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.

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.

A Rare Earth Chalcogenide Nonlinear Optical Crystal KLaGeS4: Achieving Good Balance among Band Gap, Second Harmonic Generation Effect, and Birefringence.

Midinfrared nonlinear optical (NLO) rare earth chalcogenides have attracted extensive research interest in recent several decades. Employing charge-transfer engineering strategy in the early stage, rigid tetrahedral [GeS4] was introduced into rare-earth sulfides to synthesize KYGeS4, which had an enlarged band gap while maintaining a strong second harmonic generation (SHG) effect. Based on KYGeS4, La was equivalently substituted to successfully synthesize KLaGeS4 with a stronger SHG effect (dij = 1.2 × AgGaS2) and lower cost. Meanwhile, a larger band gap (Eg = 3.34 eV) was retained and realized phase matching (Δn = 0.098 @ 1064 nm). KLaGeS4 enabled an effective balance among band gap, SHG effect, and birefringence, making it a promising candidate for infrared NLO optical materials among various rare-earth sulfides.

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.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

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.

Revealing the role of Peg13: A promising therapeutic target for mitigating inflammation in sepsis.

To investigate the role of Peg13 in modulating the inflammatory response in sepsis, we established Lipopolysaccharide (LPS)-induced 293T cells and mouse models. Peg13 expression was assessed at various time points after infection using RT-qPCR. The levels of high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) were quantified through ELISA. A total of 44 septic patients and 36 healthy participants were recruited to measure Peg13 and HMGB1 levels in the blood. Peg13 demonstrated significant down-regulation in the supernatant of LPS-induced 293T cells and in the blood of LPS-induced mice. Moreover, the levels of proinflammatory cytokines HMGB1 and IL-6 were elevated in both the supernatant of LPS-induced cell models and blood specimens from LPS-induced murine models, and this elevation could be notably reduced by Peg13 suppression. In a clinical context, Peg13 and HMGB1 levels were higher in septic patients compared to healthy subjects. Peg13 exhibited a negative correlation with HMGB1, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) among septic patients. Peg13 mitigates the inflammatory response by reducing the release of proinflammatory cytokines HMGB1 and IL-6 in sepsis, presenting a potential therapeutic target for alleviating inflammation in sepsis treatment.

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.

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.

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.

Comparison of the Spatiotemporal Expression Patterns of Three Cre Lines, Emx1IRES-Cre, D6-Cre and hGFAP-Cre, Commonly Used in Neocortical Development Research.

Emx1IRES-Cre, D6-Cre and hGFAP-Cre are commonly used to conditionally manipulate gene expression or lineage tracing because of their specificity in the dorsal telencephalon during early neurogenesis as previously described. However, the spatiotemporal differences in Cre recombinase activity would lead to divergent phenotypes. Here, we compared the patterns of Cre activity in the early embryos among the three lines by mating with reporter mice. The activities of Emx1IRES-Cre, D6-Cre and hGFAP-Cre were observed in the dorsal telencephalon, starting from approximately embryonic day 9.5, 11.5 and 12.5, respectively. Although all the three lines have activity in radial glial cells, Emx1IRES-Cre fully covers the dorsal and medial telencephalon, including the archicortex and cortical hem. D6-Cre is highly restricted to the dorsal telencephalon with anterior-low to posterior-high gradients, partially covers the hippocampus, and absent in the cortical hem. Moreover, both Emx1IRES-Cre and hGFAP-Cre exhibit Cre activity outside the dorsal neocortex. Meanwhile, we used the three Cre lines to mediate Dicer knockout and observed inconsistent phenotypes, including discrepancies in radial glial cell number, survival and neurogenesis in the neocortex and hippocampus. Together we proved differences in Cre activity can perturb the resultant phenotypes, which aid researchers in appropriate experimental design.

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.

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.

Monitoring tumour microenvironment changes during anti-angiogenesis therapy using functional MRI.

