bluuebunny/crossref_metadata_2025 huggingface dataset:
Emissive Platinum(II) Macrocycles as Tunable Cascade Energy Transfer Scaffolds
Authors: Acharyya Koushik , Bhattacharyya Soumalya , Lu Shuai , Sun Yan , Mukherjee Partha Sarathi , Stang Peter J.
Published: February 2022

Developing artificial light‐harvesting scaffolds with a cascade energy transfer process is significant for better understanding of photosynthesis. Here, we report [3+3] self‐assembled PtII fluorescent macrocycles (3 a and 3 b) as light‐harvesting platforms with cascade energy transfer. The PtII macrocycles aggregate into nanospheres and show emission‐enhancement characteristics upon increasing water content in acetone medium. These aggregates (3aa and 3ba) serve as energy donors when mixed with the hydrophobic dye Eosin‐Y (ESY). In the presence of a second dye, Nile Red (NiR), an unusual sequential two‐step energy transfer takes place from the macrocycles to NiR. In this case, ESY acts as a bridge in the relay mode. Additionally, a unique strategy to control such an energy transfer process by tuning the chain length of the alkyl group attached to the periphery of the macrocycles is demonstrated.
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Authors: Munari Francesca , Mollica Luca , Valente Carlo , Parolini Francesca , Kachoie Elham Ataie , Arrigoni Giorgio , D'Onofrio Mariapina , Capaldi Stefano , Assfalg Michael
Published: February 2022

The multi‐site ubiquitination of Tau protein found in Alzheimer's disease filaments hints at the failed attempt of neurons to remove early toxic species. The ubiquitin‐dependent degradation of Tau is regulated in vivo by the E3 ligase CHIP, a quality controller of the cell proteome dedicated to target misfolded proteins for degradation. In our study, by using site‐resolved NMR, biochemical and computational methods, we elucidate the structural determinants underlying the molecular recognition between the ligase and its intrinsically disordered substrate. We reveal a multi‐domain dynamic interaction that explains how CHIP can direct ubiquitination of Tau at multiple sites even in the absence of chaperones, including its typical partner Hsp70/Hsc70. Our findings thus provide mechanistic insight into the chaperone‐independent engagement of a disordered protein by its E3 ligase.
A Polymeric Nanobeacon for Monitoring the Fluctuation of Hydrogen Polysulfides during Fertilization and Embryonic Development
Authors: Zhou Yibo , Gu Zhengxuan , Liu Changhui , Yang Sheng , Ma Xiaofei , Chen Qiaoshu , Lei Yanli , Quan Ke , Liu Juewen , Qing Zhihe , Yang Ronghua
Published: February 2022

Fertilization and early embryonic development as the beginning of a new life are key biological events. Hydrogen polysulfide (H2Sn) plays important roles during physiological regulation, such as antioxidation‐protection. However, no report has studied in situ H2Sn fluctuation during early embryonic development because of the low abundance of H2Sn and inadequate sensitivity of probes. We herein construct a polymeric nanobeacon from a H2Sn‐responsive polymer and fluorophores, which is capable of detecting H2Sn selectively and of signal amplification. Taking the zebrafish as a model, the polymeric nanobeacon revealed that the H2Sn level was significantly elevated after fertilization due to the activation of cell multiplication, suppressed partially during embryonic development, and finally kept steady up to zebrafish emergence. This strategy is generally accessible for biomarkers by altering the responsive unit and significant for facilitating biological analysis during life development.
Haptotropism in a Nickel Complex with a Neutral, π‐Bridging cyclo‐P4 Ligand Analogous to Cyclobutadiene
Authors: Gendy Chris , Valjus Juuso , Tuononen Heikki M. , Roesler Roland
Published: February 2022

Dedicated to Professor Manfred Scheer on the occasion of his 65th birthday

The reaction of (1)Ni(η2‐cod), 2, incorporating a chelating bis(N‐heterocyclic carbene) 1, with P4 in pentane yielded the dinuclear complex [(2)Ni]2(μ2,η2 : η2‐P4), 3, formally featuring a cyclobutadiene‐like, neutral, rectangular, π‐bridging P4‐ring. In toluene, the butterfly‐shaped complex [(1)Ni]2(μ2,η2 : η2‐P2), 4, with a formally neutral P2‐unit was obtained from 2 and either P4 or 3. Computational studies showed that a haptotropic rearrangement involving two isomers of the μ2,η2 : η2‐P4 coordination mode and a low‐energy μ2,η4 : η4‐P4 coordination mode, as previously predicted for related nickel cyclobutadiene complexes, could explain the coalescence observed in the low‐temperature NMR spectra of 3. The insertion of the (1)Ni fragment into a P−P bond of P7(SiMe3)3, forming complex 5 with a norbornane‐like P7 ligand, was also observed.
Oxidative Additions of C−F Bonds to the Silanide Anion [Si(C2F5)3]−
Authors: Tiessen Natalia , Keßler Mira , Neumann Beate , Stammler Hans‐Georg , Hoge Berthold
Published: February 2022

