Nanoemulsions Stable against Ostwald Ripening.

Ostwald ripening, the dominant mechanism of droplet size growth for an O/W nanoemulsion at high surfactant concentrations, depends on micelles in the water phase and high aqueous solubility of oil, especially for spontaneously formed nanoemulsions. In our study, O/W nanoemulsions were formed spontaneously by mixing a water phase with an oil phase containing fatty alcohol polyoxypropylene polyoxyethylene ether (APE). By monitoring periodically the droplet size of the nanoemulsions via dynamic light scattering, we demonstrated that the formed O/W nanoemulsions are stable against Ostwald ripening, i.e., droplet growth. In contrast, the nanoemulsion droplets grew with the addition of micelles, demonstrating the pivotal role of the presence of micelles in the water phase in the occurrence of Ostwald ripening. The influence of the initial phase of APE, the oil or water phase in which APE is present, on the micelle formation is discussed by the partition coefficient and interfacial adsorption of APE between the oil and water phase using a surface and interfacial tensiometer. In addition, the spontaneously formed O/W nanoemulsion, which is stable against Ostwald ripening, can be used as a nanocarrier for the delivery of water-insoluble pesticides. These results provide a novel approach for the preparation of stable nanoemulsions and contribute to elucidating the mechanism of instability of nanoemulsions.

Mouse Trophoblast Cells Have Attenuated Responses to TNF-α and IFN-γ and Can Avoid Synergic Cytotoxicity of the Two Cytokines.

TNF-α and IFN-γ are two inflammatory cytokines that play critical roles in immune responses, but they can also negatively affect cell proliferation and viability. In particular, the combination of the two cytokines (TNF-α/IFN-γ) synergistically causes cytotoxicity in many cell types. We recently reported that mouse embryonic stem cells (ESCs) isolated from the blastocyst stage embryo do not respond to TNF-α and have limited response to IFN-γ, thereby avoiding TNF-α/IFN-γ cytotoxicity. The current study expanded our investigation to mouse trophoblast stem cells (TSCs) and their differentiated trophoblasts (TSC-TBs), the precursors and the differentiated cells of the placenta, respectively. In this study, we report that the combination of TNF-α/IFN-γ does not show the cytotoxicity to TSCs and TSC-TBs that otherwise effectively kills fibroblasts, similar to ESCs. Although ESCs, TSCs, and TSC-TBs are dramatically different in their growth rate, morphology, and physiological functions, they nevertheless share a similarity in being able to avoid TNF-α/IFN-γ cytotoxicity. We propose that this unique immune property may serve as a protective mechanism that limits cytokine cytotoxicity in the blastocyst. With molecular and cellular approaches and genome-wide transcriptomic analysis, we have demonstrated that the attenuated NF-κB and STAT1 transcription activation is a limiting factor that restricts the effect of TNF-α/IFN-γ on TSCs and TSC-TBs.

Post-transcriptional capping generates coenzyme A-linked RNA.

NAD can be inserted co-transcriptionally via non-canonical initiation to form NAD-RNA. However, that mechanism is unlikely for CoA-linked RNAs due to low intracellular concentration of the required initiator nucleotide, 3'-dephospho-CoA (dpCoA). We report here that phosphopantetheine adenylyltransferase (PPAT), an enzyme of CoA biosynthetic pathway, accepts RNA transcripts as its acceptor substrate and transfers 4'-phosphopantetheine to yield CoA-RNA post-transcriptionally. Synthetic natural (RNAI) and small artificial RNAs were used to identify the features of RNA that are needed for it to serve as PPAT substrate. RNAs with 4-10 unpaired nucleotides at the 5' terminus served as PPAT substrates, but RNAs having <4 unpaired nucleotides did not undergo capping. No capping was observed when the +1A was changed to G or when 5' triphosphate was removed by RNA pyrophosphohydrolase (RppH), suggesting the enzyme recognizes pppA-RNA as an ATP analog. PPAT binding affinities were equivalent for transcripts with +1A, +1 G, or 5'OH (+1A), indicating that productive enzymatic recognition is driven more by local positioning effects than by overall binding affinity. Capping rates were independent of the number of unpaired nucleotides in the range of 4-10 nucleotides. Capping was strongly inhibited by ATP, reducing CoA-RNA production ~70% when equimolar ATP and substrate RNA were present. Dual bacterial expression of candidate RNAs with different 5' structures followed by CoA-RNA CaptureSeq revealed 12-fold enrichment of the better PPAT substrate, consistent with in vivo CoA-capping of RNA transcripts by PPAT. These results suggest post-transcriptional RNA capping as a possible mechanism for the biogenesis of CoA-RNAs in bacteria.

