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Riboflavin is an essential micronutrient for humans and must be obtained exogenously from foods or supplements. Numerous studies have suggested a major role of riboflavin in the prevention and treatment of various diseases. There are mainly three strategies for riboflavin synthesis, including total chemical synthesis, chemical semi-synthesis, and microbial fermentation, the latter being currently the most promising strategy. In recent years, flavinogenic microbes have attracted increasing attention. Fungi, including Eremothecium ashbyii and Ashbya gossypii, and bacteria, including Bacillus subtilis, Escherichia coli, and lactic acid bacteria, are ideal cell factories for riboflavin overproduction. Thus they are good candidates for enhancing the level of riboflavin in fermented foods or designing novel riboflavin bio-enriched foods with improved nutritional value and/or beneficial properties for human health. This review briefly describes the role of riboflavin in human health and the historical process of its industrial production, and then highlights riboflavin biosynthesis in bacteria and fungi, and finally summarizes the strategies for riboflavin overproduction based on both the optimization of fermentation conditions and the development of riboflavin-overproducing strains via chemical mutagenesis and metabolic engineering. Overall, this review provides an updated understanding of riboflavin biosynthesis and can promote the research and development of fermented food products rich in riboflavin.

BACKGROUND: Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. OBJECTIVE: To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. METHODS: Consecutive LT patients who underwent CEUS examinations at 1–4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. RESULTS: Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2–4 (all P

Transcription activator-like (TAL) effectors are major virulence factors secreted by the type III secretion systems of Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo), causing bacterial leaf streak and bacterial blight, respectively, in rice. However, the knowledge of Xoc TAL effector function in promoting bacterial virulence remains limited. Here, we isolated the highly virulent Xoc strain HGA4 from the outbreak region of Huanggang (Hubei, China), which contains four TAL effectors not found in the Chinese model strain RS105. Among these, Tal2b was selected for introduction into RS105, which resulted in a longer lesion length than that in the control. Tal2b directly binds to the promoter region of the gene and activates the expression of OsF3H03g , which encodes 2-oxoglutarate-dependent dioxygenase in rice. OsF3H03g negatively regulates salicylic acid (SA)-related defense by directly reducing SA, and it plays a positive role in susceptibility to both Xoc and Xoo in rice. OsF3H03g interacts with a uridine diphosphate-glycosyltransferase protein (OsUGT74H4), which positively regulates bacterial leaf streak susceptibility and may inactivate SA via glycosylation modification.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant neoplasms with high relapse and mortality rate. It is of great importance to identify novel and effective molecular markers to predict prognosis for the treatment of HCC. The Ewing sarcoma breakpoint region 1 (EWSR1) gene is well known to fuse with various partner genes and involved in promoting the development of multiple sarcomas, especially the Ewing sarcoma family of tumors. Nevertheless, seldom studies have focused on the role of EWSR1 in cancers of epithelial origin, let alone in HCC. In the current study, the transcriptional and clinical data of EWSR1 in HCC patients were obtained from TCGA and GEO databases, as well as 124 cases from the department of Pathology of Sichuan Jianyang People’s Hospital. Kaplan-Meier and Cox regression analysis were used to assess patient prognosis. EWSR1 mRNA levels were significantly upregulated in HCC tissues than in normal liver tissues (P

The abnormal expression of transgelin-2 (TAGLN2) is related to tumor occurrence and progression. However, the underlying molecular mechanism of TAGLN2 in human colorectal cancer (CRC) is still poorly understood. Compared with adjacent tissues, TAGLN2 is overexpressed in CRC tissues. Its expression level is negatively correlated with the overall survival rate of patients with CRC. In addition, knockdown of TAGLN2 inhibited the proliferation and invasion of CRC cells. We also showed that TAGLN2 could interact with CD44 to regulate the Notch-1 signaling pathway. Our findings indicate there is increased TAGLN2 expression in CRC and that it may serve as a promising potential therapeutic target for CRC.

von Willebrand Factor is a mechano-sensitive protein circulating in blood that mediates platelet adhesion to subendothelial collagen and platelet aggregation at high shear rates. Its hemostatic function and thrombogenic effect, as well as susceptibility to enzymatic cleavage, are regulated by a conformational change from a collapsed globular state to a stretched state. Therefore, it is essential to account for the conformation of the vWF multimers when modeling vWF-mediated thrombosis or vWF degradation. We introduce a continuum model of vWF unfolding that is developed within the framework of our multi-constituent model of platelet-mediated thrombosis. The model considers two interconvertible vWF species corresponding to the collapsed and stretched conformational states. vWF unfolding takes place via two regimes: tumbling in simple shear and strong unfolding in flows with dominant extensional component. These two regimes were demonstrated in a Couette flow between parallel plates and an extensional flow in a cross-slot geometry. The vWF unfolding model was then verified in several microfluidic systems designed for inducing high-shear vWF-mediated thrombosis and screening for von Willebrand Disease. The model predicted high concentration of stretched vWF in key regions where occlusive thrombosis was observed experimentally. Strong unfolding caused by the extensional flow was limited to the center axis or middle plane of the channels, whereas vWF unfolding near the channel walls relied upon the shear tumbling mechanism. The continuum model of vWF unfolding presented in this work can be employed in numerical simulations of vWF-mediated thrombosis or vWF degradation in complex geometries. However, extending the model to 3-D arbitrary flows and turbulent flows will pose considerable challenges.

In this study, we aimed to explore the antidiabetic effects of Lactobacillus rhamnosus LRa05 on glucose metabolism and gut microbiota in type 2 diabetes mellitus (T2DM) mice. Our data indicated that the fasting blood glucose levels were reduced by 53.5% after treatment with LRa05 at a dose of 109 CFU·day-1. Meanwhile, LRa05 attenuated insulin resistance, relieved hepatic oxidative stress, and alleviated metabolic lipopolysaccharide-related inflammation in T2DM mice. LRa05 promoted the expression of glucose transporter 2, while it inhibited the expression of glucagon receptor, glucose-6-phosphatase, cellular adenosine-3'-5'-cyclic monophosphate-dependent protein kinase, and phosphoenolpyruvate carboxykinase in diabetic mice. Meanwhile, LRa05 reshaped gut microbiota, resulting in increased short-chain fatty acid bacteria (Alloprevotella and Bacteroides) and decreased proinflammatory bacteria (Odoribacter and Mucispirillum). Thus, LRa05 may be used as a functional food supplement for modulating the disorder glucose metabolism and gut microbiota in T2DM.

