bluuebunny/crossref_metadata_2025_split huggingface dataset:
2‐Difluoromethoxy‐Substituted Estratriene Sulfamates: Synthesis, Antiproliferative SAR, Antitubulin Activity, and Steroid Sulfatase Inhibition
Authors: Dohle Wolfgang , Asiki Hannah , Gruchot Wojciech , Foster Paul A. , Sahota Havreen K. , Bai Ruoli , Christensen Kirsten E. , Hamel Ernest , Potter Barry V. L. 
Published: September 2022

Abstract2‐Difluoromethoxyestratriene derivatives were designed to improve potency and in vivo stability of the drug candidate 2‐methoxyestradiol (2ME2). Compound evaluation in vitro against the proliferation of MCF‐7 and MDA MB‐231 breast cancer cells, as inhibitors of tubulin polymerisation and also steroid sulfatase (STS) both in cell lysates and in whole cells, showed promising activities. In antiproliferative assays 2‐difluoromethoxyestradiol was less potent than 2ME2, but its sulfamates were often more potent than their corresponding non‐fluorinated analogues. The fluorinated bis‐sulfamate is a promising antiproliferative agent in MCF‐7 cells (GI50 0.28 μM) vs the known 2‐methoxyestradiol‐3,17‐O,O‐bissulfamate (STX140, GI50 0.52 μM), confirming the utility of our approach. Compounds were also evaluated in the NCI 60‐cell line panel and the fluorinated bis‐sulfamate derivative displayed very good overall activities with a sub‐micromolar average GI50. It was a very potent STS inhibitor in whole JEG‐3 cells (IC50 3.7 nM) similar to STX140 (4.2 nM) and additionally interferes with tubulin assembly in vitro and colchicine binding to tubulin. An X‐ray study of 2‐difluoromethoxy‐3‐benzyloxyestra‐1,3,5(10)‐trien‐17‐one examined conformational aspects of the fluorinated substituent. The known related derivative 2‐difluoromethyl‐3‐sulfamoyloxyestrone was evaluated for STS inhibition in whole JEG‐3 cells and showed an excellent IC50 of 55 pM.
Synthesis and Vasorelaxant Activity of Nitrate−Coumarin Derivatives
Authors: Matos Maria João , Uriarte Eugenio , Seoane Nuria , Picos Aitor , Gil‐Longo José , Campos‐Toimil Manuel 
Published: September 2022

AbstractDue to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate−coumarins and evaluated their vasorelaxant activity in contraction‐relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC50=12.73 nM) and sodium nitroprusside (IC50=4.32 nM). Coumarin‐7‐yl‐methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC50=1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K+ channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugs.
Berberine ameliorates pulmonary inflammation in mice with influenza viral pneumonia by inhibiting NLRP3 inflammasome activation and gasdermin D‐mediated pyroptosis
Authors: An Chen , Wu Yanmin , Wu Jun , Liu Huanwei , Zhou Siyao , Ge Dongyu , Dong Ruijuan , You Leiming , Hao Yu 
Published: September 2022

AbstractViral pneumonia is a common complication caused by Influenza A virus infection and is characterized by severe pulmonary inflammation. A previous study showed that berberine (BBR) significantly ameliorated the pulmonary inflammation in mice with influenza viral pneumonia but its underlying mechanism is not entirely understood. In this study, we reproduced the mouse model of influenza viral pneumonia through intranasal infection of A/Puerto Rico/8/34 (H1N1), to further investigate the anti‐inflammatory mechanism of BBR based on nucleotide‐binding oligomerization domain‐like receptor protein (NLRP) 3 inflammasome activation and Gasdermin D (GSDMD)‐mediated pyroptosis. Consistent with MCC950 (10 mg/kg, a specific NLRP3 inflammasome inhibitor), BBR (10 mg/kg) obviously improved the weight loss and survival rate of infected mice, alleviated their pulmonary inflammation, and suppressed the accumulation of tumor necrosis factor and interleukin (IL)‐6 in lungs without obvious inhibition on viral multiplication (hemagglutinin titer and nucleoprotein messenger RNA). Moreover, BBR (10 mg/kg) reduced the expressions of NLRP3, apoptosis‐associated speck‐like protein containing a CARD (ASC), and cysteinyl aspartate‐specific proteinase (Caspase)1 (Caspase1 precursor [Pro‐caspase1] + Caspase1p20 subunit) and the ratio of Caspase1p20 subunit to Caspase1, thus inhibiting the NLRP3 inflammasome activation and resulting in the decreased contents of mature IL‐1β and IL‐18 in lungs. The GSDMD expression (GSDMD precursor [Pro‐GSDMD] + GSDMD‐N terminal [NT]) and the ratio of GSDMD‐NT to GSDMD were also declined by BBR (10 mg/kg). These evidence indicate that BBR may ameliorate pulmonary inflammation in mice with influenza viral pneumonia through inhibiting NLRP3 inflammasome activation, as well as depressing GSDMD‐mediated pyroptosis via declining GSDMD expression and restraining NLRP3 inflammasome‐mediated GSDMD activation.
Synthesis and evaluation of [177Lu]Lu‐labeled porphyrin loaded PAMAM dendrimer: Impact on tumor uptake and pharmacokinetics
Authors: Kumar Naveen , Guleria Mohini , Chakraborty Avik , Amirdhanayagam Jeyachitra , Bannore Trupti Upadhye , Damle Archana , Sarma Haladhar D. , Das Tapas 
Published: September 2022

