Multi-spectroscopic characterization of organic salt components in medicinal plant.

The characterization of structure of organic salts in complex mixtures has been a difficult problem in analytical chemistry. In the analysis of Scutellariae Radix (SR), the pharmacopoeia of many countries stipulates that the quality control component is baicalin (≥9% by high performance liquid chromatography (HPLC)). The component with highest response in SR was also baicalin detected by liquid chromatography-mass spectrometry (LC-MS). However, in the attenuated total reflection Fourier transform infrared spectroscopy, the carbonyl peak of glucuronic acid of baicalin did not appear in SR. The results of element analysis, time of flight secondary ion mass spectrometry, matrix assisted laser desorption ionization mass spectrometry and solid-state nuclear magnetic resonance all supported the existence of baicalin magnesium salt. Based on this, this study proposes an analysis strategy guided by infrared spectroscopy and combined with multi-spectroscopy techniques to analyze the structure of organic salt components in medicinal plant. It is meaningful for the research of mechanisms, development of new drugs, and quality control.

Liquid-liquid biopolymers aqueous solution segregative phase separation in food: From fundamentals to applications-A review.

As a result of the spontaneous movement of molecules, liquid-liquid biopolymer segregative phase separation takes place in an aqueous solution. The efficacy of this type of separation can be optimized under conditions where variables such as pH, temperature, and molecular concentrations have minimal impact on its dynamics. Recently, interest in the applications of biopolymers and their segregative phase separation-associated molecular stratification has increased, particularly in the food industry, where these methods permit the purification of specific particles and the embedding of microcapsules. The present review offers a comprehensive examination of the theoretical mechanisms that regulate the liquid-liquid biopolymers aqueous solution segregative phase separation, the factors that may exert an impact on this procedure, and the importance of this particular separation method in the context of food science. These discussion points also address existing difficulties and future possibilities related to the use of segregative phase separation in food applications. This highlights the potential for the design of novel functional foods and the enhancement of food properties.

Fabrication and characterization of alginate-zein core-shell microcapsules for controlled release of buckwheat honey.

In this study, extrusion method was employed to fabricate alginate-zein core-shell microcapsules loaded with buckwheat honey by dropping alginate and buckwheat honey mixture solution into a 70.0 % zein ethanol solution(v/v) containing 5.0 % CaCl2 solution (wt%). The microcapsules were constructed by two parts: 1) the formation of hydrophilic beads through the crosslinking of alginate chains with Ca2+; 2) the introduction of alginate beads into the aqueous zein ethanol solution which decreased the ethanol concentration, prompting the precipitation of zein and the deposition of zein nanoparticles onto the surfaces of alginate beads. Comparing with the alginate beads, the prepared microcapsules not only possessed better water-holding capacity, but also achieved controlled release of buckwheat honey. Importantly, the microcapsules significantly retained the antioxidant activity of the buckwheat honey. Therefore, this innovative method for fabricating alginate-zein core-shell microcapsules can suggest a promising approach to broaden the application of buckwheat honey in the food field.

Formation, influencing factors, and applications of internal channels in starch: A review.

Starch, a natural polymer, has a complex internal structure. Some starches, such as corn and wheat starches, have well-developed surface pores and internal channels. These channel structures are considered crucial in connecting surface stomata and internal cavities and have adequate space for loading guest molecules. After processing or modification, the starch-containing channel structures can be used for food and drug encapsulation and delivery. This article reviews the formation and determination of starch internal channels, and the influence of different factors (such as starch species and processing conditions) on the channel structure. It also discusses relevant starch preparation methods (physical, chemical, enzymatic, and synergistic), and the encapsulation effect of starch containing internal channels on different substances. In addition, the role of internal channels in regulating the starch digestion rate and other aspects is also discussed here. This review highlights the significant multifunctional applications of starch with a channel structure.

Impact of cod skin peptide-ι-carrageenan conjugates prepared via the Maillard reaction on the physical and oxidative stability of Antarctic krill oil emulsions.

