Fish gut-derived probiotic Pediococcus pentosaceus alleviates gossypol-induced intestinal inflammation by inhibiting NLRC3/NF-κB/IL-1ß signal pathway in Nile tilapia.

Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1ß, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-ß. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1ß signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish.

Design of Path-Planning System for Interventional Thermal Ablation of Liver Tumors Based on CT Images.

OBJECTIVE: Aiming at the shortcomings of artificial surgical path planning for the thermal ablation of liver tumors, such as the time-consuming and labor-consuming process, and relying heavily on doctors' puncture experience, an automatic path-planning system for thermal ablation of liver tumors based on CT images is designed and implemented. METHODS: The system mainly includes three modules: image segmentation and three-dimensional reconstruction, automatic surgical path planning, and image information management. Through organ segmentation and three- dimensional reconstruction based on CT images, the personalized abdominal spatial anatomical structure of patients is obtained, which is convenient for surgical path planning. The weighted summation method based on clinical constraints and the concept of Pareto optimality are used to solve the multi-objective optimization problem, screen the optimal needle entry path, and realize the automatic planning of the thermal ablation path. The image information database was established to store the information related to the surgical path. RESULTS: In the discussion with clinicians, more than 78% of the paths generated by the planning system were considered to be effective, and the efficiency of system path planning is higher than doctors' planning efficiency. CONCLUSION: After improvement, the system can be used for the planning of the thermal ablation path of a liver tumor and has certain clinical application value.

Epidemiology, risk areas and macro determinants of gastric cancer: a study based on geospatial analysis.

BACKGROUND: Both incidence and mortality of gastric cancer in Gansu rank first in china, this study aimed to describe the recent prevalence of gastric cancer and explore the social and environmental determinants of gastric cancer in Gansu Province. METHODS: The incidence of gastric cancer in each city of Gansu Province was calculated by utilizing clinical data from patients with gastric cancer (2013-2021) sourced from the medical big data platform of the Gansu Province Health Commission, and demographic data provided by the Gansu Province Bureau of Statistics. Subsequently, we conducted joinpoint regression analysis, spatial auto-correlation analysis, space-time scanning analysis, as well as an exploration into the correlation between social and environmental factors and GC incidence in Gansu Province with Joinpoint_5.0, ArcGIS_10.8, GeoDa, SaTScanTM_10.1.1 and GeoDetector_2018. RESULTS: A total of 75,522 cases of gastric cancer were included in this study. Our findings suggested a significant upward trend in the incidence of gastric cancer over the past nine years. Notably, Wuwei, Zhangye and Jinchang had the highest incidence rates while Longnan, Qingyang and Jiayuguan had the lowest. In spatial analysis, we have identified significant high-high cluster areas and delineated two high-risk regions as well as one low-risk region for gastric cancer in Gansu. Furthermore, our findings suggested that several social and environmental determinants such as medical resource allocation, regional economic development and climate conditions exerted significant influence on the incidence of gastric cancer. CONCLUSIONS: Gastric cancer remains an enormous threat to people in Gansu Province, the significant risk areas, social and environmental determinants were observed in this study, which may improve our understanding of gastric cancer epidemiology and help guide public health interventions in Gansu Province.

Environment factors, DNA methylation, and cancer.

Today, the rapid development of science and technology and the rapid change in economy and society are changing the way of life of human beings and affecting the natural, living, working, and internal environment on which human beings depend. At the same time, the global incidence of cancer has increased significantly yearly, and cancer has become the number one killer that threatens human health. Studies have shown that diet, living habits, residential environment, mental and psychological factors, intestinal flora, genetics, social factors, and viral and non-viral infections are closely related to human cancer. However, the molecular mechanisms of the environment and cancer development remain to be further explored. In recent years, DNA methylation has become a key hub and bridge for environmental and cancer research. Some environmental factors can alter the hyper/hypomethylation of human cancer suppressor gene promoters, proto-oncogene promoters, and the whole genome, causing low/high expression or gene mutation of related genes, thereby exerting oncogenic or anticancer effects. It is expected to develop early warning markers of cancer environment based on DNA methylation, thereby providing new methods for early detection of cancers, diagnosis, and targeted therapy. This review systematically expounds on the internal mechanism of environmental factors affecting cancer by changing DNA methylation, aiming to help establish the concept of cancer prevention and improve people's health.

