Recent studies have highlighted the notable involvement of the crosstalk between hypoxia-inducible factor 2 alpha (HIF2α) and Wnt signaling components in tumorigenesis. However, the cellular function and precise regulatory mechanisms of HIF2α and Wnt signaling interactions in clear cell renal cell carcinoma (ccRCC) remain elusive. To analyze the correlation between HIF2α and Wnt signaling, we utilized the Cancer Genome Atlas - Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) public database, HIF2α RNA sequencing data, and conducted luciferase reporter assays. A Wnt-related gene set was employed to identify key regulators of Wnt signaling controlled by HIF2α in ccRCC. Furthermore, we assessed the biological effects of TCF7L2 on ccRCC metastasis and lipid metabolism in both in vivo and in vitro settings. Our outcomes confirm TCF7L2 as a key gene involved in HIF2α-mediated regulation of the canonical Wnt pathway. Functional studies demonstrate that TCF7L2 promotes metastasis in ccRCC. Mechanistic investigations reveal that HIF2α stabilizes TCF7L2 mRNA in a method based on m⁶A by transcriptionally regulating METTL3. Up-regulation of TCF7L2 enhances cellular fatty acid oxidation, which promotes histone acetylation. This facilitates the transcription of genes connected to epithelial–mesenchymal transition and ultimately enhances metastasis of ccRCC. These outcomes offer a novel understanding into the involvement of lipid metabolism in the signaling pathway regulation, offering valuable implications for targeted treatment in ccRCC.

Construction of laser heterodyne interferometric bench to measure tiny translation and tilt with picometer- and nanoradian-level sensitivity in the millihertz band is critical for the success of spaceborne gravitational wave detection, including the LISA, Taiji, and Tianqin missions. In this paper, we report on the construction and testing of a laser heterodyne interferometric bench that contains two optical path designs, the dual-beam heterodyne interferometry and the polarization-multiplexing heterodyne interferometry. The measurement sensitivity of translation and tilt reaches below 3 pm/Hz^1/2 and 12 nrad/Hz^1/2 for frequencies above 10 mHz, respectively. As a technical verification platform, stabilization loops of amplitude and phase and coherence analysis are also conducted through the bench. Furthermore, we demonstrate initial implements of phase-locking technology and multiple degree of freedom measurements as the extended applications of the constructed bench. The achieved results show that the laser interferometric bench would serve as an excellent experimental platform for the technology demonstration and verification of future Chinese spaceborne gravitational wave detection.

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.

Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury. Here, we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice. Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases. In 8-week swimming model in wild-type (WT) and miR-210 knockout (KO) rats, we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity. In neonatal rat cardiomyocytes, miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size. Additionally, miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and AC16 cell line, indicating its functional roles in human cardiomyocytes. We further identified miR-210 target genes, cyclin-dependent kinase 10 (CDK10) and ephrin-A3 (EFNA3), that regulate cardiomyocyte proliferation and apoptosis. Finally, miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury. We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury. In summary, this study elucidates the role of miR-210, an exercise-responsive miRNA, in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth. Furthermore, miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury. Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210, which can alleviate I/R injury and promote cardioprotection.

Inverted perovskite solar cells based on weakly polarized hole-transporting layers suffer from the problem of polarity mismatch with the perovskite precursor solution, resulting in a nonideal wetting surface. In addition to the bottom-up growth of the polycrystalline halide perovskite, this will inevitably worse the effects of residual strain and heterogeneity at the buried interface on the interfacial carrier transport and localized compositional deficiency. Here, we propose a multifunctional hybrid pre-embedding strategy to improve substrate wettability and address unfavorable strain and heterogeneities. By exposing the buried interface, it was found that the residual strain of the perovskite films was markedly reduced because of the presence of organic polyelectrolyte and imidazolium salt, which not only realized the halogen compensation and the coordination of Pb²⁺ but also the buried interface morphology and defect recombination that were well regulated. Benefitting from the above advantages, the power conversion efficiency of the targeted inverted devices with a bandgap of 1.62 eV was 21.93% and outstanding intrinsic stability. In addition, this coembedding strategy can be extended to devices with a bandgap of 1.55 eV, and the champion device achieved a power conversion efficiency of 23.74%. In addition, the optimized perovskite solar cells retained 91% of their initial efficiency (960 h) when exposed to an ambient relative humidity of 20%, with a T80 of 680 h under heating aging at 65 °C, exhibiting elevated durability.

