Conjugated linoleic acids (CLAs) can serve as a nutritional intervention to regulate quality, function and fat infiltration in skeletal muscles but the specific cytological mechanisms are still unknown. Here, we applied single-nucleus RNA-sequencing (snRNA-seq) to characterize the cytological mechanism of CLAs regulates fat infiltration in skeletal muscles based on pig models. We investigated the regulatory effects of CLAs on cell populations and molecular characteristics in pig muscles and found CLAs could promote the transformation of fast glycolytic myofibers into slow oxidative myofibers. We also observed three subpopulations including SCD+/DGAT2+, FABP5+/SIAH1+, and PDE4D+/PDE7B+ subclusters in adipocytes and CLAs could increase the percentage of SCD+/DGAT2+ adipocytes. RNA velocity analysis showed FABP5+/SIAH1+ and PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ adipocytes. We further verified the differentiated trajectory of mature adipocytes and identified PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ and FABP5+/SIAH1+ adipocytes by using high IMF content Laiwu pig models. The cell-cell communication analysis identified the interaction network between adipocytes and other subclusters such as fibro/adipogenic progenitors (FAPs). Pseudotemporal trajectory analysis and RNA velocity analysis also showed FAPs could differentiate into PDE4D+/PDE7B+ preadipocytes and we discovered the differentiated trajectory of preadipocytes into mature adipocytes. Besides, we found CLAs could promote FAPs differentiate into SCD+/DGAT2+ adipocytes via inhibiting c-Jun N-terminal kinase (JNK) signalling pathway in vitro. This study provides a foundation for regulating fat infiltration in skeletal muscles by using nutritional strategies and provides potential opportunities to serve pig as an animal model to study human fat infiltrated diseases.
To study the feasibility of human adipose-derived stem cells (hADSCs) combined with small intestinal submucosa powder (SISP)/chitosan chloride (CSCl)-β-glycerol phosphate disodium (GP)-hydroxyethyl cellulose (HEC) for adipose tissue engineering.hADSCs were isolated from human breast fat with collagenase type I digestion, and the third passage hADSCs were mixed with SISP/CSCl-GP-HEC at a density of 1 x 10(6) cells/mL. Twenty-four healthy female nude mice of 5 weeks old were randomly divided into experimental group (n = 12) and control group (n=12), and the mice were subcutaneously injected with 1 mL hADSCs+SISP/CSCl-GP-HEC or SISP/CSCl-GP-HEC respectively at the neck. The degradation rate was evaluated by implant volume measurement at 0, 1, 2, 4, and 8 weeks. Three mice were euthanized at 1, 2, 4, and 8 weeks respectively for general, histological, and immunohistochemical observations. The ability of adipogenesis (Oil O staining), angiopoiesis (CD31), and localized the hADSCs (immunostaining for human Vimentin) were identified.The volume of implants of both groups decreased with time, but it was greater in experimental group than the control group, showing significant difference at 8 weeks (t = 3.348, P = 0.029). The general observation showed that the border of implants was clear with no adhesion at each time point; fat-liked new tissues were observed with capillaries on the surface at 8 weeks in 2 groups. The histological examinations showed that the structure of implants got compact gradually after injection, and SISP gradually degraded with slower degradation speed in experimental group; adipose tissue began to form, and some mature adipose tissue was observed at 8 weeks in the experimental group. The Oil O staining positive area of experimental group was greater than that of the control group at each time point, showing significant difference at 8 weeks (t = 3.41 1, P = 0.027). Immunohistochemical staining for Vemintin showed that hADSCs could survive at each time point in the experimental group; angiogenesis was most remarkable at 2 weeks, showing no significant differences in CD31 possitive area between 2 groups (P > 0.05), but angiogenesis was more homogeneous in experimental group.SISP/CSCl-GP-HEC can use as scaffolds for hADSCs to reconstruct tissue engineered adipose.
