Preparation, characterization, and binding mechanism of quercetin-loaded composite nanoparticles based on zein-soybean protein isolate.

In this study, quercetin (Que) was encapsulated for controlled release during gastrointestinal digestion using zein-soy isolate protein (SPI) composite nanoparticles that were made following an antisolvent precipitation technique. The average particle size of the composite nanoparticles ranged from 182.1 to 230.9 nm, and the polydispersity index (PDI) was small (0.105-0.323). The microstructure revealed that the composite nanoparticles were spherically distributed and that Que. was embedded on the surface of the nanoparticles. Que. has an encapsulation efficiency of up to 93.3 %. Spectrum analysis, molecular docking and zeta potential measurements revealed that the interactions between the composite nanoparticles and Que. occurred mainly through hydrophobic interactions, hydrogen bonding, and electrostatic interactions. Compared with single zein nanoparticles, the composite nanoparticles showed a significant and controlled release of Que. during the whole simulated gastrointestinal digestion process. This study provides a novel method for the development of a controlled-release drug delivery system for controlling the release of Que.

Unveiling the Interplay Between Depressive Symptoms' Alleviation and Quality of Life Improvement in Major Depressive Disorder: A Network Analysis Based on Longitudinal Data.

Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.

Greetings from virologists to mycologists: A review outlining viruses that live in fungi.

Viruses are genetic elements that parasitize self-replicating cells. Therefore, organisms parasitized by viruses are not limited to animals and plants but also include microorganisms. Among these, viruses that parasitize fungi are known as mycoviruses. Mycoviruses with an RNA genome persistently replicate inside fungal cells and coevolve with their host cells, similar to a cellular organelle. Within host cells, mycoviruses can modulate various fungal characteristics and activities, including pathogenicity and the production of enzymes and secondary metabolites. In this review, we provide an overview of the mycovirus research field as introduction to fungal researchers. Recognition of all genetic elements in fungi aids towards better understanding and control of fungi, and makes fungi a significant model system for studying microorganisms containing multiple genetic elements.

Knowledge of and attitude towards depression among urban and rural residents in Beijing: a cross-sectional study.

OBJECTIVES: To compare the level of knowledge of depression, recognition ability and attitudes towards depression among urban and rural residents in Beijing. DESIGN: A cross-sectional study. SETTING: Six districts in Beijing, China, 2021. PARTICIPANTS: A total of 6463 participants aged 18 years and above who had lived for more than 6 months over the last year in Beijing were selected in this study. OUTCOME: The awareness and recognition of depression and the views of residents towards people with depression. RESULTS: A total of 2554 urban and 2043 rural residents completed the survey. Urban residents of Beijing exhibited a higher average total score on the Depression Knowledge Questionnaire [(20.4±3.3) vs (18.7±3.5), p<0.001] and a higher rate of correctly identifying individuals with depression (47.9% vs 36.6%, p<0.001) than their counterparts in rural areas. Residents who correctly identified people with depression had higher scores on the Depression Knowledge Questionnaire. Depression knowledge varied significantly among urban and rural residents. The multivariate linear regression analysis revealed that rural residents scored significantly lower on measures of depression knowledge compared with urban residents (B=-0.83, 95%CI=-1.03 to -0.63, p<0.001). Older individuals (aged 50+) showed lower understanding compared with the 18-49 age group, with significant negative regression coefficients (Urban: B=-1.06, Rural: B=-1.35, both p<0.001). Higher educational levels were positively associated with greater depression knowledge (Urban: B=1.40, Rural: B=1.21, both p<0.001). Employment was linked to higher knowledge levels than unemployment (Urban: B=-0.60, Rural: B=-0.58, both p=0.00). A monthly income of 8000 yuan or more correlated with better depression understanding than lower incomes (Urban: B=0.81, Rural: B=1.04, both p<0.001). Additionally, in urban areas, unmarried residents scored higher in depression knowledge than those divorced (B=-0.55, p=0.04). Residents in urban areas had relatively positive attitudes towards individuals with depression. CONCLUSIONS: Rural residents of Beijing had lower levels of knowledge and recognition of depression and more negative attitudes towards individuals with depression than those from urban areas. The health authority needs to focus on the poor level of knowledge and increase mental health resources in rural areas as a priority site for future psychological popularisation efforts.

Associations between serum albumin level trajectories and clinical outcomes in sepsis patients in ICU: insights from longitudinal group trajectory modeling.

