A novel protein FNDC3B-267aa encoded by circ0003692 inhibits gastric cancer metastasis via promoting proteasomal degradation of c-Myc.

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.

Research Progress on the Correlation Between Hypertension and Gut Microbiota.

Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.

Metabolomic insights into the effects of seasonal shifts on the dynamic variation of non-volatile compounds of abalone (Haliotis discus hannai).

Abalone (Haliotis spp.) is a shellfish known for its exceptional nutritional value and significant economic worth. This study investigated the dynamic characteristics of non-volatile compounds over a year, including metabolites, lipids, nucleotides, and free amino acids (FAAs), which determined the nutritional quality and flavor of abalone. 174 metabolites and 371 lipids were identified and characterized, while 20 FAAs and 11 nucleotides were quantitatively assessed. These non-volatile compounds of abalone were fluctuated with months variation, which was consistent with the fluctuations of environmental factors, especially seawater temperature. Compared with seasonal variation, gender had less influence on these non-volatiles. June and July proved to be the optimal harvesting periods for abalone, with the levels of overall metabolites, lipids, FAAs, and nucleotides in abalone exhibiting a higher value in June and July over a year. Intriguingly, taurine covered 60% of the total FAAs and abalone could be used as dietary taurine supplementation.

Unraveling the relationship between aroma characteristics and lipid profile of abalone (Haliotis discus hannai) during seasonal fluctuation and thermal processing.

Abalone, a highly sought-after aquatic product, possesses significant nutritional value. In this study, the relationship between aroma characteristics and lipid profile of abalone (Haliotis discus hannai) during seasonal fluctuation and thermal processing were profiled via volatolomics and lipidomics. 46 aroma compounds and 371 lipids were identified by HS-SPME-GC-MS and UPLC-Q-Extractive Orbitrap-MS, respectively. Multivariate statistical analysis indicated that carbonyls (aldehydes and ketones) and alcohols were the characteristic aroma compounds of abalone. The fluctuations in the aroma compound and lipid composition of abalone were consistent with the seasonal variation, especially seawater temperature. In addition, based on the correlation analysis, it was found that carbonyls (aldehydes and ketones) and alcohols had a positive correlation with phospholipids (lysophosphatidylethanolamines and lysophosphatidylcholines), while a negative correlation was observed with fatty acyls. These findings suggested that the effect of seasonal variations on the aroma changes of abalone might achieved by modulating the lipids composition of abalone.

Curcumae Radix: A Review of Traditional Use, Phytochemistry, Pharmacology, Toxicology and Quality Control.

Curcumae Radix (CuR) is a traditional Chinese medicine that has been used in China for more than 1,000 years. It has the traditional efficacy of activating blood and relieving pain, promoting qi and relieving depression, clearing heart and cooling blood, and promoting gallbladder and removing jaundice. Based on this, many domestic and foreign scholars have conducted systematic studies on its chemical composition, pharmacological effects, toxicity and quality control. Currently, 250 compounds, mainly including terpenoids and curcuminoids, have been isolated and identified from CuR, which has pharmacological activities, including antitumor, anti-inflammatory and analgesic, antidepressant, hepatoprotective, hemostatic, hematopoietic, and treatment of diabetes mellitus. In modern clinical practice, CuR is widely used in the treatment of tumors, breast hyperplasia, hepatitis, and stroke. However, the generation of toxicity and clinical application of CuR and Caryophylli Flos, the determination of the concoction process of artifacts, the determination of specific Quality Marker, and the establishment of the quality control system of CuR, are problems that need to be solved urgently at present.

Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma.

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.

In Silico-Predicted Dynamic Oxlipidomics MS/MS Library: High-Throughput Discovery and Characterization of Unknown Oxidized Lipids.

