bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells
Authors: Lovison Denise , Alessi Dario , Allegri Lorenzo , Baldan Federica , Ballico Maurizio , Damante Giuseppe , Galasso Marilisa , Guardavaccaro Daniele , Ruggieri Silvia , Melchior Andrea , Veclani Daniele , Nardon Chiara , Baratta Walter 
Published: April 2022

AbstractThe chiral cationic complex [Ru(η1‐OAc)(CO)((R,R)‐Skewphos)(phen)]OAc (2R), isolated from reaction of [Ru(η1‐OAc)(η2‐OAc)(R,R)‐Skewphos)(CO)] (1R) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)‐Skewphos)(phen)]Y (X=Y=OPiv 3R; X=SAc, Y=OAc 4R). The corresponding enantiomers 2S‐4S have been obtained from 1S containing (S,S)‐Skewphos. Reaction of 2R and 2S with (S)‐cysteine and NaPF6 at pH=9 gives the diastereoisomers [Ru((S)‐Cys)(CO)(PP)(phen)]PF6 (PP=(R,R)‐Skewphos 2R‐Cys; (S,S)‐Skewphos 2S‐Cys). The DFT energetic profile for 2R with (S)‐cysteine in H2O indicates that aquo and hydroxo species are involved in formation of 2R‐Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n‐octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT‐116 and A549 cell lines with EC50 values of 2.8–0.04 μM. The (R,R)‐Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4R (EC50=0.04 μM) being 14 times more cytotoxic than 4S against the anaplastic thyroid cancer 8505 C cell line.
Copper‐Catalyzed Enantioselective Hydrosilylation of gem‐Difluorocyclopropenes Leading to a Stereochemical Study of the Silylated gem‐Difluorocyclopropanes
Authors: Sekine Keisuke , Akaishi Dai , Konagaya Kakeru , Ito Shigekazu 
Published: April 2022

AbstractOptically active cyclopropanes have been widely investigated especially from the views of pharmaceutical and agrochemical industries, and substituting one of the methylenes with the difluoromethylene unit should be promising for developing novel biologically relevant compounds and functional materials. In this paper, the copper‐catalyzed enantioselective hydrosilylation of gem‐difluorocyclopropenes to provide the corresponding chiral gem‐difluorocyclopropanes is presented. The use of copper(I) chloride, chiral ligands including bidentate BINAPs and monodentate phosphoramidites, and silylborane Me2PhSi‐Bpin accompanying sodium tert‐butoxide in methanol was appropriate for the enantioselective hydrosilylation of the strained C=C double bond, and the resultant chiral difluorinated three‐membered ring was unambiguously characterized. Subsequent activation of the silyl groups in enantio‐enriched gem‐difluorocyclopropanes showed substantial reduction of the enantiopurity, indicating cleavage of the distal C−C bond leading to the transient acyclic intermediates.
A Composite of Two Dimensional GeSe2/Nitrogen‐Doped Reduced Graphene Oxide for Enhanced Capacitive Lithium‐Ion Storage
Authors: Han Lijing , Zhao Andi , Tang Jing , Wei Qiaohua , Wei Mingdeng 
Published: April 2022

AbstractA composite of two‐dimensional (2D) GeSe2 nanosheets dispersed on N‐doped reduced graphene oxide (GeSe2/N‐rGO) is fabricated via a simple hydrothermal method combined with post‐selenization process. The high electronic conductivity and the substantial void spaces of the wrinkled N‐rGO can improve the electrical conductivity of the active material and accommodate the volume evolution of GeSe2 nanosheets during the (de)lithiation processes, while GeSe2 nanosheets can reduce ion diffusion length effectively. Meanwhile, the unique layered structure is beneficial to the contact of the active material and electrolyte, and the reversibility of conversion reaction has also been improved. Furthermore, kinetics analysis reveals a pseudocapacitance‐dominated Li+‐storage mechanism at high rates. In‐situ X‐ray diffraction analysis discloses that the conversion reaction has played a certain part in Li+‐storage. Thus, the GeSe2/N‐rGO composite delivers excellent rate capability and good long‐term stability with a high reversible capacity of 711.0 mA h g−1 after 2000 cycles at 1 A g−1.
Novel Thermal Decomposition Method for the Synthesis of Iron‐doped SnS2 Nanoparticles and Studies on their Peroxidase‐like Activity
Authors: Lather Reena , Jeevanandam Pethaiyan 
Published: April 2022

