Advanced Science

Metal–metal bonding has played a pivotal role in advancing human technologies across various industrial sectors. As devices continue to miniaturize, there is an increasing need for efficient bonding techniques capable of achieving metal–metal bonds at smaller length scales. In this study, a facile but effective bonding technique is developed that enables the bonding of randomly oriented copper with copper nanomembranes under low temperatures and pressures. The fabricated copper nanomembranes, with a thickness of ≈50 nm and a width of 1 cm or above, exhibit a unique heterogeneous nanostructure, comprising copper nanocrystals along with nano‐copper‐oxide dispersions. Consequently, these copper nanomembranes display exceptional mechanical properties, including an ultra‐low elastic modulus of ≈35 GPa, a remarkable yield strength of ≈1 GPa, and excellent ductility of ≈40%, overcoming the conventional strength‐ductility trade‐off observed in various copper alloys. Most importantly, these ultra‐soft copper nanomembranes serve as metallic “glues”, promoting grain growth across the bonding interface between randomly oriented copper surfaces. This process leads to an average interfacial shear strength of up to 73 MPa at room temperature, representing an approximate 35 times increase in bonding strength compared to direct copper–copper bonding achieved under identical temperature and pressure conditions.

Polycystic ovary syndrome (PCOS) affects reproductive and cardiometabolic health, yet its pathogenesis remains unclear. Emerging evidence links hemoglobin levels to metabolic disorders, suggesting a potential role in PCOS development. Here, we integrated a large‐scale cohort study, Mendelian randomization (A genetic tool to infer causal relationships), bioinformatics analyses, and in vitro experiments to investigate the relationship between hemoglobin levels and PCOS. In a cohort of 20 602 women, each 10 g L⁻¹ elevation in hemoglobin levels is associated with 22% higher odds of PCOS (adjusted odds ratio: 1.22, 95% confidence interval: 1.15–1.29, P < 0.001) and PCOS manifestations, particularly hyperandrogenism. Mendelian randomization analysis confirms that higher hemoglobin levels are associated with increased PCOS risk and elevated testosterone levels. The hypoxia‐inducible factor 1 (HIF‐1) pathway is enriched, identifying three testosterone‐associated genes (nuclear factor kappa B (NFKB1), insulin receptor (INSR), protein kinase C alpha. Colocalization and druggability analysis supports shared genetic regions and confirmed these genes as druggable targets. Upregulation of NFKB1 and INSR are confirmed in both blood and ovarian granulosa cells of PCOS patients. The findings demonstrate that higher‐end normal hemoglobin levels are associated with increased PCOS risk, potentially through a mechanism of elevating testosterone levels involving the HIF‐1 pathway.

Significant progress is made in the treatment of metastatic colorectal cancer (mCRC) patients, however, therapeutic options remain limited for patients with mCRC. In recent years, traditional Chinese medicine (TCM) has gained significant attention. Among these, Huangqin Houpo decoction has demonstrated efficacy in mCRC treatment. Despite its promise, the active ingredients and mechanisms underlying its anticancer effects remain unclear. Using integrative pharmacological approaches, six compounds are identified as the primary active ingredients in Huangqin Houpo decoction. Among them, honokiol (H), magnolol (M), and baicalin (B) are found to exhibit a synergistic anticancer effect on CRC. The HMB combination significantly outperforms mono‐ or bi‐agent treatments in reducing tumor growth. Furthermore, the anticancer efficacy of the HMB combination surpasses that of medium‐ and high‐dose Huangqin Houpo decoction and the FOLFOX regimen. Notably, HMB is comparable in efficacy to the FOLFOIRI regimen. Most importantly, HMB is shown to enhance the sensitivity of CRC cells to anti‐PD‐1 immunotherapy in vivo. Mechanistic studies reveal that the HMB combination exerts its synergistic anticancer effects and enhances anti‐PD‐1 immunotherapy by inducing GSDME‐dependent pyroptosis. Our study will hopefully provide a potential therapeutic strategy for mCRC patients in the future.

