Trifolium repens L. recruits root-associated Microbacterium species to adapt to heavy metal stress in an abandoned Pb-Zn mining area.

Root-associated microbiota provide great fitness to hosts under environmental stress. However, the underlying microecological mechanisms controlling the interaction between heavy metal-stressed plants and the microbiota are poorly understood. In this study, we screened and isolated representative amplicon sequence variants (strain M4) from rhizosphere soil samples of Trifolium repens L. growing in areas with high concentrations of heavy metals. To investigate the microecological mechanisms by which T. repens adapts to heavy metal stress in abandoned mining areas, we conducted potting experiments, bacterial growth promotion experiments, biofilm formation experiments, and chemotaxis experiments. The results showed that high concentrations of heavy metals significantly altered the rhizosphere bacterial community structure of T. repens and significantly enriched Microbacterium sp. Strain M4 was demonstrated to significantly increased the biomass and root length of T. repens under heavy metal stress. Additionally, L-proline and stigmasterol could promote bacterial growth and biofilm formation and induce chemotaxis for strain M4, suggesting that they are key rhizosphere secretions of T. repens for Microbacterium sp. recruitment. Our results suggested that T. repens adapted the heavy metal stress by reshaping rhizosphere secretions to modify the rhizosphere microbiota.

Roles of vaporization and thermal decomposition in the dynamic evolution of laser-induced bubble on the surface of a submerged metal plate.

This paper aims to explain when the vaporization or thermal decomposition prevails during laser-induced bubble growth and how they influence bubble morphology. Bubbles were generated by irradiating a 304 stainless steel plate submerged in degassed water using millisecond lasers with a pulse width of 0.4 ms and powers of 1.6 kW and 3.2 kW, respectively. The dynamic evolution of bubbles was recorded by a high-speed camera. Moreover, the numerical models were developed to obtain a vaporization model and a decomposition model by incorporating the source terms due to the vaporization and decomposition mass fluxes into the governing equations, respectively. The simulated dynamic bubble evolution is consistent with the experimental results. When the laser power is 1.6 kW, a thin-layer bubble is formed, which gradually shrinks and eventually disappears after the laser stops irradiating. When the laser power is 3.2 kW, a spherical bubble is formed, and its volume decreases significantly after the laser stops irradiating. Subsequently, it remains relatively stable during the observation period. The fundamental reason for the difference between the bubble morphologies obtained from the vaporization model and the decomposition model lies in the presence of a condensation zone in the gas phase. When water vaporization or thermal decomposition dominates, the temperatures obtained from the models align with the decomposition ratios at varying temperatures reported in the literature. Our findings are significant for understanding the dynamic behavior of bubbles, with implications for various laser processing underwater.

Molecular transmission network analysis of newly diagnosed HIV-1 infections in Nanjing from 2019 to 2021.

OBJECTIVE: The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing. METHODS: Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters. RESULTS: A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P < 0.05). Furthermore, the analysis of larger clusters revealed that individuals aged ≥ 60, peasants, those without TDR, and individuals infected with the CRF119_0107 were more likely to be part of these clusters. CONCLUSIONS: This study revealed the high risk of local HIV transmission and high TDR prevalence in Nanjing, especially the rapid spread of CRF119_0107. It is crucial to implement targeted interventions for the molecular transmission clusters identified in this study to effectively control the HIV epidemic.

Coronary computed tomographic angiography-derived anatomic and hemodynamic plaque characteristics in prediction of cardiovascular events.