Compounds exhibiting main group elements in low oxidation states were found to mimic the reactivity of transition metal complexes. Like the latter, such main group species show a proclivity of changing their oxidation state as well as their coordination number by +2, therefore fulfilling the requirements for oxidative additions. Prominent examples of such main group compounds that undergo oxidative additions with organohalides R−X (R=alkyl, aryl, X=F, Cl, Br, I) are carbenes and their higher congeners. Aluminyl anions, which like carbenes and silylenes oxidatively add to strong σ‐bonds in R−X species, have been recently discovered. We present the first anion based upon a Group 14 element, namely the tris(pentafluoroethyl)silanide anion, [Si(C2F5)3]−, which is capable of oxidative additions towards C−F bonds. This enables the isolation of non‐chelated tetraorganofluorosilicate salts, which to the best of our knowledge had only been observed as reactive intermediates before.
Widefield SERS for High‐Throughput Nanoparticle Screening
Authors: Liebel Matz , Calderon Irene , Pazos‐Perez Nicolas , van Hulst Niek F. , Alvarez‐Puebla Ramon A.
Published: February 2022

Surface‐enhanced Raman scattering (SERS) imaging is a powerful technology with unprecedent potential for ultrasensitive chemical analysis. Point‐by‐point scanning and often excessively long spectral acquisition‐times hamper the broad exploitation of the full analytical potential of SERS. Here, we introduce large‐scale SERS particle screening (LSSPS), a multiplexed widefield screening approach to particle characterization, which is 500–1000 times faster than typical confocal Raman implementations. Beyond its higher throughput, LSSPS simultaneously quantifies both the sample's Raman and Rayleigh scattering to directly quantify the fraction of SERS‐active particles which allows for an unprecedented correlation of SERS activity with particle size. .
Remotely triggered curcumin release from stimuli‐responsive magneto‐polymericlayer‐by‐layerengineered nanoplatforms
Authors: Jardim Katiúscia Vieira , Palomec‐Garfias Abraham F. , Araújo Marcus Vinícius , Márquez‐Beltrán César , Bakuzis Andris Figueiroa , Moya Sergio Enrique , Parize Alexandre Luis , Sousa Marcelo Henrique
Published: February 2022

Curcumin is a promising natural drug in cancer therapy. However, its therapeutic applicability is limited by its low solubility, short half‐life, and low bioavailability. In this work curcumin is encapsulated in stimuli‐responsive magneto‐polymeric nanoplatforms aiming at improving its bioavailability and efficiency for delivery in biological media. MnFe2O4magnetic nanoparticles (MNPs) were synthesized via thermal decomposition, coated with sodium citrate and then functionalized with multilayers of chitosan and sodium alginate, by means of the layer‐by‐layer deposition technique. A mesoporous polymeric‐magnetic nanoplatform was produced capable of a controlled and sustained release of curcumin under temperature, pH and alternating magnetic field (magnetic hyperthermia) stimuli. As the temperature and pH of the medium increased, an increase in the rate of curcumin release was observed in a two‐stage process, following the Gallagher‐Corrigan mathematical model. The use of magnetic hyperthermia resulted in a faster diffusion‐based release of curcumin. Increasing the number of polymer layers assembled on top of MNPs hinders the release of the curcumin molecules from innermost regions of the multilayers. These results show that magnetic hyperthermia provides a means for the controlled heat‐induced release of curcumin, which can lead to an enhanced therapeutic action for curcumin.
First‐in‐class pyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones against leishmaniasis and tuberculosis: Rationale, in vitro, ex vivo studies and mechanistic insights
Authors: Ramesh Deepthi , Sarkar Deblina , Joji Annu , Singh Monica , Mohanty Amaresh K. , G. Vijayakumar Balaji , Chatterjee Mitali , Sriram Dharmarajan , Muthuvel Suresh K. , Kannan Tharanikkarasu
Published: February 2022

Pyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones were synthesized, for the first time, from indole chalcones and 6‐aminouracil, and their ability to inhibit leishmaniasis and tuberculosis (Tb) infections was evaluated. The in vitro antileishmanial activity against promastigotes of Leishmania donovani revealed exceptional activities of compounds 3, 12 and 13, with IC50 values ranging from 10.23 ± 1.50 to 15.58 ± 1.67 µg/ml, which is better than the IC50 value of the standard drug pentostam of 500 μg/ml. The selectivity of the compounds towards Leishmania parasites was evaluated via ex vivo studies in Swiss albino mice. The efficiency of these compounds against Tb infection was then evaluated using the in vitro anti‐Tb microplate Alamar Blue assay. Five compounds, 3, 7, 8, 9 and 12, showed MIC100 values against the Mycobacterium tuberculosis H37Rv strain at 25 µg/ml, and compound 20 yielded an MIC100 value of 50 µg/ml. Molecular modelling of these compounds highlighted interactions with binding sites of dihydrofolate reductase, pteridine reductase and thymidylate kinase, thus establishing the rationale of their pharmacological activity against both pathogens, which is consistent with the in vitro results. From the above results, it is clear that compounds 3 and 12 are promising lead candidates for Leishmania and Mycobacterium infections and may be promising for coinfections.
Initial energy of a spatially flat universe: A hint of its possible origin
Authors: Melia Fulvio
Published: February 2022

The evidence for a Big Bang origin of the universe is truly compelling, though its cause remains a complete mystery. As the cosmic spacetime is revealed to us with ever‐improving detail, however, we are beginning to refine the range of its possible initial conditions—at least within the framework of current physical theories. The universe, it seems, is spatially flat, and here we discuss in clear, straightforward terms why this trait implies a cosmos with zero kinetic plus gravitational energy, though apparently not zero total energy. Such an outcome has far reaching consequences because of the possibility that the universe may have begun its existence as a quantum fluctuation. Was this from “nothing,” or perhaps a preexisting vacuum? A nonzero total energy would seemingly preclude the former scenario, but not necessarily the latter, though this would then raise the question of how a fluctuation with nonzero energy could have lived long enough, or classicalized, for us to see it 13.5 billion years later. The high‐precision measurement of the universe's spatial curvature may thus constitute the first tangible piece of evidence impacting a possible quantum beginning.
Glymphatic system function in patients with newly diagnosed focal epilepsy
Authors: Lee Dong Ah , Park Bong Soo , Ko Junghae , Park Si hyung , Park Jin‐Han , Kim Il Hwan , Lee Yoo Jin , Park Kang Min
Published: February 2022

Introduction

The aim of this study was to analyze the glymphatic system function and its relationship with clinical characteristics, global diffusion tensor imaging (DTI) parameters, and global structural connectivity in treatment‐naïve patients with newly diagnosed focal epilepsy.

