2D copper-iron bimetallic metal-organic frameworks for reduction of nitrate with boosted efficiency and ammonia selectivity.

Electrocatalytic reduction of nitrate to ammonia has been considered a promising and sustainable pathway for pollutant treatment and ammonia has significant potential as a clean energy. Therefore, the method has received much attention. In this work, Cu/Fe 2D bimetallic metal-organic frameworks were synthesized by a facile method applied as cathode materials without high-temperature carbonization. Bimetallic centers (Cu, Fe) with enhanced intrinsic activity demonstrated higher removal efficiency. Meanwhile, the 2D nanosheet reduced the mass transfer barrier between the catalyst and nitrate and increased the reaction kinetics. Therefore, the catalysts with a 2D structure showed much better removal efficiency than other structures (3D MOFs and Bulk MOFs). Under optimal conditions, Cu/Fe-2D MOF exhibited high nitrate removal efficiency (87.8%) and ammonium selectivity (89.3%) simultaneously. The ammonium yielded up to significantly 907.2 µg/(hr·mgcat) (7793.8 µg/(hr·mgmetal)) with Faradaic efficiency of 62.8% at an initial 100 mg N/L. The catalyst was proved to have good stability and was recycled 15 times with excellent effect. DFT simulations confirm the reduced Gibbs free energy of Cu/Fe-2D MOF. This study demonstrates the promising application of Cu/Fe-2D MOF in nitrate reduction to ammonia and provides new insights for the design of efficient electrode materials.

TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma.

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45+lineage-CD90.2+NK1.1-NKp46-ST2-KLRG1+IL-17RB+ memory-like ILC2s (ml-ILC2s). Regulated by CCR9/CCL25 and S1P signaling, ml-ILC2s reside in the lamina propria of small intestines (siLP) in asthma remission, and subsequently move to airway upon re-encountering antigens or alarmins. Furthermore, ml-ILC2s possess properties of longevity, potential of rapid proliferation and producing IL-13, and display transcriptional characteristics with up-regulation of Tox and Tcf-7. ml-ILC2s transplantation restore the asthmatic changes abrogated by Tox and Tcf7 knockdown. Our data identify siLP ml-ILC2s as a memory-like subset, which promotes asthma relapse. Targeting TCF-1 and TOX might be promising for preventing asthma recurrence.

Analysis of prognostic risk factors and development of a predictive model for fetuses with right aortic arch with mirror-image branching: a prognostic evaluation method based on ultrasound parameter features.

Background: Prenatal ultrasound plays a crucial role in the diagnosis and classification of right aortic arch (AO) with mirror-image branching (RAA-MB). The recent research in this area has primarily focused on qualitative diagnosis, neglecting the quantitative analysis of ultrasound factors that impact RAA-MB outcomes. This study used echocardiography to measure prenatal ultrasound parameters for vascular ring and trachea in fetuses with RAA-MB, employing a nomogram model to evaluate factors influencing their prognosis, thereby providing a comprehensive characterization of potential outcomes. Methods: A retrospective case-control study was conducted from March 2019 to March 2023. A systematic gathering of prenatal echocardiograms and clinical data was completed for a cohort comprising 92 cases of fetal RAA-MB at the Ultrasound Medicine Center of Gansu Provincial Maternity and Child Care Hospital. Participant recruitment was executed through random selection from among those receiving outpatient medical care. Within the cohort, 42 cases were categorized as fetuses with isolated RAA-MB, while the remaining 50 cases were characterized as fetuses with RAA-MB and associated anomalies. Measurements were taken of the angle between the right AO and the ductus arteriosus (DA) (AO-DA), the distance between the AO and DA, the diameter of AO and DA, and the distance growth rate (DGR) of the AO-DA distance. Additionally, measurements were taken of the tracheal anterior-posterior diameter, tracheal left-right diameter, and tracheal circumference in the three-vessel tracheal view. In the AO view, measurements were taken of the tracheal cross-sectional area (TA) and the vessel ring cross-sectional area (VRA). The relationship between these parameters and the prognosis of fetuses with RAA-MB was assessed using logistic regression analysis. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of the predictive model based on these factors. Results: The multivariate logistic regression analysis revealed that the independent predictive factors for the prognosis of fetuses with RAA-MB were the AO-DA distance [odds ratio (OR) =0.012], TA (OR =0.401), and VRA (OR =1.103) (all P values <0.001). The area under the ROC curve was 0.891 [95% confidence interval (CI): 0.789-0.914; P<0.001], indicating a high accuracy of the model's predictions. Conclusions: The AO-DA distance, TA, and VRA are factors that influence the prognosis of fetuses with RAA-MB. The column chart model constructed based on these parameters can effectively provide a reference for predicting the risk of adverse outcomes in fetuses with RAA-MB.

