Prognostic value of CDKN2A in head and neck squamous cell carcinoma via pathomics and machine learning.

This study aims to enhance the prognosis prediction of Head and Neck Squamous Cell Carcinoma (HNSCC) by employing artificial intelligence (AI) to analyse CDKN2A gene expression from pathology images, directly correlating with patient outcomes. Our approach introduces a novel AI-driven pathomics framework, delineating a more precise relationship between CDKN2A expression and survival rates compared to previous studies. Utilizing 475 HNSCC cases from the TCGA database, we stratified patients into high-risk and low-risk groups based on CDKN2A expression thresholds. Through pathomics analysis of 271 cases with available slides, we extracted 465 distinctive features to construct a Gradient Boosting Machine (GBM) model. This model was then employed to compute Pathomics scores (PS), predicting CDKN2A expression levels with validation for accuracy and pathway association analysis. Our study demonstrates a significant correlation between higher CDKN2A expression and improved median overall survival (66.73 months for high expression vs. 42.97 months for low expression, p = 0.013), establishing CDKN2A's prognostic value. The pathomic model exhibited exceptional predictive accuracy (training AUC: 0.806; validation AUC: 0.710) and identified a strong link between higher Pathomics scores and cell cycle activation pathways. Validation through tissue microarray corroborated the predictive capacity of our model. Confirming CDKN2A as a crucial prognostic marker in HNSCC, this study advances the existing literature by implementing an AI-driven pathomics analysis for gene expression evaluation. This innovative methodology offers a cost-efficient and non-invasive alternative to traditional diagnostic procedures, potentially revolutionizing personalized medicine in oncology.

Climate and soil stressed elevation patterns of plant species to determine the aboveground biomass distributions in a valley-type Savanna.

Introduction: Extreme environments such as prolonged high temperatures and droughts can cause vulnerability of vegetation ecosystems. The dry-hot valleys of Southwestern China, known for their extremely high annual temperature, lack of water, and unique non-zonal "hot island" habitat in the global temperate zone, provide exceptional sites for studying how plant adapts to the prolonged dry and hot environment. However, the specific local biotic-environment relationships in these regions remain incompletely elucidated. The study aims to evaluate how valley-type Savanna vegetation species and their communities adapt to long-term drought and high-temperature stress environments. Methods: The study investigated the changes in species diversity and communities' aboveground biomass of a valley-type Savanna vegetation along an elevation gradient of Yuanmou dry-hot valley in Jinsha River basin, southwest China. Subsequently, a general linear model was utilized to simulate the distribution pattern of species diversities and their constituent biomass along the elevation gradient. Finally, the RDA and VPH mothed were used to evaluate the impacts and contributions of environmental factors or variables on the patterns. Results and discussion: The field survey reveals an altitudinal gradient effect on the valley-type Savanna, with a dominant species of shrubs and herbs plants distribution below an elevation of 1700m, and a significant positive relationship between the SR, Shannon-Wiener, Simpson, and Pielou indices and altitudes. Relatively, the community aboveground biomass did not increase significantly with elevation, which was mainly due to a decreased biomass of herbaceous plants along the elevation. Different regulators of shrub-herbaceous plant species and their functional groups made different elevation patterns of species diversity and aboveground biomass in valley-type Savannas. Herbaceous plants are responsible for maintaining species diversity and ensuring stability in the aboveground biomass of the vegetation. However, the influence of shrubs on aboveground biomass became more pronounced as environmental conditions varied along the altitudinal gradient. Furthermore, species diversity was mainly influenced by soil and climatic environmental factors, whereas community biomass was mainly regulated by plant species or functional groups. The study demonstrates that the spatial pattern of valley-type Savanna was formed as a result of different environmental responses and the productive capacity of retained plant species or functional groups to climate-soil factors, highlighting the value of the Yuanmou dry-hot Valley as a microcosm for exploring the intricate interactions between vegetation evolution and changes in environmental factors.

Design and Biological Evaluation of the Long-Acting C5-Inhibited Ornithodoros moubata Complement Inhibitor (OmCI) Modified with Fatty Acid.

