Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Effect of hydrocolloids on starch digestion: A review.

Rapidly digestible starch can increase postprandial blood sugar rapidly, which can be overcome by hydrocolloids. The paper aims to review the effect of hydrocolloids on starch digestion. Hydrocolloids used to reduce starch digestibility are mostly polysaccharides like xanthan gum, pectin, ß-glucan, and konjac glucomannan. Their effectiveness is related to their source and structure, mixing mode of hydrocolloid/starch, physical treatment, and starch processing. The mechanisms of hydrocolloid action include increased system viscosity, inhibition of enzymatic activity, and reduced starch accessibility to enzymes. Reduced starch accessibility to enzymes involves physical barrier and structural orderliness. In the future, physical treatments and intensity used for stabilizing hydrocolloid/starch complex, risks associated with different doses of hydrocolloids, and the development of related clinical trials should be focused on. Besides, investigating the effect of hydrocolloids on starch should be conducted in the context of practical commercial applications rather than limited to the laboratory level.

Effect of tea polyphenols on chitosan packaging for food preservation: Physicochemical properties, bioactivity, and nutrition.

Chitosan packaging has been widely studied for food preservation, the application of which is expanded by the incorporation of tea polyphenols. This paper reviews the influence of tea polyphenols incorporation on chitosan-based packaging from the perspectives of physicochemical properties, bioactivity used for food preservation, and nutritional value. The physicochemical properties included optical properties, mechanical properties, water solubility, moisture content, and water vapor barrier property, concluding that the addition of tea polyphenols improved the opacity, water solubility, and water vapor barrier property of chitosan packaging, and the mechanical properties and water content were decreased. The bioactivity used for food preservation, that is antioxidant and antimicrobial properties, is enhanced by tea polyphenols, improving the preservation of food like meat, fruits, and vegetables. In the future, efforts will be needed to improve the mechanical properties of composite film and adjust the formula of tea polyphenols/chitosan composite film to apply to different foods. Besides, the identification and development of high nutritional value tea polyphenol/chitosan composite film is a valuable but challenging task. This review is expected to scientifically guide the application of tea polyphenols in chitosan packaging.

Identification and functional analysis of circulating small extracellular vesicle lncRNA signatures in children with fulminant myocarditis.

Fulminant myocarditis (FM) is the most serious type of myocarditis. However, the molecular mechanism underlying the pathogenesis of FM has not been fully elucidated. Small extracellular vesicles (sEVs) play important roles in many diseases, but any potential role in paediatric FM has not been reported. Here, the differential signatures of lncRNAs in plasma sEVs were studied in FM children and healthy children using transcriptome sequencing followed by functional analysis. Then immune-related lncRNAs were screened to study their role in immune mechanisms, the levels and clinical relevance of core immune-related lncRNAs were verified by qRT-PCR in a large sample size. Sixty-eight lncRNAs had increased levels of plasma sEVs in children with FM and 11 had decreased levels. Functional analysis showed that the sEVs-lncRNAs with different levels were mainly related to immunity, apoptosis and protein efflux. Seventeen core immune-related sEVs-lncRNAs were screened, functional enrichment analysis showed that these lncRNAs were closely related to immune activation, immune cell migration and cytokine pathway signal transduction. The results of the study show that sEVs-lncRNAs may play an important role in the pathogenesis of fulminant myocarditis in children, especially in the mechanism of immune regulation.

Inoculum Sources of Puccinia striiformis f. sp. tritici for Stripe Rust Epidemics on the Eastern Coast of China.

Stripe rust, a fungal disease caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases affecting wheat production areas worldwide. In recent years in China, wheat stripe rust has caused huge yield losses throughout the vast Huang-Huai-Hai region, including the eastern coast regions, especially Shandong province. The aim of the present study was to explore the population structure and potential inoculum sources of the pathogen in this region. A total of 234 Pst isolates in 2021 were collected and isolated from seven provinces and identified for virulence phenotypes using 19 Chinese differentials and for genotypes using 17 single-nucleotide polymorphism-based Kompetitive allele-specific PCR markers. The virulence phenotype tests identified predominant races CYR34 (18.0%) and CYR32 (16.0%) in Shandong, which were similar to the results in Henan province, also with the predominant races CYR34 (21.9%) and CYR32 (18.8%). Based on the virulence data of phenotyping, the Pst populations in Shandong, Hubei, and Henan were similar. The genotypic analysis revealed remarkable gene flows among the Shandong, Hubei, Henan, Yunnan, and Guizhou populations, showing a migration of Pst from the southwestern oversummering regions to Shandong through the winter spore production regions. Genetic structure analysis also indicated an additional migration route from the northwestern oversummering regions through winter spore production regions to Shandong. The results are useful for understanding stripe rust epidemiology in the eastern coast region and improving control of the disease throughout the country.

