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Abstract Gasdermin-E (GSDME), the executioner of pyroptosis when cleaved by caspase 3, plays a crucial role in tumor defense and the response to chemotherapy drugs in cells. So far, there are poorly known mechanisms for the expression regulation of GSDME during cell death. Here, we identify the transcription factor Sp1 (Specificity protein 1) as a positive regulator of GSDME-mediated pyroptosis. Sp1 directly interacts with the GSDME promoter at −36 ~ −28 site and promotes GSDME gene transcription. Further, Sp1 knockdown or inhibition suppresses GSDME expression, thus reducing chemotherapy drugs (topotecan, etoposide, doxorubicin, sorafinib and cisplatin) induced cell pyroptosis. The regulation process synergizes with STAT3 (Signal transducer and activator of transcription 3) activity and antagonizes with DNA methylation but barely affects GSDMD-mediated pyroptosis or TNF-induced necroptosis. Our current finding reveals a new regulating mechanism of GSDME expression, which may be a viable target for the intervention of GSDME-dependent inflammatory diseases and cancer therapy.

Abstract Parkinson’s disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl −/− ) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl −/− mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl −/− mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.

Abstract Intention estimation has been widely studied in lane change scenarios, which explains a vehicle's behaviour and implies its future motion. However, in dense traffic, lane‐changing is more tactical and interactive. Due to the conflict between merging vehicles and adjacent vehicles, driving intentions become interdependent which fuses passing and yielding. In addition, lane change occurs without a fixed location. Drivers should be aware of each other's intentions along conflict process, and take instant responses. To address these challenges, this paper proposes semantic‐based interactive intention estimation (SIIE), to understand driving intentions during lane change conflict. The problem is addressed by combining driving semantics with probability inference model based on dynamic Bayesian network (DBN). Firstly, the DBN is modelled for the interaction process with Condition‐Intention‐Behaviour relationships. Secondly, the semantics are extracted from the lane change conflict and are inferred with observation methods. Thirdly, SIIE is trained and verified with real‐world driving data. The intention estimation results are demonstrated, and then utilized for multi‐modal motion identification and trajectory prediction. Lane change in dense traffic requires interactive cognition of driving intentions, the findings of this research shall inspire future studies into related scenarios, and promote interactive driving technologies.

This study investigated the beliefs, attitudes, and motivation of Thai and Chinese undergraduate students in relation to English language learning. Utilizing a mixed-method, explanatory sequential design, it aims to provide a better understanding of the three variables mentioned above. The quantitative data analysis showed disparities between the cohorts, with Chinese undergraduate students often displaying more robust orientations. However, the qualitative data analysis showed that both groups valued immersive learning experiences and technological integration. The research advocates for pedagogical frameworks in English education that align with overarching global paradigms while respecting individual cultural nuances. Such revelations are important for refining teaching practices and curricula to enhance genuine global literacy. It is also recommended that future research efforts diversify their cultural purview and give due consideration to variations in socio-economic contexts.

Previous studies have shown that the color red can affect basic motor functioning. However, these studies utilized simple gross motor tasks rather than those assessing complex fine motor skills. Moreover, these empirical studies were theoretically based on the threat–behavior link in human and non-human animals, and neglected the relationship between arousal and motor performance. According to the Yerkes–Dodson law and the inverted-U hypothesis in sport psychology, for simple motor tasks, high arousal (associated with the color red) is more advantageous than low arousal (associated with the color blue); for complex motor tasks, low arousal (blue color) is more advantageous than high arousal (red color). The current research examined the effect of color on different kinds of motor skills (fine motor and gross motor) based on the inverted U-hypothesis. In Experiment 1, we examined the effect of red and blue on dart-throwing performance, whereas in Experiment 2, we examined the effect of red and blue on grip strength performance. The results showed that performance of fine motor skill (dart-throwing) in the blue condition was better than in the red condition, and performance of gross motor skill (handgrip) in the red context was better than in the blue context. These results indicate that the type of motor skill assessed moderates the influence of red and blue on motor performance.

Previous studies have found a link between red and aggressive behavior. For example, athletes who wear red uniforms in sports are considered to have a competitive advantage. So far, most previous studies have adopted self-report methods, which have low face validity and were easily influenced by the social expectations. Therefore, the study used two implicit methods to further explore the association between red and aggressiveness. A modified Stroop task was used in Experiment 1 to probe college students’ differences between “congruent” tasks (i.e., red–aggressiveness and blue–agreeableness) and “incongruent” tasks (i.e., red–agreeableness and blue–aggressiveness). Result showed that participants responded more quickly to the congruent tasks than the incongruent tasks. Then, in order to adapt to the competitive context, Experiment 2 used an implicit association test with photos of athletes as the stimulus to college students and athletes to evaluate “congruent” tasks (i.e., red uniform photo-aggressiveness and blue uniform photo-agreeableness) as well as “incongruent” tasks (i.e., red uniform photo-agreeableness and blue uniform photo-aggressiveness), respectively. According to the results, both college students and athletes respond faster to congruent tasks than to incongruent tasks. Besides, athletes’ reactions to the red–aggressiveness association are faster than college students, which may relate to the athletes’ professional experience. The athletes may be more aggressive and impulsive. Overall, the study has attempted to examine the association between red and aggressiveness through implicit methods, but in the future, researches are need to find a deep association from brain mechanism aspect.

