessary emotional engagement during psychotherapeutic interventions. Mechanistically, hallucinogens induce dynamic structural and functional neuroplastic changes across the fear extinction circuitry and temper amygdala's hyperreactivity to threat‐related stimuli, effectively mitigating one of the hallmarks of fear‐related disorders. This paper provides the first comprehensive review of hallucinogens' potential to alleviate symptoms of fear‐related disorders by focusing on their effects on fear extinction and the underlying molecular mechanisms. We overview both preclinical and clinical studies and emphasize the advantages of hallucinogenic drugs over current first‐line treatments. We highlight 3,4‐methylenedioxymethamphetamine and ketamine as the most effective therapeutics for fear‐related disorders and discuss the potential molecular mechanisms responsible for their potency with implications for improving hallucinogen‐assisted psychotherapy.
Asymmetrical synchronization of extreme rainfall events in southwest China
Authors: Qiao Panjie , Gong Zhiqiang , Liu Wenqi , Zhang Yongwen , Feng Guolin
Published: February 2022

Based on the complex network method, this study reveals the temporal and spatial characteristics of the synchronization of extreme rainfall events in southwest China (SWC) during the main rainfall season (May–September). Our results show the significant synchronization pattern of extreme rainfall events in SWC, which is closely associated with the convergence of warm‐wet air and cold‐dry air and the corresponding occurrence of extreme rainfall in SWC. The network divergence indicates a dominated direction of the net influence of extreme rainfall from the Sichuan Basin to the Yunnan–Guizhou Plateau, implying the extreme rainfall synchronization moving from north to south in SWC is more frequent than the opposite direction. The development of the low vortex and the north wind system usually shows a movement from north to south, resulting in the evolution of extreme rainfall events more tend to present a southward movement. The low‐reinforced latitude cyclonic circulation leads to the strengthened transportation of water vapour from the tropical area to the north and converges with the anticyclonic circulation in the mid‐latitudes to form the movement of heavy rainfall events from the Yunnan–Guizhou Plateau to the Sichuan Basin. Therefore, the synchronization direction of extreme rainfall events in SWC has obvious asymmetry spatial feature due to the more frequent and stronger circulation system moving from north to south than the opposite.