Analysis of driver behavior at grade-separated intersections to support design.

Understanding driver behaviors in varied traffic scenarios is critical to the design of safe and efficient roadways and traffic control device. This research presents an analysis of driver cognitive workload, situation awareness (SA) and performance for three different scenarios, including a standard intersection and contraflow grade-separated intersections (C-GSI) and quadrant GSI (Q-GSI) with lane assignment sign manipulations. The study used a simulator-based driving experiment with application of the NASA Task Load Index and Situation Awareness Global Assessment Technique to assess the influence of the scenarios on driver behavioral responses. The findings reveal challenges for drivers navigating the C-GSI, characterized by diminished SA and elevated workload. These states were associated with behaviors such as delayed lane changes, missed opportunities for appropriate lane changes, heightened acceleration behavior within deceleration segments, and frequent speeding. In contrast, while drivers in the Q-GSI scenario faced elevated workloads, their SA remained steady, largely due to lane-specific signs facilitating early lane changes. Although the Q-GSI led to increased speed variability and slight increases in deceleration, the use of supplementary speed signage revealed a promising alternative to the S-intersection. Correlation analysis highlighted a significant relationship between mental workload and acceleration responses, indicating that increased acceleration was associated with higher mental workload. In addition, a significant negative correlation between driver perceived performance and absolute lane deviations indicated that drivers with higher self-assessed performance were more accurate in lane-keeping. The study underscores the need for GSIs and signage designs that support driver SA, manage cognitive workload to improve driver performance and increase road safety.

Assessing workload in using electromyography (EMG)-based prostheses.

Using prosthetic devices requires a substantial cognitive workload. This study investigated classification models for assessing cognitive workload in electromyography (EMG)-based prosthetic devices with various types of input features including eye-tracking measures, task performance, and cognitive performance model (CPM) outcomes. Features selection algorithm, hyperparameter tuning with grid search, and k-fold cross-validation were applied to select the most important features and find the optimal models. Classification accuracy, the area under the receiver operation characteristic curve (AUC), precision, recall, and F1 scores were calculated to compare the models' performance. The findings suggested that task performance measures, pupillometry data, and CPM outcomes, combined with the naïve bayes (NB) and random forest (RF) algorithms, are most promising for classifying cognitive workload. The proposed algorithms can help manufacturers/clinicians predict the cognitive workload of future EMG-based prosthetic devices in early design phases.Practitioner summary: This study investigated the use of machine learning algorithms for classifying the cognitive workload of prosthetic devices. The findings suggested that the models could predict workload with high accuracy and low computational cost and could be used in assessing the usability of prosthetic devices in the early phases of the design process.Abbreviations: 3d: 3 dimensional; ADL: Activities for daily living; ANN: Artificial neural network; AUC: Area under the receiver operation characteristic curve; CC: Continuous control; CPM: Cognitive performance model; CPM-GOMS: Cognitive-Perceptual-Motor GOMS; CRT: Clothespin relocation test; CV: Cross validation; CW: Cognitive workload; DC: Direct control; DOF: Degrees of freedom; ECRL: Extensor carpi radialis longus; ED: Extensor digitorum; EEG: Electroencephalogram; EMG: Electromyography; FCR: Flexor carpi radialis; FD: Flexor digitorum; GOMS: Goals, Operations, Methods, and Selection Rules; LDA: Linear discriminant analysis; MAV: Mean absolute value; MCP: Metacarpophalangeal; ML: Machine learning; NASA-TLX: NASA task load index; NB: Naïve Bayes; PCPS: Percent change in pupil size; PPT: Purdue Pegboard Test; PR: Pattern recognition; PROS-TLX: Prosthesis task load index; RF: Random forest; RFE: Recursive feature selection; SHAP: Southampton hand assessment protocol; SFS: Sequential feature selection; SVC: Support vector classifier.

Associations of circulating immunomarkers with the efficacy of immunotherapy for primary hepatic carcinoma.

