PO-119 Adrenergic Receptor β3 Up-regulates Uncoupling Protein 1 and Cyclooxygenase 2 Expressions in The Brown Adipocyte

Objective Brown adipose tissues (BAT) activation is important for losing weight as its high energy expenditure in Mammalian. Recent studies showed that exercise may also be essential for BAT activation. Uncoupling protein 1 (UCP1), specifically expressed in BAT's mitochondria, uncouples oxidative phosphorylation and dissipates energy from Free Fatty Acids into heat. Activating the Adrenergic Receptor β3 (Adrβ3) provides fuel for mitochondrial heat production and up-regulates Cyclooxygenase 2 (COX2), which is a key factor of UCP1 synthesis. Sympathetic nerve excitement stimulated by exercise can release norepinephrine as a neurotransmitter, which can affect Adrβ3. Brown adipocyte (BAC) is a kind of adipocyte in vitro as a model to study heat production. Isoprenaline Hydrochloride (ISO) is a widely used as an Adrβ agonist. In this research, we tried to figure out the response of BAC to Adrβ3 activations with different time points and whether ISO can be used as a BAC activator. Methods C3H10T1/2 cells were maintained in a humidified, 37°C, 5% CO2 incubator in DMEM/F12 medium with 10% fetal bovine serum (FBS). For brown adipogenesis, cells were first split into differentiation medium (DMEM/F12 containing 10% FBS, 20nM insulin, 1nM 3,3’5-Triiodo-L-thyronine(T3)) for 4 days, the medium was changed every other day. Confluent cells were treated for 2 days with brown adipose adipogenesis cocktails (differentiation medium containing 2µg/mL dexamethasone, 0.5mM isobutylmethylxanthine (IBMX), 0.125mM indomethacin and 1µM rosiglitazone) on day 4. Then the medium was replaced by differentiation medium and changed every other day. At day 10, the full differentiation adipocytes were treated with 10µM ISO for 0 (as control), 1, 3, 6, 12 and 24 hours. For the lipid droplets staining, the cells were fixed by 4% paraformaldehyde solution then stained with Oil Red O. The cells were harvested and the total cell lysates were extracted for protein analysis after each time point. The UCP1, COX2, and Adrβ3 expression levels were detected by western blot, using Actin as the internal protein. The results were expressed as the mean ± standard error of the mean (SEM). Group comparisons were performed using two-way ANOVA and LSD’s post-hoc tests. Results After differentiation, the cell shapes converted from fibroblastic to a spherical shape. Dispersed small lipid droplets were observed in the cells. After ISO treatment, the red color after Oil Red Staining became lighter and the size of the lipid droplets turned to smaller. The Adrβ3 protein expressions were 1.00±0.00, 1.34±0.32, 1.07±0.50, 4.65±1.84*, 2.44±0.73, and 3.43±1.09 at 0h, 1h, 3h, 6h, 12h, and 24h after ISO treatment, respectively. After introduced to ISO, the UCP1 expression levels were 1.00±0.00, 1.95±0.39, 2.72±0.57, 5.68±1.82*, 3.49±0.92, and 2.79±1.05 at 0h, 1h, 3h, 6h, 12h, and 24h, respectively. And for COX2, the protein expressions were 1.00±0.00, 2.13±0.67, 1.82±0.33, 4.67±1.82*, 2.88±0.44, and 2.65±0.54, respectively. The * means p ˂ 0.05, compared with oh controls. The proteins expressions were reached to peak after 6 hours ISO treatment from the above results. Conclusions UCP1 and COX2 protein expressions were increased in BAC according to Adrβ3's expression in different time points, indicating that Adrβ3 may induce adipolysis in BAC and help to burn fat and produce heat

A strategy to regulate the yield ratio of a metastable high Zr-containing β titanium alloy: Synergistic effects of the β domain, β stability and β/α interfaces by varying the α phase content