The genus Bothynogria Borchmann, 1915 is reviewed, with a key to all known seven species provided in the present paper. A new species Bothynogria nigripennis sp. n., and two new record species for China, Bothynogria bicolor (Kollar et Redtenbacher, 1848) and Bothynogria meghalayana Merkl, 1990, are identified and redescribed. The habitus, male antennae and aedeagus are photographed and presented for all known species except for Bothynogria bhutanica. Ecological information and intraspecific variations are also provided for Bothynogria calcarata. www.zoobank.org/urn:lsid:zoobank.org:pub:5D8BFBCD-73AF-4AD4-94DE-3F24ECE31C1D .

Tartary buckwheat belongs to the family Polygonaceae, which is a traditionally edible and medicinal plant. Due to its various bioactive compounds, the consumption of Tartary buckwheat is correlated to a wide range of health benefits, and increasing attention has been paid to its potential as a functional food. This review summarizes the main bioactive compounds and important bioactivities and health benefits of Tartary buckwheat, emphasizing its protective effects on metabolic diseases and relevant molecular mechanisms. Tartary buckwheat contains a wide range of bioactive compounds, such as flavonoids, phenolic acids, triterpenoids, phenylpropanoid glycosides, bioactive polysaccharides, and bioactive proteins and peptides, as well as D-chiro-inositol and its derivatives. Consumption of Tartary buckwheat and Tartary buckwheat-enriched products is linked to multiple health benefits, e.g., antioxidant, anti-inflammatory, antihyperlipidemic, anticancer, antidiabetic, antiobesity, antihypertensive, and hepatoprotective activities. Especially, clinical studies indicate that Tartary buckwheat exhibits remarkable antidiabetic activities. Various tartary buckwheat -based foods presenting major health benefits as fat and blood glucose-lowering agents have been commercialized. Additionally, to address the safety concerns, i.e., allergic reactions, heavy metal and mycotoxin contaminations, the quality control standards for Tartary buckwheat and its products should be drafted and completed in the future.

In this study, the effect of coelomic fluid isolates (CFIs) from sea cucumbers (Stichopus japonicus) on autolysis of minced muscle tissue of S. japonicus was investigated. The coelomic fluid of S. japonicus at the concentration of 90% showed suppression effects on activities of papain and trypsin with inhibitory rate of 26.6% and 40.4%, respectively. Moreover, the effect of CFIs on autolysis of minced muscle tissue from S. japonicus was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and trichloroacetic acid (TCA)-soluble oligopeptide assay. CFIs exhibited significantly inhibitory effect on autolytic muscle mince samples with inhibitory rate at 56.2–87.2%. Both heat and proteinase treatments did not influence the inhibitory effect of CFIs on autolysis of minced muscle tissue from S. japonicus. These results suggest that the non-protein and thermally stable substances contribute to the inhibitory effect of CFIs, which can be used to improve sea cucumber quality.

Background The Northeast Plain of China, which is an important region for the production of high grain quality rice in China. However, the grain quality of the rice produced varies across this region, even for the same cultivar. Objective In order to explore the meteorological factors that have the greatest influence on quality and the transcriptional level differences between different cultivars and different locations at grain filling stage. Methods We grew eight rice cultivars in three locations in Northeast China during two growing seasons (2017 and 2018). We recorded meteorological conditions, including air temperature, air temperature range, and photosynthetically active radiation (PAR) during the grain-filling stage of each cultivar, and analyzed the grain quality of those eight cultivars. Results Across all eight cultivars, meteorological factors had a stronger effect on eating quality than genotype, while genotype had a stronger effect on milling quality. Of the three environmental factors assessed, PAR was significantly correlated with the most grain quality traits. Using RNA-sequencing analysis, we identified 573 environment-specific DEGs (Differentially Expressed Genes), and 119 genotype-specific DEGs; 11 DEGs were responsive to genotype × environment interactions. These DEGs were involved in many key metabolic processes. Conclusion Our results indicated that interactions among environmental factors, especially PAR, affected rice quality in Northeast China. Further analyses of the DEGs identified herein may provide useful information for future breeding programs aiming to develop high grain quality rice varieties suitable for cultivation across Northeast China.

Objectives. Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation and remodeling. Macrophage polarization is associated with inflammation and tissue remodeling, as well as immunity. Therefore, this study attempts to investigate the diagnostic value and regulatory mechanism of macrophage polarization-related genes for COPD by bioinformatics analysis and to provide a new theoretical basis for experimental research. Methods. The raw gene expression profile dataset (GSE124180) was collected from the Gene Expression Omnibus (GEO) database. Next, a weighted gene coexpression network analysis (WGCNA) was conducted to screen macrophage polarization-related genes. The differentially expressed genes (DEGs) between the COPD and normal samples were generated using DESeq2 v3.11 and overlapped with the macrophage polarization-related genes. Moreover, functional annotations of overlapped genes were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resource. The immune-related genes were selected, and their correlation with the differential immune cells was analyzed by Pearson. Finally, receiver operating characteristic (ROC) curves were used to verify the diagnostic value of genes. Results. A total of 4922 coexpressed genes related to macrophage polarization were overlapped with the 203 DEGs between the COPD and normal samples, obtaining 25 genes related to COPD and macrophage polarization. GEM, S100B, and GZMA of them participated in the immune response, which were considered the candidate biomarkers. GEM and S100B were significantly correlated with marker genes of B cells which had a significant difference between the COPD and normal samples. Moreover, GEM was highly associated with the genes in the PI3K/Akt/GSK3β signaling pathway, regulation of actin cytoskeleton, and calcium signaling pathway based on a Pearson correlation analysis of the candidate genes and the genes in the B cell receptor signaling pathway. PPI network analysis also indicated that GEM might participate in the regulation of the PI3K/Akt/GSK3β signaling pathway. The ROC curve showed that GEM possessed an excellent accuracy in distinguishing COPD from normal samples. Conclusions. The data provide a transcriptome-based evidence that GEM is related to COPD and macrophage polarization likely contributes to COPD diagnosis. At the same time, it is hoped that in-depth functional mining can provide new ideas for exploring the COPD pathogenesis.