This research aimed to construct an emulsifier by the Maillard reaction at various times using cod fish skin collagen peptide (CSCP) and ι-carrageenan (ι-car) to stabilize an Antarctic krill oil (AKO) emulsion. This emulsion was then investigated for physicochemical stability, oxidative stability, and gastrointestinal digestibility. The emulsion stability index and emulsifying activity index of Maillard reaction products (MRPs) were increased by 36.32 % and 66.30 %, respectively, at the appropriate graft degree (25.58 %) compared with the mixture of ι-car and CSCP. In vitro digestibility suggested the higher release of free fatty acids (FFAs) of 10d-MRPs-AKO-emulsion, and the highest bioavailability of AST in 10d-MRPs-AKO was found to be 28.48 %. The findings of this study showed the potential of MRPs to improve peptide function, serve as delivery vehicles for bioactive chemicals, and possibly serve as a valuable emulsifier to be used in the food industry.

Effects of Octenyl-Succinylated Chitosan-Whey Protein Isolated on Emulsion Properties, Astaxanthin Solubility, Stability, and Bioaccessibility.

The synthesis of octenyl-succinylated chitosan with different degrees of substitution resulting from chemical modification of chitosan and controlled addition of octenyl succinic acid was investigated. The modified products were characterized using 1H NMR, FTIR, and XRD, and the degree of substitution was also determined. The properties of the modified chitosan oligosaccharide in solution were evaluated by surface tension and dye solubilization, finding that the molecules self-assembled when they are above the critical aggregation concentration. The two methods yielded consistent results, showing that the self-assembly was reduced with higher levels of substitution. The antimicrobial activity of the octanyl-succinylated chitosan oligosaccharide (OSA-COS) derivatives against Staphylococcus aureus, Escherichia coli, and Fusarium oxysporum f.sp cucumerinum was investigated by the Oxford cup method. While the acetylated COS derivatives were not significantly effective against either E coli or S. aureus, they showed significant antifungal activity toward F. oxysporum that was superior to that of COS. The modified product was found to form a stable emulsion when mixed with whey protein isolate. The emulsion formed by the highly substituted derivatives have a certain stability and loading efficiency, which can be used for the encapsulation and delivery of astaxanthin.

Non-covalent binding of whey protein isolate after ultrasound pretreatment to epigallocatechin gallate: Effects on immune response and gut microbiota in BALB/c mice.

Cow's milk is one of the "big eight" most common allergenic foods, and ß-lactoglobulin and α-Lactalbumin in whey protein are two major allergens of cow's milk protein. An effective strategy for reducing the allergenicity of whey protein is needed. In the present study, protein-EGCG complexes were obtained through non-covalent interactions between untreated or sonicated whey protein isolate (WPI) and epigallocatechin gallate (EGCG), and the allergenicity of complexes was assessed in vivo. The results showed that SWPI-EGCG complex possesses low allergenicity in BALB/c mice. As compared with untreated WPI, SWPI-EGCG complex had less effect on the body weight and organ indexes. Moreover, SWPI-EGCG complex could alleviate the WPI induced allergic reactions and intestinal damage of mice by decreasing the secretion of IgE, IgG, histamine, mMCP-1, modulating the balance of Th1/Th2 and Treg/Th17 response, and increasing the diversity of intestinal flora and the relative abundances of probiotic bacteria. These findings indicate that the interaction of sonicated WPI with EGCG could reduce the allergenicity of WPI, which could provide a new strategy for reducing food allergenicity.

Characterization and Mechanism of Tea Polyphenols Inhibiting Biogenic Amine Accumulation in Marinated Spanish Mackerel.