Bacillus amyloliquefaciens protects Nile tilapia against Aeromonas hydrophila infection and alleviates liver inflammation induced by high-carbohydrate diet.

Carbohydrates are widely distributed in nature as an important nutritional substance and energy source. However, the utilization efficiency of carbohydrates is very poor in fish. Over consumption of carbohydrates will cause excessive inflammatory response and result in lower pathogen resistance in fish. Probiotics have been widely used to prevent inflammation, but the underlying mechanism still needs more exploration. In this study, three diets, including a control diet (CD), a high-carbohydrate diet (HD) and the HD supplemented with Bacillus amyloliquefaciens SS1 (HDB) were used to feed Nile tilapia for 10 weeks. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila (A. hydrophila) for 7 days. The data showed that the addition of Bacillus amyloliquefaciens SS1 (B. amyloliquefaciens SS1) significantly increased the survival rate and enhanced the respiratory burst activity of head kidney leukocytes in Nile tilapia. B. amyloliquefaciens SS1 treatment significantly elevated the anti-oxidative capability, which was evidenced by higher activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), and higher content of reduced glutathione (GSH) in the serum. Administration with B. amyloliquefaciens SS1 effectively suppressed inflammatory response in the liver by inhibiting nuclear factor kappa-B (NF-κB)/interleukin-1 beta (IL-1ß) inflammatory signaling pathway. In vitro analysis suggested that intestinal bacteria derived-acetate has the antioxidant capability, which may account for the alleviation of inflammation. Overall, this study demonstrated that dietary supplementation with B. amyloliquefaciens SS1 protected Nile Tilapia against A. hydrophila infection and suppressed liver inflammation by enhancing antioxidant capability.

Influence of dietary sodium taurocholate on the growth performance and liver health of Nile tilapia (Oreochromis niloticus).

Bile acids (BAs) are a class of cholesterol-derived amphipathic molecules approved as new animal feed additives. However, the functional researches mainly focused on BAs mixture, and the influence of the individual BA on fishes was still limited. In the present study, Nile tilapia were fed basal diet with three levels of sodium taurocholate at 0 mg/kg (CON), 300 mg/kg (TCAL), and 600 mg/kg (TCAH) for 8 weeks. The results indicated that addition of sodium taurocholate did not significantly influence the growth performance. Instead, TCAH group had higher cholesterol accumulation with liver fibrosis. In TCAH group, the level of nuclear factor E2-related factor 2 (nrf2) signaling-associated oxidative stress factors significantly increased in the liver. Additionally, fish in TCAH group had the highest expression level of genes encoding endoplasmic reticulum (ER) stress and inflammatory cytokines in the liver. In conclusion, 300 mg/kg of sodium taurocholate did not significantly influence the growth performance of fish, while 600 mg/kg of sodium taurocholate markedly induced cholesterol accumulation and liver injury, suggesting that the application of taurocholic acid in aquafeed should be re-evaluated.

Decreased infiltration of adipose tissue macrophages and amplified inflammation of adipose tissue in obese mice with severe acute pancreatitis.