Background: Sepsis triggers a strong inflammatory response, often leading to organ failure and high mortality. The role of serum albumin levels in sepsis is critical but not fully understood, particularly regarding the significance of albumin level changes over time. This study utilized Group-based Trajectory Modeling (GBTM) to investigate the patterns of serum albumin changes and their impact on sepsis outcomes. Methods: We conducted a retrospective analysis on ICU patients from West China Hospital (2015-2022), employing GBTM to study serum albumin fluctuations within the first week of ICU admission. The study factored in demographics, clinical parameters, and comorbidities, handling missing data through multiple imputation. Outcomes assessed included 28-day mortality, overall hospital mortality, and secondary complications such as AKI and the need for mechanical ventilation. Results: Data from 1,950 patients revealed four serum albumin trajectories, showing distinct patterns of consistently low, increasing, moderate, and consistently high levels. These groups differed significantly in mortality, with the consistently low level group experiencing the highest mortality. No significant difference in 28-day mortality was observed among the other groups. Subgroup analysis did not alter these findings. Conclusion: The study identified four albumin trajectory groups in sepsis patients, highlighting that those with persistently low levels had the worst outcomes, while those with increasing levels had the best. Stable high levels above 30 g/L did not change outcomes significantly. These findings can inform clinical decisions, helping to identify high-risk patients early and tailor treatment approaches.

Characteristics and partitions of traditional and emerging organophosphate esters in soil and groundwater based on machine learning.

Organophosphate esters (OPEs) pose hazards to both humans and the environment. This study applied target screening to analyze the concentrations and detection frequencies of OPEs in the soil and groundwater of representative contaminated sites in the Pearl River Delta. The clusters and correlation characteristics of OPEs in soil and groundwater were calculated by self-organizing map (SOM). The risk assessment and partitions of OPEs in industrial park soil and groundwater were conducted. The results revealed that 14 out of 23 types of OPEs were detected. The total concentrations (Σ23OPEs) ranged from 1.931 to 743.571 ng/L in the groundwater, and 0.218 to 79.578 ng/g in the soil, the former showed highly soluble OPEs with high detection frequencies and concentrations, whereas the latter exhibited the opposite trend. SOM analysis revealed that the distribution of OPEs in the soil differed significantly from that in the groundwater. In the industrial park, OPEs posed acceptable risks in both the soil and groundwater. The soil could be categorized into Zone I and II, and the groundwater into Zone I, II, and III, with corresponding management recommendations. Applying SOM to analyze the characteristics and partitions of OPEs may provide references for other new pollutants and contaminated sites.

Coke oven emissions exacerbate allergic asthma by promoting ferroptosis in airway epithelial cells.

Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of Ptgs2 and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE.

New lineages of RNA viruses from clinical isolates of Rhizopus microsporus revealed by fragmented and primer-ligated dsRNA sequencing (FLDS) analysis.

Rhizopus microsporus is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of R. microsporus for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families Mitoviridae, Narnaviridae, and Endornaviridae, ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families Virgaviridae and Phasmaviridae, and the proposed family "Ambiguiviridae." All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family Mitoviridae, whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen R. microsporus harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of R. microsporus may expand the repertoire of natural therapeutic agents for mucormycosis in the future.IMPORTANCEThe diversity of mycoviruses in fungal hosts in the division Mucoromycota has been underestimated, mainly within the species Rhizopus microsporus. Only five positive-sense RNA genomes had previously been discovered in this species. Because current sequencing methods poorly complete the termini of genomes, we used fragmented and primer-ligated double-stranded RNA sequencing to acquire the full-length genomes. Eleven novel mycoviruses were detected in this study, including the first negative-sense RNA genome reported in R. microsporus. Our findings extend the understanding of the viral diversity in clinical strains of Mucoromycota, may provide insights into the pathogenesis and ecology of this fungus, and may offer therapeutic options.

Long-term climate warming and extreme cold events driving ecological shifts in a deep oligo-mesotrophic lake.

