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This study isolated a novel peptide MMGGED with strong calcium-binding capacity from defatted walnut meal and synthesized a novel peptide­calcium chelate COS-MMGGED-Ca with high stability via glycation. Structural characterization and computer simulation identified binding sites, while in vitro digestion stability and calcium transport experiments explored the chelate's properties. Results showed that after glycation, COS-MMGGED bound Ca2+ with 88.75 ± 1.75 %, mainly via aspartic and glutamic acids. COS-MMGGED-Ca released Ca2+ steadily (60.27 %), with thermal denaturation temperature increased by 18 °C and 37 °C compared to MMGGED-Ca, indicating good processing performance. Furthermore, COS-MMGGED significantly enhanced Ca2+ transport across Caco-2 monolayers, 1.13-fold and 1.62-fold higher than CaCl2 and MMGGED, respectively, at 240 h. These findings prove glycation enhances structural properties, stability, calcium loading, and transport of peptide­calcium chelates, providing a scientific basis for developing novel efficient calcium supplements and high-value utilization of walnut meal.

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The onset and progression of colorectal cancer is intricately linked to a multitude of factors. Among these, immune cells present within the tumor microenvironment play a pivotal role, particularly natural killer (NK) cells, which are essential for mediating anti-tumor immunity. This study aims to elucidate the mechanism by which the VWA2 protein facilitates the invasion and migration of colorectal cancer cells through the inhibition of NK cell activation. Understanding this molecular mechanism is crucial for deciphering the underlying processes involved in colorectal cancer. To achieve the study's objectives, various methodologies were employed, including cell culture techniques, transgenic technology, and assessments of NK cell functionality. The "limma" bioinformatics tool was utilised to identify differentially expressed genes (DEGs) between samples of colon cancer or polyps and normal tissue through transcriptome sequencing. Subsequent Wien analysis was conducted to pinpoint overlapping genes of interest. The impact of VWA2 on both the invasion and migration of colorectal cancer cell lines was assessed through experiments designed for the overexpression and knockout of VWA2.In addition, flow cytometry was employed to evaluate the activation status of NK cells, enabling an analysis of how VWA2 modulates relevant signaling pathways. The findings revealed that overexpression of VWA2 led to a marked inhibition of NK cell activation, which corresponded with reduced cytotoxic activity against tumor cells. Further examination indicated that VWA2 significantly amplified the migration and invasion capabilities of colorectal cancer cells by upregulating immunosuppressive factors while simultaneously downregulating pro-inflammatory factors. Conversely, the reduction of VWA2 expression was shown to markedly enhance NK cell functionality and decrease the invasive potential of colorectal cancer cells. Thus, the evidence suggests that the VWA2 protein actively promotes the migration and invasion of colorectal cancer cells primarily by suppressing NK cell activation, highlighting its potential role as a significant contributor to tumor progression in colorectal cancer.

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Taste and odor (T&O) are among the most frequently encountered aesthetic issues in drinking water. While fungi have been reported to produce offensive odors, their contribution to T&O in drinking water remains understudied and often overlooked. In this study, the profiles of fungal community and odorants produced by 10 native fungal isolates were investigated in 36 samples collected from two drinking water treatment plants and a premise plumbing system. A total of 17 odorants were identified with Penicillium, Aspergillus, Paecilomyces, and Alternaria genera exhibiting the highest odorant yields. Significant concentrations of musty/earthy compounds were produced by these fungal isolates, such as 2-methylisoborneol (2-MIB) (26-256 ng/L), geosmin (10-13 ng/L), and 2-isobutyl-3-methoxy-pyrazine (IBMP) (3-13 ng/L). The high odor activity value of the odorants primarily occurred within 4 d, while toxicity continued to increase during the 8 d incubation. UV treatment in premise plumbing significantly (p < 0.05) reduced the gene read counts of Ascomycota phylum, Aspergillus spp., Fusarium spp., Rhizopus spp., and Trichoderma spp., by 2.3-4.0 times. These findings underscore the previously underestimated role of fungi in contributing to T&O issues in drinking water and corresponding risks to consumers and indicate UV as a promising strategy for fungal control in drinking water.

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Membrane fission involves a crucial step of lipid remodeling, in which the dynamin collar constricts and severs the tubulated lipid membrane at the neck of budding vesicles. Nevertheless, the difficulty in accurately determining the rotational dynamics of live endocytotic vesicles poses a limit on the elucidation of dynamin-induced membrane remodeling for endocytotic vesicle scission. Herein, we designed a DNA-modified gold homodimer (AuHD)-based anisotropic plasmonic probe with uniform surface chemistry, minimizing orientational fluctuation within vesicle encapsulation. Using AuHDs as cargos to image the dynamics of cargo-containing vesicles during endocytosis, we showed that, prior to detachment from plasma membrane, the cargo-containing vesicles underwent multiple intermittent twists of ~4° angular orientation relative to plasma membrane with a ~0.2 s dwell time. These findings suggest that the membrane torques resulting from dynamin actions in vivo constitute the pathway to membrane fission, potentially shedding light on how dynamin-mediated lipid remodeling orchestrates membrane fission.