AbstractThe objective of the present work is to evaluate the ability of the radiolabeled PAMAM dendrimers (polyamidoamine) towards facilitating the delivery of an in‐house synthesized porphyrin derivative in the tumorous lesions to evaluate their candidature for possible application in endo‐radionuclide therapy. For this, PAMAM particles were conjugated with a porphyrin derivative namely, 5,10,15,20‐tetrakis‐(4‐carboxymethyleneoxyphenyl)porphyrin (STAP), synthesized in‐house following a two‐step reaction. The average number of porphyrin molecules loaded per PAMAM particle was evaluated using ultraviolet‐visible spectrophotometry and was found to be approximately 2. STAP conjugated PAMAM particles were further conjugated with p‐NCS‐benzyl‐DOTA (subsequently referred as DOTA) to facilitate radiolabeling with 177Lu. On an average, two p‐NCS‐benzyl‐DOTA molecules were observed to be attached per PAMAM‐STAP particle. DOTA‐PAMAM‐STAP conjugate was radiolabeled with 177Lu with a final radiochemical purity of >95%, which was determined by paper chromatography using two different mobile phases viz. 0.1 M sodium citrate buffer (pH 5.0) and 10 mM DTPA. Biological behavior of [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate was investigated in fibrosarcoma bearing Swiss mice model wherein accumulation of radiolabeled particles was observed in liver, GIT, spleen, and kidneys at 3 h post‐administration. However, accumulated activity exhibited rapid clearance from majority of the organs at 24 h post‐administration. [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate exhibited an appreciable uptake in tumor mass [6.09 ± 1.22 percentage injected activity/organ (% IA/organ)] at 3 h post‐administration (p.i.) which was found to reduce to 1.05 ± 0.13 % IA/organ at 24 h post‐administration. The results obtained in biodistribution studies were further corroborated through scintigraphic imaging performed in the same animal model. Despite of an appreciable accumulation in tumor mass, the lower retention of the [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate therein, at longer time point (24 h p.i.) may limit its possible potential as a radio‐therapeutic agent and indicates towards need for further structural manoeuvring to attain favorable in vivo performance.
Blood–brain barrier permeable benzylpiperidin‐4‐yl‐linked benzylamino benzamides as dual cholinesterase inhibitors
Authors: Banoo Razia , Nuthakki Vijay K. , Abdullaha Mohd , Sharma Mohit , Bharate Sandip B. 
Published: September 2022

AbstractAlzheimer's disease (AD) is a multifaceted neurodegenerative disorder involving various pathological events. The existing options for managing the disease utterly rely on cholinesterase (ChE) inhibitors. In recent years, the dual inhibition of ChEs as a potential AD therapeutics has substantially attracted the attention of medicinal chemists. Recently, we reported benzyl piperidinyl‐linked methoxy‐naphthamides as dual ChE inhibitors. Herein, we investigated the peripheral anionic binding site‐binding methoxy‐naphthamide fragment that yielded benzyl piperidinyl‐linked benzyl aminobenzamide as another class of dual ChE inhibitors. The 3,5‐dimethoxy benzyl aminobenzamide, 8c1, exhibits inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with half‐maximal inhibitory concentration values of 0.61 and 2.04 µM, respectively. The enzyme kinetics and molecular modeling study indicated the noncompetitive and mixed‐type mode of inhibition for AChE and BChE with ki values of 0.14 and 0.46 µM, respectively. The derivative 8c1 crosses the blood–brain barrier as indicated by the Pe value of 14.34 × 10−6cm/s in the parallel artificial membrane permeability assay. Besides this, it also inhibits the self‐aggregation of amyloid‐β. The results presented herein indicate the potential of benzamide 8c1 for further investigation in preclinical models of AD.
An integrative insight into the diversity, distribution, and biogeography of the freshwater endemic clade of the Ponticola syrman group (Teleostei: Gobiidae) in the Caucasus biodiversity hotspot
Authors: Zarei Fatah , Esmaeili Hamid Reza , Sadeghi Reza , Schliewen Ulrich K. , Kovačić Marcelo , Abbasi Keyvan , Gholamhosseini Ali 
Published: September 2022