A pan-cancer analysis of prognostic significance and immunological role of lysosomal-associated membrane protein 3.

Lysosomal dysfunction can drive carcinogenesis. Lysosomal-associated membrane protein 3 (LAMP3), is a member of the Lysosome Associated Membrane Proteins and is involved in the malignant phenotype such as tumour metastasis and drug resistance, while the mechanisms that regulate the malignant progression of tumour remain vague. Our study aims to provide a more systematic and comprehensive understanding of the role of LAMP3 in the progression of various cancers by various databases.We explored the role of LAMP3 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple online web platforms and software were used for data analysis, including HPA, TIMER, TISIDB, GEPIA, UALCAN, Kaplan-Meier plotter, DAVID and TIGER. The immunohistochemistry was used to quantify the LAMP3 and PD-L1 expression levels in cancer.High LAMP3 expression was found in most cancers and differentially expressed across molecular and immune subtypes. The expression of LAMP3 was involved in the immune-associated processes of Antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and the immune-associated pathways of T cell receptor and B cell receptor signalling pathways in most cancers. It also correlated with genetic markers of immunomodulators in various cancers. LAMP3 and PD-L1 expression in BRCA and HNSC tissues was higher than that in corresponding adjacent normal tissues by immunohistochemistry. There is a significant correlation between the expression of LAMP3 and PD-L1.Our study elucidates that LAMP3 has different expression patterns and genetic alteration patterns in different tumours. It is a potential biomarker for immune-related cancer diagnosis, prognosis and efficacy prediction.

Bile acid receptors and renal regulation of water homeostasis.

The kidney is the key organ responsible for maintaining the body's water and electrolyte homeostasis. About 99% of the primary urine filtered from the Bowman's capsule is reabsorbed along various renal tubules every day, with only 1-2 L of urine excreted. Aquaporins (AQPs) play a vital role in water reabsorption in the kidney. Currently, a variety of molecules are found to be involved in the process of urine concentration by regulating the expression or activity of AQPs, such as antidiuretic hormone, renin-angiotensin-aldosterone system (RAAS), prostaglandin, and several nuclear receptors. As the main bile acid receptors, farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor 1 (TGR5) play important roles in bile acid, glucose, lipid, and energy metabolism. In the kidney, FXR and TGR5 exhibit broad expression across all segments of renal tubules, and their activation holds significant therapeutic potential for numerous acute and chronic kidney diseases through alleviating renal lipid accumulation, inflammation, oxidative stress, and fibrosis. Emerging evidence has demonstrated that the genetic deletion of FXR or TGR5 exhibits increased basal urine output, suggesting that bile acid receptors play a critical role in urine concentration. Here, we briefly summarize the function of bile acid receptors in renal water reabsorption and urine concentration.

TSTA3 overexpression promotes malignant characteristics in LUSC by regulating LAMP2-mediated autophagy and tumor microenvironment.