Methods

This retrospective single‐center study investigated patients with focal epilepsy and healthy controls. All participants underwent routine brain magnetic resonance imaging and DTI. DTI analysis along the perivascular space (DTI‐ALPS) was used to evaluate glymphatic system function. We also calculated the measures of global DTI parameters, including whole‐brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and performed a graph theoretical network analysis to measure global structural connectivity.

Results

A total of 109 patients with focal epilepsy and 88 healthy controls were analyzed. There were no significant differences in the DTI‐ALPS index (1.67 vs. 1.68, p = 0.861) between the groups. However, statistically significant associations were found between the DTI‐ALPS index and age (r = ‐0.242, p = 0.01), FA (r = 0.257, p = 0.007), MD (r = −0.469, p < 0.001), AD (r = −0.303, p = 0.001), RD (r = −0.434, p < 0.001), and the assortative coefficient (r = 0.230, p = 0.016) in patients with focal epilepsy.

Conclusion

The main finding of this study is that DTI‐ALPS index is significantly correlated with global DTI parameters and structural connectivity measures of the brain in patients with focal epilepsy. In addition, DTI‐ALPS index decreases with age in these patients. We conclude that the DTI‐ALPS index can be used to investigate glymphatic system function in patients with focal epilepsy.
Rippled Sheets: The Early Polyglycine Days and Recent Developments in Nylons
Authors: Lotz Bernard
Published: February 2022

The rippled sheet structure is a remarkable insight due to Pauling and Corey, that supplements the pleated sheet structure of homochiral proteins introduced in 1951. Whereas the pleated sheet was immediately adopted by the scientific community, the rippled sheet has remained more confidential since it applies only to blends of poly(L‐peptides) and poly(D‐peptides). The present account tells the intimate but patchy relationship developed by the author with the rippled sheet. In the 1970s, twenty years after Pauling and Corey's proposal, the rippled sheet was recognized as a valid model for the sheet structure of the achiral polyglycine, polyglycine I, which helped improve the structure of Bombyx mori silk fibroin. Very recently, pleated and rippled sheets were found to account for unsolved crystal structures of a variety of nylons. These structures help to explain a mysterious high temperature “Brill transition” first reported in nylon 6–6 by Brill in 1942.
Solid‐Phase Synthesis and Application of a Clickable Version of Epoxomicin for Proteasome Activity Analysis
Authors: Salazar‐Chaparro Andres F. , Halder Saayak , Maresh Marianne E. , Trader Darci J.
Published: February 2022

Degradation of proteins by the proteasome is an essential cellular process and one that many wish to study in a variety of disease types. There are commercially available probes that can monitor proteasome activity in cells, but they typically contain common fluorophores that limit their simultaneous use with other activity‐based probes. In order to exchange the fluorophore or incorporate an enrichment tag, the proteasome probe likely has to be synthesized which can be cumbersome. Here, we describe a simple synthetic procedure that only requires one purification step to generate epoxomicin, a selective proteasome inhibitor, with a terminal alkyne. Through a copper‐catalyzed cycloaddition, any moiety containing an azide can be incorporated into the probe. Many fluorophores are commercially available that contain an azide that can be “clicked”, allowing this proteasome activity probe to be included into already established assays to monitor both proteasome activity and other cellular activities of interest.
Nocardia asteroides occipital abscess as a cause of lupus nephritis?
Authors: Essien Francis , Wolfley Graey , Tate Joshua , Latack Wayne , Carroll Matthew
Published: February 2022

Systemic lupus erythematosus (SLE) is a multisystem disease with a complex etiology, which manifests in a multitude of manners. We present a case of lupus nephritis in a patient who developed complications of immunosuppressive treatment with eventual resolution of her nephritis following cure of her Nocardia brain abscess.
A case of a verrucous and pseudotumoral mass on the leg that resolved with cryotherapy
Authors: Rekik Mariem , Sellami Khadija , Amouri Mariem , Makni Saadia , Gouiaa Naourez , Boudaouara Tahya , Turki Hamida
Published: February 2022

Various clinical forms of cutaneous leishmaniasis can be encountered such as: ulcerated, lupoïd, sporotrichoïd and other rare forms (eczematiform, erysipeloid, psoriasiform, verrucous, and pseudotumoral). We report an atypical presentation of verrucous and pseudotumoral cutaneous leishmaniasis that resolved following a course of cryotherapy.
Rectal carcinoma revealed by isolated mixed bone metastases
Authors: Slouma Maroua , Abbes Maissa , Dhahri Rim , Gueddiche Nour Elhouda , Msekni Issam , Gharsallah Imen , Metoui Leila , Louzir Bassem
Published: February 2022

Isolated bone metastases secondary to rectal neoplasia are scarce. Radiographic findings may include lytic, sclerotic, or mixed lesions. We presented a case of rectal carcinoma revealed by isolated osseous metastases. We emphasize the radiological features of mixed bone metastases with the differential diagnoses that may be raised.
Self‐correction of a migrated power‐injectable peripherally inserted central catheter following contrast‐enhanced computed tomography
Authors: Nakayama Ryuichi , Bunya Naofumi , Yama Naoya , Nonaka Tatsuki
Published: February 2022