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Background: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice. Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1ß, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1ß were measured using Western blotting. Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1ß levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1ß, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway. Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF­κB signaling pathway in PCOS mice.

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The exploration of novel functionalized supramolecular coordination complexes (SCCs) can enable new applications in domains that include purification and sensing. In this study, employing a coordination-driven self-assembly strategy, we designed and prepared a series of benzochalcogenodiazole-based metallohelicates as high-efficiency charge transfer surface-enhanced Raman scattering (SERS) substrates, expanding the range of applications for these metallohelicates. Through structural modifications, including the substitution of single heteroatoms on ligands, replacement of coordinating metals, and alteration of ligand framework linkages, the Raman performance of these metallohelicates as substrates were systematically optimized. Notably, the SERS enhancement factors (EFs) of the metallohelicate-based SERS substrates were significantly enhanced to levels as high as 1.03 × 107, which rivals the EFs of noble metals devoid of "hot spots". Additionally, the underlying Raman enhancement mechanisms of these metallohelicates have been investigated through a combination of control experiments and theoretical calculations. This study not only demonstrates the utility of metallohelicates as SERS substrates but also offers insights and materials for the development of high-efficiency new charge transfer SERS substrates.

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Artificial intelligence (AI) researchers currently believe that the main approach to building more general model problems is the big AI model, where existing neural networks are becoming deeper, larger and wider. We term this the big model with external complexity approach. In this work we argue that there is another approach called small model with internal complexity, which can be used to find a suitable path of incorporating rich properties into neurons to construct larger and more efficient AI models. We uncover that one has to increase the scale of the network externally to stimulate the same dynamical properties. To illustrate this, we build a Hodgkin-Huxley (HH) network with rich internal complexity, where each neuron is an HH model, and prove that the dynamical properties and performance of the HH network can be equivalent to a bigger leaky integrate-and-fire (LIF) network, where each neuron is a LIF neuron with simple internal complexity.

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Background: Coronary heart disease (CHD) is one of the common chronic diseases in clinical practice, often accompanied by inflammatory reactions. In recent years, the system inflammation response index (SIRI) has aroused researchers' interest as a novel inflammatory biomarker. This study aims to explore the relationship between the SIRI and CHD through the National Health and Nutrition Examination Survey (NHANES) database. Methods: We conducted a cross-sectional study and analyzed participants aged 40 and above with complete data from the NHANES survey years 2007-2016. Logistic regression analysis was used in this study to explore the relationship between the risk of CHD and SIRI. Stratified subgroup analysis was conducted based on age, gender, race, education level, body mass index (BMI), smoking status, drinking, hypertension, diabetes and angina pectoris to evaluate the relationship between SIRI and CHD in different populations. Additionally, restricted cubic spline (RCS) analysis was employed to investigate whether there is a nonlinear association between SIRI and CHD. Results: A total of 6374 eligible participants were included, among whom 387 were diagnosed with CHD. The SIRI levels in the CHD group were significantly higher than those in the non-CHD group. After adjusting for potential confounders, an elevated SIRI level was associated with an increased risk of CHD, with an odds ratio of 1.12, 95% CI: (1.03, 1.22), P = 0.008. Subgroup analysis results indicated a significant interaction between SIRI and CHD among genders (P for interaction <0.05), especially in females. In contrast, no significant interaction was observed among age, race, education level, BMI, smoking status, drinking, hypertension, diabetes and angina pectoris (P for interaction >0.05). The RCS analysis showed a significant linear relationship between SIRI and CHD (P for non-linearity >0.05), with an inflection point at 2.86. Conclusion: Our study indicates that an elevated system inflammation response index is associated with a higher risk of CHD. Particularly among women.