AbstractIron‐doped SnS2 nanoparticles (Sn1‐xFexS2) have been synthesized by a novel thermal decomposition method. Phase analysis was done using powder XRD. FE‐SEM and TEM studies show flake‐like morphology for iron doped SnS2 nanoparticles. Diffuse reflectance spectroscopy results demonstrate blue shift of band gap of Sn1‐xFexS2 nanoparticles with respect to pure SnS2 nanoparticles. M−H measurements of iron doped SnS2 nanoparticles at 300 K and 2 K show weak ferromagnetic behaviour when x=0.10 and 0.15. When x=0.20, paramagnetic behaviour at 300 K and superparamagnetic behaviour at 2 K are observed. ZFC‐FC measurements were also carried out for the iron doped SnS2 nanoparticles. The Sn1‐xFexS2 nanoparticles were used as catalyst for peroxidase‐like activity and for the detection of H2O2.
Visualizing a Single‐Crystal‐to‐Single‐Crystal [2+2] Photodimerization through its Lattice Dynamics: An Experimental and Theoretical Investigation
Authors: Giunchi Andrea , Pandolfi Lorenzo , Salzillo Tommaso , Brillante Aldo , Della Valle Raffaele G. , d'Agostino Simone , Venuti Elisabetta 
Published: April 2022

AbstractIn homogeneous solid‐state reactions, the single‐crystal nature of the starting material remains unchanged, and the system evolves seamlessly through a series of solid solutions of reactant and product. Among [2+2] photodimerizations of cinnamic acid derivatives in the solid state, those involving salts of the 4‐aminocinnamic acid have been recognized to proceed homogeneously in a “single‐crystal‐to‐single‐crystal” fashion by X‐ray diffraction techniques. Here the bromide salt of this compound class is taken as a model system in a Raman spectroscopy study at low wavelengths, to understand how such a mechanism defines the trend of the crystal lattice vibrations during the reaction. Vibrational mode calculations, based on dispersion corrected DFT simulations of the crystal lattices involved in the transformation, have assisted the interpretation of the experiments. Such an approach has allowed us to clarify the spectral signatures and to establish a correlation between the dynamics of the monomer and dimer systems in a process where chemical progress and crystal structural changes are demonstrated to occur simultaneously.
Silver‐Catalyzed Nucleophilic Deoxydifluoromethylthiolation of Activated Aliphatic Alcohols with BT−SCF2H
Authors: Tironi Matteo , Hopkinson Matthew N. 
Published: April 2022

AbstractDeoxygenative conversion of alcohols into difluoromethylthioethers is reported using 2‐((difluoromethyl)thio)‐3‐methylbenzo[d]thiazol‐3‐ium triflate (BT−SCF2H) as a source of −SCF2H anions. The presence of silver(I) triflate as a catalyst was found to be crucial for stabilizing the in situ‐generated anion, while the concomitant formation of a reactive 2‐(alkoxy)benzothiazolium electrophile likely ensures a fast onward substitution reaction, avoiding the build‐up of −SCF2H. To the best of our knowledge, this process represents the first report of a direct nucleophilic substitution reaction with −SCF2H and delivers products containing the medicinally relevant difluoromethylthio motif in a single step from widely available alcohols.
Synthesis of Indolyl‐1,3‐dienes from β‐Sulphonyl Aldehydes through One‐Pot Sequential Brønsted Acid/Base Catalysis
Authors: Karan Ganesh , Sahu Samrat , Sudan Maji Modhu 
Published: April 2022

AbstractIntroduction of a 1,3‐diene moiety at the C3‐position of pyrrole and indole bearing various aliphatic as well as aromatic functional groups with good stereoselectivity remains a challenging task. Keeping the synthetic applicability in mind, an eccentric strategy is developed to synthesize 1,3‐dienyl pyrroles and indoles from unprotected pyrroles and indoles employing β‐sulphonyl aldehyde as a dienylating agent. This method is developed by using a one‐pot sequential Brønsted acid/base catalysis strategy. The nucleophilicity of indole is transmitted through the conjugation to eliminate the sulfonyl groups in a step‐wise manner. Further, this developed protocol was extended to the incorporation of a 1,3,5‐triene moiety at the C3‐position of indoles through unprecedented successive three sulfonyl group elimination. As an application of this strategy, a Diels−Alder reaction and hydrothiolation of 1,3‐diene were demonstrated.
Impact of human intervention structures on the rivers: An investigation of the spatiotemporal variation of grain size in the Tista River, eastern Himalayas
Authors: Ghosh Kausik , Chakraborty Tapan 
Published: April 2022