Nontargeted lipidomics using liquid chromatography-tandem mass spectrometry can detect thousands of molecules in biological samples. However, the annotation of unknown oxidized lipids is limited to the structures present in libraries, restricting the analysis and interpretation of experimental data. Here, we describe Doxlipid, a computational tool for oxidized lipid annotation that predicts a dynamic MS/MS library for every experiment. Doxlipid integrates three key simulation algorithms to predict libraries and covers 32 subclasses of oxidized lipids from the three main classes. In the evaluation, Doxlipid achieves very high prediction and characterization performance and outperforms the current oxidized lipid annotation methods. Doxlipid, combined with a molecular network, further annotates unknown chemical analogs in the same reaction or pathway. We demonstrate the broad utility of Doxlipid by analyzing oxidized lipids in ferroptosis hepatocellular carcinoma, tissue samples, and other biological samples, substantially advancing the discovery of biological pathways at the trace oxidized lipid level.

[Retracted] Upregulation of miR­183­5p is responsible for the promotion of apoptosis and inhibition of the epithelial­mesenchymal transition, proliferation, invasion and migration of human endometrial cancer cells by downregulating Ezrin.

Following the publication of this article, a concerned reader drew to the Editor's attention that, in Fig. 9C on p. 2478 showing the results of Transwell invasion assay experiments, unexpected areas of similarity were identified in terms of the cellular patterns revealed both within the data panels for the six different experiments portrayed in this figure, and comparing among them. After having conducted an internal investigation, the Editor of International Journal of Molecular Medicine has reached the conclusion that the overlapping sections of data shown in this figure were unlikely to have arisen by coincidence. Therefore, on the grounds of a lack of confidence in the integrity of these data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused, and thanks the interested reader for drawing this matter to our attention. [International Journal of Molecular Medicine 42: 2469­2480, 2018; DOI: 10.3892/ijmm.2018.3853].

Comparing verum and sham acupoint catgut embedding for adults with obesity: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Previous clinical trials have reported that acupoint catgut embedding (ACE) is a useful modality for weight loss. However, no study has specifically investigated the effectiveness and safety of comparing verum and sham ACE in adults with obesity. Thus, this study aimed to evaluate the effectiveness and safety of comparing verum and sham ACE in obese adults. METHODS: A comprehensive literature search was conducted in the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and China Biomedical Literature Service System from inception to April 1, 2022. Randomized clinical trials that focused on evaluating the effectiveness of comparing verum and sham ACE in adults with obesity were included. The primary outcomes included reduction in body weight, body mass index, hip circumference, and waist circumference. The secondary outcomes consisted of a decrease in body fat percentage and the occurrence rate of adverse events. The methodological quality of the included randomized clinical trials was evaluated using the Cochrane Risk-of-bias tool. Statistical analysis was performed using RevMan 5.4 software. RESULTS: Six trials involving 679 adults with obesity were included in this study and entered in the data analysis of systematic review and meta-analysis. Results of the meta-analysis revealed significant reduction in body weight (mean difference [MD] = -1.68, 95% confidence intervals (CI) [-2.34, -1.01], I2 = 51%, P < .001), body mass index (MD = -0.51, 95% CI [-0.81, -0.21], I2 = 74%, P < .001), hip circumference (MD = -1.11, 95% CI [-1.67, -0.55], I2 = 0%, P < .001), waist circumference (MD = -2.42, 95% CI [-3.38, -1.45], I2 = 68%, P < .001), and decrease in body fat percentage (MD = -0.83, 95% CI [-1.30, -0.36], I2 = 16%, P < .001) in comparing verum and sham ACE. However, no significant difference was identified in AEs (odds ratio = 1.53, 95% CI [0.80, 2.95], I2 = 0%, P = .20) between the 2 groups. CONCLUSION: ACE is effective in the treatment of obesity in adults with safety profile. Further studies with higher quality and larger sample size are warranted to confirm the current findings.

Photocontrolled chiroptical switch based on the self-assembly of azobenzene-bridged bis-tryptophan enantiomers.

