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Water temperature is one of the most important ecological environmental factors affecting fish survival and growth. When the water temperature is higher than the optimal temperature for fish survival, fish homeostasis may be disrupted. The heart plays a crucial role in maintaining vertebrate homeostasis. In this study, TMT and LC-MS/MS were performed to analyze differentially expressed protein (DEP) profiles in the hearts of turbot under high-temperature stress to explore the key proteins and metabolic pathways related to the high-temperature tolerance traits of turbot. Ninety turbot (mean weight 23.01±3.63 g, mean length 10.34±0.76 cm) were used in experiments. Three temperature points for heat stress experiments were designed: control=(14.0±0.5)℃, HT1=(20.0±0.5)℃, and HT2=(28.0±0.5)℃. Three parallel groups were established for each temperature group, with 10 turbots placed in each group. Fold Change≥1.2 or < 0.83, P < 0.05 was used as a criterion to screen for DEPs in turbot. Through mass spectrometry analysis of heart tissues from turbot, 85, 731 spectra were identified, with 35, 434 peptides, of which 31, 704 were unique, and 4, 765 proteins were identified. The HT1/control group in the heart of turbot had a total of 87 differentially expressed proteins, including 77 upregulated and 10 down-regulated proteins; the HT2/control group in the heart of turbot had 171 DEPs, including 149 upregulated and 22 down-regulated proteins; the HT2/HT1 group in the heart of turbot had a total of 188 DEPs, including 130 upregulated and 58 downregulated proteins. Through bioinformatics analysis, the DEPs between the 28℃ group and the 14℃ group, as well as the 28℃ group and the 20℃ group, were mainly enriched in KEGG pathways related to fatty acid metabolism, inflammation, and immune defense. Multiple proteins in the heat shock protein family (HSP90B, HSP70, etc.) were significantly upregulated in the 28℃ group compared to the 14℃ group. The protein interaction network revealed that HSP90B exhibited the highest correlation. A new discovery is that the expression levels of fibrinogen-related proteins (FGA, FGB, and FGG) increased, and their role in the thermal response requires further research. These results indicate that extremely high temperatures may cause fatty acid metabolic disorders in turbot, leading to inflammatory reactions. The upregulation of heat shock protein family proteins may have a positive effect on alleviating stress symptoms under heat stress. This study identified DEPs, such as HSP90B, HSPA5, and HYOU1, which were significantly upregulated under heat stress, as candidate proteins for high-temperature tolerance breeding in turbot and provided a theoretical basis for further elucidating the molecular mechanism of heat stress in turbot.

Abstract Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Alfin-like proteins (ALs) form a plant-specific transcription factor (TF) gene family involved in the regulation of plant growth and development, and abiotic stress response. In this study, 30 ALs were identified in Brassica napus ecotype ‘Zhongshuang 11’ genome (BnaALs), and unevenly distributed on 15 chromosomes. Structural characteristic analysis showed that all of the BnaALs contained two highly conserved domains: the N terminal DUF3594 domain and the C-terminal PHD-finger domain. The BnaALs were classified into four groups (Group I-IV), supported by conserved intron–exon and protein motif structures in each group. The allopolyploid event between B. oleracea and B. rapa ancestors and the small-scale duplication events in B. napus both contributed to the large BnaALs expansion. The promoter regions of BnaALs contained multiple abiotic stress cis-elements. The BnaALs in I-IV groups were mainly expressed in cotyledon, petal, root, silique, and seed tissues, and the duplicated gene pairs shared highly similar expression patterns. RNA-seq and RT-qPCR analysis showed that BnaALs were obviously induced by low nitrogen (LN) and low phosphorus (LP) treatments in roots. Overexpressing BnaAL02 and BnaAL28 in Arabidopsis demonstrated their functions in response to LN and LP stresses. BnaAL28 enhanced primary roots’ (PRs) length and lateral roots’ (LRs) number under LP and LN conditions, where BnaAL02 can inhibit LR numbers under the two conditions. They can promote root hair (RH) elongation under LP conditions; however, they suppressed RH elongation under LN conditions. Our result provides new insight into the functional dissection of this family in response to nutrient stresses in plants.

