bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteocytes contribute via nuclear receptor PPAR-alpha to maintenance of bone and systemic energy metabolism
Authors: Chougule Amit , Baroi Sudipta , Czernik Piotr J. , Crowe Emily , Chang Mi Ra , Griffin Patrick R. , Lecka-Czernik Beata 
Published: April 2023

IntroductionThe view that bone and energy metabolism are integrated by common regulatory mechanisms is broadly accepted and supported by multiple strands of evidence. This includes the well-characterized role of the PPARγ nuclear receptor, which is a common denominator in energy metabolism and bone metabolism. Little is known, however, about the role of PPARα nuclear receptor, a major regulator of lipid metabolism in other organs, in bone.MethodsA side-by-side comparative study of 5-15 mo old mice with global PPARα deficiency (αKO) and mice with osteocyte-specific PPARα deficiency (αOTKO) in order to parse out the various activities of PPARα in the skeleton that are of local and systemic significance. This study included transcriptome analysis of PPARα-deficient osteocytes, and analyses of bone mass and bone microarchitecture, systemic energy metabolism with indirect calorimetry, and differentiation potential of hematopoietic and mesenchymal bone cell progenitors. These analyses were paired with in vitro studies of either intact or silenced for PPARα MLO-A5 cells to determine PPARα role in osteocyte bioenergetics.ResultsIn osteocytes, PPARα controls large number of transcripts coding for signaling and secreted proteins which may regulate bone microenvironment and peripheral fat metabolism. In addition, PPARα in osteocytes controls their bioenergetics and mitochondrial response to stress, which constitutes up to 40% of total PPARα contribution to the global energy metabolism. Similarly to αKO mice, the metabolic phenotype of αOTKO mice (both males and females) is age-dependent. In younger mice, osteocyte metabolism contributes positively to global energetics, however, with aging the high-energy phenotype reverts to a low-energy phenotype and obesity develops, suggesting a longitudinal negative effect of impaired lipid metabolism and mitochondrial dysfunction in osteocytes deficient in PPARα. However, bone phenotype was not affected in αOTKO mice except in the form of an increased volume of marrow adipose tissue in males. In contrast, global PPARα deficiency in αKO mice led to enlarged bone diameter with a proportional increase in number of trabeculae and enlarged marrow cavities; it also altered differentiation of hematopoietic and mesenchymal marrow cells toward osteoclast, osteoblast and adipocyte lineages, respectively.DiscussionPPARα role in bone is multileveled and complex. In osteocytes, PPARα controls the bioenergetics of these cells, which significantly contributes to systemic energy metabolism and their endocrine/paracrine function in controlling marrow adiposity and peripheral fat metabolism.
Naringenin and β-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis
Authors: Coulter Ann A. , Greenway Frank L. , Zhang Dachuan , Ghosh Sujoy , Coulter Cathryn R. , James Sarah L. , He Yanlin , Cusimano Luke A. , Rebello Candida J. 
Published: April 2023