BACKGROUND: TSTA3 gene encoding GDP-L-fucose synthase has recently been proved to be closely related to the prognosis of patients with various tumors. However, its role in lung cancer is still unclear. The purpose of this study is to explore the expression level, prognostic effect, potential function and mechanism of TSTA3 in lung cancer. METHODS: Based on TCGA database, Kaplan-Meier and COX regression was used to analyze the relationship between TSTA3 expression and prognosis of lung cancer patients. Immunohistochemistry was used to determine the TSTA3 protein expression in lung cancer and normal tissues. The function of TSTA3 in lung squamous cell carcinoma (LUSC) cell was determined by CCK8, colony formation, transwell assay in vitro and subcutaneous xenografts in vivo. Transcriptome analysis, Lyso-Tracker Red staining and rescue experiment were used to explore the possible underlying mechanism. RESULTS: The expression of TSTA3 was significantly increased in lung cancer, especially in LUSC, and was significantly correlated with the malignant characteristics of LUSC. COX regression analysis showed that the high expression of TSTA3 was an independent prognostic factor in LUSC patients. This was also confirmed by immunohistochemical staining. Compared with the control group, the proliferation, colony formation, invasion and migration ability of LUSC cells with TSTA3 overexpression was enhanced. Similarly, the ability of cell proliferation, colony formation, invasion and migration were weakened after transient knockdown of TSTA3. In vivo experiment showed that compared with control group, TSTA3 overexpression significantly promoted the growth of tumor and shortened survival time. In addition, transcriptome sequencing analysis showed that the differentially expressed genes between TSTA3 overexpression and control group was mainly concentrated in the lysosome pathway. Further study found that TSTA3 might affect the proliferation, invasion and migration of LUSC by regulating the expression of lysosome-associated membrane protein 2 (LAMP2) in LUSC. CONCLUSION: The expression level of TSTA3 in LUSC is significantly higher than that in normal tissues. High expression of TSTA3 is associated with poor prognosis of LUSC patients. TSTA3 may affect the proliferation, invasion and migration of LUSC by regulating LAMP2.

Estrogen receptor ß attenuates renal fibrosis by suppressing the transcriptional activity of Smad3.

Renal fibrosis (RF) is a common pathway leading to chronic kidney disease (CKD), which lacks effective treatment. While estrogen receptor beta (ERß) is known to be present in the kidney, its role in RF remains unclear. The present study aimed to investigate the role and underlying mechanism of ERß during RF progression in patients and animal models with CKD. We found that ERß was highly expressed in the proximal tubular epithelial cells (PTECs) in healthy kidneys but its expression was largely lost in patients with immunoglobin A nephropathy (IgAN) and in mice with unilateral ureter obstruction (UUO) and subtotal nephrectomy (5/6Nx). ERß deficiency markedly exacerbated, whereas ERß activation by WAY200070 and DPN attenuated RF in both UUO and 5/6Nx mouse models, suggesting a protective role of ERß in RF. In addition, ERß activation inhibited TGF-ß1/Smad3 signaling, while loss of renal ERß was associated with overactivation of the TGF-ß1/Smad3 pathway. Furthermore, deletion or pharmacological inhibition of Smad3 prevented the loss of ERß and RF. Mechanistically, activation of ERß competitively inhibited the association of Smad3 with the Smad-binding element, thereby downregulating the transcription of the fibrosis-related genes without altering Smad3 phosphorylation in vivo and in vitro. In conclusion, ERß exerts a renoprotective role in CKD by blocking the Smad3 signaling pathway. Thus, ERß may represent as a promising therapeutic agent for RF.

Glucagon Promotes Gluconeogenesis through the GCGR/PKA/CREB/PGC-1α Pathway in Hepatocytes of the Japanese Flounder Paralichthys olivaceus.

In order to investigate the mechanism of glucagon regulation of gluconeogenesis, primary hepatocytes of the Japanese flounder (Paralichthys olivaceus) were incubated with synthesized glucagon, and methods based on inhibitors and gene overexpression were employed. The results indicated that glucagon promoted glucose production and increased the mRNA levels of glucagon receptor (gcgr), guanine nucleotide-binding protein Gs α subunit (gnas), adenylate cyclase 2 (adcy2), protein kinase A (pka), cAMP response element-binding protein 1 (creb1), peroxisome proliferator-activated receptor-γ coactivator 1α (pgc-1α), phosphoenolpyruvate carboxykinase 1 (pck1), and glucose-6-phosphatase (g6pc) in the hepatocytes. An inhibitor of GCGR decreased the mRNA expression of gcgr, gnas, adcy2, pka, creb1, pgc-1α, pck1, g6pc, the protein expression of phosphorylated CREB and PGC-1α, and glucose production. The overexpression of gcgr caused the opposite results. An inhibitor of PKA decreased the mRNA expression of pgc-1α, pck1, g6pc, the protein expression of phosphorylated-CREB, and glucose production in hepatocytes. A CREB-targeted inhibitor significantly decreased the stimulation by glucagon of the mRNA expression of creb1, pgc-1α, and gluconeogenic genes, and glucose production decreased accordingly. After incubating the hepatocytes with an inhibitor of PGC-1α, the glucagon-activated mRNA expression of pck1 and g6pc was significantly down-regulated. Together, these results demonstrate that glucagon promotes gluconeogenesis through the GCGR/PKA/CREB/PGC-1α pathway in the Japanese flounder.