The identification of neurodevelopmental defects in a patient harboring a heterozygous de novo missense variant (NM_006561.4, c.1517G > A, p.Arg506His) within the CELF2 gene. Here, we describe the establishment of a patient-derived induced pluripotent stem cell (iPSC) line, alongside an isogenic gene-corrected iPSC line, achieved through CRISPR/Cas9 genome editing. These lines exhibit the expression of pluripotency markers, demonstrate differentiation potential into all three germ layers, and maintain a normal karyotype. These iPSC lines serve as valuable tools for investigating the consequences of CELF2 related neurodevelopmental disorders.

Abstract Acoustic tweezing cytometry (ATC) is an ultrasound-based biophysical technique that has shown the capability to promote differentiation of human pluripotent stem cells (hPSCs). This study systematically examined how hPSCs respond to cyclic mechanical strains applied by ATC via displacement of integrin-bound microbubbles (averaged diameter of 4.3 µm) using ultrasound pulses (acoustic pressure 0.034 MPa, center frequency 1.24 MHz and pulse repetition frequency 1 Hz). Our data show downregulation of pluripotency marker Octamer-binding transcription factor 4 (OCT4) by at least 10% and increased nuclear localization of Yes-associated protein (YAP) by almost 100% in hPSCs immediately after ATC application for as short as 1 min and 5 min respectively. Analysis of the movements of integrin-anchored microbubbles under ATC stimulations reveals different stages of viscoelastic characteristic behavior and increasing deformation of the integrin-cytoskeleton (CSK) linkage. The peak displacement of integrin-bound microbubbles increased from 1.45 ± 0.16 to 4.74 ± 0.67 μm as the duty cycle of ultrasound pulses increased from 5% to 50% or the duration of each ultrasound pulse increased from 0.05 to 0.5 s. Real-time tracking of integrin-bound microbubbles during ATC application detects high correlation of microbubble displacements with OCT4 downregulation in hPSCs. Together, our data showing fast downregulation of OCT4 in hPSCs in respond to ATC stimulations highlight the unique mechanosensitivity of hPSCs to integrin-targeted cyclic force/strain dependent on the pulse duration or duty cycle of ultrasound pulses, providing insights into the mechanism of ATC-induced accelerated differentiation of hPSCs.

Abstract Hyperactivation of hypothalamic–pituitary–adrenal (HPA) axis and hypothalamic–pituitary–thyroid (HPT) axis were found in acute high altitude challenge, but the role of gut microbiota and metabolites is unknown. We utilized adult male Sprague–Dawley rats at a simulated altitude of 5500 m for 3 days in a hypobaric-hypoxic chamber. ELISA and metabolomic analyses of serum and 16S rRNA and metabolomic analyses of fecal samples were then performed. Compared with the normoxic group, serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and thyroxine (tT4) were increased in the hypoxia group, whereas thyrotropin-releasing hormone (TRH) was decreased. Bacteroides, Lactobacillus, Parabacteroides, Butyricimonas, SMB53, Akkermansia, Phascolarctobacterium, and Aerococcus were enriched in hypoxia group, whereas [Prevotella], Prevotella, Kaistobacter, Salinibacterium, and Vogesella were enriched in normoxic group. Metabolomic analysis indicated that acute hypoxia significantly affected fecal and serum lipid metabolism. In addition, we found five fecal metabolites may mediate the cross-talk between TRH, tT4, and CORT with [Prevotella], Kaistobacter, Parabacteroides, and Aerococcus, and 6 serum metabolites may mediate the effect of TRH and tT4 on [Prevotella] and Kaistobacter by causal mediation analysis. In conclusion, this study provides new evidence that key metabolites mediate the cross-talk between gut microbiota with HPA and HPT axis under acute hypobaric hypoxia challenge.

ObjectiveWinter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system (ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions.MethodsFourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale.ResultsHRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval.ConclusionProlonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.