In order to well identify the 93 wild Cortex Daphnes samples from different species and habitats in western China and develop a standard operating procedure (SOP) for the authentication and quality of them in the future, a comprehensive and efficient identification system based on DNA barcoding and HPLC fingerprint technologies has been developed. The result showed that only 17 samples (18%) were Daphne giraldii Nitsche (DG), which is recorded in Chinese Pharmacopeia, while the others (82%) might have safety hazards. Additionally, the result of HPLC fingerprint analysis indicated that samples in the same species origins and wild distributions could be clustered together, which was consistent with DNA barcoding analysis. The study can provide a significant system for the authentication and quality of commercial Cortex Daphnes herbs. Undoubtedly, this study undoubtedly confirmed that the chemical compositions of Cortex Daphnes herbs were affected by both species origins and ecological environments, which is required more in-depth research.

Background: Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. Materials & methods: This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. Results: Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. Conclusion: These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression. [ABSTRACT FROM AUTHOR]

This study investigated the beliefs, attitudes, and motivation of Thai and Chinese undergraduate students in relation to English language learning. Utilizing a mixed-method, explanatory sequential design, it aims to provide a better understanding of the three variables mentioned above. The quantitative data analysis showed disparities between the cohorts, with Chinese undergraduate students often displaying more robust orientations. However, the qualitative data analysis showed that both groups valued immersive learning experiences and technological integration. The research advocates for pedagogical frameworks in English education that align with overarching global paradigms while respecting individual cultural nuances. Such revelations are important for refining teaching practices and curricula to enhance genuine global literacy. It is also recommended that future research efforts diversify their cultural purview and give due consideration to variations in socio-economic contexts. [ABSTRACT FROM AUTHOR]

As the rapid-spreading disease COVID-19 occupies the world, most governments adopt strict control policies to alleviate the impact of the virus. These policies successfully reduced the prevalence and delayed the epidemic peak, while they are also associated with high economic and social costs. To bridge the microscopic epidemic transmission patterns and control policies, simulation systems play an important role. In this work, we propose an agent-based disease simulator for indoor public spaces, which contribute to most of the transmission in cities. As an example, we study Guangzhou Baiyun International Airport, which is one of the most bustling aviation hubs in China. Specifically, we design a high-efficiency mobility generation module to reconstruct the individual trajectories considering both lingering behavior and crowd mobility, which greatly enhances the credibility of the simulated mobility and ensures real-time performance. Based on the individual trajectories, we propose a multi-path disease transmission module optimized for indoor public spaces, which includes three main transmission paths as close contact transmission, aerosol transmission, and object surface transmission. We design a novel convolution-based algorithm to mimic the diffusion process, which can leverage the high concurrent capability of the graphics processing unit to accelerate the simulation process. Leveraging our simulation paradigm, the effectiveness of common policy interventions can be quantitatively evaluated. For mobility interventions, we find that lingering control is the most effective mobility intervention with 32.35% fewer infections, while increasing social distance and increasing walking speed have a similar effect with 15.15% and 18.02% fewer infections. It demonstrates the importance of introducing crowd mobility into disease transmission simulation. For transmission processes, we find the aerosol transmission involves in 99.99% of transmission, which highlights the importance of ventilation in indoor public spaces. Our simulation also demonstrates that without strict entrance detection to identify the input infections, only performing frequent disinfection cannot achieve desirable epidemic outcomes. Based on our simulation paradigm, we can shed light on better policy designs that achieve a good balance between disease spreading control and social costs. [ABSTRACT FROM AUTHOR]