Errate: Relationship Between Changes in Cranio-Cervical Extensor Muscles and Quality of Life: A Single-Center Study of 15 Patients with Chronic Tension-Type Headache.

The authors requested to correct the spelling of labels in Figure 3. The correct spelling should be "Healthy persons". The other elements of the figure remain the same, and the interpretation of the results remain unchanged. Reference: Xiaoman Min, Yongjun Huo, Ning Sun, Hongwei Zhi, Haitao Li, Sishuo Zhang, Wenqiang Cui, Yanlin Guo, Hongyun Wu: Relationship Between Changes in Cranio-Cervical Extensor Muscles and Quality of Life: A Single-Center Study of 15 Patients with Chronic Tension-Type Headache. Med Sci Monit, 2023; 29: e938574. DOI: 10.12659/MSM.938574.

Relationship Between Changes in Cranio-Cervical Extensor Muscles and Quality of Life: A Single-Center Study of 15 Patients with Chronic Tension-Type Headache.

BACKGROUND This single-center study of 15 patients with chronic tension-type headache aimed to compare the cranio-cervical extensor muscles between patients with chronic tension-type headache and healthy individuals and to explore the relationship between changes in cranio-cervical extensor muscles and quality of life (QoL). MATERIAL AND METHODS We recruited 15 patients with chronic tension-type headache and 15 healthy individuals. Patients with chronic tension-type headache were diagnosed by 2 neurologists according to the diagnostic criteria in the International Classification of Headache Disorders, 3rd edition (ICHD-3). Morphological changes in the cranio-cervical extensor muscle were detected using magnetic resonance imaging (MRI). QoL and the degree of neck dysfunction were assessed using the Headache Impact Test-6 (HIT-6) and Neck Disability Index (NDI), respectively. RESULTS The relative cross-sectional areas (rCSAs) of the rectus capitis posterior minor (RCPmin) were lower in patients with chronic tension-type headache than in healthy individuals. The HIT-6 scores (r=-0.93, P<0.001 and r=-0.85, P<0.001 for RCPmin right side and left side, respectively) and NDI scores (r=-0.75, P<0.001 and r=-0.70, P<0.001 for RCPmin right side and left side, respectively) were negatively associated with the rCSA of RCPmin in the chronic tension-type headache group. CONCLUSIONS Most patients with chronic tension-type headache experience RCPmin atrophy. The more evident the RCPmin atrophy, the worse the QoL of the patients with chronic tension-type headache.

Role of FXR in Renal Physiology and Kidney Diseases.

Farnesoid X receptor, also known as the bile acid receptor, belongs to the nuclear receptor (NR) superfamily of ligand-regulated transcription factors, which performs its functions by regulating the transcription of target genes. FXR is highly expressed in the liver, small intestine, kidney and adrenal gland, maintaining homeostasis of bile acid, glucose and lipids by regulating a diverse array of target genes. It also participates in several pathophysiological processes, such as inflammation, immune responses and fibrosis. The kidney is a key organ that manages water and solute homeostasis for the whole body, and kidney injury or dysfunction is associated with high morbidity and mortality. In the kidney, FXR plays an important role in renal water reabsorption and is thought to perform protective functions in acute kidney disease and chronic kidney disease, especially diabetic kidney disease. In this review, we summarize the recent advances in the understanding of the physiological and pathophysiological function of FXR in the kidney.

Regulating conduction and polarization losses by adjusting bonded N in N-doped Cu/CuO/C composites.