Chirality dynamic tuning plays fundamental roles in chemistry, material science and biological system. Herein, a pair of azobenzene-bridged bis-tryptophan enantiomers (Azo-di-d/l-Trp) were designed and synthesized via simple reactions. With the fuel of glucono-δ-lactone (GdL), releasing protons during its hydrolysis, the alkaline solution of Azo-di-d/l-Trp gradually self-assembled into contrast chiral helical structures and displayed magnitude and mirror image of circular dichroism (CD) signals. While the chiral helices converted to CD silent nanoparticles when the azobenzene moiety isomerized from trans- to cis-form under UV irradiation. More importantly, this chiroptical switch, displaying reversible interconversion between chiral amplification and silent, can be smartly controlled via photoirradiation at various wavelengths.

Mediating effect of cumulative lipid profile burden on the effect of diet and obesity on hypertension incidence: a cohort study of people aged 35-65 in rural China.

BACKGROUND AND OBJECTIVES: Cumulative lipid profile burden is designed to dynamically measure lipid accumulation, and its effect on hypertension has been poorly studied. Our main purpose was to investigate the effect of cumulative lipid profile burden on the incidence of essential hypertension (EH) and to investigate whether cumulative lipid burden mediates the pathogenesis of the effects of diet and obesity on EH. SUBJECTS AND METHODS: A total of 1295 participants were included in the study, which started in 2017. The average follow-up time was 2.98 years. A total of 240 EH patients occurred during the follow-up period. RESULTS: The HR (95% CI) of the highest quartile in cumulative Total cholesterol (TC), triglyceride (TG) and high density lipoprotein (HDL) burden were 1.747 (1.145 - 2.664), 1.502 (1.038 - 2.173), 0.615 (0.413 - 0.917) for incidence of EH respectively, compared to the respective reference groups. Participants with EH consumed more red meat and refined grains, and red meat was positively associated with cumulative TC burden. BMI and Waist-To-Height Ratio (WHtR) increased the incidence of EH, and obesity was positively correlated with cumulative TG burden. Mediating analysis showed that cumulative TG had a partial mediating effect in the causal relationship between obesity and EH, and Mendelian randomization (MR) also proved this result. Diet was not found to influence EHn through cumulative lipid profile burden. CONCLUSIONS: The cumulative TG burden partially mediates the effect of obesity on EH.

Refined Electrolyte and Interfacial Chemistry toward Realization of High-Energy Anode-Free Rechargeable Sodium Batteries.

Anode-free rechargeable sodium batteries represent one of the ultimate choices for the 'beyond-lithium' electrochemical storage technology with high energy. Operated based on the sole use of active Na ions from the cathode, the anode-free battery is usually reported with quite a limited cycle life due to unstable electrolyte chemistry that hinders efficient Na plating/stripping at the anode and high-voltage operation of the layered oxide cathode. A rational design of the electrolyte toward improving its compatibility with the electrodes is key to realize the battery. Here, we show that by refining the volume ratio of two conventional linear ether solvents, a binary electrolyte forms a cation solvation structure that facilitates flat, dendrite-free, planar growth of Na metal on the anode current collector and that is adaptive to high-voltage Na (de)intercalation of P2-/O3-type layered oxide cathodes and oxidative decomposition of the Na2C2O4 supplement. Inorganic fluorides, such as NaF, show a major influence on the electroplating pattern of Na metal and effective passivation of plated metal at the anode-electrolyte interface. Anode-free batteries based on the refined electrolyte have demonstrated high coulombic efficiency, long cycle life, and the ability to claim a cell-level specific energy of >300 Wh/kg.

Effect of sodium salt on meat products and reduction sodium strategies - A review.

