Identification and expression analysis of Sox family genes in echinoderms.

The Sox gene family, a collection of transcription factors widely distributed throughout the animal kingdom, plays a crucial role in numerous developmental processes. Echinoderms occupy a pivotal position in many research fields, such as neuroscience, sex determination and differentiation, and embryonic development. However, to date, no comprehensive study has been conducted to characterize and analyze Sox genes in echinoderms. In the present study, the evolution and expression of Sox family genes across 11 echinoderms were analyzed using bioinformatics methods. The results revealed a total of 70 Sox genes, with counts ranging from 5 to 8 across different echinoderms. Phylogenetic analysis revealed that the identified Sox genes could be categorized into seven distinct classes: the SoxB1 class, SoxB2 class, SoxC class, SoxD class, SoxE class, SoxF class and SoxH class. Notably, the SoxB1, SoxB2, and SoxF genes were ubiquitously present in all the echinoderms studied, which suggests that these genes may be conserved in echinoderms. The spatiotemporal expression patterns observed for Sox genes in the three echinoderms indicated that various Sox members perform distinct functional roles. Notably, SoxB1 is likely involved in echinoderm ovary development, while SoxH may play a crucial role in testis development in starfish and sea cucumber. In general, the present investigation provides a molecular foundation for exploring the Sox gene in echinoderms, providing a valuable resource for future phylogenetic and genomic studies.

Human biomonitoring of serum polycyclic aromatic hydrocarbons and oxygenated derivatives by gas chromatography coupled with tandem mass spectrometry.

While polycyclic aromatic hydrocarbons (PAHs) are well-known for their potential carcinogenic and mutagenic effects, the health implications of exposure to oxygenated PAHs (OPAHs), which are significant substitutes with increased persistence and bioaccumulation, are less understood. In this work, we compared the background levels of liquid-liquid, solid-phase, and supported-liquid extraction for the determination of serum PAHs and OPAHs. Liquid-liquid extraction demonstrated minimal background interference and was validated and used for human biomonitoring of PAHs and OPAHs in 240 participants using gas chromatography coupled with tandem mass spectrometry. We observed significant positive correlations between these compounds using Spearman correlation analysis. Furthermore, we investigated the concentration levels and compositions of PAHs and OPAHs among different demographic characteristics, including gender, age, and body mass index. Linear regression analysis demonstrated a weak but significant correlation between total concentrations of PAHs and OPAHs and age and body mass index. A multivariate linear regression analysis was then conducted to examine the association of exposure to individual PAHs and OPAHs with the body mass index. Naphthalene exposure and body mass index showed a statistically significant positive correlation, suggesting that higher levels of naphthalene exposure are associated with higher body mass index values. This study establishes a robust method for biomonitoring PAHs and OPAHs in serum, evaluating the exposure levels of these compounds in healthy adults and highlighting their associations with demographic characteristics.

The Aggregated and Micellar Forms of ß-Casein Purified from Donkey and Bovine Milk Present Potential as Carriers for Bioactive Nutritional Compounds.

In recent years, there has been a growing interest in the pure casein fraction of milk protein, particularly ß-casein due to its physicochemical properties as well as its bio- and techno-functional properties. The utilization of self-assembled ß-caseins from bovine origin as nanocarriers for the delivery of nutraceutical compounds or drugs has increased dramatically. Concerning ß-caseins from other milk sources, the use of hypoallergenic donkey ß-caseins as a potential delivery vehicle for nutraceutical hydrophobic compounds is beginning to generate interest. The present review deals with casein micelles models, bovine and donkey ß-casein molecular structures, as well as their physical-chemical properties that account for their exploitation in nutraceutics and pharmaceutics. This review work suggests the possibility of developing delivery systems for hydrophobic bioactive compounds using ß-casein purified from hypoallergenic donkey milk, highlighting the potential of this protein as an innovative and promising vehicle for enhancing the enrichment and bioavailability of various bioactive substances in food products.

