bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Drug–Drug Interaction Potential of Enarodustat (JTZ‐951) Using a Cytochrome P450 Probe Cocktail
Authors: Pai Sudhakar M. , Yamada Hiroyuki , Murata Hiroyuki 
Published: June 2023

AbstractThe drug interaction potential of enarodustat (doses: 25, 50 mg) on the activity of cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4 was evaluated after once‐daily administration for 15 days in a phase 1 multiple‐ascending‐dose study in healthy subjects. Probe substrates specific for the enzymes, i.e., caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4), were administered orally as a cocktail with (day 15) and without (day −3) enarodustat. Drug interaction was based on geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration‐time curve from the time of dosing to infinity (AUCinf) ratios (day 15/day −3) for CYP1A2, 2C9, 2C19, 2D6, 3A4, and urinary excretion of dextromethorphan metabolite dextrorphan for CYP2D6. At the 2 enarodustat doses, for caffeine, the geometric mean ratios (range) for Cmax and AUCinf were 0.99–1.06 and 1.61–1.63, respectively. The ratios for peak concentrations and total exposures were 0.98–1.07 and 0.71–1.78 for tolbutamide and omeprazole, respectively. For dextrorphan the Cmax and AUCinf ratios were 0.83–0.90 and 1.02–1.04, respectively. The mean dextrorphan cumulative amount excreted into the urine from the time of dosing to 24 hours values on day −3 and day 15 were 8.25 mg and 8.20 mg at the lower dose, and 9.40 mg and 9.51 mg at the higher dose. The ratios for midazolam Cmax and AUCinf were 1.42–1.63. Overall, there was a lack of enarodustat dose dependency regarding the geometric mean ratios and 90% confidence intervals and urinary excretion of dextrorphan. There were some cases where the 90% confidence intervals at the 2 enarodustat doses were outside the 0.80–1.25 range, but changes in the geometric mean ratios were all <2‐fold.
Excited State Photophysics of Curcumin and its Modulation in Alkaline Non‐Aqueous Medium
Authors: Ghosh Meghna , Parida Sanjukta , Khatoon Huma , Bera Nanigopal , Mishra Sabyashachi , Sarkar Nilmoni 
Published: June 2023

AbstractCurcumin, a well‐known medicinal pigment, has seen limited applications in biology despite having great potential as a therapeutic drug. Deprotonation is one of the possible ways to enhance solubility of curcumin in polar solvent. Here, we have explored the effect of deprotonation on the ultrafast dynamics of this biomolecule with the help of the time‐resolved fluorescence spectroscopic measurements using the femtosecond fluorescence upconversion technique. The excited state photophysics of fully deprotonated curcumin significantly differs from that of neutral curcumin. We have observed that the completely deprotonated curcumin not only has higher quantum yield, but also higher excited state lifetime and slower solvation dynamics in comparison to neutral curcumin. We propose solvation dynamics and intramolecular charge transfer as the excited state processes associated with the radiative decay of the completely deprotonated molecule, while ruling out the possibility of excited state proton exchange or proton transfer. Our results are well supported by time‐dependent density‐functional theory calculations. Lastly, we have also demonstrated the possibility of modulating the ultrafast dynamics of fully deprotonated curcumin using non‐aqueous alkaline binary solvent mixtures. We believe our results will provide significant physical insight towards unveiling the excited state dynamics of this molecule.
Comparison of the Ability of N‐Bases to Engage in Noncovalent Bonds
Authors: Amonov Akhtam , Scheiner Steve 
Published: June 2023

AbstractThe lone pair of the N atom is a common electron donor in noncovalent bonds. Quantum calculations examine how various aspects of the base on which the N is located affect the strength and other properties of complexes formed with Lewis acids FH, FBr, F2Se, and F3As that respectively encompass hydrogen, halogen, chalcogen, and pnicogen bonds. In most cases the halogen bond is the strongest, followed in order by chalcogen, hydrogen, and pnicogen. The noncovalent bond strength increases in the sp<sp2<sp3 order of hybridization of N. Replacement of H substituents on the base by a methyl group or substituting N by C atom to which the base N is attached, strengthens the bond. The strongest bonds occur for trimethylamine and the weakest for N2.
Grain yield response to planting date and cutting height of the first crop in rice ratooning
Authors: Nakano Hiroshi , Tanaka Ryo , Hakata Makoto 
Published: June 2023