A brain structure learning-guided multi-view graph representation learning for brain network analysis.

Background: Resting-state brain networks represent the interconnectivity of different brain regions during rest. Utilizing brain network analysis methods to model these networks can enhance our understanding of how different brain regions collaborate and communicate without explicit external stimuli. However, analyzing resting-state brain networks faces challenges due to high heterogeneity and noise correlation between subjects. This study proposes a brain structure learning-guided multi-view graph representation learning method to address the limitations of current brain network analysis and improve the diagnostic accuracy (ACC) of mental disorders. Methods: We first used multiple thresholds to generate different sparse levels of brain networks. Subsequently, we introduced graph pooling to optimize the brain network representation by reducing noise edges and data inconsistency, thereby providing more reliable input for subsequent graph convolutional networks (GCNs). Following this, we designed a multi-view GCN to comprehensively capture the complexity and variability of brain structure. Finally, we employed an attention-based adaptive module to adjust the contributions of different views, facilitating their fusion. Considering that the Smith atlas offers superior characterization of resting-state brain networks, we utilized the Smith atlas to construct the graph network. Results: Experiments on two mental disorder datasets, the Autism Brain Imaging Data Exchange (ABIDE) dataset and the Mexican Cocaine Use Disorders (SUDMEX CONN) dataset, show that our model outperforms the state-of-the-art methods, achieving nearly 75% ACC and 70% area under the receiver operating characteristic curve (AUC) on both datasets. Conclusions: These findings demonstrate that our method of combining multi-view graph learning and brain structure learning can effectively capture crucial structural information in brain networks while facilitating the acquisition of feature information from diverse perspectives, thereby improving the performance of brain network analysis.

Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration.

Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti-tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour-bearing mice. luteolin effectively inhibited the growth of solid tumours in a well-established mouse model of HCC. High-throughput sequencing revealed that luteolin treatment could enhance T-cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8+ T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8+ T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8+ T lymphocytes in H22 tumour-bearing mice. The CD8+ T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN-γ and TNF-α in serum. The combined administration of luteolin and the PD-1 inhibitor enhanced the anti-tumour effects in H22 tumour-bearing mice. Luteolin could exert an anti-tumour immune response by inducing CD8+ T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.

High speed enrichment of benzoylurea insecticides by hierarchical pore nitrogen doped carbon materials induced with hydrogen-bonded organic frameworks.

The high speed enrichment of benzoylurea insecticides (BUs) in complex matrices is an essential and challenging step. The present study focuses on the synthesis of a hierarchical pore nitrogen-doped carbon material for magnetic solid phase extraction (MSPE) of BUs. This material was prepared through the carbonization of a composite material ZIF-67@MCA which assembly with hydrogen-bonded organic frameworks (melamine-cyanurate, MCA) and zeolitic imidazolate framework (ZIF-67) at room temperature. The optimal adsorption effect is achieved when the mass ratio of ZIF-67 to MCA is 1/3, and the carbonization was performed at 600 °C, the such obtained carbon material was denoted as 1/3ZIF-67@MCA-DCs-600. The material was characterized with various physical methods including X-ray diffractometry (XRD), Fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET), vibrating sample magnetometer (VSM), water contact angle measurement, Raman spectrometry. 1/3ZIF-67@MCA-DCs-600 exhibits a macro-mesoporous 3D structure with a high degree of nitrogen doping and relatively large specific surface area, making it suitable for magnetic solid phase extraction (MSPE). The adsorption of BUs with concentration of 100 ng mL-1 can reach equilibrium within 5 s. The interaction between BUs and the adsorbent, facilitated by π-π stacking, hydrophobic interactions, hydrogen bonding forces, as well as the material's porosity, enables efficient extraction recoveries ranging from 45 % to 92 %. The enrichment of BUs was achieved through the establishment of an MSPE method under optimized conditions, which was further coupled with high performance liquid chromatography (HPLC) for the determination of the four BUs. The linear range spans from 5 ng ml-1 to 1000 ng ml-1 with the correlation coefficient (R2) of ≥ 0.99, Meanwhile, the detection limit for these four BUs falls within the range of 0.01 to 0.10 ng ml-1. The material exhibits good reusability and can be reused for at least 5 cycles. Inter day and intra-day precision ranges from 2.1-7.9 % and 1.0-5.4 %, respectively. The method demonstrates a high level of reliability in practical applications for the determination of BUs.

