Establishment of Cephalic Index by Computed Tomography in Sampled Chinese Children.

OBJECTIVE: Cephalic Index (CI), the ratio of head width to length, is one of the indexes reflecting cranial morphological characteristics. Current norms were established by European and American countries. The purpose of the study was to study anthropometry of cranial parameters using computed tomography scans to establish the CI of the sampled Chinese Children. METHODS: The cross-sectional study was carried out on patients of age younger than 14 years old at Shanghai Children's Medical Center. The measurement of maximum cranial breadth and maximum cranial length were taken on a computed tomography scan machine and recorded for analysis. Cephalic Index was calculated for each age and sex group and compared with previously established norms. RESULTS: Five hundred eighteen patients met the inclusion criteria, including 301 males and 217 females. The means for boys and girls were 87.1 (SD: 4.3) and 85.8 (SD: 4.3), respectively. There was a significant difference between boys and girls (P < 0.01). Cephalic Index in different ages and on applying the 1-way analysis of variance association was statistically insignificant (P = 0.19). CONCLUSIONS: Chinese head shape was brachycephalic. A statistically significant correlation was seen between the CI and sex, while not age.

Insight into the regulatory mechanism of ß-arrestin2 and its emerging role in diseases.

ß-arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein-coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that ß-arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post-transcriptional modifications can affect the expression of ß-arrestin2. Furthermore, post-translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S-nitrosylation affect the cellular localization of ß-arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of ß-arrestin2. This review summarizes the structure and function of ß-arrestin2 and reveals the mechanisms involved in the regulation of ß-arrestin2 at multiple levels. Additionally, recent studies on the role of ß-arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting ß-arrestin2.

Multifaceted roles and functions of SOX30 in human cancer.

SRY-box transcription factor 30 (SOX30) participates in tumor cell apoptosis in lung cancer. The occurrence of somatic SOX30 mutations, the expression signature of SOX30 in normal and cancer tissues, the correlation of SOX30 with immune cells and immune-related genes, and the clinical significance of SOX30 in various cancers have stimulated interest in SOX30 as a potential cancer biomarker. SOX30 influences drug sensitivity and tumor immunity in specific cancer types. In this review, we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature review. We summarize recent research on SOX30 in cancer regarding somatic mutations, trials, transcriptome analysis, clinical information, and SOX30-mediated regulation of malignant phenotypes. Additionally, we report on the diagnostic value of SOX30 mRNA expression levels across different cancer types. This review on the role of SOX30 in cancer progression may provide insights into possible research directions for SOX30 in cancer and a theoretical basis for guiding future studies.

Chemical compositions and nutritional profiles of two edible tunicate species (Halocynthia roretzi and Halocynthia aurantium).

As an abundant marine bioresource, tunicates could be exploited in the food industry. However, limited knowledge of their chemical composition and nutritional profiles prohibited further application. In this study, two common edible tunicate species, Halocynthia roretzi (HR) and Halocynthia aurantium (HA), were subjected to comprehensive composition analysis in terms of moisture, protein, lipids, cellulose, ash, amino acids, fatty acids, non-cellulose carbohydrates and minerals. Reddish HR was much bigger than purple HA with respect to body length and weight, and their moisture fell within 82.98 %-90.92 %. The non-edible outer shell part (OS) and edible internal organs part (IO) had a dry weight ratio of around 3:2 for both two species. Generally, for both HR and HA, IO was more abundant in protein and lipids. In contrast, OS had much higher cellulose contents, confirming the better suitability of IO as a nutritional seafood. IO was richer in essential amino acids and unsaturated fatty acids, while OS had more abundant saturated fatty acids. The detected non-cellulose monosugars ranged from 0.47 % to 1.18 % and indicated the presence of some sulfated glycans. IO of HR had higher contents of essential minerals, such as Cu, Zn, and Fe, while IO of HA showed a higher K content. To sum up, this study identified the chemical composition and nutritional profile variations among different tunicate species and various dissected parts, guiding the development of specific strategies to exploit tunicates for proper food applications.

Integrating network pharmacology and experimental validation reveals therapeutic effects of D-mannose on NAFLD through mTOR suppression.

