bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life experiences of boars can shape the survival, aggression, and nociception responses of their offspring
Authors: Sabei Leandro , Bernardino Thiago , Parada Sarmiento Marisol , Barbosa Bruna Stanigher , Farias Sharacely de Souza , Ghantous Giovana Fumes , de Lima César Gonçalves , Poletto Rosangela , Zanella Adroaldo José 
Published: April 2023

IntroductionBoars are often housed in stressful environments on commercial farms, experiencing poor welfare. These conditions may cause epigenetic changes in the boars' gametes, which could potentially be transmitted to their offspring. We aimed to investigate the effect of three different boars housing environments on the survival, aggression, and nociceptive responses of their offspring.MethodsFor four weeks, 18 boars were housed in three different systems: crates (C;n=6), pens (P;n=6), and enriched pens (E;n=6). The environmental enrichment was provided twice daily (brushing, shower, and hay). Thirteen gilts were housed in outdoor paddocks and inseminated with pooled semen from the boars kept in the three treatments. We evaluated the number of live-born, stillborn, and weaned piglets, sex, and mortality rate. Weaning was performed at 29 days of age. For each piglet, six body photographs were taken for five days postweaning to measure skin lesions (n=138). On Day 34, the nociceptive pressure threshold was assessed using an analgesimeter (n=138). DNA paternity tests were carried out at the end of the study (n=181). A generalized linear model with a negative binomial distribution was used to compare the number of live-born/weaned piglets and skin lesions among the treatment groups. We used a Kruskal‒Wallis test to analyze nociceptive data.ResultsMore live-born and weaned piglets were fathered from boars kept in the E group than the P group (p=0.002;p=0.001, respectively). A trend was observed in the number of skin lesions on the left side of piglets (P&lt;C;p=0.053). For nociceptive assessments, offspring from P boars showed less right leg withdrawal than piglets from E and C boars (p=0.008); the P group had a higher average nociceptive value than the C group (p=0.002). All treatments differed in the region adjacent to the tail for nociceptive pressure threshold (P&gt;E&gt;C;p&lt;0.001).Discussion and conclusionOur results suggest that providing an enriched environment for boars can increase the number of live-born and weaned piglets. Moreover, the boars housing conditions can influence nociceptive threshold in their offspring. Further research must be performed to understand the underlying mechanism associated with these changes using epigenetics protocols and measuring physiological indicators and other molecular markers in semen and/or sperm cell samples.
Mechanostat parameters estimated from time-lapsed in vivo micro-computed tomography data of mechanically driven bone adaptation are logarithmically dependent on loading frequency
Authors: Marques Francisco C. , Boaretti Daniele , Walle Matthias , Scheuren Ariane C. , Schulte Friederike A. , Müller Ralph 
Published: April 2023

Mechanical loading is a key factor governing bone adaptation. Both preclinical and clinical studies have demonstrated its effects on bone tissue, which were also notably predicted in the mechanostat theory. Indeed, existing methods to quantify bone mechanoregulation have successfully associated the frequency of (re)modeling events with local mechanical signals, combining time-lapsed in vivo micro-computed tomography (micro-CT) imaging and micro-finite element (micro-FE) analysis. However, a correlation between the local surface velocity of (re)modeling events and mechanical signals has not been shown. As many degenerative bone diseases have also been linked to impaired bone (re)modeling, this relationship could provide an advantage in detecting the effects of such conditions and advance our understanding of the underlying mechanisms. Therefore, in this study, we introduce a novel method to estimate (re)modeling velocity curves from time-lapsed in vivo mouse caudal vertebrae data under static and cyclic mechanical loading. These curves can be fitted with piecewise linear functions as proposed in the mechanostat theory. Accordingly, new (re)modeling parameters can be derived from such data, including formation saturation levels, resorption velocity moduli, and (re)modeling thresholds. Our results revealed that the norm of the gradient of strain energy density yielded the highest accuracy in quantifying mechanoregulation data using micro-finite element analysis with homogeneous material properties, while effective strain was the best predictor for micro-finite element analysis with heterogeneous material properties. Furthermore, (re)modeling velocity curves could be accurately described with piecewise linear and hyperbola functions (root mean square error below 0.2 µm/day for weekly analysis), and several (re)modeling parameters determined from these curves followed a logarithmic relationship with loading frequency. Crucially, (re)modeling velocity curves and derived parameters could detect differences in mechanically driven bone adaptation, which complemented previous results showing a logarithmic relationship between loading frequency and net change in bone volume fraction over 4 weeks. Together, we expect this data to support the calibration of in silico models of bone adaptation and the characterization of the effects of mechanical loading and pharmaceutical treatment interventions in vivo.
A fresh pH-responsive imipenem-loaded nanocarrier against Acinetobacter baumannii with a synergetic effect
Authors: Gui Shumin , Li Xisheng , Feng Mingming , Liu Hui , Huang Liwenhui , Niu Xinqing 
Published: April 2023