[The effect of different degrees of Eustachian tube dysfunction on hearing threshold in patients with acquired primary middle ear cholesteatoma after balloon eustachian tuboplasty].

Objective:To investigate the changes in hearing threshold of the acquired primary cholesteatoma of the middle ear with different degrees of eustachian tube dysfunction after balloon eustachian tuboplasty. Methods:This retrospective study included forty cases with middle ear cholesteatoma and eustachian tube dysfunction who underwent open mastoidectomy + tympanoplasty + balloon eustachian tuboplasty were enrolled. All patients were admitted from November 2020 to April 2022. The preoperative eustachian tube score of 0-2 were defined as the lower group, and the scores of 3-5 were defined as the higher group. Pure tone audiometry was measured preoperatively and 1, 3, 6 and 12 months postoperatively. The average value of bone conduction threshold and air conduction threshold of 250-4 000 Hz were calculated, and the air-bone gap was calculated simultaneously. SPSS 25.0 was used for statistical analysis. P<0.05 was considered statistically significant. Results:In the lower group, the air conduction threshold and air-bone gap at 3 months postoperatively were significantly decreased in comparison with those preoperatively（P<0.05），as was the air-bone gap at 6 months postoperatively（P<0.05）. In the higher group, the air conduction threshold and air-bone gap were significantly decreased at 3, 6 and 12 months postoperatively（P<0.05）. Conclusion:The air conduction threshold and air-bone gap of patients with the acquired primary cholesteatoma of the middle ear and eustachian tube dysfunction were significantly decreased after eustachian tube balloon dilatation. Hearing improvement lasted longer in patients with slight eustachian tube dysfunction.

Oridonin ameliorates ocular surface inflammatory responses by inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway in dry eye.

Chronic inflammation is one of the central drivers in the development of dry eye disease (DED), in which pyroptosis induced by the NLRP3/caspase-1/gasdermin D (GSDMD) pathway plays a key role. This pathway has become a major target for the treatment of a variety of inflammatory disorders. Oridonin (Ori) is a naturally occurring substance with anti-inflammatory properties obtained from Rabdosia rubescens. Whether Ori can exert an anti-inflammatory effect on DED, and its anti-inflammatory mechanism of action, are still unknown. This experiment is intended to investigate the impact of Ori on the hyperosmolarity-induced NLRP3/caspase-1/GSDMD pyroptosis pathway in immortalized human corneal epithelial (HCE-T) cells, as well as its efficacy and mechanism of action on ocular surface injury in DED mice. Our study showed that Ori could inhibit hyperosmotic-induced pyroptosis through the NLRP3/caspase-1/GSDMD pathway in HCE-T cells, and similarly, Ori inhibited the expression of this pathway in DED mice. Moreover, Ori was protective against hyperosmolarity-induced HCE-T cell damage. In addition, we found that the morphology and number of HCE-T cells were altered under culture conditions of various osmolarities. With increasing osmolarity, the proliferation, migration, and healing ability of HCE-T cells decreased significantly, and the expression of N-GSDMD was elevated. In a mouse model of DED, Ori application inhibited the expression of the NLRP3/caspase-1/GSDMD pyroptosis pathway, improved DED signs and injury, decreased corneal sodium fluorescein staining scores, and increased tear volume. Thus, our study suggests that Ori has potential applications for the treatment of DED, provides potential novel therapeutic approaches to treat DED, and provides a theoretical foundation for treating DED using Ori.

l-Carnosine loaded on carboxymethyl cellulose hydrogels for promoting wound healing.

Wound management remains a challenge in clinical practice. Nowadays, patients have an increasing demand for wound repair with enhanced speed and quality; therefore, there is a great need to seek therapeutic strategies that can promote rapid and effective wound healing. In this study, we developed a carboxymethyl cellulose hydrogel loaded with l-carnosine (CRN@hydrogel) for potential application as a wound dressing. In vitro experiments confirmed that CRN@hydrogel can release over 80% of the drug within 48 h and demonstrated its favorable cytocompatibility and blood compatibility, thus establishing its applicability for safe utilization in clinical practice. Using a rat model, we found that this hydrogel could promote and accelerate wound healing more effectively. These results indicate that the novel hydrogel can serve as an efficient therapeutic strategy for wound treatment.

