This is the first study on the effect of carbonic maceration on the quality (color, aroma profile and sensory properties) of Muscat Hamburg, contrasting two winemaking procedures used in Tianjin (classical white and red-winemaking techniques). The values of C* (psychometric chroma), a* (measure of redness) and b* (measure of yellowness) were significantly higher (p < 0.01) in the carbonic macerated wine than in red wine. However, there were no visual differences in color, and classical red wine and carbonic macerated wine had similar h (hue angle) values and located in the red region. Thirty-two aromatic compounds were identified and quantified in Muscat Hamburg wines. The content of volatile compounds (6384.97 μg/L) was significantly higher (p < 0.001) in the carbonic macerated Muscat Hamburg wine than in the other kinds of wine. This result led to the carbonic macerated wine having the highest odor activity values (OAVs) and sensory evaluation scores (86.8 points), which correlates with an "excellent" sensory perception. This study demonstrated that carbonic maceration significantly improved the quality of Muscat Hamburg wine based on volatile analysis and sensory evaluation compared with other conventional methods. Therefore, carbonic maceration could be well suited for making Muscat Hamburg wine.

Cell proliferation and migration are the determinants of malignant tumor progression, and a better understanding of related genes will lead to the identification of new targets aimed at preventing the spread of cancer. Some studies have shown that KIAA1199 (CEMIP) is a transmembrane protein expressed in many types of noncancerous cells and cancer cells. However, the potential role of KIAA1199 in the progression of cholangiocarcinoma (CCA) remains unclear.

Recognizing locomotion modes is a crucial step in controlling lower-limb exoskeletons/orthoses. Our study proposed a fuzzy-logic-based locomotion mode/transition recognition approach that uses the onrobot inertial sensors for a hip joint exoskeleton (active pelvic orthosis). The method outputs the recognition decisions at each extreme point of the hip joint angles purely relying on the integrated inertial sensors. Compared with the related studies, our approach enables calibrations and recognition without additional sensors on the feet. We validated the method by measuring four locomotion modes and eight locomotion transitions on three able-bodied subjects wearing an active pelvic orthosis (APO). The average recognition accuracy was 92.46% for intrasubject crossvalidation and 93.16% for intersubject crossvalidation. The average time delay during the transitions was 1897.9 ms (28.95% one gait cycle). The results were at the same level as the related studies. On the other side, the study is limited in the small sample size of the subjects, and the results are preliminary. Future efforts will be paid on more extensive evaluations in practical applications.

As they age, adult stem cells become more prone to functional decline, which is responsible for aging-associated tissue degeneration and diseases. One goal of aging research is to identify drugs that can repair age-associated tissue degeneration. Multiple organ development-related signaling pathways have recently been demonstrated to have functions in tissue homeostasis and aging process. Therefore, in this study, we tested several chemicals that are essential for organ development to assess their ability to delay intestinal stem cell (ISC) aging and promote gut function in adult Drosophila. We found that taurine, a free amino acid that supports neurological development and tissue metabolism in humans, represses ISC hyperproliferation and restrains the intestinal functional decline seen in aged animals. We found that taurine represses age-associated ISC hyperproliferation through a mechanism that eliminated endoplasmic reticulum (ER) stress by upregulation of the target genes of unfolded protein response in the ER (UPRER ) and inhibiting the c-Jun N-terminal kinase (JNK) signaling. Our findings show that taurine plays a critical role in delaying the aging process in stem cells and suggest that it may be used as a natural compound for the treatment of age-associated, or damage-induced intestinal dysfunction in humans.

Osteoarthritis (OA) is the most common chronic degenerative joint disorder globally that is characterized by synovitis, cartilage degeneration, joint space stenosis, and sub-cartilage bone hyperplasia. However, the pathophysiologic mechanisms of OA have not been thoroughly investigated.