In recent years, the treatment of Acinetobacter baumannii infections has become a pressing clinical challenge due to its increasing incidence and its serious pathogenic risk. The research and development of new antibacterial agents for A. baumannii have attracted the attention of the scientific community. Therefore, we have constructed a new pH-responsive antibacterial nano-delivery system (Imi@ZIF-8) for the antibacterial treatment of A. baumannii. Due to its pH-sensitive characteristics, the nano-delivery system offers an improved release of the loaded imipenem antibiotic at the acidic infection site. Based on the high loading capacity and positive charge of the modified ZIF-8 nanoparticles, they are excellent carriers and are suitable for imipenem loading. The Imi@ZIF-8 nanosystem features synergistic antibacterial effects, combining ZIF-8 and imipenem to eliminate A. baumannii through different antibacterial mechanisms. When the loaded imipenem concentration reaches 20 µg/mL, Imi@ZIF-8 is highly effective against A. baumannii in vitro. Imi@ZIF-8 not only inhibits the biofilm formation of A. baumannii but also has a potent killing effect. Furthermore, in mice with celiac disease, the Imi@ZIF-8 nanosystem demonstrates excellent therapeutic efficacy against A. baumannii at imipenem concentrations of 10 mg/kg, and it can inhibit inflammatory reaction and local leukocyte infiltration. Due to its biocompatibility and biosafety, this nano-delivery system is a promising therapeutic strategy in the clinical treatment of A. baumannii infections, providing a new direction for the treatment of antibacterial infections.
Heat stress inhibits the proliferation and differentiation of myoblasts and is associated with damage to mitochondria
Authors: Lu Jiawei , Li Huixia , Yu Debing , Zhao Peng , Liu Yuan 
Published: April 2023

Introduction: Heat stress is harmful to the health of humans and animals, more and more common, as a consequence of global warming, while the mechanism that heat stress modulates skeletal development remains unknown. Hence, we conducted a model of heat stress in vitro.Methods: We used Hu sheep myoblasts as the research object, real-time quantitative PCR (RT-qPCR) and western blot (WB) were conducted to detect the expression of mRNA and protein in heat-stressed myoblasts. The would-healing assay was used to detect the migration of myoblasts. The mitochondria were observed by a transmission electron microscope.Results: mRNA and protein expression of HSP60 was significantly enriched in the heat-stressed myoblasts during proliferation and differentiation (p &lt; 0.05). In our study, we indicated that heat stress enriched the intracellular ROS of the myoblasts (p &lt; 0.001), leading to an increase in autophagy in the myoblasts to induce apoptosis. The results demonstrated that the protein expression of LC3B-1 and BCL-2 was significantly increased in myoblasts under heat stress during proliferation and differentiation (p &lt; 0.05). Additionally, heat stress inhibited mitochondrial biogenesis and function and reduced the mitochondrial membrane potential and downregulated the expression of mtCo2, mtNd1 and DNM1L (p &lt; 0.05) in myoblasts during proliferation and differentiation. Consequently, heat stress inhibited the proliferation and differentiation of the myoblasts, in accordance with the downregulation of the expression of PAX7, MYOD, MYF5, MYOG and MYHC (p &lt; 0.05). Moreover, heat stress also inhibited the cell migration of the myoblasts.Discussion: This work demonstrates that heat stress inhibits proliferation and differentiation, and accelerates apoptosis by impairing mitochondrial function and promoting autophagy, which provides a mechanism to understand heat stress affects the development of the skeletal muscle.
Clinical application of 18F-FCH PET/CT in the diagnosis and treatment of hyperparathyroidism
Authors: Liu Shuang , Li Mengdan , Pang Hua , Zuo Rui , Kong Lingquan , Wang Zhengjie , Li Wenbo , Xia Zhu , Wang Dong , Xu Lu 
Published: April 2023