This study investigated the association of anatomic and hemodynamic plaque characteristics based on deep learning coronary computed tomography angiography (CCTA) with high-risk plaques that caused subsequent major adverse cardiovascular events (MACE). A retrospective analysis was conducted on patients who underwent CCTA between 1 month and 3 years prior to the occurrence of a MACE. Deep learning and computational fluid dynamics algorithms based on CCTA were applied to extract adverse plaque characteristics (low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification), and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFRCT], change in FFRCT across the lesion [△FFRCT], wall shear stress [WSS], and axial plaque stress [APS]). Correlation analysis, logistic regression, and Cox proportional risk analysis were conducted to understand the relationship between these measures and the occurrence of MACE and assess the value of hemodynamic parameters in predicting the incidence of MACE events and their prognosis. Our study included 86 patients with a total of 134 vessels exhibiting plaque formation and 83 culprit vessels with a subsequent coronary event. Culprit vessels had percent diameter stenosis [%DS] (0.54 ± 0.16 vs. 0.62 ± 0.13, P = 0.003), larger non-calcified plaque volume (45.8 vs. 101.7, P < 0.001), larger low-attenuation plaque volume (3.6 vs. 14.5, P < 0.001), more lesions with ≥ 3 adverse plaque characteristics (APC) (4 vs.26, P = 0.002), and worse hemodynamic features of adverse plaque. FFRCT demonstrated better visualization of maximum achievable flow in the presence of coronary stenosis and better correlation with the stenosis severity, while maximum of wall shear stress (WSSmax) was highly correlated with low-attenuation plaques and APC. The inclusion of hemodynamic parameters improved the efficacy of the predictive model, and a high WSS suggested a higher probability of MACE. Hemodynamic parameters based on CCTA are significantly correlated with plaque morphology. Importantly, integrating CCTA-derived parameters can refine the predictive performance of MACE occurrence.

Megastigmane glycosides from the traditional Uighur medicine Cydonia oblonga Mill.

Phytochemical investigation on the fruits of Cydonia oblonga Mill., a traditional Uighur medicine, led to the isolation of seven undescribed and nine known megastigmane glycosides. Their structures including absolute configurations were characterized by an extensive analysis of spectroscopic data including HRESIMS and NMR, combined with ECD calculations. Additionally, compounds 1, 2, 4, and 6-16 exhibited anti-inflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharides (LPS) with inhibitory rates of 10.79%-44.58% at 20 µM.

Non-invasive assessment of proarrhythmic risks associated with isoprenaline and the dietary supplement ingredient synephrine using human induced pluripotent stem cell-derived cardiomyocytes.

Background: There have been conflicting reports about the proarrhythmic risk of p-synephrine (SYN). To address this, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with the microelectrode array (MEA) system have been utilized to assess arrhythmia risks, particularly in the context of adrenomimetic drugs. Aim: This study aims to determine whether MEA recordings from hiPSC-CMs could predict the proarrhythmic risk of adrenomimetic drugs and to investigate the cardiovascular effects and mechanisms of SYN. Materials and methods: We employed MEA recordings to assess the electrophysiological properties of hiPSC-CMs and conducted concentration-response analyses to evaluate the effects of SYN and Isoprenaline (ISO) on beating rate and contractility. A risk scoring system for proarrhythmic risks was established based on hiPSC-CMs in this study. ISO, a classic beta-adrenergic drug, was also evaluated. Furthermore, the study evaluated the risk of SYN and recorded the concentration-response of beating rate, contractility and the change in the presence or absence of selective ß1, ß2 and ß3 adrenergic blockers. Results: Our results suggested that ISO carries a high risk of inducing arrhythmias, aligning with existing literature. SYN caused a 30% prolongation of the field potential duration (FPD) at a concentration of 206.326 µM, a change significantly different from baseline measurements and control treatments. The half maximal effective concentration (EC50) of SYN (3.31 µM) to affect hiPSC-CM beating rate is much higher than that of ISO (18.00 nM). The effect of SYN at an EC50 of 3.31 µM is about ten times more potent in hiPSC-CMs compared to neonatal rat cardiomyocytes (34.12 µM). SYN increased the contractility of cardiomyocytes by 29.97 ± 11.65%, compared to ISO's increase of 50.56 ± 24.15%. ß1 receptor blockers almost eliminated the beating rate increase induced by both ISO and SYN, while neither ß2 nor ß3 blockers had a complete inhibitory effect. Conclusion: The MEA and hiPSC-CM system could effectively predict the risk of adrenomimetic drugs. The study concludes that the proarrhythmia risk of SYN at conventional doses is low. SYN is more sensitive in increasing beating rate and contractility in human cardiomyocytes compared to rats, primarily activating ß1 receptor.

Antimicrobial and Antibiofilm Effects of Bithionol against Mycobacterium abscessus.

Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 µM against M. abscessus type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against M. abscessus were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of M. abscessus from 0.625 µM to 2.5 µM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time-kill curve study and also electron microscopy study. Interestingly, it was found that at 128 µg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 µg/mL, 99% at 32 µg/mL, and 90% at 16 µg/mL. Therefore, bithionol may be a potential candidate for the treatment of M. abscessus infections due to its significant antimicrobial and antibiofilm activities.

