High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis.

BACKGROUND: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. METHODS: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform. FINDINGS: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. INTERPRETATION: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. FUNDING: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

Effect of Exogenous and Endogenous Ectoine on Monascus Development, Metabolism, and Pigment Stability.

Monascus, a key player in fermented food production, is known for generating Monascus pigments (MPs) and monacolin K (MK), possessing bioactive properties. However, the limited stability of MPs and mycotoxin citrinin (CTN) constrain the Monascus industry. Extremolytes like ectoine, derived from bacteria, exhibit cytoprotective potential. Here, we investigated the impact of ectoine on Monascus purpureus ATCC 16365, emphasizing development and secondary metabolism. Exogenous 5 mM ectoine supplementation substantially increased the yields of MPs and MK (105%-150%) and reduced CTN production. Ectoine influenced mycelial growth, spore development, and gene expression in Monascus. Remarkably, ectoine biosynthesis was achieved in Monascus, showing comparable effects to exogenous addition. Notably, endogenous ectoine effectively enhanced the stability of MPs under diverse stress conditions. Our findings propose an innovative strategy for augmenting the production and stability of bioactive compounds while reducing CTN levels, advancing the Monascus industry.

The Effect and Mechanism of POSTN and Its Alternative Splicing on the Apoptosis of Myocardial Cells in Acute Myocardial Infarction: A Study in Vitro.

Our study aimed to investigate key molecular targets in the pathogenesis of AMI, and provide new strategy for the treatment. In this work, the myocardial ischemia and hypoxia model was constructed by using HL-1 mouse cardiomyocytes. The over-expressing POSTN wild-type, mutant and negative control lentiviruses (GV492-POSTNWT,GV492-POSTN-MUT, GV492-NC) was conducted and transfected. Cardiomyocytes were examined for cell proliferation and apoptosis to explore the effects of POSTN and its alternative splicing. The endoplasmic reticulum stess-related apoptosis proteins were selected and detected. We found that POSTN could promote the proliferation of normal and hypoxic cardiomyocytes and inhibit their apoptosis. The mechanism by which POSTN inhibited cardiomyocyte apoptosis may be through inhibiting the GRP78-eIF2α-ATF4-CHOP pathway of endoplasmic reticulum stress. Alternative splicing of POSTN could inhibit the apoptosis of ischemic and hypoxic cardiomyocytes, and its mechanism needs to be confirmed by further studies. We drawed the conclusion that POSTN might be a potential therapeutic target for AMI.

Histone Acetyltransferase Rtt109 Regulates Development, Morphogenesis, and Citrinin Biosynthesis in Monascus purpureus.

Histone acetyltransferase (HAT) has been reported to be pivotal for various physiological processes in many fungi. However, the functions that HAT Rtt109 perform in edible fungi Monascus and the underlying mechanism remains unclear. Here, we identified the rtt109 gene in Monascus, constructed the rtt109 knockout strain (Δrtt109) and its complementary strain (Δrtt109:com) by CRISPR/Cas9 methods, and functionally characterized the roles that Rtt109 play in Monascus. Deletion of rtt109 significantly reduced conidia formation and colony growth, whereas, it increased the yield of Monascus pigments (MPs) and citrinin (CTN). Further real-time quantitative PCR (RT-qPCR) analysis indicated that Rtt109 remarkably affected the transcriptional expression of key genes related to development, morphogenesis, and secondary metabolism of Monascus. Together, our results revealed the critical roles of HAT Rtt109 in Monascus, and enriched our current knowledge of the development and regulation of secondary metabolism in fungi, throwing light on restraining or eliminating citrinin in the development and industrial applications of Monascus.

Syringic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota.