In recent years, with the global environmental deterioration and air pollution, the incidence of bronchitis has increased year by year, and the sales of anti-bronchitis drugs are growing rapidly, mainly due to the long treatment cycle and the difficulty of curing. Developing available traditional Chinese medicines with significant curative effect against bronchitis would be a promising strategy; for instance, Ginkgo seeds, as the fruit of natural plant ginkgo, has been used in ancient times to cure coughs. However, the detailed mechanism of curing cough has not been shown yet. Investigate the mechanism of Ginkgo seeds in the treatment of bronchitis by establishing a series of molecular networks including active ingredients-targets, proteins interactions, biological functions, pathway, and biological processes of targets. In this study, the main active ingredients of Ginkgo seeds and the potential targets related to bronchitis could be obtained by retrieving corresponding database. The molecular docking study between active molecules and protein targets was performed by Glide 6.6. Subsequently, a total of forty potential targets were manually selected. Based on this, the ingredients-target network was constructed using Cytoscape software, as well as proteins interactions network combing with the String database. Finally, the molecular biological function, metabolic pathway, and biological processes of these forty targets were analyzed by Clue GO plug-in. The results indicated that these protein targets were closely related to lipid transport, positive regulation of DNA replication, cAMP metabolic pathway, and other processes, which played a vital role in the treatment of bronchitis by mediating interleukin 17, fluid shear stress and atherosclerosis, asthma, renin secretion, p53, and other signaling pathways. Among these targets, the two protein ALB (Albumin) and DHRS2 (Dehydrogenase 2) can interact with compounds more frequently, and the top three compounds ranked by the docking scores were amentoflavone, (+)-catechin-5-O-glucoside, and liquiritin, implying that these compounds might be used for the treatment of bronchitis. It is obvious that the pharmacological effect of Ginkgo seeds on bronchitis displayed a characteristic of multi-components, multi-targets, and multi-pathways. Nevertheless, the two protein targets and three compounds derived from Ginkgo seeds could be further used for the explanation for Ginkgo seeds in curing bronchitis. This research can provide a scientific basis for studying on the anti-bronchitis mechanism of Ginkgo seeds.

Givosiran is an N-acetylgalactosamine-conjugated RNA interference therapeutic that targets 5'-aminolevulinate synthase 1 mRNA in the liver and is currently marketed for the treatment of acute hepatic porphyria. Herein, nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion properties of givosiran were characterized. Givosiran was completely absorbed after subcutaneous administration with relatively short plasma elimination half-life (t1/2; less than 4 hours). Plasma exposure increased approximately dose proportionally with no accumulation after repeat doses. Plasma protein binding was concentration dependent across all species tested and was around 90% at clinically relevant concentration in human. Givosiran predominantly distributed to the liver by asialoglycoprotein receptor-mediated uptake, and the t1/2 in the liver was significantly longer (∼1 week). Givosiran was metabolized by nucleases, not cytochrome P450 (P450) isozymes, across species with no human unique metabolites. Givosiran metabolized to form one primary active metabolite with the loss of one nucleotide from the 3' end of antisense strand, AS(N-1)3' givosiran, which was equipotent to givosiran. Renal and fecal excretion were minor routes of elimination of givosiran as approximately 10% and 16% of the dose was recovered intact in excreta of rats and monkeys, respectively. Givosiran is not a substrate, inhibitor, or inducer of P450 isozymes, and it is not a substrate or inhibitor of uptake and most efflux transporters. Thus, givosiran has a low potential of mediating drug-drug interactions involving P450 isozymes and drug transporters. SIGNIFICANCE STATEMENT: Nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Givosiran shows similar pharmacokinetics and ADME properties across rats and monkeys in vivo and across human and animal matrices in vitro. Subcutaneous administration results in adequate exposure of givosiran to the target organ (liver). These studies support the interpretation of toxicology studies, help characterize the disposition of givosiran in humans, and support the clinical use of givosiran for the treatment of acute hepatic porphyria.

BackgroundCold stress is the main abiotic stress in rice, which seriously affects the growth and yield of rice. Identification of cold tolerance genes is of great significance for rice to solve these problems. GATA-family transcription factors involve diverse biological functions, however, their role in cold tolerance in rice remains unclear.ResultsIn this study, a GATA-type zinc finger transcription factorOsGATA16, which can improve cold tolerance, was isolated and characterized from rice. OsGATA16 belongs to OsGATA subfamily-II and contains 11 putative phosphorylation sites, a nuclear localization signal (NLS), and other several conserved domains.OsGATA16was expressed in all plant tissues, with the strongest in panicles. It was induced by cold and ABA treatments, but was repressed by drought, cytokinin and JA, and acted as a transcriptional suppressor in the nucleus. Overexpression ofOsGATA16improves cold tolerance of rice at seedling stage. Under cold stress treatments, the transcription of four cold-related genesOsWRKY45–1,OsSRFP1,OsCYL4, andOsMYB30was repressed inOsGATA16-overexpressing (OE) rice compared with wild-type (WT). Interestingly, OsGATA16 bound to the promoter ofOsWRKY45–1and repressed its expression.In addition, haplotype analysis showed thatOsGATA16polarized between the two major rice subspeciesjaponicaandindica, and had a non-synonymous SNP8 (336G) associated with cold tolerance.ConclusionOsGATA16 is a GATA transcription factor, which improves cold tolerance at seedling stage in rice. It acts as a positive regulator of cold tolerance by repressing some cold-related genes such asOsWRKY45–1,OsSRFP1,OsCYL4andOsMYB30. Additionally, OsGATA16 has a non-synonymous SNP8 (336G) associated with cold tolerance on CDS region. This study provides a theoretical basis for elucidating the mechanism of cold tolerance in rice and new germplasm resources for rice breeding.

This study evaluated the gel and microstructure properties of scallop (Patinopecten yessoensis) male gonads hydrolysates (SMGHs) combined with xanthan gum (XG). SMGHs/XG hydrogel matrix properties and structures were elucidated via different analysis tools such as rheometry, LF-NMR, FTIR, AFM, and Cryo-SEM. The addition of XG significantly improved the rheological properties of SMGHs, as indicated by 3.1-fold G' and 1.3-fold melting temperature with increasing the XG dose to 5.6 mg/ml. The corresponding decrease in the T23 relaxation time from 450.3 to 365.6 ms also signified the strong binding between SMGHs and XG. SMGHs/XG also had a higher proton density (T1 and T2 weighted images) due to the higher bound and free water content of the hybrid gel systems, respectively. Additionally, the blueshift in the amide I and II bands in SMGHs/XG further indicated stronger electrostatic interactions between SMGHs and XG. Such scenarios resulted in a well-distributed and compact network with a rougher surface of SMGHs/XG in comparison to pure SMGHs and XG, as assessed by AFM and SEM. These results suggest that SMGHs/XG gel could be a potential hybrid gel applied in the food industry. PRACTICAL APPLICATION: Scallop (Patinopecten yessoensis) male gonads are edible, but are usually discarded during processing of scallop adductor. Because of its rich nutrition and gelation properties, scallop male gonads have a potential role in developing marine source-protein as a functional food base. The SMGHs/XG binary gel would be potentially applied in delivery system in food and biological fields. Further study is undergoing to apply SMGHs/XG binary gel to embed bioactive compounds, such as curcumin and β-carotene.