Putrescine is a low-molecular-weight organic compound that is widely found in pickled foods. Although the intake of biogenic amines is beneficial to humans, an excessive intake can cause discomfort. In this study, the ornithine decarboxylase gene (ODC) was involved in putrescine biosynthesis. After cloning, expression and functional verification, it was induced and expressed in E. coli BL21 (DE3). The relative molecular mass of the recombinant soluble ODC protein was 14.87 kDa. The function of ornithine decarboxylase was analyzed by determining the amino acid and putrescine content. The results show that the ODC protein could catalyze the decarboxylation of ornithine to putrescine. Then, the three-dimensional structure of the enzyme was used as a receptor for the virtual screening of inhibitors. The binding energy of tea polyphenol ligands to the receptor was the highest at -7.2 kcal mol-1. Therefore, tea polyphenols were added to marinated fish to monitor the changes in putrescine content and were found to significantly inhibit putrescine production (p < 0.05). This study lays the foundation for further research on the enzymatic properties of ODC and provides insight into an effective inhibitor for controlling the putrescine content in pickled fish.

Synthesis of acylated derivatives of chitosan oligosaccharide and evaluation of their potential antifungal agents on Fusarium oxysporum.

Chitosan oligosaccharide (COS) is an important carbohydrate-based biomaterial for synthesizing candidate drugs and biological agents. This study synthesized COS derivatives by grafting acyl chlorides of different alkyl chain lengths (C8, C10, and C12) onto COS molecules and further investigated their physicochemical properties and antimicrobial activity. The COS acylated derivatives were characterized using Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, X-ray diffraction, and thermogravimetric analysis. COS acylated derivatives were successfully synthesized and possessed high solubility and thermal stability. As for the evaluation of antibacterial activity, COS acylated derivatives did not significantly inhibit Escherichia coli and Staphylococcus aureus, but they significantly inhibited Fusarium oxysporum, which was superior to that of COS. Transcriptomic analysis revealed that COS acylated derivatives exerted antifungal activity mainly by downregulating the expression of efflux pumps, disrupting cell wall integrity, and impeding normal cell metabolism. Our findings provided a fundamental theory for the development of environmentally friendly antifungal agents.

Mechanism of Reduced Glutathione Induced Lysozyme Defolding and Molecular Self-Assembly.

The distinctive assembly behaviors of lysozyme (Lys) feature prominently in food, materials, biomedicine, and other fields and have intrigued many scholars. Although our previous work suggested that reduced glutathione (GSH) could induce lysozyme to form interfacial films at the air/water interface, the underlying mechanism is still obscure. In the present study, the effects of GSH on the disulfide bond and protein conformation of lysozyme were investigated by fluorescence spectroscopy, circular dichroism spectroscopy, and infrared spectroscopy. The findings demonstrated that GSH was able to break the disulfide bond in lysozyme molecules through the sulfhydryl/disulfide bond exchange reaction, thereby unraveling the lysozyme. The ß-sheet structure of lysozyme expanded significantly, while the contents of α-helix and ß-turn decreased. Furthermore, the interfacial tension and morphology analysis supported that the unfolded lysozyme tended to arrange macroscopic interfacial films at the air/water interface. It was found that pH and GSH concentrations had an impact on the aforementioned processes, with higher pH or GSH levels having a positive effect. This paper on the exploration of the mechanism of GSH-induced lysozyme interface assembly and the development of lysozyme-based green coatings has better instructive significance.

Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer via Circulating Tumor DNA Methylation.

