A review: targeting UBR5 domains to mediate emerging roles and mechanisms: chance or necessity?

Ubiquitinases are known to catalyze ubiquitin chains on target proteins to regulate various physiological functions like cell proliferation, autophagy, apoptosis, and cell cycle progression. As a member of E3 ligase, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) belongs to the HECT E3 ligase and has been reported to be correlated with various pathophysiological processes. In this review, we give a comprehensive insight into the structure and function of UBR5. We discuss the specific domains of UBR5 and explore their biological functions separately. Furthermore, we describe the involvement of UBR5 in different pathophysiological conditions, including immune response, virus infection, DNA damage response and protein quality control. Moreover, we provide a thorough summary of the important roles and regulatory mechanisms of UBR5 in cancers and other diseases. On the whole, investigating the domains and functions of UBR5, elucidating the underlying mechanisms of UBR5 with various substrates in detail may provide new theoretical basis for the treatment of diseases, including cancers, which could improve future studies to construct novel UBR5-targeted therapy strategies.

The spontaneous activities of the multiple demand network are related to individual differences in indirect replies comprehension.

This study aims to investigate the brain networks engaged in the comprehension of indirect language, as well as the individual difference in this capacity. Specially, we aim to determine whether the difference is solely influenced by the difference in individuals' default network (DN)/language network or whether it also relies on the networks associated with processing of complex cognitive tasks, particularly the multiple demand network (MDN). Conversational indirectness scale (CIS) scores in the interpretation dimension were used as a behavioral indicator of the indirect comprehension tendency. Reading time difference between indirect replies and direct replies collected through a self-paced reading experiment was deemed as a behavioral indicator of comprehension speed of indirect replies comprehension. The two behavioral indicators were combined with resting-state functional magnetic resonance imaging (rs-fMRI). The behaviour-rfMRI analysis showed that ALFF value of right SPL and the functional connectivity (FC) between the right SPL and right IPL/SMA/ITG/Precuneus/bilateral IFG were positively correlated with the interpretation dimension of CIS scores. In addition, the ALFF value of right fusiform gyrus, the FC between the right fusiform gyrus and right precuneus, and the FCs between right SPL and right IPL/Precuneus/IFG were negatively correlated with indirect replies comprehension speed. Overlapping of these regions with large-scale brain network revealed that the right SPL was mainly located in the MDN, and the right fusiform gyrus was mainly located in the language network. Additionally, the areas showing functional connectivity with these regions were primarily located in the MDN, with a smaller subset located in the DN. Our findings suggest that the ability of individuals to actively and rapidly acquire indirect meaning relies not only on the support of the DN and the language network, but also requires collective support from the MDN.

Ubiquitin specific peptidase 3: an emerging deubiquitinase that regulates physiology and diseases.

Proteins are the keystone for the execution of various life activities, and the maintenance of protein normalization is crucial for organisms. Ubiquitination, as a post-transcriptional modification, is widely present in organisms, and it relies on the sophisticated ubiquitin-proteasome (UPS) system that controls protein quality and modulates protein lifespan. Deubiquitinases (DUBs) counteract ubiquitination and are essential for the maintenance of homeostasis. Ubiquitin specific peptidase 3 (USP3) is a member of the DUBs that has received increasing attention in recent years. USP3 is a novel chromatin modifier that tightly regulates the DNA damage response (DDR) and maintains genome integrity. Meanwhile, USP3 acts as a key regulator of inflammatory vesicles and sustains the normal operation of the innate immune system. In addition, USP3 is aberrantly expressed in a wide range of cancers, such as gastric cancer, glioblastoma and neuroblastoma, implicating that USP3 could be an effective target for targeted therapies. In this review, we retrace all the current researches of USP3, describe the structure of USP3, elucidate its functions in DNA damage, immune and inflammatory responses and the cell cycle, and summarize the important role of USP3 in multiple cancers and diseases.

Functional screening of the Arabidopsis 2C protein phosphatases family identifies PP2C15 as a negative regulator of plant immunity by targeting BRI1-associated receptor kinase 1.