Background: Approximately 10-20 million Americans have been clinically diagnosed with thyroid nodules. Shear wave elastography (SWE) and real-time elastography (RTE) are two primary forms of elastography for identifying the status of thyroid nodules. The aim of this study is to assess the performance of RTE and SWE in identifying malignant thyroid nodules. Methods: Relevant articles were systematically retrieved from PubMed, Embase and Cochrane Library. In order to evaluate the overall diagnostic accuracy, we have considered pooled sensitivity (SEN), specificity (SPE), area under the curve (AUC) and partial AUC with corresponding 95% confidence intervals (95%CIs). Stratified analyses by ethnicity (Caucasian, Asian), the number of malignant nodules (> 50, < 50), score system (elasticity scores: ES and strain ration: SR) and ES (> 4, < 4) were performed to explore potential sources of heterogeneity. All statistical tests were performed using the R 3.2.1 software package. Results: We analyzed 80 trials from 71 studies with 16,624 subjects (12,348 for SWE, 4,276 for RTE). The pooled results suggested that RTE is more accurate than SWE in diagnosing malignant cases (RTE: SEN= 0.829, 95%CI = 0.799-0.855, SPE = 0.828, 95%CI = 0.789-0.862, AUC = 0.889; SWE: SEN = 0.784, 95%CI = 0.732-0.828, SPE = 0.824, 95%CI = 0.766-0.871, AUC = 0.859). No significant difference was found in the subgroup analyses. Conclusion: Our findings revealed that RTE is superior to SWE in differentiating malignant and benign thyroid nodules. Nevertheless, more studies focusing on the diagnostic accuracy of RTE and SWE during different stages of thyroid nodules development should be carried out in the future.
Abstract The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.
Abstract Mammalian male germ cell development is a stepwise cell-fate transition process; however, the full-term developmental profile of male germ cells remains undefined. Here, by interrogating the high-precision transcriptome atlas of 11,598 cells covering 28 critical time-points, we demonstrate that cell-fate transition from mitotic to post-mitotic primordial germ cells is accompanied by transcriptome-scale reconfiguration and a transitional cell state. Notch signaling pathway is essential for initiating mitotic arrest and the maintenance of male germ cells’ identities. Ablation of HELQ induces developmental arrest and abnormal transcriptome reprogramming of male germ cells, indicating the importance of cell cycle regulation for proper cell-fate transition. Finally, systematic human-mouse comparison reveals potential regulators whose deficiency contributed to human male infertility via mitotic arrest regulation. Collectively, our study provides an accurate and comprehensive transcriptome atlas of the male germline cycle and allows for an in-depth understanding of the cell-fate transition and determination underlying male germ cell development.
Abstract α-Synuclein (α-syn) strains can serve as discriminators between Parkinson’s disease (PD) from other α-synucleinopathies. The relationship between α-syn strain dynamics and clinical performance as patients transition from normal cognition (NC) to cognitive impairment (CI) is not known. Here, we show that the biophysical properties and neurotoxicity of α-syn strains change as PD cognitive status transitions from NC to mild cognitive impairment (PD-MCI) and dementia (PD-D). Both cross-sectional and longitudinal analyses reveal distinct α-syn strains in PD patients correlating to their level of cognitive impairment. This study presents evidence that individuals with PD have different α-syn strains that change in accordance with their cognitive status and highlights the potential of α-syn strain dynamics to guide future diagnosis, management, and stratification of PD patients. One Sentence Summary Distinct features of α-syn strains change with cognitive decline in Parkinson’s disease.
Objective To investigate the relationship between insulin like growth factor (IGF Ⅰ)、IGF Ⅱ and IGFBP 3 and Child Pugh classification in patients with liver cirrhosis and to determine the potential clinical markers of functional hepatic reserves. Methods Forty four patients with posthepatitic cirrhosis were divided into 3 groups according to disease severity (Child Pugh Score) and 38 healthy subjects severed as controls. Serum levels of IGF Ⅰ, IGF Ⅱ and IGFBP 3 were measured in these groups by immunoradiometric assay. Results Baseline IGF Ⅰ, IGF Ⅱ and IGFBP 3 levels were significantly lower in patients with cirrhosis than in controls, and the serum concentrations of IGF Ⅰ, IGF Ⅱ and IGFBP 3 were associated with the marked changes of liver function due to Child Pugh score. They all showed a significant correlation with the degree of hepatic dysfunction and dropped markedly during the progression of liver failure. The sensitivity of IGF Ⅱ is much higher than that of IGF Ⅰ and IGFBP 3. It was found that IGF Ⅰ30 ng/ml, IGF Ⅱ200 ng/ml, and IGFBP 36 ng/ml might be true predictors of a negative prognosis in patients with liver cirrhosis. Conclusions Serum IGF Ⅰ, IGF Ⅱ and IGFBP 3 may provide new markers in the assessment of liver function, and more importantly, the results indicate that the combination of IGF Ⅰ, IGF Ⅱ and IGFBP 3 with the Child Pugh score is more effective in predicting prognosis than the Child Pugl score alone.
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