The fungus Puccinia striiformis f. sp. tritici (Pst) is an important threat to wheat production because it can cause wheat stripe rust. The present study aimed to identify new stripe rust resistance genes and to provide a theoretical and practical basis for breeding wheat varieties with broad spectrum, stable, and durable resistance. Wheat leaves inoculated with wheat stripe rust fungus Chinese yellow rust 34 were collected at different time points for transcriptomic analysis based on the wheat stripe rust susceptible varieties AVOCET S (AVS) and AVSYr15NIL [near-isogenic line (NIL) derived from AVS]. The results showed that the number of upregulated genes in the two varieties was 294, 364, 398, and 604, and the number of downregulated genes was 520, 178, 570, and 345 on the 1st, 3rd, 5th, and 7th days post inoculation, respectively. Gene Ontology and Kyoto Encyclopedia of Gene and Genomes enrichment analyses found enrichment of differentially expressed genes in the peroxisome proliferators-activated receptor signaling pathways, plant-pathogen interaction, and styrene acrylic acid biosynthesis that encoded protein kinases, signal transduction, transcription factors, and functional protein components. Differentially expressed genes were randomly selected for quantitative reverse transcription PCR analysis, and the change trend was the same as in the transcriptome data. The results of this study suggest that genes in AVSYr15NIL related to the stripe rust response could be valuable for understanding the mechanisms involved in stripe rust resistance.

This study designs a two-stage algorithm to address the bid generation problem of carriers when adding new vehicle routes in the presence of the existing vehicle routes to provide transportation service. To obtain the best auction combination and bid price of the carrier, a hybrid integer nonlinear programming model is introduced. According to the characteristics of the problem, a set of two-stage hybrid algorithms is proposed, innovatively integrating block coding within a genetic algorithm framework with a depth-first search approach. This integration effectively manages routing constraints, enhancing the algorithm’s efficiency. The block coding and each route serve as decision variables in the set partition formula, enabling a comprehensive exploration of potential solutions. After a simulation-based analysis, the algorithm has been comprehensively validated analytically and empirically. The improvement of this research lies in the effectiveness of the proposed algorithm, i.e., the ability to handle a broader range of problem scales with less time in addressing complex operator bid generation in combinatorial auctions.

The fatigue failure of the piston pin hole is considered as a key factor affecting the service life of engines. In this work, the piston pin hole profile was designed as tapered shape following a power law. By combining finite element analysis and hydraulic pulsating fatigue tests, the pin hole profile was optimized. It has been found that the maximum contact pressure on the pin hole surface was reduced by 16,7% with appropriate increasing the radius enlarging rate of the piston pin hole, the maximum tensile stress of the piston pin seat was reduced by 13,1%, and the piston pin seat fatigue safety factor was increased by 41,4%, the piston pin hole fatigue safety factor was increased by 15,9%. The piston pin hole’s hydraulic pulsating fatigue test results were found to be consistent with the FEA results. It could be concluded that appropriate increasing the radius enlarging rate of the pin hole could significantly weaken the fatigue wear of the pin hole, further improving its fatigue resistance.

Polygenic risk scores (PRS) based on genome-wide discoveries are promising predictors or classifiers of disease development, severity, and/or progression for common clinical outcomes. A major limitation of most risk scores is the paucity of genome-wide discoveries in diverse populations, prompting an emphasis to generate these needed data for trans-population and population-specific PRS construction. Given diverse genome-wide discoveries are just now being completed, there has been little opportunity for PRS to be evaluated in diverse populations independent from the discovery efforts. To fill this gap, we leverage here summary data from a recent genome-wide discovery study of lipid traits (HDL-C, LDL-C, triglycerides, and total cholesterol) conducted in diverse populations represented by African Americans, Hispanics, Asians, Native Hawaiians, Native Americans, and others by the Population Architecture using Genomics and Epidemiology (PAGE) Study. We constructed lipid trait PRS using PAGE Study published genetic variants and weights in an independent African American adult patient population linked to de-identified electronic health records and genotypes from the Illumina Metabochip (n = 3,254). Using multi-population lipid trait PRS, we assessed levels of association for their respective lipid traits, clinical outcomes (cardiovascular disease and type 2 diabetes), and common clinical labs. While none of the multi-population PRS were strongly associated with the tested trait or outcome, PRSLDL-Cwas nominally associated with cardiovascular disease. These data demonstrate the complexity in applying PRS to real-world clinical data even when data from multiple populations are available.