AbstractRice (Oryza sativa L.) ratooning is one of the most essential production strategies to increase grain yield. Field experiments were conducted in southwestern Japan in 2021 and 2022 to determine the effects of planting date and cutting height of the first crop on grain yield. Grain yield of the second crop was higher at early planting date than at late planting date in 2021, but the yield difference was narrowed in 2022. The higher grain yield at early planting date resulted from the higher number of spikelets and percentage of filled spikelets due to the higher stubble nonstructural carbohydrate (NSC) content, leaf area index (LAI), and air temperatures. Grain yield of the second crop was higher at high cutting height than at low cutting height in 2021, but the yield difference was narrowed in 2022. The higher grain yield at high cutting height resulted from the higher number of spikelets due to the higher NSC content and LAI. In the weather conditions, grain yield had a strong positive correlation with the air temperature, which had positive correlations with the number of panicle and percentage of filled spikelets. In the stubble conditions, grain yield had a strong positive correlation with NSC content, which had positive correlations with the number of panicle and percentage of filled spikelets. Therefore, early planting, which secures high air temperatures, and high cutting height, which produces high NSC content, are recommended to increase grain yield of the second crop.
Hexahydrocannabinol and closely related semi‐synthetic cannabinoids: A comprehensive review
Authors: Ujváry István 
Published: June 2023

AbstractSince the early 2000s, there has been a turmoil on the global illicit cannabinoid market. Parallel to legislative changes in some jurisdictions regarding herbal cannabis, unregulated and cheap synthetic cannabinoids with astonishing structural diversity have emerged. Recently, semi‐synthetic cannabinoids manufactured from hemp extracts by simple chemical transformations have also appeared as recreational drugs. The burst of these semi‐synthetic cannabinoids into the market was sparked by legislative changes in the United States, where cultivation of industrial hemp restarted. By now, hemp‐derived cannabidiol (CBD), initially a blockbuster product on its own, became a “precursor” to semi‐synthetic cannabinoids such as hexahydrocannabinol (HHC), which appeared on the drug market in 2021. The synthesis and cannabimimetic activity of HHC were first reported eight decades ago in quest for the psychoactive principles of marijuana and hashish. Current large‐scale manufacture of HHC is based on hemp‐derived CBD extract, which is converted first by cyclization into a Δ8/Δ9‐THC mixture, followed by catalytic hydrogenation to afford a mixture of (9R)‐HHC and (9S)‐HHC epimers. Preclinical studies indicate that (9R)‐HHC has THC‐like pharmacological properties. The animal metabolism of HHC is partially clarified. The human pharmacology including metabolism of HHC is yet to be investigated, and (immuno)analytical methods for the rapid detection of HHC or its metabolites in urine are lacking. Herein, the legal background for the revitalization of hemp cultivation, and available information on the chemistry, analysis, and pharmacology of HHC and related analogs, including HHC acetate (HHC‐O) is reviewed.
Social situations differ in their contribution to population‐level social structure in griffon vultures
Authors: Sharma Nitika , Anglister Nili , Spiegel Orr , Pinter‐Wollman Noa 
Published: June 2023