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.

Studies on Candidate Genes Related to Flowering Time in a Multiparent Population of Maize Derived from Tropical and Temperate Germplasm.

A comprehensive study on maize flowering traits, focusing on the regulation of flowering time and the elucidation of molecular mechanisms underlying the genes controlling flowering, holds the potential to significantly enhance our understanding of the associated regulatory gene network. In this study, three tropical maize inbreds, CML384, CML171, and CML444, were used, along with a temperate maize variety, Shen137, as parental lines to cross with Ye107. The resulting F1s underwent seven consecutive generations of self-pollination through the single-seed descent (SSD) method to develop a multiparent population. To investigate the regulation of maize flowering time-related traits and to identify loci and candidate genes, a genome-wide association study (GWAS) was conducted. GWAS analysis identified 556 SNPs and 12 candidate genes that were significantly associated with flowering time-related traits. Additionally, an analysis of the effect of the estimated breeding values of the subpopulations on flowering time was conducted to further validate the findings of the present study. Collectively, this study offers valuable insights into novel candidate genes, contributing to an improved understanding of maize flowering time-related traits. This information holds practical significance for future maize breeding programs aimed at developing high-yielding hybrids.

Genome-Wide Association Studies on the Kernel Row Number in a Multi-Parent Maize Population.

Kernel row number (KRN) is a crucial trait in maize that directly influences yield; hence, understanding the mechanisms underlying KRN is vital for the development of high-yielding inbred lines and hybrids. We crossed four excellent panicle inbred lines (CML312, CML444, YML46, and YML32) with Ye107, and after eight generations of selfing, a multi-parent population was developed comprising four subpopulations, each consisting of 200 lines. KRN was accessed in five environments in Yunnan province over three years (2019, 2021, and 2022). The objectives of this study were to (1) identify quantitative trait loci and single nucleotide polymorphisms associated with KRN through linkage and genome-wide association analyses using high-quality genotypic data, (2) identify candidate genes regulating KRN by identifying co-localized QTLs and SNPs, and (3) explore the pathways involved in KRN formation and identify key candidate genes through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Our study successfully identified 277 significant Quantitative trait locus (QTLs) and 53 significant Single Nucleotide Polymorphism (SNPs) related to KRN. Based on gene expression, GO, and KEGG analyses, SNP-177304649, SNP-150393177, SNP-135283055, SNP-138554600, and SNP-120370778, which were highly likely to be associated with KRN, were identified. Seven novel candidate genes at this locus (Zm00001d022420, Zm00001d022421, Zm00001d016202, Zm00001d050984, Zm00001d050985, Zm00001d016000, and Zm00014a012929) are associated with KRN. Among these, Zm00014a012929 was identified using the reference genome Mo17. The remaining six genes were identified using the reference genome B73. To our knowledge, this is the first report on the association of these genes with KRN in maize. These findings provide a theoretical foundation and valuable insights into the genetic mechanisms underlying maize KRN and the development of high-yielding hybrids through heterosis.

How CLSPN could demystify its prognostic value and potential molecular mechanism for hepatocellular carcinoma: A crosstalk study.

BACKGROUND & AIMS: CLSPN, a critical component of the S-phase checkpoint in response to DNA replication stress, has been implicated in the pathogenesis of multiple tumor types. The rising incidence of hepatocellular carcinoma (HCC) poses a significant challenge to global public health. Despite this, the specific functions of CLSPN in the development of HCC remain poorly understood. METHODS: We systematically evaluated the expression of CLSPN, prognosis and immune infiltration in patients with HCC and identified a competing endogenous RNA (ceRNA) network by using public database. The RT-qPCR, western blot, CCK8, transwell, flow cytometry, animal experiments, proteasome inhibition experiment, Co-IP assay and mass spectrometry were applied to explore its biological functions, post-transcriptional modifications and potential molecular mechanisms of CLSPN in HCC. RESULTS: We verified the expression of CLSPN, and its high expression is an independent prognostic factor in HCC. The expression of CLSPN is also associated with the immune microenvironment of HCC. CLSPN silencing inhibited the proliferation, migration, invasion and cell cycle progression of HCC cells. We established a PSMA3-AS1/hsa-miR-101-3p/CLSPN regulator axis in HCC. CLSPN was influenced by ubiquitination and was involved in the Wnt/ß-catenin pathway to regulate HCC progression. CONCLUSIONS: It was the first time to comprehensively discover and identify the expression, prognosis, immunotherapy, RNAs regulator, posttranscriptional modification, and molecular mechanisms of CLSPN in HCC. These novel insights have the potential to expedite the development of personalized treatment strategies and translational medicine approaches for HCC patients.

Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.

Ubiquitination is one of the most significant post-translational modifications that regulate almost all physiological processes like cell proliferation, autophagy, apoptosis, and cell cycle progression. Contrary to ubiquitination, deubiquitination removes ubiquitin from targeted protein to maintain its stability and thus regulate cellular homeostasis. Ubiquitin-Specific Protease 12 (USP12) belongs to the biggest family of deubiquitinases named ubiquitin-specific proteases and has been reported to be correlated with various pathophysiological processes. In this review, we initially introduce the structure and biological functions of USP12 briefly and summarize multiple substrates of USP12 as well as the underlying mechanisms. Moreover, we discuss the influence of USP12 on tumorigenesis, tumor immune microenvironment (TME), disease, and related signaling pathways. This study also provides updated information on the roles and functions of USP12 in different types of cancers and other diseases, including prostate cancer, breast cancer, lung cancer, liver cancer, cardiac hypertrophy, multiple myeloma, and Huntington's disease. Generally, this review sums up the research advances of USP12 and discusses its potential clinical application value which deserves more exploration in the future.

An elaborate biomolecular keypad lock based on electrochromism of viologen derivatives and bioelectrocatalytic reduction of CO2 at supramolecular hydrogel film electrodes.

Herein, the short peptide N-fluorenemethoxycarbonyl diphenylalanine (Fmoc-FF) was used to immobilize both diallyl viologen (DAV) and the enzyme formate dehydrogenase (FDH) to form Fmoc-FF/DAV/FDH supramolecular hydrogel films on an electrode surface by a simple solvent-controlled self-assembly method. The DAV component in the films exhibited multiple properties, such as electrochromism and electrofluorochromism, and acted as an electrochemical mediator. A high efficiency of bioelectrocatalytic reduction of CO2 to formate (HCOO-) was obtained by the natural FDH enzyme and the artificial coenzyme factor DAV both immobilized in the same films. The supramolecular hydrogel films with CO2, voltage and light as stimulating factors and current, fluorescence and UV-vis extinction as responsive signals, were further applied for the construction of complex biomolecular logic systems and information encryption. A 3-input/7-output biomolecular logic gate and several logic devices, including an encoder/decoder, a parity checker, and a keypad lock, were constructed. Especially, the biomolecular keypad lock with 3 types of signals as outputs significantly enhanced the security level of information encryption. In this work, a supramolecular self-assembly interface was simply fabricated with complex biomolecular computational functions using immobilized molecules as the computational core, greatly broadening the application range of supramolecular hydrogel films and providing an idea for new designs of bioinformation encryption through the use of a simple film system.

N6-methyladenosine with immune infiltration and PD-L1 in hepatocellular carcinoma: novel perspective to personalized diagnosis and treatment.