Is the application of organic fertilizers becoming an undeniable source of microplastics and resistance genes in agricultural systems?

The application of organic fertilizers is becoming an undeniable source of microplastics and antibiotic resistance genes (ARGs) in agricultural soils. The complex microbial activity further transfers resistance genes and their host bacteria to agricultural products and throughout the entire food chain. Therefore, the current main focus is on reducing the abundance of microplastics and ARGs in organic fertilizers at the source, as well as managing microplastics and ARGs in soil. The control of microplastic abundance in organic fertilizers is currently only achieved through pre-composting selection and other methods. However, there are still many shortcomings in the research on the distribution characteristics, propagation and diffusion mechanisms, and control technologies of ARGs, and some key scientific issues still need to be urgently addressed. The high-temperature composting of organic waste can effectively reduce the abundance of ARGs in organic fertilizers to a certain extent. However, it is also important to consider the spread of ARGs in residual antibiotic-resistant bacteria (ARB). This article systematically explores the pathways and interactions of microplastics and resistance genes entering agricultural soils through the application of organic fertilizers. The removal of microplastics and ARGs from organic fertilizers was discussed in detail. Based on the limitations of existing research, further investigation in this area is expected to provide valuable insights for the development and practical implementation of technologies aimed at reducing soil microplastics and resistance genes.

Four new constituents from the fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1-2), two new geranyl glucosides (3-4), and nine known compounds (5-13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

Expedient and divergent synthesis of unnatural peptides through cobalt-catalyzed diastereoselective umpolung hydrogenation.

The development of a reliable method for asymmetric synthesis of unnatural peptides is highly desirable and particularly challenging. In this study, we present a versatile and efficient approach that uses cobalt-catalyzed diastereoselective umpolung hydrogenation to access noncanonical aryl alanine peptides. This protocol demonstrates good tolerance toward various functional groups, amino acid sequences, and peptide lengths. Moreover, the versatility of this reaction is illustrated by its successful application in the late-stage functionalization and formal synthesis of various representative chiral natural products and pharmaceutical scaffolds. This strategy eliminates the need for synthesizing chiral noncanonical aryl alanines before peptide formation, and the hydrogenation reaction does not result in racemization or epimerization. The underlying mechanism was extensively explored through deuterium labeling, control experiments, HRMS identification, and UV-Vis spectroscopy, which supported a reasonable CoI/CoIII catalytic cycle. Notably, acetic acid and methanol serve as safe and cost-effective hydrogen sources, while indium powder acts as the terminal electron source.

Stable and oxidative charged Ru enhance the acidic oxygen evolution reaction activity in two-dimensional ruthenium-iridium oxide.

The oxygen evolution reactions in acid play an important role in multiple energy storage devices. The practical promising Ru-Ir based catalysts need both the stable high oxidation state of the Ru centers and the high stability of these Ru species. Here, we report stable and oxidative charged Ru in two-dimensional ruthenium-iridium oxide enhances the activity. The Ru0.5Ir0.5O2 catalyst shows high activity in acid with a low overpotential of 151 mV at 10 mA cm-2, a high turnover frequency of 6.84 s-1 at 1.44 V versus reversible hydrogen electrode and good stability (618.3 h operation). Ru0.5Ir0.5O2 catalysts can form more Ru active sites with high oxidation states at lower applied voltages after Ir incorporation, which is confirmed by the pulse voltage induced current method. Also, The X-ray absorption spectroscopy data shows that the Ru-O-Ir local structure in two-dimensional Ru0.5Ir0.5O2 solid solution improved the stability of these Ru centers.