To meet the demands of both processing and serving, to the best of our knowledge, this is the first report exhibiting large range control of the yield ratio from 0.31 to 0.96 with decent elongations over 10% in the same alloy with low-cost thermal treatments. The yield ratio of the metastable Ti-30Zr-5Mo alloy was regulated via adjusting trigger stress of the stress-induced phase transformation and work-hardening ability through changing the α phase content. Materials with acicular α phase of different contents were successfully prepared via low-cost thermal treatment. The effects of the α phase content on the stress-induced α' martensite phase transformation and work hardening behavior were then investigated. In the Ti-30Zr-5Mo alloy with dual phases, due to the crystal difference and element partitioning, the hardness of the α phase is higher than that of the β matrix, and the hardness difference between the phases increases with increasing α phase. In addition to Mo, Zr plays an important role in stabilizing the β phase in high-Zr-containing alloys. Deformation initiates in the β phase of both single-phase and duplex-phase alloys. The deformation mechanism of the β phase is dependent on both the β domain and β stability. Due to the low trigger stress and excellent work hardening ability, stress-induced α' martensite phase transformation is helpful to lower the yield ratio. As the α phase content increases, the trigger stress increases, and when the α phase content increases to 40%, dislocation slip dominates rather than stress-induced α' martensite phase transformation, and a high yield strength of 944 MPa is obtained. The α/β phase interfaces act as effective obstacles to hinder dislocation movement and provide working hardening, and the obstruction effect is more significant with an increase in the hardness difference between the α and β phases. The stress-induced α' phase transformation and/or the deformation coordination between the α and β phases guarantee decent elongations of no less than 10% in the large control of the yield ratio from 0.31 to 0.96 with a yield strength from 254 to 1013 MPa. It paves the way to develop “Unititaniam” alloys for wide possible applications.Zhao X., Zhu R., Song W., et al. A strategy to regulate the yield ratio of a metastable high Zr-containing β titanium alloy: Synergistic effects of the β domain, β stability and β/α interfaces by varying the α phase content. Journal of Alloys and Compounds 952, 170024 (2023); https://doi.org/10.1016/j.jallcom.2023.170024

Miniature bioinspired artificial compound eyes: microfabrication technologies, photodetection and applications

As an outstanding visual system for insects and crustaceans to cope with the challenges of survival, compound eye has many unique advantages, such as wide field of view, rapid response, infinite depth of field, low aberration and fast motion capture. However, the complex composition of their optical systems also presents significant challenges for manufacturing. With the continuous development of advanced materials, complex 3D manufacturing technologies and flexible electronic detectors, various ingenious and sophisticated compound eye imaging systems have been developed. This paper provides a comprehensive review on the microfabrication technologies, photoelectric detection and functional applications of miniature artificial compound eyes. Firstly, a brief introduction to the types and structural composition of compound eyes in the natural world is provided. Secondly, the 3D forming manufacturing techniques for miniature compound eyes are discussed. Subsequently, some photodetection technologies for miniature curved compound eye imaging are introduced. Lastly, with reference to the existing prototypes of functional applications for miniature compound eyes, the future development of compound eyes is prospected

miRNA expression differentiation induced by polyploidization in newly formed triploids of black poplar

During whole genomic duplication (WGD) events, micro RNAs (miRNAs) are involved in stabilization of chromatin and genome and epigenetic regulation of gene expression. In this study, a newly induced triploid group of hybrids between sect. Tacamahaca and sect. Aigeiros in Populus, was characterized for genome-wide miRNA expression after WGD. Seven miRNA libraries (male parent, female parent, group of triploid offspring’s, group of diploid offspring, and three triploid individuals) were constructed and variation of miRNA expression from diploid parents to triploid offspring’s as well as distinction between triploid and diploid offspring were analyzed. The results showed that a total of 240 miRNAs were predicted including 187 known miRNAs and 53 novel miRNAs. 81.25% of miRNAs in triploid offspring were non-additively expressed in which 52.31% were down-regulated. A novel miRNA with 24nt in length choosing adenine as its first base was found in triploid offspring group suggesting its potential role in regulation of DNA methylation after WGD. A total of 18 novel miRNAs were specifically expressed in the library of triploid group. Targeted genes of different expressed miRNAs in three comparison sets (triploid offspring group vs female parent, male parent, and diploid offspring group) were all enriched in ADP binding (GO: 0043531; FDR < 0.05). KEGG enrichment pathway of all three comparison sets was plant-pathogen interaction. This study revealed an essential role of miRNAs involving in epigenetic regulation after WGD in poplar and provided a good model for further studies of polyploidization advantages in woody plant

Abnormal Alterations of Regional Spontaneous Neuronal Activity in Inferior Frontal Orbital Gyrus and Corresponding Brain Circuit Alterations: A Resting-State fMRI Study in Somatic Depression