Importance: Detection of molecular residual disease and risk stratification as early as possible may improve the treatment of patients with cancer. Efficient pragmatic tests are therefore required. Objective: To measure circulating tumor DNA (ctDNA) with 6 DNA methylation markers in blood samples and to evaluate the association of the presence of ctDNA with colorectal cancer (CRC) recurrence throughout the disease course. Design, Setting, and Participants: In this multicenter prospective longitudinal cohort study performed from December 12, 2019, to February 28, 2022, 350 patients with stage I to III CRC were recruited from 2 hospitals for collection of blood samples before and after surgery, during and after adjuvant chemotherapy, and every 3 months for up to 2 years. A multiplex, ctDNA methylation, quantitative polymerase chain reaction assay was used to detect ctDNA in plasma samples. Results: A total of 299 patients with stage I to III CRC were evaluated. Of 296 patients with preoperative samples, 232 (78.4%) tested positive for any of the 6 ctDNA methylation markers. A total of 186 patients (62.2%) were male, and the mean (SD) age was 60.1 (10.3) years. At postoperative month 1, ctDNA-positive patients were 17.5 times more likely to relapse than were ctDNA-negative patients (hazard ratio [HR], 17.5; 95% CI, 8.9-34.4; P < .001). The integration of ctDNA and carcinoembryonic antigen tests showed risk stratification for recurrence with an HR of 19.0 (95% CI, 8.9-40.7; P < .001). Furthermore, ctDNA status at postoperative month 1 was strongly associated with prognosis in patients treated with adjuvant chemotherapy of different durations and intensities. After adjuvant chemotherapy, ctDNA-positive patients had a significantly shorter recurrence-free survival than did the ctDNA-negative patients (HR, 13.8; 95% CI, 5.9-32.1; P < .001). Longitudinal ctDNA analysis after the postdefinitive treatment showed a discriminating effect in that ctDNA-positive patients had poorer recurrence-free survival than did the ctDNA-negative patients (HR, 20.6; 95% CI, 9.5-44.9; P < .001). The discriminating effect was enhanced (HR, 68.8; 95% CI, 18.4-257.7; P < .001) when ctDNA status was maintained longitudinally. Postdefinitive treatment analysis detected CRC recurrence earlier than radiologically confirmed recurrence, with a median lead time of 3.3 months (IQR, 0.5-6.5 months). Conclusions and Relevance: The findings of this cohort study suggest that longitudinal assessment of ctDNA methylation may enable the early detection of recurrence, potentially optimizing risk stratification and postoperative treatment of patients with CRC.

The health-related quality of life for hemiarthroplasty and total hip arthroplasty in the elderly: A meta-analysis.

Purpose: What constitutes the optimal surgical plan for femoral neck fractures (FNFs) in elderly patients is controversial. The European quality of life 5-Dimension Questionnaire (EU-5Q) is an international scale used to measure the health-related quality of life (HRQoL) after surgery. We aim to verify the hip arthroplasty effect in elderly patients by analyzing HRQoL scores in the EU-5Q scale. Methods: We searched the EBSCO, Embase, PubMed, Ovid, Cochrane Library, and Web of Science databases using strict searching from established to 30 November 2022; used the Cochrane Library's Risk of Bias Assessment Tool and the Newcastle-Ottawa Scale to evaluate the literature; and used RevMan5.4.1 software to perform a meta-analysis. All the included studies used the EU-5Q scale to validate the overall outcomes for elderly hip arthroplasty. Results: The final included literature is composed of four RCTs, two cohort studies, three case-control trials, and three cross-sectional surveys. This study compared HRQoL scores measured by the EU-5Q scale, including 328 elderly patients with total hip arthroplasty (THA) and 323 elderly patients with hemiarthroplasty, which is statistically significant (OR = 0.05; 95% CI, 0.02~0.08; P = 0.002). The subgroups were as follows: unipolar vs. bipolar and cemented vs. uncemented hemiarthroplasty (OR = 0.06; 95% CI, 0.03~0.08; P < 0.001), follow-up time and age arthroplasty (OR = 0.16; 95% CI, 0.11~0.22; P < 0.001), molecular exercise and enhanced recovery after surgery (ERAS) (OR = 0.02; 95% CI,-0.03~0.07; P = 0.38), and analysis of hemiarthroplasty with cognitive dysfunction vs. the normal group (OR = 0.17; 95% CI, 0.08~0.26; P < 0.001). The outcome analysis was consistent with the included studies, and HRQoL of the EU-5Q scale is sensitive to surgical outcomes between THA and hemiarthroplasty. Conclusion: Surgeons still need to further evaluate and verify whether the hip arthroplasty surgical program or effect in elderly patients is optimal. Hemiarthroplasty operations in elderly patients have pointed toward a new direction for clinical treatment, and HRQoL scores measured by the EU-5Q can sensitively reflect the rehabilitation status after hip arthroplasty surgery. Moreover, the extensive correlation between surgical outcomes and perioperative neurocognitive function should be further investigated.

Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer.

BACKGROUND: Oxaliplatin is one of the most widely used chemotherapy drugs for colorectal cancer (CRC). Resistance to oxaliplatin threatens the prognosis of CRC. Since previous studies have aroused interest in fatty acid metabolism in cancer, in this study, we determined whether fatty acid biosynthesis and the related regulating mechanism contribute to oxaliplatin resistance in CRC. METHODS: The effect of the fatty acid synthase (FASN) and its inhibitor Orlistat was characterized in Gene Expression Omnibus (GEO) databases, oxaliplatin-resistant cell lines, and xenografts. MRNA-seq and analysis identified related pathway changes after the application of Orlistat, which was verified by Western blotting. RESULTS: By leveraging the GEO databases, FASN and closely related gene signatures were identified as being correlated with the response to oxaliplatin-based chemotherapy and poor prognosis. Additionally, FASN-upregulated expression promoted oxaliplatin resistance in CRC cell lines. We then applied Orlistat, a typical FASN inhibitor, in cell culture and xenograft models of oxaliplatin-resistant CRC, which attenuated the resistance to oxaliplatin. Additionally, the combination of the FASN inhibitor and oxaliplatin significantly increased cell cycle arrest and facilitated apoptosis, partly due to the diminished phosphorylation of the MAPK/ERK and PI3K/AKT pathways. In vivo studies showed that inhibiting fatty acid biosynthesis with Orlistat restrained the growth of xenograft tumors and increased the responsiveness to oxaliplatin. CONCLUSIONS: Our study revealed that FASN enhanced resistance to oxaliplatin in CRC. The inhibition of FASN could rescue the response to oxaliplatin by regulating MAPK/ERK and PI3K/AKT pathways.

Characterizations and the Mechanism Underlying Cryoprotective Activity of Peptides from Enzymatic Hydrolysates of Pseudosciaena crocea.

Antifreeze peptides are a class of small molecule protein hydrolysates that protect frozen products from cold damage under freezing or subcooling conditions. In this study, three different Pseudosciaena crocea (P. crocea) peptides were from pepsin, trypsin, and neutral protease enzymatic hydrolysis. It aimed to elect the P. crocea peptides with better activity through molecular weight, antioxidant activity, and amino acid analysis, as well as to compare the cryoprotective effects with a commercial cryoprotectant. The results showed that the untreated fillets were prone to be oxidized, and the water-holding capacity after freeze-thaw cycle decreased. However, the treatment of the trypsin hydrolysate of P. crocea protein significantly promoted the water-holding capacity level and reduced the loss of Ca2+-ATP enzyme activity and the structural integrity damage of myofibrillar protein in surimi. Moreover, compared with 4% sucrose-added fillets, trypsin hydrolysate treatment enhanced the umami of frozen fillets and reduced the unnecessary sweetness. Therefore, the trypsin hydrolysate of P. crocea protein could be used as a natural cryoprotectant for aquatic products. Hence, this study provides technical support for its use as a food additive to improve the quality of aquatic products after thawing and provides a theoretical basis and experimental foundation for the in-depth research and application of antifreeze peptides.

Enhancement of lycopene bioaccessibility in tomatoes using excipient emulsions: Effect of dark tea polysaccharides.