Deep lakes are critical for freshwater storage, yet they are struggling against major ecological issues from climate change and nutrient pollution. A comprehensive understanding of internal feedback mechanisms is crucial for regulating nutrients in these lakes. A five-year study was conducted on the diatom community and environment in Lake Fuxian, China's largest deep freshwater lake, which is becoming eutrophic. The results indicate a shift in the diatom community from a stable state dominated by a single species to a rapid seasonal fluctuation, and there is a significant increase in diatom biomass. Specifically, stable stratification and low nutrient concentrations are limiting the growth of diatom biomass and maintaining the dominance of Cyclotella. Nutrients in the hypolimnion were replenished in the epilimnion during the extreme cold of winter, triggering a shift in the diatom community. This shift may imply that future climate change will exacerbate the positive feedback of hypoxia-nutrient release of algal blooms, potentially triggering a regime shift in the ecosystem of the entire lake. This study underscores the fact that climate change alters the internal feedback mechanisms of deep lakes, reducing ecosystem stability, and provides a scientific basis for further clarification of protection measures for deep lakes.

Radiomics using multiparametric magnetic resonance imaging to predict postoperative visual outcomes of patients with pituitary adenoma.

BACKGROUND: Preoperative prediction of visual outcomes following pituitary adenoma surgery is challenging yet crucial for clinical decision-making. We aimed to develop models using radiomics from multiparametric MRI to predict postoperative visual outcomes. METHODS: A cohort of 152 patients with pituitary adenoma was retrospectively enrolled and divided into recovery and non-recovery groups based on visual examinations performed six months after surgery. Radiomic features of the optic chiasm were extracted from preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1-weighted imaging (T1CE). Predictive models were constructed using the least absolute shrinkage and selection operator wrapped with a support vector machine through five-fold cross-validation in the development cohort and evaluated in an independent test cohort. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Four models were established based on radiomic features selected from individual or combined sequences. The AUC values of the models based on T1WI, T2WI and T1CE were 0.784, 0.724, 0.822 in the development cohort, and 0.767, 0.763, 0.794 in the independent test cohort. The multiparametric model demonstrated superior performance among the four models, with AUC of 0.851, accuracy of 0.832. sensitivity of 0.700, specificity of 0.910 in the development cohort, and AUC of 0.847, accuracy of 0.800, sensitivity of 0.882 and specificity of 0.750 in the independent test cohort. CONCLUSION: The multiparametric model utilizing radiomics of optic chiasm outperformed single-sequence models in predicting postoperative visual recovery in patients with pituitary adenoma, serving as a novel approach for enhancing personalized treatment strategies.

The Importance of Knowledge on Dementia Risk Factors in the General Public: A Cross-Sectional Study.

ABSTRACT: The purpose of this study was to determine the influence of knowledge and beliefs on beneficial behaviors and dementia risk scores. A online survey was conducted among Chinese community residents over 18 years old. Multivariate logistic regression was used to identify the impact of knowledge and beliefs on dementia risk scores and beneficial behaviors. The respondents were 760 adults (mean age = 47.6 years, 60.8% female). Knowledge and beliefs were associated with cognitive activities (knowledge, odds ratio [OR] = 1.04; beliefs, OR = 1.17) and dementia risk scores (knowledge, OR = 0.95; beliefs, OR = 0.82). Additionally, lower perceived susceptibility (OR = 1.68; 95% CI, 1.04 to 2.72) and higher perceived benefits (OR = 0.68; 95% CI, 0.57 to 0.80) were associated with lower dementia risk scores. Knowledge and beliefs can promote beneficial behaviors and reduce dementia risk. In particular, perceptions of dementia susceptibility and benefits should be enhanced, which will greatly reduce dementia risk in the general public.

An analysis of factors influencing cognitive dysfunction among older adults in Northwest China based on logistic regression and decision tree modelling.