BACKGROUND: Peripheral blood immunomarkers are associated with prognosis in patients with solid tumors receiving chemotherapy or immunotherapy. In this study, the associations of circulating neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR), as well as their dynamic changes were investigated in relation to the efficacy of immunotherapy in patients with primary liver cancer. METHODS: Comparisons were made between NLR, MLR, and PLR among individuals exhibiting disease control (defined as the best response of partial response [PR] or stable disease [SD]) and those with progressive disease (PD). Additionally, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) were compared between individuals with different NLR, MLR, and PLR levels before initiating palliative immunotherapy. Furthermore, comparisons were made between patients with different alterations in the ratios at the second cycle of immunotherapy compared to baseline. These analyses were performed using univariate and multivariate approaches. A total of 119 Chinese patients with liver cancer who underwent immunotherapy were included in this study, which focused on hepatocellular carcinoma (HCC). RESULTS: In cases with HCC (n = 104), the cutoffs of NLR, MLR, and PLR to differentiate treatment responders from nonresponders were 3.38, 0.28, and 227.18, respectively. Patients with the best response of PR or SD had significantly lower NLR and MLR. Patients with NLR <3.38 and those with MLR <0.28 significantly had longer OS and PFS than their counterparts, and those with PLR <227.18 had significantly longer PFS, both in overall patients and in various patient subgroups. Lower NLR, MLR, or PLR was associated with earlier BCLC stage, fewer metastatic sites, less frequent extrahepatic metastasis, or better performance status. For individuals who had an unfavorable baseline NLR ≥3.38, MLR ≥0.28, or a favorable baseline PLR <227.18 prior to first immunotherapy, a decrease in NLR, MLR, or PLR at Cycle 2 of immunotherapy was significantly associated with a higher DCR. CONCLUSIONS: Among patients with HCC who received immunotherapy, lower NLR, and MLR at baseline in overall patients were significantly associated with better disease control and more favorable survival outcomes (both OS and PFS), and lower PLR was significantly associated with longer PFS. The findings of this research may offer useful hints foranoptimized selection of patients with liver cancer who may benefit more from immunotherapy.

ROS-mediated Therapeutics Combined with Metal-based Porphyrin Nanoparticles and their Applications in Tumor Treatment.

High concentrations of reactive oxygen species (ROS) can disrupt cell structure and induce apoptosis and necrosis of tumor cells. Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are two cancer treatments mediated by reactive oxygen species. Oxygen molecules (O2 ) are one of the indispensable factors in PDT and hypoxic tumor sites limit its application. However, another ROS-mediated method, CDT, can generate •OH and O2 in situ by Fenton reaction or Fenton-like reaction. Synergistic PDT/CDT therapy is a strategy to overcome the limitations of tumor microenvironment therapy. In this review, PDT and CDT therapies are briefly introduced, with an emphasis on metal-basrd porphyrin nanoparticles constructed in different ways for PDT/CDT dual-mode therapy. By introducing the history and latest design schemes of the treatment model, it provides ideas for researchers engaged in ROS-mediated cancer therapies.

Enhanced Photodynamic Therapy by Improved Light Energy Capture Efficiency of Porphyrin Photosensitizers.

OPINION STATEMENT: Photodynamic therapy (PDT) has garnered increasing attention in cancer treatment because of its advantages such as minimal invasiveness and selective destruction. With the development of PDT, impressive progress has been made in the preparation of photosensitizers, particularly porphyrin photosensitizers. However, the limited tissue penetration of the activating light wavelengths and relatively low light energy capture efficiency of porphyrin photosensitizers are two major disadvantages in conventional photosensitizers. Therefore, tissue penetration needs to be enhanced and the light energy capture efficiency of porphyrin photosensitizers improved through structural modifications. The indirect excitation of porphyrin photosensitizers using fluorescent donors (fluorescence resonance energy transfer) has been successfully used to address these issues. In this review, the enhancement of the light energy capture efficiency of porphyrins is discussed.

Insight into the electron transfer regime of periodate activation on MnO2: The critical role of surface Mn(IV).