This study fabricated a novel excipient emulsion by adding dark tea polysaccharides to improve the bioaccessibility of lycopene from tomatoes. Results indicated that addition of tea polysaccharides greatly increased the antioxidant activity of excipient emulsions. Additionally, tea polysaccharides markedly improved the physical stability of excipient emulsion when being mixed with tomato puree and passing through a simulated gastrointestinal tract, contributing to an increase in electrostatic and steric repulsion between the droplets. Besides, certain amount of tea polysaccharides (0.05 - 0.2 wt%) could increase the rate and extent of lipid digestion in tomato-emulsion mixtures. Finally, lycopene bioaccessibility was significantly increased (from 16.95 % to 26.21 %) when 0.1 wt% tea polysaccharides were included, which was mainly ascribed to the ability of tea polysaccharides to increase lipid digestion and reduce carotenoid oxidation within the gastrointestinal tract. These results suggest that well-designed excipient emulsions may increase carotenoids bioavailability in the complex food matrices.

Nutritional properties and osteogenic activity of simulated digestion components and peptides from Larimichthys crocea.

Fish provides a range of health benefits due to its nutritional and bioactive components. However, the bioactive peptides derived from Larimichthys crocea proteins were not fully investigated, especially the beneficial effects related to bone growth in vitro. In this study, the water extract protein was subjected to the simulated in vitro digestion process, and the osteogenic effect of enzymatic hydrolysate at different digestion stages was evaluated by the proliferation of osteoblast. The protein hydrolyzates of group pepsin treatment for 1 h and pepsin treatment for 2 h showed higher osteogenic activity in vitro. Two peptides including IERGDVVVQDSPSD from pepsin treatment for 1 h and RGDLGIEIPTEK from pepsin treatment for 2 h were identified, which revealed eminent effects in terms of promoting osteoblast proliferation and enhancing ALP activity. Moreover, the available nutrients in the proteins were determined by the molecular weight distribution and free amino acid composition. Those peptides also showed stronger interaction with RGD than integrins. Therefore, the peptides from Larimichthys crocea can be used as an effective ingredient for promoting bone growth in the future.

Effects of pile fermentation on the physicochemical, functional, and biological properties of tea polysaccharides.

This study investigated the influence of pile fermentation on the physicochemical, functional, and biological properties of tea polysaccharides (TPS). Results indicated that the extraction yield, uronic acid content, and polyphenol content of TPS greatly increased from 1.8, 13.1 and 6.3 % to 4.1, 27.9, and 7.8 %, respectively, but the molecular weight markedly decreased from 153.7 to 76.0 kDa after pile fermentation. Additionally, the interfacial, emulsion formation, and emulsion stabilization properties of TPS were significantly improved after pile fermentation. For instance, 1.0 wt% TPS isolated from dark tea (D-TPS) can fabricate 8.0 wt% MCT oil-in-water nanoemulsion (d32 ≈ 159 nm) with potent storage stability. Moreover, the antioxidant and α-glucosidase inhibitory activities of D-TPS was higher than that of TPS isolated from sun-dried raw tea (R-TPS). Overall, this study indicated that pile fermentation markedly affected the physicochemical and structural characteristics of TPS, thereby improving their functional and biological properties.

Reconstruction of Gap-Free Land Surface Temperature at a 100 m Spatial Resolution from Multidimensional Data: A Case in Wuhan, China.

Land surface temperatures (LST) are vital parameters in land surface-atmosphere interactions. Constrained by technology and atmospheric interferences, LST retrievals from various satellite sensors usually return missing data, thus negatively impacting analyses. Reconstructing missing data is important for acquiring gap-free datasets. However, the current reconstruction methods are limited for maintaining spatial details and high accuracies. We developed a new gap-free algorithm termed the spatial feature-considered random forest regression (SFRFR) model; it builds stable nonlinear relationships to connect the LST with related parameters, including terrain elements, land coverage types, spectral indexes, surface reflectance data, and the spatial feature of the LST, to reconstruct the missing LST data. The SFRFR model reconstructed gap-free LST data retrieved from the Landsat 8 satellite on 27 July 2017 in Wuhan. The results show that the SFRFR model exhibits the best performance according to the various evaluation metrics among the SFRFR, random forest regression and spline interpolation, with a coefficient of determination (R2) reaching 0.96, root-mean-square error (RMSE) of 0.55, and mean absolute error (MAE) of 0.55. Then, we reconstructed gap-free LST data gathered in Wuhan from 2016 to 2021 to analyze urban thermal environment changes and found that 2020 presented the coolest temperatures. The SFRFR model still displayed satisfactory results, with an average R2 of 0.91 and an MAE of 0.63. We further discuss and discover the factors affecting the visual performance of SFRFR and identify the research priority to circumvent these disadvantages. Overall, this study provides a simple, practical method for acquiring gap-free LST data to help us better understand the spatiotemporal LST variation process.