Worldwide trend in research on Candida albicans and cancer correlations: a comprehensive bibliometric analysis.

Objective: Candida albicans (C. albicans), an opportunistic pathogen, is implicated in the carcinogenesis of various cancers, thereby significantly impacting human health. This study conducts an in-depth analysis of the prevailing research dynamics concerning the relationship between C. albicans and cancer over the past decade, offering a comprehensive overview of the knowledge structure and emerging focal points in this field through bibliometric scrutiny. Methods: A methodical quantitative and visual scrutiny of pertinent literature from the Web of Science Core Collection (WoSCC) spanning the previous decade was carried out employing VOS Viewer and CiteSpace software. Results: From January 1, 2014, to January 1, 2024, a comprehensive corpus of 1,259 articles was delineated. Prominent research institutions included the Egyptian Knowledge Bank, Cairo University, and King Saud University. The top three prolific countries were the United States, China, and India. Among the authors, Mohamed, Gehad G., Mahmoud, Walaa H., and Netea, Mihai G., emerged as the most prolific, with Pfaller, Ma being distinguished as the most frequently cited author. The journal Molecules published the highest number of articles, while PLoS One had the highest citation count. Nature had the highest impact factor. The research focal points in this field encompassed the interactions between C. albicans and cancer, the correlation with oral cancer, the underlying mechanisms of C. albicans carcinogenic potential, as well as antifungal and anticancer therapies. Conclusion: This investigation constitutes a pioneering bibliometric analysis elucidating the trends and advancements in research regarding the correlation between C. albicans and cancer. Said analyses uncover the prevailing research focal points and trends, offering insightful guidance for subsequent inquiry in this domain. Systematic review registration: https://www.webofscience.com/wos/woscc/summary/df33afba-f843-41e8-b932-cb3678eb8243-e92e7316/relevance/1.

Effects of ultraviolet C on the quality and aroma volatile in peach fruit during postharvest storage.

The study investigated the impact of UV-C irradiation on peach fruit quality during postharvest storage, with a focus on aroma changes and the mechanisms involving lipoxygenase metabolism. Results showed that UV-C irradiation at a dosage of 1.5 kJ/m2 was found to preserve the quality attributes of peach fruit during ambient storage, as evidenced by high flesh firmness, inhibition of weight loss and respiration rate, as well as high values of L* and ascorbic acid. Meanwhile, UV-C irradiation led to an increase in the contents of aroma-related volatiles, particularly esters and lactones, compared to non-irradiated fruit. Our results suggested that the enhanced emission of aroma-related volatiles in UV-C irradiated peach fruit was linked to elevated levels of unsaturated fatty acids. Besides, UV-C induced the expressions and activities of enzymes in the lipoxygenase pathway, thus promoting the synthesis of esters and lactones, which contribute to the enhanced aroma in peach fruit.

The impact of internet use and cognitive conflict on farmer IPM technology adoption: evidence from China.