IntroductionNaringenin, a peroxisome proliferator-activated receptor (PPAR) activator found in citrus fruits, upregulates markers of thermogenesis and insulin sensitivity in human adipose tissue. Our pharmacokinetics clinical trial demonstrated that naringenin is safe and bioavailable, and our case report showed that naringenin causes weight loss and improves insulin sensitivity. PPARs form heterodimers with retinoic-X-receptors (RXRs) at promoter elements of target genes. Retinoic acid is an RXR ligand metabolized from dietary carotenoids. The carotenoid β-carotene reduces adiposity and insulin resistance in clinical trials. Our goal was to examine if carotenoids strengthen the beneficial effects of naringenin on human adipocyte metabolism.MethodsHuman preadipocytes from donors with obesity were differentiated in culture and treated with 8µM naringenin + 2µM β-carotene (NRBC) for seven days. Candidate genes involved in thermogenesis and glucose metabolism were measured as well as hormone-stimulated lipolysis.ResultsWe found that β-carotene acts synergistically with naringenin to boost UCP1 and glucose metabolism genes including GLUT4 and adiponectin, compared to naringenin alone. Protein levels of PPARα, PPARγ and PPARγ-coactivator-1α, key modulators of thermogenesis and insulin sensitivity, were also upregulated after treatment with NRBC. Transcriptome sequencing was conducted and the bioinformatics analyses of the data revealed that NRBC induced enzymes for several non-UCP1 pathways for energy expenditure including triglyceride cycling, creatine kinases, and Peptidase M20 Domain Containing 1 (PM20D1). A comprehensive analysis of changes in receptor expression showed that NRBC upregulated eight receptors that have been linked to lipolysis or thermogenesis including the β1-adrenergic receptor and the parathyroid hormone receptor. NRBC increased levels of triglyceride lipases and agonist-stimulated lipolysis in adipocytes. We observed that expression of RXRγ, an isoform of unknown function, was induced ten-fold after treatment with NRBC. We show that RXRγ is a coactivator bound to the immunoprecipitated PPARγ protein complex from white and beige human adipocytes.DiscussionThere is a need for obesity treatments that can be administered long-term without side effects. NRBC increases the abundance and lipolytic response of multiple receptors for hormones released after exercise and cold exposure. Lipolysis provides the fuel for thermogenesis, and these observations suggest that NRBC has therapeutic potential.
Characteristics of thermophysical parameters in the Wugongshan area of South China and their insights for geothermal genesis
Authors: Liu Kai , Zhang Yaoyao , He Qingcheng , Zhang Shouchuan , Jia Wuhui , He Xiaolong , Zhang Haoran , Wang Luyao , Wang Shuxun 
Published: April 2023

The Wugongshan area is rich in medium–low temperature convective geothermal resources, among which there are more than 10 geothermal fields in Wentang, Wanlongshan, Wenjia, Hongjiang, etc. There are few basic geothermal geological studies in the geothermal fields and their peripheral areas; thus far, no systematic research work into the thermophysical parameters has been carried out. In this paper, 85 rock samples were collected from the surface and boreholes covering the strata and magmatic rocks in the study area. The results show that the average radioheat generation rate, the average thermal conductivity, and the average specific heat are 0.24–5.49 (μW/m3), 1.995–4.390 (W/mK), and 1.318–4.829 (MJ/m3K), respectively. The average thermal diffusivity ranges from 1.115 to 1.611 × 10-6 m2/s. The highest radioheat generation rate is Jurassic granite, and the lowest is quartz vein. The largest thermal conductivity and specific heat is the siliceous quartzite, and the smallest is the quartz vein. The highest thermal diffusivity is Cambrian metamorphic mica schist, and the lowest is siliceous quartzite. The radioactive heat generation rate, thermal conductivity, specific heat, and thermal diffusivity are closely related to the chemical composition, mineral composition, rock fabric, porosity, water content, and temperature and pressure conditions of rocks in the whole area. There is a linear relationship between thermal conductivity (K) and thermal diffusivity (κ), and the correlation equation is K = −0.3144k + 3.2172. Combined with the characteristics of thermophysical parameters, the genetic theory of deep crust heat generation + structural heat accumulation + siliceous quartzite heat conduction + granite heat preservation is preliminarily proposed.
Orb weaver aggregate glue protein composition as a mechanism for rapid evolution of material properties
Authors: Ayoub Nadia A. , DuMez Lucas , Lazo Cooper , Luzaran Maria , Magoti Jamal , Morris Sarah A. , Baker Richard H. , Clarke Thomas , Correa-Garhwal Sandra M. , Hayashi Cheryl Y. , Friend Kyle , Opell Brent D. 
Published: April 2023