Antituberculosis drug-induced liver injury (ATDILI) has received increasing attention globally, which may limit the effectiveness of the anti-tuberculosis (anti-TB) treatment. Many host genetic determinants of ATDILI have been identified, recently. Whereas, little knowledge about the association between aldehyde dehydrogenase 1 family member A1 (ALDH1A1) polymorphisms and ATDILI is currently available, so we investigated the association between their variants and the susceptibility to ATDILI. A total of 747 TB patients treated by first-line antituberculosis drugs were prospectively enrolled at West China Hospital. Genomic DNA was extracted from the peripheral blood sample of each patient and 7 single-nucleotide polymorphisms (SNPs) of ALDH1A1 gene were screened and genotyped with a custom-designed 2x48-plex SNP Scan TM Kit. The patients were followed up monthly to monitor the development of ATDILI. The C allele and the CA genotype of rs7852860 was significantly associated with an elevated risk for ATDILI (p = 0.006 and 0.005, respectively), which was consistent with the results in the dominant and additive models. No allele, genotype or genetic model of the other 6 SNPs (rs3764435, rs348471, rs63319, rs610529, rs7027604, rs8187876) were found to be associated with the susceptibility to ATDILI. Our findings firstly demonstate that rs7852860 variants in ALDH1A1 gene is associated with susceptibility to ATDILI in the Chinese Han population. Validation studies with larger sample sizes and other ethnic groups are needed to confirm our findings. This article is protected by copyright. All rights reserved.

Echinococcus shiquicus is currently limited to the Qinghai–Tibet plateau, a large mountainous region in China. Although the zoonotic potential remains unknown, progress is being made on the distribution and intermediate host range. In this study, we report E. shiquicus within Gansu and Qinghai provinces in regions located not only around the central areas but also the southeast edge of the plateau and describe their genetic relationship with previous isolates from the plateau. From 1879 plateau pikas examined, 2.39% (95% CI 1.79–3.18) were infected with E. shiquicus. The highest prevalence of 10.26% (4.06–23.58) was recorded in Makehe town, Qinghai province. Overall the prevalence was marginally higher in Qinghai (2.5%, CI 1.82–3.43) than in Gansu (2%, CI 1.02–3.89). The cox1 and nad1 genes demonstrated high and low haplotype and nucleotide diversities, respectively. The median-joining network constructed by the cox1–nad1 gene sequences demonstrated a star-like configuration with a median vector (unsampled haplotype) occupying the centre of the network. No peculiar distinction or common haplotype was observed in isolates originating from the different provinces. The presence of E. shiquicus in regions of the southeast and northeast edges of the Qinghai–Tibet plateau and high genetic variation warrants more investigation into the haplotype distribution and genetic polymorphism by exploring more informative DNA regions of the mitochondrial genome to provide epidemiologically useful insight into the population structure of E. shiquicus across the plateau and its axis.

This study was designed to investigate the relationship between Delta-like 1 homolog (DLK1) polymorphisms and the occurrence of antituberculosis drug-induced hepatotoxicity (ATDH) in the Western Ch...

In order to study Fe3O4-Polypyrrole (Fe3O4-PPy) core-shell nanocomposite in the diagnosis of tumor markers in the diseased gastric tissues of early cancer patients, a total of 160 cases of patients, who were confirmed as early gastric cancer by gastroscopy or postoperative pathology at a designated hospital of the study from December 2014 to December 2018, were selected as research objects and were divided into two groups of observation and control group with 80 cases in each group. For each patient in the two groups, two pieces of diseased gastric tissue were firstly taken through gastroscopy; then the observation group applied Fe3O4-PPy with the particle diameter of 150-350 nm as carrier to detect the contents of carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4) in the diseased gastric tissue, while the control group directly detected the contents of corresponding tumor markers; after the detections, the sensitivity, specificity and diagnostic efficiency of each marker in the two groups of patients were calculated, and receiver operating characteristics (ROC) curves with the areas under the curves (AUC) were drawn to analyze the correlation between the level of Fe3O4-PPy and the detection efficiency of gastric cancer markers. The results show that the detection sensitivity (82.17%, 80.32%, 79.48%, 84.63%, and 85.66%) and specificity (76.75%, 79.66%, 81.07%, 83.47%, and 85.24%) of CA19-9, AFP, CA242, CEA, and CA72-4 in the tumor tissue of patients in observation group for the diagnosis of early gastric cancer are higherthan the sensitivity (78.66%, 79.25%, 76.18%, 82.11%, and 83.45%) and specificity (74.37%, 76.94%, 77.24%, 81.22%, and 81.59%) of that in control group with statistically significant differences (P < 0.05). Therefore, it is believed that the Fe3O4-PPy is of great significance for the detection of early gastric tumor markers in the tissues of patients with early gastric cancer, and has certain value for the auxiliary diagnosis of early gastric cancer and the observation of therapeutic effects. This study results provide a reference for the further researches of Fe3O4-PPy in the diagnosis of tumor markers in patients with early gastric cancer.

Microbial secondary metabolites have long been considered as potential sources of lead compounds for medicinal use due to their rich chemical diversity and extensive biological activities. However, many biosynthetic gene clusters remain silent under traditional laboratory culture conditions, resulting in repeated isolation of a large number of known compounds. The co-culture strategy simulates the complex ecological environment of microbial life by using an ecology-driven method to activate silent gene clusters of microorganisms and tap their metabolic potential to obtain novel bioactive secondary metabolites. In this review, representative studies from 2017 to 2020 on the discovery of novel bioactive natural products from co-cultured microorganisms are summarized. A series of natural products with diverse and novel structures have been discovered successfully by co-culture strategies, including fungus–fungus, fungus–bacterium, and bacterium–bacterium co-culture approaches. These novel compounds exhibited various bioactivities including extensive antimicrobial activities and potential cytotoxic activities, especially when it came to disparate marine-derived species and cross-species of marine strains and terrestrial strains. It could be concluded that co-culture can be an effective strategy to tap the metabolic potential of microorganisms, particularly for marine-derived species, thus providing diverse molecules for the discovery of lead compounds and drug candidates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42995-020-00077-5) contains supplementary material, which is available to authorized users.