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Background: In this study, deep eutectic solvents (DESs) combined with ultrasound-assisted extraction (UAE) were used to extract bioactive compounds from the leaves of Moringa oleifera Lam. Methods: The FT-IR method was used to analyze the structural characteristics of the DESs, and the extraction efficiencies of the DESs for total phenolic content (TPC) and total flavonoid content (TFC) were evaluated. The stability of the extracts under high temperature and UV radiation was assessed, and their antioxidant activity was investigated after undergoing in vitro simulated digestion. Results: The results show that the seven DESs extracted more TPC and TFC than did the 70% ethanol (36.27 ± 1.58 mg GAE/g, 23.09 ± 1.47 mg RT/g), and the extraction process of UAE-DES was optimized by selecting choline chloride: citric acid as the DES solvent, which has the highest extraction of TPC (86.92 ± 1.34 mg GAE/g) and TFC (49.73 ± 0.85 mg RT/g). The stability results indicated that the DES phenolic extracts were less stable when exposed to high temperature and UV radiation, indicating that DES extracts have better bioactivity. Moreover, after in vitro simulated digestion, the DES extract shows a higher DPPH free radical scavenging capacity (12.79 ± 3.88 mmol Trolox/g of DES extracts, 6.99 ± 4.02 mmol Trolox/g of ethanol extracts) and ferric ion reducing antioxidant power (62.61 ± 1.71 mmol Trolox/g of DES extracts, 55.07 ± 1.66 mmol Trolox/g of ethanol extracts) than ethanol extracts. Conclusion: This study confirmed that DESs are a new and environmentally friendly solvent that can be used for the extraction of phenolic compounds.

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Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.

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The self-renewal and regeneration of intestinal epithelium are mainly driven by intestinal stem cells resided in crypts, which are crucial for rapid recovery intestinal tissue following injury. Latexin (LXN) is a highly expressed stem cell proliferation and differentiation related gene in intestinal tissue. However, it is still ambiguous whether LXN participates in intestine regeneration by regulating intestinal stem cells (ISCs). Here, we report that LXN colocalizes with Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) in intestinal crypts, and deletion of LXN upregulates the expression of Lgr5 in intestinal crypts. LXN deficiency promotes the proliferation of ISCs, thereby enhances the development of intestinal organoids. Mechanically, we show that LXN deficiency enhances the expression of Lgr5 in ISCs by activating the Yes-associated protein (YAP) and wingless (Wnt) signal pathways, thus accelerating intestinal normal growth and regeneration post-injury. In summary, these findings uncover a novel function of LXN in intestinal regeneration post-injury and intestinal organogenesis, suggesting the potential role of LXN in the treatment of inflammatory bowel diseases.

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Foot-and-mouth disease virus (FMDV) 2C protein is a conserved non-structural protein and crucial for replication of the virus. In this study, FMDV 2C protein was prepared and the enzymatic activities were investigated in detail. The protein could digest ssDNA or ssRNA into a small fragment at about 10 nt, indicating that the protein has nuclease activity. But it did not show digestion to blunt-end dsDNA or dsRNA. The nuclease activity of 2C protein could be inhibited in 2 mM Zn2+ or Ca2+ while enhanced by Mg2+ or Mn2+. FMDV 2C protein exhibited unwinding activity to all the three kinds of dsDNA and dsRNA (5' protruded, 3' protruded, and blunt-end). The unwinding velocity to 5' protruded dsRNA was higher than to the blunt-end dsRNA. 2C protein only showed unwinding activity in high concentration of Mg2+, but no unwinding activity in physiological concentrations of Mg2+ and Ca2+, as well as in cell lysate. The 2C protein could catalyze two structured ssRNA to form double strand, thus it was proved to have RNA chaperone activity. The Mg2+ and ATP in different concentrations did not show promotion to the RNA chaperone activity. Finally, six mutant proteins (K116A, D160A, D170A, N207A, R226A, and F316A) were constructed and the enzymatic activities were analyzed. All the six mutations reduced the ATPase activity, D170A and F361A could inactivate the nuclease activity, while the N207A and F316A could inactivate the helicase activity. Our study provides a comprehensive understanding of the enzymatic activities of FMDV 2C protein.

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Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-[Formula: see text], and IL-1[Formula: see text]) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

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How do heterogeneous individual behaviors arise in response to sudden events and how do they shape large-scale social dynamics? Based on a five-year naturalistic observation of individual purchasing behaviors, we extract the long-term consumption dynamics of diverse commodities from approximately 2.2 million purchase orders. We subdivide the consumption dynamics into trend, seasonal, and random components and analyze them using a renormalization group. We discover that the coronavirus pandemic, a sudden event acting on the social system, regulates the scaling and criticality of consumption dynamics. On a large time scale, the long-term dynamics of the system, regardless of arising from trend, seasonal, or random individual behaviors, is pushed toward a quasi-critical region between independent (i.e., the consumption behaviors of different commodities are irrelevant) and correlated (i.e., the consumption behaviors of different commodities are interrelated) phases as the pandemic erupts. On a small time scale, short-term consumption dynamics exhibits more diverse responses to the pandemic. While the trend and random behaviors of individuals are driven to quasi-criticality and exhibit scale-invariance as the pandemic breaks out, seasonal behaviors are more robust against regulations. Overall, these discoveries provide insights into how quasi-critical macroscopic dynamics emerges in heterogeneous social systems to enhance system reactivity to sudden events while there may exist specific system components maintaining robustness as a reflection of system stability.