IntroductionOrb web and cobweb weaving spiders in the superfamily Araneoidea are distinguished by their ability to make a chemically sticky aqueous glue in specialized aggregate silk glands. Aggregate glue is an environmentally responsive material that has evolved to perform optimally around the humidity at which a spider forages. Protein components and their post-translational modifications confer stickiness to the glue, but the identities of these proteins have not been described for orb web weavers.MethodsUsing biomechanics, gene expression data, and proteomics, we characterized the glue’s physical properties and molecular components in two congeners that live in different environments, Argiope argentata (dry southwest US) and Argiope trifasciata (humid southeast US).ResultsThe droplets of A. argentata are less hygroscopic than those of A. trifasciata and have proportionately smaller viscoelastic protein cores, which incorporate a smaller percentage of absorbed water as humidity increases. Argiope argentata protein cores were many times stiffer and tougher than A. trifasciata protein cores. Each species’ glue included ~30 aggregate-expressed proteins, most of which were homologous between the two species, with high sequence identity. However, the relative contribution and number of gene family members of each homologous group differed. For instance, the aggregate spidroins (AgSp1 and AgSp2) accounted for nearly half of the detected glue composition in A. argentata, but only 38% in A. trifasciata. Additionally, AgSp1, which has highly negatively charged regions, was ~2X as abundant as the positively charged AgSp2 in A. argentata, but ~3X as abundant in A. trifasciata. As another example, A. argentata glue included 11 members of a newly discovered cysteine-rich gene family, versus 7 members in A. trifasciata.DiscussionCysteines form disulfide bonds that, combined with the higher potential for electrostatic interactions between AgSp1 and AgSp2, could contribute to the greater stiffness of A. argentata glue. The ability to selectively express different glue protein genes and/or to extrude their products at different rates provides a faster mechanism to evolve material properties than sequence evolution alone.
Identification and verification of ferroptosis-related genes in gastric intestinal metaplasia
Authors: Song Biao , Li Tingting , Zhang Yi , Yang Qi , Pei Bei , Liu Yun , Wang Jieyu , Dong Gang , Sun Qin , Fan Shanshan , Li Xuejun 
Published: April 2023

Background: Gastric intestinal metaplasia (IM) is the key link of gastric precancerous lesions. Ferroptosis is a novel form of programmed cell death. However, its impact on IM is unclear. The focus of this study is to identify and verify ferroptosis-related genes (FRGs) that may be involved in IM by bioinformatics analysis.Materials and methods: Differentially expressed genes (DEGs) were obtained from microarray dataset GSE60427 and GSE78523 downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed ferroptosis-related genes (DEFRGs) were obtained from overlapping genes of DEGs and FRGs got from FerrDb. DAVID database was used for functional enrichment analysis. Protein-protein interaction (PPI) analysis and Cytoscape software were used to screen hub gene. In addition, we built a receiver operating characteristic (ROC) curve and verified the relative mRNA expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the CIBERSORT algorithm was used to analyze the immune infiltration in IM.Results: First, a total of 17 DEFRGs were identified. Second, a gene module identified by Cytoscape software was considered as hub gene: PTGS2, HMOX1, IFNG, and NOS2. Third, ROC analysis showed that HMOX1 and NOS2 had good diagnostic characteristics. qRT-PCR experiments confirmed the differential expression of HMOX1 in IM and normal gastric tissues. Finally, immunoassay showed that the proportion of T cells regulatory (Tregs) and macrophages M0 in IM was relatively higher, while the proportion of T cells CD4 memory activated and dendritic cells activated was lower.Conclusion: We found significant associations between FRGs and IM, and HMOX1 may be diagnostic biomarkers and therapeutic targets for IM. These results may enhance our understanding of IM and may contribute to its treatment.
Preparation of graphene oxide–stabilized Pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against Chlamydia Trachomatis infection
Authors: Zhao Lanhua , Shu Mingyi , Chen Hongliang , Shi Keliang , Li Zhongyu 
Published: April 2023

BackgroundTraditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and therefore has potential to be used as a surfactant substitute to stabilize Pickering emulsions.MethodsIn this study, GO–stabilized Pickering emulsion (GPE) was prepared and used as an adjuvant to facilitate an enhanced immune response to the Chlamydia trachomatis (Ct) Pgp3 recombinant vaccine. Firstly, GPE was prepared by optimizing the sonication conditions, pH, salinity, GO concentration, and water/oil ratio. GPE with small-size droplets was characterized and chosen as the candidate. Subsequently, controlled-release antigen delivery by GPE was explored. Cellular uptake behaviors, M1 polarization, and cytokine stimulation by GPE + Pgp3 was considered in terms of the production of macrophages. Finally, GPE’s adjuvant effect was evaluated by vaccination with Pgp3 recombinant in BALB/c mouse models.ResultsGPE with the smallest droplet sizes was prepared by sonication under 163 W for 2 min at 1 mg/mL GO in natural salinity with a pH of 2 when the water/oil ratio was 10:1 (w/w). The optimized average GPE droplet size was 1.8 μm and the zeta potential was –25.0 ± 1.3 mv. GPE delivered antigens by adsorption onto the droplet surface, demonstrating the controlled release of antigens both in vitro and in vivo. In addition, GPE promoted antigen uptake, which stimulated proinflammatory tumor necrosis factor alpha (TNF-α), enhancing the M1 polarization of macrophages in vitro. Macrophage recruitment was also significantly promoted by GPE at the injection site. In the GPE + Pgp3 treatment group, higher levels of immunoglobin (IgG), immunoglobin G1 (IgG1), immunoglobin G2a (IgG2a) sera, and immunoglobin A (IgA) were detected in vaginal fluid, and higher levels of IFN-γ and IL-2 secretion were stimulated, than in the Pgp3 group, showing a significant type 1 T helper (Th1)-type cellular immune response. Chlamydia muridarum challenging showed that GPE enhanced Pgp3’s immunoprotection through its advanced clearance of bacterial burden and alleviation of chronic pathological damage in the genital tract.ConclusionThis study enabled the rational design of small-size GPE, shedding light on antigen adsorption and control release, macrophage uptake, polarization and recruitment, which enhanced augmented humoral and cellular immunity and ameliorated chlamydial-induced tissue damage in the genital tract.
Retrospective analysis of the long-term therapeutic effectiveness and safety profile of rituximab in the treatment of mucous membrane pemphigoid in a German university center between 2008 and 2019
Authors: Bamberger Florian , König Inke R. , Gola Damian , Zillikens Detlef , Sadik Christian D. 
Published: April 2023

BackgroundThe B-cell-depleting anti-CD20 antibody rituximab (RTX) is often used as an adjuvant drug for the treatment of refractory cases of mucous membrane pemphigoid (MMP).ObjectiveThis study aims to determine the therapeutic effectiveness and the safety profile of RTX in MMP.MethodsThe medical records of all cases of MMP treated with RTX between 2008 and 2019 in our university medical center located in northern Germany, which specialized in autoimmune blistering skin diseases, were retrieved and systemically analyzed for treatment responses and potential adverse events over a median period of 27 months.ResultsWe identified 18 MMP patients who received at least one cycle of RTX to treat MMP. RTX was always used as an adjuvant treatment, and its application did not change concomitant treatments. Under treatment with RTX, 67% of the patients achieved an improvement in their disease activity within 6 months. This was also reflected in a statistically significant reduction in the Mucous Membrane Pemphigoid Disease Index (MMPDAI) activity score. The frequency of infections under RTX treatment increased only slightly.ConclusionsThe use of RTX is associated with an attenuation of MMP in a large proportion of MMP patients in our study. At the same time, its application was not found to further increase the susceptibility of the most strongly immunocompromised population of MMP patients to opportunistic infections. Collectively, our results suggest that the potential benefits of RTX outweigh its risks in patients with refractory MMP.
Sources and sinks of bottom water oxygen in a seasonally hypoxic fjord
Authors: Rakshit Subhadeep , Dale Andrew W. , Wallace Douglas W. , Algar Christopher Kenneth 
Published: April 2023

Deoxygenation of the ocean has been occurring over the last half century, particularly in poorly ventilated coastal waters. In coastal and estuarine environments, both the water column and sediments play key roles in controlling oxygen variability. In this study, we focus on controls of oxygen concentration in Bedford Basin (BB), a 70 m deep, seasonally hypoxic semi-enclosed fjord on the West Atlantic coast in Nova Scotia. The basin is connected to the Scotian Shelf via a narrow 20 m deep sill that restricts the resupply of bottom water. Hypoxia was recorded seasonally in 2018, 2019 and 2021 with minimum oxygen concentration of 5, 6.7 and 2.7 μM, respectively. Using a 1-D benthic-pelagic coupled model we investigate oxygen consumption and resupply processes during these years. The model was constrained with weekly water column measurements of temperature, salinity, chlorophyll-a fluorescence and dissolved oxygen from a monitoring station in the central basin together with seasonal measurements of benthic diffusive oxygen uptake. Our model suggested that 29-81%, and up to 36% of bottom water re-oxygenation occurred during the winter mixing period and through summer/fall intrusions of Scotian Shelf water, respectively. Occasional shelf water intrusions occurred rapidly, on a timescale of a few hours, and delivered equivalent amounts of oxygen as winter mixing and were sufficient to end bottom water hypoxia. Collectively, these mechanisms supplied the majority of the oxygen delivered to the bottom water. Oxygen supply to bottom waters during periods of water column stratification accounted for 19-36% of the annual flux. The mean benthic uptake was 12 ± 8 mmol m-2 d-1 and contributed ~20% of the total oxygen consumption below the sill depth. In 2021, sea surface temperature (SST) was unusually high and likely resulted in 50% less bottom water oxygenation compared to 2018 and 2019 due to increased stratification; SST in BB was found to be increasing at a rate of 0.11 ± 0.02 °C/year. Climate control on water column stratification are discussed and numerical experiments are used to compare the effects of different water column mixing scenarios on bottom water oxygenation.
Role of luteinizing hormone elevation in outcomes of ovulation induction with letrozole for polycystic ovary syndrome
Authors: Fu Wenyan , Kuang Yanping 
Published: April 2023