Context Salidroside, a compound extracted from Rhodiola rosea L. (Crassulaceae), possesses many beneficial pathological effects. Objective To explore the effect of salidroside on ventilator-induced lung endothelial dysfunction in vivo and in vitro. Materials and methods In vivo, male ICR mice were divided into sham, ventilation, salidroside, and ventilation plus salidroside groups. The mice were ventilated for 4 h, salidroside (50 mg/kg) was administrated intraperitoneally before ventilation, dexamethasone (Dex) (5 mg/kg) was used as a positive control. In vitro, mouse lung vascular endothelial cells (MLVECs) were treated with salidroside, MMP-9 siRNA, and BAY11-7082 (10 μM), and then exposed to cyclic stretch for 4 h. Afterward, lung tissues and MLVECs were collected for further analysis. Results Salidroside pre-treatment significantly reversed the expression of vascular endothelial cadherin (VE-cadherin) and zonula occluden-1 (ZO-1) proteins in cyclic stretch-treated MLVECs (0.46 ± 0.09 vs. 0.80 ± 0.14, 0.49 ± 0.05 vs. 0.88 ± 0.08) and ventilated lung tissues (0.56 ± 0.06 vs. 0.83 ± 0.46, 0.49 ± 0.08 vs. 0.80 ± 0.12). The results further indicated that salidroside inhibited the expression of matrix metalloproteinase-9 (MMP-9), whereas knockdown of its expression restored the expression levels of VE-cadherin (0.37 ± 0.08 vs. 0.85 ± 0.74) and ZO-1 (0.48 ± 0.08 vs. 0.81 ± 0.11) in stretched MLVECs. Meanwhile, salidroside inhibited the NF-κB signalling pathway and alleviated lung injury. Conclusions Salidroside protected against stretch-induced endothelial barrier function, improving lung injury after ventilation. Thus, salidroside may be a promising therapeutic agent for patients with MV-induced lung injury.

Previous study suggests that Lactobacillus casei exhibits antihyperglycemic activity, however, the molecular mechanism of this has yet to be elucidated. Here, the anti-diabetic effects and underlying mechanisms of Lactobacillus casei LC89 are investigated in type 2 diabetes mellitus (T2DM) mice, which was induced by a high-fat diet (HFD) with streptozotocin (100 mg per kg BW). The results show that LC89 at a dose of 109 CFU day−1 decreases fasting blood glucose (FBG) and insulin levels by 35.12% and 28.37%, respectively, compared to the diabetes control (DC) group. Moreover, LC89 treatment improved the insulin resistance index (HOMA-IR), serum lipid profiles and inflammation cytokines. The real-time polymerase chain reaction indicated that LC89 markedly downregulates the mRNA expression of hepatic glucagon (GCG), glucagon receptor (GCGR), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Meanwhile, LC89 significantly decreases the abundance of Odoribacter, but increases the Alloprevotella, Bacteroides, Parabacteroides and Ruminococcus content. Therefore, LC89 plays a positive role in alleviating T2DM by regulating gut microbiota and glucagon signal pathway-related genes, and it may be a beneficial dietary supplement to regulate glucose metabolism in T2DM.

In this paper, some cationic dipeptides from scallop (Patinopecten yessoensis) male gonads (SMGs), which can synergistically gel with ι-carrageenan (ι-C), were screened by the in silico approach. Fourteen protein sequences of SMGs were obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nano liquid chromatography-mass spectrometry/mass spectrometry (nanoLC-MS/MS) analysis and were then hydrolyzed via in silico simulation. A total of 414 sequences were obtained with 56 duplicates, half of which were positively charged at pH 7. Among the cation sequences, 171 had good water solubility, including two amino acids (Lys and Arg). The molecular weight analysis of the cationic water-soluble sequences showed that 0.2–0.3 kDa accounted for the highest proportion. Based on the obvious synergistic effect of Lys and ι-C, 11 Lys-containing dipeptides, including Ser-Lys (SK), Thr-Lys (TK), Trp-Lys (WK), Ala-Lys (AK), Leu-Lys (LK), Gly-Lys (GK), Val-Lys (VK), Cys-Lys (CK), Asn-Lys (NK), Phe-Lys (FK), and Met-Lys (MK), were finally screened out to study gelation with ι-C. It was found that the dipeptides/ι-C formed firm gels except WK/ι-C. The values of the storage modulus (G′) of 11 dipeptides/ι-C were investigated by a rheometer. The G′ of 8 dipeptides/ι-C was higher than 1000 Pa. These results indicated that the in silico-screened dipeptides from SMGs can form composite gels with ι-C, which can be used for the design and development of functional hydrogels.

The present study investigated the induction of the glycolysis product methylglyoxal by trimethylamine (TMA) lyase synthesis in the intestinal microbiota and investigated the intervention mechanism of the effects of dietary fiber on methylglyoxal formation. Intestinal digesta samples, collected from the ceca of mice fed with choline-rich and fiber-supplemented diets, were incubated in an anaerobic environment at 37 °C and pH 7.0 with choline, glycine, and methylglyoxal as inductive factors. The differences between the gut microbiota and its metagenomic and metabonomics profiles were determined using 16S rRNA gene sequencing analysis. The results elucidated that the different dietary interventions could induce differences in the composition of the microbiota, gene expression profiles associated with glycine metabolism, and glycolysis. As compared to the gut microbiota of choline-diet fed mice, fiber supplementation effectively altered the composition of the microbiota and inhibited the genes involved in choline metabolism, glycine and methylglyoxal accumulation, and TMA lyase expression, and improved the methylglyoxal utilization by regulating the pathway related to pyruvate production. However, the intervention of exogenous methylglyoxal significantly decreased these effects. These findings successfully revealed the correlations between the TMA lyase expression and glycine level, as well as the inhibitory effects of dietary fiber on the glycine level, thereby highlighting the role of common glycolytic metabolites as a potential target for TMA production.

The aim of this study was to well understand the dynamic changes of physicochemical properties of polysaccharides from loquat leaves (LLP) during in vitro simulated saliva-gastrointestinal digestion and fecal fermentation and its related impacts on human gut microbiota. Results showed that the contents of reducing sugar of LLP slightly increased during the gastrointestinal digestion, and its molecular weight also slightly decreased, suggesting that LLP could be slightly degraded under the gastrointestinal digestion conditions. Moreover, during the fecal fermentation, the molecular weight of the indigestible LLP (LLP-I) significantly decreased, and the molar ratio of constituent monosaccharides of LLP-I, such as glucuronic acid, galacturonic acid, galactose, and arabinose, significantly changed, indicating that LLP-I could be degraded and consumed by human gut microbiota. Indeed, some beneficial bacteria such as Megasphaera, Megamonas, Bifidobacterium, Phascolarctobacterium, and Desulfovibrio significantly increased, suggesting that LLP-I could change the composition and abundance of gut microbiota. LLP-I could also promote the production of health-promoting short chain fatty acids. Results from this study are benefical to well understand the in vitro digestion and fecal fermentation behaviors of LLP, and LLP can be developed as a potential prebiotic in the functional food industry.