Disorder of complement response is a significant pathogenic factor causing some autoimmune and inflammation diseases. The Ornithodoros moubata Complement Inhibitor (OmCI), a small 17 kDa natural protein, was initially extracted from soft tick salivary glands. The protein was found binding to complement C5 specifically, inhibiting the activation of the complement pathway, which is a successful therapeutic basis of complement-mediated diseases. However, a short half-life due to rapid renal clearance is a common limitation of small proteins for clinical application. In this study, we extended the half-life of OmCI by modifying it with fatty acid, which was a method used to improve the pharmacokinetics of native peptides and proteins. Five OmCI mutants were initially designed, and single-site cysteine mutation was introduced to each of them. After purification, four OmCI mutants were obtained that showed similar in vitro biological activities. Three mutants of them were subsequently coupled with different fatty acids by nucleophilic substitution. In total, 15 modified derivatives were screened and tested for anticomplement activity in vitro. The results showed that coupling with fatty acid would not significantly affect their complement-inhibitory activity (CH50 and AH50). OmCIT90C-CM02 and OmCIT90C-CM05 were validated as the applicable OmCI bioconjugates for further pharmacokinetic assessments, and both showed improved plasma half-life in mice compared with unmodified OmCI (15.86, 17.96 vs 2.57 h). In summary, our data demonstrated that OmCI conjugated with fatty acid could be developed as the potential long-acting C5 complement inhibitor in the clinic.

Aptamer-based fluorescent sensor for highly sensitive detection of methamphetamine.

The construction of a fluorescence aptamer sensor was achieved by employing the fundamental principle of fluorescence resonance energy transfer. By employing molecular modeling technologies to identify the binding site, the high-affinity aptamer APT-40nt was derived from the whole sequence and utilized on the graphene oxide (GO) fluorescent platform for the purpose of achieving a highly sensitive detection of methamphetamine (METH). The aptamer tagged with fluorescein (FAM) dye undergoes quenching in the presence of GO due to π-stacking interaction. With the addition of the target, the aptamer that has been tagged was detached from the GO surface, forming a stable complex with METH. This process resulted in fluorescence restoration of the system, and the degree of fluorescence restoration was proportional to METH concentration in the linear range of 1-50 and 50-200 nM. Notably, under optimized conditions, the detection limit of this aptasensor was as low as 0.78 nM, which meets the detection limit requirements of METH detection in saliva and urine in some countries and regions. Moreover, other common illicit drugs and metabolites had minimizing interference with the determination. The established aptasensor, therefore, has been successfully applied to detect METH in saliva and urine samples and exhibited satisfactory recoveries (87%-111%). This aptasensor has the advantages of low detection limit, excellent selectivity, ease of operation, and low cost, providing a promising strategy for on-site detection of METH in saliva and urine.

Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases.

A gas chromatography-mass spectrometry (GC-MS) method for the determination of difenidol hydrochloride in biological specimens has been developed. The method exhibited excellent recovery (> 90%) and precision (RSD < 10%), and the LOD was 0.05 µg/mL or µg/g, which met the requirements of bioanalytical method. Through the animal model of the forensic toxicokinetics, the dynamic distribution, postmortem redistribution (PMR) and stability in specimen preservation process of difenidol in animals were studied. The experimental results showed that after intragastric administration, the difenidol's concentrations in the heart-blood and various organs increased over time except stomach, and then decreased gradually after reaching the peaks of concentration. The toxicological kinetics equation and toxicokinetic parameters were established by processing the data of the mean drug concentration of difenidol changing with time. In PMR experiment, the concentrations of difenidol in some organs closer to the gastrointestinal tract (heart-blood, heart, liver, lung, kidney, and spleen) changed significantly at different time points. But the concentration of difenidol in brain tissues which were far away from the gastrointestinal tract and muscles with larger overall mass was relatively stable. PMR of difenidol was therefore confirmed. Thus, the effect of PMR on the concentration of difenidol in the specimens should be considered in cases involving difenidol poisoning or death. Furthermore, the stability of difenidol in heart-blood samples from poisoned rats was investigated at various time points and under different preservation conditions (20 °C, 4 °C, - 20 °C and 20 °C (1% NaF)) for a period of two months. Difenidol was stable and did not decompose in the preserved blood. Therefore, this study provided the experimental basis for the forensic identification of the cases of difenidol hydrochloride poisoning (death). PMR has been verified by practical lethal cases.