Background: Increasing evidence elucidated N6-methyladenosine (m6A) dysregulation participated in regulating RNA maturation, stability, and translation. This study aimed to demystify the crosstalk between m6A regulators and the immune microenvironment, providing a potential therapeutic target for patients with hepatocellular carcinoma (HCC). Methods: Totals of 371 HCC and 50 normal patients were included in this study. GSE121248 and GSE40367 datasets were used to validate the expression of HNRNPC. The R package "ConsensusClusterPlus" was performed to screen consensus clustering types based on the expression of m6A regulators in HCC. The R package "pheatmap", "immunedeconv", "survival", "survminer" and "RMS" were applied to investigate the expression, immunity, overall survival, and clinical application in different clusters and expression groups. Comprehensive analysis of HNRNPC in pan-cancer was conducted by TIMER2 database. Besides, HNRNPC mRNA and protein expression were verified by qRT-PCR and immunohistochemistry analysis. Results: Most of m6A regulators were over-expressed excerpt for ZC3H13 in HCC. Three independent clusters were screened based on m6A regulators expression, and the cluster 2 had a favorable prognosis in HCC. Then, the cluster 2 was positively expression in macrophage, hematopoietic stem cell, endothelial cell, and stroma score, while negatively in T cell CD4+ memory and mast cell. We identified HNRNPC was an independent prognostic factor in HCC, and nomogram performed superior application value for clinical decision making. Moreover, PD-L1 was significantly up-regulated in HCC tissues, cluster 1, and cluster 3, and we found PD-L1 expression was positively correlated with HNRNPC. Patients with HCC in high-expression groups was associated with tumor-promoting cells. Besides, HNRNPC was correlated with prognosis, TMB, and immune checkpoints in cancers. Particularly, the experiments confirmed that HNRNPC was positively expression in HCC cells and tissues. Conclusion: The m6A regulators play irreplaceable roles in prognosis and immune infiltration in HCC, and the relationship of HNRNPC and PD-L1 possesses a promising direction for therapeutic targets of immunotherapy response. Exploration of m6A regulators pattern could be build the prognostic stratification of individual patients and move toward to personalized treatment.

Crosstalk of ferroptosis regulators and tumor immunity in pancreatic adenocarcinoma: novel perspective to mRNA vaccines and personalized immunotherapy.

Pancreatic adenocarcinoma (PAAD) is the eighth leading cause of cancer-related mortality that causes serious physical and mental burden to human. Reactive oxygen species accumulation and iron overload might enable ferroptosis-mediated cancer therapies. This study was to elusive novel ferroptosis regulator and its association with immune microenvironment and PD-L1 in PAAD. RNA-seq data and relevant information were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression. The R packages "ggplot2" and "pheatmap" were used to the expression of 20 ferroptosis regulators between PAAD and normal tissues. The R package "ConsensusClusterPlus", "survival", "survminer", "immunedeconv", and TIDE algorithm performed consensus clustering, overall survival, progression-free survival, disease free survival, immune infiltration level, and immunotherapy responses between cluster 1 and cluster 2. The prognostic value was confirmed by the Kaplan-Meier curves, receiver operating characteristic curve, univariate and multivariate cox regression, and nomogram. Moreover, the relationship of FANCD2 and immunity, drug sensitivity was investigated by R package "ggstatsplot", "immunedeconv", "ggalluvial" and "pRRophetic". Besides, the qRT-PCR, immunohistochemistry and western blotting detected the expression of FANCD2 in PAAD cell lines. Most ferroptosis regulators were up-regulated in PAAD, while the expression of LPCAT3, MT1G, and GLS2 was down-regulated in PAAD (P < 0.05), indicting there was a positively correlation among ferroptosis regulators. Based on clustering parameter, we identified cluster 1 and cluster 2, and cluster 2 had a better prognosis for patients with PAAD. The immune infiltration level of cluster 1 was higher in macrophage M1, myeloid dendritic cell, T cell CD4 + Th2, B cell, T cell CD8 + central memory, immune score, and microenvironment score than cluster 2 in PAAD. Moreover, FANCD2 was up-regulated in PAAD by public databases, immunohistochemistry, qRT-PCR and Western blotting, which had closely related to overall survival, immune microenvironment, and drug sensitivity. A novel crosstalk of ferroptosis exhibits a favourable prognostic performance and builds a robust theoretical foundation for mRNA vaccine and personalized immunotherapy. FANCD2 could be an effective for prognostic recognition, immune efficacy evaluation, and mRNA vaccine for patients with PAAD, providing a vital guidance for further study of regulating tumor immunity and vaccine development.