Polyacetylenes with xanthine oxidase inhibitory activity from the medicinal and edible fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Five new polyacetylene derivatives (1-5), cyclocodonlandiynosides A-E, and eight known analogues (6-13) were isolated and identified from the fruits of Cyclocodon lancifolius. Their structures were established via spectroscopic and chemical methods, including NMR, HRESIMS, enzymatic hydrolysis, Mo2(OAc)4-induced circular dichroism and sugar derivatization. Compound 1 contains a nitrogenous fragment, which was rarely found in C14 polyacetylenes. Compounds 3 and 4 are polyacetylene glucosides possessing novel aglycones. All the isolated polyacetylenes (except 12) were screened for their xanthine oxidase (XO) inhibitory activity. All the tested compounds, at the concentration of 62.5 µg/mL, showed XO inhibiting effects. Among them, 13 and 3 showed the most potent XO inhibitory activity with IC50 values of 87.65 and 96.32 µM, compared to the positive control allopurinol with an IC50 value of 19.25 µM.

Oxidation of Cathepsin D by Hydroxy Radical: Its Effect on Enzyme Structure and Activity against Myofibrillar Proteins Extracted from Coregonus peled.

In this study, cathepsin D was oxidized in vitro with different concentrations of H2O2, and the activity, structure, and extent of myofibrillar protein degradation by oxidized cathepsin D were evaluated. The sulfhydryl content of cathepsin D decreased to 9.20% after oxidation, while the carbonyl content increased to 100.06%. The ß-sheet in the secondary structure altered due to oxidation as well. The changes in the intrinsic fluorescence and UV absorption spectra indicated that oxidation could cause swelling and aggregation of cathepsin D molecules. The structure of cathepsin D could change its activity, and the activity was highest under 1 mM H2O2. Cathepsin D could degrade myofibrillar proteins in different treatment groups, and the degree of degradation is various. Therefore, this study could provide a scientific basis for the mechanism of interaction among hydroxyl radical oxidation, cathepsin D, and MP degradation.

The potential of curcumin-based co-delivery systems for applications in the food industry: Food preservation, freshness monitoring, and functional food.

Currently, curcumin-based co-delivery systems are receiving widespread attention. However, a systematic summary of the possibility of curcumin-based co-delivery systems used for the food industry from multiple directions based on the functional characteristics of curcumin is lacking. This review details the different forms of curcumin-based co-delivery systems including the single system of nanoparticle, liposome, double emulsion, and multiple systems composed of different hydrocolloids. The structural composition, stability, encapsulation efficiency, and protective effects of these forms are discussed comprehensively. The functional characteristics of curcumin-based co-delivery systems are summarized, involving biological activity (antimicrobial and antioxidant), pH-responsive discoloration, and bioaccessibility/bioavailability. Correspondingly, potential applications for food preservation, freshness detection, and functional foods are introduced. In the future, more novel co-delivery systems for active ingredients and food matrices should be developed. Besides, the synergistic mechanisms between active ingredients, delivery carrier/active ingredient, and external physical condition/active ingredient should be explored. In conclusion, curcumin-based co-delivery systems have the potential to be widely used in the food industry.

Effects of CaCl2 on 3D Printing Quality of Low-Salt Surimi Gel.

In order to develop low-salt and healthy surimi products, we limited the amount of NaCl to 0.5 g/100 g in this work and studied the effect of CaCl2 (0, 0.5, 1.0, 1.5, and 2.0 g/100 g) on the 3D printing quality of low-salt surimi gel. The results of rheology and the 3D printing showed that the surimi gel with 1.5 g/100 g of CaCl2 added could squeeze smoothly from the nozzle and had good self-support and stability. The results of the chemical structure, chemical interaction, water distribution, and microstructure showed that adding 1.5 g/100 g of CaCl2 could enhance the water-holding capacity and mechanical strength (the gel strength, hardness, springiness, etc.) by forming an orderly and uniform three-dimensional network structure, which limited the mobility of the water and promoted the formation of hydrogen bonds. In this study, we successfully replaced part of the salt in surimi with CaCl2 and obtained a low-salt 3D product with good printing performance and sensory properties, which could provide theoretical support for the development of healthy and nutritious surimi products.