Prenatal dexamethasone exposure (PDE) can impact adrenal corticosteroid synthesis in adult offspring. Furthermore, the adrenal gland can autonomously synthesize bile acids, but local bile acids accumulation has cytotoxic effects. This study found that PDE increased histone 3 lysine 27 acetylation (H3K27ac) levels in the promoter region of cholesterol 27 hydroxylase (CYP27A1) and its expression, as well as total bile acids (TBA) concentrations and enhanced endoplasmic reticulum stress (ERS) and inhibit steroid synthesis in adult male offspring rat adrenal glands. However, it is reversed in females. Tracing back to the prenatal stage and in combination with cellular experiments, it is further revealed that dexamethasone can regulate glucocorticoid receptor (GR)/SET binding protein 1 (SETBP1)/CYP27A1 signal pathway, consequently cause intracellular increase of bile acids. Finally, administration of nilvadipine (CYP27A1 inhibitor) to male offspring for 4 weeks after birth resulted in the reversal of PDE‐induced adrenal morphological and functional damage. In conclusion, PDE induces fetal adrenal corticosteroid dysfunction in adult male offspring by upregulating CYP27A1 promoter region H3K27ac levels and expression in the adrenal gland through the GR/SETBP1 signaling pathway. This effect persists beyond birth, leading to bile acids local increase and subsequent enhancement of ERS, ultimately inducing cellular dysfunction in adult adrenal glands.

Traditional imaging modalities used to monitor the diameter of aortic aneurysms (AAs) often fail to follow pathological progression. Fibroblast activation protein (FAP), a key regulator of extracellular matrix (ECM) remodeling, plays a pivotal role in aortic disease. However, its expression in the aortic wall during aneurysm progression and its potential correlation with disease severity remains unexplored. Here, utilizing histology the levels of FAP are higher in the aortic wall of patients with AA compared to healthy controls. In three distinct animal models of AA, a progressive increase in FAP expression, coincides with the advancement of ECM remodeling. Notably, the levels of ⁶⁸Ga‐FAPI‐04 uptake in a rabbit model of abdominal AA (AAA) is positively correlated with aortic dilation (r = 0.84, p < 0.01), and the histological examination further confirmed that regions of high ⁶⁸Ga‐FAPI‐04 uptake exhibited both increased FAP expression and more severe pathological changes. The ⁶⁸Ga‐FAPI‐04 imaging in AA patients showed that the radiotracer specifically accumulated in the aortic walls of persistently dilated AA. These findings suggest that ⁶⁸Ga‐FAPI‐04 positron emission tomographic (PET) imaging, by visualizing FAP localization, allows for a non‐invasive approach to potentially monitor ECM remodeling during the AA progression.

Many cancer risk variants are located within enhancer regions and lack sufficient molecular interpretation. Here, we constructed the first comprehensive atlas of enhancer RNA (eRNA)‐mediated genetic effects from 28 033 RNA sequencing samples across 11 606 individuals, identifying 21 073 eRNA quantitative trait loci (eRNA‐QTLs) significantly associated with eRNA expression. Mechanistically, eRNA‐QTLs frequently altered binding motifs of transcription factors. In addition, 28.48% of cancer risk variants are strongly colocalized with eRNA‐QTLs. A pan‐cancer eRNA‐based transcriptome‐wide association study is conducted across 23 major cancer types, identifying 626 significant cancer susceptibility eRNAs predicted to modulate cancer risk via eRNA, from which 54.90% of the eRNA target genes are overlooked by traditional gene expression studies, and most are essential for cancer cell proliferation. As proof of principle validation, the enhancer functionality of two newly identified susceptibility eRNAs, CCND1e and SNAPC1e, is confirmed through CRISPR inhibition and shRNA‐mediated knockdown, resulting in a marked decrease in the expression of their respective target genes, consequently suppressing the proliferation of prostate cancer cells. The study underscores the essential role of eRNA in unveiling new cancer susceptibility genes and establishes a strong framework for enhancing our understanding of human cancer etiology.