AbstractIn order to investigate the effect of intervention structures like dams and barrage on the sediment grain size distribution, we examined a ~75 km stretch of the Tista River in the foothill alluvial plain of the eastern Himalayas. However, studies on the impact of dams on streamflow and sediment in the Himalayan rivers are constrained due to inadequate historical gauge data. Therefore, we employed a simple method to track the initial formation of some of the existing river landforms that formed before the dam/barrage operations from yearly satellite images (1987–2017) for in situ sediment sample collection. Hence, the collected sediment grain sizes analysis is used here as a proxy to comprehend the pre‐, syn‐ and post‐dam river sediment‐transport pattern. We have grouped 23 landforms into three temporal clusters: (i) those formed before 1997, earlier than the dams/barrage interventions (TOL); (ii) formed between 1998 and 2010 during the upstream dam construction (TML) and (iii) formed after 2010 (TNL) when upstream dams and the barrage were fully operational. A total of 116 sediment samples from these landforms indicate the overall grain size reduction for TML and TNL sediment due to reservoir sequestration of coarser grains. In comparison, the coarsest TOL sediment with downstream fining trend represents the pristine river condition. The coarsening trend with a poor correlation coefficient of TML is primarily assigned to partial trapping of the coarse bedload and massive sediment generation by the upstream under‐construction dams, resulting in the downstream erosion of the riverbed and transport of the coarser bedload further down. Similarly, post‐dam sediment trapping and controlled flow were responsible for the weaker trend with a distinctly finer size of TNL. The historical satellite images and data on streamflow and suspended sediment reveal that contemporary river behaviour is consistent with the earlier interpretation.
Inhibition of PDK1 enhances radiosensitivity and reverses epithelial–mesenchymal transition in nasopharyngeal carcinoma
Authors: Zhang Wei , Li Lingling , Guo Ergang , Zhou Haiting , Ming Jun , Sun Lu , Hu Guoqing , Zhang Linli 
Published: April 2022

AbstractBackgroundRadioresistance challenges the clinical outcomes of nasopharyngeal carcinoma (NPC). The 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) is a crucial kinase of PI3K/AKT signaling pathway which has been implicated in the process of radioresistance. However, the role of PDK1 in NPC remains largely unclear.MethodsThe expression of PDK1 was determined by immunohistochemistry and Western blot. The effects of RNA interference and pharmacologic inhibitor of PDK1 in combination with irradiation were investigated.ResultsOverexpression of PDK1 was correlated with poor prognosis in patients with NPC. PDK1 depletion enhanced radiosensitivity of NPC cells both in vitro and in vivo. Additionally, a specific PDK1 inhibitor also had the potential to enhance radiosensitivity in radioresistant NPC cells. Mechanistically, PDK1 depletion inhibited various targets of AKT including mTOR and GSK‐3β and reversed the epithelial–mesenchymal transition.ConclusionsThese findings indicated that PDK1 might be a potential target for NPC.
Beneficial effect of ursodeoxycholic acid in patients with acyl‐CoA oxidase 2 (ACOX2) deficiency–associated hypertransaminasemia
Authors: Alonso‐Peña Marta , Espinosa‐Escudero Ricardo , Herraez Elisa , Briz Oscar , Cagigal Maria Luisa , Gonzalez‐Santiago Jesus M. , Ortega‐Alonso Aida , Fernandez‐Rodriguez Conrado , Bujanda Luis , Calvo Sanchez Marta , D´Avola Delia , Londoño Maria‐Carlota , Diago Moises , Fernandez‐Checa Jose C. , Garcia‐Ruiz Carmen , Andrade Raul J. , Lammert Frank , Prieto Jesus , Crespo Javier , Juamperez Javier , Diaz‐Gonzalez Alvaro , Monte Maria J. , Marin Jose J. G. 
Published: April 2022

Abstract

Background and Aims
A variant (p.Arg225Trp) of peroxisomal acyl‐CoA oxidase 2 (ACOX2), involved in bile acid (BA) side‐chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27‐BAs, mainly 3α,7α,12α‐trihydroxy‐5β‐cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency‐associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration.