AbstractFreshwater habitats of the Caucasus biodiversity hotspot represent a center of endemism for the gobiid genus Ponticola Iljin, 1927. Hitherto, large‐scale molecular studies, owing to restricted taxon and geographical sampling, have failed to give an elaborate picture of diversity and evolutionary history of these species. Here, to contribute to filling this gap, we assessed taxonomic diversity, phylogeography and evolutionary history for the south Caspian populations of Ponticola presently classified as P. iranicus and P. patimari, using an integrative taxonomic approach comprising an entire geographic range sampling, and analyses of mitochondrial DNA haplotypes, the head lateral line system, otolith shape, and meristic and morphometric variation. All freshwater samples of the P. syrman group belong to a monophyletic clade with two main subclades: a small subclade confined to the upper Sefidroud sub‐basin including the type locality of P. iranicus and a large subclade with three geographically constrained haplogroups (Hg1, Hg2, and Hg3), comprising the rest of the distribution. Hg1 showed an eastern distribution including the type locality of P. patimari, while Hg2 and Hg3 are sister groups with central and western‐central distributions, respectively. The freshwater clade diverged from P. syrman during the Tyurkyanian low stand (~150 m b.s.l. lasting ~0.1 Myr), while the divergence of P. iranicus and P. patimari and radiations within P. patimari took place during the Bakunian high stand (up to 50 m a.s.l. lasting ~378–480 kya). Species delimitation analyses indicated two distinct species, corresponding to each main subclade. Although the otolith shape and lateral line analyses did not reflect with phylogeographic pattern, PCA and DFA plots of meristic and morphometric data showed a clear separation of the two major subclades corresponding to P. iranicus and P. patimari, suggesting the presence of significant morphological variation meriting formal taxonomic recognition. Overall, our findings (i) reveal the presence of two freshwater endemic species in the P. syrman group, and pending further investigation, hypothesize the presence of a third cryptic species; (ii) revise and document a narrow distributional range and low diversity for P. iranicus, in contrast to a wider distributional range and high diversity for P. patimari; (iii) suggest that the climatic oscillations of the Pleistocene were associated with the cladogenesis within the P. syrman group; and (iv) allowed for the recognition of conservation units and proposition of management measures.
Trichlorosilyl Anions of p‐Block Elements – New Applications for Simple Molecules
Authors: Böhme Uwe , Riedel Sophie 
Published: September 2022

AbstractRecently several trichlorosilyl anions of main group elements have been isolated and characterized. Since 2015 anions [E(SiCl3)n]−, which are stabilized solely by trichlorosilyl groups, have been prepared with E=B, C, Si, Ge, P, S. These compounds have long been overlooked due to their high reactivity. This disadvantage is also an advantage, since the high reactivity makes these anions useful as reagents in a number of transformations. Anions of this kind have been used so far in substitution reactions, as superacids, and weakly coordinating anions. This review summarizes present methods for the synthesis of these compounds. Possible applications and future developments are outlined.
Acid‐Promoted Carbon‐Carbon Triple Bond Cleavage of Ynones for the Synthesis of Benzo[d]oxazoles/Benzo[d]thiazoles and 1‐Arylethan‐1‐ones
Authors: Guo Zi‐Yi , Li Ke‐Ru , Li Hang , Wang Xu , Zhang Ji‐Tan , Xie Mei‐Hua 
Published: September 2022

AbstractA synchronous synthesis of benzo[d]oxazoles/benzo [d]thiazoles and 1‐arylethan‐1‐ones enabled by acid‐promoted C−C triple bond cleavage of ynones is disclosed. This reaction was accomplished with good tolerance of various functional groups and aminophenols/aminobenzenethiols to access the corresponding products, especially some structurally special 1‐arylethan‐1‐ones, in moderate to good yield. Furthermore, the readily accessible synthesis of some biologically active molecules has highlighted the synthetic utility of this strategy.
Fabrication and Characterization of Sulphur‐doped Graphitic Carbon Nitride Nanosheets as a Highly Selective and Ultrasensitive Electrochemical Sensor for Detection of 2,4‐Dinitrophenol in Real Gym Supplements
Authors: Pratibha  , Kumar Nikhil , Kapoor Atul , Rajput Jaspreet Kaur , Singh Dinesh , Varnika  
Published: September 2022