ObjectivesFor Crohn’s disease (CD), the alternation of the active phase and inactive phase may be related to humoral immunity and cellular immunity. This study aims to understand the characteristics of immune cells in patients with active CD (CDa) and inactive CD (CDin).MethodsMass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq) data about CDa, CDin, and healthy control (HC) were included. CyTOF analysis was performed to capture gated subsets, including T cells, T regulatory (Treg) cells, B cells, innate immune cells, and natural killer (NK) cells. Differential analysis was used to identify different immune cell subsets among CDa, CDin, and HC. ScRNA-seq analysis was used to verify the results of CyTOF. CD-related signaling pathways were obtained using KEGG pathway enrichment analysis. CellChat analysis was used to infer the cell communication network among immune cell subsets.ResultsCompared to patients with CDin, patients with CDa had higher abundances of CD16+CD38+CD4+CXCR3+CCR6+ naive T cells, HLA-DR+CD38+IFNγ+TNF+ effector memory (EM) T cells, HLA-DR+IFNγ+ naive B cells, and CD14++CD11C+IFNγ+IL1B+ monocytes. KEGG analysis showed the similarity of pathway enrichment for the earlier four subsets, such as thermogenesis, oxidative phosphorylation, and metabolic pathways. The patients with CDin were characterized by an increased number of CD16+CD56dimCD44+HLA-DR+IL22+ NK cells. Compared to HC, patients with CDa demonstrated a low abundance of HLA-DR+CCR6+ NK cells and a high abundance of FOXP3+CD44+ EM Tregs. CellChat analysis revealed the interaction network of cell subsets amplifying in CDa compared with CDin.ConclusionSome immune subsets cells were identified for CDa and CDin. These cells may be related to the occurrence and development of CD and may provide assistance in disease diagnosis and treatment.

The tiger puffer (Takifugu rubripes) is an important economic fish species in northern China. However, it is a warm-temperature species, and low winter temperatures can result in high mortality in aquaculture. Understanding the mechanisms of cold resistance in tiger puffers will thus provide critical information to help cope with winter cold. In this study, we performed transcriptome analysis of livers from puffer fish kept at different temperatures (18°C, 13°C, and 8°C) to identify the key pathways and genes involved in the response to low-temperature stress. We also detected serum levels of proteases, arginine, and proline to obtain further information on the response to cold adaption. Totals of 51, 942, and 195 differentially expressed genes were identified in the 18°C vs 13°C, 18°C vs 8°C, and 13°C vs 8°C groups, respectively. Pathway analysis showed that significantly enriched pathways were mainly related to digestion, metabolism, and environmental adaptation. Most genes in the pathways related to digestion and metabolism were down-regulated, while most genes in the pathways related to environmental adaptation were up-regulated. Serum levels of proteases were significantly lower in the low-temperature groups (13°C and 8°C) compared with the control group (18°C), while arginine and proline levels were significantly higher in the 8°C group compared with the other two groups. These results suggest that low temperature caused digestive and metabolic disorders, as well as adaptive changes to low temperature in tiger puffers. On this premise, we found that some up-regulated genes in the pancreatic secretion pathway, arginine and proline metabolism pathway, and circadian rhythm pathway played important roles in the survival, growth, and development of tiger puffers under low-temperature stress. The accumulation of arginine and proline can maintain metabolism and circulation and resist cold stress. The circadian rhythm is closely related to digestion and metabolism, which is an adaptive change and plays a positive role in the resistance to low temperature. The results of this study provide new insights and a theoretical basis for the study of cold tolerance in tiger puffers.