Endometrial carcinoma (EC) is a malignant neoplasm of the endometrial epithelium, which may be diagnosed by pathological investigations. The aim of the current study was to identify new markers for the diagnosis of EC using machine learning. The association between human T cell lymphotropic virus type 1 (HTLV-1) infection and endometrial cancer risk have not been widely reported. It remains ambiguous whether HTLV-1 infection is associated with several types of cancer. The present study investigated the association between HTLV-1 infection-associated genes and EC risk. RNA sequencing uterine cancer expression data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified between normal and matched tumor samples. A total of 41 genes were selected by an overlap between HTLV-1 infection pathway-associated genes and the DEGs. Two-way hierarchical clustering analysis (HCA) and a support vector machine (SVM) classifier were constructed using the 41 genes. The accuracy of the candidate genes in risk-stratifying the samples was 100%. The accuracy of the proposed SVM model was 100%. In addition, the classification power of the SVM model was validated using a merged dataset (TCGA and the Genotype-Tissue Expression project). This predictive feature achieved reliable outcomes with risk-stratifying samples of almost 99% in two-way HCA, and an accuracy yield of 98% of the SVM classifier. In conclusion, the 41 genes identified in the current study may be implicated in the development of EC and may be of prognostic value for the disease. The results obtained the current study suggest that HTLV-1 may be potentially associated with EC and highlight potential disease mechanisms.

The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5'-untranslated region (5'UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5'UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5'UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.

To identify why tree growth differs by afforestation type is a matter of prime concern in forestry. A study was conducted to determine why oriental arborvitae (Platycladus orientalis) grows better in the presence of black locust (Robinia pseudoacacia) than in monoculture. Different types of stands (i.e., monocultures and mixture of black locust and oriental arborvitae, and native grassland as a control) were selected in the Loess Plateau, China. The height and diameter at breast height of each tree species were measured, and soil, shoot, and root samples were sampled. The arbuscular mycorrhizal (AM) attributes, shoot and root nutrient status, height and diameter of black locust were not influenced by the presence of oriental arborvitae. For oriental arborvitae, however, growing in mixture increased height and diameter and reduced shoot Mn, Ca, and Mg contents, AM fungal spore density, and colonization rate. Major changes in soil properties also occurred, primarily in soil water, NO 3-N, and available K levels and in soil enzyme activity. The increase in soil water, N, and K availability in the presence of black locust stimulated oriental arborvitae growth, and black locust in the mixed stand seems to suppress the development of AM symbiosis in oriental arborvitae roots, especially the production of AM fungal spores and vesicles, through improving soil water and N levels, thus freeing up carbon to fuel plant growth. Overall, the presence of black locust favored oriental arborvitae growth directly by improving soil water and fertility and indirectly by repressing AM symbiosis in oriental arborvitae roots.

It was recently reported that increased SOX9 expression drives tumor growth and promotes cancer invasion during human tumorigenicity and metastasis. However, the prognostic value of SOX9 for the survival of patients with solid tumors remains controversial. The present meta-analysis was thus performed to highlight the link between dysregulated SOX9 expression and prognosis in cancer patients. A systematic literature search was conducted using the electronic databases PubMed, Web of Science and Embase to identify eligible studies. A random-effects meta-analytical model was employed to correlate SOX9 expression with overall survival (OS), disease-free survival (DFS) and clinicopathological features. In total, 17 studies with 3307 patients were eligible for the final analysis. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9 expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36-2.02, P < 0.001) and DFS (HR = 3.54, 95% CI 2.29-5.47, P = 0.008) in multivariate analysis. Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is associated with large tumor size, lymph node metastasis, distant metastasis and a higher clinical stage. Overall, these results indicated that SOX9 over-expression in patients with solid tumors might be related to poor prognosis and could serve as a potential predictive marker of poor clinicopathological prognosis factor.