Rationale: Endoglin, also known as CD105, is a homo-dimeric membrane glycoprotein required for angiogenesis and serves as a marker for cancer vasculature. In this study, we constructed a bispecific T-cell engager (BiTE) antibody that targets human endoglin and CD3 (hEND-CD3/BiTE). We examined BiTE binding to endoglin-expressing cells and its effects on the cytolytic activity of T cells and cancer development. Methods: The in vitro effects of hEND-CD3/BiTE, including binding to target cells, T-cell activation, proliferation, and cytotoxicity, were examined in endoglin-expressing 293T cells, human umbilical vascular endothelial cells, tumor-derived endothelial cells, and CD3+ T cells. An in vivo xenograft tumor model was established using A549 human lung cancer cells. The therapeutic efficacy of hEND-CD3/BiTE was assessed by monitoring tumor growth, angiogenesis, and mouse survival. Results: hEND-CD3/BiTE specifically bound to endoglin-expressing cells and CD3+ T cells in vitro and stimulated T-cell activation, proliferation, and Th1 cytokine secretion, and promoted T-cell-mediated cytolysis of endoglin-expressing cells. The hEND-CD3/BiTE in vivo caused minimal toxicity to major organs, reduced tumor neoangiogenesis, inhibited tumor growth, and significantly improved mouse survival. Conclusions: Our study demonstrated the therapeutic potential of hEND-CD3/BiTE and provided a novel approach to clinical cancer treatment.

Cadherin is an important cell-cell adhesion molecule, which mediates intercellular adhesion through calcium dependent affinity interaction. Cadherin-11 (CDH11, OB-cadherin) is a member of cadherin family, and its gene is situated on chromosome 16q22.1. Increasing lines of researches have proved that CDH11 plays important roles in the occurrence and development of a lot of diseases, such as tumors, arthritis and so on. CDH11 often leads to promoter methylation inactivation, which can induce cancer cell apoptosis, suppress cell motility and invasion, and can inhibit cancer through Wnt/β-catenin, AKT/Rho A and NF-κB signaling pathways. This review focused on the current knowledge of CDH11, including its function and mechanism in different diseases. In this article, we aimed to have a more comprehensive and in-depth understanding of CDH11 and to provide new ideas for the treatment of some diseases.

ShLysG is a novel g-type lysozyme isolated from Hippocampus abdominalis in 2016. However, its antibacterial, antioxidant and anti-inflammatory properties have not been investigated. In this study, a recombinant ShLysG (rShLysG) fused with a 6×His tag was produced in Escherichia coli with barely any hemolytic activity or cytotoxicity. It exhibited a broad antimicrobial spectrum against gram-positive and gram-negative bacteria with minimum inhibitory concentration (MIC) values between 20 and 60 μg/mL. The bioactivity of rShLysG was stable in high temperature and extreme acid base conditions. In addition, rShLysG was resistant to papain and pepsin, and it showed a concentration-dependent antioxidant activity. By inhibiting the phosphorylation of NF-κB, the inflammatory cytokines expression level, including TNF-α, IL-6, and IL-8 in RAW264.7 macrophage cells induced by LPS were decreased. Taken together, rShLysG is a promising substitute to antibiotics as an antimicrobial and immunoregulatory pharmaceutical peptide for clinical use.

A wheat germ polysaccharide (WGP-1) was isolated from wheat germ through hot-water (pH = 7.3) extraction and further fractionated by anion-exchange column using DEAE-52 cellulose column and purified by gel-permeation chromatography using Sephacryl S-500 column. WGP-1 was mainly consisted with rhamnose, arabinose, xylose, mannose, galactose and glucose, and linked with 1→, 1 → 2, 1 → 4, 1 → 3 and 1 → 6 glucosidic bands. The present study was designed to evaluate the antioxidant activities of WGP-1 in oleic acid (OA)-induced HepG2 cell model with its related mechanisms. Results showed that WGP-1 remarkably elevated the expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and total antioxidant capacity (T-AOC), and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in OA-treated cell. WGP-1 was found to promote the expression of PI3K, the phosphorylation of AKT and the translocation of Nrf2, further increased the expression of HO-1 in OA-induced cells. These results demonstrate again that WGP-1 can effectively improve OA-induced oxidative damage, probably by up-regulating of PI3K expression, Nrf2 translocation, and AKT phosphorylation.

Iron walnut, Juglans sigillata Dode, restricted to southwestern China, has its centre of distribution in Yunnan Province which has a varied climate, geography and rich plant diversity. Yunnan contains abundant J. sigillata germplasm. In this study, a provincial-scale set of walnut germplasm resources (14 populations comprising 1122 individuals) was evaluated for genetic diversity based on 20 simple sequence repeat (SSR) loci. The number of SSR alleles per locus ranged from 7 to 27, with an average of 17.55. Mean allelic richness and mean private allelic richness ranged from 3.40 to 4.62 and 0.11 to 0.36, with average of 3.93 and 0.30, respectively. Expected heterozygosity (He) varied from 0.26 to 0.78, with an average of 0.57. Polymorphism information content ranged from 0.22 to 0.79, with an average of 0.57. Genetic differentiation (FST) was 0.05, indicating that only 5% of total genetic variability was inter-populational, a finding supported by an analysis of molecular variance and STRUCTURE analysis. Relatively high gene flow (Nm = 6.70) was observed between populations. A unweighted pair-group method with arithmetic analysis classified the 14 populations into two major groups. Mantel testing uncovered a significant correlation between geographic distance and genetic distance (r = 0.33, P = 0.04). Overall, the research revealed a moderately high level of genetic diversity in the germplasm and low genetic differentiation among populations, which showed great potential for further development and exploitation of this resource.

Objective Glioma is one of the most common central nervous system malignant tumors, accounting for 45%-60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. Materials and methods Microarray is used to identify the lncRNAs that are differentially expressed in glioma. The expression of long non-coding RNA (lncRNA) ROR1-AS1 and miR-4686 was detected by qRT-PCR. Exosomes were isolated from the supernatant of normal and cancerous cells, and TEM was used for exosomes identification. MTT assay, wound healing assay, transwell assay, and colony formation assay were used to detect the exo-ROR1-AS1 function on proliferation, migration, and invasion in glioma cells. Luciferase assay and RIP assay were used to identify the relationship between lncRNA ROR1-AS1 and miR-4686. The effect of exo-ROR1-AS1 on tumorigenesis of glioma was confirmed by the xenograft nude mice model. Results ROR1-AS1 was up-regulated in glioma tissues, and the high expression of ROR1-AS1 indicated a poor prognosis in glioma patients. Interestingly, ROR1-AS1 was packaged into exosomes and derived from tumor cells. Functional analysis showed exo-ROR1-AS1 promoted the progression of glioma cell lines SHG44 and U251. Furthermore, ROR1-AS1 acted as a sponge of miR-4686 and inhibited its expression. Functionally, forced expression of miR-4686 removed the promoted effects of lncRNA ROR1-AS1 on glioma development. In vivo tumorigenesis experiments showed that exo-ROR1-AS1 promoted glioma development via miR-4686 axis. Conclusion Our study suggested tumor cells derived exo-ROR1-AS1 promoted glioma progression by inhibiting miR-4686, which might be a potential therapeutic target for glioma clinical treatment.