As a rare complication of rheumatoid arthritis (RA) in the central nervous system (CNS), rheumatoid meningitis (RM) mainly affects the meninges and has various clinical symptoms. The diagnostic and treatment approaches currently used are not practical. RM cases with positive NMDAR antibodies (Abs) have never been reported. In the present study, a 66-year-old man with a 1-year history of RA presented recurrent left lower limb weakness during activities for 1 month. The results showed that rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were positive in the serum, and NMDAR Abs were present in cerebrospinal fluid (CSF). Hyperintensity was observed in the leptomeninges of the right frontal and parietal lobes, and subtle hyperintensity was observed in the left frontal and parietal lobes, as indicated by brain MRI. A meningeal biopsy revealed non-specific inflammation with the absence of rheumatoid nodules. The patient was given IVIg on day 7 after admission. The clinical symptoms were relieved, the lesions were alleviated, and abnormal biochemical indicators were gradually recovered 1 week after initiation of the treatment, while NMDAR Abs were present in CSF even after treatment. After 5 months of follow-up, the patient’s serum and CSF ACPA and IL-6 levels were still high. The findings showed that brain MRI was adequate for the diagnosis of RM. ACPA and IL-6 might be the specific biomarkers for disease activity in RM. IVIg was effective as induction therapy for RM. Further studies should explore whether the presence of NMDAR Abs is associated with RM.

Low-molecular-weight oyster peptides (LOPs) are typical bioactive peptides with ameliorated immunomodulatory properties. However, the mechanism underlying its effect on immune functions and intestinal flora after chemotherapy has not been reported. In this study, Lewis lung cancer mice were used along with cytotoxic chemotherapy to establish model to investigate the ameliorative effects of LOPs on immunomodulatory function and intestinal flora structure. Our results showed that administration of LOPs alleviated weight loss, reduced spleen tissue damage, increased splenic T-lymphocytes, and markedly increased secretion of serum immunoglobulins and decreased inflammatory factors. Additionally, LOPs significantly increased the abundance of beneficial bacteria (Lactobacillus and Coriobacteriaceae_UCG) and decreased pathogenic bacteria (Clostridium) present in intestine. Hydrophobic amino acids and glutamate may be the underlying components to mitigate negative effects of chemotherapy. This study provides a theoretical basis for the use of LOPs as a nutritional base for the development of formula foods for cancer patients undergoing chemotherapy.

Background: The pathogenesis of ulcerative colitis (UC) is closely related to immunity. The immune characteristic differences between active UC (UCa) and inactive UC (UCin) have not been completely explained. Mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq) were used to analyze the immune cells of UCa, UCin and healthy control (HC) subjects to determine the specific immune characteristics.Methods: The immune cell subsets among UCa, UCin, HC were distinguished using CyTOF analysis. scRNA-seq analysis was used to validate the results of CyTOF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the roles of differential immune cell subsets.Results: After CyTOF analysis and validation of scRNA-seq analysis, differential immune cell subsets mainly contained TNF+IL-17A++ effector memory (EM) Tregs, CXCR3+CTLA4+ EM Tregs, CXCR3++CCR7+ B cells, HLA-DR+CCR7+ dendritic cells (DCs) and CTLA-4+ natural killer (NK) cells. In comparison to HC, CCR6+TNF+CD161+ EM T cells were highly enriched in UCa and UCin. Besides, UCa was characterized by an increase in CD38+TNF+ EM Tregs, CXCR3+CCR4+ naïve B cells, HLA-DR+CD14+IL21+ macrophages/monocytes, HLA-DR+CCR7+ DCs, AHR+CD14+ cytotoxic NK (cNK) cells and CD8A+IFNG+ cNK cells. Decreases in CD38+CD27+ plasmablasts, CXCR3+CD38+ regulatory NK cells, and CXCR3+CCR7+ tolerant NK cells in UCa were discovered.Conclusions: Novel immune cell subsets which was used to distinguish UCa, UCin and HC were identified. This information might be utilized to distinguish the patients with UCa and UCin.