Aerosolization ocular surface microorganisms accumulation effect during non-contact tonometer measurements.

PURPOSE: This study aimed to verify that aerosolization ocular surface microorganisms (AOSMs) accumulated during non-contact tonometry (NCT) measurements. METHODS: A total of 508 participants (740 eyes) were enrolled in the study. In Experiment 1, before NCT was performed on each eye, the air was disinfected, and environment air control samples were collected via Air ideal® 3P (Bio Merieux). During NCT measurements, microbial aerosol samples were collected once from each eye. In Experiment 2, we collected initial blank control samples and then repeated Experiment 1. Finally, in Experiment 3, after the background microbial aerosol investigation, we cumulatively sampled AOSMs from each 10 participants then culture once, without any interventions to interrupt the accumulation. The collected samples were incubated and identified using matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: Pathogenic Aerococcus viridans and other microorganisms from human eyes can spread and accumulate in the air during NCT measurements. The species and quantity of AOSMs produced by NCT measurements can demonstrate an accumulation effect. CONCLUSION: AOSMs generated during NCT measurements are highly likely to spread and accumulate in the air, thereby may increase the risk of exposure to and transmission of bio-aerosols.

Pathogenic Aerococcus viridans and other species of aerosolization ocular surface microorganisms (AOSMs) can spread and accumulate with the increase of NCT measurement person times, demonstrating an accumulation effect.

Change in volatile profiles of wheat flour during maturation.

The volatile profiles of wheat flour during maturation were examined through headspace solid-phase micro-extraction gas chromatography-mass spectrometry (HS-SPME-GC/MS) combined with electronic nose (E-nose) and electronic tongue (E-tongue) analyses. The wheat flour underwent maturation under three distinct conditions for predetermined durations. While GC/MS coupled with E-tongue exhibited discernment capability among wheat flour samples subjected to varying maturation conditions, E-nose analysis solely relying on principal component analysis failed to achieve discrimination. 83 volatile compounds were identified in wheat flour, with the highest abundance observed in samples matured for 50 d at 25 °C. Notably, trans-2-Nonenal, decanal, and nonanal were the main contributors to the characteristic flavor profile of wheat flour. Integration of HS-SPME-GC/MS with E-tongue indicated superior flavor development and practical viability in wheat flour matured for 50 d at 25 °C. This study furnishes a theoretical groundwork for enhancing the flavor profiles of wheat flour and its derivative products.

Association Between Prior Antiplatelet Therapy and Prognosis in Patients With Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

PURPOSE: Approximately 20% to 30% of intracerebral hemorrhage (ICH) patients were reported to be on antiplatelet therapy (APT), and association between prior APT and prognosis was unclear. We aimed to clarify the impact of APT on the prognosis of ICH through an updated systematic review and meta-analysis, and to further compare the risk of single APT (SAPT) or dual APT (DAPT) prior to ICH as well as the risk associated with various antiplatelet drugs. METHODS: EMBASE, MEDLINE via Ovid SP and Web of Science were searched from inception of each database to November 4, 2023. Included studies reported prognosis in both patients with prior APT and those without. FINDINGS: A total of 433,103 patients from 43 studies were included in the meta-analysis. Both univariate and multivariate analyses demonstrated a significant association between prior-APT and an increased mortality risk (odd ratio [OR] 1.43, 95% confidence interval [CI] 1.28-1.59; OR 1.20, 95%CI 1.10-1.30, respectively). The risk was higher in short term follow-up (Univariate OR 1.73, 95%CI 1.22-2.46; Multivariate OR 1.94, 95%CI 1.48-2.55). A notably increased risk of hematoma expansion was also observed in patients previously treated with APT (Univariate OR 1.47, 95%CI 1.12-1.94; Multivariate OR 1.88, 95%CI 1.30-2.71), which were mainly attributed to events within 24 hours. The impact of prior-APT on poor functional outcome was inconsistent between univariate and multivariate analyses. Both direct and indirect comparisons showed that SAPT significantly reduced the risk of mortality (OR 0.67, 95%CI 0.64-0.70; OR 0.84, 95%CI 0.71-0.99) and poor functional outcome (OR 0.84, 95%CI 0.72-0.98; OR 0.81, 95%CI 0.72-0.91) compared to DAPT. IMPLICATIONS: Prior-APT increased the risk of mortality and hematoma expansion in patients with ICH. The increased risk of mortality and hematoma expansion was more obvious in the short term follow-up and within 24 hours, respectively. The effect of APT on poor functional outcome exhibited inconsistency between univariate and multivariate analyses, suggesting that further investigation is warranted to clarify this relationship. In comparison with DAPT, SAPT could decrease the risk of mortality and poor functional outcome. Further studies focusing on antiplatelet drug response, racial differences, and specific APT regimens may help verify the influence.