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BACKGROUND: Application of indocyanine green (ICG) fluorescence has led to new developments in gastrointestinal surgery. However, little is known about the use of ICG for the diagnosis of postoperative gut leakage (GL). In addition, there is a lack of rapid and intuitive methods to definitively diagnose postoperative GL. AIM: To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery patients. METHODS: Sixteen rats were divided into two groups: GL group (n = 8) and sham group (n = 8). Approximately 0.5 mL of ICG (2.5 mg/mL) was intravenously injected postoperatively. The peritoneal fluid was collected for the fluorescence test at 24 and 48 h. Six patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG (2.5 mg/mL) on postoperative day 1. Their ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy stoma. Participants who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic test. The peritoneal fluids from drainage were collected 24 h after ICG injection. The ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging system. RESULTS: The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham group. Six samples of ostomy fluids showed green fluorescence, indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in patients. The peritoneal fluid ICG test exhibited a sensitivity of 100% and a specificity of 83.3% for the diagnosis of GL. The positive predictive value was 71.4%, while the negative predictive value was 100%. The likelihood ratios were 6.0 for a positive test result and 0 for a negative result. CONCLUSION: The postoperative ICG test in a drainage tube is a valuable and simple technique for the diagnosis of GL. Hence, it should be employed in clinical settings in patients with suspected GL.

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The rhizosphere constitutes a dynamic interface between plant hosts and their associated microbial communities. Despite the acknowledged potential for enhancing plant fitness by manipulating the rhizosphere, the engineering of the rhizosphere microbiome through inoculation has posed significant challenges. These challenges are thought to arise from the competitive microbial ecosystem where introduced microbes must survive, and the absence of adaptation to the specific metabolic and environmental demands of the rhizosphere. Here, we engineered a synthetic rhizosphere community (SRC1) with the anticipation that it would exhibit a selective advantage in colonizing the host Sorghum bicolor, thereby potentially fostering its growth. SRC1 was assembled from bacterial isolates identified either for their potential role in community cohesion through network analysis or for their ability to benefit from host-specific exudate compounds. The growth performance of SRC1 was assessed in vitro on solid media, in planta under gnotobiotic laboratory conditions, and in the field. Our findings reveal that SRC1 cohesion is most robust when cultivated in the presence of the plant host under laboratory conditions, with lineages being lost from the community when grown either in vitro or in a native field setting. We establish that SRC1 effectively promotes the growth of both above- and below-ground plant phenotypes in both laboratory and native field contexts. Furthermore, in laboratory conditions, these growth enhancements correlate with the transcriptional dampening of lignin biosynthesis in the host. Collectively, these results underscore the potential utility of synthetic microbial communities for modulating crop performance in controlled and native environments alike.

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The ecological impact of emerging contaminants (ECs) in aquatic environments has raised concerns, particularly with regards to urine as a significant source of such contaminants in wastewater. The current investigation used the UV/Peracetic Acid (UV/PAA) processes, an innovative advanced oxidation technology, to effectively separate two emerging pollutants from urine at its source, namely, ciprofloxacin (CIP) and bisphenol A(BPA). The research findings demonstrate that the presence of the majority of characteristic ions has minimal impact on the degradation of ECs. However, in synthetic hydrolyzed urine, only NH4+ inhibits the degradation of two types of ECs, with a more pronounced effect observed on CIP degradation compared to BPA.The impact of halogen ions, specifically Cl- and I-, on the degradation of CIP in synthetic hydrolyzed urine was a complex phenomenon. When these two halogen ions are present individually, the generation of reactive halogen species (RHS) within the system enhances the degradation of CIP. However, when both types of ions coexist, the formation of diatomic radical species partially inhibits degradation. In terms of BPA degradation, while the production of reactive chlorine species (RCS) to some extent hinders the reaction rate, the generation of reactive iodine species (RIS) promotes the overall process. CIP undergoes fragmentation of the piperazine and quinoline rings, decarboxylation, defluorination reactions, as well as substitution reactions, leading to the formation of products with simplified structures. The degradation of BPA occurs gradually through hydroxyl and halogen substitution as well as isopropyl cleavage. The preliminary toxicity analysis confirmed that the presence of halogen ions in urine resulted in the formation of halogenated products in two types of ECs, albeit with an overall reduction in toxicity. The UV/PAA processes was considered to be an effective and relatively safe approach for the separation of ECs in urine.

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BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

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Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

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BACKGROUND: Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access. METHODS: The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed. RESULTS: The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058). CONCLUSION: Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.

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