Objective. The chest computed tomography (CT) examination is an important clinical examination in the diagnosis and monitoring of paraquat- (PQ-) induced lung injury. The aim of this study was to explore the prognostic value of the average lung CT number acquired by quantitative CT techniques in patients with acute paraquat poisoning in the early stages of the disease. Methods. 46 patients who suffered from acute PQ poisoning in the emergency department of the Nanjing Drum Tower Hospital from January 2015 to June 2020 were enrolled in the present study. The patients were divided into survival group (n = 21) and nonsurvival group (n = 25). Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. The average lung CT numbers of each patient were obtained by quantitative CT techniques. Receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of average lung CT number in patients with acute paraquat poisoning. Results. The average CT numbers of the middle-lung, lower-lung, and whole lung fields in the nonsurvival group were significantly higher than those of the survival group (p < 0.0001). However, the upper-lung field was not significantly different between the two groups (p = 0.7765). The AUCs of different levels ranged from 0.554 to 0.977, among which the lower-lung field presented the largest AUC of 0.977 (95% CI: 0.943∼1; cut-off value: −702Hu; sensitivity 96%; specificity, 90.5%; YI: 0.865), followed by the whole lung field 0.914 (95% CI: 0.830∼0.999; cut-off value: −727Hu; sensitivity 76%; specificity, 95.2%; YI: 0.712) and the middle-lung field 0.87 (95% CI: 0.768∼0.971; cut-off value: −779Hu; sensitivity 80%; specificity, 85.7%; YI: 0.657). Conclusion. The present study indicated that the average lung CT number could be used to evaluate the relationship between the severity of PQ-induced lung injury and prognosis, especially in the lower-lung field. However, further research is needed to draw a clear conclusion. [ABSTRACT FROM AUTHOR]

This study presents a method for a one-step co-encapsulation of PLGA nanoparticles in hydrophilic nanofibers. The aim is to effectively deliver the drug to the lesion site and achieve a longer release time. The celecoxib nanofiber membrane (Cel-NPs-NFs) was prepared by emulsion solvent evaporation and electrospinning with celecoxib as a model drug. By this method, nanodroplets of celecoxib PLGA are entrapped within polymer nanofibers during an electrospinning process. Moreover, Cel-NPs-NFs exhibited good mechanical strength and hydrophilicity, with a cumulative release of 67.74% for seven days, and the cell uptake at 0.5 h was 2.7 times higher than that of pure nanoparticles. Furthermore, pathological sections of the joint exhibited an apparent therapeutic effect on rat OA, and the drug was delivered effectively. According to the results, this solid matrix containing nanodroplets or nanoparticles could use hydrophilic materials as carriers to prolong drug release time. [ABSTRACT FROM AUTHOR]

In this article we suggest a new odd entire function of order one. We discover that it is the solution of the heat equation. We propose a new conjecture that this function has only real zeros. The obtained result gives a connection with the heat problem and number theory. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) and culture in pathogen detection among intensive care unit (ICU) and non-ICU patients with suspected pulmonary infection. Methods: In this prospective study, sputum samples were collected from patients with suspected pulmonary infection for 2 consecutive days and then subjected to DNA or RNA sequencing by mNGS or culture; 62 ICU patients and 60 non-ICU patients were admitted. In the end, comparisons were made on the pathogen species identified by mNGS and culture, the overall performance of these two methods in pathogen detection, and the most common pathogens detected by mNGS between the ICU and non-ICU groups. Results: In DNA and RNA sequencing, the positive rate of pathogen detection reached 96.69% (117/121) and 96.43% (108/112), respectively. In culture tests, the positive rate of the pathogen was 39.34% (48/122), much lower than that of DNA and RNA sequencing. In general, the positive rate of pathogen detection by sputum mNGS was significantly higher than that of sputum culture in the total and non-ICU groups (p < 0.001) but did not show a significant difference when compared to the result of sputum culture in the ICU group (p = 0.08). Haemophilus spp., Candida albicans, Enterococcus spp., and viruses from the mNGS results were excluded before comparing the overall performance of these two methods in pathogen detection. Specifically, among the 10 most common bacteria implied from the mNGS results, significant differences were observed in the number of cases of Haemophilus parainfluenzae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, and Enterococcus faecalis between the ICU and non-ICU groups (p < 0.05). Conclusions: This study demonstrated the superiority of mNGS over culture in detecting all kinds of pathogen species in sputum samples. These results indicate that mNGS may serve as a valuable tool to identify pathogens, especially for ICU patients who are more susceptible to mixed infections. [ABSTRACT FROM AUTHOR]

As a sort of model-free tracking approach, discriminative correlation filter (DCF)-based trackers have shown prominent performance in unmanned aerial vehicle (UAV) tracking. Nevertheless, typical DCFs acquire all samples oriented to filter training merely from the current frame by cyclic shift operation in the spatial domain but ignore the consistency between samples across the timeline. The lack of temporal cues restricts the performance of DCFs under object appearance variations arising from object/UAV motion, scale variations, and viewpoint changes. Besides, many existing methods commonly neglect the channel discrepancy in object position estimation and generally treat all channels equally, thus limiting the further promotion of the tracking discriminability. To these concerns, this work proposes a novel tracking approach based on a multi-regularized correlation filter (MRCF), i.e., MRCF tracker. By regularizing the deviation of responses and the reliability of channels, the tracker enables smooth response variations and adaptive channel weight distributions simultaneously, leading to favorable adaption to object appearance variations and enhancement of discriminability. Exhaustive experiments on five authoritative UAV-specific benchmarks validate the competitiveness and efficiency of MRCF against top-ranked trackers. Furthermore, we apply our proposed tracker to monocular UAV self-localization under air–ground robot coordination. Evaluations indicate the practicability of the presented method in UAV localization applications. [ABSTRACT FROM AUTHOR]