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.

Construction of a ferroptosis-based prognostic model for breast cancer helps to discriminate high/low risk groups and treatment priority.

Introduction: Breast cancer is a common malignant tumor associated with high morbidity and mortality. The role of ferroptosis, a regulated form of cell death, in breast cancer development and prognosis remains unclear. This study aims to investigate the relationship between ferroptosis-related genes and breast cancer and develop a prognostic model. Methods: RNA-seq expression datasets and clinical samples of breast cancer patients were obtained from public databases. Immunity- and drug resistance-related data were integrated. A preliminary screening was performed, resulting in the identification of 73 candidate ferroptosis factors. Univariate Cox regression analysis was conducted to select 12 genes, followed by LASSO Cox regression analysis to construct a prognostic risk prediction model consisting of 10 ferroptosis-related genes. The model was further characterized by immune cell infiltration. The expression levels of ferroptosis-related genes were validated in human breast cancer cell lines, and immunohistochemical (IHC) analysis was conducted on cancer specimens to assess ferroptosis-related protein expression. Results: The study identified 10 ferroptosis-related genes that were significantly associated with breast cancer prognosis. The constructed prognostic risk prediction model showed potential for predicting the prognostic value of these genes. In addition, the infiltration of immune cells was observed to be a characteristic of the model. The expression levels of ferroptosis-related genes were confirmed in human breast cancer cell lines, and IHC analysis provided evidence of ferroptosis-related protein expression in cancer specimens. Discussion: This study provides a novel prognostic model for breast cancer, incorporating 10 ferroptosis-related genes. The model demonstrates the potential for predicting breast cancer prognosis and highlights the involvement of immune cell infiltration. The expression levels of ferroptosis-related genes and proteins further support the association between ferroptosis and breast cancer development.

Tunicates as Sources of High-Quality Nutrients and Bioactive Compounds for Food/Feed and Pharmaceutical Applications: A Review.

Tunicates are widely distributed worldwide and are recognized as abundant marine bioresources with many potential applications. In this review, state-of-the-art studies on chemical composition analyses of various tunicate species were summarized; these studies confirmed that tunicates contain nutrients similar to fish (such as abundant cellulose, protein, and ω-3 fatty acid (FA)-rich lipids), indicating their practical and feasible uses for food or animal feed exploration. However, the presence of certain toxic elements should be evaluated in terms of safety. Moreover, recent studies on bioactive substances extracted from tunicates (such as toxins, sphingomyelins, and tunichromes) were analyzed, and their biological properties were comprehensively reviewed, including antimicrobial, anticancer, antioxidant, antidiabetic, and anti-inflammatory activities. In addition, some insights and prospects for the future exploration of tunicates are provided which are expected to guide their further application in the food, animal feed, and pharmaceutical industries. This review is critical to providing a new pathway for converting the common pollution issues of hydroponic nutrients into valuable marine bioresources.

Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis.

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

The beneficial potential of protein hydrolysates as prebiotic for probiotics and its biological activity: a review.

Probiotics are not only a food supplement, but they have shown great potential in their nutritional, health and therapeutic effects. To maximize the beneficial effects of probiotics, it is commonly achieved by adding prebiotics. Prebiotics primarily comprise indigestible carbohydrates, specific peptides, proteins, and lipids, with oligosaccharides being the most extensively studied prebiotics. However, these rapidly fermenting oligosaccharides have many drawbacks and can cause diarrhea and flatulence in the body. Hence, the exploration of new prebiotic is of great interest. Besides oligosaccharides, protein hydrolysates have been demonstrated to enhance the expression of beneficial properties of probiotics. Consequently, this paper outlines the mechanism underlying the action of protein hydrolysates on probiotics, as well as the advantageous impacts of proteins hydrolysates derived from various food sources on probiotics. In addition, this paper also reviews the currently reported biological activities of protein hydrolysates. The aim is a theoretical basis for the development and implementation of novel prebiotics.

Porous Ni3Fe intermetallic compounds as efficient and stable catalysts for the hydrogen evolution reaction in alkaline solutions.

