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Abstract Objective This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. Methods HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. Results ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. Conclusion This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Due to their high reactivity, volatile organic compounds (VOCs) can engage in physical and chemical reactions with particulate matter in the atmosphere, leading to air pollution. Extended exposure to VOCs may result in various health concerns, including respiratory system problems, neurological effects, skin and eye irritation, and an increased risk of certain cancers. Traditional benchtop mass spectrometers possess the advantages of high sensitivity and rapid analysis capabilities, but the large size typically confines their applications to professional laboratories. To overcome this limitation, portable mass spectrometers are emerging as a new tool for in-situ analysis. In this study, a portable mass spectrometer based on discontinuous atmosphere pressure interface was developed, which combined with a sub-vacuum plasma ionization source. Ion trap, known for its small size and adequate performance, was adopted in this miniaturized mass spectrometer. This portable mass spectrometer features a total weight of about 4.6 kg, with the dimensions of 217 mm×162 mm×106 mm, and operates with a power consumption under 150 W. On this design, a fully metallic solenoid valve was selected as the core component to limit atmospheric pressure, eliminating the need for the rubber tubing used in traditional pinch valves. Compared to traditional pinch valves, this solenoid valve ensures a more stable airflow during experiments. As a result, the repeatability and environmental adaptability of the portable mass spectrometer were improved. A certain delay marked as radio freqency (RF) delay was introduced between the injection and cooling periods, and the RF-delay time was optimized. Frequency scanning mode and amplitude scanning mode were tested in parallel. Despite of a trade-off in size, amplitude scanning offered improved resolution, enabling the differentiation of ions with close mass to charge ratios. After systematic optimization, satisfactory performances in mass resolution and sensitivity were achieved. The mass resolution of the mass spectrometer for dimethyl carbonate was improved to 0.2 u (FWHM), and a sensitivity of 60 μg/m3 for naphthalene was achieved. The capability of mixed VOCs was also validated using dimethyl carbonate and trimethyl phosphate. This mass spectrometer developed in this study, characterized by its high portability and satisfactory performance, is expected to hold great potential for applications in VOCs analysis.

The Xiaoqinling gold province, located in the southern margin of the North China Craton (NCC), is the second largest gold-enriched region in China. In this region, the Mesozoic Huashan (HS) and Wenyu (WY) plutons are the major magmatic intrusions coeval with gold mineralization, although they show contrasting characteristics in the distribution of gold. In this study, we use geochemical features of titanite determined by LA-ICP-MS and EPMA analyses and elemental mapping to decipher the mechanisms that led to the difference in gold enrichment related to the two plutons. Titanite from the Wenyu granitic pluton exhibits significantly higher (La/Sm)N, (La/Yb)N, ΣLREE/ΣHREE ratios, and ΣREE concentration and slightly higher (Gd/Yb)N values than those of the Huashan Pluton, suggesting that the Wenyu pluton might have experienced more complex magmatic evolution, widespread hydrothermal alteration, and higher silica activity in the melt than the Huashan pluton. The titanite grains from the Huashan pluton show higher (Nb/Ta)N and (Lu/Hf)N values and significantly lower Zr concentration than those of the Wenyu pluton. The titanite grains from the Wenyu pluton show higher vanadium and gallium concentrations and Fe/Al ratio than those of the Huashan pluton, indicating comparatively higher fo2. Furthermore, the titanite grains from Wenyu pluton indicate higher water content in the magma. In addition, magma mingling and magmatic hydrothermal fluids derived from the crust/mantle are critical sources for ore-forming materials. These results suggest that the Wenyu pluton is more conducive to gold migration and enrichment than the Huashan pluton.

Abstract Background Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters. Methods Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups (n = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis. Results HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2. Conclusions HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation. Graphical Abstract

Abstract We aimed to examine whether the efficacy of the risk of poor prognosis in patients with coronary artery disease is jointly affected by total cholesterol and baseline serum albumin in a secondary analysis of previous study. We analyzed the data of 204 patients from October 2014 to October 2017 for newly diagnosed stable CAD. The outcome was major adverse cardiac events (MACE; defined as all cause mortality, non fatal myocardial infarction, and non fatal stroke). The median duration of follow-up was 783 days. Multivariable COX model was performed to revalidate the relationship between the sALB and MACE and interaction tests were conducted to find the effects of total cholesterol on their association. A total of 28 MACE occurred among the 204 participants. The risk of MACE varied by baseline serum albumin and total cholesterol. Specifically, lower serum albumin indicated higher risk of MACE (HR 3.52, 95% CI 1.30–9.54), and a test for interaction between baseline serum albumin and total cholesterol on MACE was significant (P = 0.0005). We suggested that baseline serum albumin and total cholesterol could interactively affect the risk of poor prognosis of patients with coronary artery diseases. Our findings need to be confirmed by further randomized trials.