OBJECTIVE: Macrophages are involved in obesity-associated inflammation and severe acute pancreatitis (SAP) development. However, the role of adipose tissue macrophages (ATMs) in obesity-related SAP has not been fully elucidated. We investigated the relationship between ATMs and inflammatory responses in SAP model mice fed a high-fat diet (HFD). METHODS: SAP was induced in animal models via intraperitoneal injections of caerulein and lipopolysaccharide (LPS). SAP severity was evaluated, both morphologically and biochemically, and macrophage infiltration in the pancreas and epididymal adipose tissue was measured. We also analyzed apoptosis levels, polarization of the ATMs, and expression of inflammatory mediators in epididymal adipose tissue. RESULTS: Obesity increased disease severity in SAP animals. Increased macrophage infiltration in the pancreas induced by SAP was found in both normal diet (ND)- and HFD-fed mice. Total ATM infiltration in epididymal adipose tissue was elevated by HFD, while a significant decrease in infiltration was observed in both the ND + SAP and HFD + SAP groups. The apoptosis levels of ATMs were reduced in the HFD group, but were markedly enhanced in both the ND + SAP and HFD + SAP groups compared to their respective control groups. Higher levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were observed in the HFD + SAP than in the ND + SAP group. Increased proportion of M1 type ATMs was induced by both HFD and SAP. CONCLUSIONS: Total ATM infiltration was decreased in epididymal adipose tissue of SAP animals. ATM polarization to the M1 type resulted in an amplified inflammatory response in obese mice with SAP.

Immune and gut bacterial successions of large yellow croaker (Larimichthys crocea) during Pseudomonas plecoglossicida infection.

Large yellow croaker (Larimichthys crocea, LYC) aquaculture is being threatened by intensive infectious diseases. Relevant studies have focused on LYC immune responses to infection. By contrast, little is known how and to what extent the gut microbiota responds to infection. Here, we explored the interactions between LYC immune responses and gut bacterial communities during Pseudomonas plecoglossicida infection. P. plecoglossicida successfully colonized into LYC gut microbiota, resulting in an increasing mortality rate. Relative gene expressions of pro-inflammatory cytokines (TNF-α1, TNF-α2 and IL-1ß) and anti-inflammatory cytokine (IL-10) were consistently and significantly induced by P. plecoglossicida infection, whereas non-specific immune enzymes activities were only enhanced at the early infection stages. P. plecoglossicida infection caused an irreversible disruption in the gut microbiota, of which infection and hours post infection constrained 16.2% and 5.6% variations, respectively. In addition, top 18 discriminatory taxa that were responsible for the difference between treatments were identified, whose abundances were significantly associated with the immune activities of LYC. Using a structural equation modeling (SEM), we found that gut bacterial communities were primarily governed by the conjointly direct (-0.33) and indirect (0) effects of infection, which subsequently affect host immune responses. Our results suggest that an irreversible dysbiosis in gut microbiota could be the causality of increasing mortality. To our knowledge, this is the first study to provide an integrated overview among pathogen infection, immune response and gut microbiota of LYC.

Molecular characterization of the NK-lysin in a teleost fish, Boleophthalmus pectinirostris: Antimicrobial activity and immunomodulatory activity on monocytes/macrophages.

NK-lysin (NKL) is a cationic host defense peptide that plays an important role in host immune responses against various pathogens. However, the immunomodulatory activity of NKL in fishes is rarely investigated. In this study, we characterized a cDNA sequence encoding an NK-lysin homolog (BpNKL) from the fish, mudskipper (Boleophthalmus pectinirostris). Sequence analysis revealed that BpNKL is most closely related to tiger puffer (Takifugu rubripes) NKL. BpNKL transcript was detected in all the tested tissues, with the highest level in the gill, followed by the spleen and kidney. Upon Edwardsiella tarda infection, the mRNA expression of BpNKL in the mudskipper was significantly upregulated in the spleen, kidney, and gill. A shortened peptide derived from BpNKL, BpNKLP40, was then chemically synthesized and its biological functions were investigated. BpNKLP40 exhibited a direct antibacterial activity against some Gram-negative bacteria, including E. tarda, Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi, and induced hydrolysis of E. tarda genomic DNA. Intraperitoneal injection of 1.0 µg/g BpNKLP40 significantly improved the survival of mudskipper following E. tarda infection and reduced the bacterial burden in tissues and blood. Moreover, 1.0 µg/ml BpNKLP40 treatment had an enhanced effect on the intracellular killing of E. tarda by monocytes/macrophages (MO/MФ) as well as on the mRNA expression of pro-inflammatory cytokines in MO/MФ. In conclusion, our study reveals that BpNKL plays a role against E. tarda infection in the mudskipper by not only directly killing bacteria but also through an immunomodulatory activity on MO/MФ.

