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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.

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.

[Objective] The study of genetic diversity in oat germplasm resources not only contributes to the collection and evaluation of germplasm resources, but also has important guiding significance for the production and breeding of oats. [Methods] This study analyzed the diversity, variation, and clustering of 20 morphological traits in 260 oat germplasm resources, evaluated the genetic variation level of their morphological traits, and examined the traits and genetic diversity of oat germplasm resources, aiming to provide a basis for oat germplasm innovation and variety improvement. [Results] There was a significant genetic diversity of morphological traits in the 260 oat germplasm resources. The genetic diversity index of the qualitative traits was the highest in grain color (1.53) and the lowest in awn color (0.76). The genetic diversity index of the 12 quantitative traits was normally distributed, and that of the quantitative traits was the largest in thousand grain weight (2.03) and the smallest in effective tillers (1.22). The highest variable coefficient was the effective tillering number (89.02%), while the lowest was the plant height (11.19%). According to genetic difference of each characteristic varieties, the 260 accessions should be classified into 6 categories by cluster analysis. Germplasm group Ⅰ included 42 accessions which could be used as parent materials for seed type selection. Germplasm group Ⅱ had 31 accessions that could be used as parent materials for breeding high-yield forage varieties. Germplasm group Ⅳ includes 41 accessions that could be used for breeding large grain varieties. Germplasm group Ⅴ includes 46 accessions that could be used as parents for oat dwarfing. Germplasm group Ⅲ included 46 accessions and group Ⅵ included 54 accessions, and both were not outstanding in comprehensive characters analyzed. [Conclusion] This study could provide theoretical basis for the protection, development and utilization of oat germplasm resources in eastern Inner Mongolia.

Dysregulation of the microRNA machinery has crucial roles in cancer development. Here the authors show that inactivation of proteins involved in microRNA-mediated gene silencing, such as ANKRD52 or AGO2, confers resistance to T cell-mediated immune response in a preclinical cancer model.

ObjectiveTo 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.MethodsIn 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.ResultsIn 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).ConclusionsThis 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.

We described the first results of a quantitative ultra performance liquid chromatographyâtandem mass spectrometry method for a novel antimicrobial peptide (phylloseptin, PSN-1). Chromatographic separation was accomplished on a Waters bridged ethyl hybrid (BEH) C18 (50 mmÃ2.1 mm, 1.7 μm) column with acetonitrileâwater (25:75, v/v) as isocratic mobile phase. Mass spectrometry detection was performed in the positive electrospray ionization mode and by monitoring of the transitions at m/z 679.6/120, 509.6/120 (PSN-1) and m/z 340.7/165 (Thymopentin, IS). Protein precipitation was investigated and the recovery was satisfactory (above 82%). The method was shown to be reproducible and reliable with intra-day precision below 5.3%, inter-day precision below 14.2%, and linear range from 0.02 to 2 μg/mL with r>0.994. The method was successfully applied to a pharmacokinetic study of PSN-1 in rats after intravenous administration. Keywords: Antimicrobial peptide, Phylloseptin, Ultra performance liquid chromatographyâtandem mass spectrometry, Pharmacokinetic