Inflammatory bowel disease is known to be associated with alterations in gut microbiota. The bioactive compound syringic acid has been shown to alleviate inflammatory bowel disease, but its interaction with gut microbiota and mechanism of action remain unclear. To address this, we conducted a study in which we investigated the potential benefits of syringic acid in a mouse model of dextran sulfate sodium-induced colitis through gut microbiota modulation. Our results show that oral administration of syringic acid effectively reduced symptoms of colitis, as indicated by reduced disease activity index, and histopathology scores. Moreover, syringic acid administration enriched the abundance of Alistipes and norank_f__norank_o__Gastranaerophilales in mice, suggesting a restoration of impaired gut microbiota. Notably, we found that the effects of syringic acid were similar to those of fecal microbiota transplantation in dextran sulfate sodium-induced mice. Further analysis revealed that syringic acid inhibited the NLRP3-Cas-1-GSDMD-IL-1ß inflammatory vesicle signaling pathway, leading to amelioration of colonic inflammation in a gut microbiota-dependent manner. Our findings demonstrate the potential of syringic acid as a preventive and therapeutic agent for inflammatory bowel disease.

A Novel Microbial Consortia Catalysis Strategy for the Production of Hydroxytyrosol from Tyrosine.

Hydroxytyrosol, a valuable plant-derived phenolic compound, is increasingly produced from microbial fermentation. However, the promiscuity of the key enzyme HpaBC, the two-component flavin-dependent monooxygenase from Escherichia coli, often leads to low yields. To address this limitation, we developed a novel strategy utilizing microbial consortia catalysis for hydroxytyrosol production. We designed a biosynthetic pathway using tyrosine as the substrate and selected enzymes and overexpressing glutamate dehydrogenase GdhA to realize the cofactor cycling by coupling reactions catalyzed by the transaminase and the reductase. Additionally, the biosynthetic pathway was divided into two parts and performed by separate E. coli strains. Furthermore, we optimized the inoculation time, strain ratio, and pH to maximize the hydroxytyrosol yield. Glycerol and ascorbic acid were added to the co-culture, resulting in a 92% increase in hydroxytyrosol yield. Using this approach, the production of 9.2 mM hydroxytyrosol was achieved from 10 mM tyrosine. This study presents a practical approach for the microbial production of hydroxytyrosol that can be promoted to produce other value-added compounds.

Preconceptional exposure of adult male rats to bisphenol S impairs insulin sensitivity and glucose tolerance in their male offspring.

Since the use of bisphenol A (BPA) has been restricted because of its endocrine disruptor properties, bisphenol S (BPS) has been widely used as a substitute of BPA. However, BPS exerts similar effects on metabolic health as BPA. The effects of maternal exposure to BPA and BPS on the metabolic health of offspring have been largely documented during the past decade. However, the impact of preconceptional paternal exposure to BPS on progenies remains unexplored. In this study we investigated the impact of paternal exposure to BPS before conception, on the metabolic phenotype of offspring. Male Wistar rats were administered BPS through drinking water at the dose of 4 µg/kg/day (BPS-4 sires) or 40 µg/kg/day (BPS-40 sires) for 2 months before mating with females. The progenies (F1) were studied at fetal stage and in adulthood. We showed that preconceptional paternal exposure to BPS for 2 months did not alter the metabolic status of sires. The female offspring of sires exposed to lower or higher doses of BPS showed no alteration of their metabolic phenotype compared to females from control sires. In contrast, male offspring of BPS-4 sires exhibited increased body weight and body fat/lean ratio, decreased insulin sensitivity and increased glucose-induced insulin secretion at adult age, compared to the male offspring of control sires. Moreover, male offspring of BPS-4 sires developed glucose intolerance later in life. None of these effects were apparent in male offspring of BPS-40 sires. In conclusion, our study provides the first evidence of the non-monotonic and sex-specific effects of preconceptional paternal exposure to BPS on the metabolic health of offspring, suggesting that BPS is not a safe BPA substitute regarding the inter-generational transmission of metabolic disorders through the paternal lineage.

Linoleic acid functions as a quorum-sensing molecule in Monascus purpureus-Saccharomyces cerevisiae co-culture.