[Simultaneous Determination of Five Astragalosides in Astragali Radix and Jinqi Jiangtang Tablet by HPLC-ELSD].

OBJECTIVE: To develop an HPLC-ELSD method for simultaneous determination of Astragaloside IV Astragaloside I, Astragaloside II, Astragaloside III and Isostragaloside II in Astragali Radix and Jinqi Jiangtang tablet. METHODS: The chromatographic conditions were as follows: Grace Apollo C18 column (250 mm x 4. 6 mm, 5 µm), acetonitrile (A) and water(B) as mobile phases for gradient elution, and the flow rate being 1. 0 mL/min. RESULTS: Five components showed good linearity. The average recoveries were between 95% - 105%. Five Astragalosides were determined in twelve batches of Astragali Radix and ten batches of Jinqi Jiangtang tablet. CONCLUSION: This is a specific, sensitive and simple method for simultaneous determination of Astragaloside IV, Astragaloside I Astragaloside II, Astragaloside III and Isostragaloside II in Astragali Radix and Jinqi Jiangtang tablet.

Xylanase enhances gut microbiota-derived butyrate to exert immune-protective effects in a histone deacetylase-dependent manner.

BACKGROUND: Commensal bacteria in the intestine release enzymes to degrade and ferment dietary components, producing beneficial metabolites. However, the regulatory effects of microbial-derived enzymes on the intestinal microbiota composition and the influence on host health remain elusive. Xylanase can degrade xylan into oligosaccharides, showing wide application in feed industry. RESULTS: To validate the immune-protective effects of xylanase, Nile tilapia was used as the model and fed with xylanase. The results showed that dietary xylanase improved the survival rate of Nile tilapia when they were challenged with Aeromonas hydrophila. The transcriptome analysis showed significant enrichment of genes related to interleukin-17d (il-17d) signaling pathway in the xylanase treatment group. High-throughput sequencing revealed that dietary xylanase altered the composition of the intestinal microbiota and directly promoted the proliferation of Allobaculum stercoricanis which could produce butyrate in vitro. Consequently, dietary xylanase supplementation increased the butyrate level in fish gut. Further experiment verified that butyrate supplementation enhanced the expression of il-17d and regenerating islet-derived 3 gamma (reg3g) in the gut. The knockdown experiment of il-17d confirmed that il-17d is necessary for butyrate to protect Nile tilapia from pathogen resistance. Flow cytometry analysis indicated that butyrate increased the abundance of IL-17D+ intestinal epithelial cells in fish. Mechanistically, butyrate functions as an HDAC3 inhibitor, enhancing il-17d expression and playing a crucial role in pathogen resistance. CONCLUSION: Dietary xylanase significantly altered the composition of intestinal microbiota and increased the content of butyrate in the intestine. Butyrate activated the transcription of il-17d in intestinal epithelial cells by inhibiting histone deacetylase 3, thereby protecting the Nile tilapia from pathogen infection. This study elucidated how microbial-derived xylanase regulates host immune function, providing a theoretical basis for the development and application of functional enzymes. Video Abstract.

Probiotic Pediococcus pentosaceus restored gossypol-induced intestinal barrier injury by increasing propionate content in Nile tilapia.

BACKGROUND: Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. RESULTS: A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate's function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. CONCLUSIONS: The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations.

Ligand-Induced In Situ Epitaxial Growth of PbI2 Nanosheets/MAPbI3 Heterojunction Realizes High-Performance HTM-Free Carbon-Based MAPbI3 Solar Cells.