ObjectiveWe evaluated the difference in parathyroid visualization on 18F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at different time points, to determine the best imaging time for FCH PET/CT.MethodsThis retrospective study included 73 patients with hyperparathyroidism (HPT) who underwent 18F-FCH PET/CT imaging between December 2017 and December 2021. The diagnostic efficiency of 5- and 60-min dual time point imaging for the diagnosis of hyperparathyroidism and parathyroid adenoma and hyperplasia, were compared using visual and quantitative analyses.ResultsDual-time 18F-FCH PET/CT imaging visual analysis had diagnostic value for HPT. The receiver operating characteristic curve of PET/CT quantitative parameters for the diagnosis of HPT and lesions showed that the parathyroid/thyroid SUVmax ratio for 60-min imaging had a higher sensitivity and specificity (based on patient, sensitivity: 90.90% and specificity: 85.71%; based on focus, sensitivity: 83.06% and specificity: 85.71%) compared to that for 5-min imaging. PET/CT quantitative parameters can distinguish parathyroid adenoma and hyperplasia. The 60-min parathyroid SUVmax value had the highest diagnostic value (cutoff: 3.945; area under the curve: 0.783).ConclusionThe quantitative parameters of 60min 18F-FCH PET/CT have more advantages in aiding in the pathologica diagnosis and clinical treatment of HPT.
Integrative analyses of biomarkers and pathways for diabetic nephropathy
Authors: Li Bo , Zhao Xu , Xie Wanrun , Hong Zhenzhen , Zhang Yi 
Published: April 2023

Background: Diabetic nephropathy (DN) is a widespread diabetic complication and a major cause of terminal kidney disease. There is no doubt that DN is a chronic disease that imposes substantial health and economic burdens on the world’s populations. By now, several important and exciting advances have been made in research on etiopathogenesis. Therefore, the genetic mechanisms underlying these effects remain unknown.Methods: The GSE30122, GSE30528, and GSE30529 microarray datasets were downloaded from the Gene Expression Omnibus database (GEO). Analyses of differentially expressed genes (DEGs), enrichment of gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed. Protein-protein interaction (PPI) network construction was completed by the STRING database. Hub genes were identified by Cytoscape software, and common hub genes were identified by taking intersection sets. The diagnostic value of common hub genes was then predicted in the GSE30529 and GSE30528 datasets. Further analysis was carried out on the modules to identify transcription factors and miRNA networks. As well, a comparative toxicogenomics database was used to assess interactions between potential key genes and diseases associated upstream of DN.Results: Samples from 19 DNs and 50 normal controls were identified in the GSE30122 dataset. 86 upregulated genes and 34 downregulated genes (a total of 120 DEGs). GO analysis showed significant enrichment in humoral immune response, protein activation cascade, complement activation, extracellular matrix, glycosaminoglycan binding, and antigen binding. KEGG analysis showed significant enrichment in complement and coagulation cascades, phagosomes, the Rap1 signaling pathway, the PI3K-Akt signaling pathway, and infection. GSEA was mainly enriched in the TYROBP causal network, the inflammatory response pathway, chemokine receptor binding, the interferon signaling pathway, ECM receptor interaction, and the integrin 1 pathway. Meanwhile, mRNA-miRNA and mRNA-TF networks were constructed for common hub genes. Nine pivotal genes were identified by taking the intersection. After validating the expression differences and diagnostic values of the GSE30528 and GSE30529 datasets, eight pivotal genes (TYROBP, ITGB2, CD53, IL10RA, LAPTM5, CD48, C1QA, and IRF8) were finally identified as having diagnostic values.Conclusion: Pathway enrichment analysis scores provide insight into the genetic phenotype and may propose molecular mechanisms of DN. The target genes TYROBP, ITGB2, CD53, IL10RA, LAPTM5, CD48, C1QA, and IRF8 are promising new targets for DN. SPI1, HIF1A, STAT1, KLF5, RUNX1, MBD1, SP1, and WT1 may be involved in the regulatory mechanisms of DN development. Our study may provide a potential biomarker or therapeutic locus for the study of DN.
Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine
Authors: Huang Ruoqiong , Ying Liyang , Wang Jiangmei , Xia Jie , Zhang Yanjun , Mao Haiyan , Zhang Ruoyang , Zang Ruoxi , Le Zhenkai , Shu Qiang , Xu Jianguo 
Published: April 2023