When Monascus purpureus was co-cultured with Saccharomyces cerevisiae, we noted significant changes in the secondary metabolism and morphological development of Monascus. In yeast co-culture, although the pH was not different from that of a control, the Monascus mycelial biomass increased during fermentation, and the Monacolin K yield was significantly enhanced (up to 58.87% higher). However, pigment production did not increase. Co-culture with S. cerevisiae significantly increased the expression levels of genes related to Monacolin K production (mokA-mokI), especially mokE, mokF, and mokG. Linoleic acid, that has been implicated in playing a regulating role in the secondary metabolism and morphology of Monascus, was hypothesized to be the effector. Linoleic acid was detected in the co-culture, and its levels changed during fermentation. Addition of linoleic acid increased Monacolin K production and caused similar morphological changes in Monascus spores and mycelia. Exogenous linoleic acid also significantly upregulated the transcription levels of all nine genes involved in the biosynthesis of Monacolin K (up to 69.50% higher), consistent with the enhanced Monacolin K yield. Taken together, our results showed the effect of S. cerevisiae co-culture on M. purpureus and suggested linoleic acid as a specific quorum-sensing molecule in Saccharomyces-Monascus co-culture.

Candidate genes and their alternative splicing may be potential biomarkers of acute myocardial infarction: a study of mouse model.

BACKGROUND: Acute myocardial infarction (AMI) is one of the leading causes of death in human being, and an effective diagnostic biomarker is still lacking. Whilst some gene association with AMI has been identified by RNA sequencing (RNA-seq), the relationship between alternative splicing and AMI is not clear. METHODS: We retrieved myocardial tissues within 24 h from mice with induced AMI and sham, and analysed the differentially expressed genes (DEGs) and differential alternative splicing genes (DASGs) by RNA-seq. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein interaction network analysis were performed on DEGs-DASGs-overlap genes. PCR was used to verify the expression levels of representative genes and alternative splicing in myocardial tissues of AMI and sham mice. RESULTS: 1367 DEGs were identified, including 242 up-regulated and 1125 down-regulated genes, among which there were 42 DASGs. GO analysis showed that the cellular component was primarily enriched in plasma membrane, cell membrane integrity and extracellular region. The molecular function was enriched in protein binding and metal ion binding. The biological process was primarily enriched in cell adhesion, immune system process and cell differentiation. KEGG analysis showed the enrichment was mainly in JAK-STAT and PI3K-AKT signalling pathway. Postn, Fhl1, and Fn1 were low-expressed while Postn alternative splicing was high-expressed in myocardial tissue of AMI mice, which was consistent with sequencing results. CONCLUSIONS: The pathogenesis of AMI involves differentially expressed genes and differential alternative splicing. These differentially expressed genes and their alternative splicing, especially, Fhl1, Fn1 and Postn may become new biomarkers of AMI.

The effect of copper grain size on laser ultrasonic backscattered signal.

Grain size has an essential influence on the serviceability of metallic materials. In this paper, a noncontact laser ultrasonic testing platform is built to study the effect of copper grain size on the laser ultrasonic backscattered signal. According to the correlation between grain size and ultrasonic wavelength, the ultrasonic scattering by copper grains in the experiment contains not only Rayleigh scattering but also the transition region from Rayleigh scattering to stochastic scattering. Using time-frequency analysis, the influence of copper grain size on the characteristic parameters of backscattering was explored, and a prediction model of grain size was established, which was compared with the prediction model based on the attenuation method to verify the accuracy of the backscattering model. The results show that the backscattered signal can adequately characterize the grain size information and laser ultrasonics is a method that can realize on-line detection of grain size.

[Long-term intermittent fasting induces abnormal lipid accumulation in mouse liver].