Identification of ARF Genes and Elucidation of the Regulatory Effects of PsARF16a on the Dormancy of Tree Peony Plantlets.

The low survival rate of transplanted plantlets, which has limited the utility of tissue-culture-based methods for the rapid propagation of tree peonies, is due to plantlet dormancy after rooting. We previously determined that the auxin response factor PsARF may be a key regulator of tree peony dormancy. To clarify the mechanism mediating tree peony plantlet dormancy, PsARF genes were systematically identified and analyzed. Additionally, PsARF16a was transiently expressed in the leaves of tree peony plantlets to examine its regulatory effects on a downstream gene network. Nineteen PsARF genes were identified and divided into four classes. All PsARF genes encoded proteins with conserved B3 and ARF domains. The number of motifs, exons, and introns varied between PsARF genes in different classes. The overexpression of PsARF16a altered the expression of NCED, ZEP, PYL, GA2ox1, GID1, and other key genes in abscisic acid (ABA) and gibberellin (GA) signal transduction pathways, thereby promoting ABA synthesis and decreasing GA synthesis. Significant changes to the expression of some key genes contributing to starch and sugar metabolism (e.g., AMY2A, BAM3, BGLU, STP, and SUS2) may be associated with the gradual conversion of sugar into starch. This study provides important insights into PsARF functions in tree peonies.

Learning locality-sensitive bucketing functions.

MOTIVATION: Many tasks in sequence analysis ask to identify biologically related sequences in a large set. The edit distance, being a sensible model for both evolution and sequencing error, is widely used in these tasks as a measure. The resulting computational problem-to recognize all pairs of sequences within a small edit distance-turns out to be exceedingly difficult, since the edit distance is known to be notoriously expensive to compute and that all-versus-all comparison is simply not acceptable with millions or billions of sequences. Among many attempts, we recently proposed the locality-sensitive bucketing (LSB) functions to meet this challenge. Formally, a (d1,d2)-LSB function sends sequences into multiple buckets with the guarantee that pairs of sequences of edit distance at most d1 can be found within a same bucket while those of edit distance at least d2 do not share any. LSB functions generalize the locality-sensitive hashing (LSH) functions and admit favorable properties, with a notable highlight being that optimal LSB functions for certain (d1,d2) exist. LSB functions hold the potential of solving above problems optimally, but the existence of LSB functions for more general (d1,d2) remains unclear, let alone constructing them for practical use. RESULTS: In this work, we aim to utilize machine learning techniques to train LSB functions. With the development of a novel loss function and insights in the neural network structures that can potentially extend beyond this specific task, we obtained LSB functions that exhibit nearly perfect accuracy for certain (d1,d2), matching our theoretical results, and high accuracy for many others. Comparing to the state-of-the-art LSH method Order Min Hash, the trained LSB functions achieve a 2- to 5-fold improvement on the sensitivity of recognizing similar sequences. An experiment on analyzing erroneous cell barcode data is also included to demonstrate the application of the trained LSB functions. AVAILABILITY AND IMPLEMENTATION: The code for the training process and the structure of trained models are freely available at https://github.com/Shao-Group/lsb-learn.

The Closer Vicinity to Treated Vertebrae in Percutaneous Vertebroplasty, the Higher Rate of New Vertebral Compression Fractures at Follow-up.

OBJECTIVE: To investigate whether risk of new vertebral compression fractures (NVCFs) was associated with vicinity to treated vertebrae in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs). METHODS: All OVCF (T6-L5) patients treated with PVP between January 2016 and December 2020 were retrospectively reviewed. Vicinity to treated vertebrae was defined as the number of vertebrae between an untreated and its closest treated level. The closest treated level was chosen as reference vertebra. Clinical, radiologic, and surgical parameters were compared between groups of reference vertebrae for each vicinity NVCF. RESULTS: In total, 1348 patients with 1592 fractured and 14,584 normal vertebrae were enrolled. NVCF was identified in 20.1% (271 of 1348) patients in 2.2% (319 of 14584) vertebrae in a mean follow-up time of 24.3 ± 11.9 months. Rate of NVCF in vicinity 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 level were 4.6% (130 of 2808), 2.4% (62 of 2558), 1.8% (42 of 2365), 1.5% (31 of 2131), 1.3% (23 of 1739), 1.3% (17 of 1298), 0.8% (7 of 847), 0.9% (4 of 450), 0.8% (2 of 245), 0.9% (1 of 117), and 0% (0 of 26), respectively. Rate of NVCF in vicinity 1 level was significantly higher than that in vicinity 2, 3, 4, 5, 6, 7, 8, and 9 level, respectively. However, compared to reference vertebrae for vicinity 1 NVCF, any clinical, radiologic, or surgical parameters were not significantly different in those for vicinity 2, 3, and 4 NVCF, respectively. CONCLUSIONS: The closer vicinity to treated vertebrae in PVP, the higher rate of NVCF at follow-up. However, any clinical, radiologic, or surgical parameters might not matter in this phenomenon of vicinity-related NVCF.