Sodium salt is one of the important additives in food processing. However, excessive intake of sodium salt may cause a series of cardiovascular diseases. Nowadays, sodium intake in most countries is higher than the World Health Organization recommends maximum consumption (5 g/d). 20% of the sodium intake in diets comes from meat products. Therefore, reducing the content of sodium salt in meat products and developing sodium salt-reduction meat products have attracted more and more attention for consumers. In this paper, the roles of sodium salt in meat product processing were reviewed. At the same time, sodium salt reduction strategies and existing problems were summarized and discussed. Multiple factors need to be considered to improve the salt-reduction meat product's quality. Relying on a single technology has a narrow application area, and it is difficult to achieve salt reduction. Therefore, a combination of multiple strategies could obtain a more ideal effect.

Analysis of Lipid Molecule Profiling and Conversion Pathway in Mandarin Fish (Siniperca chuatsi) during Fermentation via Untargeted Lipidomics.

Lipids are the key aroma contributors and nutrients in fermented fish products. A total of 376 lipid molecules were identified in mandarin fish during fermentation by untargeted lipidomics, including glycerolipids, glycerophospholipids, lysoglycerophospholipid, sphingolipids, fatty acids (FAs), and sterol lipids. Both lipid composition and content changed dynamically during fermentation. Triglyceride (TAG, 30.05%) and phosphatidylcholine (PC, 14.87%) were the two major lipids, with especially 39.36% saturated FAs in PCs and 35.34% polyunsaturated FAs in TAGs. The content of TAGs and PCs reached a peak point at 0 and 6 days, respectively. Fermented mandarin fish expressed a high nutritional value, and the ratio of total linoleic acid/total linolenic acid was about 5:1. Glycerophospholipid metabolism was a potential metabolic pathway, and the oxidation of derived FAs contributed to flavor. These data progress in understanding lipid dynamic variation during fermentation and provide thoughts on controlling the flavor quality and safety of fermented fish products.

Comprehensive Multi-Spectroscopy and Molecular Docking Understanding of Interactions between Fermentation-Stinky Compounds and Mandarin Fish Myofibrillar Proteins.

The release of flavor compounds is a critical factor that influences the quality of fermented foods. A recent study investigated the interactions between four fermentation-stinky compounds (indole, isovaleric acid, dimethyl disulfide, and dibutyl phthalate) and myofibrillar proteins (MPs). The results indicated that all four fermentation-stinky compounds had different degrees of binding to MPs, with dibutyl phthalate and dimethyl disulfide exhibiting stronger interactions. Reduced hydrophobicity enhanced these interactions. Multi-spectroscopy showed that static fluorescence quenching was dominant in the MPs-fermentation-stinky compound complexes. The interaction altered the secondary structure of MPs, predominantly transitioning from ß-sheets to α-helix or random coil structures via hydrogen bond interactions. Molecular docking confirmed that these complexes maintained steady states due to stronger hydrogen bonds, van der Waals forces, ionic bonds, conjugate systems, and lower hydrophobicity interactions. Hence, it is a novel sight that the addition of hydrophobic bond-disrupting agents could improve the flavor of fermented foods.

eccDB: a comprehensive repository for eccDNA-mediated chromatin contacts in multi-species.

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.

Integrated volatolomics and metabolomics analysis reveals the characteristic flavor formation in Chouguiyu, a traditional fermented mandarin fish of China.

Volatolomics and metabolomics were performed to explore the generation mechanism of the characteristic flavor of mandarin fish during fermentation. This study revealed a novel finding that umami-tasting amino acids, succinic acid, and peptides increased, while taste-presenting nucleotides decreased after fermentation. The results showed that 19 key aroma compounds were identified. The most nitrogenous compounds were produced after fermentation, the total concentration of which was >5 mg/kg. A high odor activity value of 443 was established for stinky indole. PLS-DA showed that sn-glycero-3-phosphocholine, hypoxanthine, creatine, and trimethylamine N-oxide were the key metabolites associated with the key volatiles. Umami-tasting amino acids could contribute to the characteristic taste. Metabolic pathway analysis revealed that tryptophan metabolism, trimethylamine metabolism, and monoterpenoid biosynthesis were the potential generation pathways of indole, trimethylamine, and terpenoids, respectively. Collectively, the results provide thoughts for targeted controlling the flavor of fermented mandarin fish.