Methods and Results
Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27‐BA levels (>50% of total BAs) were identified by high‐performance liquid chromatography‐mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH‐7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1‐S/XBP1‐U ratio), and BAXα expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt‐based cell viability test). THCA‐induced cell toxicity was higher than that of major C24‐BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site‐directed mutagenesis) and expressed in HuH‐7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH.

Conclusions
Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.
Comparing apples and oranges: The ZUMA‐7, TRANSFORM and BELINDA trials
Authors: Bommier Côme , Lambert Jérôme , Thieblemont Catherine 
Published: April 2022

AbstractIn December 2021, three phase III trials investigating Chimeric Antigen Receptor (CAR) T‐cell for large B‐cell lymphoma were published, only one of which showed no treatment effect on Event‐Free Survival (EFS). All compared anti‐CD19 CAR T‐cell as second‐line treatment with immunochemotherapy plus autologous stem cell transplant if an adequate response to chemotherapy was achieved. In this letter, we discuss the methodological reasons that partially explain the discrepant results observed between the ZUMA‐7, TRANSFORM and BELINDA trials. A raw comparison shows that BELINDA simultaneously had the worst experimental arm and the best control arm among the three trials. This could be partially related to differences in the event definition and time of assessment. Stable Disease was considered an event as early as W9 in TRANSFORM, W12 in BELINDA and only W21 in ZUMA‐7. Since tisa‐cel had the longest manufacturing time, the time window may have been too short to assess its full potential compared with axi‐cel and liso‐cel. In comparison, a patient with stable disease in ZUMA‐7 would not be considered an event until W21. On the other hand, a second salvage regimen was allowed before considering stable disease as an event only in the BELINDA control arm which could have delayed EFS. Many of these issues could be avoided if progression‐free survival was preferred to EFS and if the time to manufacture CAR‐T cells was shortened, as long delays can result in a higher tumor volume and more refractory diseases at the time of infusion.
Genetic characterization of P[8] rotavirus strains circulated in Iran between 2009 and 2017
Authors: Latifi Tayebeh , Eybpoosh Sana , Afchangi Atefeh , Jalilvand Somayeh , Shoja Zabihollah 
Published: April 2022

AbstractGroup A rotavirus (RVA) is the most common cause of acute gastroenteritis worldwide, which is responsible for causing an estimated 120 000 deaths in children under 5 years of age, which mostly occur in the lower‐income countries of Asia and Africa. The G1P[8] is a common genotype of RVA that has spread throughout the world, including Iran and this genotype is present in two commonly used RVA vaccines, RotarixTM and RotaTeqTM. In this study, we investigated the genetic diversity, viral evolution, and differences between antigenic epitopes of Iran's P[8] strains and two licensed vaccines. The phylogenetic and evolutionary analysis was carried out, using MEGA version 6.0 and BEAST, respectively. Antigenic epitopes of VP8* were compared to determine the differences between strains from Iran and RotarixTM and RotaTeqTM. The P[8]‐lineages III and IV were found as the predominant P genotype that circulated in Iran. The TMRCA of P[8]‐lineages III and IV was estimated in 1987 and 2009, respectively. The P[8]‐lineage III strains showed 12 amino acid changes compared to RotarixTM and 10 amino acid changes compared to RotaTeqTM. The P[8]‐lineage IV strains showed 10 amino acid variations for both RotarixTM and RotaTeqTM strains. The results revealed that the P[8] strains circulating in Iran differ from RotarixTM and RotaTeqTM strains. To monitor the long‐term effects of vaccines on the emergence of P[8] strains with different lineages, routine and successful monitoring of these strains will be crucial.
Abnormal dynamic functional connectivity in first‐episode, drug‐naïve adolescents with major depressive disorder
Authors: Zheng Ruiping , Chen Yuan , Jiang Yu , Zhou Bingqian , Li Shuying , Wei Yarui , Wang Caihong , Han Shaoqiang , Zhang Yong , Cheng Jingliang 
Published: April 2022