Design, synthesis and biological evaluation of artesunate-Se derivatives as anticancer agents by inducing GPX4-mediated ferroptosis.

A series of organoselenium compounds based on the hybridization of artesunate (ART) scaffolds and Se functionalities (-SeCN and -SeCF3) were synthesized. The redox properties of artesunate-SeCN and artesunate-SeCF3 derivatives were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), and the results showed that compounds 2c, 2f and 3e have a good free radical scavenging activity. Their cytotoxicity was evaluated against four types of cancer cell lines, SW480 (human colon adenocarcinoma cells), HCT116 (human colorectal adenocarcinoma cells), HepG2 (human hepatocellular carcinoma cells), MCF-7 (human breast cancer cells). The MTT results showed that compared with ART and 5-FU, compound 2c exhibited potent in vitro antiproliferative activity in SW480, HCT116, and MCF-7 cancer cell lines, and was thus chose for further antitumor mechanism investigation. The antitumor mechanism study revealed that compound 2c induced ferroptosis in HCT116 cells by inhibiting the expression of GPX4 protein, accompanying by the up-regulation of intracellular ROS levels. Mitochondria in HCT116 cells exhibit depolarization of mitochondrial membrane potential (MMP) and ultrastructural changes in morphology, which indicated that 2c resulted in mitochondrial dysfunction and ferroptosis. Moreover, 2c could increase the levels of lipid peroxidation and ferrous ion, which further confirm that compound 2c may exert its antitumor effect through ferroptosis. Overall, these results suggest that the artesunate-Se candidates could provide promising new lead derivatives for further potential anticancer drug development.

Visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates to access seleno-substituted isocoumarins.

A simple and efficient method to access 4-selenyl-isocoumarin derivatives through visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates has been developed. This transformation is performed under mild conditions and has the advantages of functional group tolerance and broad substrate scope.

Lacticaseibacillus rhamnosus inhibits the development of dental caries in rat caries model and in vitro.

OBJECTIVES: Dental caries result from a microbial imbalance in the oral cavity. Probiotics ecologically modulate the oral microflora to prevent caries. This study evaluated the anti-cariogenic effects of two Lacticaseibacillus rhamnosus strains in vitro and in vivo to provide a more theoretical basis for its clinical applications in caries prevention. METHODS: In the study, cariogenic biofilms were grown with L. rhamnosus (LGG) or L. rhamnosus ATCC 7469 and analyzed. Quantitative real-time PCR (qPCR), Scanning Electron Microscope (SEM), and Confocal laser scanning microscope (CLSM) were used to detect the changes in the composition and architectures; cariogenic activity was measured by the lactic acid production and Transverse Microradiography (TMR). The effects of LGG on the 12 Sprague-Dawley rat caries model were assessed using Keyes scores and micro-CT analysis. Oral microbiome changes were evaluated through 16S rRNA gene high-throughput sequencing. RESULTS: L. rhamnosus can reduce cariogenic bacteria in biofilm by 14.7 % to 48.9 %, with LGG exhibiting more potent inhibitory effects. Both strains of L. rhamnosus can adhere to the surface of biofilms, reduce the extracellular polysaccharides (EPS) matrix, and loosen the biofilm structure. L. rhamnosus inhibited cariogenic activity by reducing the lactic acid production in biofilms. The bovine enamel blocks presented lower mineral loss values and lesion depth values in the group Core+L.rh and Core+LGG. LGG-ingested rats had significantly lower levels of moderate dentin lesions and higher mineral density than the control group. The 16 s rRNA gene sequencing revealed that LGG regulated the beta diversity of the oral microbial community in the rat dental caries model. CONCLUSIONS: This study revealed the promising potential of L. rhamnosus, especially the LGG strain, in the ecological prevention of dental caries. CLINICAL SIGNIFICANCE: Probiotics may provide a strategy for preventing caries by regulating the oral microecological balance. The study revealed the promising anti-caries potential of the LGG probiotic strain in vivo and in vitro. It is expected that LGG could be used as an oral probiotic for the clinical prevention and treatment of caries.

