Unveiling the enigmatic role of MYH9 in tumor biology: a comprehensive review.

Non-muscle myosin heavy chain IIA (MYH9), a member of the non-muscle myosin II (NM II) family, is widely expressed in cells. The interaction of MYH9 with actin in the cytoplasm can hydrolyze ATP, completing the conversion of chemical energy to mechanical motion. MYH9 participates in various cellular processes, such as cell adhesion, migration, movement, and even signal transduction. Mutations in MYH9 are often associated with autosomal dominant platelet disorders and kidney diseases. Over the past decade, tumor-related research has gradually revealed a close relationship between MYH9 and the occurrence and development of tumors. This article provides a review of the research progress on the role of MYH9 in cancer regulation. We also discussed the anti-cancer effects of MYH9 under special circumstances, as well as its regulation of T cell function. In addition, given the importance of MYH9 as a key hub in oncogenic signal transduction, we summarize the current therapeutic strategies targeting MYH9 as well as the ongoing challenges.

Clinical nomogram prediction model to assess the risk of prolonged ICU length of stay in patients with diabetic ketoacidosis: a retrospective analysis based on the MIMIC-IV database.

BACKGROUND: The duration of hospitalization, especially in the intensive care unit (ICU), for patients with diabetic ketoacidosis (DKA) is influenced by patient prognosis and treatment costs. Reducing ICU length of stay (LOS) in patients with DKA is crucial for optimising healthcare resources utilization. This study aimed to establish a nomogram prediction model to identify the risk factors influencing prolonged LOS in ICU-managed patients with DKA, which will serve as a basis for clinical treatment, healthcare safety, and quality management research. METHODS: In this single-centre retrospective cohort study, we performed a retrospective analysis using relevant data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Clinical data from 669 patients with DKA requiring ICU treatment were included. Variables were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) binary logistic regression model. Subsequently, the selected variables were subjected to a multifactorial logistic regression analysis to determine independent risk factors for prolonged ICU LOS in patients with DKA. A nomogram prediction model was constructed based on the identified predictors. The multivariate variables included in this nomogram prediction model were the Oxford acute severity of illness score (OASIS), Glasgow coma scale (GCS), acute kidney injury (AKI) stage, vasoactive agents, and myocardial infarction. RESULTS: The prediction model had a high predictive efficacy, with an area under the curve value of 0.870 (95% confidence interval [CI], 0.831-0.908) in the training cohort and 0.858 (95% CI, 0.799-0.916) in the validation cohort. A highly accurate predictive model was depicted in both cohorts using the Hosmer-Lemeshow (H-L) test and calibration plots. CONCLUSION: The nomogram prediction model proposed in this study has a high clinical application value for predicting prolonged ICU LOS in patients with DKA. This model can help clinicians identify patients with DKA at risk of prolonged ICU LOS, thereby enhancing prompt intervention and improving prognosis.

Incorporating environmental capacity considerations to prioritize control factors for the management of heavy metals in soil.

Heavy metals (HMs) pollution threatens food security and human health. While previous studies have evaluated source-oriented health risk assessments, a comprehensive integration of environmental capacity risk assessments with pollution source analysis to prioritize control factors for soil contamination is still lacking. Herein, we collected 837 surface soil samples from agricultural land in the Nansha District of China in 2019. We developed an improved integrated assessment model to analyze the pollution sources, health risks, and environmental capacities of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn. The model graded pollution source impact on environmental capacity risk to prioritize control measures for soil HMs. All HMs except Pb exceeded background values and were sourced primarily from natural, transportation, and industrial activities (31.26%). Approximately 98.92% (children), 97.87% (adult females), and 97.41% (adult males) of carcinogenic values exceeded the acceptable threshold of 1E-6. HM pollution was classified as medium capacity (3.41 kg/hm2) with mild risk (PI = 0.52). Mixed sources of natural backgrounds, transportation, and industrial sources were identified as priority sources, and As a priority element. These findings will help prioritize control factors for soil HMs and direct resources to the most critical pollutants and sources of contamination, particularly when resources are limited.

Discovery of selective and potent USP22 inhibitors via structure-based virtual screening and bioassays exerting anti-tumor activity.

Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development, invasion, metastasis and immune reprogramming, which has been proposed as a potential therapeutic target for cancer. Herein, we employed a structure-based discovery and biological evaluation and discovered that Rottlerin (IC50 = 2.53 µM) and Morusin (IC50 = 8.29 µM) and as selective and potent USP22 inhibitors. Treatment of HCT116 cells and A375 cells with each of the two compounds resulted in increased monoubiquitination of histones H2A and H2B, as well as reduced protein expression levels of Sirt1 and PD-L1, all of which are known as USP22 substrates. Additionally, our study demonstrated that the administration of Rottlerin or Morusin resulted in an increase H2Bub levels, while simultaneously reducing the expression of Sirt1 and PD-L1 in a manner dependent on USP22. Furthermore, Rottlerin and Morusin were found to enhance the degradation of PD-L1 and Sirt1, as well as increase the polyubiquitination of endogenous PD-L1 and Sirt1 in HCT116 cells. Moreover, in an in vivo syngeneic tumor model, Rottlerin and Morusin exhibited potent antitumor activity, which was accompanied by an enhanced infiltration of T cells into the tumor tissues. Using in-depth molecular dynamics (MD) and binding free energy calculation, conserved residue Leu475 and non-conserved residue Arg419 were proven to be crucial for the binding affinity and inhibitory function of USP22 inhibitors. In summary, our study established a highly efficient approach for USP22-specific inhibitor discovery, which lead to identification of two selective and potent USP22 inhibitors as potential drugs in anticancer therapy.

Prioritization of control factors for heavy metals in groundwater based on a source-oriented health risk assessment model.

Heavy metals (HMs) in groundwater seriously threaten ecological safety and human health. To facilitate the effective management of groundwater contamination, priority control factors of HMs in groundwater need to be categorized. A total of 86 groundwater samples were collected from the Huangpi district of Wuhan city, China, during the dry and wet seasons. To determine priority control factors, a source-oriented health risk assessment model was applied to compare the pollution sources and health risks of seven HMs (Cu, Pb, Zn, Cr, Ni, As, and Fe). The results showed that the groundwater had higher As and Fe contents. The sources of HM pollution during the wet period were mainly industrial and agricultural activities and natural sources. During the dry period, origins were more complex due to the addition of domestic discharges, such as sewage wastewater. Industrial activities (74.10% during the wet period), agricultural activities (53.84% during the dry period), and As were identified as the priority control factors for groundwater HMs. The results provide valuable insights for policymakers to coordinate targeted management of HM pollution in groundwater and reduce the cost of HM pollution mitigation.

Specific surface modification of liposomes for gut targeting of food bioactive agents.

Liposomes have become a research hotspot in recent years as food delivery systems with attractive properties, including the bilayer structure assembled like the cell membrane, reducing the side-effect and improving environmental stability of cargos, controlling release, extending duration of functional ingredients, and high biodegradable and biocompatible abilities in the body. However, the conventional liposomes lack stability during storage and are weak in targeted absorption in the gastrointestinal track. At present, surface modification has been approved to be an effective platform to shield these barricades and help liposomes deliver the agents safely and effectively to the ideal site. In this review, the gastrointestinal stability of conventional liposomes, cargo release models from liposomes, and the biological fate of the core materials after release were emphasized. Then, the strategies in both physical and chemical perspectives to improve the stability and utilization of liposomes in the gastrointestinal tract, and the emerging approaches for improving gut targeting by specifically modified liposomes and the intestinal receptors relative to liposomes/cargos absorption were highlighted. Last but not the least, the safety, challenges, and opportunities for the improvement of liposomal bioavailability were also discussed to inspire new applications of liposomes as oral carriers.

The paradox of obesity in pressure ulcers of critically ill patients.

The relationship between body mass index and pressure ulcers in critically ill patients is controversial. We aimed to investigate the association between body mass index and pressure ulcers by analysing data from the Medical Information Mart for Intensive Care IV (version 2.0) database. Eligible data (21 835 cases) were extracted from the database (2008-2019). The association between body mass index and pressure ulcers in critically ill patients was investigated by adjusting multivariate trend analysis, restricted cubic spline analysis, and segmented linear models. Subgroup analyses and sensitivity analyses were used to ensure the stability of the results. Trend analysis and restricted cubic spline analysis showed an approximate U-shaped correlation between body mass index and the occurrence of pressure ulcers in critically ill patients, with the risk of pressure ulcers decreasing rapidly with increasing body mass index (8.6% decrease per unit) after adjusting for relevant factors; the trend reached its minimum at a body mass index of 27.5 kg/m2, followed by a slow increase in the risk of pressure ulcers with increasing body mass index (1.4% increase per unit). Among the subgroups, the highest overall risk of pressure ulcers and the risk of severe pressure ulcers were significantly higher in the underweight group than in the other subgroups, and the risk associated with the overweight group was the lowest. There is a U-shaped association between body mass index and pressure ulcers in critically ill patients, and being underweight and obese both increase the risk of pressure ulcers. The risk is highest among underweight patients and lowest among overweight patients (but not patients of normal weight), necessitating targeted prevention strategies for critically ill patients with different body mass indexes.