Conduction and polarization losses are the main forms of dielectric loss, and regulating these mechanisms is key to obtaining favorable electromagnetic wave absorption performance. In this study, the conversion of graphite N and pyridine N in Cu-based metal-organic framework (MOF)-derived composites was adopted to modulate conduction and polarization losses by tuning the pyrolysis temperature and Cu salt concentration. The results show that increasing the pyrolysis temperature facilitates the conversion of pyridine N to graphite N, which is beneficial for conduction loss. Moreover, increasing the Cu concentration promotes the transformation of pyridine N to graphite N as well as, and then promotes the reverse conversion of graphite N to pyridine N, which is conducive to defect-induced polarization. The unique layered Cu/CuO/C composite obtained at 700 °C with a moderate Cu content exhibited the optimal performance with an effective absorption bandwidth of 5.5 GHz (11.6 âˆ¼ 17.1 GHz) at an ultra-thin thickness of 1.56 mm. This is owed to its favorable impedance matching, significant conduction loss, and polarization loss (defect-induced polarization and interfacial polarization). This study provides a novel strategy for regulating conduction and polarization losses.

Vitamin D3/VDR inhibits inflammation through NF-κB pathway accompanied by resisting apoptosis and inducing autophagy in abalone Haliotis discus hannai.

Vitamin D3 is believed to be a contributing factor to innate immunity. Vitamin D receptor (VDR) has a positive effect on inhibiting nuclear factor κB (NF-κB)-mediated inflammation. The underlying molecular mechanisms remain unclear, particularly in mollusks. Consequently, this study will investigate the process of vitamin D3/VDR regulating NF-κB pathway and further explore their functions on inflammation, autophagy, and apoptosis in abalone Haliotis discus hannai. Results showed that knockdown of VDR by using siRNA and dsRNA of VDR in vitro and in vivo led to more intense response of NF-κB signaling to lipopolysaccharide and higher level of apoptosis and autophagy. In addition, 1,25(OH)2D3 stimulation after VDR silencing could partially alleviate apoptosis and induce autophagy. Overexpression of VDR restricted the K48-polyubiquitin chain-dependent inhibitor of κB (IκB) ubiquitination and apoptosis-associated speck-like protein containing CARD (ASC) oligomerization. Besides, VDR silencing resulted in increase of ASC speck formation. In further mechanistic studies, we showed that VDR can directly bind to IκB and IKK1 in vitro and in vivo. In the feeding trial, H&E staining, TUNEL, and electron microscope results showed that vitamin D3 deficiency (0 IU/kg) could recruit more basophilic cells and increase more TUNEL-positive apoptotic cells and lipid droplets (LDs) than vitamin D3 supplement (1000 IU/kg and 5000 IU/kg). In summary, abalone VDR plays a negative regulator role in NF-κB-mediated inflammation via interacting with IκB and inhibiting ubiquitin-dependent degradation of IκB. Vitamin D3 in combination with VDR is essential to establish a delicate balance between autophagy and apoptosis in response to inflammation.

Comprehensive Analysis of Cuproptosis-Related Genes in Prognosis and Immune Infiltration of Hepatocellular Carcinoma Based on Bulk and Single-Cell RNA Sequencing Data.

Background: Studies on prognostic potential and tumor immune microenvironment (TIME) characteristics of cuproptosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are limited. Methods: A multigene signature model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The cuproptosis-related multivariate cox regression analysis and bulk RNA-seq-based immune infiltration analysis were performed. The results were verified using two cohorts. The enrichment of CRGs in T cells based on single-cell RNA sequencing (scRNA-seq) was performed. Real-time polymerase chain reaction (RT-PCR) and multiplex immunofluorescence staining were performed to verify the reliability of the conclusions. Results: A four-gene risk scoring model was constructed. Kaplan−Meier curve analysis showed that the high-risk group had a worse prognosis (p < 0.001). The time-dependent receiver operating characteristic (ROC) curve showed that the OS risk score prediction performance was good. These results were further confirmed in the validation queue. Meanwhile, the Tregs and macrophages were enriched in the cuproptosis-related TIME of HCC. Conclusions: The CRGs-based signature model could predict the prognosis of HCC. Treg and macrophages were significantly enriched in cuproptosis-related HCC, which was associated with the depletion of proliferating T cells.

Effects of dietary yeast culture on health status in digestive tract of juvenile Pacific white shrimp Litopenaeus Vannamei.