High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging.

INTRODUCTION: Bacterial living states and the distribution of microbial colony signaling molecules are widely studied using mass spectrometry imaging (MSI). However, current approaches often treat 3D colonies as flat 2D disks, inadvertently omitting valuable details. The challenge of achieving 3D MSI in biofilms persists due to the unique properties of microbial samples. OBJECTIVES: The study aimed to develop a new biofilm sample preparation method that can realize high-resolution 3D MSI of bacterial colonies to reveal the spatial organization of bacterial colonies. METHODS: This article introduces the moisture-assisted cryo-section (MACS) method, enabling embedding-free sectioning parallel to the growth plane. The MACS method secures intact sections by controlling ambient humidity and slice thickness, preventing molecular delocalization. RESULTS: Combined with matrix-assisted laser desorption ionization mass spectrometry (MALDI)-MSI, the MACS method provides high-resolution insights into endogenic and exogenous molecule distributions in Pseudomonas aeruginosa (P. aeruginosa) biofilms, including isomeric pairs. Moreover, analyzed colonies are revived into 3D models, vividly depicting molecular distribution from inner to outer layers. Additionally, we investigated metabolite spatiotemporal dynamics in multiple colonies, observing changes over time and distinct patterns in single versus merged colonies. These findings shed light on the repel-merge process for multi-colony formation. Furthermore, our study monitored chemical responses inside biofilms after antibiotic treatment, showing increased antibiotic levels in the outer biofilm layer over time while maintaining low levels in the inner region. Moreover, the MACS method demonstrated its universality and applicability to other bacterial strains. CONCLUSION: These results unveil complex cell activities within biofilm colonies, offering insights into microbe communities. The MACS method is universally applicable to loosely packed microorganism colonies, overcoming the limitations of previously reported MSI methods. It has great potential for studying bacterial-infected cancer tissues and artificial organs, making it a valuable tool in microbiological research.

Changes in Lipid Metabolites and Enzyme Activities of Wheat Flour during Maturation.

The maturation of wheat flour is a transformative process that elevates its processing and culinary attributes to their peak performance levels. Despite extensive research on starch and gluten protein modifications, the impact of lipid changes has been largely unexplored. This study addresses this gap by examining the maturation of freshly milled wheat flour at 15 °C, 25 °C, and 40 °C over 60 days, focusing on enzymatic activities-lipase, lipoxidase, and catalase-and lipid metabolites, including free fatty acids, conjugated trienes, p-anisidine value, and total oxidation value. The results of this study showed that free fatty acids continued to increase at all temperatures, with the most significant increase of 50% at 15 °C. The p-anisidine value followed a pattern of initial increase followed by a decline, while conjugated trienes were markedly higher at 40 °C, suggesting temperature's significant influence on lipid peroxidation. Notably, total oxidation values became erratic post 30 days, indicating a shift in oxidative dynamics. This study underscores the correlation between lipid metabolites and enzymatic activities, revealing the enzymes' pivotal role in lipid oxidation. The interplay of temperature and time offers valuable insights for optimizing wheat flour maturation, ensuring superior quality for various applications.

Influence of impaired glucose tolerance alone and combined with metabolic syndrome on long-term risk of cardiovascular events and mortality.

BACKGROUND: This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. METHODS: Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. RESULTS: Over the 30-year follow-up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38-2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09-4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19-1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58-2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all-cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. CONCLUSION: IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.

Considering multi-scale built environment in modeling severity of traffic violations by elderly drivers: An interpretable machine learning framework.