Pouring hot water through drip bags releases thousands of microplastics into coffee.

Microplastics (MPs) released from food packaging have attracted widespread attention. In this study, drip bags made from polyethylene (PE), polypropylene (PP), polyester (PET), and rayon selected from eight brands were employed to investigate MPs releasing. Fourier-transform infrared microspectroscopy (µ-FTIR), optical microscope and scanning electron microscope (SEM) were used to study the effects of brewing time and temperature on the release of MPs. The results showed that a single plastic coffee bag steeped at 95 ℃ for 5 min could release more than 10,000 MPs particles into a cup of coffee. Irregular blocks, long strips, and size range of 10-500 µm MPs were easier to be released, implying that consuming 3-4 cups of coffee will lead to an intake of 50 thousand MPs particles daily. Rayon was the primary type of released MPs, accounting for over 80% of the total amount of the released MPs. Our results are hoped to provide evaluation standards of material selection for processing coffee bags.

Unraveling the Thermal Oxidation Products and Peroxidation Mechanisms of Different Chemical Structures of Lipids: An Example of Molecules Containing Oleic Acid.

Lipid structures affect lipid oxidation, causing differences in types and contents of volatiles and nonvolatiles in various foods. In this study, the oxidation differences of monoacylglycerol (MAG), triacylglycerol (TAG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) with oleoyl residues and oleic acid (FA) during thermal treatment were investigated. Volatiles and nonvolatiles were monitored by gas chromatography-mass spectrometry and ultrahigh-performance liquid chromatography-Q-Exactive HF-X Orbitrap Mass Spectrometer, respectively. The results showed that the structures of MAG and TAG could delay the chain initiation reaction. The polar heads of PC and PE remarkably influenced the oxidation rate and the formation of the oxidation products probably due to the hydrogen bonds formed with free radicals. Among the volatile oxidation products, aldehydes, acids, and furans with eight or nine carbon atoms accounted for the majority in FA, MAG, TAG, and PC samples, but PE samples mainly generated ketones with nine or 10 carbon atoms. The formation of nonvolatile products in TAG samples possessed significant stage-specific changes. Fatty acid esters of hydroxy fatty acids were only produced in the free fatty acid oxidation model. The activity of chemical bonds participating in the truncation reaction decreased to both sides from the double bond position.

Metal Ion-Mediated Pro-oxidative Reactions of Different Lipid Molecules: Revealed by Nontargeted Lipidomic Approaches.

Unsaturated fatty acids are easily affected by metal ions, leading to the changes of their flavor, nutrition, and safety through lipid oxidation. Nevertheless, there is a lack of comprehensive evaluation of the pro-oxidative ability of different metal ions, which have different effects on different lipids. Thus, in this work, crude lipids extracted from abalone were incubated with different metal ions, and the comprehensive lipid oxidation products were analyzed by nontargeted lipidomics approaches using an ultra-high-performance liquid chromatography-Q-Exactive HF-X Orbitrap Mass Spectrometer (UPLC-Q-Exactive HF-X). Results showed that the overall pro-oxidative ability from strong to weak was Fe3+, Fe2+, Cu2+, Zn2+, Mn2+, Mg2+, Na+, and K+. Among them, Fe3+ and Fe2+ could promote the accumulation of oxidation intermediates and branched fatty acid esters of hydroxy fatty acids. Na+, K+, Cu2+, and Mg2+ could accelerate the oxidation of N-acyl ethanolamines and ceramides. K+ and Na+ had more influences on the free fatty acids than Zn2+ and Mn2+. Slow oxidation of triglyceride may be attributed to its long distance from the oil-water interface and the restriction of the polar headgroups of phospholipids on free radicals.