It is crucial to develop cost-effective novel non-noble metal catalysts with high activity and durability for large-scale industrial hydrogen production via water splitting. Here, based on a facile powder metallurgy method, Ni3Fe intermetallic electrodes with porous structures and controllable phases have been designed and fabricated by sintering mixed Ni and Fe powders under an Ar atmosphere. The effects of sintering temperature on the morphology, porous structure and phase composition of the intermetallic were studied. The resultant Ni3Fe-900 intermetallic electrode exhibits promising HER activity in alkaline electrolytes with an overpotential of 112 mV to drive a current density of 10 mA cm-2. Additionally, the Ni3Fe-900 intermetallic electrode shows good alkali corrosion resistance and stability in the HER process at a current density as high as 500 mA cm-2 for 24 h with no significant changes of the surface morphology, porous structure and phases. The efficient HER performance of the Ni3Fe-900 electrode is attributed to the unique intrinsic activity of the intermetallic electrode, increased accessible active sites originating from the porous structure and accelerated charge transfer. This work provides new insights into the design of electrocatalysts for industrial large-scale hydrogen production by water splitting.

Investigating the role of FADS family members in breast cancer based on bioinformatic analysis and experimental validation.

Breast cancer (BC) is the most common malignant tumor in women worldwide. Emerging evidence indicates the significance of fatty acid metabolism in BC. Fatty acid desaturase (FADS) is closely associated with cancer occurrence and development. Here, bioinformatic analysis and experimental validation were applied to investigate the potential functions of FADS in BC. Several public databases, including TCGA, GEO, HPA, Kaplan-Meier plotter, STRING, DAVID, cBioPortal, TIMER, TRRUST, and LinkedOmics were used to determine mRNA/protein expression levels, prognostic significance, functional enrichment, genetic alterations, association with tumor-infiltrating immune cells, and related transcription factors and kinases. BC tissues showed higher and lower mRNA expression of FADS2/6/8 and FADS3/4/5, respectively. FADS1/2/6 and FADS3/4/5 showed higher and lower protein expression levels, respectively, in BC tissues. Moreover, FADS1/7 up- and FADS3/8 down-regulation predicted poor overall and recurrence-free survival, while FADS2/5 up- and FADS4 down-regulation were associated with poor recurrence-free survival. Receiver operating characteristic curves revealed that FADS2/3/4/8 were indicative diagnostic markers. FADS family members showing differential expression levels were associated with various clinical subtypes, clinical stages, lymph node metastasis status, copy number variants, DNA methylation, and miRNA regulation in BC. The mRNA expression level of FADS1/2/3/4/5/7/8 was observed to be significantly negatively correlated with DNA methylation. FADS1/2 upregulation was significantly correlated with clinical stages. FADS1/4 expression was obviously lower in BC patients with higher lymph node metastasis than lower lymph node metastasis, while FADS7/8 expression was obviously higher in BC patients with higher lymph node metastasis than lower lymph node metastasis. FADS family members showed varying degrees of genetic alterations, and Gene Ontology and KEGG pathway enrichment analyses suggested their involvement in lipid metabolism. Their expression level was correlated with immune cell infiltration levels. FADS2 was chosen for further validation analyses. We found FADS2 to be significantly over-expressed in clinical BC tissue samples. The proliferation, migration, and invasion abilities of MDA-MB-231 and BT474 cells were significantly reduced after FADS2 knockdown. Furthermore, FADS2 may promote the occurrence and development of BC cells via regulating the epithelial-mesenchymal transition (EMT) pathway. Altogether, our results suggest that FADS1/2/3/4 can serve as potential therapeutic targets, prognostic indicators, and diagnostic markers in patients with BC.

Whole-genome resequencing reveals genetic differences and the genetic basis of parapodium number in Russian and Chinese Apostichopus japonicus.

