Predicting driver's takeover time based on individual characteristics, external environment, and situation awareness.

The driver's takeover time is crucial to ensure a safe takeover transition in conditional automated driving. The study aimed to construct a prediction model of driver's takeover time based on individual characteristics, external environment, and situation awareness variables. A total of 18 takeover events were designed with scenarios, non-driving-related tasks, takeover request time, and traffic flow as variables. High-fidelity driving simulation experiments were carried out, through which the driver's takeover data was obtained. Fifteen basic factors and three dynamic factors were extracted from individual characteristics, external environment, and situation awareness. In this experiment, these 18 factors were selected as input variables, and XGBoost and Shapely were used as prediction methods. A takeover time prediction model (BM + SA model) was then constructed. Moreover, we analyzed the main effect of input variables on takeover time, and the interactive contribution made by the variables. And in this experiment, the 15 basic factors were selected as input variables, and the basic takeover time prediction model (BM model) was constructed. In addition, this study compared the performance of the two models and analyzed the contribution of input variables to takeover time. The results showed that the goodness of fit of the BM + SA model (Adjusted_R2) was 0.7746. The XGBoost model performs better than other models (support vector machine, random forest, CatBoost, and LightBoost models). The relative importance degree of situation awareness variables, individual characteristic variables, and external environment variables to takeover time gradually reduced. Takeover time increased with the scan and gaze durations and decreased with pupil area and self-reported situation awareness scores. There was also an interaction effect between the variables to affect takeover time. Overall, the performance of the BM + SA model was better than that of the BM model. This study can provide support for predicting driver's takeover time and analyzing the mechanism of influence on takeover time. This study can provide support for the development of real-time driver's takeover ability prediction systems and optimization of human-machine interaction design in automated vehicles, as well as for the management department to evaluate and improve the driver's takeover performance in a targeted manner.

Characterization of Ovarian Progenitor Cells for Their Potentials to Generate Steroidogenic Theca Cells in Vitro.

BACKGROUND: Adult mammalian ovaries contain stem/progenitor cells necessary for folliculogenesis and ovulation-related tissue rupture repair. Theca cells are recruited and developed from progenitors during the folliculogenesis. Theca cell progenitors were not well-defined. The aim of current study is to compare the potential of four ovarian progenitors with defined markers (LY6A, EPCR, LGR5and PDGFRA) to form steroidogenic theca cells in vitro. METHODS: Ovarian progenitors were identified by the above four makers reported previously. The location of the cells was determined by immunohistochemistry and immunofluorescence staining of ovarian sections of adult mice. Different progenitor populations were purified by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) techniques from ovarian cell preparation and were tested for their abilities to generate steroidogenic theca cells in vitro. The cells were differentiated with a medium containing LH, ITS and DHH agonist for 12 days. RESULTS: EPCR+ and LGR5+ cells primarily distributed along ovarian surface epitheliums (OSE), while LY6A+ cells distributed in both OSE and parenchyma. However, PDGFRA+ cells were exclusively located in interstitial compartment. When the progenitors were purified by these markers and differentiated in vitro, LY6A+ and PDGFRA+ cells formed steroidogenic cells expressing both CYP11A1 and CYP17A1 and primarily producing androgens, showing characteristics of theca-like cells, while LGR5+ cells generated steroidogenic cells devoid of CYP17A1 expression and androgen production, showing a characteristic of progesterone-producing cells (granulosa- or lutea-like cells). CONCLUSION: Progenitors from both OSE and parenchyma of adult mice are capable of generating steroidogenic cells with different steroidogenic capacities, showing a possible lineage preference.

Association between blood lead levels and unfavorable IVF outcomes: potential involvement of endoplasmic reticulum stress response in granulosa cells.

PURPOSE: To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process. METHODS: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined. RESULTS: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs. CONCLUSIONS: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.

Study on the benefit analysis based on whole life cycle carbon emission calculation after the construction of photovoltaic systems in macau's construction waste landfills.

This study seeks to assess both environmental and economic effects associated with installing photovoltaic systems within construction waste landfills in Macau by employing an effective carbon emissions calculation methodology and benefit analysis method. Beginning by outlining characteristics and challenges associated with construction waste landfills, as well as photovoltaic systems used for this application in this paper. Here, we present a detailed outline of our methodology design, outlining its principles of life cycle analysis, data collection processes and the creation of carbon emissions calculation models. Subsequently, we examine photovoltaic systems within Macau's construction waste landfills by studying system design, component selection and operational strategies as well as carbon emission data collection during their operational time period. Under life cycle carbon emissions calculations, we assess the carbon emissions generated from photovoltaic systems as well as conduct an environmental and economic benefit analysis for carbon reduction benefit analysis purposes. This research incorporates sensitivity analysis and uncertainty consideration in order to conduct an extensive benefit analysis. The research results offer strong support for sustainable photovoltaic systems within Macau waste landfills as well as insights to inform planning and policy formation for similar future projects.