At present, the potential mechanism of manganese oxide (MnO2) activation of PI and the key active sites of PI activation are still unclear and controversial. To this end, three different crystal forms of MnO2 were prepared in this study and used to activate PI to degrade pollutants. The results showed that different crystal types of MnO2 showed different catalytic abilities, and the order was γ-MnO2 > α-MnO2 > ß-MnO2. Through quenching experiments, EPR tests, Raman experiments and in situ electrochemical experiments, it has been confirmed that electron transfer-mediated non-free radical process is the main mechanism of pollutant degradation, in which the active substance is the highly active metastable intermediate complex (MnO2/PI*). Hydroxyl radical (HO•), superoxide radical (O2•-), singlet oxygen (1O2) and iodine radical (IO3•) did not participate in pollutant degradation. The quantitative structure-activity relationship analysis confirmed that the catalytic performance of MnO2 was highly positively correlated with the surface Mn(IV) content, which indicated that the surface Mn(IV) site was the main active site. Overall, this study will be of great help to the design and application of manganese dioxide activation for periodate degradation of pollutants.

Design, synthesis, antitumor activity and ct-DNA binding study of photosensitive drugs based on porphyrin framework.

Photodynamic therapy is a promising novel tumor treatment method. In this study, novel porphyrin-chrysin photosensitizer derivatives were synthesized. Most of the compounds showed antitumor activity against human cervical cancer HeLa cells and human lung cancer A549 cells, among which compound 4c had the best photodynamic therapy effect on HeLa cells and A549 cells, with IC50 values of 6.26 µM and 23.37 µM, respectively. Free-base porphyrin-chrysin derivatives bind to DNA through surface self-stacking, and zinc metalloporphyrin-chrysin derivatives bind to ct-DNA through intercalation. Notably, the tightness of compound binding to ct-DNA was positively correlated with its antitumor activity. What's more, three-dimensional quantitative conformation studies have shown that increasing the positive charge of the porphyrin ring and introducing a strong electron-withdrawing group at the meso position of the porphyrin ring at the para-position of the benzene ring or reducing the space volume of the compound can enhance the antitumor activity.

Reaction mechanism of nanomedicine based on porphyrin skeleton and its application prospects.

Research on porphyrin-based photosensitizing drugs is becoming increasingly popular. They possess unique diagnostic capabilities and therapeutic effects that have gained wide recognition in oncology drug development. In recent years, the rapid growth of nanotechnology has brought great hope for nanopharmaceutical formulations. By combining porphyrins with various nanomaterials, people have improved the properties of porphyrin compounds, making drug delivery easier. Porphyrin-based nanoparticles can enhance the effect of photodynamic therapy for cancer treatment, providing opportunities for achieving complex targeting strategies and versatility with promising applications in drug carriers, tumor imaging, and treatment. This paper reviews recent porphyrin nanodrugs, including inorganic-organic hybrid nanoparticles, nanomicelles, self-assembled nanoparticles, and combination therapeutic nanodrugs, and their actions and effects on cancer cells when performing photodynamic therapy. It also discusses the drawbacks as well as the prospects for development.

Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm.

Evidence has proved that intracranial aneurysm (IA) formation and rupture might be closely related to inflammatory response and oxidative stress. Our objective was to evaluate the potential of CD36 and glutathione (GSH) as biomarkers for IA. In this study, the enzyme-linked immunosorbent assay was used to measure the plasma levels of CD36 and GSH in 30 IA patients and 30 healthy controls. Then, correlation analysis, receiver operating characteristic (ROC) curve, and logistic regression analysis were performed. The results showed that the plasma level of CD36 in IA patients was significantly higher than that in the control group (P < 0.0001), and plasma GSH was significantly lower compared with that in the control group (P < 0.0001). ROC analysis showed that CD36 and GSH had high sensitivity (90.0 and 96.6%) and specificity (96.6 and 86.6%) for IA diagnosis. The combined sensitivity and specificity achieved were 100 and 100%, respectively. The plasma levels of CD36 and GSH did not show a significant correlation with age, the Glasgow Coma Scale, Hunter-Hess score, aneurysm size, aneurysm height, aneurysm neck, and aspect ratio. The AUC of the logistic regression model based on CD36 and GSH was 0.505. Our results suggested that the combination of plasma CD36 and GSH could serve as potential biomarkers for IA rupture.

