bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the main flavonoids of Abelmoschus manihot (L.) medik and their metabolites in the treatment of diabetic nephropathy
Authors: Diao Zhipeng , Yu Hongmei , Wu Yapeng , Sun Yuanbo , Tang Haitao , Wang Mei , Li Nan , Ge Haitao , Sun Jianguo , Gu Harvest F. 
Published: January 2024

Introduction: Huangkui capsule (HKC) is made from the ethanol extract of Abelmoschus manihot (L.) Medik [Malvaceae; abelmoschi corolla] and received approval from the China Food and Drug Administration (Z19990040) in 1999. Currently, HKC is used for treatment of the patients with diabetic nephropathy (DN) in China. The bioactive chemical constituents in HKC are total flavonoids of A. manihot (L.) Medik (TFA). The present study aims to identify the primary flavonoid metabolites in HKC and TFA and their metabolism fates in db/db mice, the animal model for the study of type 2 diabetes and DN.Methods: HKC (0.84 g/kg/d) and TFA (0.076 g/kg/d) or vehicle were respectively administered daily via oral gavage in db/db mice for 4 weeks. The metabolism fate of the main metabolites of HKC in serum, liver, kidney, heart, jejunum, colon, jejunal contents, colonic contents, and urine of db/db mice were analyzed with a comprehensive metabolite identification strategy.Results and Discussion: In db/db mice administered with HKC and TFA, 7 flavonoid prototypes and 38 metabolites were identified. The related metabolic pathways at Phases I and II reactions included dehydroxylation, deglycosylation, hydrogenation, methylation, glucuronidation, sulphation, and corresponding recombined reactions. Quercetin, isorhamnetin, quercetin sulphate, quercetin monoglucuronide, and isorhamnetin monoglucuronide presented a high exposure in the serum and kidney of db/db mice. Thereby, the present study provides a pharmacodynamic substance basis for better understanding the mechanism of A. manihot (L.) Medik for medication of DN.
Anti-seizure effects of JNJ-54175446 in the intra-amygdala kainic acid model of drug-resistant temporal lobe epilepsy in mice
Authors: Mamad Omar , Heiland Mona , Lindner Andreas U. , Hill Thomas D. M. , Ronroy Ronan M. , Rentrup Kilian , Sanz-Rodriguez Amaya , Langa Elena , Heller Janosch P. , Moreno Oscar , Llop Jordi , Bhattacharya Anindya , Palmer James A. , Ceusters Marc , Engel Tobias , Henshall David C. 
Published: January 2024

There remains a need for new drug targets for treatment-resistant temporal lobe epilepsy. The ATP-gated P2X7 receptor coordinates neuroinflammatory responses to tissue injury. Previous studies in mice reported that the P2X7 receptor antagonist JNJ-47965567 suppressed spontaneous seizures in the intraamygdala kainic acid model of epilepsy and reduced attendant gliosis in the hippocampus. The drug-resistance profile of this model is not fully characterised, however, and newer P2X7 receptor antagonists with superior pharmacokinetic profiles have recently entered clinical trials. Using telemetry-based continuous EEG recordings in mice, we demonstrate that spontaneous recurrent seizures in the intraamygdala kainic acid model are refractory to the common anti-seizure medicine levetiracetam. In contrast, once-daily dosing of JNJ-54175446 (30 mg/kg, intraperitoneal) resulted in a significant reduction in spontaneous recurrent seizures which lasted several days after the end of drug administration. Using a combination of immunohistochemistry and ex vivo radiotracer assay, we find that JNJ-54175446-treated mice at the end of recordings display a reduction in astrogliosis and altered microglia process morphology within the ipsilateral CA3 subfield of the hippocampus, but no difference in P2X7 receptor surface expression. The present study extends the characterisation of the drug-resistance profile of the intraamygdala kainic acid model in mice and provides further evidence that targeting the P2X7 receptor may have therapeutic applications in the treatment of temporal lobe epilepsy.
CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation
Authors: Seligson Nathan D. , Zhang Xunjie , Zemanek Mark C. , Johnson Jasmine A. , VanGundy Zachary , Wang Danxin , Phelps Mitch A. , Roddy Julianna , Hofmeister Craig C. , Li Junan , Poi Ming J. 
Published: January 2024

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described.Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642).Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p &lt; 0.001) and throughout the entirety of the study period (p &lt; 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population.Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.
Protocol for 3D virtual histology of unstained human brain tissue using synchrotron radiation phase-contrast microtomography
Authors: Lee Ju Young , Donato Sandro , Mack Andreas F. , Mattheus Ulrich , Tromba Giuliana , Longo Elena , D’Amico Lorenzo , Mueller Sebastian , Shiozawa Thomas , Bause Jonas , Scheffler Klaus , Longo Renata , Hagberg Gisela E. 
Published: January 2024