Assessing bioartificial organ function: the 3P model framework and its validation.

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based "3P model" framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning.

Serological Exosome Metabolic Biopsy of Hepatocellular Carcinoma via Designed Core-Shell Nanoparticles.

Exosome metabolite-based liquid biopsy is a promising strategy for large-scale application in practical clinics toward precise medicine. Given the current challenges in successive isolation and analysis of exosomes and their metabolites in this field, we established a low-cost, high-throughput, and rapid platform for serological exosome metabolic biopsy of hepatocellular carcinoma (HCC) via designed core-shell nanoparticles. It starts with the efficient extraction of high-quality serum exosomes and exosome metabolic features, based on which significantly obvious sample clusters are observed by unsupervised cluster analysis. The following integration of feature selection and supervised machine learning enables the identification of six key metabolites and achieves high-performance prediction between HCC, liver cirrhosis, and healthy controls. Specifically, both sensitivity and accuracy achieve 100% among any pairwise intergroup discrimination in a blind test. The quality and reliability of six key metabolites are further evaluated and validated by using different machine learning algorithms and pathway exploration. Our platform contributes to the future growth of new liquid biopsy technologies for precision diagnosis and real-time monitoring of HCC, among other conditions.

High-throughput detection allied with machine learning for precise monitoring of significant serum metabolic changes in Helicobacter pylori infection.

High-throughput detection of large-scale samples is the foundation for rapidly accessing massive metabolic data in precision medicine. Machine learning is a powerful tool for uncovering valuable information hidden within massive data. In this work, we achieved the extraction of a single fingerprinting of 1 µL serum within 5 s through a high-throughput detection platform based on functionalized nanoparticles. We quickly obtained over a thousand serum metabolic fingerprintings (SMFs) including those of individuals with Helicobacter pylori (HP) infection. Combining four classical machine learning models and enrichment analysis, we attempted to extract and confirm useful information behind these SMFs. Based on all fingerprint signals, all four models achieved area under the curve (AUC) values of 0.983-1. In particular, orthogonal partial least squares discriminant analysis (OPLS-DA) model obtained value of 1 in both the discovery and validation sets. Fortunately, we identified six significant metabolic features, all of which can greatly contribute to the monitoring of HP infection, with AUC values ranging from 0.906 to 0.985. The combination of these six significant metabolic features can enable the precise monitoring of HP infection in serum, with over 95 % of accuracy, specificity and sensitivity. The OPLS-DA model displayed optimal performance and the corresponding scatter plot visualized the clear distinction between HP and HC. Interestingly, they exhibit a consistent reduction trend compared to healthy controls, prompting us to explore the possible metabolic pathways and potential mechanism. This work demonstrates the potential alliance between high-throughput detection and machine learning, advancing their application in precision medicine.

Heterogeneous MXene Hybrid-Oriented Exosome Isolation and Metabolic Profiling for Early Screening, Subtyping and Follow-up Evaluation of Bladder Cancer.

Exosome metabolite-based noninvasive liquid biopsy is an emerging research hotspot that tends to substitute current means in clinics. Nanostructure-based mass spectrometry enables continuous exosome isolation and metabolic profiling with superior analysis speed and high efficiency. Herein, we construct a heterogeneous MXene hybrid that possesses ternary binding sites for exosome capture and outstanding matrix performance for metabolite analysis. Upon optimizing experimental conditions, the average extraction of exosomes and their metabolic patterns from a 60 mL urine sample is completed within 45 s (40 samples per batch for 30 min). According to the exosomal metabolic patterns and the subsequently established biomarker panel, we distinguish early bladder cancer (BCa) from healthy controls with an area under the curve (AUC) value greater than 0.995 in model training and validation sets. As well, we realize subtype classification of BCa in the blind test on metabolic patterns, with an AUC value of 0.867. We also explore the significant biomarkers that are sensitive to follow-up patients, which indeed present reverse change levels compared with pathological progression. This study has the potential to guide the development of the liquid biopsy approach.

Transcriptomic characterization of interactions between sodium selenite and coenzyme Q10 on preventing cadmium-induced testicular defects.

The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.

"Afterglow" Photodynamic Therapy Based on Carbon Dots Embedded Silica Nanoparticles for Nondestructive Teeth Whitening.