Knockdown of Rice MicroRNA166 Confers Drought Resistance by Causing Leaf Rolling and Altering Stem Xylem Development.

MicroRNAs are 19- to 22-nucleotide small noncoding RNAs that have been implicated in abiotic stress responses. In this study, we found that knockdown of microRNA166, using the Short Tandem Target Mimic (STTM) system, resulted in morphological changes that confer drought resistance in rice (Oryza sativa). From a large-scale screen for miRNA knockdown lines in rice, we identified miR166 knockdown lines (STTM166); these plants exhibit a rolled-leaf phenotype, which is normally displayed by rice plants under drought stress. The leaves of STTM166 rice plants had smaller bulliform cells and abnormal sclerenchymatous cells, likely causing the rolled-leaf phenotype. The STTM166 plants had reduced stomatal conductance and showed decreased transpiration rates. The STTM166 lines also exhibited altered stem xylem and decreased hydraulic conductivity, likely due to the reduced diameter of the xylem vessels. Molecular analyses identified rice HOMEODOMAIN CONTAINING PROTEIN4 (OsHB4), a member of HD-Zip III gene family, as a major target of miR166; moreover, rice plants overexpressing a miR166-resistant form of OsHB4 resembled the STTM166 plants, including leaf rolling and higher drought resistance. The genes downstream of miR166-OsHB4 consisted of polysaccharide synthesis-related genes that may contribute to cell wall formation and vascular development. Our results suggest that drought resistance in rice can be increased by manipulating miRNAs, which leads to developmental changes, such as leaf rolling and reduced diameter of the xylem, that mimic plants' natural responses to water-deficit stress.

Four Natural Compounds Separated from Folium Isatidis: Crystal Structures and Antibacterial Activity.

Four natural compounds were obtained by concentrating, separating and purifying from the Folium isatidis. These natural compounds have been characterized by elemental analysis, IR spectrum, NMR and single-crystal X-ray diffraction analysis. The results show that these natural compounds are 4(3H)-quinazolinone (I), 2,4(1H,3H)-quinazolinedione (II), methyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate (III) and ethyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate (IV). The antibacterial activity experiment showed that I and II had better activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Salmonella than III, IV and other multiple components, because III and IV have long branches and steric hindrance effect. Compounds I and II have planar structure, which can more easily combine with these bacteria and kill them. The above results have good guiding significance for studying the antibacterial activity for single components or mixtures from natural origin.

[Predictive value of plasma exosome count for the prognosis in septic patients].