Comparision of nitrogen removal characteristic and microbial community in freshwater and marine recirculating aquaculture systems.

Recirculating aquaculture system (RAS) has a good prospect in aquaculture, but its nitrogen removal characteristics and microbial community changes in freshwater and marine water remain unclear. In this study, six RAS were designed and divided into freshwater group and marine water group with salinity of 0‰ and 32‰, respectively, and operated for 54 days to test changes in nitrogen (NH4+-N, NO2--N, NO3--N), extracellular polymeric substances and microbial communities. The results showed that ammonia nitrogen was rapidly reduced and almost converted to nitrate nitrogen in the freshwater RAS but to nitrite nitrogen in marine RAS. Compared with freshwater RAS, marine RAS had lower tightly bound extracellular polymeric substances and worse stability and settleability condition. 16S rRNA amplicon sequencing reflected significantly lower bacterial diversity and richness in marine RAS. Microbial community structure at phylum level showed lower relative abundance of Proteobacteria, Actinobacteria, Firmicutes, Nitrospirae, but higher abundance of Bacteroidetes under a salinity of 32‰. High salinity decreased the abundance of funtional genera (Nitrosospira, Nitrospira, Pseudomonas, Rhodococcus, Comamonas, Acidovorax, f_Comamonadaceae), which may account for nitrite accumulation and low nitrogen removal capacity in marine RAS. These findings could provide theoretical and practical basis for improving the start-up speed of high-salinity nitrification biofilm.

Prognostic value of ASXL1 mutations in patients with myelodysplastic syndromes and acute myeloid leukemia: A meta-analysis.

Additional sex combs-like 1 (ASXL1) mutations, a hotspot in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have been frequently reported for their potential prognostic value, but the results are controversial. Therefore, a meta-analysis was performed. Databases, including PubMed, Embase, and Cochrane Library, were searched for relevant studies published up to January 13, 2022. STATA v16.0 software was used to calculate the combined hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and AML transformation. Subgroup analysis was used to explore the effects of the grouping factors on heterogeneity.Ten studies on ASXL1 mutations and the prognosis of MDS were selected. Our results indicate that ASXL1 mutations have an adverse prognostic impact on OS (HR = 1.68,95%CI:1.45-1.94, p < .0001) and AML transformation (HR = 2.20,95% CI:1.68-2.87, p < .0001). The results for different age groups were not significantly different (HR = 1.87,95% CI: 1.31-2.67; HR = 1.62,95% CI:1.35-2.07). Ten studies covering 5816 patients with AML were included. The pooled HR for OS was 1.37 (95% CI:1.20-1.56, p < .0001). ASXL1 mutations were especially associated with a poorer OS in the subgroup aged ≥60 years (HR = 2.86, 95% CI:1.34-6.08, p = .006); when considering cytogenetically normal AML (CN-AML), the HR was 1.78(95% CI:1.27-2.49, p = .001). This meta-analysis indicates an independent, adverse prognostic impact of ASXL1 mutations in patients with MDS and AML, which also applies to patients with CN-AML. Age was a risk factor for patients with AML and ASXL1 mutations but not for patients with MDS.

Metabolomics and network pharmacological analysis to explore the mechanism of ginseng treatment for spleen-qi deficiency.

Ginseng is the main Chinese herbal medicine for tonifying Qi and invigorating the spleen. It has been used to treat spleen-qi deficiency with good protective effects for thousands of years, however, its biological mechanism has not been fully elucidated. This study aims to explore the mechanism of ginseng in the treatment of spleen-qi deficiency by using a comprehensive method combining metabolomics and network pharmacological analysis. Gas chromatography-mass spectroscopy was applied for investigating the changes in urine metabolites in spleen-qi deficiency rats and after treatment with ginseng. Metabolomics and network pharmacology analysis were applied to screen potential biomarkers and therapeutic targets of ginseng in the treatment of spleen-qi deficiency, respectively. Molecular docking was employed to further evaluate the docking mode of potential biomarkers and therapeutic target proteins. The results of metabolomics showed that the therapeutic effects of ginseng are mainly related to its regulation of three metabolic pathways. The molecular structure of potential biomarkers and common proteins was further analyzed by molecular docking to verify its effectiveness. Ginseng has good pharmacological effects by controlling key targets of related metabolic pathways, signal pathways, and potential biomarkers.