Severe bone and cartilage defects caused by trauma are challenging to treat, often resulting in poor outcomes. An endogenous electric field (EnEF) is crucial for bone regeneration, making electrical materials a promising therapy. This review provides a comprehensive overview of the role of bioelectric signals in bone and cartilage cells, alongside recent advancements in electrical biomaterials, with particular emphasis on nanogenerators, piezoelectric materials, triboelectric scaffolds, and zwitterionic hydrogels. It further investigates the impact of these electrical biomaterials on bone and cartilage regeneration, as well as the applications of both endogenous and exogenous electrical stimulation (ES) and the mechanisms underlying ES‐induced cellular and molecular responses. Finally, the review underscores future directions for ES systems in tissue engineering, emphasizing the critical importance of integrating structural integrity, mechanical properties, and electrical signal delivery into intelligent implantable scaffolds.

The current treatment of triple‐negative breast cancer (TNBC) is still primarily based on platinum‐based chemotherapy. However, TNBC cells frequently develop resistance to platinum and experience relapse after drug withdrawal. It is crucial to specifically target and eliminate cisplatin‐tolerant cells after platinum administration. Here, it is reported that upregulated N ⁶‐methyladenosine (m⁶A) modification drives the development of resistance in TNBC cells during cisplatin treatment. Mechanistically, histone deacetylase 2 (HDAC2) mediates delactylation of methyltransferase‐like 3 (METTL3), facilitating METTL3 interaction with Wilms’‐tumor‐1‐associated protein and subsequently increasing m⁶A of transcript‐associated DNA damage repair. This ultimately promotes cell survival under cisplatin. Furthermore, pharmacological inhibition of HDAC2 using Tucidinostat can enhance the sensitivity of TNBC cells to cisplatin therapy. This study not only elucidates the biological function of lactylated METTL3 in tumor cells but also highlights its negative regulatory effect on cisplatin resistance. Additionally, it underscores the nonclassical functional mechanism of Tucidinostat as a HDAC inhibitor for improving the efficacy of cisplatin against TNBC.

Chemo‐immunotherapy, combining systemic chemotherapeutic drugs and immune checkpoint blockers, is a promising paradigm in cancer treatment. However, challenges such as limited induction of immune responses and systemic immune toxicity have hindered its clinical applications. Here, a zeolite imidazolate framework‐8 (ZIF‐8) that encapsulates mitoxantrone (MIT), an immune cell death (ICD)‐inducing chemotherapeutic agent (MIT@ZIF‐8), is synthesized using a one‐pot aqueous‐phase process. ZIF‐8 serves as a dual‐functional nanomaterial for chemo‐immunotherapy: a carrier to enhance tumor uptake of MIT for improved chemotherapy efficacy, and a pyroptosis inducer to amplify MIT‐induced ICD for augmented anti‐tumor immune responses. As a result, in vivo administration of MIT@ZIF‐8 markedly inhibits tumor growth in both immunologically “hot” colon cancer and immunologically “cold” prostate cancer. Moreover, MIT@ZIF‐8 treatment increases the abundance of cytotoxic CD8⁺ T cells and reduces the amount of immunosuppressive regulatory T cells in tumors, thereby enhancing anti‐tumor immunity and sensitizing prostate cancer to anti‐CTLA‐4 immunotherapy. In summary, MIT@ZIF‐8 offers a highly translational approach for chemo‐immunotherapy.

Sensitized triplet–triplet annihilation photon upconversion (sTTA‐UC) allows blue‐shifting non‐coherent low‐intensity light and is potentially useful in solar‐powered devices, bioimaging, 3D printing, and other applications. For technologically viable solar energy harvesting systems, solid materials that capture a large fraction of the solar spectrum and efficiently upconvert the absorbed energy must be developed. Here, it is shown that broadband‐to‐blue UC is possible in air‐tolerant, easy‐to‐access, nanostructured polymers comprising a rigid hydrophilic matrix and liquid nanodroplets with dimensions on the order of tens of nanometers. The droplets contain 9,10‐bis[(triisopropylsilyl)ethynyl] anthracene (TIPS‐Ac) as emitter/annihilator and palladium(II) octaethyl porphyrin (PdOEP) and palladium(II) meso‐tetraphenyl tetrabenzoporphine (PdTPBP) as sensitizers. The confinement of the three dyes in the liquid domains renders the various bimolecular energy transfer processes that are pivotal for the TIPS‐Ac's triplet sensitization highly efficient, and the simultaneous use of multiple light harvesters with triplet energy levels resonant with the emitter/annihilator increases the absorption bandwidth to ca. 150 nm. The UC process at low power densities is most efficient when both sensitizers are simultaneously excited, thanks to their confinement in the nanodroplets, which leads to an increase in the triplet density, and therefore TTA rate and yield, optimizing the use of the harvested energy.