Teeth staining is a common dental health challenge in many parts of the world. Traditional teeth whitening techniques often lead to enamel damage and soft tissue toxicity due to the use of bioincompatible whitening reagents and continuous strong light irradiation. Herein, an "afterglow" photodynamic therapy (aPDT) for teeth whitening is proposed, which is realized by energy transition pathways of intersystem crossing. The covalent and hydrogen bonds formed by carbon dots embedded in silica nanoparticles (CDs@SiO2) facilitate the passage of energy through intersystem crossing (ISC), thereby extending the half-life of reactive oxygen species (ROS). The degradation efficiency of aPDT on dyes was higher than 95% in all cases. It can thoroughly whiten teeth by eliminating stains deep in the enamel without damaging the enamel structure and causing any tissue toxicity. This study illustrates the superiority of aPDT for dental whitening and the approach to exploring carbon-dots-based nanostructures in the treatment of oral diseases.

Silver@Prussian Blue Core-Satellite Nanostructures as Multimetal Ions Switch for Potent Zero-Background SERS Bioimaging-Guided Chronic Wound Healing.

Metal-organic framework-based metal ion therapy has attracted increasing attention to promote the cascade wound-healing process. However, multimetal ion synergistic administration and accurately controlled ion release are still the challenges. Herein, an aptamer-functionalized silver@cupriferous Prussian blue (ACPA) is established as a metal-based theranostic nanoagent for a chronic nonhealing diabetic wound treatment. Prussian blue offers a programmable nanoplatform to formulate metal ion prescriptions, achieving cooperative wound healing. Silver, copper, and iron ions are released from ACPA controlled by the near-infrared-triggered mild hyperthermia and then synergistically participate in antipathogen, cell migration, and revascularization. ACPA also demonstrates a unique core-satellite nanostructure which enables it with improved surface-enhanced Raman scattering (SERS) capability as potent bacteria-targeted Raman-silent nanoprobe to monitor the residual bacteria during wound healing with nearly zero background. The theranostic feature of ACPA allows high-performance SERS imaging-guided chronic wound healing in infectious diabetic skin and keratitis.

Metabolic profiling of urinary exosomes for systemic lupus erythematosus discrimination based on HPL-SEC/MALDI-TOF MS.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which leads to the formation of immune complex deposits in multiple organs and has heterogeneous clinical manifestations. Currently, exosomes for liquid biopsy have been applied in diagnosis and monitoring of diseases, whereas SLE discrimination based on exosomes at the metabolic level is rarely reported. Herein, we constructed a protocol for metabolomic study of urinary exosomes from SLE patients and healthy controls (HCs) with high efficiency and throughput. Exosomes were first obtained by high-performance liquid size-exclusion chromatography (HPL-SEC), and then metabolic fingerprints of urinary exosomes were extracted by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with high throughput and high efficency. With the statistical analysis by orthogonal partial least-squares discriminant analysis (OPLS-DA) model, SLE patients were efficiently distinguished from HCs, the area under the curve (AUC) of the receiver characteristic curve (ROC) was 1.00, and the accuracy of the unsupervised clustering heatmap was 90.32%. In addition, potential biomarkers and related metabolic pathways were analyzed. This method, with the characteristics of high throughput, high efficiency, and high accuracy, will provide the broad prospect of exosome-driven precision medicine and large-scale screening in clinical applications.

Endophytic Beauveria bassiana of Tomato Resisted the Damage from Whitefly Bemisia tabaci by Mediating the Accumulation of Plant-Specialized Metabolites.

Beauveria bassiana acts as an endophytic fungus that controls herbivorous pests by stimulating plant defenses and inducing systemic resistance. Through multiomics analysis, 325 differential metabolites and 1739 differential expressed genes were observed in tomatoes treated with B. bassiana by root irrigation; meanwhile, 152 differential metabolites and 1002 differential genes were observed in tomatoes treated by local leaf spraying. Among the upregulated metabolites were α-solanine, 5-O-caffeoylshikimic acid, clerodendrin A, and peucedanin, which demonstrated anti-insect activity. These differential metabolites were primarily associated with alkaloid biosynthesis, flavonoid biosynthesis, and tryptophan metabolism pathways. Furthermore, the gene silencing of UDP-glucose:sterol glucosyltransferase, a gene involved in α-solanine synthesis, indicated that B. bassiana could inhibit the reproduction of whiteflies by regulating α-solanine. This study highlighted the ability of B. bassiana to modulate plant secondary metabolites and emphasized the significance of understanding and harnessing multitrophic interactions of endophytic B. bassiana for sustainable agriculture.

Cerebral delivery of redox-responsive lenalidomide prodrug plus methotrexate for primary central nerve system lymphoma combination therapy.