AbstractSocial relationships among animals emerge from interactions in multiple ecological and social situations. However, we seldom ask how each situation contributes to the global structure of a population, and whether different situations contribute different information about social relationships and the position of individuals within the social fabric. Griffon vultures (Gyps fulvus) interact socially in multiple situations, including communal roosting, joint flights, and co‐feeding. These social interactions can influence population‐level outcomes, such as disease transmission and information sharing that determine survival and response to changes. We examined the unique contribution of each social and ecological situation to the social structure of the population and individuals' positions within the overall social network using high‐resolution GPS tracking. We found that the number of individuals each vulture interacted with (degree) was best predicted by diurnal interactions—both during flights and on the ground (such as when feeding). However, the strength of social bonds, that is, the number of interactions an individual had (strength), was best predicted by interactions on the ground—both during the day (e.g., while feeding) and at night (e.g., while roosting) but not by interactions while flying. Thus, social situations differ in their impact on the relationships that individuals form. By incorporating the ecological situations in which social interactions occur we gain a more complete view of how social relationships are formed and which situations are important for different types of interactions.
Challenging state authority and hierarchical power: A case study of the engagement of Peru's Amazonian Indigenous Peoples' organizations in the governance of REDD+
Authors: Lozano Flores Liliana , Delgado Pugley Deborah , Casas Luna Santiago , Van den Broeck Pieter , Parra Constanza 
Published: June 2023

AbstractThe reducing emissions from deforestation and degradation (REDD+) mechanism is a climate change mitigation policy tool widely used in tropical forested countries that faces institutional and governance challenges in its implementation. Peru provides a particularly rich case study to analyze the agency of Amazonian Indigenous Peoples' organizations (IPOs) in the development of a national REDD+ policy. We examine the multi‐scalar interaction between the Peruvian State and IPOs in the governance of REDD+, identifying the role of Amazonian Indigenous groups in this process. Drawing on socio‐ecological governance and political economy approaches, we analyze data collected through interviews and participant observation. The article provides a case study of how IPOs work within the evolving governance system of REDD+ in Peru—both in responding to opportunities and in shaping the emergent system. Furthermore, it reveals that IPOs' rights and equity frame—deployed through several multi‐scalar strategies—has finally found a place in Peru's REDD+ governance. This has resulted in a more pluralistic mode of coordination between the State and IPOs and in the increase of the socio‐political empowerment of Indigenous Peoples. Our analysis suggests that Peru's REDD+ policies could progress toward more equitable outcomes through a true operationalization of cohesiveness and inclusiveness that encourages a meaningful relationship building between the state and Indigenous Peoples.
Ligusticum chuanxiong prevents high‐fat‐diet‐induced lipid metabolism disorder in mice by modulating the genes in the cholesterol pathway
Authors: Ge Huifang , Ye Xianjiang , Chen Qihe , Ye Jia , Chen Jicheng 
Published: June 2023

AbstractLigusticum chuanxiong (LC) has been widely used for cardiovascular and cerebrovascular diseases. LC Hort extraction (LCE) can regulate high‐fat‐diet (HFD)‐induced lipid metabolic disorders (LMDs). However, the potential mechanism of LCE alleviates LMDs has not been entirely determined. This study aimed to investigate the potential effect of LCE in regulating LMDs and reveal its intervention mechanism. LCE was used as the alternative constituent to intervene in HFD‐induced LMDs. LCE antioxidant activity, toxicity, and the effects on serum lipid metabolism index were also determined. The potential intervention mechanism was investigated using the transcriptome analysis. Results confirmed that LCE administration remarkably decreased mice body weight, serum lipid indexes (total cholesterol [TC], triglyceride, low‐density lipoprotein cholesterol, nonesterified fatty acid, and total bile acid), and liver malondialdehyde levels. LCE intervention increased the serum high‐density lipoprotein cholesterol concentration and LPS enzyme activities, and LCE was nontoxic. The liver antioxidantive enzymes, such as catalase, superoxide dismutase, glutathione, lipoprotein lipase, and hepatic lipase, were enhanced. RNA‐seq Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis confirmed that LCE was mainly involved in the lipid metabolism–related signaling pathways, especially for cholesterol biogenesis and metabolic signaling pathways. Besides, genes, such as Cyp51, Msoml, Apof, Pmvk, Nsdh1, ApoA‐1, ApoC‐1, and Lcat, might have been upregulated, thus further inhibiting cholesterol synthesis. By upregulating genes related to the bile acid signaling pathway, such as CYP7A1, CYP27A1, and ABCG5/8, the conversion of TC into bile acid was accelerated, and cholesterol levels decreased. LCE could serve as an alternative Chinese medicine for alleviating HFD‐induced LMDs symptoms through multichannel interactions. This study provides a reference for exploring new functions of LC, especially for regulating LMDs.
Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome
Authors: Whiteside David J. , Street Duncan , Murley Alexander G. , Jones P. Simon , Malpetti Maura , Ghosh Boyd C. P. , Coyle‐Gilchrist Ian , Gerhard Alexander , Hu Michele T. , Klein Johannes C. , Leigh P. Nigel , Church Alistair , Burn David J. , Morris Huw R. , Rowe James B. , Rittman Timothy 
Published: June 2023