The causes of traffic violations by elderly drivers are different from those of other age groups. To reduce serious traffic violations that are more likely to cause serious traffic crashes, this study divided the severity of traffic violations into three levels (i.e., slight, ordinary, severe) based on point deduction, and explore the patterns of serious traffic violations (i.e., ordinary, severe) using multi-source data. This paper designed an interpretable machine learning framework, in which four popular machine learning models were enhanced and compared. Specifically, adaptive synthetic sampling method was applied to overcome the effects of imbalanced data and improve the prediction accuracy of minority classes (i.e., ordinary, severe); multi-objective feature selection based on NSGA-II was used to remove the redundant factors to increase the computational efficiency and make the patterns discovered by the explainer more effective; Bayesian hyperparameter optimization aimed to obtain more effective hyperparameters combination with fewer iterations and boost the model adaptability. Results show that the proposed interpretable machine learning framework can significantly improve and distinguish the performance of four popular machine learning models and two post-hoc interpretation methods. It is found that six of the top ten important factors belong to multi-scale built environment attributes. By comparing the results of feature contribution and interaction effects, some findings can be summarized: ordinary and severe traffic violations have some identical influencing factors and interactive effects; have the same influencing factors or the same combinations of influencing factors, but the values of the factors are different; have some unique influencing factors and unique combinations of influencing factors.

Identification and validation of autophagy-related genes influenced by paris polyphylla in tongue cancer using network pharmacology.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) represents the most prevalent form of head and neck squamous cell carcinomas, comprising approximately one-third of all oral cancers. Paris polyphylla(PP) exhibit promising anti-tumor properties, yet their underlying mechanisms remain elusive. This study offers novel insights into the molecular mechanisms underlying TSCC treatment with PP and establishes a theoretical basis for their clinical application. METHODS: Employing transcriptomics and network pharmacology methodologies, we identified autophagy-related key genes associated with the effects of PP. These genes were subjected to KEGG and GO enrichment analyses to determine their related functions. In vitro, CAL-27 cells were treated with 10, 30, and 60 µg/ml of PP for 24 h to assess tumor cell proliferation, apoptosis, and autophagy-related markers. KEY FINDINGS: Molecular docking of MAPK3 and PSEN1 with PP revealed stable hydrogen bond interactions, indicating the therapeutic potential of these saponins in TSCC through the autophagy pathway. In vitro experiments demonstrated significant inhibition of proliferative activity in tongue squamous carcinoma CAL-27 cells and promotion of tumor cell apoptosis by PP. Western blot analysis confirmed alterations in the expression of autophagy markers P62, LC3B, and Beclin1 following treatment, suggesting activation of the autophagy pathway. CONCLUSIONS: Our results suggest that PP inhibits tumor cells through the autophagy pathway, in which MAPK3 and PSEN1 play a role as potential functional molecules.

Current Status of Shared Decision-Making in Intraocular Lens Selection for Cataract Surgery: A Cross-Sectional Study.

Purpose: To explore 1) the level of shared decision-making (SDM) participation in intraocular lens (IOL) selection in cataract patients and the factors that influence this participation and 2) the relationships between preparation for decision-making (PrepDM)and the level of SDM participation and satisfaction with the decision (SWD). Provide guidance for improving SDM in ophthalmology. Patients and Methods: 176 cataract patients were asked to complete the PrepDM scale, the 9-item Shared Decision Making Questionnaire (SDM-Q-9) and the SWD instrument in IOL decision-making process. Multiple linear regression was used to analyze the influencing factors of the level of SDM. The Process program and bootstrap sampling method was used to test whether the level of participation in SDM was a mediating variable among the three. Results: The SDM-Q-9 median score was 77.78 (IQR 31.11-88.89). Patients with a history of surgery in the operative eye (P=0.022) or PrepDM <60 points (P<0.001) had lower SDM-Q-9 scores than patients with no history of surgery in the operative eye or PrepDM ≥60 points. Patients with an education level lower than primary school had lower SDM-Q-9 scores than patients with other education levels (P<0.05). The PrepDM of cataract patients was positively correlated with the level of SDM (r=0.768, P<0.001) and with the SWD (r=0.727, P<0.001), and the level of SDM was positively correlated with the SWD (r=0.856, P<0.001). The level of SDM fully mediated PrepDM and SDW, with a mediating effect value of 0.128 and a mediating effect of 86.66% of the total effect. Conclusion: The SDM of cataract patients involved in IOL selection was in the upper middle range. Education, history of surgery in the operated eye, and PrepDM were factors that influenced the level of SDM. The level of participation in SDM fully mediated the relationship between PrepDM and SWD.

Exploring nicotinamide adenine dinucleotide precursors across biosynthesis pathways: Unraveling their role in the ovary.

Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value.