Porphyrin-Based Nanoparticles: A Promising Phototherapy Platform.

Phototherapy, including photodynamic therapy and photothermal therapy, is an emerging form of non-invasive treatment. The combination of imaging technology and phototherapy is becoming an attractive development in the treatment of cancer, as it allows for highly effective therapeutic results through image-guided phototherapy. Porphyrins have attracted significant interest in the treatment and diagnosis of cancer due to their excellent phototherapeutic effects in phototherapy and their remarkable imaging capabilities in fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. However, porphyrins suffer from poor water solubility, low near-infrared absorption and insufficient tumor accumulation. The development of nanotechnology provides an effective way to improve the bioavailability, phototherapeutic effect and imaging capability of porphyrins. This review highlights the research results of porphyrin-based small molecule nanoparticles in phototherapy and image-guided phototherapy in the last decade and discusses the challenges and directions for the development of porphyrin-based small molecule nanoparticles in phototherapy.

The echo chamber effect of rumor rebuttal behavior of users in the early stage of COVID-19 epidemic in China.

During public health emergencies, as one of the most effective rumor management strategies, rumor rebuttals depend on users' cognition, decision-making and interactive behaviors. Taking the dissemination of rumor rebuttals related to COVID-19 epidemic in the early stage in China as an example, we firstly adapted network analysis to construct representative networks of information and communication flow networks of users based on users' retweeting and commenting behaviors. Then quantitative indicators and exponential random graph models were used to evaluate the level of homophily based on topic and veracity in information networks, identity and standpoint in user networks. Meanwhile, chi square tests were added to compare the degree of echo chamber effect in retweeting and commenting. Findings showed that, users did show significant echo chamber effect when retweeting or commenting on rumor rebuttal information with different veracity. They showed diversification when retweeting but a certain tendency and pertinence when commenting in topic selection. Weibo's direct and open platform for retweeting and commenting broke the boundaries between stakeholders from different professional fields. However, the retweeting mechanism promoted self-isolation of users' standpoints, while the commenting mechanism provided an understanding and integrating channel for groups with opposing standpoints.

Metal-free regioselective nitration of quinoxalin-2(1H)-ones with tert-butyl nitrite.

A metal-free coupling of quinoxalin-2(1H)-ones with tert-butyl nitrite has been developed. Distinctly from the previous functionalization of quinoxalin-2(1H)-ones, this nitration reaction took place selectively at the C7 or C5 position of the phenyl ring, affording a series of 7-nitro and 5-nitro quinoxalin-2(1H)-ones in moderate to good yields. Preliminary mechanistic studies revealed that the reaction may involve a radical process.

A Nanoparticle Delivery of Plasmid Encoding Hepatocyte Growth Factor for Gene Therapy of Silicosis in Mice.

PURPOSE: Silicosis is a serious occupational disease that is characterized by pulmonary infiltrates and fibrosis and is often refractory to current treatments. New therapeutic strategies for silicosis are needed. Hepatocyte growth factor (HGF) is a latent anti-inflammatory and anti-fibrotic growth factor. METHODS: We prepared a polyethyleneimine-polyethylene glycol/pHGF/hyaluronic acid (PEG-PEI/pHGF/HA) nanomaterials loaded with plasmid DNA encoding HGF gene to increase its transfection efficiency. The characterization, including DNA entrapment efficiency, morphology, particle size, and zeta-potential of PEG-PEI/pHGF/HA was studied. And a PEG-PEI/pHGF/HA (N/P=30:1) nanoparticle with low toxicity and high transfection efficiency was used in treatment for silicosis in mice. RESULTS: The results showed that the human HGF expression in the lungs of the mice was increased, and the inflammatory cell infiltration and fibrous collagen deposition was significantly reduced. CONCLUSION: Therefore, PEG-PEI/pHGF/HA nanoparticle warrant further investigation and may be a potential therapeutic strategy for silicosis.