BACKGROUND: Integrated pest management (IPM) plays a crucial role in protecting agricultural environments and enhancing the quality of agricultural products. However, a major challenge in China is the conflicting understanding of IPM among farmers, leading to low adoption rates. This undermines farmers' ability to control pests and diseases while increasing risks to agricultural quality and safety. This study aimed to investigate the impact of cognitive conflicts on farmers' adoption of IPM in kiwifruit farms in Shaanxi and Sichuan provinces. Additionally, the study explored the moderating role of internet use in the relationship between cognitive conflicts and farmer adoption of IPM. Data were collected from 686 kiwifruit farms through field surveys in 2018. The binary Probit model and moderating effect models were used to assess the influence of internet use and cognitive conflict on farmer adoption of IPM. RESULTS: The study found that cognitive conflicts significantly hindered farmers' adoption of IPM. Higher levels of cognitive conflict were associated with lower likelihoods of adopting IPM. Internet use and frequency had positive effects on farmer adoption of IPM, promoting its implementation. Moreover, internet use and frequency helped alleviate the inhibitory effect of cognitive conflicts on farmer adoption IPM. CONCLUSION: This research enhances our understanding of cognitive conflicts among farmers when promoting IPM and provides viable strategies to improve the effectiveness of public sector promotion and stimulate farmers' willingness to adopt IPM. It emphasizes the importance of addressing cognitive conflicts and utilizing internet resources to enhance IPM adoption among kiwifruit growers in China. © 2024 Society of Chemical Industry.

Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

Purpose: The purpose of this study was to investigate the involvement of the TLR4/NF-κB/NLRP3 signaling pathway and its underlying mechanism in diabetic dry eye. Methods: Two models of diabetic dry eye were established in high glucose-induced human corneal epithelial (HCE-T) cells and streptozotocin (STZ)-induced C57BL/6 mice, and the TLR4 inhibitor fosfenopril (FOS) was utilized to suppress the TLR4/NF-κB/NLRP3 signaling pathway. The expression changes in TLR4, NF-κB, NLRP3, and IL-1ß, and other factors were detected by Western blot and RT‒qPCR, the wound healing rate was evaluated by cell scratch assay, and the symptoms of diabetic mice were evaluated by corneal sodium fluorescein staining and tear secretion assay. Results: In the diabetic dry eye model, the transcript levels of TLR4, NF-κB, NLRP3, and IL-1ß were raised, and further application of FOS, a TLR4 inhibitor, downregulated the levels of these pathway factors. In addition, FOS was found to be effective in increasing the wound healing rate of high glucose-induced HCE-T cells, increasing tear production, and decreasing corneal fluorescence staining scores in diabetic mice, as measured by cell scratch assay, corneal sodium fluorescein staining assay, and tear production. Conclusions: The current study found that the TLR4/NF-κB/NLRP3 signaling pathway regulates diabetic dry eye in an in vitro and in vivo model, and that FOS reduces the signs of dry eye in diabetic mice, providing a new treatment option for diabetic dry eye.

p39 Affects Myelin Formation in Cerebral Ischemic Injury.

Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator, p39 plays a crucial role in various diseases. In this article, we will explore the role and mechanism of p39 in cerebral ischemic injury. We measured the level of p39 using western blot and QPCR at various time points following cerebral ischemia-reperfusion (I/R) injury. The results indicated a significant reduction in the level of p39. TTC staining and behavioral results indicate that the knockout of p39 (p39KO) provides neuroprotection in the short-term. Interestingly, the behavioral dysfunction in p39KO mice was exacerbated after the repair phase of I/R. Further study revealed that this deterioration may be due to demyelination induced by elevated p35 levels. In summary, our study offers profound insights into the significance of p39 in both the acute and repair stages of ischemic injury recovery and a theoretical foundation for future therapeutic drug exploration.