Soil salinization and the associated land degradation are major and growing ecological problems. Excess salt in soil impedes plant photosynthetic processes and root uptake of water and nutrients such as K+. Arbuscular mycorrhizal (AM) fungi can mitigate salt stress in host plants. Although, numerous studies demonstrate that photosynthesis and water status are improved by mycorrhizae, the molecular mechanisms involved have received little research attention. In the present study, we analyzed the effects of AM symbiosis and salt stress on photosynthesis, water status, concentrations of Na+ and K+, and the expression of several genes associated with photosynthesis (RppsbA, RppsbD, RprbcL, and RprbcS) and genes coding for aquaporins or membrane transport proteins involved in K+ and/or Na+ uptake, translocation, or compartmentalization homeostasis (RpSOS1, RpHKT1, RpNHX1, and RpSKOR) in black locust. The results showed that salinity reduced the net photosynthetic rate, stomatal conductance, and relative water content in both non-mycorrhizal (NM) and AM plants; the reductions of these three parameters were less in AM plants compared with NM plants. Under saline conditions, AM fungi significantly improved the net photosynthetic rate, quantum efficiency of photosystem II photochemistry, and K+ content in plants, but evidently reduced the Na+ content. AM plants also displayed a significant increase in the relative water content and an evident decrease in the shoot/root ratio of Na+ in the presence of 200 mM NaCl compared with NM plants. Additionally, mycorrhizal colonization upregulated the expression of three chloroplast genes (RppsbA, RppsbD, and RprbcL) in leaves, and three genes (RpSOS1, RpHKT1, and RpSKOR) encoding membrane transport proteins involved in K+/Na+ homeostasis in roots. Expression of several aquaporin genes was regulated by AM symbiosis in both leaves and roots depending on soil salinity. This study suggests that the beneficial effects of AM symbiosis on the photosynthetic capacity, water status, and K+/Na+ homeostasis lead to the improved growth performance and salt tolerance of black locust exposed to salt stress.

The age-associated decline of adult stem cell function is closely related to the decline in tissue function and age-related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigated Drosophila midguts and found a continuous downregulation of lipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha-lipoic acid (ALA), upon aging. Importantly, orally administration of ALA significantly reversed the age-associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan of Drosophila. This study reports that ALA reverses age-associated ISC dysfunction by promoting the activation of the endocytosis-autophagy network, which decreases in aged ISCs. Moreover, this study suggests that ALA may be used as a safe and effective anti-aging compound for the treatment of ISC-dysfunction-related diseases and for the promotion of healthy aging in humans.

Glioblastoma multiform (GBM) is the most lethal intracranial tumor in adults. Glioblastoma stem-like cells (GSCs) are responsible for tumorigenesis and chemotherapy resistance. BMPs are known to increase temozolomide (TMZ) response in GSCs, however, the intracellular molecular mechanism remains largely unknown. In this study, we built a GSC cell model called U87S, and performed RNA sequencing to identify differentially expressed (DE) miRNA profiles in U87S cells treated with BMP2, TMZ or combined BMP2 and TMZ respectively. Bioinformatics analysis revealed that most DE miRNAs were involved in the cancer pathways, suggesting their crucial roles in gliomagenesis. Eight miRNAs from RNA-seq were validated. Four out of these miRNAs (has-miR-199a-3p, hsa-miR-374b-5p, hsa-miR-320d, and hsa-miR-339-5p) were found significantly up-regulated in GBM tumor tissues. One of them, hsa-miR-199a-3p, was significantly correlated with the survival of GBM patients, and differentially expressed in U87S cells. Expression of hsa-miR-199a-3p was up-regulated by BMP. Overexpression of hsa-miR-199a-3p in U87S cells inhibited cell viability and enhanced the cytotoxicity of TMZ. And activation of BMP boosted the effect of hsa-miR-199a-3p on cell viability and TMZ-mediated cytotoxicity. Besides, expressions of five predicted targets of hsa-miR-199a-3p were evaluated. Four of them were differentially expressed in GBM tumors. And one of them, SLC22A18, was associated with the survival of GBM patients. In the end, a hsa-miR-199a-3p-mediated ceRNA network was constructed for the convenience of future study. Together, our data provided DE miRNA expression profiles associated with BMP2 and TMZ in GSCs, which might lead to finding out miRNA-based target therapies that specially target GSCs.

