Lunar far-side samples returned by the Chang’e-6 mission offer unprecedented insights into regolith properties within the South Pole–Aitken basin, essential for advancing lunar exploration and in situ resource utilization. This paper presents an integrated characterization framework combining high-resolution x-ray micro-computed tomography with semisupervised machine learning to reconstruct and analyze 349,740 individual particles at high throughput. Morphological analysis demonstrates that far-side regolith exhibits greater irregularity than previously characterized near-side samples, with a median particle diameter of 60.51 μm and a mean 3-dimensional sphericity of 0.74—values distinct from those reported for Apollo and Chang’e-5 materials. Discrete element method simulations incorporating these high-fidelity morphologies under representative lunar surface confining pressures (5 to 15 kPa) reveal a high internal friction angle of 47.96° and a cohesion of 1.08 kPa. These parameters exceed Surveyor mission estimates and align with the upper range of Apollo program values, indicating enhanced mechanical strength and cohesion in far-side regolith. The superior mechanical properties arise primarily from pronounced particle irregularity promoting strong mechanical interlocking, potentially augmented by cementation from abundant glassy agglutinate phases. These findings establish critical geotechnical benchmarks for lunar far-side materials, providing essential design parameters for future robotic and crewed missions, landing site selection, and infrastructure development.

Triple-negative breast cancer (TNBC) represents a notably aggressive form of breast cancer, distinguished by heightened invasiveness and an important propensity for metastasis. The expression of ubiquitin D (UBD) is significantly increased in lung metastases associated with TNBC, correlating with unfavorable patient outcomes. Functional assays indicate that UBD promotes invasion, migration, and pulmonary colonization of TNBC cells in vivo. At the mechanistic level, UBD preserves matrix metalloproteinase 3 (MMP3) levels by inhibiting proteasomal degradation. A proteomic analysis has identified MMP3 as a crucial downstream mediator of UBD. Concurrently, chromatin immunoprecipitation and luciferase reporter assays demonstrate that the Spi-B transcription factor (SPIB) directly interacts with the UBD promoter, leading to the activation of its transcription. Collectively, these findings identify the SPIB/UBD/MMP3 axis as a pivotal regulator of TNBC metastasis, indicating its value for prognostic evaluation and targeted therapy.

Plasmacytoid dendritic cells (pDCs) are innate immune cells that produce type I interferons (IFNs) upon sensing nucleic acids via Toll-like receptor 9 (TLR9). Synthetic oligodeoxynucleotides CpGA and CpGB are widely used TLR9 agonists, yet only CpGA robustly induces IFN-α in pDCs. In contrast, CpGB drives much less IFN production. The mechanism underlying this ligand-specific response is not known. Here, we identify PIEZO1, a mechanosensory ion channel, as a regulator for this ligand-specific response. We show that CpGA, unlike CpGB, self-associates into large aggregates that generate membrane tension during cellular uptake, activating PIEZO1. This triggers calcium influx and localized F-actin assembly, retaining CpGA in early endosomes to sustain IRF7 activation and IFN production. PIEZO1 deficiency or inhibition abolishes CpGA-induced IFN responses, while PIEZO1 activation enhances IFN production by CpGB. Our findings reveal a hitherto unknown biophysical checkpoint in TLR9 signaling, where PIEZO1 translates membrane tension into spatially controlled TLR9 signaling. This study uncovers a novel role for mechanosensing in nucleic acid immunity, with implications for modulating IFN responses in infections and autoimmunity.