The use of power‐injectable peripherally inserted central catheter (PIPICC) is a common practice, but displacement of these lines following injection of contrast media has been reported in 15.4% of cases. This report presents imaging evidence of displacement and self‐correction of a PIPICC line following contrast‐enhanced computed tomography.
Properties of Bromine Fused Salts Based on Quaternary Ammonium Molecules and Their Relevance for Use in a Hydrogen Bromine Redox Flow Battery
Authors: Küttinger Michael , Loichet Torres Paulette A. , Meyer Emeline , Fischer Peter
Published: February 2022

Bromine complexing agents (BCA) in aqueous electrolytes for hydrogen bromine flow batteries are used to reduce bromine‘s vapour pressure, while an insoluble and liquid fused salt is formed. The properties (concentrations, composition, conductivity and viscosity) of this fused salt are investigated in this study systematically ex situ by using 7 BCAs at different state of charge in HBr/Br2/H2O electrolytes with a theoretical capacity of 179.6 Ah L−1. Bromine is stored in the fused salt at concentrations up to 13.6 M, reaching theoretical volumetrical capacities up to 730 Ah L−1 in fused salts. The fused salt consists of a pure, bromine‐ and water‐free ionic liquid of organic [BCA]+ cations and polybromides, and its conductivity bases on a hopping mechanism among the polybromides. Alkyl side chain length of the BCAs and distribution of polybromides influence strongly the conductivity and viscosity of the fused salts. 1‐ethylpyridin‐1‐iumbromide results to be favoured BCA for application.
Designable Guest‐Molecule Encapsulation in Metal–Organic Frameworks for Proton Conductivity
Authors: Wang Feng‐Dong , Wang Bin‐Cheng , Hao Biao‐Biao , Zhang Chen‐Xi , Wang Qing‐Lun
Published: February 2022

Metal–organic frameworks (MOFs), as a porous frame material, exhibit considerable electrical conductivity. In recent decades, research on the proton conductivity of MOFs has made gratifying progress. In this review, the designable guest molecules encapsulated into MOFs are summarized and generalized into four types in terms of promoting proton conductive performance, and then recent progress in the promotion of proton conductivity by MOFs encapsulating guest molecules is discussed. The existing challenges and prospects for the development of this strategy for promoting MOFs’ proton conductivity are also listed.
Tribo‐Excited Chemical Reaction Using an EuIII Complex with a Stacked Anthracene Framework
Authors: Kitagawa Yuichi , Naito Ayu , Aikawa Kota , Shima Kaori , Shoji Sunao , Fushimi Koji , Hasegawa Yasuchika
Published: February 2022

A spin‐selective tribo‐chemical reaction using a dinuclear lanthanide complex is demonstrated for the first time. The dinuclear complex is composed of two EuIII ions, hexafluoroacetylacetonato ligands, and anthracene‐based phosphine oxide bridges. Single‐crystal analysis revealed a face‐to‐face‐type anthracene dimer structure in the dinuclear EuIII complex. Mechanical stimulus on the dinuclear EuIII complex induced selective formation of oxidized anthracene. The tribo‐chemical reaction is based on a characteristic energy‐transfer pathway for the selective formation of an excited triplet state.
Synthetic Antibody‐Rhamnose Cluster Conjugates Show Potent Complement‐Dependent Cell Killing by Recruiting Natural Antibodies
Authors: Ou Chong , Prabhu Sunaina Kiran , Zhang Xiao , Zong Guanghui , Yang Qiang , Wang Lai‐Xi
Published: February 2022

Monoclonal antibodies (mAbs) are one of the most rapidly growing drug classes used for the treatment of cancer, infectious and autoimmune diseases. Complement‐dependent cytotoxicity (CDC) is one of the effector functions for antibodies to deplete target cells. We report here an efficient chemoenzymatic synthesis of structurally well‐defined conjugates of a monoclonal antibody with a rhamnose‐ and an αGal trisaccharide‐cluster to recruit natural anti‐rhamnose and anti‐αGal antibodies, respectively, to enhance the CDC‐dependent targeted cell killing. The synthesis was achieved by using a modular antibody Fc‐glycan remodeling method that includes site‐specific chemoenzymatic Fc‐glycan functionalization and subsequent click conjugation of synthetic rhamnose‐ and αGal trisaccharide‐cluster to provide the respective homogeneous antibody conjugates. Cell‐based assays indicated that the antibody‐rhamnose cluster conjugates could mediate potent CDC activity for targeted cancer cell killing and showed much more potent efficacy than the antibody‐αGal trisaccharide cluster conjugates for CDC effects.
Auf Sand gebaut
Authors: Tetsch Larissa
Published: February 2022

Pollenwespen der Gattung Quartinia leben in trockenen, wüstenartigen Gebieten (Abbildung 1). Für ihren Nachwuchs graben sie Nester mit Brutzellen in den lockeren Sandboden. Um zu verhindern, dass beim Graben Sand nachrutscht, stützen die Wespen die Wände geschickt ab. Dazu benutzen sie Seidenfäden, die sie mit den Mundwerkzeugen auftragen.
A modeling framework for computational simulations of thoracic endovascular aortic repair
Authors: Shahbazian Negin , Doyle Matthew G. , Forbes Thomas L. , Amon Cristina H.
Published: February 2022