AbstractPrevious neuroimaging studies have identified disrupted large‐scale functional brain networks in major depressive disorder (MDD); however, most of them focused on adult patients and were based on static functional connectivity (FC). Thus, we aimed to investigate the patterns of change in dynamic FC in depressed adolescents. Resting‐state functional magnetic resonance imaging data were acquired from 60 first‐episode, drug‐naïve adolescents with MDD and 60 matched healthy controls (HCs). Then, the dynamic FC properties were analyzed using a sliding windows approach, k‐means clustering, and graph theory methods. The intrinsic brain FC were clustered into two configuration states—a more frequent and relatively sparsely connected State 1 and a less frequent and more strongly interconnected State 2. Compared with HCs, depressed adolescents had higher reoccurrence fraction and dwell time in State 1, and lower reoccurrence fraction and dwell time in State 2, and higher total number of transitions between the two states. Depressed adolescents showed decreased FC within the default mode network (DMN) and between the DMN and other networks in State 1. Additionally, the MDD group showed higher variances in the global and local efficiency. Furthermore, the duration of illness was positively correlated with the number of state transitions, and the 17‐item Hamilton Depression Rating Scale score was positively correlated with the mean dwell time in State 1. This study demonstrated abnormal dynamic FC in depressed adolescents, which provided new insights into the pathophysiological mechanisms of adolescent‐onset depression.
Trends in intraseasonal temperature variability in Europe, 1961–2018
Authors: Krauskopf Tomáš , Huth Radan 
Published: April 2022

AbstractWhile long‐term changes in measures of central tendency of climate elements, that is, mean temperature, are well acknowledged, studies of trends in measures of their variability are much less common. This is despite the fact that trends in variability can have higher effect on climate extremes than trends in mean. Here, four measures of intraseasonal variability are examined: (a) standard deviation of mean daily temperature, (b) the range between the 90th and 10th quantile of mean daily temperature, (c) mean absolute value of day‐to‐day temperature change, and (d) one‐day lagged temporal autocorrelation. ECA&D daily data from 168 stations and linear regression method are utilized to calculate trends of these characteristics in period from 1961 to 2018. Significant trends (positive and negative) are revealed with substantial differences between seasons, regions and measures. The most considerable decreases in temperature variability were recorded in winter, for temporal autocorrelation in eastern Europe and for variance‐based measures in northern Europe. For example, the standard deviation has decreased by more than 10% in the Arctic Ocean. This can indicate a decrease in the frequency of cold extremes in Scandinavia. On the contrary, increasing persistence may suggest a greater likelihood of cold extremes in the East European Plain. Increases in variability prevail only in summer, but not for all measures and not as clearly as decreases in winter. Trends in temporal autocorrelation and day‐to‐day change appear to be sensitive to data issues, such as inhomogeneities and changes in observational procedures.
Prevalence and correlates of self‐reported cognitive difficulties in deployment‐injured U.S. military personnel
Authors: Jurick Sarah M. , McCabe Cameron T. , Watrous Jessica R. , Walker Lauren E. , Stewart Ian J. , Galarneau Michael R. 
Published: April 2022

AbstractCognitive difficulties typically resolve within days to weeks following mild traumatic brain injury (mTBI); however, a sizable proportion of individuals continue to report cognitive symptoms months to years later that are often associated with posttraumatic stress disorder (PTSD) and depression to a greater degree than a history of mTBI. The current study sought to evaluate the prevalence of self‐reported cognitive difficulties as well as the relative contributions of demographic, injury‐related, and mental health variables in a large study of U.S. military personnel injured during deployment since 2001. Slightly fewer than half (42.0%) of participants reported elevated cognitive difficulties compared with a normative population; however, this was driven primarily by those who screened positive for PTSD or depression. Hierarchical linear regression revealed that various demographic and injury factors, including lower educational attainment, retired or separated military status, enlisted rank, and a history of deployment‐related mTBI, were associated with more self‐reported cognitive difficulties, f2 = 0.07. Screening positive for PTSD or depression accounted for 32.1% of the variance in self‐reported cognitive symptoms, f2 = 0.63, whereas injury variables, including a history of deployment‐related mTBI, albeit significant in the model, accounted for 1.6%. The current findings add to the growing body of literature underscoring the importance of screening for and treating mental health conditions in injured military personnel.