BACKGROUND: Cognitive dysfunction is one of the leading causes of disability and dependence in older adults and is a major economic burden on the public health system. The aim of this study was to investigate the risk factors for cognitive dysfunction and their predictive value in older adults in Northwest China. METHODS: A cross-sectional study was conducted using a multistage sampling method. The questionnaires were distributed through the Elderly Disability Monitoring Platform to older adults aged 60 years and above in Northwest China, who were divided into cognitive dysfunction and normal cognitive function groups. In addition to univariate analyses, logistic regression and decision tree modelling were used to construct a model to identify factors that can predict the occurrence of cognitive dysfunction in older adults. RESULTS: A total of 12,494 valid questionnaires were collected, including 2617 from participants in the cognitive dysfunction group and 9877 from participants in the normal cognitive function group. Univariate analysis revealed that ethnicity, BMI, age, educational attainment, marital status, type of residence, residency status, current work status, main economic source, type of chronic disease, long-term use of medication, alcohol consumption, participation in social activities, exercise status, social support, total scores on the Balanced Test Assessment, total scores on the Gait Speed Assessment total score, and activities of daily living (ADL) were significantly different between the two groups (all P < 0.05). According to logistic regression analyses, ethnicity, BMI, educational attainment, marital status, residency, main source of income, chronic diseases, annual medical examination, alcohol consumption, exercise status, total scores on the Balanced Test Assessment, and activities of daily living (ADLs) were found to influence cognitive dysfunction in older adults (all P < 0.05). In the decision tree model, the ability to perform activities of daily living was the root node, followed by total scores on the Balanced Test Assessment, marital status, educational attainment, age, annual medical examination, and ethnicity. CONCLUSIONS: Traditional risk factors (including BMI, literacy, and alcohol consumption) and potentially modifiable risk factors (including balance function, ability to care for oneself in daily life, and widowhood) have a significant impact on the increased risk of cognitive dysfunction in older adults in Northwest China. The use of decision tree models can help health care workers better assess cognitive function in older adults and develop personalized interventions. Further research could help to gain insight into the mechanisms of cognitive dysfunction and provide new avenues for prevention and intervention.

The relative contribution of PM2.5 components to the obstructive ventilatory dysfunction-insights from a large ventilatory function examination of 305,022 workers in southern China.

BACKGROUND: The new round of WHO/ILO Joint Estimates of the Work-related Burden of Disease assessment requires futher research to provide more evidence, especially on the health impact of ambient air pollution around the workplace. However, the evidence linking obstructive ventilatory dysfunction (OVD) to fine particulate matter (PM2.5) and its chemical components in workers is very limited. Evidence is even more scarce on the interactive effects between occupational factors and particle exposures. We aimed to fill these gaps based on a large ventilatory function examination of workers in southern China. METHODS: We conducted a cross-sectional study among 363,788 workers in southern China in 2020. The annual average concentration of PM2.5 and its components were evaluated around the workplace through validated spatiotemporal models. We used mixed-effect models to evaluate the risk of OVD related to PM2.5 and its components. Results were further stratified by basic characteristics and occupational factors. FINDINGS: Among the 305,022 workers, 119,936 were observed with OVD. We found for each interquartile range (IQR) increase in PM2.5 concentration, the risk of OVD increased by 27.8 (95 % confidence interval (CI): 26.5-29.2 %). The estimates were 10.9 % (95 %CI: 9.7-12.1 %), 15.8 % (95 %CI: 14.5-17.2 %), 2.6 % (95 %CI: 1.4-3.8 %), 17.1 % (95 %CI: 15.9-18.4 %), and 11 % (95 %CI: 9.9-12.2 %), respectively, for each IQR increment in sulfate, nitrate, ammonium salt, organic matter and black carbon. We observed greater effect estimates among females, younger workers, workers with a length of service of 24-45 months, and professional skill workers. Furthermore, it is particularly noteworthy that the noise-exposed workers, high-temperature-exposed workers, and less-dust-exposed workers were at a 5.7-68.2 % greater risk than others. INTERPRETATION: PM2.5 and its components were significantly associated with an increased risk of OVD, with stronger links among certain vulnerable subgroups.

Clinical characteristics and prognostic factors of adult brainstem gliomas: A retrospective analysis of histologically-proven 40 cases.

To illustrate the clinical characteristics and prognostic factors of adult patients pathologically confirmed with brainstem gliomas (BSGs). Clinical data of 40 adult patients pathologically diagnosed with BSGs admitted to Beijing Shijitan Hospital from 2009 to 2022 were recorded and retrospectively analyzed. The primary parameters included relevant symptoms, duration of symptoms, Karnofsky performance status (KPS), tumor location, type of surgical resection, diagnosis, treatment, and survival. Univariate and multivariate analyses were evaluated by Cox regression models. The gliomas were located in the midbrain of 9 patients, in the pons of 14 cases, in the medulla of 5 cases, in the midbrain and pons of 6 cases and invading the medulla and pons of 6 cases, respectively. The proportion of patients with low-grade BSGs was 42.5%. Relevant symptoms consisted of visual disturbance, facial paralysis, dizziness, extremity weakness, ataxia, paresthesia, headache, bucking, dysphagia, dysacousia, nausea, dysphasia, dysosmia, hypomnesia and nystagmus. 23 (57.5%) patients accepted stereotactic biopsy, 17 (42.5%) patients underwent surgical resection. 39 patients received radiotherapy and 34 cases were treated with temozolomide. The median overall survival (OS) of all patients was 26.2 months and 21.5 months for the median progression-free survival (PFS). Both duration of symptoms (P = .007) and tumor grading (P = .002) were the influencing factors for OS, and tumor grading was significantly associated with PFS (P = .001). Duration of symptoms for more than 2 months and low-grade are favorable prognostic factors for adult patients with BSGs.