Characterizing the COVID-19 Infodemic on Chinese Social Media: Exploratory Study.

BACKGROUND: The COVID-19 infodemic has been disseminating rapidly on social media and posing a significant threat to people's health and governance systems. OBJECTIVE: This study aimed to investigate and analyze posts related to COVID-19 misinformation on major Chinese social media platforms in order to characterize the COVID-19 infodemic. METHODS: We collected posts related to COVID-19 misinformation published on major Chinese social media platforms from January 20 to May 28, 2020, by using PythonToolkit. We used content analysis to identify the quantity and source of prevalent posts and topic modeling to cluster themes related to the COVID-19 infodemic. Furthermore, we explored the quantity, sources, and theme characteristics of the COVID-19 infodemic over time. RESULTS: The daily number of social media posts related to the COVID-19 infodemic was positively correlated with the daily number of newly confirmed (r=0.672, P<.01) and newly suspected (r=0.497, P<.01) COVID-19 cases. The COVID-19 infodemic showed a characteristic of gradual progress, which can be divided into 5 stages: incubation, outbreak, stalemate, control, and recovery. The sources of the COVID-19 infodemic can be divided into 5 types: chat platforms (1100/2745, 40.07%), video-sharing platforms (642/2745, 23.39%), news-sharing platforms (607/2745, 22.11%), health care platforms (239/2745, 8.71%), and Q&A platforms (157/2745, 5.72%), which slightly differed at each stage. The themes related to the COVID-19 infodemic were clustered into 8 categories: "conspiracy theories" (648/2745, 23.61%), "government response" (544/2745, 19.82%), "prevention action" (411/2745, 14.97%), "new cases" (365/2745, 13.30%), "transmission routes" (244/2745, 8.89%), "origin and nomenclature" (228/2745, 8.30%), "vaccines and medicines" (154/2745, 5.61%), and "symptoms and detection" (151/2745, 5.50%), which were prominently diverse at different stages. Additionally, the COVID-19 infodemic showed the characteristic of repeated fluctuations. CONCLUSIONS: Our study found that the COVID-19 infodemic on Chinese social media was characterized by gradual progress, videoization, and repeated fluctuations. Furthermore, our findings suggest that the COVID-19 infodemic is paralleled to the propagation of the COVID-19 epidemic. We have tracked the COVID-19 infodemic across Chinese social media, providing critical new insights into the characteristics of the infodemic and pointing out opportunities for preventing and controlling the COVID-19 infodemic.

Synthesis and biological evaluation of amino acid derivatives containing chrysin that induce apoptosis.

A series of chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities against several cancer cell lines. Among the compounds tested, N-(2-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)octanoyl)-L-leucine methyl ester(5d) presented a good anti-proliferative activity in MDA-MB-231 and MCF-7 cells. Flow cytometry analysis showed that 5d induced apoptosis and prolonged cell cycle progression in MDA-MB-231 and MCF-7 cells. Western blot analysis showed that 5d significantly inhibited Akt phosphorylation (Ser473) in MDA-MB-231 and MCF-7 cells. In addition, 5d treatment markedly downregulated Bcl-2 and upregulated Bax in a dose-dependent manner. In vitro caspase activation assay showed that 5d induced apoptosis of MDA-MB-231 cells by enhancing caspase 3/7 activity. The regulatory effect of 5d on apoptosis of MDA-MB-231 and MCF-7 cells may be induced by mitochondrial apoptosis pathway. This study is of great significance for designing and developing more effective chrysin amino acid derivatives.

Synthesis, characterization and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and EGFR downregulation.

Chrysin amino acid derivatives were synthesized to evaluate for their antiproliferative activities. Among them, N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)valeryl)-L-leucine (8c) displayed the most remarkable inhibitory activities against MCF-7 cells with IC50 values of 16.6 µM. Preliminary mechanistic studies showed that 8c could inhibit the colony formation and migration of MCF-7 cells. Flow cytometry analysis demonstrated that 8c mediated cell apoptosis and the prolongation of cell cycle progression in G1/S-phase against MCF-7 cells. Besides, 8c displayed the moderate inhibition against EGFR. Western blot assay suggested that 8c significantly inhibited EGFR phosphorylation. Molecular docking showed that 8c can bind the EGFR kinase well.

