新疆医科大学

The rapid advancement of Large Multimodal Models (LMMs) for 2D images and videos has motivated extending these models to understand 3D scenes, aiming for human-like visual-spatial intelligence. Nevertheless, achieving deep spatial understanding comparable to human capabilities poses significant challenges in model encoding and data acquisition. Existing methods frequently depend on external depth sensors for geometry capture or utilize off-the-shelf algorithms for pre-constructing 3D maps, thereby limiting their scalability, especially with prevalent monocular video inputs and for time-sensitive applications. In this work, we introduce VLM-3R, a unified framework for Vision-Language Models (VLMs) that incorporates 3D Reconstructive instruction tuning. VLM-3R processes monocular video frames by employing a geometry encoder to derive implicit 3D tokens that represent spatial understanding. Leveraging our Spatial-Visual-View Fusion and over 200K curated 3D reconstructive instruction tuning question-answer (QA) pairs, VLM-3R effectively aligns real-world spatial context with language instructions. This enables monocular 3D spatial assistance and embodied reasoning. To facilitate the evaluation of temporal reasoning, we introduce the Vision-Spatial-Temporal Intelligence benchmark, featuring over 138.6K QA pairs across five distinct tasks focused on evolving spatial relationships. Extensive experiments demonstrate that our model, VLM-3R, not only facilitates robust visual-spatial reasoning but also enables the understanding of temporal 3D context changes, excelling in both accuracy and scalability.

The KEAP1–NRF2 pathway is a pivotal regulator of cellular antioxidant responses and is implicated in chronic kidney disease (CKD) pathogenesis. Inhibiting KEAP1 to activate NRF2 signaling offers a promising therapeutic strategy. We used the GSE180393 and GSE180394 to evaluate the KEAP1 expression in CKD patient. We conducted the PPI network and functional enrichment analysis. We constructed a pharmacophore model based on the KEAP1–IQK co-crystal structure. We performed virtual screening, molecular docking, and ADMET to identify potential drug-like inhibitors. We conducted 200 ns molecular dynamics simulations (MDS), MM/GBSA, and per-residue decomposition of KEAP1-ligand complexes. Finally, density functional theory (DFT) analyses were assessed. KEAP1 was significantly overexpressed in glomerular and tubular compartments of CKD patients with high diagnostic efficacy. The KEAP1-interacting PPI network is functionally linked to the KEAP1–NRF2 pathway. Pharmacophore-based virtual screening, molecular docking, and ADMET explored several inhibitors with CPD0297, CPD0298, and CPD0301 showing the most promising profiles. MDS parameters, including RMSD, RMSF, RG, SASA, BSASA, average-distance, minimum-distance, number of contacts, hydrogen-bond dynamics, PCA, FEL, DCCM, porcupine plot, correlated-anticorrelated 3D network, and secondary structure analysis, confirmed the stability of KEAP1–ligand complexes. MM/GBSA algorithm estimated binding free energies between -27.27 and -23.26 kcal/mol. Per-residue decomposition analysis revealed that the contributed residues to the binding free energy. DFT calculations demonstrated stable electronic properties and reactivity profiles of these ligands. We explored CPD0297, CPD0298, and CPD0301 as promising KEAP1 inhibitors, representing lead compounds for the development of targeted therapeutics in the treatment of CKD.

Aspergillus lentulus (A. lentulus) is an emerging pathogenic fungus with intrinsic resistance to multiple antifungal agents. Understanding its pathogenic mechanisms and the host’s responses is essential for the development of effective therapeutic strategies. The Galleria mellonella (G. mellonella) larvae model offers a convenient and physiologically relevant in vivo system to investigate fungal virulence and host–pathogen interactions, including the dynamics of oxidative stress. In this study, G. mellonella larvae were infected with A. lentulus to assess its virulence. Larval survival rates and intestinal histopathology were evaluated post-infection. Oxidative stress responses were characterized by quantifying intracellular reactive oxygen species (ROS) levels and measuring the activity of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). Additionally, malondialdehyde (MDA) levels were measured as an indicator of lipid peroxidation. At 24h post-infection, A. lentulus significantly reduced larval survival and caused notable intestinal tissue damage, although its virulence was lower compared to Aspergillus fumigatus (A. fumigatus). The infection induced a marked increase in oxidative stress, as indicated by elevated ROS levels (p < 0.01), reduced activities of the antioxidant enzymes SOD, CAT, and GST, and a 57

Esophageal squamous cell carcinoma (ESCC) is characterized by immune evasion and poor clinical outcomes. Autophagy has been implicated in tumor-immune interactions, but the molecular factors linking autophagy-associated processes to immune modulation in ESCC remain incompletely defined. We analyzed PSD3 expression in ESCC tissues and its association with prognosis and MHC-I-related molecules. Protein interactions were assessed by co-immunoprecipitation. Autophagy-associated marker changes, autophagic flux, total MHC-I protein levels, and immune cell infiltration were evaluated following PSD3 knockdown in murine and human ESCC models using Western blotting, tandem fluorescent LC3 reporter assays, immunohistochemistry, and single-cell RNA sequencing. Epistasis analysis was performed by silencing ATG7 following PSD3 knockdown. PSD3 was upregulated in ESCC and associated with unfavorable prognosis. PSD3 knockdown was accompanied by changes in autophagy-associated markers and reduced autophagosome abundance. In KYSE150 cells, tandem fluorescent mCherry-eGFP-LC3B analysis showed that PSD3 silencing impaired autophagic flux. PSD3 co-immunoprecipitated with ATG7, BAG3 and TBK1, supporting its association with autophagy-related protein complexes. PSD3 knockdown increased total MHC-I protein levels and was associated with enhanced immune cell infiltration in syngeneic tumor models. Furthermore, ATG7 silencing following PSD3 knockdown selectively restored HLA-E expression, while HLA-ABC and HLA-F showed no clearly distinguishable change. These findings support a working model in which PSD3 is linked to autophagy-associated immune modulation in ESCC. While additional studies are required to define pathway hierarchy and antigen-presentation function more directly, PSD3 emerges as a candidate molecular node for further mechanistic and translational investigation.

Large segmental bone defects have long posed a significant clinical challenge in orthopedics, primarily due to limited osteogenic potential and extended healing durations. Metallic biomaterials, such as tantalum, have been extensively employed in bone regeneration due to their superior mechanical strength and favorable early-stage osseointegration. However, their inherent bioinertness frequently results in complications, including implant subsidence and aseptic loosening over prolonged periods, ultimately compromising the repair outcome. To address these challenges, we developed a porous tantalum–biodegradable polymer composite scaffold with a triply periodic minimal surface (TPMS) architecture, aiming to systematically elucidate how structural design modulates polymer degradation kinetics and regulates the biological behavior of bone marrow mesenchymal stem cells (BMSCs). Through evaluating composite hydrogels composed of lithium magnesium silicate (LAP), gelatin (GE), and sodium alginate (SA) at various concentrations, we identified the 20 g/L LAP formulation as injectable and capable of forming a well-organized porous architecture upon freeze-drying. Subsequently, three distinct TPMS-based porous tantalum scaffolds, i.e., Diamond (D)-type, Gyroid (G)-type, and fused D–G (FDG) hybrid, were fabricated, and the optimized GE–SA–LAP polymer hydrogel was infused into each structure. The results demonstrated that the pore architecture played a decisive role in regulating polymer degradation dynamics: the D-type scaffold exhibited slower degradation (35.2