A feeding trial was conducted to investigate the effects of dietary yeast culture (YC) on health status in digestive tract of juvenile Pacific white shrimp Litopenaeus Vannamei. Shrimps (initial weight: 3.33 ± 0.06 g) were fed with graded levels of dietary YC (control, 0.3%, 0.5% and 1.0%). Results of the present study showed that villus height and the ratio between villus height and crypt depth in the digestive tract of juvenile shrimp was significantly increased by dietary 0.5% and 1.0%YC (P < 0.05). Besides, dietary 0.5% and 1.0%YC significantly activities of phenoloxidase (PO), lysozyme (LZ), acid phosphatase (ACP) and alkaline phosphatase (AKP) (P < 0.05), significantly up-regulated mRNA levels of prophenoloxidase (propo), lysozyme (lz), anti-lipopolysaccharide factor (alf), crustin and penaienadin (P < 0.05) and down-regulated mRNA levels of caspase-1, nuclear factor κB p65 (nf-κbp65) myeloid differentiation primary response protein (myd88) and toll like receptor (tlr) in the digestive tract of juvenile shrimp (P < 0.05). Compared with the control, dietary 0.5%YC increased Chao1 index in the digestive tract of juvenile shrimp. In addition, compared with the control, dietary 0.5% and 1.0%YC significantly increased relative abundance of Lactobacillus (P < 0.05). It can be concluded that dietary YC made positive contribution to health status in digestive tract of juvenile shrimp through improving morphology and microbiota, enhancing immune function, and inhibiting inflammation of digestive tract.

Phosphorylation of 17ß-hydroxysteroid dehydrogenase 13 at serine 33 attenuates nonalcoholic fatty liver disease in mice.

17ß-hydroxysteroid dehydrogenase-13 is a hepatocyte-specific, lipid droplet-associated protein. A common loss-of-function variant of HSD17B13 (rs72613567: TA) protects patients against non-alcoholic fatty liver disease with underlying mechanism incompletely understood. In the present study, we identify the serine 33 of 17ß-HSD13 as an evolutionally conserved PKA target site and its phosphorylation facilitates lipolysis by promoting its interaction with ATGL on lipid droplets. Targeted mutation of Ser33 to Ala (S33A) decreases ATGL-dependent lipolysis in cultured hepatocytes by reducing CGI-58-mediated ATGL activation. Importantly, a transgenic knock-in mouse strain carrying the HSD17B13 S33A mutation (HSD17B1333A/A) spontaneously develops hepatic steatosis with reduced lipolysis and increased inflammation. Moreover, Hsd17B1333A/A mice are more susceptible to high-fat diet-induced nonalcoholic steatohepatitis. Finally, we find reproterol, a potential 17ß-HSD13 modulator and FDA-approved drug, confers a protection against nonalcoholic steatohepatitis via PKA-mediated Ser33 phosphorylation of 17ß-HSD13. Therefore, targeting the Ser33 phosphorylation site could represent a potential approach to treat NASH.

An N-glycoproteomic site-mapping analysis reveals glycoprotein alterations in esophageal squamous cell carcinoma.

BACKGROUND: Aberrant glycosylation has been recognized as a hallmark of cancer and N-glycosylation is one of the main types of glycosylation in eukaryotes. Although N-glycoproteomics has made contributions to the discovery of biomarkers in a variety of cancers, less is known about the abnormal glycosylation signatures in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we reported the proteomics and N-glycoproteomic site-mapping analysis of eight pairs of ESCC tissues and adjacent normal tissues. With zic-HILIC enrichment, TMT-based isobaric labeling, LC-MS/MS analysis, differentially expressed N-glycosylation was quantitatively characterized. Lectin affinity enrichment combined with western blot was used to validate the potential biomarkers in ESCC. RESULTS: A series of differentially expressed glycoproteins (e.g., LAMP2, PLOD2) and enriched signaling pathways (e.g., metabolism-related pathway, ECM-receptor interaction, focal adhesion) were identified. Besides that, seven significantly enriched motifs were found from the identified N-glycosylation sites. Three clusters were identified after conducting the dynamic profiling analysis of glycoprotein change during lymph node metastasis progression. Further validation found that the elevated fucosylation level of ITGB1, CD276 contributed to the occurrence and development of ESCC, which might be the potential biomarkers in ESCC. CONCLUSION: In summary, we characterized the N-glycosylation and N-glycoprotein alterations associated with ESCC. The typical changes in glycoprotein expression and glycosylation occupancy identified in our study will not only be used as ESCC biomarkers but also improve the understanding of ESCC biology.