BackgroundCardiovascular diseases (CVDs) have been the major cause of mortality in type 2 diabetes. However, new approaches are still warranted since current diabetic medications, which focus mainly on glycemic control, do not effectively lower cardiovascular mortality rate in diabetic patients. Protocatechuic acid (PCA) is a phenolic acid widely distributed in garlic, onion, cauliflower and other plant-based foods. Given the anti-oxidative effects of PCA in vitro, we hypothesized that PCA would also have direct beneficial effects on endothelial function in addition to the systemic effects on vascular health demonstrated by previous studies.Methods and resultsSince IL-1β is the major pathological contributor to endothelial dysfunction in diabetes, the anti-inflammatory effects of PCA specific on endothelial cells were further verified by the use of IL-1β-induced inflammation model. Direct incubation of db/db mouse aortas with physiological concentration of PCA significantly ameliorated endothelium-dependent relaxation impairment, as well as reactive oxygen species overproduction mediated by diabetes. In addition to the well-studied anti-oxidative activity, PCA demonstrated strong anti-inflammatory effects by suppressing the pro-inflammatory cytokines MCP1, VCAM1 and ICAM1, as well as increasing the phosphorylation of eNOS and Akt in the inflammatory endothelial cell model induced by the key player in diabetic endothelial dysfunction IL-1β. Upon blocking of Akt phosphorylation, p-eNOS/eNOS remained low and the inhibition of pro-inflammatory cytokines by PCA ceased.ConclusionPCA exerts protection on vascular endothelial function against inflammation through Akt/eNOS pathway, suggesting daily acquisition of PCA may be encouraged for diabetic patients.

The gut microbiota serves as a pivotal mediator between diet and human health. Emerging evidence has shown that the gut microbiota may play an important role in cholesterol metabolism. In this review, we delve into five possible mechanisms by which the gut microbiota may influence cholesterol metabolism: (1) the gut microbiota changes the ratio of free bile acids to conjugated bile acids, with the former being eliminated into feces and the latter being reabsorbed back into the liver; (2) the gut microbiota can ferment dietary fiber to produce short-chain fatty acids (SCFAs) which are absorbed and reach the liver where SCFAs inhibit cholesterol synthesis; (3) the gut microbiota can regulate the expression of some genes related to cholesterol metabolism through their metabolites; (4) the gut microbiota can convert cholesterol to coprostanol, with the latter having a very low absorption rate; and (5) the gut microbiota could reduce blood cholesterol by inhibiting the production of lipopolysaccharides (LPS), which increases cholesterol synthesis and raises blood cholesterol. In addition, this review will explore the natural constituents in foods with potential roles in cholesterol regulation, mainly through their interactions with the gut microbiota. These include polysaccharides, polyphenolic entities, polyunsaturated fatty acids, phytosterols, and dicaffeoylquinic acid. These findings will provide a scientific foundation for targeting hypercholesterolemia and cardiovascular diseases through the modulation of the gut microbiota.

ObjectiveThis study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.MethodsOncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan–Meier technique, Cox regression analysis, LinkedOmics, Pearson’s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein–protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.ResultsIn HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.ConclusionFCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

Repeated reuse of frying oil raises health concerns due to the accumulation of oxidative products after each frying cycle. Gut microbiota is integral in lipid metabolism and immune regulation. The present study was designed to investigate the effects of thermally-oxidized corn oil and lard on gut microbiota in relation to atherosclerosis, inflammatory cytokines, and plasma lipids. Male Golden Syrian hamsters were randomly divided into four groups and fed one of four diets containing fresh corn oil (CF), oxidized corn oil (CO), fresh lard (LF), and oxidized lard (LO), for six weeks. CO and LO were prepared by deep-frying potatoes in corn oil or lard for seven days. Results indicated that oxidized oil and lard caused the loss of species diversity and richness of gut microbiota. Feeding CO and LO also reduced the body and adipose tissue weights, associated with genus Acetatifactor and Allobaculum. Plasma triacylglycerols significantly increased by 51% in the CO and 35% in the LO group compared with that in their CF and LF counterparts, respectively. CO could also affect the abundance of specific bacteria genera: Bacteroides, Barnesiella, Acetatifactor, Allobaculum, Clostridium_IV, Clostridium_XIVa, Coprococcus, Lactococcus, Paraprevotella, Parasutterella, and Oscillibacter. In addition, CO and LO could adversely remodel gut composition and affect intestinal production of short-chain fatty acids, pro-inflammatory biomarkers (LPS and IL-6), anti-inflammatory biomarker IL-10, and atherosclerotic progression. It was concluded that frying oil could adversely modulate the gut microbiota and exacerbate the atherosclerosis at least in a hypercholesterolemia hamster model.

Objective: This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics. Methods: Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan-Meier technique, Cox regression analysis, LinkedOmics, Pearson's correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein-protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors. Results: In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alphafetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors. Conclusion: FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Abstract: With the continuous development of science and technology, battery storage systems for clean energy have become crucial for global economic transformation. Among various rechargeable batteries, lithium-ion batteries are widely used, but face issues like limited resources, high costs, and safety concerns. In contrast, zinc-ion batteries, as a complement to lithium-ion batteries, are drawing increasing attention. In the exploration of zinc-ion batteries, especially of phosphate-based cathodes, the battery action mechanism has a profound impact on the battery performance. In this paper, we first review the interaction mechanism of multi-ion, dual-ion, and single-ion water zinc batteries. Then, the impact of the above mechanisms on battery performance was discussed. Finally, the application prospects of the effective use of multi-ion, dual-ion, and single-ion intercalation technology in zinc-ion batteries is reviewed, which has significance for guiding the development of rechargeable water zinc-ion batteries in the future.

This article reviews the physical and chemical properties and development prospects of lignin. The classification and extraction methods of lignin,as well as the latest research progress of lignin-based functional materials in adsorption,ultraviolet protection, and drug release are summarized. The current research status was summarized and the high-value utilization of lignin is prospected. [ABSTRACT FROM AUTHOR]