IntroductionThe effect of elevated luteinizing hormone (LH) on the clinical outcomes of ovulation induction (OI) in infertile anovulatory patients with polycystic ovary syndrome (PCOS) remains controversial. This retrospective study included PCOS patients undergoing intrauterine insemination (IUI) following letrozole (LE) stimulation without OC pretreatment.Materials and methodsA retrospective cohort analysis was conducted in a single, academic ART center from January 2013 to May 2019. In total, 835 IUI cycles of PCOS patients treated with letrozole were collected for the analysis. Cohorts were separated based on the level of basal LH (bLH) and LH level after letrozole administration (LHle) during OI. OI response and reproductive outcomes were evaluated for each cohort.ResultsNo adverse effects of dysregulated levels of either bLH or LHle on ovulation rate or reproductive outcomes were observed. Furthermore, the cohort of individuals with normal bLH and high LHle levels, exclusive of LH surge, exhibited significantly higher rates of clinical pregnancy (30.3% vs. 17.3%, p = 0.002) and live birth (24.2% vs. 15.2%, p = 0.024) than those with normal bLH and normal LHle.ConclusionThese results indicated that high LH levels in PCOS are not solid evidence of poor prognosis of letrozole-induced ovulation, while elevated LHle may be a prospective predictor for better OI outcomes. It seems that preinhibition of LH secretion is not needed.
Prehospital qSOFA, mSOFA, and NEWS2 performance for sepsis prediction: A prospective, multi-center, cohort study
Authors: Melero-Guijarro Laura , Sanz-García Ancor , Martín-Rodríguez Francisco , Lipari Vivian , Mazas Perez Oleaga Cristina , Carvajal Altamiranda Stefanía , Martínez López Nohora Milena , Domínguez Azpíroz Irma , Castro Villamor Miguel A. , Sánchez Soberón Irene , López-Izquierdo Raúl 
Published: April 2023

BackgroundNowadays, there is no gold standard score for prehospital sepsis and sepsis-related mortality identification. The aim of the present study was to analyze the performance of qSOFA, NEWS2 and mSOFA as sepsis predictors in patients with infection-suspected in prehospital care. The second objective is to study the predictive ability of the aforementioned scores in septic-shock and in-hospital mortality.MethodsProspective, ambulance-based, and multicenter cohort study, developed by the emergency medical services, among patients (n = 535) with suspected infection transferred by ambulance with high-priority to the emergency department (ED). The study enrolled 40 ambulances and 4 ED in Spain between 1 January 2020, and 30 September 2021. All the variables used in the scores, in addition to socio-demographic data, standard vital signs, prehospital analytical parameters (glucose, lactate, and creatinine) were collected. For the evaluation of the scores, the discriminative power, calibration curve and decision curve analysis (DCA) were used.ResultsThe mSOFA outperformed the other two scores for mortality, presenting the following AUCs: 0.877 (95%CI 0.841–0.913), 0.761 (95%CI 0.706–0.816), 0.731 (95%CI 0.674–0.788), for mSOFA, NEWS, and qSOFA, respectively. No differences were found for sepsis nor septic shock, but mSOFA’s AUCs was higher than the one of the other two scores. The calibration curve and DCA presented similar results.ConclusionThe use of mSOFA could provide and extra insight regarding the short-term mortality and sepsis diagnostic, backing its recommendation in the prehospital scenario.