Porphyrin-Based Metal-Organic Framework Compounds as Promising Nanomedicines in Photodynamic Therapy.

Porphyrin photosensitizers are widely used in photodynamic therapy (PDT) because of their unique diagnostic and therapeutic functions. However, many factors such as poor water solubility and instability of porphyrin compounds have limited their clinical application. Metal-organic frameworks (MOFs) have the beneficial characteristics of versatility, high porosity, and excellent biocompatibility. Porphyrin-MOF nanomaterials have attracted the attention of researchers because MOFs can effectively suppress the quenching caused by the self-aggregation of porphyrin compounds and promote drug delivery. This article reviews the latest applications of porphyrin-MOF nanomedicine in type II photodynamic therapy by increasing tumour cell oxygen concentration, depleting tumour cell functional molecules and releasing signal molecules. Current potential limitations and future applications are also emphasized and discussed herein.

A promising anticancer drug: a photosensitizer based on the porphyrin skeleton.

Photodynamic therapy (PDT) is a minimally invasive combination of treatments that treat tumors and other diseases by using photosensitizers, light and oxygen to produce cytotoxic reactive oxygen species (ROS) inducing tumor cell apoptosis. Photosensitizers are the key part of PDT for clinical application and experimental research, and most of them are porphyrin compounds at present. Due to their unique affinity for tumor tissues, porphyrins are not only excellent photosensitizers, but also good carriers to transport other active drugs into tumor tissues, which can exert synergistic anticancer effects of PDT and chemotherapy. This article reviews the clinical development of porphyrin photosensitizers and the research status of porphyrin containing bioactive groups. Finally, future perspectives and the current challenges of photosensitizers based on the porphyrin skeleton are discussed.

Design, synthesis, and preliminary biological evaluation of chrysin amino acid derivatives that induce apoptosis and suppress cell migration.

Amino acid derivatives containing chrysin were synthesized for evaluating their anticancer effects. Among them, compound N-(7-((5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy)heptanoyl)-L-isoleucine (6e) displayed the most potent antiproliferative activity against MGC-803 cells with IC50 value of 20.0 µM. Preliminary mechanistic studies showed that compound 6e could inhibit the colony formation and migration of MGC-803 cells. Flow cytometry analysis demonstrated that compound 6e mediated cell apoptosis of MGC-803 cells and arrested cell cycle in G2/M-phase. Moreover, 6e treatment in MGC-803 cells downregulated anti-apoptotic protein Bcl-2 and upregulated pro-apoptotic gene Bax in a concentration-dependent manner. Our studies suggest that compound 6e may sever as an effective chemotherapeutic candidate. [Formula: see text].

The association between anti-tumor potency and structure-activity of protein-kinases inhibitors based on quinazoline molecular skeleton.

Quinazoline was originally utilized as an anti-tumor treatment, and its various derivatives can be directly extracted from plants. In recent years, protein kinases (PK) have been well recognized in the development of tumor drugs. Functionally, PK serves a vital role in the apoptosis, proliferation, differentiation, migration and cell cycle of tumor cells. Due to its good physicochemical properties, quinazoline skeleton, a superior type of PK inhibitor, has been extensively used in anti-tumor drug design. An increasing number of studies on quinazoline synthesis have been reported and used by different groups to effectively develop novel derivatives. Thus, several studies have been approved for the use of quinazoline derivatives as inhibitors of other kinases, including Src and histone deacetylase. The aim of the present review was to summarize the mechanism of quinazoline compounds as PK inhibitors, their biological structure-activity relationship such as the substituted quinazoline compounds with different functional groups in the apoptotic process, and their effect on the proliferation of tumor cells. The development of novel agents based on the antitumor functions of quinazoline molecular compounds may improve the clinical outcomes of the affected population, particularly in patients with cancer.