Background: Neonatal mortality rates remain high in Sub-Saharan African countries. Improving the newborn resuscitation skills of healthcare professionals is important in addressing this challenge. The aim of this study was to evaluate a neonatal resuscitation training programme delivered over a two-year period for healthcare professionals in Zanzibar, Tanzania.Methods: A pre- and post-intervention study was designed. We delivered neonatal resuscitation training over a 2-day period in 2017 and 2 days of refresher training in 2018. Knowledge was evaluated by a self-designed survey (11 items with a total score of 22) before and after the two training periods, and skills were evaluated by a skills checklist (six domains with 25 items with a total score of 50) completed by the trainers based on their observations. Statistical analysis included differences in the knowledge and skills scores before and after the training sessions and between the two periods.Results: A total of 23 healthcare professionals participated and completed both neonatal resuscitation training sessions. The knowledge mean scores before and after the training in 2017 increased from 9.60 to 13.60 (95% CI: −5.900; −2.099, p < 0.001), and in 2018, the scores increased from 10.80 to 15.44 (95% CI: −6.062; −3.217, p < 0.001). The mean knowledge scores post-training over time were 13.60 in 2017 and 15.44 in 2018 (95% CI: −3.489; 0.190, p = 0.030). The resuscitation skills performance between the two time periods increased from a mean of 32.26 (SD = 2.35) to a mean of 42.43 (SD = 1.73) (95% CI: −11.402; −8.945, p < 0.001).Conclusion: The neonatal resuscitation training programme increased the theoretical knowledge and resuscitation skills before and after the two training sessions and over time after a 9-month period. Continuous neonatal resuscitation training based on the local needs in resource-limited countries is essential to provide confidence in healthcare professionals to initiate resuscitation and to improve newborn outcomes.

Abstract Background Previous studies have suggested that Toxoplasma gondii (T. gondii) infection might be associated with fatty liver disease. However, the relationship between non-alcoholic fatty liver disease (NAFLD) and T. gondii infection has not been investigated in a large population. We aimed to study the relationship between those two diseases using a population-based dataset from the United States. Methods The data were collected from the third National Health and Nutrition Examination Survey (NHANES III) between 1988 and 1994. Statistical analysis was applied to compare the prevalence of NAFLD in anti-T. gondii antibody-positive participants with antibody-negative ones. Results A total of 9465 persons with a mean age of 44.33 ± 16.21 years, 46.9% of which were males, were included in the final analysis. Their mean BMI was 27.60 ± 5.96 kg/m2. A total of 2520 participants (26.62%) were positive for the T. gondii antibody. There was an increasing trend of seroprevalence of T. gondii with age (P for trend

Objectives To investigate the relationship between vitamin D-related gene single nucleotide polymorphisms (SNPs) and hepatitis B-related liver cirrhosis. Methods This study included patients with chronic hepatitis B who were admitted to the Liver Research Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to August 2016. SNPs rs1544410 and rs2228570 in the vitamin D receptor gene and rs2282679 in the vitamin D-binding protein gene were detected using the imLDR™ multiple SNP typing kit. Genotype and allele frequencies were compared between groups using the chi-square test or Fisher’s exact test. Results A total of 226 patients with hepatitis B virus (HBV) infection were enrolled, including 116 with HBV-related cirrhosis and 110 patients without. The distributions of vitamin D-related gene SNPs in both groups were in accordance with the Hardy–Weinberg equilibrium. There was no significant difference in the frequency or allelic distributions of rs1544410, rs2228570, and rs2282679 between the two groups. Additionally, the SNPs were not associated with the severity of cirrhosis. Conclusion No significant connection was identified between vitamin D-related SNPs and HBV-related liver cirrhosis.