OBJECTIVE: To investigate the predictive value of plasma exosome count for the prognosis of patients with sepsis. METHODS: A prospective observational study was conducted. The patients with sepsis admitted to intensive care unit (ICU) of Zhejiang Hospital from November 2020 to December 2021 were enrolled as the study subjects. On the 1st day of admission to the ICU, the patient's gender, age, underlying disease, infection site, mean arterial pressure (MAP) and severity scores were recorded, and venous blood was taken for detecting the blood routine, blood biochemistry, and procalcitonin (PCT), and arterial blood was taken for blood gas analysis, simultaneously, the patient's noradrenaline (NA) dosage was recorded. On the 1st, 3rd, 5th, and 7th day of ICU admission, plasma exosomes were extracted, and the number of exosomes was detected by nanoparticle tracking analyzer. The endpoint of observation was the death of the patient 28 days after admission to the ICU. The differences in baseline data and plasma exosome counts of patients with different 28-day prognosis were analyzed and compared. The Spearman correlation method was used to analyze the correlation between plasma exosome counts and other clinical indicators. Binary multivariate Logistic regression analysis was used to screen the 28-day death risk factors of septic patients. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of each index on the 28-day death of septic patients. The Kaplan-Meier method was used to analyze the 28-day survival curve. RESULTS: A total of 26 patients with sepsis were enrolled, of whom 21 survived and 5 died on the 28th day. Compared with the survival group, the patients in the death group had lower MAP, higher sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, white blood cell count (WBC), cardiac troponin I (cTnI), and worse oxygenation. The plasma exosome count on the 1st day of ICU admission in the death group was significantly higher than that in the survival group (×1015/L: 16.96±9.11 vs. 5.20±2.42, P < 0.05). Subsequently, the plasma exosome counts in both groups continued to decrease, and there was no statistically significant difference between the two groups. Spearman correlation analysis showed that the plasma exosome count on the 1st day of ICU admission in septic patients was significantly positively correlated with SOFA score, APACHE II score, blood lactic acid (Lac), alanine aminotransferase (ALT) and NA dosage (r values were 0.572, 0.585, 0.463, 0.411, 0.696, all P < 0.05), and it significantly negatively correlated with MAP and oxygenation index (PaO2/FiO2; r values were -0.392 and -0.496, both P < 0.05). Multivariate Logistic regression analysis showed that plasma exosome count on the 1st day of ICU admission was an independent risk factor for 28-day death in septic patients [odds ratio (OR) = 1.385, 95% confidence interval (95%CI) was 1.075-1.785, P = 0.012]. ROC curve analysis showed that the area under the ROC curve (AUC) of plasma exosome count on the 1st day of ICU admission for predicting 28-day death in septic patients was 0.800 (95%CI was 0.449-1.000); when the optimal cut-off value was 14.50×1015/L, the sensitivity was 80.0% and the specificity was 100%. According to the optimal cut-off value of 1-day plasma exosome count, the patients were divided into two groups for Kaplan-Meier survival curve analysis, and the results showed that the cumulative survival rate of patients with plasma exosome count < 14.50×1015/L was significantly higher than that of patients with plasma exosome count ≥ 14.50×1015/L (Log-Rank test: χ 2 = 19.100, P < 0.001). CONCLUSIONS: The plasma exosome count of septic patients is significantly increased on the 1st day of admission to the ICU, which is related to the severity, and can predict the risk of death at 28 days.

Effects of Multicomponent Exercise on Community-Dwelling Older Adults With Mild Cognitive Impairment.

PURPOSE: To explore the effects of a group-based multicomponent exercise program on general cognitive functioning, depression, and social functioning in community-dwelling older adults with mild cognitive impairment (MCI) and whether the effects can be maintained. METHOD: Fifty older adults with MCI were conveniently recruited from two communities in the study area and randomly assigned to the intervention group or control group. The intervention group received three sessions of 60-minute, multicomponent exercise per week for 3 months, plus MCI-related health education. The control group only received MCI-related health education. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Beijing Version (MoCA-BJ) were used to assess general cognitive function. The Functional Activities Questionnaire (FAQ) and Geriatric Depression Scale (GDS-30) were used to evaluate participants' social function and depression, respectively. Participants' exercise intensity was assessed using the Category Ratio Scale. RESULTS: After the 3-month intervention, there were significant improvements in general cognitive function (p = 0.046), attention (p = 0.009), delayed recall (p = 0.015), and social function (p = 0.011) in the intervention group compared with the control group. However, after 3-month postintervention follow up, no significant differences in MMSE, MoCA-BJ, GDS-30, and FAQ scores were noted between groups. CONCLUSION: The 3-month multicomponent exercise program improved general cognitive function and social functioning in community-dwelling older adults with MCI. However, there was no evidence that these benefits lasted for another 3 months after stopping the exercise program. [Research in Gerontological Nursing, 17(2), 65-79.].

Prenatal risk assessment of Xp21.1 duplication involving the DMD gene by optical genome mapping.