Short-term intermittent fasting (IF) is beneficial to weight control in patients with nonalcoholic fatty liver disease, but the impact of long-term IF is not clear. In this study, healthy C57BL/6N mice with 4-month alternate day fasting (ADF) were used to study the effects of long-term IF on systemic and liver lipid metabolism. The results showed that, compared with the Ad Libitum group, the weight and food conversion rate of mice in the ADF group were markedly decreased and increased respectively, and the liver index and the liver content of triglyceride were significantly increased by pathological examination. qRT-PCR analysis revealed that the mRNA expression of the lipogenesis gene Pparγ and lipolysis gene Atgl was up-regulated in the ADF group (P < 0.05). Western blot analysis showed that the ratio of microtubule associated protein LC3-II/LC3-I was increased, while the abundance of autophagy adaptor protein p62 was decreased in the ADF group. In addition, autophagy signal positive regulation key factor AMPK phosphorylation was increased (P < 0.05), and negative regulation factor mTOR phosphorylation was decreased (P < 0.05) in the ADF group, indicating that hepatocyte autophagy activity was elevated. Taken together, ADF for 4 months results in an excessive liver triglyceride accumulation, accompanied by a marked decrease in liver mTOR phosphorylation and a significant increase in hepatic autophagy.

Photoinduced atom transfer radical polymerization combined with click chemistry for highly sensitive detection of tobacco mosaic virus RNA.

An electrochemical biosensor for highly sensitive detection of tobacco mosaic virus (TMV) RNA (tRNA) based on click chemistry and photoinduced atom transfer radical polymerization (photoATRP) is developed for the first time. Herein, tRNA is recognized and captured by hairpin DNA immobilized on the gold electrode surface by Au-S self-assembly. Propyl 2-bromoisobutyrate (PBIB), a photoATRP initiator containing an alkyne group, is conjugated to the azide group of hairpin DNA via a Cu(I)-catalyzed azidoalkyl cyclization reaction (CuAAC). Under the irradiation of 470 nm blue light, photoATRP is activated by the photoredox catalyst (eosin Y, EY), resulting in the formation of a large number of electroactive probes (ferrocenylmethyl methacrylate, FMMA), which significantly amplifies the signal. Under the optimal experimental parameters, the strategy has a wide linear detection (0.1 pM-10 nM) (R2 = 0.995) with a limit of detection (LOD) as low as 3.5 fM. In addition, the biosensor also exhibited good selectivity for mismatched bases, excellent stability and reproducibility. Moreover, satisfactory result was achieved when the biosensor was applied to the detection of tRNA from healthy rehmannia total RNA extracts, which demonstrates the great potential of the method in the practical detection of TMV.

Paternal High-Protein Diet Programs Offspring Insulin Sensitivity in a Sex-Specific Manner.

The impact of maternal nutrition on offspring is well documented. However, the implication of pre-conceptional paternal nutrition on the metabolic health of the progeny remains underexplored. Here, we investigated the impact of paternal high-protein diet (HPD, 43.2% protein) consumption on the endocrine pancreas and the metabolic phenotype of offspring. Male Wistar rats were given HPD or standard diet (SD, 18.9% protein) for two months. The progenies (F1) were studied at fetal stage and in adulthood. Body weight, glycemia, glucose tolerance (GT), glucose-induced insulin secretion in vivo (GIIS) and whole-body insulin sensitivity were assessed in male and female F1 offspring. Insulin sensitivity, GT and GIIS were similar between F1 females from HPD (HPD/F1) and SD fathers (SD/F1). Conversely, male HPD/F1 exhibited increased insulin sensitivity (p < 0.05) and decreased GIIS (p < 0.05) compared to male SD/F1. The improvement of insulin sensitivity in HPD/F1 was sustained even after 2 months of high-fat feeding. In male HPD/F1, the ß cell mass was preserved and the ß cell plasticity, following metabolic challenge, was enhanced compared to SD/F1. In conclusion, we provide the first evidence of a sex-specific impact of paternal HPD on the insulin sensitivity and GIIS of their descendants, demonstrating that changes in paternal nutrition alter the metabolic status of their progeny in adulthood.

Screening of Reference Genes for RT-qPCR in Chicken Adipose Tissue and Adipocytes.