Thoracic endovascular aortic repair (TEVAR) is a minimally invasive treatment for thoracic aortic conditions including aneurysms and is associated with a number of postoperative stent graft related complications. Computational simulations of TEVAR have the potential to predict surgical outcomes and complications preoperatively. When using simulations for stent graft design and prediction of complications in a population, it is difficult to generalize patient‐specific TEVAR computational models due to patient variability. This study proposes a novel modeling framework for creating realistic population‐based computational models of TEVAR focused on aneurysms that allow for developing various clinically relevant geometric configurations and scenarios that are not easily attainable with limited patient data. The framework includes a methodology for developing population‐based thoracic aortic geometries and defining age‐dependent aortic tissue material models, as well as detailed steps and boundary conditions for finite element modeling of stent graft deployment during TEVAR. The simulation framework is illustrated for predicting the formation of a bird‐beak configuration, a wedge‐shaped gap at the proximal end of the deployed stent graft in TEVAR that leads to incomplete seal. A baseline TEVAR simulation model was developed along with three simulations in which the value of aortic curvature, aortic arch angle, or aortic tissue properties varied from the baseline model. Analyzing the length and angle of the bird‐beak configuration in each case shows that the bird‐beak size is sensitive to different values of the aortic geometry highlighting the importance of using realistic parameter values.
Mechanistic Investigation of H2O2‐dependent Chemiluminescence from Tetrabromo‐1,4‐Benzoquinone
Authors: Quan Zhuo , Mao Li , Tang Yi‐Qi , Lei Ming , Zhu Ben‐Zhan , Liu Ya‐Jun
Published: February 2022

As a H2O2‐dependent bioluminescent substrate, tetrabromo‐1,4‐benzoquinone (TBBQ) was first isolated from acorn worm. The mechanism of chemiluminescence (CL) corresponding to the bioluminescence (BL) of acorn worm is largely unknown, let alone the mechanism of BL. In this article, we firstly studied the chemical and physical processes, and mechanism of H2O2‐dependent CL from TBBQ by theoretical and experimental methods. The research results indicate: the CL process is initiated by a nucleophilic substitution reaction, which leads to the formation of an anionic dioxetane through five consecutive reactions; the anionic dioxetane decomposes to the first singlet excited state (S1) via a conical interaction of the potential energy surfaces (PESs) between the ground (S0) and S1 state; the anionic S1‐state changes to its neutral form by a proton transfer from the solvent and this neutral product is assigned as the actual luminophore. Moreover, the experimental detection of CL, .OH and the identifications of 2,3‐dibromo maleic acid and 2‐bromo malonic acid as the major final products provide direct evidence of the theoretically suggested mechanism. Finally, this study proves that the activity of the H2O2‐dependent CL from TBBQ is significantly lower than the one from tetrachloro‐1,4‐benzoquinone (TCBQ), which is caused by the weaker electron withdrawing effect and the stronger heavy atomic effect of bromine.
Recent advancement in drug development of nitro(NO2)‐heterocyclic compounds as lead scaffolds for the treatment of Mycobacterium tuberculosis
Authors: Scarim Cauê Benito , Pavan Fernando Rogério
Published: February 2022

Tuberculosis (TB) is an infectious disease caused predominantly by Mycobacterium tuberculosis (Mtb). It was responsible for approximately 1.4 million deaths worldwide in 2019. The lack of new drugs to treat drug‐resistant strains is a principal factor for the slow rise in TB infections. Our aim is to aid the development of new TB treatments by describing improvements (last decade, 2011–2021) to nitro(NO2)‐based compounds that have shown activity or pharmacological properties (e.g., anti‐proliferative, anti‐kinetoplastid) against Mtb. For all compounds, we have included final correlations of minimum inhibitory concentrations against Mtb (H37Rv).
A variation in SORBS1 is associated with type 2 diabetes and high‐density lipoprotein cholesterol in Chinese population
Authors: Gong Siqian , Huo Shaofeng , Luo Yingying , Li Yufeng , Ma Yumin , Huang Xiuting , Hu Mengdie , Liu Wei , Zhang Rui , Cai Xiaoling , Zhou Lingli , Chen Ling , Ren Qian , Zhang Simin , Zhu Yu , Zhang Xiuying , Chen Jing , Wu Jing , Zhou Xianghai , Lin Xu , Han Xueyao , Ji Linong
Published: February 2022

Aim

Sorbin and SH3‐domain‐containing‐1 (SORBS1) play important roles in insulin signalling and cytoskeleton regulation. Variants of the SORBS1 gene have been inconsistently reported to be associated with type 2 diabetes or diabetic kidney disease (DKD).

Methods

Two independent case‐control studies based on two randomized sampling cohorts (cohort 1, n = 3345; cohort 2, n = 2282) were used to confirm the association between rs2281939 of SORBS1 and impaired glucose regulation (IGR). An additional hospital‐based cohort (cohort 3, n = 2135) and cohort 1 were used to investigate the association between rs2281939 and DKD. The phenotype of rare variants of SORBS1 was explored in 453 patients with early onset type 2 diabetes (diagnosed before 40 years of age, EOD).

Results

The G allele was associated with type 2 diabetes (additive model: OR = 1.25, 95% CI [1.03–1.52], p = 0.022) in cohort 1, and IGR in cohort 2 (additive model: OR = 1.22, 95% CI [1.05–1.43], p = 0.01). We found that the G allele was also associated with HDL‐c levels in women in both cohort 1 (p = 0.03) and 2 (p = 0.029) in the dominant model. The rare variant carriers also had lower HDL‐c and LDL‐c levels than non‐carriers in patients with EOD. No association between rs2281939 or rare variants and DKD was observed.