Ferroptosis, a nonapoptotic form of cell death, is an emerging potential therapeutic target for various diseases, including cancer. However, the role of ferroptosis in pancreatic cancer remains poorly understood. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis and chemotherapy resistance, attributed to its high Kirsten rats arcomaviral oncogene homolog mutation rate and severe nutritional deficits resulting from a dense stroma. Several studies have linked rat sarcoma (RAS) mutations to ferroptosis, suggesting that inducing ferroptosis may be an effective strategy against oncogenic RAS-bearing tumors. We investigated the role of Family With Sequence Similarity 60 Member A (FAM60A) in this study, a protein closely associated with a poor prognosis and highly expressed in PDAC and tumor tissue from Kras^G12D/+;Trp53^R172H/+; Pdx1-Cre mice, in regulating ferroptosis, tumor growth, and gemcitabine sensitivity in vitro and in vivo. Our results demonstrate that FAM60A regulates 3 essential metabolic enzymes, ACSL1/4 and GPX4, to protect PDAC cells from ferroptosis. Furthermore, we found that YY1 transcriptionally regulates FAM60A expression by promoting its transcription, and the Hippo-YY1 pathway is restricted in the low-amino-acid milieu in the context of nutrient deprivation, leading to downstream suppression of peroxisome proliferator-activated receptor and ACSL1/4 and activation of GPX4 pathways. Importantly, FAM60A knockdown sensitized PDAC cells to gemcitabine treatment. A new understanding of FAM60A transcriptional regulation pattern in PDAC and its dual function in ferroptosis reliever and chemotherapy resistance is provided by our study. Targeting FAM60A may therefore offer a promising therapeutic approach for PDAC by simultaneously addressing 2 major features of the disease (high RAS mutation rate and tumor microenvironment nutrient deficiency) and preventing tumor cell metabolic adaptation.

Achieving antitumor immunotherapy based on hybridization of multiple types of inactivated cells has attracted a lot of attention. However, the hybridized cells of disordered structure could result in the shedding of antigens and their transfer to immune cells, which suppresses tumor immunity through trogocytosis. Here, we report a strategy for in situ solidification of tumor whole cell by biomineralization for sustained stimulation of antitumor immunity. The near-infrared light was used to accelerate the breaking of Au=P bonds in auranofin, and the exposed Au atoms biomineralize at the secondary structure (β-corner) of the protein to form Au nanocrystals with in situ protein coronas in tumor cells. Au nanocrystals are anchored to the tumor cells through protein coronas, which fixes the morphology and antigens of whole tumor cells, rendering them physiologically inactive. Interestingly, this solidified tumor cell prevents immune cells from undergoing trogocytosis, which inhibits proximal and distal tumor growth. Thus, this study presents the strategy of solidified cells and its potential application in tumor immunotherapy.

Silica glass, known for its brittleness, weight, and non-biodegradable nature, faces challenges in finding suitable alternatives. Transparent wood, made by infusing polymers into wood, shows promise but is hindered by limited availability of wood in China and fire risks associated with its use. This study explores the potential of utilizing bamboo, which has a shorter growth cycle, as a valuable resource for developing flame-retardant, smoke-suppressing, and superhydrophobic transparent bamboo. A 3-layered flame-retardant barrier, composed of a top silane layer, an intermediate layer of SiO₂ formed through hydrolysis-condensation of Na₂SiO₃ on the surface, and an inner layer of Na₂SiO₃, has been confirmed to be effective in reducing heat release, slowing flame spread, and inhibiting the release of combustible volatiles, toxic smoke, and CO. Compared to natural bamboo and other congeneric transparent products, the transparent bamboo displays remarkable superiority, with the majority of parameters being notably lower by an entire order of magnitude. It achieves a long ignition time of 116 s, low total heat release (0.7 MJ/m²), low total smoke production (0.063 m²), and low peak CO concentration (0.008 kg/kg). Moreover, when used as a substrate for perovskite solar cells, the transparent bamboo displays the potential to act as a light management layer, leading to a marked efficiency enhancement of 15.29%. The excellent features of transparent bamboo make it an enticing choice for future advancements in flame-retardant glasses and optical devices.

Photodynamic therapy (PDT) has emerged as a promising approach for squamous cell carcinoma treatment but hindered by tumor hypoxia, acquired resistance, phototoxicity, and so on. To address these issues, we developed a smart strategy utilizing activable photosensitizers delivered by an aptamer-functionalized DNA probe (ADP). The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide (ASO) for recognition of Survivin mRNA. In the absence of the target, PDT remained quenched, thereby avoiding phototoxicity during circulation and nonselective distribution. With the aid of the aptamer, ADP achieved selective targeting of tumors. Upon internalization, ADP targeted recognized Survivin mRNA, triggering PDT activation, and releasing ASO to down-regulate Survivin expression and reverse tumor resistance. Consequently, the activable photosensitizers exhibited an “AND” logic gate, combining tumor-targeting delivery and tumor-related gene activation, thus enhancing its specificity. Additionally, the incorporation of hemin into the ADP provided catalase activity, converting tumor-abundant H₂O₂ into O₂, thereby ameliorating tumor hypoxia. The resulting functionalized G-quadruplex/hemin–DNA probe complex demonstrated targeted delivery and activation, minimized side effects, and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models. This study offers a unique and promising platform for efficient and safe PDT, thus holding great potential for future clinical translation and improved cancer therapy.