As pioneering immunotherapy approaches, chimeric antigen receptor T cell (CAR-T) and natural killer cell (CAR-NK) therapies have shown notable clinical effectiveness when addressing different kinds of hematologic malignancies. For example, the application and efficacy of CAR-T cell therapy in acute lymphocytic leukemia, large B cell lymphoma, mantle cell lymphoma, and multiple myeloma have been widely recognized. In addition, the safety and feasibility of CAR-NK therapy when used to treat refractory/recurrent large B cell lymphoma have been verified. In particular, CD19-targeted CAR-T cell therapy has achieved marked efficacy and breakthrough progress in treating relapsed and refractory B cell leukemia and lymphoma. Although CAR-T cell therapy has achieved significant effectiveness in treating these diseases, patients still face challenges, including primary resistance and secondary recurrence after treatment. The complex mechanisms of resistance and recurrence involve multiple factors, such as target cells, CAR cell characteristics, and immune suppression conditions. This review examines resistance and recurrence mechanisms in CAR-T and CAR-NK therapies while exploring current therapeutic strategies and future research directions.

The NLRP3 inflammasome is a pivotal component of the innate immune system, responding to infections and cellular damage. Its dysregulation has been implicated in numerous inflammatory diseases, although the mechanisms controlling its activation remain incompletely elucidated. Recent studies have highlighted the importance of posttranslational modifications, such as ubiquitination and SUMOylation, in regulating inflammasome activation. In this study, we demonstrate that SENP6, a SUMO-specific protease, negatively regulates NLRP3 inflammasome activation by promoting K48-linked polyubiquitination of NLRP3. SENP6-deficient macrophages exhibit enhanced NLRP3 activation and increased secretion of interleukin-1β (IL-1β) and IL-18, resulting in amplified inflammatory responses. Mechanistically, SENP6 interacts with NLRP3 and promotes its degradation through the autophagy–lysosomal pathway via K48-linked polyubiquitination. We further identified that SENP6 deSUMOylated NLRP3 at specific lysine residues (K23, K204, and K689), which was essential for maintaining NLRP3 stability. Additionally, SENP6 recruits the E3 ubiquitin ligase MARCHF7 to promote NLRP3 ubiquitination and subsequent degradation. In vivo, SENP6 deficiency exacerbates NLRP3 activation and lung inflammation in lipopolysaccharide-induced endotoxic shock-associated lung injury, and enhances inflammatory responses in alum-induced peritonitis. Our findings reveal a novel mechanism whereby SENP6 modulates NLRP3 inflammasome activation via SUMOylation, ubiquitination, and degradation, providing new insights into potential therapeutic strategies for inflammasome-related pathologies.

Autophagy is integral to the rapid proliferation of esophageal squamous cell carcinoma (ESCC), and its regulation presents a promising avenue for therapeutic intervention. Recent studies have elucidated the interplay between autophagy and glucose metabolism, while there is a paucity of anticancer drugs that concurrently target these 2 biological processes. In this study, we identified a natural compound, p-hydroxylcinnamaldehyde (CMSP), originally isolated from Cochinchina momordica seed (CMS) by our research team, which exhibits substantial anticancer activity against ESCC in both in vitro and in vivo models. The study demonstrates that CMSP induces apoptosis in ESCC cell lines and patient-derived organoid (PDO) models by disrupting autophagic flux. Mechanistically, CMSP specifically binds to the glycolytic enzyme LDHA in the cytoplasm, hindering its phosphorylation by blocking its membrane translocation and thereby disrupting its interaction with FGFR1. This inhibition results in decreased lactate production from glycolysis, reduced lysosomal acidity, and suppression of the AMPK/mTOR pathway, ultimately resulting in the blockade of autophagy and the induction of apoptosis. Furthermore, in vivo studies underscore the potential clinical application of CMSP in ESCC by disrupting autophagy. In summary, we propose a novel therapeutic strategy for the precision treatment of ESCC by simultaneously targeting glycolysis-mediated autophagy.