Identification and chemical profiling of anti-alcoholic liver disease biomarkers of ginseng Huang jiu using UPLC-Q-Orbitrap-HRMS and network pharmacology-based analyses.

This study investigated the mechanism of characteristic non-volatile organic compounds (NVOCs) from ginseng Huang jiu (GH) in the treatment of alcoholic liver disease through UPLC-Q-Orbitrap-HRMS and network pharmacological analyses. Changes in NVOC contents in ginseng Huang jiu and ginseng-soaked wine fermented by different processing technologies were analyzed through liquid chromatography-mass spectrometry (LC-MS). A total of 96 ginsenosides were identified in ginseng Huang jiu throughout the fermentation process, which included 37 protopanaxadiol-type ginsenosides, 47 protopanaxatriol-type ginsenosides, and 4 oleanolic acid-type ginsenosides. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that 20(R)-Rg2, Gypenoside XVII, 20(S)-Rf3, CK, Rg5, Rh2, and other rare ginsenosides in ginseng Huang jiu could be the potential index for determining ginseng Huang jiu. In addition, ginseng Huang jiu could improve alcoholic liver disease by regulating the GSTP1, HRAS, AKR1B1, GSTA1, Androgen receptor (AR), GSR, and LDHB genes through bioinformatics analysis. This study provides new insights into improving the industrial production of ginseng Huang jiu and treating alcoholic liver disease with medicinal and food products.

Subset selection strategy-based pancreas segmentation in CT.

Background: Although convolutional neural network (CNN)-based methods have been widely used in medical image analysis and have achieved great success in many medical segmentation tasks, these methods suffer from various imbalance problems, which reduce the accuracy and validity of segmentation results. Methods: We proposed two simple but effective sample balancing methods, positive-negative subset selection (PNSS) and hard-easy subset selection (HESS) for foreground-to-background imbalance and hard-to-easy imbalance problems in medical segmentation tasks. The PNSS method gradually reduces negative-easy slices to enhance the contribution of positive pixels, and the HESS method enhances the iteration of hard slices to assist the model in paying greater attention to the feature extraction of hard samples. Results: The proposed methods greatly improved the segmentation accuracy of the worst case (samples with the worst segmentation results) on the public National Institutes of Health (NIH) clinical center pancreatic segmentation dataset, and the minimum dice similarity coefficient (DSC) was improved by nearly 5%. Furthermore, performance gains were also observed with the proposed methods in liver segmentation (the minimum DSC increased from 75.03% to 84.29%), liver tumor segmentation (the minimum DSC increased from 20.92% to 35.73%), and brain tumor segmentation (the minimum DSC increased from 21.97% to 30.38%) on different neural networks. These results indicate that the proposed methods are effective and robust. Conclusions: Our proposed method can effectively alleviate foreground-to-background imbalance and hard-to-easy imbalance problems, and can improve segmentation accuracy, especially for the worst case, which guarantees the reliability of the proposed methods in clinical applications.

Intervention effects of ginseng on spleen-qi deficiency in rats revealed by GC-MS-based metabonomic approach.