Conclusions

The variants in the SORBS1 gene were associated with IGR and HDL‐c levels but not with DKD in the Chinese Han population.
Early detection of anthracycline‐ and trastuzumab‐induced cardiotoxicity: value and optimal timing of serum biomarkers and echocardiographic parameters
Authors: Díaz‐Antón Belén , Madurga Rodrigo , Zorita Blanca , Wasniewski Samantha , Moreno‐Arciniegas Andrea , López‐Melgar Beatriz , Ramírez Merino Natalia , Martín‐Asenjo Roberto , Barrio Patricia , Amado Escañuela Maximiliano German , Solís Jorge , Parra Jiménez Francisco Javier , Ciruelos Eva , Castellano José María , Fernández‐Friera Leticia
Published: February 2022

Aims

To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation.

Methods and results

Seventy‐two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high‐sensitivity cardiac troponin T, NT‐proBNP, global longitudinal strain (GLS), left ventricle end‐systolic volume (LVESV), left ventricle end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High‐sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT‐proBNP augmented after each anthracycline cycle (mean pre‐cycle levels of 72 ± 68 pg/mL and post‐cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post‐anthracycline treatment and the decline in GLS was more pronounced (−17.6% vs. −21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02–1.24), odds ratio = 0.66 (0.44–0.92), P < 0.05] at 1 month post‐anthracycline treatment. Neither high‐sensitivity troponin T nor NT‐proBNP was capable of predicting subsequent cardiotoxicity.

Conclusions

One month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab‐induced cardiotoxicity.
Isotopic signature of a glacial influenced hydrological system in northern Patagonia, Argentina
Authors: Sepúlveda Laura Daniela , Echegoyen Cecilia Vanina , Martin Maria Eugenia , Campodonico Verena Agustina , Pasquini Andrea Inés , Temporetti Pedro , Lecomte Karina Leticia
Published: February 2022

High glacial mountain environments around the world are important water reservoirs and are extremely sensitive to the effects of climate change. Considering that climate change affects snow accumulation and glacial melting, it is essential to understand the runoff generation and hydrological dynamics in these type of systems. Andean glaciers have shown a retreating and thinning pattern since the start of the 21st century. Regarding this, the stable isotopic composition of waters is useful to assess the contributions from different sources (i.e., glaciers, precipitation, and tributaries' inputs) to rivers. Several Patagonian mountain rivers have Andean glaciers in their headwaters, one of which is the Manso River. In this basin, over the last 30 years, the Ventisquero Negro Glacier (Manso Glacier's regenerated tongue) experienced a rapid thinning and recession that generated a proglacial lake, called Manso proglacial Lake. In this study, topographic effects upon the stable isotopic composition of river waters (δ2H and δ18O) are recognized, particularly, the altitude effect. The stable isotope composition of the Manso River varies downstream, evolving to a composition more enriched in heavy isotopes in the lower basin, likely due to altitude effects and the progressive evaporation that mainly occurs in the lakes' surfaces that the river crosses. Results show that glacial meltwater is the major water contributor in the upper basin during early fall. In the rest of the basin the stable isotopic composition of the Manso River is mainly controlled by the lakes' isotopic signatures and is highly influenced by two tributary rivers. The concordance between isotopic models and hydrological data demonstrates that stable isotopes constitute a valuable tool to quantify the contribution of different water sources. This has the potential to be particularly useful in areas where discharge data is unavailable.
Groundwater‐surface water exchange as key control for instream and groundwater nitrate concentrations along a first‐order agricultural stream
Authors: Jimenez‐Fernandez Oscar , Schwientek Marc , Osenbrück Karsten , Glaser Clarissa , Schmidt Christian , Fleckenstein Jan H.
Published: February 2022

Lower‐order streams (first‐ and second‐order) define the initial, landscape‐related, chemical signature of stream water in catchments. To date, first‐order streams have been perceived as predominantly draining systems, which collect water and solutes from the surrounding groundwater and surface runoff and simply mirror the chemical composition of the inputs. In this study, the impact of stream‐groundwater exchange fluxes on water chemistry of a first order agricultural stream (Schönbrunnen) and its connected groundwater in south‐western Germany was assessed combining222Rn, dissolved ions (chloride, sulphate, nitrate), and salt tracer tests with investigations of stream discharge and groundwater hydraulic gradients. The findings suggest that stream‐water chemistry in lower‐order streams is governed by an intricate interplay between dynamic, bidirectional water and solute exchange between groundwater and the stream leading to a pronounced hydrologic turnover along the studied reaches. High nitrate concentrations (up to 79 mg/L as NO3−) in stream water were attenuated in downstream direction (a mean value of 39 mg/L) without an increase in discharge, suggesting that redox processes occurring during sediment passage in sequential infiltration and exfiltration zones affect stream water chemistry. Nitrate in stream water infiltrating into the aquifer at distinct losing spots was subject to denitrification within the first few decimetres of the streambed, while concurrent exfiltration of low‐nitrate groundwater into the stream at gaining spots compensated for flow losses and in turn diluted instream nitrate concentrations. In summary the findings imply that (1) instream mixing resulting from the bidirectional exchange of water between groundwater and the stream (hydrologic turnover) affects instream nitrate concentrations, (2) denitrification in the streambed of losing reaches and the near‐stream aquifer significantly contributes to reactive nitrate turnover and elimination, and (3) oxidation of ammonium could be a secondary source of nitrate inputs into the stream.
Block‐transitive automorphism groups of 2‐(v,k,λ) $(v,k,\lambda )$ designs with (r,k)=1 $(r,k)=1$
Authors: Zhang Wanbao , Zhou Shenglin
Published: February 2022