Background: Pancreatic fibrosis is a pathophysiological process associated with excessive deposition of extracellular matrix in pancreas, leading to reduced insulin secretion and derangement of glucose metabolism. X/A-like cells, a group of unique endocrine cells in gastric oxyntic mucosa, produce and secret ghrelin to influence energy balance. Whether gastric X/A-like cells affect pancreatic fibrosis and subsequent glucose homeostasis remains unclear. Methods: We established a Ghrl-cre transgene in which the cre enzyme is expressed in X/A-like cells under the control of ghrelin-promoter. TSC1flox/flox mice were bred with Ghrl-cre mice to generate Ghrl-TSC1−/− (TG) mice, within which mTORC1 signaling was activated in X/A-like cells. Pancreatic fibrosis and insulin secretion were analyzed in the TG mice. Findings: Activation of mTORC1 signaling by deletion of TSC1 gene in gastric X/A-like cells induced spontaneous pancreatic fibrosis. This alteration was associated with reduced insulin expression and secretion, as well as impaired glucose metabolism. Activation of mTORC1 signaling in gastric X/A-like cells reduced gastric and circulating ghrelin levels. Exogenous ghrelin reversed pancreatic fibrosis and glucose intolerance induced by activation of mTORC1 signaling in these cells. Rapamycin, an inhibitor of mTOR, reversed the decrease of ghrelin levels and pancreatic fibrosis. Interpretation: Activation of mTORC1 signaling in gastric X/A-like cells induces spontaneous pancreatic fibrosis and subsequently impairs glucose homeostasis via suppression of ghrelin. Keywords: Ghrelin, Fibrosis, Matrix metalloproteinases, Glucose metabolism, Pancreatic islets

Growth models and high magnetic field (HMF) are employed to affect diluted magnetic performance of Co-doped ZnO (ZnO:Co) films which oxidize Co-Zn evaporated films at 300 °C for 120 min in open air. Nanograined boundaries and dense structure obtained in the co-deposition films are helpful to present a better diluted magnetic performance. Two phases of Zn and ZnO coexist in the films at a low oxidation temperature. Both the bilayer Co/Zn film and the application of HMF during the oxidation process offer an easy way to increase oxygen vacancies, which are inconducive to improve the ferromagnetism. The co-deposition 0 T film has the best diluted magnetic performance compared with the bilayer 0 T film. To be specific, saturation magnetization MS of the co-deposition 0 T film (100.1 emu/cm3) increases by 190%, squareness S increases from 0.31 to 0.75 and coercivity HC increases from 34.6 Oe to 183.5 Oe. With the application of HMF, the MS of the co-deposition films decreases by 44% to approximately 55.8 emu/cm3 and the HC increases to 118.4 Oe.

Objective:To observe the effect of moxibustion according to syndrome differentiation on the rehabilitation of muscle function in patients with maintenance hemodialysis.Methods:A total of 92 patients seclected from five hospitals with maintenance hemodialysis were randomly assigned to the treatment group and the control group by using central randomization system. Both groups received Western conventional treatment, while the treatment group were added with moxibustion according to syndrome differentiation. The observation cycle was twelve weeks. Cardiopulmonary endurance (six minutes walking distance, heart rate and blood pressure product), muscle endurance (such as grip strength, grip strength endurance) and the quality of life assessment (the score of kidney disease quality of life KDQOL-SFTM1.3) were observed and recorded before and after treatment to evaluate the efficiency of moxibustion based on syndrome differentiation.Results:After twelve-week treatment, the six minutes walking distance was extended in the treatment group (PPPP

An improved understanding of the pluripotency maintenance of embryonic stem (ES) cells is important for investigations of early embryo development and for cell replacement therapy, but the mechanism behind pluripotency is still incompletely understood. Recent findings show that zinc, an essential trace element in humans, is critically involved in regulating various signaling pathways and genes expression. However, its role in ES cell fate determination remains to be further explored. Here we showed that 2μM zinc chloride (ZnCl2) transiently maintained mouse ES cell pluripotency in vitro. The cultured mouse ES cells remained undifferentiated under 2μM ZnCl2 treatment in leukemia inhibitory factor (LIF) withdrawal, retinoic acid (RA) or embryoid bodies (EBs) differentiation assays. In addition, ZnCl2 increased pluripotency genes expression and inhibited differentiation genes expression. Further mechanistic studies revealed that ZnCl2 transiently activated signal transducers and activators of transcription 3 (Stat3) signaling through promoting Stat3 phosphorylation. Inhibition of Stat3 signaling abrogated the effects of ZnCl2 on mouse ES cell pluripotency. Taken together, this study demonstrated a critical role of zinc in the pluripotency maintenance of mouse ES cells, as well as an important regulator of Stat3 signaling.