Panax ginseng C. A. Mey. (Ginseng) is a famous Chinese medicine with tonifying middle and replenishing qi effects and has been applied for the treatment of spleen-qi deficiency for many years. However, its potential therapeutic mechanisms have not been thoroughly studied. In this study, the metabolomic technique was applied to explore the therapeutic effect of ginseng on the spleen-qi deficiency. A rat model of spleen-qi deficiency was generated via the fatigue swimming method. After 3 weeks of treatment with ginseng, the entire metabolic changes in rat serum were profiled by gas chromatography-mass spectroscopy (GC-MS). The metabolic profiles in serum taurine and hypotaurine metabolism significantly differed among groups, in which a total of 17 metabolites were identified. Ginseng reversed the metabolic changes in the difference involving some metabolic pathways. Among them, beta-alanine metabolism, taurine and hypotaurine metabolism, and the pentose phosphate pathway are the key metabolic pathways. The therapeutic effects of ginseng on spleen-qi deficiency rats could be achieved by regulating multiple metabolic pathways, metabolites can be used as potential biomarkers for the diagnosis and monitoring of spleen-qi deficiency.

Effects of Scutellaria baicalensis Georgi. on intestinal flora in rats with spleen deficiency and damp-heat.

The effects of Scutellaria baicalensis Georgi. (S. baicalensis Georgi.) on the diversity of intestinal flora in rats with spleen deficiency and damp-heat was explored in the present study. 51 compounds in S. baicalensis Georgi. extract, including 37 flavonoids, 9 dihydroflavone, and 5 flavanols, were identified by ultra-high performance liquid chromatography-Q-Orbitrap-mass spectrometry(UPLC-Q-Orbitrap-MS/MS). Ethanol extract from Scutellariae Radix and fresh feces from rats with spleen deficiency and damp-heat were incubated in vitro for 48 h. At the phylum level, the ethanol extract noticeably increased the relative abundance of Firmicutes in the feces and effectively reduced those of Proteobacteria and Actinobacteria. At the genus level, the extract increased the relative abundance of the Lactobacillus and Bifidobacterium and reduced those of pathogenic bacteria, including Clostridium, Escherichia, Enterococcus, and Streptococcus. The results suggest that S. baicalensis Georgi. can regulate the structure and diversity of intestinal flora in rats with spleen deficiency and damp-heat and balance the body's metabolism.

Glycosylation-related molecular subtypes and risk score of hepatocellular carcinoma: Novel insights to clinical decision-making.

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer deaths worldwide, seriously affecting human community health and care. Emerging evidence has shown that aberrant glycosylation is associated with tumor progression and metastasis. However, the role of glycosylation-related genes in HCC has notbeen reported. Methods: Weighted gene coexpression network analysis and non-negative matrix factorization analysis were applied to identify functional modules and molecularm subtypes in HCC. The least absolute shrinkage and selection operator Cox regression was used to construct the glycosylation-related signature. The independent prognostic value of the risk model was confirmed and validated by systematic techniques, including principal component analysis, T-distributed random neighbor embedding analysis, Kaplan-Meier survival analysis, the ROC curve, multivariate Cox regression, the nomogram, and the calibration curve. The single-sample gene set enrichment analysis, gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were evaluated by the immune microenvironment and potential biological processes. The quantitative real-time polymerase chain reaction and immunohistochemistry analysis were used to verify the expression of five genes. Results: We identified the glycosylation-related genes with bioinformatics analysis to construct and validate a five-gene signature for the prognosis of HCC patients. Patients with HCC in the high-risk group had a worse prognosis. The risk score could be an independent factor and was associated with clinical features, such as the grade and stage. The nomogram exhibited an accurate score that included the risk score and clinical parameters. The infiltration levels of antitumor cells were upregulated in the low-risk group, including B_cells, Mast_cells, neutrophils, NK_cells, and T_helper_cells. Moreover, glycosylation was more sensitive to immunotherapy, and may play a critical role in the metabolic processes of HCC, such as bile acid metabolism and fatty acid metabolism. In addition, the five-gene messenger RNA (mRNA) and protein expression were overexpressed in HCC cells and tissues. Conclusions: The glycosylation-related signature is effective for prognostic recognition, immune efficacy evaluation, and substance metabolism in HCC, providing a novel insight for therapeutic target prediction and clinical decision-making.