In 1984, Camina and Gagen gave the result that the block‐transitive automorphism group of a 2‐ design with must be flag‐transitive, moreover, is point‐primitive of affine or almost simple type. As a generalization of this result, the purpose of this paper is to study block‐transitive automorphism groups of nontrivial 2‐ designs with , where is the number of blocks incident with a given point. We prove that, for a 2‐ design with , if is block‐transitive, then must be flag‐transitive, and furthermore, is point‐primitive of affine or almost simple type. Moreover, the classification of this type of 2‐designs is given when the socle of is sporadic. There are thirteen 2‐designs up to isomorphism.
Circ_0072088 knockdown contributes to cisplatin sensitivity and inhibits tumor progression by miR‐944/LASP1 axis in non‐small cell lung cancer
Authors: Zhang Lei , Wu Yuanzhou , Hou Chunyang , Li Fangzhi
Published: February 2022

Background

Non‐small cell lung cancer (NSCLC) is an aggressive tumor that accounts for a large proportion of cancer‐related deaths. Cisplatin (CDDP) has been utilized to treat NSCLC. However, the efficacy of CDDP is usually restrained owing to the development of drug resistance. This study aims to reveal the molecular mechanism of the resistance of NSCLC cells to CDDP.

Methods

The expression levels of circRNA_0072088 (circ_0072088), microRNA‐944 (miR‐944), and LIM and SH3 protein 1 (LASP1) were measured by quantitative real‐time PCR (qRT‐PCR) in CDDP‐resistant NSCLC tissues and cells. Protein expression was determined by Western blotting in CDDP‐resistant NSCLC tissues and cells. The functional effects of circ_0072088, miR‐944, and LASP1 on CDDP sensitivity and NSCLC progression were revealed by Cell Counting Kit‐8 (CCK‐8), flow cytometry, cell colony formation, wound healing, and transwell invasion assays. The binding relationship between miR‐944 and circ_0072088 or LASP1 was identified by a dual‐luciferase reporter and RNA immunoprecipitation assay. The effects of circ_0072088 knockdown on tumor growth in vivo were analyzed by an in vivo tumor formation assay.

Results

Circ_0072088 and LASP1 expression were significantly upregulated, while miR‐944 expression was downregulated in CDDP‐resistant NSCLC tissues and cells as compared with control groups. Circ_0072088 expression was significantly associated with tumor–node–metastasis stage and tumor size. Functionally, circ_0072088 knockdown improved CDDP sensitivity and repressed NSCLC cell malignancy, whereas miR‐944 inhibitor hindered these effects. Mechanistically, circ_0072088 functioned as a sponge for miR‐944 and miR‐944 targeted LASP1. Circ_0072088 knockdown improved the sensitivity of tumor to CDDP in vivo.

Conclusion

Circ_0072088 silencing improved CDDP sensitivity and inhibited NSCLC progression by downregulating LASP1 expression through sponging miR‐944. These data provide novel insight into the resistance of NSCLC to CDDP.
Immunogenicity and safety of the BNT162b2 COVID‐19 mRNA vaccine in PLWH: A monocentric study in Bari, Italy
Authors: Milano Eugenio , Ricciardi Aurelia , Casciaro Raffaella , Pallara Elisabetta , De Vita Elda , Bavaro Davide F. , Larocca Angela Maria Vittoria , Stefanizzi Pasquale , Tafuri Silvio , Saracino Annalisa
Published: February 2022

In March, people living with HIV infection (PLWH) were included in the risk category of fragile people for severe COVID‐19 receiving priority access to vaccination with BNT162b2 vaccine. The aim of the study was to evaluate the immunogenicity and safety of the two doses regimen. The antibodies titer for severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2) was evaluated after 21 days since the first administration (Time 1), 1 (Time 2), and 3 (Time 3) months post‐vaccination. Information regarding virological and immunological conditions at baseline, previous SARS‐CoV‐2 state of infection, other immunodeficiencies, current antiretroviral therapy (ART), comorbidities, and severe adverse events (SAE) to vaccination was collected. Six hundred and ninety‐seven patients were tested for quantitative anti‐spike antibodies at Time 1, 577 patients had a second detection at Time 2, and 491 patients had the third detection. Baseline characteristics of the study population are reported in Table 1. At the time of vaccine administration, all patients were on ART (except one long‐term nonprogressor); 632 (90.7%) patients had undetectable HIV‐RNA; 12 (1.7%) patients were immunosuppressed due to chemotherapy or other immunosuppressive drugs; 345 (49.5%) patients had at least one COVID‐19 related comorbidity and 155 (22.2%) had two or more comorbidities. No SAEs were reported. Final serological results are available for 694 patients after the first dose, 577 and 491 after the second and third ones, respectively; positive titer (values ≥ 50 AU/ml) was demonstrated in 653 (94.1%), 576 (99.8%), 484 (98.6%) patients, respectively. Only one patient was a nonresponder after completing vaccination, who was a newly diagnosed one for HIV infection. All vaccinations were well tolerated, with no SAEs. BNT162b2 mRNA vaccine was immunogenic and safe in PLWH.
Development of a wind and Pasquill stability class climate dataset for the North American Great Lakes region
Authors: Kiefer Michael T. , Andresen Jeffrey A. , Rozeboom Dale W. , Bian Xindi
Published: February 2022