The tumor microenvironment (TME) plays an important role in the occurrence and development of soft tissue sarcoma (STS). A number of studies have shown that to inhibit tumor growth, the TME can be remodeled into an environment unsuitable for tumor proliferation. However, a lack of understanding exists regarding the dynamic regulation of TME.In this study, we used CIBERSORT and ESTIMATE calculation methods from the Cancer Genome Atlas (TCGA) database to calculate the proportion of tumor infiltrating immune cells (TICs) and the number of immune and stromal components in 263 STS samples. Differential expression genes (DEGs) shared by Immune Score and Stromal Score were obtained via difference analysis. Univariate Cox regression analysis and construction of protein-protein interaction (PPI) networks were applied to the DEGs.Through intersection analysis of univariate COX and PPI, PLCG2 was determined as the indicator. Further analysis showed that PLCG2 expression was positively correlated with the survival of STS patients. Gene set enrichment analysis (GSEA) showed that genes in the highly expressed PLCG2 group were enriched in immune-related activities. In the low-expression PLCG2 group, genes were enriched in the E2F, G2M, and MYC pathways. Difference analysis and correlation analysis showed that CD8+ T cells, gamma delta T cells, monocytes, and M1 macrophages were positively correlated with PLCG2 expression, indicating that PLCG2 may represent the immune status of TME.Therefore, the level of PLCG2 may aid in determining the prognosis of STS patients, especially the status of TME. These data provide additional insights into the remodeling of TME.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.

Mounting evidences have indicated that RNA N6-methyladenosine (m6A) modification played important roles in tumor formation and growth. However, it is rarely reported that m6A modifications are involved in the immune regulation and tumor microenvironment (TME) formation. In this study, we aimed to investigate the correlation between m6A modifications and TME regulation of colon adenocarcinoma (COAD) by bioinformatic analysis. NMF algorithm was applied to carry out consensus molecular subtype analysis on 36 selected m6A regulators regarding methylation modification, to identify m6A modification patterns and characteristics of m6A related genes in colon adenocarcinoma (COAD). Further, the relative infiltration levels of different immune cell subsets were quantified by ssGSEA and CIBERSORT algorithms, and a m6Sig scoring scheme was constructed to predict the prognosis and evaluate the response to immunotherapy in the patients with COAD. Among 579 COAD samples, we identified three different m6A modification patterns which were related to different biological pathways and clinical outcomes. Then, a scoring scheme termed "m6Sig score" was developed based on m6A-related characteristic genes, and was utilized to score patients with COAD into groups. We found that COAD patients with lower m6Sig scores exhibited prolonged survival and potentiated immune infiltration, which were associated with higher tumor mutation load, lower PD-L1 expression, and higher mutation rates of SMG (such as TTN and KRAS). Moreover, analysis regarding evaluation of immune response revealed that the patients with lower m6Sig scores had higher Immunophenoscore. Collectively, our study provided in depth insight into the interactions between m6A modification and regulation of TME. In addition, the quantitative evaluation of m6A modification patterns in our results may have implications in further immunotherapy for individual COAD patients.

Insomnia is a common diseases of the elderly, tuina is a widely used treatment. At present, there is a lack of supportive evidence on efficacy and safety of tuina for senile insomnia. The purpose of this systematic review is to assess the effectiveness and safety of tuina therapy in the treatment of senile insomnia.

Epithelial-repair-dependent mucosal healing (MH) is associated with a more favorable prognosis for patients with inflammatory bowel disease (IBD). MH is accomplished via repair and regeneration of the intestinal epithelium. However, the mechanism underlying MH is ill defined. We found a striking upregulation of peroxisomes in the injured crypts of IBD patients. By increasing peroxisome levels in Drosophila midguts, we found that peroxisome elevation enhanced RAB7-dependent late endosome maturation, which then promoted stem and/or progenitor-cell differentiation via modulation of Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-SOX21A signaling. This in turn enhanced ISC-mediated regeneration. Importantly, RAB7 and SOX21 were upregulated in the crypts of IBD patients. Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.