Hole-transporting layer-free carbon-based perovskite solar cells (HTL-free C-PSCs) hold great promise for photovoltaic applications due to their low cost and outstanding stability. However, the low power conversion efficiency (PCE) of HTL-free C-PSCs mainly results from grain boundaries (GBs). Here, epitaxial growth is proposed to rationally design a hybrid nanostructure of PbI2 nanosheets/perovskite with the desired photovoltaic properties. A post-treatment technique using tri(2,2,2-trifluoromethyl) phosphate (TFEP) to induce in situ epitaxial growth of PbI2 nanosheets at the GBs of perovskite films realizes high-performance HTL-free C-PSCs. The structure model and high-resolution transmission electron microscope unravel the epitaxial growth mechanism. The epitaxial growth of oriented PbI2 nanosheets generates the PbI2/perovskite heterojunction, which not only passivates defects but forms type-I band alignment, avoiding carrier loss. Additionally, Fourier-transform infrared spectroscopy, 31P NMR, and 1H NMR spectra reveal the passivation effect and hydrogen bonding interaction between TFEP and perovskite. As a result, the VOC is remarkably boosted from 1.04 to 1.10 V, leading to a substantial gain in PCE from 14.97% to 17.78%. In addition, the unencapsulated PSC maintains the initial PCE of 80.1% for 1440 h under air ambient of 40% RH. The work offers a fresh perspective on the rational design of high-performance HTL-free C-PSCs.

A practical recurrence risk model based on Lasso-Cox regression for gastric cancer.

INTRODUCTION: Gastric cancer remains huge cancer threat worldwide. Detecting the recurrence of gastric cancer after treatment is especially important in improving the prognosis of patients. We aim to fit different risk models with different clinical variables for patients with gastric cancer, which further provides applicable guidance to clinical doctors for their patients. METHODS: We collected the primary data from the medical record system in Lanzhou University Second Hospital and further cleaned the primary data via assessing data integrity artificially; meanwhile, detailed conclusion criteria and exclusion criteria were made. We used R software (version 4.1.3) and SPSS 25.0 to analyze data and build models, in which SPSS was used to analyze the correlation and difference of different items in the training set and testing set, and different R packages were used to run LASSO regression, Cox regression and nomogram for variable selection, model construction and model validation. RESULT: A total of 649 patients were included in our data analysis and model building. In LASSO regression selection, seven variables, pathological stage, tumor size, the number of total lymph nodes, the number of metastatic lymph nodes, intraoperative blood loss (IBL), the level of AFP and CA199, showed their correlation to the dependent variable. The multivariable Cox regression model fitted using these seven variables showed medium prediction ability, with an AUC of 0.840 in the training set and 0.756 in the testing set. CONCLUSIONS: Pathological stage, tumor size, the number of total lymph nodes, the number of metastatic lymph nodes, IBL, the level of AFP and CA199 are significant in identifying recurrence risk for gastric cancer patients after radical gastrectomy.

Government drivers of gastric cancer prevention: The identification of risk areas and macro factors in Gansu, China.

The threat of gastric cancer remains significant worldwide, especially in Gansu, located in northwestern China. However, the spatiotemporal distribution characteristics and the impacts of macro factors such as social-economic, climatic conditions, and healthcare resources allocation were less reported before. Based on the data from the medical big data platform of the Gansu Province Health Commission, Gansu Province Bureau of Statistics and some public databases, we conducted joinpoint regression analysis, spatial autocorrelation analysis, trend surface analysis, space scanning analysis, geographically and temporally weighted regression (GTWR) analysis with Joinpoint_5.0, ArcGIS_10.8, GeoDa, and SaTScanTM_10.1.1. Finally, we have found that the increasing trend of gastric cancer incidence in Gansu has reached a turning point and is now declining. Moreover, significant spatial heterogeneity exists in the distribution of gastric cancer across Gansu Province. The identified risk areas and the impacts of macro factors on gastric cancer and their temporal trends could provide evidence for governments to develop specific policies for gastric cancer prevention.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature.