Virtual reality-based dementia educational programmes for formal and informal caregivers of people with dementia: A scoping review.

AIM: To map evidence of the existing virtual reality-based dementia educational programmes and the effects of these educational programmes on dementia formal and informal caregivers. DESIGN: A scoping review. METHODS: A comprehensive search of nine databases was conducted to find studies from the inception of the databases to October 2023. Two authors independently screened the titles and abstracts related to the eligibility criteria. Full texts of potentially relevant studies were read by one author and checked by a second. Data extraction and synthesis using NVivo 12 were undertaken by one author and checked by two other authors. RESULTS: Nineteen studies published between 2002 and 2022. The four randomised controlled studies and five qualitative studies were of moderate to good methodological quality. The 10 quasi-experimental studies were of weak to moderate quality. Fifteen virtual reality-based educational programmes had a positive influence on formal and informal caregivers, including improving caregivers' perceptions changing attitudes towards people with dementia, while the nursing competence of formal caregivers did not improve in short term. Educational programmes that covered dementia-related information and care strategies better improved the knowledge level of dementia formal and informal caregivers. CONCLUSIONS: The qualitative and quantitative studies of moderate to good quality included in this study support the idea that virtual reality-based dementia educational programmes may be a safe and effective way and have potential benefits for improving knowledge, perceptions, attitudes and nursing competence. IMPACT: This scoping review will provide an emerging teaching model for formal and informal caregivers of people with dementia and help them better understand the types and the influence of virtual reality-based dementia educational programmes. REPORTING METHOD: PRISMA-ScR. NO PATIENT OR PUBLIC CONTRIBUTION: Not required as this review in accordance with the aim to map existing literature from the dementia formal and informal caregivers' perspective.

Robot obstacle avoidance optimization by A* and DWA fusion algorithm.

The current robot path planning methods only use global or local methods, which is difficult to meet the real-time and integrity requirements, and can not avoid dynamic obstacles. Based on this, this study will use the improved A-star global planning algorithm to design a hybrid robot obstacle avoidance path planning algorithm that integrates sliding window local planning methods to solve related problems. Specifically, A-star is optimized by evaluation function, sub node selection mode and path smoothness, and fuzzy control is introduced to optimize the sliding window algorithm. The study conducted algorithm validation on the TurtleBot3 mobile robot, with data sourced from experimental data from a certain college. The results showed that hybrid algorithm enabled the planned path to effectively navigate around dynamic obstacles and reach the target point accurately. When compared with traditional methods, path length reduced by 9.6%, path planning time decreased by 29% with an approximate 26.7% increase in the average speed of the robot. Compared with the traditional methods, the research algorithm has greatly improved in avoiding dynamic obstacles, path planning efficiency, model adaptability and so on, which has important value for relevant research. It can be seen that the algorithm proposed in the study has performance advantages, demonstrating the effectiveness and advantages of robot path planning, and can provide reference for robot obstacle avoidance optimization. Research can complete tasks for robots in practical environments, which has certain reference value for the research of robots in path planning and the development of path obstacle avoidance planning.

Ultrasound modification on milk fat globule membrane and soy lecithin to improve the physicochemical properties, microstructure and stability of mimicking human milk fat emulsions.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

miR-145a-5p/SIK1/cAMP-dependent alteration of synaptic structural plasticity drives cognitive impairment induced by coke oven emissions.

Exposure to fine particulate matter (PM) is associated with the neurodegenerative diseases. Coke oven emissions (COEs) in occupational environment are important sources of PM. However, its neurotoxicity is still unclear. Therefore, evaluating the toxicological effects of COE on the nervous system is necessary. In the present study, we constructed mouse models of COE exposure by tracheal instillation. Mice exposed to COE showed signs of cognitive impairment. This was accompanied by a decrease in miR-145a-5p and an increase in SIK1 expression in the hippocampus, along with synaptic structural damage. Our results demonstrated that COE-induced miR-145a-5p downregulation could increase the expression of SIK1 and phosphorylated SIK1, inhibiting the cAMP/PKA/CREB pathway by activating PDE4D, which was associated with reduced synaptic structural plasticity. Furthermore, restoring of miR-145a-5p expression based on COE exposure in HT22 cells could partially reversed the negative effects of COE exposure through the SIK1/PDE4D/cAMP axis. Collectively, our findings link epigenetic regulation with COE-induced neurotoxicity and imply that miR-145a-5p could be an early diagnostic marker for neurological diseases in patients with COE occupational exposure.