Structural variants (SVs) of unknown significance are great challenges for prenatal risk assessment, especially when involving dose-sensitive genes such as DMD The pathogenicities of 5'-terminal DMD duplications in the database remain controversial. Four prenatal cases with Xp21.1 duplications were identified by routine prenatal genomic testing, encompassing the 5'-UTR to exons 1-2 in family 1 and family 2, and to exons 1-9 in family 3. The duplication in family 4 was non-contiguous covering the 5'-UTR to exon 1 and exons 3-7. All were traced to unaffected males in the family pedigrees. A new genome-wide approach of optical genome mapping was performed in families 1, 2, and 3 to delineate the breakpoints and orientation of the duplicated fragments. The extra copies were tandemly inserted into the upstream of DMD, preserving the integrity of ORF from the second copy. The pathogenicities were thus reclassified as likely benign. Our data highlight the importance of structural delineation by optical genome mapping in prenatal risk assessment of incidentally identified SVs involving DMD and other similar large dose-sensitive genes.

Uncovering the differentiated impacts of carbon neutrality and clean air policies in multi-provinces of China.

Ambitious action plans have been launched to address climate change and air pollution. Through coupling the IMED|CGE, GAINS, and IMED|HEL models, this study investigate the impacts of implementing carbon neutrality and clean air policies on the energy-environment-health-economy chain in the Beijing-Tianjin-Hebei-Henan-Shandong-Shanxi region of China. Results show that Shandong holds the largest reduction in energy consumption and carbon emissions toward the 1.5°C target. Shandong, Henan, and Hebei are of particularly prominent pollutant reduction potential. Synergistic effects of carbon reduction on decreasing PM2.5 concentration will increase in the future, specifically in energy-intensive regions. Co-deployment of carbon reduction and end-of-pipe technologies are beneficial to decrease PM2.5-related mortalities and economic loss by 4.7-12.9% in 2050. Provincial carbon reduction cost will be higher than monetary health benefits after 2030, indicating that more zero-carbon technologies should be developed. Our findings provide scientific enlightenment on policymaking toward achieving carbon reduction and pollution mitigation from multiple perspectives.

Understanding the mechanism of high viscosity food delaying gastric emptying.

Controlling the structure and viscosity of food can influence the development of diet-related diseases. Food viscosity has been linked with health through its impact on human digestion and gastrointestinal transit, however, there is limited understanding of how the viscosity of food regulates gastric emptying. Here, we used model food preparations with different viscosities using guar gum, to explore the mechanism underlying the influence of viscosity on gastric motility, gastric emptying and postprandial blood glucose. Based on experiments in human volunteers and animals, we demonstrated that high viscosity meals increased gastric antrum area and gastric retention rate. Viscosity also affected gut hormone secretion, reduced the gene expression level of interstitial cells of Cajal, resulting in a delay of gastric emptying and limiting the increase in postprandial glucose. This improved mechanistic understanding of food viscosity during gastric digestion is important for designing new foods to benefit human health.

Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) holds a prominent position among global cancer types. Classically, HCC manifests in individuals with a genetic predisposition when they encounter risk elements, particularly in the context of liver cirrhosis. Peroxisome proliferator-activated receptors (PPARs), which are transcription factors activated by fatty acids, belong to the nuclear hormone receptor superfamily and play a pivotal role in the regulation of energy homeostasis. At present, three distinct subtypes of PPARs have been recognized: PPARα, PPARγ, and PPARß/δ. They regulate the transcription of genes responsible for cellular development, energy metabolism, inflammation, and differentiation. In recent years, with the rising incidence of HCC, there has been an increasing focus on the mechanisms and roles of PPARs in HCC. PPARα primarily mediates the occurrence and development of HCC by regulating glucose and lipid metabolism, inflammatory responses, and oxidative stress. PPARß/δ is closely related to the self-renewal ability of liver cancer stem cells (LCSCs) and the formation of the tumor microenvironment. PPARγ not only influences tumor growth by regulating the glucose and lipid metabolism of HCC, but its agonists also have significant clinical significance for the treatment of HCC. Therefore, this review offers an exhaustive examination of the role of the three PPAR subtypes in HCC progression, focusing on their mediation of critical cellular processes such as glucose and lipid metabolism, inflammation, oxidative stress, and other pivotal signaling pathways. At the end of the review, we discuss the merits and drawbacks of existing PPAR-targeted therapeutic strategies and suggest a few alternative combinatorial therapeutic approaches that diverge from conventional methods.

MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma.

BACKGROUND: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells. METHODS: Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation. RESULTS: MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions. CONCLUSIONS: Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.

Early prognosis prediction for non-variceal upper gastrointestinal bleeding in the intensive care unit: based on interpretable machine learning.