AbstractThere is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson‐plus and the UK National PSP Research Network (PROSPECT‐MR). Resting‐state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large‐scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between‐network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five‐fold cross‐validation. In PSP and CBS, between‐network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between‐network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics.
The impact of leadership styles on employee safety behaviour among Chinese healthcare workers: The moderating role of cooperation facilitation
Authors: Li Cai , Murad Majid , Awais‐E‐Yazdan Muhammad 
Published: June 2023

AbstractWith the support of social exchange theory and social impact theory, this study aimed to examine the impact of transactional and transformational leadership on safety behaviour with the moderating role of cooperation facilitation in Chinese healthcare workers. This study used a simple random sampling method and data were collected from healthcare workers in Zhenjiang city, Jiangsu province, China. A total of 376 questionnaires were utilised and partial least squares structural equation modelling (PLS‐SEM) technique was used for data analysis. The result showed that transactional and transformational leadership positively impact safety behaviour of health care workers. The findings also indicated that cooperation facilitation positively moderates the relationship between transactional and transformational leadership on safety behaviour. This study provides an insightful contribution that leadership must encourage the workers to cooperate in safety‐related activities to make the work environment healthier and safer. Lastly, this study also discussed some theoretical and practical implications for researchers and policymakers.
Ruptured splenic artery aneurysm in pregnancy
Authors: Momoh Rabiu , Kent Olivia , Lambourne Joanna , Fernandes Roland 
Published: June 2023

SynopsisA rare case of a massive hemorrhage from a ruptured splenic artery aneurysm (SAA) in pregnancy that resulted in an emergency laparotomy, splenectomy, and cesarean section with maternal survival, but fetal loss, is presented. The development of protocols or guidelines for the early identification or prevention of SAA rupture in pregnancy would be of greater importance than reactive measures to control acute SAA bleeds.
Sweroside alleviates hepatic steatosis in part by activating AMPK/mTOR‐mediated autophagy in mice
Authors: Ding Yan , Chen Yuefu , Hu Ke , Yang Qiansheng , Li Yuxian , Huang Minjiang 
Published: June 2023

AbstractIn this study, we investigated the effect of sweroside (SOS) on hepatic steatosis in mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of nonalcohol fatty liver disease (NAFLD) to explore the effect of SOS on hepatic steatosis in NAFLD mice. In in vitro experiments, primary mouse hepatocytes were treated with palmitic acid and SOS, and the protective effects of SOS on inflammation, lipogenesis, and fat deposition were analyzed. Autophagy‐related protein levels and their related signaling pathways were evaluated in both in vivo and in vitro experiments. The results demonstrated that SOS decreased the high‐fat‐induced intrahepatic lipid content both in vivo and in vitro. The autophagy level in the liver was decreased in NAFLD mice but was reactivated following SOS intervention. SOS intervention was found to partially activate autophagy via the adenosine monophosphate‐activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Consequently, when the AMPK/mTOR pathway was suppressed or autophagy was inhibited, the beneficial effects of SOS intervention on hepatic steatosis were diminished. These results indicate that SOS intervention attenuates hepatic steatosis by promoting autophagy in the liver of NAFLD mice, in part by activating the AMPK/mTOR signaling pathway.
Osteohematology: To be or Notch to be
Authors: Rothzerg Emel , Erber Wendy N. , Gibbons Christopher L. M. H. , Wood David , Xu Jiake 
Published: June 2023