Motion-aware Dynamic Graph Neural Network for Video Compressive Sensing.

Video snapshot compressive imaging (SCI) utilizes a 2D detector to capture sequential video frames and compress them into a single measurement. Various reconstruction methods have been developed to recover the high-speed video frames from the snapshot measurement. However, most existing reconstruction methods are incapable of efficiently capturing long-range spatial and temporal dependencies, which are critical for video processing. In this paper, we propose a flexible and robust approach based on the graph neural network (GNN) to efficiently model non-local interactions between pixels in space and time regardless of the distance. Specifically, we develop a motion-aware dynamic GNN for better video representation, i.e., represent each node as the aggregation of relative neighbors under the guidance of frame-by-frame motions, which consists of motion-aware dynamic sampling, cross-scale node sampling, global knowledge integration, and graph aggregation. Extensive results on both simulation and real data demonstrate both the effectiveness and efficiency of the proposed approach, and the visualization illustrates the intrinsic dynamic sampling operations of our proposed model for boosting the video SCI reconstruction results. The code and model will be released.

The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.

Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.

Prevalence of anal cytology screening among persons with HIV and lack of access to high-resolution anoscopy at HIV care facilities.

BACKGROUND: Persons with HIV (PWH) at highest risk of anal cancer include gay, bisexual, and other men who have sex with men (GBMSM) and transgender women aged ≥ 35 years, and other PWH aged ≥ 45 years. Identifying and treating precancerous lesions can reduce anal cancer incidence in these groups. We assessed prevalence of anal cytology and access to high-resolution anoscopy (HRA) among PWH, overall and those at highest risk. METHODS: Data were obtained from the CDC's Medical Monitoring Project (MMP), a population-based survey of PWH aged ≥ 18 years, and a supplemental MMP facility survey. We report weighted percentages of PWH receiving anal cytology during the past 12 months, access to HRA, and characteristics of HIV care facilities by availability of HRA. RESULTS: Overall, 4.8% (95% CI 3.4 to 6.1) of PWH had anal cytology in the prior 12 months. Only 7.7% (95% CI 5.1 to 10.6) of GBMSM and transgender women aged ≥ 35 years, and 1.9% (95% CI 0.9 to 2.9) of all other PWH aged ≥ 45 years, had anal cytology. Prevalence was statistically significantly low among PWH with the following characteristics: non-Hispanic/Latino Black/African American, ≤ high school education, heterosexual orientation, and living in Southern MMP states. Among PWH, 32.8% (95% CI 28.0 to 37.7) had no HRA access on-site/through referral at their care facility; 22.2% (95% CI 19.5 to 24.9) had on-site access; 45.0% (95% CI 41.5 to 48.5) had HRA available through referral. Most facilities that received Ryan White HIV/AIDS Program funding, cared for > 1000 PWH, or provided on-site colposcopy also provided HRA on-site/through referral. CONCLUSIONS: Anal cytology and access to HRA was low among PWH, including those at highest risk of anal cancer. Our data may inform large-scale implementation of anal cancer prevention efforts.

Advancing Hyperspectral and Multispectral Image Fusion: An Information-Aware Transformer-Based Unfolding Network.