Early detection and prognosis prediction for colorectal cancer by circulating tumour DNA methylation haplotypes: A multicentre cohort study.

Background: Early detection and prognosis prediction of colorectal cancer (CRC) can significantly reduce CRC-related mortality. Recently, circulating tumour DNA (ctDNA) methylation has shown good application foreground in the early detection and prognosis prediction of multiple tumours. Methods: This multicentre cohort study evaluated ctDNA methylation haplotype patterns based on archived plasma samples (collected between 2010 and 2018) from 1138 individuals at two medical centres: Fudan University Shanghai Cancer Center (Shanghai, China) and Southern Medical University Nanfang Hospital (Guangzhou, Guangdong, China), including 366 healthy individuals, 182 patients with advanced adenoma (AA), and 590 patients with CRC. Samples were processed using the ColonES assay, a targeted bisulfite sequencing method that detects ctDNA methylation haplotype patterns in 191 genomic regions. Among these 1138 samples, 748 were used to develop a classification model, and 390 served as a blinded cohort for independent validation. The study is registered at https://register.clinicaltrials.gov with the unique identifier NCT03737591. Results: The model obtained from unblinded samples discriminated patients with CRC or AA from normal controls with high accuracy. In the blinded validation set, the ColonES assay achieved sensitivity values of 79.0% (95% confidence interval (CI), 66%-88%) in AA patients and 86.6% (95% CI, 81%-91%) in CRC patients with a specificity of 88.1% (95% CI, 81%-93%) in healthy individuals. The model area under the curve (AUC) for the blinded validation set was 0.903 for AA samples and 0.937 for CRC samples. Additionally, the prognosis of patients with high preoperative ctDNA methylation levels was worse than that of patients with low ctDNA methylation levels (p = 0.001 for relapse-free survival and p = 0.004 for overall survival). Interpretation: We successfully developed and validated an accurate, noninvasive detection method based on ctDNA methylation haplotype patterns that may enable early detection and prognosis prediction for CRC. Funding: The Grant of National Natural Science Foundation of China (No.81871958), National Natural Science Foundation of China (No. 82203215), Shanghai Science and Technology Committee (No. 19140902100), Scientific Research Fund of Fudan University (No.IDF159052), Shanghai Municipal Health Commission (SHWJRS 2021-99), and Shanghai Sailing Program (22YF1408800).

Octenyl-succinylated inulins for the delivery of hydrophobic drug.

The efficacy of hydrophobic anticancer drugs is limited by their poor solubility in water, inefficient target delivery, and toxic side effects. In this work, doxorubicin (DOX) was solubilized using OSA-inulins which created micellar aggregates in aqueous solution above a critical concentration. In vitro delivery of OSA-inulin-DOX micelles resulted in strong inhibition of the growth of MCF-7 breast cancer cells as compared to free DOX. They also displayed a faster cellular uptake rate, indicating that the micelles were promptly internalized into the cells through CD44 receptor-mediated endocytosis. During in vivo tumor suppression experiments in tumor-bearing mice, the OSA-inulin-DOX micelles strongly hindered tumor growth and showed substantially lower systemic toxicity compared with free DOX. Our achievements demonstrate that OSA-inulin has great potential for the encapsulating, dissolving, and targeted delivery of hydrophobic drugs, especially antitumor drugs, for nutraceutical, medical, and pharmaceutical applications.