Primary central nervous system lymphoma (PCNSL) is an extremely malignant CNS tumor with high incidence and mortality rates. Its chemotherapy in the clinic has been restricted owing to unsatisfactory drug distribution in the cerebral tissues. In this study, a redox-responsive prodrug of disulfide-lenalidomide-methoxy polyethylene glycol (LND-DSDA-mPEG) was successfully developed for the cerebral delivery of lenalidomide (LND), and methotrexate (MTX) via subcutaneous (s.c.) administration at the neck for combined anti-angiogenesis and chemotherapy on PCNSL. Both the subcutaneous xenograft tumor model and orthotopic intracranial tumor model demonstrated that the co-delivery of LND and MTX nanoparticles (MTX@LND NPs) may significantly inhibit the growth of lymphoma and effectively prevent liver metastasis by downregulating CD31 and VEGF expression. Moreover, an orthotopic intracranial tumor model further verified that through s.c. administration at the neck, redox-responsive MTX@LND NPs could bypass the blood-brain barrier (BBB), efficiently distribute into brain tissues, and effectively inhibit lymphoma growth in the brain, as detected by magnetic resonance imaging (MRI). Taken together, this biodegradable, biocompatible, and redox-responsive nano-prodrug with highly effective targeted delivery of LND and MTX in the brain through the lymphatic vasculature may provide a facile and feasible treatment strategy for PCNSL in the clinic.

Effect of NaClO and ClO2 on the bacterial properties in a reclaimed water distribution system: efficiency and mechanisms.

Extensive application of reclaimed water alleviated water scarcity obviously. Bacterial proliferation in reclaimed water distribution systems (RWDSs) poses a threat to water safety. Disinfection is the most common method to control microbial growth. The present study investigated the efficiency and mechanisms of two widely used disinfectants: sodium hypochlorite (NaClO) and chlorine dioxide (ClO2) on the bacterial community and cell integrity in effluents of RWDSs through high-throughput sequencing (Hiseq) and flow cytometry, respectively. Results showed that a low disinfectant dose (1 mg/L) did not change the bacterial community basically, while an intermediate disinfectant dose (2 mg/L) reduced the biodiversity significantly. However, some tolerant species survived and multiplied in high disinfectant environments (4 mg/L). Additionally, the effect of disinfection on bacterial properties varied between effluents and biofilm, with changes in the abundance, bacterial community, and biodiversity. Results of flow cytometry showed that NaClO disturbed live bacterial cells rapidly, while ClO2 caused greater damage, stripping the bacterial membrane and exposing the cytoplasm. This research will provide valuable information for assessing the disinfection efficiency, biological stability control, and microbial risk management of reclaimed water supply systems.

Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation in vitro.

Background: Testosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear. Methods: SLCs and macrophages were purified from adult and aged mice via FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured in vitro to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages. Results: CD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs. Conclusion: The results suggest that aging affected both SLC function and their regulatory niche cell, macrophages.

CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy.

Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy-M-Exo) is developed via fusing tumor-derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T-cell response. Moreover, the nanovaccine Hy-M-Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy-M-Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy.

Nanovaccines Fostering Tertiary Lymphoid Structure to Attack Mimicry Nasopharyngeal Carcinoma.

Tertiary lymphoid structures (TLSs) are formed in inflamed tissues, and recent studies demonstrated that the appearance of TLSs in tumor sites is associated with a good prognosis for tumor patients. However, the process of natural TLSs' formation was slow and uncontrollable. Herein, we developed a nanovaccine consisting of Epstein-Barr virus nuclear antigen 1 (EBNA1) and a bi-adjuvant of Mn2+ and cytosine-phosphate-guanine (CpG) formulated with tannic acid that significantly inhibited the development of mimicry nasopharyngeal carcinoma by fostering TLS formation. The nanovaccine activated LT-α and LT-ß pathways, subsequently enhancing the expression of downstream chemokines, CCL19/CCL21, CXCL10 and CXCL13, in the tumor microenvironment. In turn, normalized blood and lymph vessels were detected in the tumor tissues of the nanovaccine group, correlated with increased infiltration of lymphocytes. Especially, the proportion of the B220+ CD8+ T, which was produced via trogocytosis between T and B cells during activation of T cells, was increased in tumors of the nanovaccine group. Furthermore, the intratumoral effector memory T cells (Tem), CD45+, CD3+, CD8+, CD44+, and CD62L-, did not decrease after blocking the egress of T cells from tumor-draining lymph nodes by FTY-720. These results demonstrated that the nanovaccine can foster TLS formation, which thus enhances local immune responses significantly, delays tumor outgrowth, and prolongs the median survival time of murine models of mimicry nasopharyngeal carcinoma, demonstrating a promising strategy for nanovaccine development.