BACKGROUND: To evaluate the clinicopathological features and prognosis of gastric cancer (GC) occurring synchronously with gastrointestinal stromal tumor (GIST). CASE SUMMARY: We report 19 patients with concurrent GC and GIST (17 male and 2 female, median age 62 years). GC was most often located in the lower third of the stomach. GIST was diagnosed preoperatively in four patients. GIST was most often located in the gastric body (n = 8, 42%). The most common growth pattern in GIST was extraluminal (n = 12, 63%). The positive expression rates of CD117 and CD34 in GIST were 100% and 95%, respectively. Most patients with GIST (n = 17, 89%) were very low or low risk. There was no recurrence of GIST during follow-up. The 3-year cumulative survival rate was 73.9%, and the 5-year cumulative survival rate was 59.2%. The combined analysis of this study and literature reports (47 reports, 157 patients) found that GC and GIST were usually located in the lower third (42%) and middle third (51%) of the stomach. GC was usually early (stage I: 42%), poorly differentiated (42%) intestinal-type adenocarcinoma (51%). GISTs were primarily small in diameter (median: 1.2 cm) and very low or low risk (89%). CONCLUSION: Synchronous GC and GIST may not be rare. They have specific clinicopathological characteristics, and may have mutual inhibition in pathogenesis and progression.

Uridine alleviates high-carbohydrate diet-induced metabolic syndromes by activating sirt1/AMPK signaling pathway and promoting glycogen synthesis in Nile tilapia (Oreochromis niloticus).

Carbohydrates have a protein sparing effect, but long-term feeding of a high-carbohydrate diet (HCD) leads to metabolic disorders due to the limited utilization efficiency of carbohydrates in fish. How to mitigate the negative effects induced by HCD is crucial for the rapid development of aquaculture. Uridine is a pyrimidine nucleoside that plays a vital role in regulating lipid and glucose metabolism, but whether uridine can alleviate metabolic syndromes induced by HCD remains unknown. In this study, a total of 480 Nile tilapia (Oreochromis niloticus) (average initial weight 5.02 ± 0.03 g) were fed with 4 diets, including a control diet (CON), HCD, HCD + 500 mg/kg uridine (HCUL) and HCD + 5,000 mg/kg uridine (HCUH), for 8 weeks. The results showed that addition of uridine decreased hepatic lipid, serum glucose, triglyceride and cholesterol (P < 0.05). Further analysis indicated that higher concentration of uridine activated the sirtuin1 (sirt1)/adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway to increase lipid catabolism and glycolysis while decreasing lipogenesis (P < 0.05). Besides, uridine increased the activity of glycogen synthesis-related enzymes (P < 0.05). This study suggested that uridine could alleviate HCD-induced metabolic syndrome by activating the sirt1/AMPK signaling pathway and promoting glycogen synthesis. This finding reveals the function of uridine in fish metabolism and facilitates the development of new additives in aquatic feeds.

The Contributions of Trace Elements on Molecular Subtype-Specific Colorectal Cancer.

Purpose: Although growing studies have reported the disturbances of trace elements (TEs) homeostasis was closely associated with the occurrence of colorectal cancer (CRC), the clinical value of TEs in CRC with different molecular subtypes was largely unknown. This study aimed to explore the correlation between KRAS mutations/MSI status and serum TEs levels in patients with CRC. Methods: The serum concentrations of 18 TEs were detected by inductively coupled plasma emission spectrometry (ICP-MS). MSI status (two mononucleotides: BAT25, BAT26, three dinucleotides: D2S123, D5S346, and D17S250), KRAS (G516T, G517A, G518C, G520T, G521A, G522C, and G532A) mutations were detected by the multiplex fluorescent PCR and the real-time fluorescent quantitative PCR, respectively. The correlations among KRAS mutations/MSI status, demographic and clinical characteristics, and TEs were analyzed by Spearman correlation analysis. Results: The propensity score matching (PSM) analysis was adopted to minimize differences between groups. Before PSM, 204 CRC patients were recruited in this study, including 123 KRAS-negative patients and 81 KRAS-positive patients according to the test results of KRAS mutations, and 165 MSS patients and 39 MSI patients based on MSI detection. After PSM, the serum concentration of Mn was significantly lower in CRC patients with KRAS mutations than those without KRAS mutations, and a significant negative correlation was observed between Mn and Pb in the KRAS-positive cases. CRC patients carrying MSI had a significantly lower level of Rb compared to MSS patients. Importantly, Rb was significantly positively correlated with Fe, Mn, Se, and Zn in patients with MSI. Collectively, all our data indicated that the occurrence of different molecular events might be accompanied by different alterations in types and levels of serum TEs. Conclusions: CRC patients with different molecular subtypes presented different alterations in types and levels of serum TEs. Mn was significantly negatively correlated with the KRAS mutations, and Rb was noticeably negatively correlated with the MSI status, indicating certain TEs might contribute to the pathogenesis of molecular subtype-specific colorectal cancer.

