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Understanding agents’ motion behaviors under complex scenes is crucial for intelligent autonomous moving systems (like delivery robots and self-driving cars). It is challenging duo to the inherent uncertain of future trajectories and the large variation in the scene layout. However, most recent approaches ignored or underutilized the scenario information. In this work, a Multi-Granularity Scenarios Understanding framework, MGSU, is proposed to explore the scene layout from different granularity. MGSU can be divided into three modules: (1) A coarse-grained fusion module uses the cross-attention to fuse the observed trajectory with the semantic information of the scene. (2) The inverse reinforcement learning module generates optimal path strategy through grid-based policy sampling and outputs multiple scene paths. (3) The fine-grained fusion module integrates the observed trajectory with the scene paths to generate multiple future trajectories. To fully explore the scene information and improve the efficiency, we present a novel scene-fusion Transformer, whose encoder is used to extract scene features and the decoder is used to fuse scene and trajectory features to generate future trajectories. Compared with the current state-of-the-art methods, our method decreases the ADE errors by 4.3% and 3.3% by gradually integrating different granularity of scene information on SDD and NuScenes, respectively. The visualized trajectories demonstrate that our method can accurately predict future trajectories after fusing scene information.

Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease. In order to design cancer immune therapies, it is important to understand how tumours evade the immune response that is mounted against them. Authors here analyse the distribution and properties of immune cells in hepatocellular carcinoma and describe a progressive tumour-immune co-evolution programme from early to late stage cancer.

Ship weather routing has always been an important issue in the research field of navigation, and many scholars have been devoted to this research for a long time. To study the route strategies of different shipping companies, this paper proposes an improved multi-objective ant colony optimization (IMACO) algorithm based on the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). It can comprehensively consider ship navigation risk and fuel consumption cost under complex sea conditions. First, the grid method is used to model the marine environment. Then, we calculate the fuel consumption and the ship navigation risk of each grid and use the TOPSIS method to evaluate these two indicators for each grid. The results show that due to the different strictness of navigation management requirements of different companies, different routes are selected in the same sea area at the same time. Compared with the single-objective ant colony optimization (SACO) algorithm, the algorithm proposed in this paper can more comprehensively and effectively solve the problem of route strategy selection of shipping companies, which has great practical significance for ship operations management.

This paper presents a comprehensive study based on multiphase-seepage and wellbore multiphase-flow theories. It establishes a model for calculating the rate of gas intrusion that considers various factors, including formation pore permeability, bottomhole pressure difference, rheology of the drilling fluid, and surface tension. Experiments were conducted to investigate the mechanism of gas intrusion under shut-in conditions, and the experimental results were employed to validate the reliability of the proposed method for calculating the gas intrusion rate. Furthermore, this research explores the transportation rates of single bubbles and bubble clusters in drilling fluid under shut-in conditions. Additionally, empirical expressions were derived for the drag coefficient for single bubbles and bubble clusters in the wellbore. These expressions can be used to calculate gas transportation rates for various equivalent radii of single bubbles and bubble clusters. The initial bubble size of intrusive gas, the transportation speed of intrusive gas in the wellbore, the rate of gas intrusion, and variations in the wellbore pressure after gas intrusion were analyzed. Additionally, a method was developed to calculate the rising velocity of bubble clusters in water based on experimental results. The study reveals that the average bubble size in the bubble cluster is significantly smaller than the size of single bubbles generated from the orifice. When the viscosity of the drilling fluid is low, the transportation velocity of the bubble cluster exhibits a positive correlation with the average bubble diameter. When the average bubble diameter exceeds 1 mm, the bubble velocity no longer varies with changes in the bubble-cluster diameter. The research results provide theoretical support for wellbore pressure prediction and pressure control under shutdown conditions.