X-ray phase-contrast micro computed tomography using synchrotron radiation (SR PhC-µCT) offers unique 3D imaging capabilities for visualizing microstructure of the human brain. Its applicability for unstained soft tissue is an area of active research. Acquiring images from a tissue block without needing to section it into thin slices, as required in routine histology, allows for investigating the microstructure in its natural 3D space. This paper presents a detailed step-by-step guideline for imaging unstained human brain tissue at resolutions of a few micrometers with SR PhC-µCT implemented at SYRMEP, the hard X-ray imaging beamline of Elettra, the Italian synchrotron facility. We present examples of how blood vessels and neurons appear in the images acquired with isotropic 5 μm and 1 µm voxel sizes. Furthermore, the proposed protocol can be used to investigate important biological substrates such as neuromelanin or corpora amylacea. Their spatial distribution can be studied using specifically tailored segmentation tools that are validated by classical histology methods. In conclusion, SR PhC-µCT using the proposed protocols, including data acquisition and image processing, offers viable means of obtaining information about the anatomy of the human brain at the cellular level in 3D.
Comparison of effects of modafinil and caffeine on fatigue-vulnerable and fatigue-resistant aircrew after a limited period of sleep deprivation
Authors: Wingelaar-Jagt Yara Q. , Wingelaar Thijs T. , Riedel Wim J. , Ramaekers Johannes G. 
Published: January 2024

Introduction: Literature suggests pilots experience fatigue differently. So-called fatigue-resistant or -vulnerable individuals might also respond differently to countermeasures or stimulants. This study, which is part of a larger randomized controlled clinical trial, aims to investigate the effect of caffeine and modafinil on fatigue-resistant and -vulnerable pilots.Methods: This study included 32 healthy employees of the Royal Netherlands Air Force, who completed three test days, separated by at least 7 days. After a regular work day, the subjects were randomly administered either 300 mg caffeine, 200 mg modafinil or placebo at midnight. Hereafter the subjects performed the psychomotor vigilance test (PVT), vigilance and tracking test (VigTrack) and Stanford sleepiness scale (SSS) six times until 8 a.m. the next day. Subjects were ranked on the average number of lapses on the PVT during the placebo night and divided into three groups: fatigue-vulnerable (FVUL), -intermediate (FINT) and -resistant (FRES), with 11, 10 and 11 subjects in each group, respectively. Area under the curve (AUC) of the PVT, VigTrack and SSS during the test nights were calculated, which were used in univariate factorial analysis of variance (ANOVA). Tukey’s HSD post hoc tests were used to differentiate between the groups.Results: A significant effect of treatment was found in the ANOVA of both PVT parameters, VigTrack mean reaction time and SSS. There was a statistically significant effect of fatigue group on all PVT parameters and VigTrack mean percentage omissions, where FINT and FRES scored better than FVUL. There was a significant interaction effect between treatment and fatigue group for PVT number of lapses. This is congruent for the AUC analyses in which for all parameters (except for the SSS) the performance of the FVUL group was consistently worse than that of the FINT and FRES groups.Discussion: This study demonstrates that the performance of individuals with different fatigue tolerances are differently affected by simulants after a limited period of sleep deprivation. The classification of fatigue tolerance through PVT lapses when sleep deprived seems to be able to predict this.
Effects of photon irradiation in the presence and absence of hindlimb unloading on the behavioral performance and metabolic pathways in the plasma of Fischer rats
Authors: Raber Jacob , Holden Sarah , Kessler Kat , Glaeser Breanna , McQuesten Chloe , Chaudhari Mitali , Stenzel Fiona , Lenarczyk Marek , Leonard Scott Willem , Morré Jeffrey , Choi Jaewoo , Kronenberg Amy , Borg Alexander , Kwok Andy , Stevens Jan Frederik , Olsen Christopher , Willey Jeffrey S. , Bobe Gerd , Minnier Jessica , Baker John E. 
Published: January 2024

Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures.Methods: A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses.Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&amp;M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures.Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.
Active vitamin D increases myogenic differentiation in C2C12 cells via a vitamin D response element on the myogenin promoter
Authors: Alliband Kathryn H. , Parr Tim , Jethwa Preeti H. , Brameld John M. 
Published: January 2024