Characterization and transcriptomic analysis of a native fungal pathogen against the rice pest Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Given the threats posed by insecticide resistance to its control, eco-friendly strategies based on microbial pathogens emerged as a promising biocontrol alternative. In the present study, we isolated a native fungal pathogen against BPH from infected BPH cadavers and preliminarily identified as a strain of Aspergillus fumigatus based on morphological and molecular methods. Laboratory bioassay revealed that this fungal strain was highly virulent to BPH both at nymphal and adult stages, with the median lethal times (LT50) of 7.5 and 5.8 days under high conidial concentration of 1 × 109 conidia mL-1. A genome-wide view of gene expressions in BPH against fungal attack was analyzed by transcriptomic sequencing and consequently a large number of differentially expressed genes that mainly involved in host immune defense and cell detoxification were found. RNAi-mediated knockdown of an upregulated gene encoding a serine protease (NlSPN) could cause a significant decrease in BPH survival. Combination of dsRNA injection and fungal infection showed an additive effect on BPH mortality, which provided clues to develop new pest management strategies against BPH.

Characteristics of Cephalotaxus fortunei kernel oil and its digestion behaviors.

Cephalotaxus fortunei, a potential underutilized oil resource, contains various active ingredients that exert positive effects on human health. In the present study, characteristics of C. fortunei kernel oil and its digestion properties were systematically investigated. Results indicated that C. fortunei kernels contained high oil content (64.59%), of which over 90% was triacylglycerols (TAGs). The kernel oil was rich in oleic acid (C18:1n-9, 42.88%), linoleic acid (C18:2n-6, 31.05%), and sciadonic acid (C20:3n-6, 10.78%). The kernel oil also contained some beneficial fat-soluble nutrients, such as tocopherols (143 mg/kg) and phytosterols (1474 mg/kg). Thirty-five kinds of TAGs were identified, among which O-O-L (17.96%), O-O-O (12.12%), L-L-O (11.79%), O-L-Et (8.59%), and O-O-Et (8.76%) were the most abundant. In vitro digestion experiments showed that after 120 min of small intestine digestion, the maximum FFAs release level of the kernel oil was 75.02%, which was lower than that of soybean oil (89.63%).

Does omega-3 PUFAs supplementation improve metabolic syndrome and related cardiovascular diseases? A systematic review and meta-analysis of randomized controlled trials.

Literature is inconsistent regarding the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) supplementation on patients with metabolic syndrome (MetS) and related cardiovascular diseases (CVDs). Therefore, the aim of this systematic review and meta-analysis is to summarize data from available randomized controlled trials (RCTs) on the effect of omega-3 PUFAs on lipid profiles, blood pressure, and inflammatory markers. We systematically searched PubMed, Embase, and Cochrane Library databases to identify the relevant RCTs until 1 November 2022. Weighed mean difference (WMD) was combined using a random-effects model. Standard methods were applied to assess publication bias, sensitivity analysis, and heterogeneity among included studies. A total of 48 RCTs involving 8,489 subjects met the inclusion criteria. The meta-analysis demonstrated that omega-3 PUFAs supplementation significantly reduced triglyceride (TG) (WMD: -18.18 mg/dl; 95% CI: -25.41, -10.95; p < 0.001), total cholesterol (TC) (WMD: -3.38 mg/dl; 95% CI: -5.97, -0.79; p = 0.01), systolic blood pressure (SBP) (WMD: -3.52 mmHg; 95% CI: -5.69, -1.35; p = 0.001), diastolic blood pressure (DBP) (WMD: -1.70 mmHg; 95% CI: -2.88, -0.51; p = 0.005), interleukin-6 (IL-6) (WMD: -0.64 pg/ml; 95% CI: -1.04, -0.25; p = 0.001), tumor necrosis factor-α (TNF-α) (WMD: -0.58 pg/ml; 95% CI: -0.96, -0.19; p = 0.004), C-reactive protein (CRP) (WMD: -0.32 mg/l; 95% CI: -0.50, -0.14; p < 0.001), and interleukin-1 (IL-1) (WMD: -242.95 pg/ml; 95% CI: -299.40, -186.50; p < 0.001), and significantly increased in high-density lipoprotein (HDL) (WMD: 0.99 mg/dl; 95% CI: 0.18, 1.80; p = 0.02). However, low-density lipoprotein (LDL), monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1 (ICAM-1), and soluble endothelial selectin (sE-selectin) were not affected. In subgroup analyses, a more beneficial effect on overall health was observed when the dose was ≤ 2 g/day; Omega-3 PUFAs had a stronger anti-inflammatory effect in patients with CVDs, particularly heart failure; Supplementation with omega-3 PUFAs was more effective in improving blood pressure in MetS patients and blood lipids in CVDs patients, respectively. Meta-regression analysis showed a linear relationship between the duration of omega-3 PUFAs and changes in TG (p = 0.023), IL-6 (p = 0.008), TNF-α (p = 0.005), and CRP (p = 0.025). Supplementation of omega-3 PUFAs had a favorable effect on improving TG, TC, HDL, SBP, DBP, IL-6, TNF-α, CRP, and IL-1 levels, yet did not affect LDL, MCP-1, ICAM-1, and sE-selectin among patients with MetS and related CVDs.