AbstractOsteohematology is an emerging research field that studies the crosstalk between hematopoietic and bone stromal cells, to elucidate the mechanisms of hematological and skeletal malignancies and diseases. The Notch is an evolutionary conserved developmental signaling pathway, with critical roles in embryonic development by controlling cell proliferation and differentiation. However, the Notch pathway is also critically involved in cancer initiation and progression, such as osteosarcoma, leukemia, and multiple myeloma. The Notch‐mediated malignant cells dysregulate bone and bone marrow cells in the tumour microenvironment, resulting in disorders ranging from osteoporosis to bone marrow dysfunction. To date, the complex interplay of Notch signaling molecules in hematopoietic and bone stromal cells is still poorly understood. In this mini‐review, we summarize the crosstalk between cells in bone and bone marrow and their influence under the Notch signaling pathway in physiological conditions and in tumour microenvironment.
RIG‐I contributes to keratinocyte proliferation and wound repair by inducing TIMP‐1 expression through NF‐κB signaling pathway
Authors: Zhu Huiyuan , Li Qianyu , Huang Qiongyi , Yang Huiqiong , Zheng Jiayi , Xie Ruting , Han Dongyan , Wei Qing 
Published: June 2023

AbstractEpithelial keratinocyte proliferation is an essential element of wound repair, and chronic wound conditions, such as diabetic foot, are characterized by aberrant re‐epithelialization. In this study, we examined the functional role of retinoic acid inducible‐gene I (RIG‐I), a key regulator of epidermal keratinocyte proliferation, in promoting TIMP‐1 expression. We found that RIG‐I is overexpressed in keratinocytes of skin injury and underexpressed in skin wound sites of diabetic foot and streptozotocin‐induced diabetic mice. Moreover, mice lacking RIG‐I developed an aggravated phenotype when subjected to skin injury. Mechanistically, RIG‐I promoted keratinocyte proliferation and wound repair by inducing TIMP‐1 via the NF‐κB signaling pathway. Indeed, recombinant TIMP‐1 directly accelerated HaCaT cell proliferation in vitro and promoted wound healing in Ddx58−/− and diabetic mice in vivo. In summary, we demonstrated that RIG‐I is a crucial factor that mediates epidermal keratinocyte proliferation and may be a potential biomarker for skin injury severity, thus making it an attractive locally therapeutic target for the treatment of chronic wounds such as diabetic foot.
Pit 1 transporter (SLC20A1) as a key factor in the NPP1‐mediated inhibition of insulin signaling in human podocytes
Authors: Kulesza Tomasz , Typiak Marlena , Rachubik Patrycja , Rogacka Dorota , Audzeyenka Irena , Saleem Moin A. , Piwkowska Agnieszka 
Published: June 2023

AbstractPodocytes are crucially involved in blood filtration in the glomerulus. Their proper function relies on efficient insulin responsiveness. The insulin resistance of podocytes, defined as a reduction of cell sensitivity to this hormone, is the earliest pathomechanism of microalbuminuria that is observed in metabolic syndrome and diabetic nephropathy. In many tissues, this alteration is mediated by the phosphate homeostasis‐controlling enzyme nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). By binding to the insulin receptor (IR), NPP1 inhibits downstream cellular signaling. Our previous research found that hyperglycemic conditions affect another protein that is involved in phosphate balance, type III sodium‐dependent phosphate transporter 1 (Pit 1). In the present study, we evaluated the insulin resistance of podocytes after 24 h of incubation under hyperinsulinemic conditions. Thereafter, insulin signaling was inhibited. The formation of NPP1/IR complexes was observed at that time. A novel finding in the present study was our observation of an interaction between NPP1 and Pit 1 after the 24 h stimulation of podocytes with insulin. After downregulation of the SLC20A1 gene, which encodes Pit 1, we established insulin resistance in podocytes that were cultured under native conditions, manifested as a lack of intracellular insulin signaling and the inhibition of glucose uptake via the glucose transporter type 4. These findings suggest that Pit 1 might be a major factor that participates in the NPP1‐mediated inhibition of insulin signaling.