Predicting the outcome after a cancer diagnosis is critical. Advances in high-throughput sequencing technologies provide physicians with vast amounts of data, yet prognostication remains challenging because the data are greatly dimensional and complex. We evaluated Wnt/β-catenin, carbohydrate metabolism, and PI3K-Akt signaling pathway-related genes as predictive features for classifying tumors and normal samples. Using differentially expressed genes as controls, these pathway-related genes were assessed for accuracy using support-vector machines and three other recommended machine learning models, namely, the random forest, decision tree, and k-nearest neighbor algorithms. The first two outperformed the others. All candidate pathway-related genes yielded areas under the curve exceeding 95.00% for cancer outcomes, and they were most accurate in predicting colorectal cancer. These results suggest that these pathway-related genes are useful and accurate biomarkers for understanding the mechanisms behind cancer development.

Some patients with advanced colon adenocarcinoma (COAD) are not sensitive to radiotherapy and chemotherapy, and as such, immunotherapy has become the most popular option for these patients. However, different patients respond differently to immunotherapy. Tumor mutational burden (TMB) has been used as a predictor of the response of advanced COAD patients to immunotherapy. A high TMB typically indicates that the patient's immune system will respond well to immunotherapy. In addition, while microRNAs (miRNA) have been shown to play an important role in treatment responses associated with the immune system, the relationship between miRNA expression levels and TMB has not been clarified in COAD.We downloaded miRNA data and mutational files of COAD from the Cancer Genome Atlas database. Differentially expressed miRNAs were screened in the training group, and miRNAs used to construct the model were further identified using the LASSO logistic regression method. After building the miRNA-based model, we explored the correlation between the model and TMB. The model was verified by a receiver operating characteristic curve, and the correlation between it and 3 widely used immune checkpoints (programmed death receptor-1, programmed death-ligand 1, and cytotoxic T-lymphocyte associated protein-4) was explored. Functional enrichment analysis of the selected miRNAs was performed, and these respective miRNA target genes were predicted using online tools.Our results showed that a total of 32 differentially expressed miRNAs were used in the construction of the model. The accuracies of the models of the 2 datasets (training and test sets) were 0.987 and 0.934, respectively. Correlation analysis showed that the correlation of the model with programmed death-ligand 1 and cytotoxic T-lymphocyte associated protein-4, as well as TMB, was high, but there was no correlation with programmed death receptor-1. The results of functional enrichment analysis indicated that these 32 miRNAs were involved in many immune-related biological processes and tumor-related pathways.Therefore, this study demonstrated that differentially expressed miRNAs can be used to predict the TMB level, which can help identify advanced COAD patients who will respond well to immunotherapy. The miRNA-based model may be used as a tool to predict the TMB level in patients with advanced COAD.

Cuproptosis caused by copper overload is mediated by a novel regulatory mechanism that differs from previously documented mechanisms regulating cell death. Cells dependent on mitochondrial respiration showed increased sensitivity to a copper ionophore elesclomol that induced cuproptosis. Maternal embryonic leucine zipper kinase(MELK) promotes tumorigenesis and tumor progression through the PI3K/mTOR pathway, which exerts its effects partly by targeting the pyruvate dehydrogenase complex(PDHc) and reprogramming the morphology and function of mitochondria. However, the role of MELK in cuproptosis remains unclear. Here, we validated that elevated MELK expression enhanced the activity of PI3K/mTOR signaling and subsequently promoted Dihydrolipoamide S-Acetyltransferase (DLAT) expression and stabilized mitochondrial function. This regulatory effect helped to improve mitochondrial respiration, eliminate excessive intracellular reactive oxygen species (ROS), reduce intracellular oxidative stress/damage and the possibility of mitochondria-induced cell fate alternations, and ultimately promote the progression of HCC. Meanwhile, elesclomol reduced translocase of outer mitochondrial membrane 20(TOM 20) expression and increased DLAT oligomers. Moreover, the above changes of MELK to HCC were abolished by elesclomol. In conclusion, MELK enhanced the levels of the cuproptosis-related signature(CRS) gene DLAT (especially the proportion of DLAT monomer) by activating the PI3K/mTOR pathway, thereby promoting elesclomol drug resistance, altering mitochondrial function, and ultimately promoting HCC progression.