Background: Skeletal muscle development during embryogenesis depends on proliferation of myoblasts followed by differentiation into myotubes/multinucleated myofibers. Vitamin D (VD) has been shown to affect these processes, but there is conflicting evidence within the current literature on the exact nature of these effects due to a lack of time course data. With 20%–40% of pregnant women worldwide being VD deficient, it is crucial that a clearer understanding of the impact of VD on myogenesis is gained.Methods: A detailed 8-day differentiation time course was used where C2C12 cells were differentiated in control media (2% horse serum) or with different concentrations of active VD, 1,25 (OH)2D3 (10−13 M, 10−11 M, 10−9 M or 10−7 M), and measurements were taken at 6 time points. DNA, creatine kinase and protein assays were carried out as well as quantitative PCR to determine expression of Myf5, MyoD, myogenin, MHC I, and MHC neonatal, MHC embryonic, MHC IIa, MHC IIx, and MHC IIb mRNAs. Transfections were carried out using one vector containing the myogenin promoter and another containing the same promoter with a 3 base mutation within a putative vitamin D response element (VDRE) to determine effects of 1,25 (OH)2D3 on myogenin transcription. Finally, a ChIP assay was performed to determine whether the VD receptor (VDR) binds to the putative VDRE.Results: 1,25(OH)2D3 caused an inhibition of proliferation and an increase in differentiation in C2C12 cells. Myf5, myogenin, MHC I, and MHC neonatal, MHC embryonic, MHC IIa, MHC IIx, and MHC IIb expression were all increased by 1,25(OH)2D3. Myotube size was also increased by VD. When the putative VDRE on the myogenin promoter was mutated, the increase in expression by VD was lost. ChIP analysis revealed that the VDR does bind to the putative VDRE on the myogenin promoter.Conclusion: Active VD directly increases myogenin transcription via a functional VDRE on the myogenin promoter, resulting in increased myogenic differentiation, increased expression of both the early and late MHC isoforms, and also increased myotube size. These results highlight the importance of VD status during pregnancy for normal myogenesis to occur, but further in vivo work is needed.
Spatial prediction of winter wheat yield gap: agro-climatic model and machine learning approaches
Authors: Mousavi Seyed Rohollah , Jahandideh Mahjenabadi Vahid Alah , Khoshru Bahman , Rezaei Meisam 
Published: January 2024

This study aimed to identify the most influential soil and environmental factors for predicting wheat yield (WY) in a part of irrigated croplands in southwest Iran, using the FAO-Agro-Climate method and machine learning algorithms (MLAs). A total of 60 soil samples and wheat grain (1 m × 1 m) in 1200 ha of Pasargad plain were collected and analyzed in the laboratory. Attainable WY was assessed using the FAO method for the area. Pearson correlation analysis was used to select the best set of soil properties for modeling. Topographic attributes and vegetation indices were used as proxies of landscape components and cover crop to map actual WY in the study area. Two well-known MLAs, random forest (RF) and artificial neural networks (ANNs), were utilized to prepare an actual continuous WY map. The k-fold method was used to determine the uncertainty of WY prediction and quantify the quality of prediction accuracy. Results showed that soil organic carbon (SOC) and total nitrogen (TN) had a positive and significant correlation with WY. The SOC, TN, normalized different vegetation index (NDVI), and channel network base level (CHN) were recognized as the most important predictors and justifying more than 50% of actual WY. The ANNs outperformed the RF algorithm with an R2 of 0.75, RMSE of 400 (kg ha−1), and RPD of 2.79, according to statistical indices. The uncertainty analysis showed that the maximum uncertainty of the prediction map [400 (kg ha−1)] was very low compared to the mean value [4937 (kg ha−1)] of WY map. Calculation yield gap using the FAO-agro-climatic model showed that the average yield gap of the region was about 50% of actual yield. The findings of this study demonstrated that integrating simulated attainable crop growth using crop model and a set of soil and environmental covariates with the ANNs algorithm can effectively predict WY gaps in large areas with acceptable and reasonable accuracy. The study emphasizes that the implementation of efficient management practices has the potential to enhance agricultural production in the study area and similar regions. These results represent a significant advancement of sustainable agriculture and provide valuable insights for ensuring global food security.
Genome-wide analysis of transmembrane 9 superfamily genes in wheat (Triticum aestivum) and their expression in the roots under nitrogen limitation and Bacillus amyloliquefaciens PDR1 treatment conditions
Authors: Li Fei , Xi Kuanling , Li Yuke , Ming Tang , Huang Yufeng , Zhang Lijun 
Published: January 2024