Automatic detection and recognition of nasopharynx gross tumour volume (GTVnx) by deep learning for nasopharyngeal cancer radiotherapy through magnetic resonance imaging.

BACKGROUND: In this study, we propose the deep learning model-based framework to automatically delineate nasopharynx gross tumor volume (GTVnx) in MRI images. METHODS: MRI images from 200 patients were collected for training-validation and testing set. Three popular deep learning models (FCN, U-Net, Deeplabv3) are proposed to automatically delineate GTVnx. FCN was the first and simplest fully convolutional model. U-Net was proposed specifically for medical image segmentation. In Deeplabv3, the proposed Atrous Spatial Pyramid Pooling (ASPP) block, and fully connected Conditional Random Field(CRF) may improve the detection of the small scattered distributed tumor parts due to its different scale of spatial pyramid layers. The three models are compared under same fair criteria, except the learning rate set for the U-Net. Two widely applied evaluation standards, mIoU and mPA, are employed for the detection result evaluation. RESULTS: The extensive experiments show that the results of FCN and Deeplabv3 are promising as the benchmark of automatic nasopharyngeal cancer detection. Deeplabv3 performs best with the detection of mIoU 0.8529 ± 0.0017 and mPA 0.9103 ± 0.0039. FCN performs slightly worse in term of detection accuracy. However, both consume similar GPU memory and training time. U-Net performs obviously worst in both detection accuracy and memory consumption. Thus U-Net is not suggested for automatic GTVnx delineation. CONCLUSIONS: The proposed framework for automatic target delineation of GTVnx in nasopharynx bring us the desirable and promising results, which could not only be labor-saving, but also make the contour evaluation more objective. This preliminary results provide us with clear directions for further study.

The structure of triglycerides impacts the digestibility and bioaccessibility of nutritional lipids during in vitro simulated digestion.

The triglyceride (TAG) structure of lipids may affect their nutritional properties by affecting the process of digestion and absorption. In this paper, a mixture of medium-chain triglycerides and long-chain triglycerides (PM) and medium- and long-chain triglycerides (MLCT) were selected to explore the effects of triglyceride structure on in vitro digestion and bioaccessibility. The results showed that MLCT released more free fatty acids (FFAs) than PM (99.88% vs 92.82%, P < 0.05). The first-order rate constant for FFA release from MLCT was lower than that for PM (0.0395 vs 0.0444 s-1, P < 0.05), which suggests that the rates of PM digestion were faster than those of MLCT. Our results demonstrated that DHA and EPA were more bioaccessible from MLCT than from PM. These results highlighted the important role of TAG structure in regulation of lipid digestibility and bioaccessibility.

An airway-to-brain sensory pathway mediates influenza-induced sickness.

Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes1,2. On infection, immune cells release a 'storm' of cytokines and other mediators, many of which are detected by neurons3,4; yet, the responding neural circuits and neuro-immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis5. A leading model is that PGE2 crosses the blood-brain barrier and directly engages hypothalamic neurons2. Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection.