A systematic review on botany, ethnopharmacology, phytochemistry and pharmacology of Potentilla anserina L.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla Anserina Linnaeus, a traditional Chinese herb with ethnic characteristics, is considered a superior material by the people of Qinghai and Tibet. Traditionally, it has been used to invigorate the spleen, quench thirst, tonify the blood, astringing to stop bleeding, and relieve diarrhea. This is the reason for its frequent usage in treating spleen deficiency, diarrhea, and various bleeding disorders. At the same time, P. anserina is often consumed as food by the Tibetan people to obtain nourishment and health benefits. AIM OF THE REVIEW: The present review provides a systematic description of P. anserina, covering its botany, ethnopharmacology, phytochemical constituents, and various pharmacological activities of extracts. This overview aims to provide insights into research directions and potential applications of P. anserina. MATERIALS AND METHODS: Information on P. anserina was gathered through various sources, including Google Scholar, PubMed, Elsevier, CNKI, and Web of Science. In addition, information was available from native texts and prominent ethnopharmacologists. RESULTS: So far, 154 different chemical substances have been isolated and identified from P. anserina, with tannins, flavonoids, and triterpenes accounting for the majority. Polysaccharides and triterpenes are the main material components responsible for the pharmacological activity of P. anserina. Research shows that P. anserina exhibits rich pharmacological activities, including antioxidant, antiviral, blood tonic, immune regulation, cardiovascular system treatment, diabetes treatment, and liver protection. CONCLUSIONS: Some traditional applications of P. anserina have been confirmed. However, due to incomplete evaluation indicators and other reasons, further in vitro and in vivo studies are needed to clarify its pharmacological evaluation, which remains a focus of future research. Additionally, we recommend that future studies concentrate on the quality control and safety evaluation of P. anserina to address research gaps and offer theoretical support for the plant's potential functions and clinical applications.

Macrophage-derived CD36 + exosome subpopulations as novel biomarkers of Candida albicans infection.

Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments.

Mendelian randomization analysis of the brain, cerebrospinal fluid, and plasma proteome identifies potential drug targets for attention deficit hyperactivity disorder.

BACKGROUND: The need for new therapeutics for attention deficit hyperactivity disorder (ADHD) is evident. Brain, cerebrospinal fluid (CSF), and plasma protein biomarkers with causal genetic evidence could represent potential drug targets. However, a comprehensive screen of the proteome has not yet been conducted. METHODS: We employed a three-pronged approach using Mendelian Randomization (MR) and Bayesian colocalization analysis. Firstly, we studied 608 brains, 214 CSF, and 612 plasma proteins as potential causal mediators of ADHD using MR analysis. Secondly, we analysed the consistency of the discovered biomarkers across three distinct subtypes of ADHD: childhood, persistent, and late-diagnosed ADHD. Finally, we extended our analysis to examine the correlation between identified biomarkers and Tourette syndrome and pervasive autism spectrum disorder (ASD), conditions often linked with ADHD. To validate the MR findings, we conducted sensitivity analysis. Additionally, we performed cell type analysis on the human brain to identify risk genes that are notably enriched in various brain cell types. FINDINGS: After applying Bonferroni correction, we found that the risk of ADHD was increased by brain proteins GMPPB, NAA80, HYI, CISD2, and HYI, TIE1 in CSF and plasma. Proteins GMPPB, NAA80, ICA1L, CISD2, TIE1, and RMDN1 showed overlapped loci with ADHD risk through Bayesian colocalization. Overexpression of GMPPB protein was linked to an increase in the risk for all three ADHD subtypes. While ICA1L provided protection against both ASD and ADHD, CISD2 increased the probability of both disorders. Cell-specific studies revealed that GMPPB, NAA80, ICA1L, and CISD2 were predominantly present on the surface of excitatory-inhibitory neurons. INTERPRETATION: Our comprehensive MR investigation of the brain, CSF, and plasma proteomes revealed seven proteins with causal connections to ADHD. Particularly, GMPPB and TIE1 emerged as intriguing targets for potential ADHD therapy. FUNDING: This work was partly funded by the Key R & D Program of Zhejiang (T.L. 2022C03096); the National Natural Science Foundation of China Project (C.Z. 82001413); Postdoctoral Foundation of West China Hospital (C.Z. 2020HXBH163).

Fabrication of blueberry anthocyanins-rich gels based on the apricot polysaccharides with different esterification degrees.