Reverse transcription quantitative real-time PCR is the most commonly used method to detect gene expression levels. In experiments, it is often necessary to correct and standardize the expression level of target genes with reference genes. Therefore, it is very important to select stable reference genes to obtain accurate quantitative results. Although application examples of reference genes in mammals have been reported, no studies have investigated the use of reference genes in studying the growth and development of adipose tissue and the proliferation and differentiation of preadipocytes in chickens. In this study, GeNorm, a reference gene stability statistical algorithm, was used to analyze the expression stability of 14 candidate reference genes in the abdominal adipose tissue of broilers at 1, 4, and 7 weeks of age, the proliferation and differentiation of primary preadipocytes, as well as directly isolated preadipocytes and mature adipocytes. The results showed that the expression of the TATA box binding protein (TBP) and hydroxymethylbilane synthase (HMBS) genes was most stable during the growth and development of abdominal adipose tissue of broilers, the expression of the peptidylprolyl isomerase A (PPIA) and HMBS genes was most stable during the proliferation of primary preadipocytes, the expression of the TBP and RPL13 genes was most stable during the differentiation of primary preadipocytes, and the expression of the TBP and HMBS genes was most stable in directly isolated preadipocytes and mature adipocytes. These results provide reference bases for accurately detecting the mRNA expression of functional genes in adipose tissue and adipocytes of chickens.

Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines.

Genetic selection for meat production performance of broilers concomitantly causes excessive abdominal fat deposition, accompanied by several adverse effects, such as the reduction of feed conversion efficiency and reproduction performance. Our previous studies have identified important genes regulating chicken fat deposition, using the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) as an animal model. However, the molecular mechanism underlying fat deposition differences between fat and lean broilers remains largely unknown. Here, we integrated the transcriptome (RNA-Seq) and quantitative proteome (isobaric tags for relative and absolute quantitation, iTRAQ) profiling analyses on abdominal fat tissues from NEAUHLF chicken lines. Differentially expressed genes (2167 DEGs, corrected p-value < 0.01) and differentially abundant proteins (199 DAPs, corrected p-value < 0.05) were identified in lean line compared to fat line. Down-regulated DEGs and DAPs mainly enriched in pathways related to fatty acid metabolism, fatty acid biosynthesis, and PPAR signaling, and interestingly, up-regulated DEGs and DAPs enriched both in lysosome pathway. Moreover, numerous key DEGs and DAPs involved in long-chain fatty acid uptake, in situ lipogenesis (fatty acid and cholesterol synthesis), and lipid droplet accumulation were discovered after integrated transcriptome and proteome analysis. SIGNIFICANCE: Excessive abdominal fat deposition critically affects the health of broilers and causes economic loss to broiler producers, but the molecular mechanism of abdominal fat deposition is still unclear in chicken. We identified key DEGs/DAPs and potential pathways through an integration of chicken abdominal fat tissues transcriptome and proteome analyses. Our findings will facilitate a better revealing the mechanism and provide a novel insight into abdominal fat content discrepancy between the fat and lean chicken lines.

Effect of Postnatal Nutritional Environment Due to Maternal Diabetes on Beta Cell Mass Programming and Glucose Intolerance Risk in Male and Female Offspring.

Besides the fetal period, the suckling period is a critical time window in determining long-term metabolic health. We undertook the present study to elucidate the impact of a diabetic suckling environment alone or associated with an in utero diabetic environment on beta cell mass development and the risk of diabetes in the offspring in the long term. To that end, we have compared two experimental settings. In setting 1, we used Wistar (W) rat newborns resulting from W ovocytes (oW) transferred into diabetic GK rat mothers (pGK). These oW/pGK neonates were then suckled by diabetic GK foster mothers (oW/pGK/sGK model) and compared to oW/pW neonates suckled by normal W foster mothers (oW/pW/sW model). In setting 2, normal W rat newborns were suckled by diabetic GK rat foster mothers (nW/sGK model) or normal W foster mothers (nW/sW model). Our data revealed that the extent of metabolic disorders in term of glucose intolerance and beta cell mass are similar between rats which have been exposed to maternal diabetes both pre- and postnatally (oW/pGK/sGK model) and those which have been exposed only during postnatal life (nW/sW model). In other words, being nurtured by diabetic GK mothers from birth to weaning was sufficient to significantly alter the beta cell mass, glucose-induced insulin secretion and glucose homeostasis of offspring. No synergistic deleterious effects of pre-and postnatal exposure was observed in our setting.