Synthesis of eicosapentaenoic acid-enriched medium- and long-chain triglyceride by lipase-catalyzed transesterification: a novel strategy for clinical nutrition intervention.

BACKGROUND: Eicosapentaenoic acid (EPA) has been recognized as a promising nutrient to improve therapeutic efficacy for cancer patients. Nevertheless, there are certain limitations to the application of EPA due to its structural characteristics. To maximize the nutritive value of EPA, a type of medium- and long-chain triacylglycerol (MLCT) enriched with EPA was designed and synthesized using the lipase-catalyzed transesterification of medium-chain triglyceride (MCT) and EPA-enriched fish oil (FO). RESULTS: The optimum synthesis conditions for EPA-enriched MLCT used Lipozyme RM as catalyst, and had a substrate mass ratio (MCT/EPA-enriched FO) of 3:1, lipase loading of 80 g kg-1 , a reaction temperature of 60 °C, and a reaction time of 6 h. The MLCT content was as high as 80.79% after the transesterification reaction and the purification, and the content of MLCT containing EPA accounted for 70.21%. The distribution of EPA at the sn-2 position showed a significant increase in MLCT compared with the original substrate, from 18.89% to 26.93%. The in vitro digestion results demonstrated that MLCT had a significantly higher EPA bioaccessibility than the original substrate. CONCLUSION: Eicosapentaenoic acid-enriched MLCT was developed. This may provide a novel strategy for clinical nutritional intervention. © 2023 Society of Chemical Industry.

Does omega-3 PUFA-enriched oral nutritional intervention benefit cancer patients receiving chemo (radio) therapy? A systematic review and meta-analysis of randomized controlled trials.

Although data indicate omega-3 polyunsaturated fatty acids are beneficial nutrients in cancer therapy, the evidences for efficacy of nutritional interventions during chemo (radio) therapy are still limited. The leading goal of the present meta-analysis was to summarize randomized controlled trials involving the administration of ω-3 PUFA-enriched oral nutritional supplements during chemo (radio) therapy, and evaluate the effects on nutritional status and clinical outcomes in patients. We systematically searched PubMed, Embase, Web of Science, Cochrane databases to identify interventions assessing body weight, BMI, immune and inflammatory indicators, plasma omega-3 fatty acids and adverse events, with subgroup analyses for region, types of ω-3 fatty acids, dose, duration and dosage form. In total, 22 studies including 1155 participants met the inclusion criteria. Meta-analysis showed a significant increase in body weight (BW) (WMD = 0.59 kg, 95% CI: 0.06, 1.13, P = 0.03), body mass index (BMI) (WMD = 0.43 kg/m2, 95% CI: 0.07, 0.79, P = 0.02), and plasma total ω-3 fatty acids (SMD = 2.52, 95% CI: 1.27, 3.78, P<0.0001), and a significant reduction in plasma levels of C-reactive protein (CRP) (SMD= -0.53, 95% CI: -0.80, -0.25, P = 0.0001), tumor necrosis factor-α (TNF-α) (WMD = -0.40 pg/mL, 95% CI: -0.80, -0.01, P = 0.05), interleukin 6 (IL-6) (WMD = -1.25 pg/mL, 95% CI: -2.41, -0.10, P = 0.03) and the incidence of adverse events (RR= 0.72, 95% CI: 0.54, 0.95, P = 0.02). However, plasma albumin levels (WMD = 0.02 mg/dL, 95% CI: -0.13, 0.18, P = 0.75) was remained unaffected. Overall, our meta-analysis provides evidences that the consumption of ω-3 PUFA-enriched oral nutritional supplements exert beneficial effects on nutritional status and clinical outcomes in patients undergoing chemo (radio) therapy.

Topical Fungal Infection Induces Shifts in the Gut Microbiota Structure of Brown Planthopper, Nilaparvata lugens (Homoptera: Delphacidae).