BackgroundDuring the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited.MethodsIn this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4+ and CD8+ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose. ResultsThe booster dose elevated cytokine response in CD4+ and CD8+ T cells as well as expression of cytotoxic marker CD107a in CD8+ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4+ and CD8+ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4+ and CD8+ T cell responses. In addition, booster vaccination produced similar spike-specific AIM+CD4+ and AIM+CD8+ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4+ and CD8+ T cells. ConclusionsThese data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.
Application of single cell multiomics points to changes in chromatin accessibility near calcitonin receptor like receptor and a possible role for adrenomedullin in the post-shock lung
Authors: Armstead Brandon E. , Lee Chung Sunny , Chen Yaping , Zhao Runping , Chung Chun-Shiang , Fredericks Alger M. , Monaghan Sean F. , Ayala Alfred 
Published: April 2023

IntroductionAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a commonly occurring sequelae of traumatic injury resulting from indirect insults like hypovolemic shock and/or extrapulmonary sepsis. The high lethality rate associated with these pathologies outlines the importance of clarifying the “priming” effects seen in the post-shock lung microenvironment, which are understood to bring about a dysregulated or overt immune response when triggered by a secondary systemic infectious/septic challenge culminating in ALI. In this pilot project, we test the hypothesis that application of a single cell multiomics approach can elucidate novel phenotype specific pathways potentially contributing to shock-induced ALI/ARDS.MethodsHypovolemic shock was induced in C57BL/6 (wild-type), PD-1, PD-L1, or VISTA gene deficient male mice, 8–12 weeks old. Wild-type sham surgeries function as negative controls. A total of 24-h post-shock rodents were sacrificed, their lungs harvested and sectioned, with pools prepared from 2 mice per background, and flash frozen on liquid nitrogen. N = 2 biological replicates (representing 4 mice total) were achieved for all treatment groups across genetic backgrounds. Samples were received by the Boas Center for Genomics and Human Genetics, where single cell multiomics libraries were prepared for RNA/ATAC sequencing. The analysis pipeline Cell Ranger ARC was implemented to attain feature linkage assessments across genes of interest.ResultsSham (pre-shock) results suggest high chromatin accessibility around calcitonin receptor like receptor (CALCRL) across cellular phenotypes with 17 and 18 feature links, exhibiting positive correlation with gene expression between biological replicates. Similarity between both sample chromatin profiles/linkage arcs is evident. Post-shock wild-type accessibility is starkly reduced across replicates where the number of feature links drops to 1 and 3, again presenting similar replicate profiles. Samples from shocked gene deficient backgrounds displayed high accessibility and similar profiles to the pre-shock lung microenvironment.ConclusionHigh pre-shock availability of DNA segments and their positive correlation with CALCRL gene expression suggests an apparent regulatory capacity on transcription. Post-shock gene deficient chromatin profiles presented similar results to that of pre-shock wild-type samples, suggesting an influence on CALCRL accessibility. Key changes illustrated in the pre-ALI context of shock may allow for additional resolution of “priming” and “cellular pre-activation/pre-disposition” processes within the lung microenvironment.
Case report: Continuous spinal cord physiologic monitoring following traumatic spinal cord injury—A report from the Winnipeg Intraspinal Pressure Study (WISP)
Authors: Dhaliwal Perry , Gomez Alwyn , Zeiler Frederick Adam 
Published: April 2023