Effective management of serious respiratory diseases, such as asthma and recalcitrant rhinitis, remains a global challenge. Here, it is shown that induced sputum supernatants (ISS) from patients with asthma contain higher levels of cell‐free DNA (cfDNA) compared to that of healthy volunteers. Although cfDNA scavenging strategies have been developed for inflammation modulation in previous studies, this fall short in clinical settings due to the excessive neutrophil extracellular trap (NET) formation, reactive oxygen and nitrogen species (RONS) and bacterial infections in injured airway tissues. Based on this, a multifunctional boron‐based 2D nanoplatform B‐PM is designed by coating boron nanosheets (B‐NS) with polyamidoamine generation 1 (PG1) dendrimer, which can simultaneously target cfDNA, NETs, RONS, and bacteria. The effects of B‐PM in promoting mucosal repair, reducing airway inflammation, and mucus production have been demonstrated in model mice, and the therapeutic effect is superior to dexamethasone. Furthermore, flow cytometry with clustering analysis and transcriptome analysis with RNA‐sequencing are adopted to comprehensively evaluate the in vivo anti‐inflammation therapeutic effects. These findings emphasize the significance of a multi‐targeting strategy to modulate dysregulated inflammation and highlight multifunctional boron‐based 2D nanoplatforms for the amelioration of respiratory inflammatory diseases.

The hypermetabolic response associated with burns is characterized by skeletal muscle atrophy and an increased incidence of disability and death. Significant remodeling of the gut microbiota occurs after severe burn trauma. However, the specific mechanisms by which gut microbiota contribute to burn‐induced muscle atrophy remain unexplored. The results showed that the disruption of the gut microbiota exacerbated skeletal muscle atrophy. Fecal metabolite analysis revealed perturbations, primarily within the tryptophan (Trp) metabolic pathway. Animal models further demonstrated that gut microbiota disorder enhanced the expression of indoleamine 2,3‐dioxygenase 1 (IDO‐1) in the colon, ultimately resulting in Trp depletion and increased kynurenine (Kyn) levels in the serum and skeletal muscle. Excessive colonic Kyn is released into circulation, transported into skeletal muscle cells, and binds to the aryl hydrocarbon receptor (AHR), consequently triggering AHR nuclear translocation and initiating the transcription of skeletal muscle atrophy‐related genes. Notably, serum samples from patients with burns exhibited Trp depletion, and Trp supplementation alleviated skeletal muscle atrophy in rats with burns. This study, for the first time, demonstrates that gut microbiota dysbiosis upregulates colonic IDO‐1, promotes Trp‐Kyn metabolism, and exacerbates burn‐induced skeletal muscle atrophy, suggesting that Trp supplementation may be a potential therapeutic strategy.

Supramolecular dynamic room temperature phosphorescence (RTP) is the focus of current research because of its wide application in biological imaging and information anti‐counterfeiting. Herein, a time‐dependent supramolecular lanthanide phosphorescent 4D assembly material with multicolor luminescence including white, which is composed of 4‐(4‐bromophenyl)‐pyridine salt derivative (G), inorganic clay (LP)/Eu complex and pyridine dicarboxylic acid (DPA) is reported. Compared with the self‐assembled nanoparticle G, the lamellar assembly G/LP showed the double emission of fluorescence at 380 nm and phosphorescence at 516 nm over time. Within 60 min, the phosphorescence lifetime and the quantum yield increases from none to 7.4 ms and 27.53% respectively, achieving the time‐dependent phosphorescence emission, due to the limitation of progressive stacking of LP electrostatically driven “domino effect.” Furthermore, the 4D assembly of DPA and G/LP/Eu leads to a time‐resolved multicolor emission from colorless to purple to white, which is successfully applied to information multi‐level logic anti‐counterfeiting and efficiently antibiotic selective sensor.