Pertya multiflora (Asteraceae) is a rare wild plant species narrowly distributed in Zhejiang province, China. In our present study, we assembled its complete chloroplast genome using high-throughput sequencing data. The results indicated that the whole chloroplast genome of P. multiflora was 153,396 bp in length. Its large single copy, small single copy, and inverted region sequences were 84,575 bp, 18,451 bp, and 25,185 bp. The P. multiflora chloroplast genome was composed of 134 genes, including 87 protein-coding genes, 37 tRNA genes, eight rRNA genes, and two pseudogenes. Phylogenetic analysis results showed that P. multiflora was grouped with Gerbera jamesonii, with 100% bootstrap support.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Sweet tea (Lithocarpus polystachyus Rehd.) has been consumed as herbal tea to prevent and manage diabetes for a long time. Recent studies indicate that sweet tea is rich in a variety of bioactive compounds, especially a class of nonclassical flavonoids, dihydrochalcones. In order to provide a better understanding of sweet tea and its main dihydrochalcones on human health, this review mainly summarizes related literature in the recent ten years, with the potential molecular mechanisms emphatically discussed. Phlorizin, phloretin, and trilobatin, three natural sweeteners, are the main dihydrochalcones in sweet tea. In addition, sweet tea and its dihydrochalcones exhibit plenty of health benefits, such as antioxidant, anti-inflammatory, antimicrobial, cardioprotective, hepatoprotective, antidiabetic, and anticancer effects, which are associated with the regulation of different molecular targets and signaling pathways. Therefore, sweet tea, as a rare natural source of dihydrochalcones, can be processed and developed into nutraceuticals or functional foods, with the potential application in the prevention and management of certain chronic diseases.

Sea urchin Mesocentrotus nudus, Glyptocidaris crenularis, and Strongylocentrotus intermedius gonad protein isolates (mnGPIs, gcGPIs, and siGPIs) were extracted by isoelectric solubilization/precipitation (ISP) from the defatted gonads, and their functional properties were compared. Sodium dodecyl sulfate polyacrylamide gel electrophoresis results showed the similar protein pattern between each protein isolate and defatted gonad, indicating the high efficiency of ISP processing for protein recovery. Amino acid profileconfirmed that the mnGPIs and siGPIs could be potential sources of essential amino acid in nature. As regard to functional properties, mnGPIs showed higher water- and oil- holding capacities followed bysiGPIs and gcGPIs and all protein isolates presented great foaming property. As for emulsifying activity index (EAI), mnGPIs, gcGPIs, and siGPIs showed the minimum solubility and EAI at pH 5, 3, and 4, respectively, and behaved a pH-dependent manner. The gcGPIs revealed the highest EAI from pH 6 to 8 among the samples. In addition, circular dichroism showed increased content of β-sheet at the expense of α-helix and β-turn, suggesting the structure denaturation of the protein isolates. Indeed, no statistical difference was observed between secondary structure of mnGPIs and siGPIs. Moreover, ISP processing increased free sulfhydryl content of sea urchin protein isolates, but no difference was observed among the samples. Furthermore, siGPIs revealed the highest amount of total sulfhydryl and disulfide bonds, whereas both defatted gonads and protein isolates from G. crenularis presented the maximum surface hydrophobicity. These results suggest that gonad protein isolates from three species of sea urchin possess various functionalities and therefore can be potentially applied in food system. PRACTICAL APPLICATION: Sea urchin M. nudus, G. crenularis, and S. intermedius gonads are edible, whereas the functional properties of protein isolates from sea urchin gonad remain unknown. In this case, the extraction and comparison of three species of sea urchin gonad protein isolates will not only confirm functional properties but also screen food ingredients with suitable functions. In this study, functionalities of protein isolates derived from M. nudus, G. crenularis, and S. intermedius gonads would provide potential application in bakery food and meat products or as emulsifier candidates in food system.

We found that a rice NADPH oxidase gene OsRbohB contributes drought tolerance and its functions are involved in the interaction of the OsRbohB-mediated ROS production and ABA signaling. The plasma membrane NADPH oxidases, also known as respiratory burst oxidase homologs, are the key producers of ROS under both normal and stress conditions in plants. However, their functions in rice development and stress tolerance are still under investigation. Here, we found that a rice NADPH oxidase gene OsRbohB, also named OsNOX1, is expressed in all tissues examined throughout the development stages with higher transcripts in leaves. The transcriptional expression of OsRbohB is also strongly stimulated by dehydration, salt and several phytohormonal treatments. Compared with wide-type and the OsRbohB-overexpressing transgenic plants, osrbohB, a Tos17 insertion knockout mutant of OsRbohB, shows lower ROS production, abscisic acid (ABA) content and transcripts of a series of stress-related genes. The osrbohB mutant also exhibits lower seed germination rate, organ size and thousand seed weight, but higher stomatal aperture and sensitivity to drought. Moreover, a number of genes involved in plant development, stress response, transcriptional regulation, and particularly ABA signaling are differentially expressed in osrbohB plants under both normal growth and drought conditions. All these results suggest the roles of OsRbohB in drought tolerance of rice, which probably performed through the interaction of the OsRbohB-mediated ROS production and ABA signaling.