Acyl Hydrazides and Acyl Hydrazones as High-Performance Chemical Exchange Saturation Transfer MRI Contrast Agents.

Chemical exchange saturation transfer (CEST) MRI is a versatile molecular imaging approach that holds great promise for clinical translation. A number of compounds have been identified as suitable for performing CEST MRI, including paramagnetic CEST (paraCEST) agents and diamagnetic CEST (diaCEST) agents. DiaCEST agents are very attractive because of their excellent biocompatibility and potential for biodegradation, such as glucose, glycogen, glutamate, creatine, nucleic acids, et al. However, the sensitivity of most diaCEST agents is limited because of small chemical shifts (1.0-4.0 ppm) from water. To expand the catalog of diaCEST agents with larger chemical shifts, herein, we have systematically investigated the CEST properties of acyl hydrazides with different substitutions, including aromatic and aliphatic substituents. We have tuned the labile proton chemical shifts from 2.8-5.0 ppm from water while exchange rates varied from ~680 to 2340 s-1 at pH 7.2, which allows strong CEST contrast on scanners down to B0 = 3 T. One acyl hydrazide, adipic acid dihydrazide (ADH), was tested on a mouse model of breast cancer and showed nice contrast in the tumor region. We also prepared a derivative, acyl hydrazone, which showed the furthest shifted labile proton (6.4 ppm from water) and excellent contrast properties. Overall, our study expands the catalog of diaCEST agents and their application in cancer diagnosis.

Optimal Design of Mid-Infrared Nonlinear-Optical Crystals: From SrZnSnSe4 to SrZnSiSe4.

Improving the laser damage threshold (LDT) of mid-infrared nonlinear-optical (MIR NLO) crystal materials is crucial for their applications in areas such as environmental monitoring and pharmaceutical detection. This paper presents the successful synthesis of SrZnSiSe4, a new MIR NLO crystal material that balances the LDT and second-harmonic-generation (SHG) effects and achieves phase matching. By replacement of Sn with Si in the existing SrZnSnSe4 material, the band gap of the material was increased, resulting in an LDT that is twice that of SrZnSnSe4, while maintaining the 2 × AgGaS2 effect. The SHG and band gap of SrZnSiSe4 derived from the experiments are 2 × AgGaS2 and 1.95 eV. The band gap of SrZnSiSe4 is better than that of SrZnSnSe4 (1.82 eV), and the LDT of SrZnSiSe4 is about twice that of SrZnSnSe4. Moreover, first-nature principal calculations confirm that SrZnSiSe4 can achieve phase matching after 1520 nm with a birefringence of 0.10, making it an excellent candidate for MIR NLO crystals.

Altered plasma exosome miRNAs and novel potential biomarkers in pediatric fulminant myocarditis.

Previous studies have indicated that exosome-mediated intercellular microRNAs (miRNA) can influence fulminant myocarditis (FM) pathogenesis between immune and cardiac cells. This study explored plasma exosome miRNA profile in pediatric FM using a small RNA microarray. As per our analysis, we observed the differential expression of 266 miRNAs, including 197 upregulated and 69 downregulated candidate genes. Differentially expressed mRNAs in pediatric FM patients' peripheral blood mononuclear cells (PBMCs) were intersected with miRNA target genes predicting tools to screen for FM-specific target genes. The hub genes and their biological and mechanistic pathways related to inflammation and/or the immune system were identified. CeRNA networks of lncRNAs, circRNAs, miRNAs, and mRNAs between cardiomyocytes and PBMCs were finally established. Furthermore, we verified that hsa-miR-146a-5p, hsa-miR-23a-3p, and hsa-miR-27a-3p had higher expression levels in exosomes of pediatric FM patients by qRT-PCR, and hsa-miR-146a-5p shown high sensitivities and specificities for FM diagnosis. Overall, the results demonstrate that the exosome miRNAs play a regulatory role between immune and cardiac cells and provide research targets.

Metastable Hexagonal Phase SnO2 Nanoribbons with Active Edge Sites for Efficient Hydrogen Peroxide Electrosynthesis in Neutral Media.