Background: Sepsis and septic shock, a subset of sepsis with higher risk stratification, are hallmarked by high mortality rates and necessitated early and accurate biomarkers. Methods: Untargeted metabolomic analysis was performed to compare the metabolic features between the sepsis and control systemic inflammatory response syndrome (SIRS) groups in discovery cohort, and potential metabolic biomarkers were selected and quantified using multiple reaction monitoring based target metabolite detection method. Results: Differentially expressed metabolites including 46 metabolites in positive electrospray ionization (ESI) ion mode, 22 metabolites in negative ESI ion mode, and 4 metabolites with dual mode between sepsis and SIRS were identified and revealed. Metabolites 5-Oxoproline, L-Kynurenine and Leukotriene D4 were selected based on least absolute shrinkage and selection operator regularization logistic regression and differential expressed between sepsis and septic shock group in the training and test cohorts. Respective risk scores for sepsis and septic shock based on a 3-metabolite fingerprint classifier were established to distinguish sepsis from SIRS, septic shock from sepsis. Significant relationship between developed sepsis risk scores, septic shock risk scores and Sequential (sepsis-related) Organ Failure Assessment (SOFA), procalcitonin (PCT) and lactic acid were observed. Conclusions: Collectively, our findings demonstrated that the characteristics of plasma metabolites not only manifest phenotypic variation in sepsis onset and risk stratification of sepsis but also enable individualized treatment and improve current therapeutic strategies. [ABSTRACT FROM AUTHOR]

Due to the antioxidant properties of lignin, it has been demonstrated as an active substance for treating oxidation-related and inflammatory diseases. However, how the structural properties of lignin affect its biological activities is still ambiguous. In this study, Kraft lignin from wheat straw (KL-A) was used as the raw material to fractionate into three fractions (e.g. , KL-B, KL-C, and KL-D) with different molecular weight by ultrafiltration, which possessed different physicochemical properties. The biocompatibility, in vivo and in vitro scavenging abilities for reactive oxygen species (ROS), and anti-apoptotic abilities of the lignin fractions were evaluated using SW1353 chondrocyte cell lines and were quantitatively fitted to their physicochemical properties. The results showed that lignin fractions with lower molecular weights, lower G/S ratios, and higher non-condensed phenolic OH contents endowed lignin with stronger ROS scavenging ability in vivo and in vitro , but was accompanied by increased cytotoxicity to cells. The half maximal inhibitory concentration (IC50) of KL-A, KL-B, KL-C, and KL-D were separately determined as 44.02, 33.43, 32.41, and 18.40 μg/mL. Furthermore, KL-D, with the lowest molecular weight and highest number of functional groups, showed the best antioxidant ability, while it performed poorly in inhibiting cellular apoptosis of chondrocytes. Compared to KL-D, KL-C with inverse structural properties, performed better in anti-apoptosis of SW1353 cells, which is the optimum lignin as promising active substances to be applied in the treatment of osteoarthritis in biomedical engineering. [Display omitted] [ABSTRACT FROM AUTHOR]

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. Mycobacterium tuberculosis (M. tuberculosis)- encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified M. tuberculosis encoded-sRNAs in the serum/plasm of M. tuberculosis- infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles M. tuberculosis encoded sRNA (sRNA) by qRT-PCR. The results showed that M. tuberculosis- encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), one of the ancient and deadliest diseases, is a chronic immune disorder caused by Mycobacterium tuberculosis (Mtb) infection. Due to the lack of ideal diagnostic and therapeutic markers, TB is still posing a major health, social, and economic burden worldwide. Circular RNA (circRNA), a newly discovered endogenous RNA, is abundant and stable in the cytoplasm and has tissue specificity. More and more studies suggested circRNA is involved in a variety of human pathological and physiological processes. Recently, several studies have confirmed circRNAs not only existed in the serum but also could serve as ideal biomarkers for detecting diseases since the circRNAs have continuous, stable, and covalently closed circular structures and are not easily degraded by nucleases. In this study, we screened the circRNA expression profiles in active TB serum samples and healthy volunteers serum samples by circRNA microarrays. Then, we performed qRT-PCR to verified the dysregulated circRNAs and ROC curve analysis to evaluate the value of circRNAs for TB diagnosis. The results showed circRNA_051239, circRNA_029965, and circRNA_404022 could serve as biomarkers for TB diagnosis. [ABSTRACT FROM AUTHOR]