Objective: Cold stress induces oxidative damage and impairs energy status of broilers. N-acetylcysteine (NAC) exhibits antioxidant properties and modulates energy metabolism of animals. This study was conducted to investigate the effects of NAC on energy status and antioxidant capacity of heart and liver in the cold-stressed broilers.Methods: The experiment consisted of 4 treatments in a 2×2 factorial arrangement with two diets (basal diet or plus 0.1% NAC) and two ambient temperatures (thermoneutral [conventional ambient temperature] or cold stress [10°C±1°C during days 15 to 42]).Results: No ascites were seen in cold-stressed broilers. NAC did not attenuate the impaired growth performance of stressed birds. However, NAC decreased plasma asparagine but increased aspartate levels in cold-stressed birds (p

Renal cell carcinoma (RCC) has a high mortality rate among urological malignancies, and its underlying mechanisms remain unclear. Steroid receptor RNA coactivator (SRA) belongs to the long non‑coding RNAs (lncRNAs) and has been demonstrated to be closely related to various types of cancer. In the present study, the decreased expression level of SRA was first confirmed in RCC tissues and cell lines by RT‑qPCR. Using knockdown or overexpression systems, it was then found that SRA inhibited the proliferation of RCC cell lines and promoted their apoptosis. In addition, SRA suppressed the migration and invasion, and altered EMT‑related markers in RCC cells. More importantly, it was demonstrated that SRA reduced percentage of CD44+/CD24‑ cells and the sphere‑forming efficiency. SRA also attenuated the expression levels of CD44, SOX‑2, ABCG2 and OCT‑4, which are all associated with cancer cell stemness characteristics. Although SRA increased the phosphorylation of extracellular‑regulated protein kinase (ERK), the ERK1/2 pathway could not further interfere with the alteration of EMT‑related markers mediated by SRA. Notably, the ERK inhibitor, PD98059, abolished ERK1/2 phosphorylation, whereas it did not exert any marked effects on cell proliferation and EMT‑related markers mediated by SRA. Taken together, the findings of the present study indicate that SRA is an important molecule that inhibits the migration, invasion and stem cell characteristics of RCC cells; the ERK signaling pathway may not be involved in this process.

The soybean soluble polysaccharide was prepared by mixed fermentation of lactic acid bacteria and Neurospora crassa and microwave treatment. The functional properties and structure characteristics of soybean soluble polysaccharide before and after modification were compared. Results revealed that after fermentation treatment, the content of soybean soluble polysaccharide increased to 7.09%, which was 3.16 times that of raw materials, and the microwave treatment was further increased to 7.69%. The glucose adsorption capacity, glucose dialysis retardation index and the α-amylase activity inhibition ration of soybean soluble polysaccharides increased significantly, promotes intestinal flora growth in vitro after fermentation of mixed bacteria and microwave treatment. At the same time, the analysis of monosaccharide composition and structural characteristics showed that the monosaccharide components of soybean soluble polysaccharide were redistributed after modification treatment, Scanning electron microscopy showed that modified soybean soluble polysaccharide has a larger surface area; Fourier Transform Infrared spectroscopy and X-ray Diffraction proved that the modification has slight changes in the functional groups and crystal structure of soybean soluble polysaccharide. These results suggested that okara may be a potentially inexpensive source of natural soybean soluble polysaccharide and a potential functional food ingredient.

Paxillin (PXN) is a cytoplasmic protein that plays an important role in regulating focal adhesion, cytoskeletal rearrangements and cell motility. The present study aimed to investigate the role of PXN in the metastasis of human colorectal cancer (CRC) and its possible mechanisms. Immunohistochemical staining of tissues from 102 surgical CRC patients revealed that high PXN expression was positively correlated with tumour-node-metastasis (TNM) stage, lymph node metastasis, distant metastasis, and recurrence at distant sites after radical surgery. In 24 cases of stage IV CRC, PXN expression in liver metastasis was higher than that in the matched primary tumour. The knockdown of PXN inhibited the proliferation, migration and invasion potential of SW480 cells in vitro and in vivo. Transmission electron microscopy revealed the effect of PXN on ultrastructural characteristics, observed mainly in microvilli and desmosomes. The downregulation of PXN decreased the activation of extracellular regulated protein kinase (ERK) and suppressed the epithelial-mesenchymal transition (EMT) process. Following the downregulation of PXN, the addition of an ERK activator or inhibitor restored or further suppressed EMT, respectively, accompanied by corresponding changes in cell migration and invasion. Collectively, the present results confirmed the important role of PXN in CRC metastasis and revealed that PXN regulated EMT progression via the ERK signalling pathway. PXN may represent a future therapeutic strategy to prevent the EMT-associated progression and invasion of CRC.

The recent discovery of N6-methyladenine (N6-mA) in mammalian genomes suggests that it may serve as an epigenetic regulatory mechanism1. However, the biological role of N6-mA and the molecular pathways that exert its function remain unclear. Here we show that N6-mA has a key role in changing the epigenetic landscape during cell fate transitions in early development. We found that N6-mA is upregulated during the development of mouse trophoblast stem cells, specifically at regions of stress-induced DNA double helix destabilization (SIDD)2-4. Regions of SIDD are conducive to topological stress-induced unpairing of the double helix and have critical roles in organizing large-scale chromatin structures3,5,6. We show that the presence of N6-mA reduces the in vitro interactions by more than 500-fold between SIDD and SATB1, a crucial chromatin organizer that interacts with SIDD regions. Deposition of N6-mA also antagonizes SATB1 function in vivo by preventing its binding to chromatin. Concordantly, N6-mA functions at the boundaries between euchromatin and heterochromatin to restrict the spread of euchromatin. Repression of SIDD-SATB1 interactions mediated by N6-mA is essential for gene regulation during trophoblast development in cell culture models and in vivo. Overall, our findings demonstrate an unexpected molecular mechanism for N6-mA function via SATB1, and reveal connections between DNA modification, DNA secondary structures and large chromatin domains in early embryonic development.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2–infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2–infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies., The serum levels of IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, IP-10, MCP-1, MCP-3, MIG, and MIP-1α were associated with the severity of COVID-19. Men had higher levels of cytokines/chemokines than women. Some cytokines/chemokines were weakly correlated with the viral load.

Controlled perturbation of protein activity is essential to study protein function in cells and living organisms. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest, so-called degraders, have recently emerged as alternatives to selective chemical inhibitors, both as therapeutic modalities and as powerful research tools. These systems offer unprecedented temporal and spatial control over protein function. Here, we review recent developments in this field, with a particular focus on the use of degraders as research tools to interrogate complex biological problems. Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest have emerged as therapeutic modalities and powerful research tools. This Review summarizes recent developments in this field, with a focus on the use of degraders as research tools.

Postmenopausal osteoporosis is a common chronic dynamic bone disorder, caused by estrogen deficiency. To address this issue, we constructed a controlled drug-release system composed of poly (N-isopropylacrylamide) brush modified mesoporous hydroxyapatite (MHA-SIM-P) loaded with simvastatin (SIM) using an ovariectomised (OVX) rat model. Quantitative alkaline phosphatase activity assay, alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro. The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells (BMSCs) in vitro. In osteoporotic animal model, the therapeutic efficiency for bone defect was evaluated by μCT analysis, tartrate-resistant acid phosphatase, haematoxylin and eosin staining, which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks. This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis. Thus, this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects., Graphical abstract Image 1, Highlights • Sustained release of hydrophobic simvastatin controlled by polymer brush. • Mesoporous HA used as bone substitute for bone defect in osteoporosis model. • A feasible way to promote osteogenesis and reduce osteoporosis.