AbstractHerein, an effective template assisted calcination procedure has been adopted to synthesize the Sulphur‐doped graphitic carbon nitride (SXGCN). Furthermore, the SXGCN/GCE was then utilized for the electrochemical determination of 2,4‐Dinitrophenol (2,4‐DNP). It has been inferred that among the variously prepared SXGCN (x=0 %, 20 %, 40 %, 60 %, 80 %, and 100 %), S80GCN afforded the excellent electrochemical response for detection of 2,4‐DNP. The synthesized SXGCN/GCE (x=80 %) demonstrates with a low detection limit of 0.9083 μM with linear range of 1–90 μM. Furthermore, the practical application of this sensor was successfully proved by detecting spiked 2,4‐dinitrophenol in a real gym supplements sample.
A Comparative Study of Voltammetric vs Impedimetric Immunosensor for Rapid SARS‐CoV‐2 Detection at the Point‐of‐care
Authors: Tortolini Cristina , Angeloni Antonio , Antiochia Riccarda 
Published: September 2022

AbstractHere, a novel biosensing platform for the detection of SARS‐CoV‐2 usable both at voltammetric and impedimetric mode is reported. The platform was constructed on a multi‐walled carbon nanotubes (MWCNTs) screen‐printed electrode (SPE) functionalized by methylene blue (MB), antibodies against SARS‐CoV‐2 spike protein (SP), a bioactive layer of chitosan (CS) and protein A (PrA). The voltammetric sensor showed superior performances both in phosphate buffer solution (PBS) and spiked‐saliva samples, with LOD values of 5.0±0.1 and 30±2.1 ng/mL, compared to 20±1.8 and 50±2.5 ng/mL for the impedimetric sensor. Moreover, the voltammetric immunosensor was tested in real saliva, showing promising results.
UV-dependent freshwater effect factor of nanoscale titanium dioxide for future life cycle assessment application
Authors: Zhang Shaoqiong , Ke Mingyan , Li Liang , Chen Keyan , Hicks Andrea , Wu Fan , You Jing 
Published: September 2022

Abstract
Environmental impacts of nanoscale titanium dioxide (TiO2) should be assessed throughout the lifetime of nanoparticles (NPs) to improve the state of knowledge of the overall sustainability. Life cycle assessment (LCA) has been previously recognized as a promising approach to systematically evaluating environmental impacts of NPs. As a result of their unique nanospecific properties, characterization factors (CF) were previously used for compensating the release and potential impacts of TiO2 NPs. However, because TiO2 NPs are known to generate reactive oxygen species and elicit toxicity to freshwater organisms, the lack of adequate UV-dependent effect factors (EFs) remains a major shortcoming when addressing their life cycle impacts. To complement the LCA of TiO2-NPs-enabled products under their specific applications, we recapitulated the freshwater toxicity of TiO2 NPs and then modeled in USEtox to determine trophic level EF ranges under UV and non-UV exposure conditions. Results indicate that EFs derived for non-UV exposure were 52 (42.9‒65) potentially affected fraction (PAF) m3/kg, and combined toxicity data derived EFs were 70.1 (55.6‒90.5) PAF m3/kg. When considering only the UV-induced exposure condition, the modeled EF increased to 500 (333‒712) PAF m3/kg. Our work highlights that case-dependent EFs should be considered and applied to reflect more realistic ecological impacts and illustrate comprehensive life cycle environmental impacts for nanoenabled products. Integr Environ Assess Manag 2023;19:578–585. © 2022 SETAC
Social environment risk factors for violence, family context, and trajectories of social‐emotional functioning among Latinx adolescents
Authors: Stoner Marie C. D. , Browne Erica N. , Raymond‐Flesch Marissa , McGlone Linda , Morgan‐Lopez Antonio , Minnis Alexandra M. 
Published: September 2022