BACKGROUND: Apostichopus japonicus is an economically important species in the global aquaculture industry. Russian A. japonicus, mainly harvested in the Vladivostok region, exhibits significant phenotypic differentiation, including in many economically important traits, compared with Chinese A. japonicus owing to differences in their habitat. However, both the genetic basis for the phenotypic divergence and the population genetic structure of Russian and Chinese A. japonicus are unknown. RESULT: In this study, 210 individuals from seven Russian and Chinese A. japonicus populations were sampled for whole-genome resequencing. The genetic structure analysis differentiated the Russian and Chinese A. japonicus into two groups. Population genetic analyses indicated that the Russian population showed a high degree of allelic linkage and had undergone stronger positive selection compared with the Chinese populations. Gene ontology terms enriched among candidate genes with group selection analysis were mainly involved in immunity, such as inflammatory response, antimicrobial peptides, humoral immunity, and apoptosis. Genome-wide association analysis yielded eight single-nucleotide polymorphism loci significantly associated with parapodium number, and these loci are located in regions with a high degree of genomic differentiation between the Chinese and Russia populations. These SNPs were associated with five genes. Gene expression validation revealed that three of these genes were significantly differentially expressed in individuals differing in parapodium number. AJAP08772 and AJAP08773 may directly affect parapodium production by promoting endothelial cell proliferation and metabolism, whereas AJAP07248 indirectly affects parapodium production by participating in immune responses. CONCLUSIONS: This study, we performed population genetic structure and GWAS analysis on Chinese and Russian A. japonicus, and found three candidate genes related to the number of parapodium. The results provide an in-depth understanding of the differences in the genetic structure of A. japonicus populations in China and Russia, and provide important information for subsequent genetic analysis and breeding of this species.

Collagens for surimi gel fortification: Type-dependent effects and the difference between type I and type II.

Surimi products have unsatisfactory gel properties. Hence, this study evaluates the effect of collagen-adding on surimi gel properties and provides the first observation results regarding collagen type influence. With higher water solubility and more charged amino acids than type II, collagen type I intertwines with surimi myofibrillar proteins better to induce higher exposure of protein functional domains, more sufficient conformational changes of myosin and greater formation of chemical forces among proteins. These enhancements accelerate the gelation rate, leading to a well-stabilized surimi gel. The collagen I-containing surimi gels show more compact structures with uniformly distributed smaller pores than those containing collagen II, thereby providing the final products with higher water holding capacity and better textural profiles. As such, the surimi gel fortification performance of collagen I and the well-elucidated collagen-myofibrillar protein interaction mechanism will guide the further exploitation of collagen as an effective additive in the food industry.

Emerging Food Packaging Applications of Cellulose Nanocomposites: A Review.

Cellulose is the most abundant biopolymer on Earth, which is synthesized by plants, bacteria, and animals, with source-dependent properties. Cellulose containing ß-1,4-linked D-glucoses further assembles into hierarchical structures in microfibrils, which can be processed to nanocellulose with length or width in the nanoscale after a variety of pretreatments including enzymatic hydrolysis, TEMPO-oxidation, and carboxymethylation. Nanocellulose can be mainly categorized into cellulose nanocrystal (CNC) produced by acid hydrolysis, cellulose nanofibrils (CNF) prepared by refining, homogenization, microfluidization, sonification, ball milling, and the aqueous counter collision (ACC) method, and bacterial cellulose (BC) biosynthesized by the Acetobacter species. Due to nontoxicity, good biodegradability and biocompatibility, high aspect ratio, low thermal expansion coefficient, excellent mechanical strength, and unique optical properties, nanocellulose is utilized to develop various cellulose nanocomposites through solution casting, Layer-by-Layer (LBL) assembly, extrusion, coating, gel-forming, spray drying, electrostatic spinning, adsorption, nanoemulsion, and other techniques, and has been widely used as food packaging material with excellent barrier and mechanical properties, antibacterial activity, and stimuli-responsive performance to improve the food quality and shelf life. Under the driving force of the increasing green food packaging market, nanocellulose production has gradually developed from lab-scale to pilot- or even industrial-scale, mainly in Europe, Africa, and Asia, though developing cost-effective preparation techniques and precisely tuning the physicochemical properties are key to the commercialization. We expect this review to summarise the recent literature in the nanocellulose-based food packaging field and provide the readers with the state-of-the-art of this research area.

A novel pyroptosis-related indicator of immune infiltration features and prognosis in breast cancer.