The brown planthopper (Nilaparvata lugens, BPH) is a destructive insect pest posing a serious threat to rice production. The fungal entomopathogen Metarhizium anisopliae is a promising alternative that can be used for BPH biocontrol. Recent studies have highlighted the significant involvement of gut microbiota in the insect-fungus interactions. In the presented study, we investigated the effects of topical fungal infection on the gut microbial community structure in BPH. Our results revealed that topical infection with M. anisopliae increased the bacterial load and altered the bacterial community structure in the gut of BPH. The relative abundances of the dominant gut bacteria at the order, family and genus level were significantly different between fungus-infected and uninfected groups. At the genus level, the uninfected BPH harbored high proportions of Pantoea and Enterobacter in the gut, whereas the fungus-infected BPH gut was absolutely dominated by Acinetobacter. Moreover, topical fungal infection significantly inhibited the expressions of immune-related genes encoding anti-microbial protein and dual oxidase that were involved in the maintenance of gut microbiota homeostasis, indicating that gut bacteria imbalance might be attributed in part to the suppression of gut immunity caused by fungal pathogen. Our results highlighted the importance of the gut microbial community during interactions between fungal pathogens and insect hosts.

Reviews of medium- and long-chain triglyceride with respect to nutritional benefits and digestion and absorption behavior.

With the progress in the study of functional lipid, interest has turned recently to the medium- and long-chain triglyceride (MLCT) obtained by modification of natural oil. From a health perspective, MLCT not only provides us with the essential fatty acids, but,moreimportantly,it also reduces body fat accumulation, improves insulin resistance and plays an important role in clinical nutritional treatment. The potential effectiveness of MLCT in the human body is influenced mainly byits digestion and absorption in thegastrointestinaltract. However, the current understanding of the digestion and absorption mechanism of MLCT is still not comprehensive. Thisreview first presents the nutritional properties, digestion and absorption of MLCT. Then it will focus on the effects of MLCT compositions and structures (eg, fatty acid chain length, saturation, and location distribution) on its digestion and absorption process for a better understanding of its nutritional properties. This review also presents the synthesis methods and current application status of MLCT. Finally, the advantages, challenges and future prospects of MLCT are discussed. With its potential health benefits, MLCT is widely being used as nutraceutical in food and pharmaceutical sectors. In the future, the purpose of modifying the digestion and absorption of MLCT can be realized by structural design and other means, to achieve nutritional supplement and precise therapy.

Highly sensitive visual colorimetric sensor for xanthine oxidase detection by using MnO2-nanosheet-modified gold nanoparticles.

In this study, a highly sensitive colorimetric assay has been constructed for the determination of xanthine oxidase (XOD) activity by the GNP@MnO2 core-shell nanoparticles as probe. In the presence of XOD, xanthine can be oxidized to produce H2O2, which makes the MnO2 shell fallen off. With the single particle detection (SPD) based dark field microscopy (DFM), the scattering color of GNP@MnO2 NP probe shows obvious change before and after etching process. At the single particle level, noticeable color change of the single probe can be easily detected in the existence of trace XOD. This SPD-based colorimetric strategy displays broad linear dynamic range (0.02-4 mU/mL) and low detection limit of 7.82 µU/mL, which is more sensitive than the results from ensemble sample measurement. In addition, we tested the inhibitory effect of quercetin on the activity of XOD and obtained good inhibition effect. As a consequence, this SPD-based colorimetric strategy provides new perception for the ultrasensitive detection of molecules in complex system.

Ratiometric fluorimetric and colorimetric probe for sensing and imaging pH changes in living cells.

Cell, enzyme, and tissue activity in living organisms are closely related to intracellular pH. Detecting the changes of intracellular pH is important to understanding the physiological and pathological changes in the process of crucial cell metabolism. A pH probe (HTBI) based on hemicyanine was synthesized. The probe solution displayed a marked colour change from yellow to amaranth with the pH increase from neutral to basic; simultaneously, the emission spectra showed a significant red shift. The probe exhibited a ratiometric fluorescence emission (F586nm /F542nm ) characteristic of pKa 8.82. As expected, HTBI exhibited high sensitivity and selectivity for pH, fine photostability, reversibility, and low cytotoxicity. Therefore, it would be a very useful tool for measuring the intracellular pH changes.

Medium and long-chain structured triacylglycerol enhances vitamin D bioavailability in an emulsion-based delivery system: combination of in vitro and in vivo studies.