Whole-genome bisulfite sequencing of abdominal adipose reveals DNA methylation pattern variations in broiler lines divergently selected for fatness.

The methylation status of pivotal genes involved in fat deposition in chickens has been extensively studied. However, the whole-genome DNA methylation profiles of broiler abdominal adipose tissue remain poorly understood. Using whole-genome bisulfite sequencing, we generated DNA methylation profiles of chicken abdominal adipose tissue from Northeast Agricultural University broiler lines divergently selected for abdominal fat content. We aimed to explore whether DNA methylation was associated with abdominal fat deposition in broilers. The whole-genome DNA methylation profiles of fat- and lean-line broilers abdominal adipose tissue were constructed. The DNA methylation levels of functional genomic regions in the fat broiler were higher than those in the lean broiler, especially in the 3' untranslated regions (UTRs) and exons in the non-CG contexts. Additionally, we identified 29,631 differentially methylated regions and, subsequently, annotated 6,484 and 2,016 differentially methylated genes (DMGs) in the gene body and promoter regions between the two lines, respectively. Functional annotation showed that the DMGs in promoter regions were significantly enriched mainly in the triglyceride catabolic process, lipid metabolism-related pathways, and extracellular matrix signal pathways. When the DMG in promoter regions and differentially expressed genes were integrated, we identified 30 genes with DNA methylation levels that negatively correlated with their messenger RNA (mRNA) expression, of which CMSS1 reached significant levels (false discovery rate < 0.05). These 30 genes were mainly involved in fatty acid metabolism, peroxisome-proliferator-activated receptor signaling, Wnt signaling pathways, transmembrane transport, RNA degradation, and glycosaminoglycan degradation. Comparing the DNA methylation profiles between fat- and lean-line broilers demonstrated that DNA methylation is involved in regulating broiler abdominal fat deposition. Our study offers a basis for further exploring the underlying mechanisms of abdominal adipose deposition in broilers.

Effect of Different Clarification Treatments on the Volatile Composition and Aromatic Attributes of 'Italian Riesling' Icewine.

The aim of this study was to evaluate the influence of clarification treatments on volatile composition and aromatic attributes of wine samples. 'Italian Riesling' icewines from the Hexi Corridor Region of China were clarified by fining agents (bentonite (BT) and soybean protein (SP)), membrane filtration (MF), and centrifugation (CF) methods. The clarity, physicochemical indexes, volatile components, and aromatic attributes of treated wines were investigated. Both the fining agents and mechanical clarification treatments increased the transmittance and decreased the color intensity of icewine samples. Bentonite fining significantly influenced the total sugar content, total acidity and volatile acidity. Total acidity decreased 2-3.5% and volatile acidity 2-12%. MF showed the greatest influence on total phenol content, decreasing the initial content by 12%, while other treatments by less than 8%. Volatile analysis indicated that both the categories and contents of volatile compounds of wine samples decreased. MF treatment showed the most significant influence, while SP fining showed much lower impact. Odor activity values indicated the compound with the highest odor activity in Italian Riesling icewines was ß-damascenone. For this compound, BT and SP did not show significant differences, however, in MF and CF it decreased by 20% and 63%, respectively. Furthermore, with high impact on aroma were: ethyl hexanoate which reduced by 20-80% especially in MF; rose oxide which extremely reduced in MF and undetected in BT, SP, and CF; isoamyl acetate which reduced by 3-33% and linalool decreased by 10-20% and undetected for BT. Principle component analysis indicated that icewine clarified by different methods could be distinguished and positively correlated with odor-active compounds. Floral and fruity were the dominant aroma series in icewine samples followed by fatty, earthy, spicy, vegetative and pungent flavor. The total odor active value of these series significantly (p < 0.5) decreased in different clarification treatments. Sensory evaluation showed similar results, but the SP and CF wine samples achieved better sensory quality. This study provides information that could help to optimize the clarification of ice wines.

The role of fibroblast activation protein in progression and development of osteosarcoma cells.

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.