In hyperspectral image (HSI) processing, the fusion of the high-resolution multispectral image (HR-MSI) and the low-resolution HSI (LR-HSI) on the same scene, known as MSI-HSI fusion, is a crucial step in obtaining the desired high-resolution HSI (HR-HSI). With the powerful representation ability, convolutional neural network (CNN)-based deep unfolding methods have demonstrated promising performances. However, limited receptive fields of CNN often lead to inaccurate long-range spatial features, and inherent input and output images for each stage in unfolding networks restrict the feature transmission, thus limiting the overall performance. To this end, we propose a novel and efficient information-aware transformer-based unfolding network (ITU-Net) to model the long-range dependencies and transfer more information across the stages. Specifically, we employ a customized transformer block to learn representations from both the spatial and frequency domains as well as avoid the quadratic complexity with respect to the input length. For spatial feature extractions, we develop an information transfer guided linearized attention (ITLA), which transmits high-throughput information between adjacent stages and extracts contextual features along the spatial dimension in linear complexity. Moreover, we introduce frequency domain learning in the feedforward network (FFN) to capture token variations of the image and narrow the frequency gap. Via integrating our proposed transformer blocks with the unfolding framework, our ITU-Net achieves state-of-the-art (SOTA) performance on both synthetic and real hyperspectral datasets.

Integrated Communication, Sensing, and Computation Framework for 6G Networks.

In the sixth generation (6G) era, intelligent machine network (IMN) applications, such as intelligent transportation, require collaborative machines with communication, sensing, and computation (CSC) capabilities. This article proposes an integrated communication, sensing, and computation (ICSAC) framework for 6G to achieve the reciprocity among CSC functions to enhance the reliability and latency of communication, accuracy and timeliness of sensing information acquisition, and privacy and security of computing to realize the IMN applications. Specifically, the sensing and communication functions can merge into unified platforms using the same transmit signals, and the acquired real-time sensing information can be exploited as prior information for intelligent algorithms to enhance the performance of communication networks. This is called the computing-empowered integrated sensing and communications (ISAC) reciprocity. Such reciprocity can further improve the performance of distributed computation with the assistance of networked sensing capability, which is named the sensing-empowered integrated communications and computation (ICAC) reciprocity. The above ISAC and ICAC reciprocities can enhance each other iteratively and finally lead to the ICSAC reciprocity. To achieve these reciprocities, we explore the potential enabling technologies for the ICSAC framework. Finally, we present the evaluation results of crucial enabling technologies to show the feasibility of the ICSAC framework.

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

Differential Gene Analysis of Langerhans Cell Histiocytosis and the Significance of MMP1-Targeted Drug Repositioning.

Langerhans cell histiocytosis (LCH) is a rare condition predominantly affecting young children. Activation of the MAPK pathway has offered key new insights into the pathogenesis of LCH; however, the precise mechanisms underlying its occurrence and development are still far from being completely elucidated. There is still a relapse/reactivation rate in patients with multisystem LCH. Therefore, this study aimed to investigate other potential LCH pathophysiologies and prospective therapeutic targets. The gene expression omnibus (GEO) database was used to retrieve gene expression profiles of LCH (GSE16395). Three distinct types of analyses were performed after identifying the common differentially expressed genes (DEGs) in LCH: hub gene identification, functional annotation, module construction, drug repositioning, and expression analysis via immunohistochemistry (IHC). We identified 417 common DEGs and 50 central hub genes. This functional study highlighted the significance of keratinization, skin development, and inflammation. In addition, we predicted new drug candidates (RS2 drugs targeting matrix metalloprotease1, MMP1) that could be used for LCH treatment. Finally, gene-miRNA and gene-TF networks and immune cell infiltration were analyzed for MMP1-related genes. MMP1 expression levels in LCH tissues were validated by IHC. Our study identified the central communal genes and novel drug candidates. These shared pathways and hub genes offer new perspectives on future mechanisms of action and therapeutic targets.

Learning autonomous race driving with action mapping reinforcement learning.

Autonomous race driving poses a complex control challenge as vehicles must be operated at the edge of their handling limits to reduce lap times while respecting physical and safety constraints. This paper presents a novel reinforcement learning (RL)-based approach, incorporating the action mapping (AM) mechanism to manage state-dependent input constraints arising from limited tire-road friction. A numerical approximation method is proposed to implement AM, addressing the complex dynamics associated with the friction constraints. The AM mechanism also allows the learned driving policy to be generalized to different friction conditions. Experimental results in our developed race simulator demonstrate that the proposed AM-RL approach achieves superior lap times and better success rates compared to the conventional RL-based approaches. The generalization capability of driving policy with AM is also validated in the experiments.