AbstractIntroductionHigh social‐emotional functioning, including emotion regulation and nonviolent conflict resolution, constitute developmental competencies of adolescence that promote health and well‐being. We used prospective longitudinal data from a predominantly Latinx population to understand how family context and social environment risk factors for violence related to patterns of social‐emotional functioning during the transition between middle school and high school.MethodsWe prospectively interviewed 599 8th graders every 6 months for 2 years. We used trajectory models to explore longitudinal patterns of emotion regulation and nonviolent problem solving and multinomial regression to distinguish how these groups were associated with family context, partner and peer gang involvement, and neighborhood social disorder.ResultsYouth reporting lower neighborhood disorder in 8th grade were more likely to be in the high emotion regulation trajectory group. Youth without exposure to gangs through peers and partners in 8th grade were more likely to be in the high nonviolent problem‐solving skills trajectory group. Family cohesion was associated with being in the high trajectory groups for both emotional regulation and problem‐solving skills.ConclusionEmotion regulation and nonviolent problem‐solving skills had different associations with the social environment risk factors for violence examined, indicating that mechanisms of influence and strategies for intervention may vary. The association between problem‐solving skills and exposure to gangs through peers and partners shows that social norms may be important targets of change. Additionally, interventions with parents that build family cohesion during adolescence may buffer environmental exposures that shape adolescents' ability to practice protective social‐emotional behaviors.
Bradykinin/bradykinin 1 receptor promotes brain microvascular endothelial cell permeability and proinflammatory cytokine release by downregulating Wnt3a
Authors: Huang Linqiang , Liu Mengting , Jiang Wenqiang , Ding Hongguang , Han Yongli , Wen Miaoyun , Li Ya , Liu Xiaoyu , Zeng Hongke 
Published: September 2022

AbstractStroke is a life‐threatening disease with limited therapeutic options. Damage to the blood–brain barrier (BBB) is the key pathological feature of ischemic stroke. This study explored the role of the bradykinin (BK)/bradykinin 1 receptor (B1R) and its mechanism of action in the BBB. Human brain microvascular endothelial cells (BMECs) were used to test for cellular responses to BK by using the Cell Counting Kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine staining, enzyme‐linked immunosorbent assay, flow cytometry, immunofluorescence, cellular permeability assays, and western blotting to evaluate cell viability, cytokine production, and reactive oxygen species (ROS) levels in vitro. A BBB induced by middle cerebral artery occlusion was used to evaluate BBB injuries, and the role played by BK/B1R in ischemic/reperfusion (I/R) was explored in a rat model. Results showed that BK reduced the viability of BMECs and increased the levels of proinflammatory cytokines (interleukin 6 [IL‐6], IL‐18, and monocyte chemoattractant protein‐1) and ROS. Additionally, cellular permeability was increased by BK treatment, and the expression of tight junction proteins (claudin‐5 and occludin) was decreased. Interestingly, Wnt3a expression was inhibited by BK and exogenous Wnt3a restored the effects of BK on BMECs. In an in vivo I/R rat model, knockdown of B1R significantly decreased infarct volume and inflammation in I/R rats. Our results suggest that BK might be a key inducer of BBB injury and B1R knockdown might provide a beneficial effect by upregulating Wnt3a.
Exploration of the underlying mechanisms of isoniazid/rifampicin‐induced liver injury in mice using an integrated proteomics and metabolomics approach
Authors: Song Yanqing , Qu Xiaoyu , Tao Lina , Gao Huan , Zhang Yueming , Zhai Jinghui , Gong Jiawei , Hu Tingting 
Published: September 2022

AbstractThe hepatotoxic mechanism resulting from coadministration of isoniazid (INH) and rifampicin (RIF) are complex and studies remain inconclusive. To systematically explore the underlying mechanisms, an integrated mass‐based untargeted metabolomics and label‐free quantitative proteomics approach was used to clarify the mechanism of INH/RIF‐induced liver injury. Thirty male mice were randomly divided into three groups: control (receiving orally administered vehicle solution), INH (150 mg/kg) + RIF (300 mg/kg) orally administered for either 7 or 14 days, respectively. Serum was collected for the analysis of biochemical parameters and liver samples were obtained for mass spectrum‐based proteomics, metabolomics, and lipidomics analysis. Overall, 511 proteins, 31 metabolites, and 23 lipids were dysregulated and identified, and disordered biological pathways were identified. The network of integrated multiomics showed that glucose, lipid, and amino acid metabolism as well as energy metabolism were mainly dysregulated and led to oxidative stress, inflammation, liver steatosis, and cell death induced by INH and RIF. Coadministration of INH and RIF can induce liver injury by oxidative stress, inflammation, liver steatosis, and cell death, and the reduction in glutathione levels may play a critical role in these systematic changes and warrants further study.