OBJECTIVE: This study aims to explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in assessing vessel function and tumour aggressiveness during anti-angiogenesis treatment. MATERIALS AND METHODS: A colon cancer xenograft model was established in BALB/C nude mice with the HCT116 cell line. Sixteen mice were randomly divided into Group A and Group B, which were treated with saline or bevacizumab by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th days and underwent DCE-MRI and BOLD-MRI examinations before and on the 3rd, 6th, 9th, 12th and 15th days after treatment. Group C was treated with oxaliplatin monotherapy, and Group D was treated with bevacizumab and oxaliplatin as a point of comparison for therapeutic effects. The pathological examinations included HE, HIF-1α, fibronectin and TUNEL staining, as well as α-SMA and CD31 double staining. One-way analysis of variance and correlation analysis were the main methods used for statistical analysis. RESULTS: Group D manifested the highest tumour inhibition rate and smallest tumour volume on day 15, followed by Group C, Group B and Group A. Ktrans (F = 81.386, P < 0.001), Kep (F = 45.901, P < 0.001), Ve (F = 384.290, P < 0.001) and R2* values (F = 89.323, P < 0.001) showed meaningful trends with time in Group B but not Group A. The Ktrans values and tumour vessel maturity index (VMI) were higher than baseline values 3-12 days after bevacizumab treatment. The CD31 positive staining rate and VMI had the strongest correlations with Ktrans values, followed by AUC180, Ve and Kep values. The R2* value positively correlated with the positive staining rates of HIF-1α and fibronectin. CONCLUSION: Intermittent application of low-dose anti-angiogenic inhibitor treatment may help improve the effect of chemotherapy by reducing hypoxia-related treatment resistance and improving drug delivery. DCE-MRI is useful for evaluating vessel maturity and vascular normalization, while BOLD-MRI may help to predict tumour hypoxia and metastatic potential after anti-vascular treatment.

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.

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.

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.

Phthalocyanine-sensitized graphene-CdS nanocomposites: an enhanced photoelectrochemical immunosensing platform.

A novel strategy is developed for the fabrication of graphene-CdS (G-CdS) nanocomposites by in situ growth of CdS nanoparticles onto simultaneously reduced graphite oxide, which is noncovalently functionalized by sodium 1-pyrene sulfonate through strong π-π stacking interactions. Subsequently, cobalt 2,9,16,23-tetraaminophthalocyanine (CoTAPc) is self-assembled on the G-CdS nanocomposites through electrostatic interactions to produce phthalocyanine-sensitized G-CdS nanocomposites. The photoactive superstructure enhances the photocurrent generation capability, and presents an efficient photoelectrochemical immunosensing platform for the ultrasensitive detection of the prostate-specific antigen (PSA). The quantitative measurement of PSA is based on the decrease in the photocurrent intensity of the phthalocyanine-sensitized G-CdS nanocomposites, which results from an increase in the steric hindrance due to the formation of the immunocomplex. A linear relationship between the photocurrent decrease and the PSA concentration is obtained in the wide range from 1 pgmL(-1) to 5 µgmL(-1) with a detection limit of 0.63 pgmL(-1). The proposed sensor shows high sensitivity, stability, reproducibility, and can become a promising platform for other biomolecular detection.

Recent advances in delivery systems of fucoxanthin.

Fucoxanthin is a carotenoid derived from marine algae/microalgae, which has wide application in the food industry. This review first proposes the promotion development of fucoxanthin delivery systems from the perspective of diverse biological activities, extraction complexity, instability, poor aqueous solubility, and low bioavailability. The materials for the delivery systems of fucoxanthin mainly include protein, polysaccharide, and lipid. Colloidal structures include nanoparticles, microcapsules, emulsions, gels, coacervates, and nanofibers. Delivery systems exhibited positive effects on the stability, release, bioavailability, and bioactivity of fucoxanthin. Currently, the reported applications of fucoxanthin in food are limited. A variety of colloidal structures should be constructed to provide options for fucoxanthin applications in different foods, and the applicability of fucoxanthin colloidal structures in commercial products should be advanced. Additionally, a set of internationally unified evaluation criteria for fucoxanthin stability and bioavailability should be established.