Vitamin D (VitD) is an essential fat-soluble micronutrient required for maintaining and regulating calcium homeostasis. Although sunlight can provide VitD, epidemiological studies indicate that the occurrence of VitD deficiency and insufficiency is widespread. Lipids are required at all stages of VitD digestion and absorption. In this research two different medium and long-chain triacylglycerol structures, possessing identical fatty acid composition lipids, namely structured triacylglycerol (STG), and physical mixtures of medium/long-chain triacylglycerol (MCT/LCT), were selected. Our results demonstrated that STG had a significant VitD bioavailability compared to MCT/LCT. In terms of the lipid digestion and absorption, the extent of the higher free fatty acid released (69.42%, p < 0.05), extent of lipolysis (89.28%, p < 0.05), lipolysis rate (0.06 s-1, p < 0.05), and the ratio of the long-chain fatty acid to medium-chain fatty acid of STG (4.8, p < 0.05), result in a higher capacity for accommodating VitD when forming mixed micelles (61.31%, p < 0.05). An in vivo animal study also demonstrated that STG significantly increases the delivery ability of VitD (18.75 ng mL-1, p < 0.05). The findings of this work may have unique applications for designing novel interesterified lipids with an effective delivery capacity for fat-soluble nutrients.

The enzymatic synthesis of EPA-rich medium- and long-chain triacylglycerol improves the digestion behavior of MCFA and EPA: evidence on in vitro digestion.

Medium-chain triglyceride (MCT) and eicosapentaenoic acid (EPA) have been widely applied in nutritional supplementation. However, when administered individually or mixed, they were unable to maximize their nutritional value. Hence, EPA-rich medium- and long-chain triacylglycerol (MLCT) was synthesized from MCT and EPA-rich fish oil (FO) by enzymatic transesterification. The fatty acids in triglyceride (TAG) were rearranged which resulted in significant changes in TAG profiles compared to the physical mixture of MCT and FO (PM). EPA-containing MML (MML, MLM and LMM) and LLM (LLM, LML and MLL) type TAGs account for 70.21%. The fate of different oils (MCT, FO, PM, and MLCT) across the gastrointestinal tract was subsequently simulated using an in vitro digestion model. The results showed that the physical and structural characteristics of different oils during digestion depended upon the oil type and the microenvironment they were in. After 120 min of small intestine digestion, the degree of hydrolysis for MLCT was higher than that for the other three oils. The final FFA release level was in the following order: MLCT (102.79%) > MCT (95.20%) > PM (85.81%) > FO (74.18%). This can be attributed to the composition and positional distribution of fatty acids in TAGs. What's more, LCFAs (EPA) in MLCT mainly existed in the form of sn-2 MAG, which was conducive to their subsequent absorption and transport. These results may aid in the future rational design of structural lipids, thereby regulating lipid digestion and maximizing the nutritional value of oils.

Effects of oral vitamin D supplementation on inflammatory bowel disease: a systematic review and meta-analysis.

Vitamin D (VitD) is a fat-soluble micronutrient that plays a critical role in inflammatory bowel disease (IBD). Although the effective properties of VitD in anti-inflammatory and immune moderation were reviewed, some important issues still remain uncovered. Considering the practicability and high bioavailability, as a more recommended therapeutic approach, the effects of oral VitD supplementation on IBD remain inconclusive. This study aims to investigate the effect and safety of oral VitD supplementation on IBD patients, which has already been registered on PROSPERO (no. CRD42020165045). A pooled analysis of 17 trials with 1127 patients revealed that as a safety therapeutic strategy, oral VitD supplementation effectively increased the concentration of serum 25-hydroxyvitamin D [weighted mean difference 12.15 ng mL-1; 95% confidence interval (CI) 9.26, 15.03; I2 = 90%] and decreased serum C-reactive protein levels [standard mean difference (SMD) -0.33; 95% CI -0.61, -0.05; I2 = 55%], but it did not decrease erythrocyte sedimentation rate levels (SMD 0.35; 95% CI -4.33, 5.03; I2 = 57%), disease activity index (SMD -0.13; 95% CI -0.66, 0.39; I2 = 84%) and relapse rate (RR 0.59; 95% CI 0.19, 1.86; I2 = 79%). These findings suggest that oral VitD supplementation has a role to play in the therapeutic management of IBD. These findings may contribute to public health and clinical dietary guidelines and improve the health of IBD patients.