IntroductionAcute traumatic spinal cord injury is routinely managed by surgical decompression and instrumentation of the spine. Guidelines also suggest elevating mean arterial pressure to 85 mmHg to mitigate secondary injury. However, the evidence for these recommendations remains very limited. There is now considerable interest in measuring spinal cord perfusion pressure by monitoring mean arterial pressure and intraspinal pressure. Here, we present our first institutional experience of using a strain gauge pressure transducer monitor to measure intraspinal pressure and subsequent derivation of spinal cord perfusion pressure.Case presentationThe patient presented to medical attention after a fall off of scaffolding. A trauma assessment was completed at a local emergency room. He did not have any motor strength or sensation to the lower extremities. A computed tomography (CT) scan of the thoracolumbar spine confirmed a T12 burst fracture with retropulsion of bone fragments into the spinal canal. He was taken to surgery for urgent decompression of the spinal cord and instrumentation of the spine. A subdural strain gauge pressure monitor was placed at the site of injury through a small dural incision. Mean arterial pressure and intraspinal pressure were then monitored for 5 days after surgery. Spinal cord perfusion pressure was derived. The procedure was performed without complication and the patient underwent rehabilitation for 3 months where he regained some motor and sensory function in his lower extremities.ConclusionThe first North American attempt at insertion of a strain gauge pressure monitor into the subdural space at the site of injury following acute traumatic spinal cord injury was performed successfully and without complication. Spinal cord perfusion pressure was derived successfully using this physiological monitoring. Further research efforts to validate this technique are required.
Effect of aging on the cerebral metabolic mechanism of electroacupuncture treatment in rats with traumatic brain injury
Authors: Huo Bei-Bei , Zheng Mou-Xiong , Hua Xu-Yun , Wu Jia-Jia , Xing Xiang-Xin , Ma Jie , Fang Min , Xu Jian-Guang 
Published: April 2023

ObjectiveAging has great influence on the clinical treatment effect of cerebrovascular diseases, and evidence suggests that the effect may be associated with age-related brain plasticity. Electroacupuncture is an effective alternative treatment for traumatic brain injury (TBI). In the present study, we aimed to explore the effect of aging on the cerebral metabolic mechanism of electroacupuncture to provide new evidence for developing age-specific rehabilitation strategies.MethodsBoth aged (18 months) and young (8 weeks) rats with TBI were analyzed. Thirty-two aged rats were randomly divided into four groups: aged model, aged electroacupuncture, aged sham electroacupuncture, and aged control group. Similarly, 32 young rats were also divided into four groups: young model, young electroacupuncture, young sham electroacupuncture, and young control group. Electroacupuncture was applied to “Bai hui” (GV20) and “Qu chi” (LI11) for 8 weeks. CatWalk gait analysis was then performed at 3 days pre- and post-TBI, and at 1, 2, 4, and 8 weeks after intervention to observe motor function recovery. Positron emission computed tomography (PET/CT) was performed at 3 days pre- and post-TBI, and at 2, 4, and 8 weeks after intervention to detect cerebral metabolism.ResultsGait analysis showed that electroacupuncture improved the forepaw mean intensity in aged rats after 8 weeks of intervention, but after 4 weeks of intervention in young rats. PET/CT revealed increased metabolism in the left (the injured ipsilateral hemisphere) sensorimotor brain areas of aged rats during the electroacupuncture intervention, and increased metabolism in the right (contralateral to injury hemisphere) sensorimotor brain areas of young rats.ResultsThis study demonstrated that aged rats required a longer electroacupuncture intervention duration to improve motor function than that of young rats. The influence of aging on the cerebral metabolism of electroacupuncture treatment was mainly focused on a particular hemisphere.