To enhance the stability of anthocyanins under conditions such as light, temperature, and pH, an apricot polysaccharide hydrogel for anthocyanins encapsulation was prepared in this study. Apricot polysaccharides with different DEs were prepared by an alkaline de-esterification method. A gel was prepared by mixing the apricot polysaccharides with CaCl2 to encapsulate the anthocyanins; the encapsulation efficiency reached 69.52 ± 0.31 %. Additionally, the gel exhibited favorable hardness (144.17 ± 2.33 g) and chewiness (64.13 ± 1.53 g). Fourier transform infrared (FTIR) and X-ray diffractometer (XRD) spectra confirmed that the formation of the hydrogel primarily relied on electrostatic interactions and hydrogen bonding. Compared with free anthocyanins, it was also found that the gel-encapsulated anthocyanins had a higher retention rate (RR) under different temperatures and light.

Unraveling the determinants of antibiotic resistance evolution in farmland under fertilizations.

Organic fertilization is a major driver potentiating soil antibiotic resistance in farmland. However, it remains unclear how bacterial antibiotic resistance evolves in fertilized soils and even spreads to crops. Compared with no fertilizer and commercial fertilizer treatments, organic fertilizers markedly increased the abundance of soil antibiotic resistance genes (ARGs) but the relatively weaker transfer of resistance genes from soil to crops. The introduction of organic fertilizers enriches the soil with nutrients, driving indigenous microorganisms towards a K-strategy. The pH, EC, and nutrients as key drivers influenced the ARGs abundance. The neutral (pH 7.2), low salt (TDS 1.4 %) and mesotrophic (carbon content 3.54 g/L) habitats similar to the soil environment conditioned by organic fertilizers. These environmental conditions clearly prolonged the persistence of resistant plasmids, and facilitated their dissemination to massive conjugators soil microbiome but not to plant endophytes. This suggested that organic fertilizers inhibited the spread of ARGs to crops. Moreover, the composition of conjugators showed differential selection of resistant plasmids by endophytes under these conditions. This study sheds light on the evolution and dissemination of antibiotic resistance in farmlands and can aid in the development of antimicrobial resistance control strategies in agriculture.

Remodeling of tumor microenvironment by extracellular matrix protein 1a differentially regulates ovarian cancer metastasis.

We previously reported that extracellular matrix protein 1 isoform a (ECM1a) promotes epithelial ovarian cancer (EOC) through autocrine signaling by binding to cell surface receptors αXß2. However, the role of ECM1a as a secretory molecule in the tumor microenvironment is rarely reported. In this study, we constructed murine Ecm1-knockout mice and human ECM1a-knockin mice and further generated orthotopic or peritoneal xenograft tumor models to mimic the different metastatic stages of EOC. We show that ECM1a induces oncogenic metastasis of orthotopic xenograft tumors, but inhibits early-metastasis of peritoneal xenograft tumors. ECM1a remodels extracellular matrices (ECM) and promotes remote metastases by recruiting and transforming bone marrow mesenchymal stem cells (BMSCs) into platelet-derived growth factor receptor beta (PDGFRß+) cancer-associated fibroblasts (CAFs) and facilitating the secretion of angiopoietin-like protein 2 (ANGPTL2). Competing with ECM1a, ANGPTL2 also binds to integrin αX through the P1/P2 peptides, resulting in negative effects on BMSC differentiation. Collectively, this study reveals the dual functions of ECM1a in remodeling of TME during tumor progression, emphasizing the complexity of EOC phenotypic heterogeneity and metastasis.

New insights into resveratrol attenuates hepatotoxicity in emamectin benzoate-exposed grass carp (Ctenopharyngodon idella) via NO system/NF-κB signaling pathway.