Breast cancer is the most common malignancy in women, and there is evidence for the dual role of cell pyroptosis in tumor development. However, little is known about the relationship between cell pyroptosis and breast cancer and its prognostic value. We aimed to construct a prognostic model using cell-pyroptosis-related genes to provide innovative insights into the prognosis and treatment of breast cancer. We screened candidate genes for pyroptosis using public databases and identified 10 cell pyroptosis signature genes with the random forest method. Finally, a nomogram for predicting 1-, 3-, and 5-year survival probabilities was constructed. The differences in immune cell distributions between survival periods were similar across the breast cancer datasets. The 10 identified key pyroptosis factors showed a significant correlation with Her2, tumor-node-metastasis (TNM) stage, and survival of breast cancer. The risk scores correlated positively with the infiltration features of naive B cells, CD8+ T cells, atpdelnd mast cells, while they correlated negatively with those of M0 macrophages and dendritic cells. In conclusion, our findings confirm that cell pyroptosis is closely associated with breast cancer. Importantly, the prognostic complex values generated from the 10 cell-pyroptosis-related genes based on various clinical features may provide an important basis for future studies on the prognosis of breast cancer.

Constructing an In Situ Polymer Electrolyte and a Na-Rich Artificial SEI Layer toward Practical Solid-State Na Metal Batteries.

Sodium is one of the most promising anode candidates for the beyond-lithium-ion batteries. The development of Na metal batteries with a high energy density, high safety, and low cost is desirable to meet the requirements of both portable and stationary electrical energy storage. However, several problems caused by the unstable Na metal anode and the unsafe liquid electrolyte severely hinder their practical applications. Herein, we report a facile but effective methodology to construct an in situ polymer electrolyte and Na-rich artificial solid-electrolyte interface (SEI) layer concurrently. The obtained integrated Na metal batteries display long cycling life and admirable dynamic performance with total inhibition of dendrites, excellent contact of the cathode/polymer electrolyte, and reduction of side reactions during cycling. The modified Na metal electrode with the in situ polymer electrolyte is stable and dendrite-free in repeated plating/stripping processes with a life span of above 1000 h. Moreover, this method is compatible with different cathodes that demonstrate outstanding electrochemical performance in full cells. We believe that this approach provides a practical solution to solid-state Na metal batteries.

Identification of an Epigenetic Signature for Coronary Heart Disease in Postmenopausal Women's PBMC DNA.

Menopause is accompanied with an increased risk of cardiovascular disease. DNA methylation may have a significant impact on postmenopausal women's development of coronary heart disease. DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) from women with coronary heart disease and healthy controls were detected using the Illumina Infinium MethylationEPIC BeadChip platform in this work. We employed Sangerbox technology and the GO and KEGG databases to further study the pathogenesis of coronary heart disease in postmenopausal women. After that, we used functional epigenetic module analysis and Cytoscape to remove the hub genes from the protein-protein interaction networks. Five genes (FOXA2, PTRD, CREB1, CTNAP2, and FBN2) were the hub genes. Lipid accumulation, endothelial cell failure, inflammatory responses, monocyte recruitment and aggregation, and other critical biological processes were all influenced by these genes. Finally, we employed methylation-specific PCR to demonstrate that FOXA2 was methylated at a high level in postmenopausal women with coronary heart disease. To better understand coronary heart disease in postmenopausal women's molecular mechanisms, our study examine the major factors contributing to the state of DNA methylation modification, which will help discover novel diagnostic tools and treatment options.

Identification of Five Hub Genes Based on Single-Cell RNA Sequencing Data and Network Pharmacology in Patients With Acute Myocardial Infarction.