Head-mounted miniaturized microscopes have provided new capabilities for neuroscience by enabling neural imaging in freely behaving animals. The long-term application of these microscopes, however, is contingent upon specific and reliable cranial window designs. Here, we introduce optically guided and pre-assembled implantation (OGPI), a standardized cranial window technique designed for head-mounted miniaturized microscope imaging. OGPI employs a cost-effective, minimalist design and offers robust compatibility with miniaturized microscopes. This integrated method ensures precise implantation and supports chronic large-scale neural imaging in freely behaving animals for periods exceeding 8 months. The OGPI method is adaptable, supporting both semiautomated operation for enhanced throughput and manual operation for standard laboratory settings. Through behavioral assessments, we further demonstrate that animals with OGPI cranial windows exhibit preserved locomotor and spatial cognitive abilities. Leveraging this chronic window, we performed large-scale cortical imaging in mice engaged in a Y-maze navigation task. We found that the neurons’ tuning position, path, and acceleration were distributed in a “salt-and-pepper” pattern across multiple cortices. A subpopulation of neurons exhibiting conjunctive tuning to both spatial information and linear acceleration was identified, suggesting that the acceleration-tuned neurons required for the generation and updating of the spatial signal exist in the cortex. Further, population-level analyses of spatial representation in the cortex were conducted. A decoder and a classifier based on cortical activity accurately predicted the animal’s position and path. Altogether, our results establish OGPI as an enabling platform and a key methodological advancement for chronic imaging in freely behaving animals and reveal a widespread representation of spatial information in the cortex.

Fibroblast–myofibroblast transition (FMT) and the resultant renal fibrosis are central pathological features of chronic kidney disease (CKD). Epigenetic suppression of RASAL1 (Ras protein activator like 1), an antifibrotic regulator in fibroblasts, is a key driver of this process. However, the underlying mechanisms are only partially understood. Here, we identify histone deacetylase 3 (HDAC3) as a critical epigenetic suppressor of RASAL1 expression in FMT of renal fibrosis. In mouse models of renal fibrosis induced by unilateral ureteral obstruction and aristolochic acid I, RASAL1 suppression coincided with a preferential increase in HDAC3. Fibroblast-specific Hdac3 knockout mice exhibited preserved RASAL1 expression, attenuated FMT, and reduced renal fibrosis compared to wild-type controls. Consistently, pharmacological inhibition of HDAC3 with RGFP966 similarly restored RASAL1 expression, inhibited FMT, and alleviated renal fibrotic pathology. In cultured renal fibroblasts, HDAC3 overexpression or inhibition by RGFP966 inversely affected RASAL1 abundance and major FMT parameters, which was coregulated by the repressive transcriptional factor YY1 (Yin Yang 1). Notably, targeted silencing of RASAL1 abrogated the antifibrotic effects of HDAC3 inhibition both in vitro and in vivo, underscoring the functional significance of the HDAC3–YY1–RASAL1 axis in FMT and fibrogenesis. Given that FMT is a conserved feature of fibrotic diseases across multiple organs, restoring RASAL1 expression via HDAC3 and YY1 modulation offers promising therapeutic strategies for CKD and potentially broader fibrotic disorders.

The integration of multiband and multimode systems has substantially increased the complexity of electromagnetic interference, revealing critical limitations of existing absorbers in tuning efficiency and structural resilience. Here, we propose a nested microaerogel strategy to simultaneously improve the mechanical strength and microwave absorption (MA) performance of polyimide (PI) aerogel. By incorporating pomelo-peel-derived cellulose micronetworks and helical carbon nanocoil microaerogels to construct a gradient-nested framework, the long-standing issues of filler agglomeration and structural shrinkage in aerogels are effectively resolved. The aerogel combines low density, impact resistance, and thermal insulation with remarkable MA performance. The compressive strength reaches 1.3 MPa, which is about 20 times higher than pristine PI aerogel. Furthermore, it exhibits a minimum reflection loss of −50.16 dB, a broad effective absorption bandwidth of 7.44 GHz, and an ultrawide tunable range of 5.6 to 16.4 GHz. Benefiting from its exceptional mechanical properties and pressure-dependent tunability, the aerogel establishes a clear correlation between compression-induced capacitive response and MA performance. These features highlight its potential as a new generation of intelligent microwave absorbers with integrated sensing and adaptive regulation capabilities.