Lactobacillus plantarum Ameliorates High-Carbohydrate Diet-Induced Hepatic Lipid Accumulation and Oxidative Stress by Upregulating Uridine Synthesis.

The overconsumption of carbohydrates induces oxidative stress and lipid accumulation in the liver, which can be alleviated by modulation of intestinal microbiota; however, the underlying mechanism remains unclear. Here, we demonstrated that a strain affiliated with Lactobacillus plantarum (designed as MR1) efficiently attenuated lipid deposition, oxidative stress, as well as inflammatory response, which are caused by high-carbohydrate diet (HC) in fish with poor utilization ability of carbohydrates. Serum untargeted metabolome analysis indicated that pyrimidine metabolism was the significantly changed pathway among the groups. In addition, the content of serum uridine was significantly decreased in the HC group compared with the control group, while it increased by supplementation with L. plantarum MR1. Further analysis showed that addition of L. plantarum MR1 reshaped the composition of gut microbiota and increased the content of intestinal acetate. In vitro experiment showed that sodium acetate could induce the synthesis of uridine in hepatocytes. Furthermore, we proved that uridine could directly ameliorate oxidative stress and decrease liver lipid accumulation in the hepatocytes. In conclusion, this study indicated that probiotic L. plantarum MR1 ameliorated high-carbohydrate diet-induced hepatic lipid accumulation and oxidative stress by increasing the circulating uridine, suggesting that intestinal microbiota can regulate the metabolism of nucleotides to maintain host physiological homeostasis.

Development of Machine Learning Tools for Predicting Coronary Artery Disease in the Chinese Population.

Purpose: Coronary artery disease (CAD) is one of the major cardiovascular diseases and the leading cause of death globally. Blood lipid profile is associated with CAD early risk. Therefore, we aim to establish machine learning models utilizing blood lipid profile to predict CAD risk. Methods: In this study, 193 non-CAD controls and 2001 newly-diagnosed CAD patients (1647 CAD patients who received lipid-lowering therapy and 354 who did not) were recruited. Clinical data and the result of routine blood lipids tests were collected. Moreover, low-density lipoprotein cholesterol (LDL-C) subfractions (LDLC-1 to LDLC-7) were classified and quantified using the Lipoprint system. Six predictive models (k-nearest neighbor classifier (KNN), logistic regression (LR), support vector machine (SVM), decision tree (DT), multilayer perceptron (MLP), and extreme gradient boosting (XGBoost)) were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), recall (sensitivity), accuracy, precision, and F1 score. The selected features were analyzed and ranked. Results: While predicting the CAD development risk of the CAD patients without lipid-lowering therapy in the test set, all models obtained AUC values above 0.94, and the accuracy, precision, recall, and F1 score were above 0.84, 0.85, 0.92, and 0.88, respectively. While predicting the CAD development risk of all CAD patients in the test set, all models obtained AUC values above 0.91, and the accuracy, precision, recall, and F1 score were above 0.87, 0.94, 0.87, and 0.92, respectively. Importantly, small dense LDL-C (sdLDL-C) and LDLC-4 play pivotal roles in predicting CAD risk. Conclusions: In the present study, machine learning tools combining both clinical data and blood lipid profile showed excellent overall predictive power. It suggests that machine learning tools are suitable for predicting the risk of CAD development in the near future.