Hair follicles cycle through expansion, regression and quiescence. To investigate the role of MCL‑1, a BCL‑2 family protein with anti‑apoptotic and apoptosis‑unrelated functions, we delete Mcl‑1 within the skin epithelium using constitutive and inducible systems. Constitutive Mcl‑1 deletion does not impair hair follicle organogenesis but leads to gradual hair loss and elimination of hair follicle stem cells. Acute Mcl‑1 deletion rapidly depletes activated hair follicle stem cells and completely blocks depilation‑induced hair regeneration in adult mice, while quiescent hair follicle stem cells remain unaffected. Single‑cell RNA‑seq profiling reveals the engagement of P53 and DNA mismatch repair signaling in hair follicle stem cells upon depilation‑induced activation. Trp53 deletion rescues hair regeneration defects caused by acute Mcl‑1 deletion, highlighting a critical interplay between P53 and MCL‑1 in balancing proliferation and death. The ERBB pathway plays a central role in sustaining the survival of adult activated hair follicle stem cells by promoting MCL‑1 protein expression. Remarkably, the loss of a single Bak allele, a pro‑apoptotic Bcl‑2 effector gene, rescues Mcl‑1 deletion‑induced defects in both hair follicles and mammary glands. These findings demonstrate the pivotal role of MCL‑1 in inhibiting proliferation stress‑induced apoptosis when quiescent stem cells activate to fuel tissue regeneration. Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Background After millions of years of coevolution, symbiotic microbiota has become an integral part of the host and plays an important role in host immunity, metabolism, and health. Vaccination, as an effective means of preventing infectious diseases, has been playing a vital role in the prevention and control of human and animal diseases for decades. However, so far, minimal is known about the effect of vaccination on fish symbiotic microbiota, especially mucosal microbiota, and its correlation with intestinal metabolism remains unclear. Methods Here we reported the effect of an inactivated bivalent Aeromonas hydrophila / Aeromonas veronii vaccine on the symbiotic microbiota and its correlation with the intestinal metabolism of farmed adult Nile tilapia ( Oreochromis niloticus ) by 16S rRNA gene high-throughput sequencing and gas chromatography-mass spectrometry metabolomics. Results Results showed that vaccination significantly changed the structure, composition, and predictive function of intestinal mucosal microbiota but did not significantly affect the symbiotic microbiota of other sites including gill mucosae, stomach contents, and stomach mucosae. Moreover, vaccination significantly reduced the relative abundance values of potential opportunistic pathogens such as Aeromonas , Escherichia – Shigella , and Acinetobacter in intestinal mucosae. Combined with the enhancement of immune function after vaccination, inactivated bivalent Aeromonas vaccination had a protective effect against the intestinal pathogen infection of tilapia. In addition, the metabolite differential analysis showed that vaccination significantly increased the concentrations of carbohydrate-related metabolites such as lactic acid, succinic acid, and gluconic acid but significantly decreased the concentrations of multiple lipid-related metabolites in tilapia intestines. Vaccination affected the intestinal metabolism of tilapia, which was further verified by the predictive function of intestinal microbiota. Furthermore, the correlation analyses showed that most of the intestinal differential microorganisms were significantly correlated with intestinal differential metabolites after vaccination, confirming that the effect of vaccination on intestinal metabolism was closely related to the intestinal microbiota. Conclusions In conclusion, this paper revealed the microbial and metabolic responses induced by inactivated vaccination, suggesting that intestinal microbiota might mediate the effect of vaccination on the intestinal metabolism of tilapia. It expanded the novel understanding of vaccine protective mechanisms from microbial and metabolic perspectives, providing important implications for the potential influence of vaccination on human intestinal microbiota and metabolism. -tufGxbkxhm-UiFTxxYHNi Video Abstract

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases.