Acute myocardial infarction (AMI) has a high mortality. The single-cell RNA sequencing (scRNA-seq) method was used to analyze disease heterogeneity at the single-cell level. From the Gene Expression Omnibus (GEO) database (GSE180678), AMI scRNA-seq were downloaded and preprocessed by the Seurat package. Gene expression data came from GSE182923. Cell cluster analysis was conducted. Cell types were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on hub genes. Drugs were predicted by protein-protein interaction (PPI) and molecular docking. In total, 7 cell clusters were defined based on the scRNA-seq dataset, and the clusters were labeled as 5 cell types by marker genes. Hematopoietic stem cell types as a differential subgroups were higher in AMI than in healthy tissues. From available databases and PPI analysis, 52 common genets were identified. Based on 52 genes, 5 clusters were obtained using the MCODE algorithm, and genes in these 5 clusters involved in immune and inflammatory pathways were determined. Correlation analysis showed that hematopoietic stem cell types were negatively correlated with ATM, CARM1, and CASP8 but positively correlated with CASP3 and PPARG. This was reversed with immune cells. Molecular docking analysis showed that DB05490 had the lowest docking score with PPARG. We identified 5 hub genes (ATM, CARM1, CASP8, CASP3, and PPARG) involved in AMI progression. Compound DB05490 was a potential inhibitor of PPAG.

Indigenous Non-Saccharomyces Yeasts With ß-Glucosidase Activity in Sequential Fermentation With Saccharomyces cerevisiae: A Strategy to Improve the Volatile Composition and Sensory Characteristics of Wines.

Non-Saccharomyces (NS) yeasts with high ß-glucosidase activity play a vital role in improving the aroma complexity of wines by releasing aroma compounds from glycosidic precursors during fermentation. In this study, the effect of sequential inoculation fermentation of Meyerozyma guilliermondii NM218 and Hanseniaspora uvarum BF345 with two Saccharomyces cerevisiae strains [Vintage Red™ (VR) and Aroma White™ (AW)] on volatile compounds and sensory characteristics of wines was investigated. Prior to winemaking trials, the sequential inoculation times of the two NS yeasts were evaluated in synthetic must, based on changes in strain population and enzyme activity. The intervals for inoculation of NM218 and BF345 with the S. cerevisiae strains were 48 and 24 h, respectively. In the main experiment, sequential inoculation fermentations of the two strains with S. cerevisiae were carried out in Cabernet Sauvignon (CS) and Chardonnay (CH) grape must. The oenological parameters, volatile composition, and sensory characteristics of the final wines were assessed. No clear differences were observed in the oenological parameters of the sequentially fermented CH wines compared with the control, except for residual sugar and alcohol. However, in CS wines, the total acid contents were significantly lower in the wines fermented by sequential inoculation compared to the control. Both NM218 and BF345 improved the aroma complexity of wines by increasing esters and terpenes when inoculated with S. cerevisiae strains compared to inoculation with S. cerevisiae strains alone. NM218 resulted in a more positive effect on CS wine aroma, with higher levels of citronellol and trans-nerolidol. BF345 significantly enhanced the floral and fruity aromas of CH wine by producing higher concentrations of geranyl acetone, ß-damascenone, trans-nerolidol, and nerol. Both NM218 and BF345 yeasts could potentially be used to improve wine aroma and overall quality, especially wine floral and fruity aromas, when used in sequential inoculation with S. cerevisiae.

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR-21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia.

Innervation and extracellular vesicle secretion co-exist in the local tissue microenvironment for message transfer, but whether they are interconnected to regulate organ homeostasis remains unknown. Sympatho-adrenergic activation is implicated in stress-induced depression and leads to bone loss, but the mechanisms and therapeutics are incompletely elucidated. Here, it is revealed that sympathetic neurostress through the ß1/2 -adrenergic receptor (ß1/2-AR) signaling triggers the transcription response of a microRNA, miR-21, in osteoblasts, which is transferred to osteoclast progenitors via exosomes for dictating osteoclastogenesis. After confirming that miR-21 deficiency retards the ß1/2-AR agonist isoproterenol (ISO)-induced osteopenia, it is shown that the pharmacological inhibition of exosome release by two clinically-relevant drugs, dimethyl amiloride and omeprazole, suppresses osteoblastic miR-21 transfer and ameliorates bone loss under both ISO and chronic variable stress (CVS)-induced depression conditions. A targeted delivery approach to specifically silence osteoblastic miR-21 is further applied, which is effective in rescuing the bone remodeling balance and ameliorating ISO- and CVS-induced osteopenias. These results decipher a previously unrecognized paradigm that neural cues drive exosomal microRNA communication to regulate organ homeostasis and help to establish feasible strategies to counteract bone loss under psychological stresses.