INTRODUCTION: This study aims to construct a mortality prediction model for patients with non-variceal upper gastrointestinal bleeding (NVUGIB) in the intensive care unit (ICU), employing advanced machine learning algorithms. The goal is to identify high-risk populations early, contributing to a deeper understanding of patients with NVUGIB in the ICU. METHODS: We extracted NVUGIB data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.2) database spanning from 2008 to 2019. Feature selection was conducted through LASSO regression, followed by training models using 11 machine learning methods. The best model was chosen based on the area under the curve (AUC). Subsequently, Shapley additive explanations (SHAP) was employed to elucidate how each factor influenced the model. Finally, a case was randomly selected, and the model was utilized to predict its mortality, demonstrating the practical application of the developed model. RESULTS: In total, 2716 patients with NVUGIB were deemed eligible for participation. Following selection, 30 out of a total of 64 clinical parameters collected on day 1 after ICU admission remained associated with prognosis and were utilized for developing machine learning models. Among the 11 constructed models, the Gradient Boosting Decision Tree (GBDT) model demonstrated the best performance, achieving an AUC of 0.853 and an accuracy of 0.839 in the validation cohort. Feature importance analysis highlighted that shock, Glasgow Coma Scale (GCS), renal disease, age, albumin, and alanine aminotransferase (ALP) were the top six features of the GBDT model with the most significant impact. Furthermore, SHAP force analysis illustrated how the constructed model visualized the individualized prediction of death. CONCLUSIONS: Patient data from the MIMIC database were leveraged to develop a robust prognostic model for patients with NVUGIB in the ICU. The analysis using SHAP also assisted clinicians in gaining a deeper understanding of the disease.

Thermal stability and in vitro biological fate of lactoferrin-polysaccharide complexes.

Lactoferrin (LF) is a thermally sensitive iron-binding globular glycoprotein. Heat treatment can induce its denaturation and aggregation and thus affect its functional activity. In this study, carrageenan (CG), xanthan gum (XG) and locust bean gum (LBG), allowed to apply in infant food, were used to form protein-polysaccharide complexes to improve the thermal stability of LF. Meanwhile, in vitro simulated infant digestion and absorption properties of LF were also estimated. The results showed that the complexes formed by CG and XG with LF (LF-CG and LF-XG) could significantly inhibit the loss of α-helix structure of LF against heating. LF-CG and LF-LBG could protect LF from digestion in simulated infant gastric fluid and slow down the degradation of LF under the simulated intestinal conditions. Besides, LF, LF-CG and LF-XG showed no adverse effects on the growth of Caco-2 cells in the LF concentration range of 10-300 µg/mL, and LF-XG exhibited better beneficial to improve the cell uptake of the digestive product than the other protein-polysaccharides at the LF concentration of 100 µg/mL. This study may provide a reference for the enhancement of thermal processing stability of LF and development infant food ingredient with high nutrients absorption efficiency in the gastrointestinal environment in the future.

Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk.

BACKGROUND: Soy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. METHODS: A two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. RESULTS: A nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57-0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). CONCLUSIONS: We identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

The novel lactoferrin and DHA-codelivered liposomes with different membrane structures: Fabrication, in vitro infant digestion, and suckling pig intestinal organoid absorption.

Inspired by membrane structure of breast milk and infant formula fat globules, four liposomes with different particle size (large and small) and compositions (Single phospholipids contained phosphatidylcholine, complex phospholipids contained phosphatidylcholine, phosphatidylethanolamine and sphingomyelin) were fabricated to deliver lactoferrin and DHA. In vitro infant semi-dynamic digestive behavior and absorption in intestinal organoids of liposomes were investigated. Liposomal structures were negligible changed during semi-dynamic gastric digestion while damaged in intestine. Liposomal degradation rate was primarily influenced by particle size, and complex phospholipids accelerated DHA hydrolysis. The release rate of DHA (91.7 ± 1.3 %) in small-sized liposomes (0.181 ± 0.001 µm) was higher than free DHA (unencapsulated, 64.6 ± 3.4 %). Complex phospholipids liposomal digesta exhibited higher transport efficiency (3.4-fold for fatty acids and 2.0-fold for amino acids) and better organoid growth than digesta of bare nutrients. This study provided new insights into membrane structure-functionality relationship of liposomes and may aid in the development of novel infant nutrient carriers.