Tetraspanins, a superfamily of small integral membrane proteins, are characterized by four transmembrane domains and conserved protein motifs that are configured into a unique molecular topology and structure in the plasma membrane. They act as key organizers of the plasma membrane, orchestrating the formation of specialized microdomains called “tetraspanin-enriched microdomains (TEMs)” or “tetraspanin nanodomains” that are essential for mediating diverse biological processes. TSPAN8 is one of the earliest identified tetraspanin members. It is known to interact with a wide range of molecular partners in different cellular contexts and regulate diverse molecular and cellular events at the plasma membrane, including cell adhesion, migration, invasion, signal transduction, and exosome biogenesis. The functions of cell-surface TSPAN8 are governed by ER targeting, modifications at the Golgi apparatus and dynamic trafficking. Intriguingly, limited evidence shows that TSPAN8 can translocate to the nucleus to act as a transcriptional regulator. The transcription of TSPAN8 is tightly regulated and restricted to defined cell lineages, where it can serve as a molecular marker of stem/progenitor cells in certain normal tissues as well as tumors. Importantly, the oncogenic roles of TSPAN8 in tumor development and cancer metastasis have gained prominence in recent decades. Here, we comprehensively review the current knowledge on the molecular characteristics and regulatory mechanisms defining TSPAN8 functions, and discuss the potential and significance of TSPAN8 as a biomarker and therapeutic target across various epithelial cancers.

Gas-phase studies of fullerenes and metallofullerenes, though less well explored compared to condensed-phase research in recent years, offer critical insights into the mechanisms governing their formation and behavior. In this study, we re-examined the coalescence reactions of fullerenes using a high-resolution Fourier transform ion cyclotron resonance (FT ICR) mass spectrometer, especially the effect of electric fields in the source region on the formation of large-sized fullerenes. By varying the voltages on the metal plate where the C60 was deposited, we achieved enhanced control over the coalescence process, revealing distinct distributions of fullerene products that differ from those reported in earlier studies. What is the most attractive is that a negative voltage applied on the metal plate is actually more conducive to the production of large-sized fullerene cations. Notably, we identified previously unobserved species, including doubly charged fullerene cations (e.g., C1602+) and metallofullerene ions (e.g., Y1–2C94–124+), providing new evidence for the complexity of gas-phase fullerene chemistry. These findings underscore the importance of source region electric fields in shaping coalescence outcomes and highlight the potential of gas-phase approaches for synthesizing novel metallofullerenes.

Symbiotic microorganisms in the digestive and circulatory systems are found in various crustaceans, and their essential roles in crustacean health, nutrition, and disease have attracted considerable interest. Although the intestinal microbiota of the Chinese mitten crab (Eriocheir sinensis) has been extensively studied, information on the symbiotic microbiota at various sites of this aquatic economic species, particularly the hepatopancreas and hemolymph, is lacking. This study aimed to comprehensively characterize the hemolymph, hepatopancreas, and intestinal microbiota of Chinese mitten crab through the high-throughput sequencing of the 16S rRNA gene. Results showed no significant difference in microbial diversity between the hemolymph and hepatopancreas (Welch t-test; p > 0.05), but their microbial diversity was significantly higher than that in the intestine (p < 0.05). Distinct differences were found in the structure, composition, and predicted function of the symbiotic microbiota at these sites. At the phylum level, the hemolymph and hepatopancreas microbiota were dominated by Proteobacteria, Firmicutes, and Acidobacteriota, followed by Bacteroidota and Actinobacteriota, whereas the gut microbiota was mainly composed of Firmicutes, Proteobacteria, and Bacteroidota. At the genus level, Candidatus Hepatoplasma, Shewanella, and Aeromonas were dominant in the hepatopancreas; Candidatus Bacilloplasma, Roseimarinus, and Vibrio were dominant in the intestine; Enterobacter, norank_Vicinamibacterales, and Pseudomonas were relatively high-abundance genera in the hemolymph. The composition and abundance of symbiotic microbiota in the hemolymph and hepatopancreas were extremely similar (p > 0.05), and no significant difference in functional prediction was found (p > 0.05). Comparing the hemolymph in the intestine and hepatopancreas, the hemolymph had lower variation in bacterial composition among individuals, having a more uniform abundance of major bacterial taxa, a smaller coefficient of variation, and the highest proportion of shared genera. Network complexity varied greatly among the three sites. The hepatopancreas microbiota was the most complex, followed by the hemolymph microbiota, and the intestinal microbiota had the simplest network. This study revealed the taxonomic and functional characteristics of the hemolymph, hepatopancreas, and gut microbiota in Chinese mitten crab. The results expanded our understanding of the symbiotic microbiota in crustaceans, providing potential indicators for assessing the health status of Chinese mitten crab.