Emamectin benzoate (EMB) is extensively used as a crop protection agent. Overuse of EMB poses a serious threat to the quality of water and non-target organisms in the environment. Resveratrol (RES) is a natural phytoalexin with the function of anti-oxidation and anti-inflammation. Nonetheless, it is unclear whether EMB affects the expression of cytokines and induces autophagy, apoptosis, and necroptosis of hepatocytes (L8824 cell) in grass carp (Ctenopharyngodon idella), and whether RES has an attenuate function in this process. Therefore, we established the L8824 cells model of EMB exposure and treated it with RES. The results showed that compared with the control (CON) group, EMB exposure significantly increased the nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) activity, and the expression of iNOS and phosphorylated nuclear factor kappa B (p-NF-κB) (P < 0.05). In addition, compared with the CON group, the results of flow cytometry and dansylcadaverine (MDC) staining showed a significant increase in apoptosis and autophagy in the EMB-exposed group (P < 0.05) with the activation of the B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X (Bax)/cysteine-aspartic acid protease 3 (Caspase-3)/cysteine-aspartic acid protease 9 (Caspase-9) pathway and microtubule-associated protein light chain 3 (LC3)/sequestosome 1 (p62)/Beclin1 pathway. EMB exposure significantly increased the mRNA and protein expression of receptor-interacting protein 1 (RIPK1)/receptor-interacting protein 3 (RIPK3)/mixed the lineage kinase domain-like (MLKL) pathway (P < 0.05). Moreover, EMB exposure significantly increased the expression of genes related to immunity (immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin D (IgD), and antimicrobial peptide-related genes expression including ß-defensin and hepcidin) (P < 0.05). The addition of RES significantly diminished autophagy, apoptosis, necroptosis, and immunity-related gene expression by inhibiting iNOS activity, NO content, and the protein expression of iNOS and p-NF-κB. In conclusion, RES attenuated autophagy, apoptosis, and necroptosis in EMB-exposed L8824 cells via suppression of the NO system/NF-κB signaling pathway.

Proteomic profiling and biomarker discovery for predicting the response to PD-1 inhibitor immunotherapy in gastric cancer patients.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, a significant proportion of gastric cancer (GC) patients do not respond to this therapy. Consequently, there is an urgent need to elucidate the mechanisms underlying resistance to ICIs and identify robust biomarkers capable of predicting the response to ICIs at treatment initiation. Methods: In this study, we collected GC tissues from 28 patients prior to the administration of anti-programmed death 1 (PD-1) immunotherapy and conducted protein quantification using high-resolution mass spectrometry (MS). Subsequently, we analyzed differences in protein expression, pathways, and the tumor microenvironment (TME) between responders and non-responders. Furthermore, we explored the potential of these differences as predictive indicators. Finally, using machine learning algorithms, we screened for biomarkers and constructed a predictive model. Results: Our proteomics-based analysis revealed that low activity in the complement and coagulation cascades pathway (CCCP) and a high abundance of activated CD8 T cells are positive signals corresponding to ICIs. By using machine learning, we successfully identified a set of 10 protein biomarkers, and the constructed model demonstrated excellent performance in predicting the response in an independent validation set (N = 14; area under the curve [AUC] = 0.959). Conclusion: In summary, our proteomic analyses unveiled unique potential biomarkers for predicting the response to PD-1 inhibitor immunotherapy in GC patients, which may provide the impetus for precision immunotherapy.

Rheological properties, multiscale structure, and in vitro digestibility of a maize starch-konjac glucomannan-bamboo leaf flavonoid complex modified by dynamic high-pressure microfluidization.

The effects of dynamic high-pressure microfluidization (DHPM) treatment on the rheological properties, multiscale structure and in vitro digestibility of complex of maize starch (MS), konjac glucomannan (KGM), and bamboo leaf flavonoids (BLFs) were investigated. Compared with MS, the MS-KGM-BLF complex exhibited reduced viscosity and crystallinity, along with increased lamellar thickness to 10.26 nm. MS-KGM-BLF complex had lower viscosity after DHPM treatment. The highest ordered structure and crystallinity were observed at 50 MPa, with the α value increasing from 3.40 to 3.59 and the d value decreasing from 10.26 to 9.81 nm. However, higher DHPM pressures resulted in a decrease in the α value and an increase in the d value. The highest gelatinization enthalpy and resistant starch content were achieved at 100 MPa DHPM, while the fractal structure shifted from surface fractal to mass fractal at 150 MPa. This study presents an innovative method for enhancing the properties of MS.