Mouse Trophoblast Cells Can Provide IFN-Based Antiviral Protection to Embryonic Stem Cells via Paracrine Signaling.

The blastocyst is the preimplantation stage embryo that consists of two major components: the inner cell mass (ICM) and the trophectoderm (TE). The ICM gives rise to the fetus and some extraembryonic tissues whereas the TE contributes to development of the placenta. Previous studies have demonstrated that both human and mouse embryonic stem cells (ESCs) derived from the ICM are deficient in expressing type I IFNs in response to viral infection. In this study, we investigated the IFN response in mouse trophoblast stem cells (TSCs) and their in vitro differentiated trophoblasts (TSC-TBs). In this study, we report that, unlike ESCs, TSCs have a functional IFN system. They can express type I IFNs in response to viral stimuli and express IFN-stimulated genes in response to type I IFNs. TSC-TBs have a further developed IFN system and acquired the ability to express specialized type III IFN-λ. Furthermore, TSCs and TSC-TBs can provide ESCs with antiviral activity against Chikungunya, West Nile, and Zika virus infection, as demonstrated with a novel coculture model that simulates the temporal and spatial relationship between the ICM and the TE in a blastocyst. Taken together, our data demonstrate that mouse ESCs can respond to type I IFNs and gain IFN-based antiviral protection from TSCs and TSC-TBs via paracrine signaling mechanisms even though they themselves are unable to express type I IFNs.

Dicer and PKR as Novel Regulators of Embryonic Stem Cell Fate and Antiviral Innate Immunity.

Embryonic stem cells (ESCs) represent a unique cell population in the blastocyst stage embryo. They have been intensively studied as a promising cell source for regenerative medicine. Recent studies have revealed that both human and mouse ESCs are deficient in expressing IFNs and have attenuated inflammatory responses. Apparently, the ability to express IFNs and respond to certain inflammatory cytokines is not "innate" to ESCs but rather is developmentally acquired by somatic cells during differentiation. Accumulating evidence supports a hypothesis that the attenuated innate immune response may serve as a protective mechanism allowing ESCs to avoid immunological cytotoxicity. This review describes our current understanding of the molecular basis that shapes the immune properties of ESCs. We highlight the recent findings on Dicer and dsRNA-activated protein kinase R as novel regulators of ESC fate and antiviral immunity and discuss how ESCs use alternative mechanisms to accommodate their stem cell properties.

High glucose induces apoptosis, glycogen accumulation and suppresses protein synthesis in muscle cells of olive flounder Paralichthys olivaceus.

The effect and the mechanism of high glucose on fish muscle cells are not fully understood. In the present study, muscle cells of olive flounder (Paralichthys olivaceus) were treated with high glucose (33 mM) in vitro. Cells were incubated in three kinds of medium containing 5 mM glucose, 5 mM glucose and 28 mM mannitol (as an isotonic contrast) or 33 mM glucose named the Control group, the Mannitol group and the high glucose (HG) group, respectively. Results showed that high glucose increased the ADP:ATP ratio and the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (MMP), induced the release of cytochrome C (CytC) and cell apoptosis. High glucose also led to cell glycogen accumulation by increasing the glucose uptake ability and affecting the mRNA expressions of glycogen synthase and glycogen phosphorylase. Meanwhile, it activated AMP-activated protein kinase (AMPK), inhibited the activity of mammalian target of rapamycin (mTOR) signalling pathway and the expressions of myogenic regulatory factors (MRF). The expressions of myostatin-1 (mstn-1) and E3 ubiquitin ligases including muscle RING-finger protein 1 (murf-1) and muscle atrophy F-box protein (mafbx) were also increased by the high glucose treatment. No difference was found between the Mannitol group and the Control group. These results demonstrate that high glucose has the effects of inducing apoptosis, increasing glycogen accumulation and inhibiting protein synthesis on muscle cells of olive flounder. The mitochondria-mediated apoptotic signalling pathway, AMPK and mTOR pathways participated in these biological effects.