IntroductionTransmembrane 9 superfamily (TM9SF) proteins play significant roles in plant physiology. However, these proteins are poorly characterized in wheat (Triticum aestivum). The present study aimed at the genome-wide analysis of putative wheat TM9SF (TraesTM9SF) proteins and their potential involvement in response to nitrogen limitation and Bacillus amyloliquefaciens PDR1 treatments.MethodsTraesTM9SF genes were retrieved from the wheat genome, and their physiochemical properties, alignment, phylogenetic, motif structure, cis-regulatory element, synteny, protein-protein interaction (PPI), and transcription factor (TF) prediction analyses were performed. Transcriptome sequencing and quantitative real-time polymerase reaction (qRT-PCR) were performed to detect gene expression in roots under single or combined treatments with nitrogen limitation and B. amyloliquefaciens PDR1.Results and discussionForty-seven TraesTM9SF genes were identified in the wheat genome, highlighting the significance of these genes in wheat. TraesTM9SF genes were absent on some wheat chromosomes and were unevenly distributed on the other chromosomes, indicating that potential regulatory functions and evolutionary events may have shaped the TraesTM9SF gene family. Fifty-four cis-regulatory elements, including light-response, hormone response, biotic/abiotic stress, and development cis-regulatory elements, were present in the TraesTM9SF promoter regions. No duplication of TraesTM9SF genes in the wheat genome was recorded, and 177 TFs were predicted to target the 47 TraesTM9SF genes in a complex regulatory network. These findings offer valued data for predicting the putative functions of uncharacterized TM9SF genes. Moreover, transcriptome analysis and validation by qRT-PCR indicated that the TraesTM9SF genes are expressed in the root system of wheat and are potentially involved in the response of this plant to single or combined treatments with nitrogen limitation and B. amyloliquefaciens PDR1, suggesting their functional roles in plant growth, development, and stress responses.ConclusionThese findings may be vital in further investigation of the function and biological applications of TM9SF genes in wheat.
Strategies of state penetration: a network analysis of community governance in Shanghai
Authors: Tian Felicia F. , Chen Lin , Wang Yihan 
Published: January 2024

IntroductionThe Chinese state has been found to penetrate community participation to strengthen state infrastructure power, but understanding of these strategies remains equivocal.MethodsThis paper collect complete network data from a sample of 112 residents who were active in community activities in Kang community in Shanghai, China. Kang is an award-winning community for its active participation and excellent governance. We examine the strategies of state penetration on the relation between residents' committee (RC) and the thick network through routine community activities.ResultsThe network is indeed horizontal (rather than hierarchical) around the RC. Instead of manifesting state power, popularity within the network translates to decision-making power in deciding routine community activities. However, residents with high network popularity are affiliated with the state, and this association may be generated by the state itself through a deliberate process of cultivation and co-optation.DiscussionThese findings shed light on the nuanced strategies of state penetration. Rather than overt suppression or infiltration, the state exerts authority over a horizontal network, which ensures that self-organized community participation occurs under state domination.
Individual differences in scientists’ aesthetic disposition, aesthetic experiences, and aesthetic sensitivity in scientific work
Authors: Jacobi Christopher , Varga Peter J. , Jessani Zohaib , Vaidyanathan Brandon 
Published: January 2024

IntroductionThe role of personality in shaping engagement with aesthetics in science has been almost entirely unexplored. Whereas artists and arts settings (e.g., museums) are well-studied from a psychological perspective, the practice of science has often been seen as purely rational or dry. In response, this study presents novel findings on the critical role of scientists’ individual differences, which shape their engagement with aesthetics, such as the frequency of their experiences of beauty, wonder, and awe in their scientific work.MethodsBased on a very large and representative four-country study of scientists in the fields of biology and physics (N = 3,092), this study analyzed the associations of Big Five personality traits among scientists with (i) dispositional aesthetics (DPES-awe), (ii) the frequency of aesthetic experiences in scientific work, and (iii) aesthetic sensitivity in science. These survey-weighted OLS regression models included extensive statistical controls for sociodemographic factors.ResultsAs hypothesized, openness is positively, and neuroticism is negatively linked with dispositional aesthetics, the frequency of aesthetic experiences in scientific work, and aesthetic sensitivity in science. Unexpectedly, agreeableness and conscientiousness (but not extraversion) are highly significant and strong predictors of the three trait and state aesthetic engagement variables.DiscussionThe aesthetic engagement and personality framework of this paper is empirically supported and demonstrates the importance of personality types of scientists in the practice of science. The unexpectedly strong association of agreeableness with aesthetic engagement points to the importance of cooperation, collaboration, and communication to maximize scientific creativity.