In this study, a North American Regional Reanalysis (NARR)‐based climate dataset of wind and Pasquill stability class is developed for the North American Great Lakes region. Motivated by the need to update the limited wind and Pasquill stability class climatology previously incorporated into a livestock odour nuisance‐mitigation application used in Michigan, this study is motivated more generally by the lack of a long‐term climate dataset suitable for studies of atmospheric dispersion in the Great Lakes region. As a preliminary step, NARR 10‐m wind speed, 10‐m wind direction, and 2‐m temperature are evaluated at eight weather stations in Michigan and northern Indiana, and the wind speed variable is subsequently bias‐corrected. To derive a Pasquill stability class dataset from the NARR variables, an existing empirical relationship between Pasquill stability class and Richardson number is applied to a previously developed NARR‐derived Richardson number dataset covering the period 1979–2008. Pasquill stability class frequency in NARR is subsequently evaluated using observations at two flux towers in Illinois. Although a tendency is noted for the NARR‐derived Pasquill stability class dataset to underestimate the frequency of stable and unstable conditions, and overestimate the frequency of neutral conditions, the analysis shows that the 10‐m wind speed bias‐correction procedure yields a frequency distribution that is in better agreement with the observations than the non‐bias‐corrected dataset. Finally, an analysis of the spatial and temporal variability of livestock odour dispersion potential in Michigan is provided as an example application of the NARR‐based wind and Pasquill stability class climate dataset.
Comparing the performance of high‐resolution global precipitation products across topographic and climatic gradients of Central Asia
Authors: Peña‐Guerrero Mayra Daniela , Umirbekov Atabek , Tarasova Larisa , Müller Daniel
Published: February 2022

Accurate and reliable precipitation data with high spatial and temporal resolution are essential in studying climate variability, water resources management, and hydrological forecasting. A range of global precipitation data are available to this end, but how well these capture actual precipitation remains unknown, particularly for mountain regions where ground stations are sparse. We examined the performance of three global high‐resolution precipitation products for capturing precipitation over Central Asia, a hotspot of climate change, where reliable precipitation data are particularly scarce. Specifically, we evaluated MSWEP, CHIRPS, and GSMAP against independent gauging stations for the period 1985–2015. Our results show that MSWEP and CHIRPS outperformed GSMAP for wetter periods (i.e., winter and spring) and wetter locations (150–600 mm·year−1), lowlands, and mid‐altitudes (0–3,000 m), and regions dominated by winter and spring precipitation. MSWEP performed best in representing temporal precipitation dynamics and CHIRPS excelled in capturing the volume and distribution of precipitation. All precipitation products poorly estimated precipitation at higher elevations (>3,000 m), in drier areas (<150 mm), and in regions characterized by summer precipitation. All products accurately detected dry spells, but their performance decreased for wet spells with increasing precipitation intensity. In sum, we find that CHIRPS and MSWEP provide the most reliable high‐resolution precipitation estimates for Central Asia. However, the high spatial and temporal heterogeneity of the performance call for a careful selection of a suitable product for local applications considering the prevailing precipitation dynamics, climatic, and topographic conditions.
Spatial patterns of atmospheric vapour transport and their connection to drought in New Zealand
Authors: Bennet Morgan J. , Kingston Daniel G.
Published: February 2022

The impacts of drought can be substantial, particularly for primary producing nations such as New Zealand. Despite the importance of drought, identifying connections to atmospheric drivers remains a challenge. Vertically integrated water vapour transport (IVT) is critical to understanding the connection between ocean, atmosphere and the land surface, and as such the drivers of drought events. Self‐organizing maps (SOMs) are used here to characterize the spatial patterns of IVT over New Zealand. In turn, the occurrence of these patterns during drought conditions (defined using the standardized precipitation and evapotranspiration index) across New Zealand is then identified and discussed. The resulting classification highlights a collection of high and low IVT magnitude nodes (i.e., spatial patterns). Low IVT nodes occur 40.57% of the time during all drought events and 45.86% during the top 99th percentile events. Conversely, high IVT magnitude nodes occur less frequently during drought events, at 23.77 and 20.96% of the time during all drought events and the top 99th percentile events, respectively. The low IVT nodes are also particularly dominant during summer and autumn season drought events. An increase in the frequency of occurrence of drought‐associated nodes is observed over the course of the study period, which may in part be associated with El Niño–Southern Oscillation (ENSO)‐driven interannual variability in New Zealand climate. Overall, the results demonstrate the importance of atmospheric circulation‐driven disruptions in moisture transport for drought development, while also providing a first moisture transport weather classification for New Zealand.
Lifestyle entrepreneurship innovation and self‐efficacy: Exploring the direct and indirect effects of marshaling
Authors: Dias Álvaro , Cascais Eduardo , Pereira Leandro , Lopes da Costa Renato , Gonçalves Rui
Published: February 2022

Lifestyle entrepreneurs play a key role in the destination sustainable development by providing more authentic and innovative experiences. However, the determinants of the innovation generated by these entrepreneurs are not fully understood. This study explores the key factors influencing innovation and entrepreneurial self‐efficacy (ESE) in lifestyle entrepreneurs. Survey data allowed to identify the effect of marshaling, place familiarity, and communication on innovation and ESE. Findings reveal several direct and indirect relationships between these variables. The results indicate that marshaling has a significantly positive and direct effect on both ESE and communication. Communication has a direct and positive relationship with innovation. Place familiarity perception has a significantly positive and direct relation to communication and innovation on ESE. It was also found an indirect link between marshaling and innovation via communication as a mediator.