Effects of Metformin on JNK Signaling Pathway and PD-L1 Expression in Triple Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Metformin has been shown to have the potential to inhibit the proliferation of malignant cells. This study aimed to investigate the regulatory effect of metformin on the expression of programmed death protein ligand 1(PD-L1) and mechanisms in TNBC. Methods: Mouse breast cancer cell line 4T1 was co-cultured with metformin, and the effect of metformin on cell proliferation was detected by MTT assay. The effect of metformin on the expression of JNK, RSK2 and CREB was detected by MAPK pathway protein chip. BALB/c mice were inoculated with 4T1 cells with knockdown/overexpression of C-Jun N-terminal kinase (JNK), and administered with metformin. The weight of tumor tissue was observed at the end of the experiment. The expression of PD-L1 in tumor cells was observed by immunofluorescence staining and the level of INF-γwas quantitatively determined by ELISA. Results: Metformin inhibited the viability of 4T1 cells and increased the phosphorylation of JNK to reduce the phosphorylation of RSK2 and CREB. Metformin and JNK knockdown reduced the expression of PD-L1 in tumor cells, but there was no significant difference in the weight of tumor tissue. Metformin can reduce the level of INF-γ in tumor tissues, but JNK has no effect. Conclusion: Metformin can inhibit the expression of PD-L1 in triple-negative breast cancer mice and improve the tumor microenvironment, but does not reduce the size of the tumor.

Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study.

Background: Autoimmune diseases exhibit heterogenous dysregulation of pro-inflammatory or anti-inflammatory cytokine expression, akin to the pathophysiology of sepsis. It is speculated that individuals with autoimmune diseases may have an increased likelihood of developing sepsis and face elevated mortality risks following septic events. However, current observational studies have not yielded consistent conclusions. This study aims to explore the causal relationship between autoimmune diseases and the risks of sepsis and mortality using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR study involving a European population, with 30 autoimmune diseases as the exposure factors. To assess causal relationships, we employed the inverse variance-weighted (IVW) method and used Cochran's Q test for heterogeneity, as well as the MR pleiotropy residual sum and outlier (MR-PRESSO) global test for potential horizontal pleiotropy. Results: Genetically predicted Crohn's disease (ß = 0.067, se = 0.034, p = 0.046, OR = 1.069, 95% CI = 1.001-1.141) and idiopathic thrombocytopenic (ß = 0.069, se = 0.031, p = 0.023, OR = 1.071, 95% CI = 1.009-1.136) were positively associated with an increased risk of sepsis in critical care. Conversely, rheumatoid arthritis (ß = -0.104, se = 0.047, p = 0.025, OR = 0.901, 95% CI = 0.823-0.987), ulcerative colitis (ß = -0.208, se = 0.084, p = 0.013, OR = 0.812, 95% CI = 0.690-0.957), and narcolepsy (ß = -0.202, se = 0.092, p = 0.028, OR = 0.818, 95% CI = 0.684-0.978) were associated with a reduced risk of sepsis in critical care. Moreover, Crohn's disease (ß = 0.234, se = 0.067, p = 0.001, OR = 1.263, 95% CI = 1.108-1.440) and idiopathic thrombocytopenic (ß = 0.158, se = 0.061, p = 0.009, OR = 1.171, 95% CI = 1.041-1.317) were also linked to an increased risk of 28-day mortality of sepsis in critical care. In contrast, multiple sclerosis (ß = -0.261, se = 0.112, p = 0.020, OR = 0.771, 95% CI = 0.619-0.960) and narcolepsy (ß = -0.536, se = 0.184, p = 0.003, OR = 0.585, 95% CI = 0.408-0.838) were linked to a decreased risk of 28-day mortality of sepsis in critical care. Conclusion: This MR study identified causal associations between certain autoimmune diseases and risks of sepsis in critical care, and 28-day mortality in the European population. These findings suggest that exploring the mechanisms underlying autoimmune diseases may offer new diagnostic and therapeutic strategies for sepsis prevention and treatment.