Electrochemical two-electron oxygen reduction reaction (2 e- ORR) to produce hydrogen peroxide (H2 O2 ) is a promising alternative to the energetically intensive anthraquinone process. However, there remain challenges in designing 2 e- ORR catalysts that meet the application criteria. Here, we successfully adopt a microwave-assisted mechanochemical-thermal approach to synthesize hexagonal phase SnO2 (h-SnO2 ) nanoribbons with largely exposed edge structures. In 0.1 M Na2 SO4 electrolyte, the h-SnO2 catalysts achieve the excellent H2 O2 selectivity of 99.99 %. Moreover, when employed as the catalyst in flow cell devices, they exhibit a high yield of 3885.26 mmol g-1 h-1 . The enhanced catalytic performance is attributed to the special crystal structure and morphology, resulting in abundantly exposed edge active sites to convert O2 to H2 O2 , which is confirmed by density functional theory calculations.

Efficient Utilization of Tea Resources through Encapsulation: Dual Perspectives from Core Material to Wall Material.

With the high production and consumption of tea around the world, efficient utilization of tea byproducts (tea pruning, tea residues after production, and drinking) is the focus of improving the economy of the tea industry. This review comprehensively discusses the efficient utilization of tea resources by encapsulation from the dual perspectives of core material and wall material. The core material is mainly tea polyphenols, followed by tea oils. The encapsulation system for tea polyphenols includes microcapsules, nanoparticles, emulsions, gels, conjugates, metal-organic frameworks, liposomes, and nanofibers. In addition, it is also diversified for the encapsulation of tea oils. Tea resources as wall materials refer to tea saponins, tea polyphenols, tea proteins, and tea polysaccharides. The application of the tea-based delivery system widely involves functionally fortified food, meat preservation, film, medical treatment, wastewater treatment, and plant protection. In the future, the coencapsulation of tea resources as core materials and other functional ingredients, the precise targeting of these tea resources, and the wide application of tea resources in wall materials need to be focused on. In conclusion, the described technofunctional properties and future research challenges in this review should be followed.

A review of factors affecting the stability of zein-based nanoparticles loaded with bioactive compounds: from construction to application.

Zein-based nanoparticles loaded with bioactive compounds have positive prospects in the food industry, but an important limiting factor for development is colloidal instability. Currently, extensive researches are focused on solving the instability of zein nanoparticles, but since the beginning of the studies, there has not been a summary of the factors affecting the stability of zein-based nanoparticles. In the present work, the factors were reviewed comprehensively from the perspective of carrier construction and application evaluation. The former mainly includes type, quantity, and characteristics of biopolymer, the mass ratio of biopolymer/bioactive compound to zein, blending sequence of biopolymer, and location of encapsulated bioactive compounds. The latter mainly includes pH, heating, ionic strength, storage, freeze-drying, and gastrointestinal digestion. The former is the prerequisite for the success of the latter. The challenge is that stability research is limited to the laboratory level, and it is difficult to ensure that the stability results are suitable for commercial food matrices due to their complexity. At the laboratory level, the future trends are the influence of external energy and the cross-complexity and uniformity of stability research. The review is expected to provide systematic understanding and guidance for the development of zein-based nanoparticles stability.

Construction of biopolymer-based nanoencapsulation of functional food ingredients using the pH-driven method: a review.

Biopolymer-based nanoencapsulation presents great performance in the delivery of functional food ingredients. In recent years, the pH-driven method has received considerable attention due to its unique characteristics of low energy and organic solvent-free during the construction of biopolymer-based nanoencapsulation. This review summarized the fundamental knowledge of pH-driven biopolymer-based nanoencapsulation. The principle of the pH-driven method is the protonation reaction of functional food ingredients that change with pH. The stability of functional food ingredients in an alkaline environment is a prerequisite for the adoption of this method. pH regulator is also an important influencing factor. Different coating materials used to the pH-driven nanoencapsulation were discussed, including single and composite materials, mainly focusing on proteins. Besides, the application evaluations of pH-driven nanoencapsulation in food were analyzed. The future development trends will be the influence of pH regulators on the carrier, the design of new non-protein-based carriers, the quantification of driving forces, the absorption mechanism of encapsulated nutrients, and the molecular interaction between the wall material and the intestinal mucosa. In conclusion, pH-driven biopolymer-based nanoencapsulation of functional food ingredients will have broad prospects for development.