Background: Major depressive disorders often involve somatic symptoms and have been found to have fundamental differences from non-somatic depression (NSD). However, the neural basis of this type of somatic depression (SD) is unclear. The aim of this study is to use the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses to examine the abnormal, regional, spontaneous, neuronal activity and the corresponding brain circuits in SD patients.Methods: 35 SD patients, 25 NSD patients, and 27 matched healthy controls were selected to complete this study. The ALFF and seed-based FC analyses were employed, and the Pearson correlation was determined to observe possible clinical relevance.Results: Compared with NSD, the SD group showed a significant ALFF increase in the right inferior temporal gyrus; a significant ALFF decrease in left hippocampus, right inferior frontal orbital gyrus and left thalamus; and a significant decrease in the FC value between the right inferior frontal orbital gyrus and the left inferior parietal cortex (p &lt; 0.05, corrected). Within the SD group, the mean ALFF value of the right inferior frontal orbital gyrus was associated with the anxiety factor scores (r = –0.431, p = 0.010, corrected).Conclusions: Our findings suggest that abnormal differences in the regional spontaneous neuronal activity of the right inferior frontal orbital gyrus were associated with dysfunction patterns of the corresponding brain circuits during rest in SD patients, including the limbic-cortical systems and the default mode network. This may be an important aspect of the underlying mechanisms for pathogenesis of SD at the neural level

TPH-2 Gene Polymorphism in Major Depressive Disorder Patients With Early-Wakening Symptom

Background: Sleep disturbances, such as early wakening, are frequently observed in patients with major depressive disorder (MDD). The suprachiasmatic nuclei (SCN), which controls circadian rhythm, is innervated by the raphe nucleus, a region where Tryptophan hydroxylase-2 (TPH-2) gene is primarily expressed. Although TPH-2 is often implicated in the pathophysiology of depression, few studies have applied a genetic and imaging technique to investigate the mechanism of early wakening symptom in MDD. We hypothesized that TPH-2 variants could influence the function of SCN in MDD patients with early wakening symptom.Methods: One hundred and eighty five MDD patients (62 patients without early wakening and 123 patients with early wakening) and 64 healthy controls participated in this study. Blood samples were collected and genotyping of rs4290270, rs4570625, rs11178998, rs7305115, rs41317118, and rs17110747 were performed by next-generation sequencing (NGS) technology. Logistic regression model was employed for genetic data analysis using the PLINK software. Based on the allele type, rs4290270, which was significant in the early wakening MDD group, participants were categorized into two groups (A allele and T carrier). All patients underwent whole brain resting-state functional magnetic resonance imaging (rs-fMRI) scanning and a voxel-wise functional connectivity comparison was performed between the groups.Results: rs4290270 was significantly linked to MDD patients who exhibited early wakening symptom. The functional connectivities of the right SCN with the right fusiform gyrus and right middle frontal gyrus were increased in the T carrier group compared to the A allele group. In addition, the functional connectivities of the left SCN with the right lingual gyrus and left calcarine sulcus were decreased in the T carrier group compared to the A allele group.Conclusion: These findings suggested that the TPH-2 gene variant, rs4290270, affected the circadian regulating function of SCN. The altered functional connectivities, observed between the SCN and right fusiform gyrus, right middle frontal gyrus, the right lingual gyrus and left calcarine sulcus, could highlight the neural mechanism by which SCN induces sleep-related circadian disruption in T carrier MDD patients. Hence, rs4290270 could potentially serve as a reliable biomarker to identify MDD patients with early wakening symptom

Radiogenomics analysis reveals the associations of dynamic contrast-enhanced–MRI features with gene expression characteristics, PAM50 subtypes, and prognosis of breast cancer

BackgroundTo investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively.MethodsTwo radiogenomics cohorts with paired DCE-MRI and RNA-sequencing (RNA-seq) data were collected from local and public databases and divided into discovery (n = 174) and validation cohorts (n = 72). Six external datasets (n = 1,443) were used for prognostic validation. Spatial–temporal features of DCE-MRI were extracted, normalized properly, and associated with gene expression to identify the imaging features that can indicate subtypes and prognosis.ResultsExpression of genes including RBP4, MYBL2, and LINC00993 correlated significantly with DCE-MRI features (q-value &lt; 0.05). Importantly, genes in the cell cycle pathway exhibited a significant association with imaging features (p-value &lt; 0.001). With eight imaging-associated genes (CHEK1, TTK, CDC45, BUB1B, PLK1, E2F1, CDC20, and CDC25A), we developed a radiogenomics prognostic signature that can distinguish BC outcomes in multiple datasets well. High expression of the signature indicated a poor prognosis (p-values &lt; 0.01). Based on DCE-MRI features, we established classifiers to predict BC clinical receptors, PAM50 subtypes, and prognostic gene sets. The imaging-based machine learning classifiers performed well in the independent dataset (areas under the receiver operating characteristic curve (AUCs) of 0.8361, 0.809, 0.7742, and 0.7277 for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-enriched, basal-like, and obtained radiogenomics signature). Furthermore, we developed a prognostic model directly using DCE-MRI features (p-value &lt; 0.0001).ConclusionsOur results identified the DCE-MRI features that are robust and associated with the gene expression in BC and displayed the possibility of using the features to predict clinical receptors and PAM50 subtypes and to indicate BC prognosis