The 3D human pituitary organoid represents a promising laboratory model for investigating human pituitary diseases. Nonetheless, this technology is still in its nascent stage, with uncertainties regarding the cellular composition, intercellular interactions, and spatial distribution of the human pituitary organoids. To address these gaps, the culture conditions are systematically adjusted and the efficiency of induced pluripotent stem cells’ (iPSCs’) differentiation into pituitary organoids is successfully improved, achieving results comparable to or exceeding those of previous studies. Additionally, single‐cell RNA‐sequencing (scRNA‐seq) and stereomics sequencing (Stereo‐seq) are performed on the pituitary organoids for the first time, and unveil the diverse cell clusters, intricate intercellular interactions, and spatial information within the organoids. Furthermore, the SOX3 gene interference impedes the iPSCs’ differentiation into pituitary organoids, thereby highlighting the potential of pituitary organoids as an ideal experimental model. Altogether, the research provides an optimized protocol for the human pituitary organoid culture and a valuable transcriptomic dataset for future explorations, laying the foundation for subsequent research in the field of pituitary organoids or pituitary diseases.

Non‐coding RNAs (ncRNAs) are widespread across various genomic regions and play a crucial role in modulating gene expression and cellular functions, thereby increasing biological complexity. However, the relationship between ncRNAs and the production of heterologous recombinant proteins (HRPs) remains elusive. Here, a yeast library is constructed by deleting long intergenic ncRNAs (lincRNAs), and 21 lincRNAs that affect α‐amylase secretion are identified. Targeted deletions of SUT067, SUT433, and CUT782 are found to be particularly effective. Transcriptomic and metabolomic analyses of the top three strains indicate improvements in energy metabolism and cytoplasmic translation, which enhances ATP supply and protein synthesis. Moreover, a yeast strain, derived from the SUT433 deletion, that can secrete ≈4.1 g L⁻¹ of α‐amylase in fed‐batch cultivation through the modification of multiple targets, is engineered. This study highlights the significant potential of lincRNAs in modulating cellular metabolism, providing deep insights and strategies for the development of more efficient protein‐producing cell factories.

The use of piezoelectric devices as wireless electrical stimulators is an emerging research topic. In this study, piezoelectric microdevices, consisting of ZnO nanosheets (NSs) functioning as piezoelectric nanogenerators (NGs) grown on top of silicon microparticles, to electrically stimulate cell are designed. The morphology of the ZnO NSs is optimized by tuning the thickness of the aluminum nitride (AlN) catalyst layer and adjusting the growth duration. ZnO NSs grown on thinner AlN layers (≤ 200 nm) and subjected to 9 h of hydrothermal growth exhibit the most suitable characteristics for cell stimulation, balancing crystal size, and electric field generation. The generation of a local electric field capable of exciting osteoblast cells is inferred from finite element simulations and intracellular calcium influx measurements. The internalization rate of silicon microdevices of varying sizes (3 × 3, 6 × 10, 12 × 18 µm²) by osteosarcoma (Saos‐2) and primary human osteoblast (hOB) cells.is assessed The results show that smaller devices have higher internalization rates, particularly in tumoral Saos‐2 cells, while primary cells exhibit minimal internalization (< 10%) across all particle sizes. This study presents an optimized piezoelectric microdevice, based on a scalable and customizable fabrication process, for minimally invasive bioelectronic applications, offering accurate electrical cell stimulation while minimizing unwanted internalization.

The freezing of water drops on cold solid surfaces is ubiquitous in nature, and generally causes serious technological, engineering, and economic issues in industrial applications. Despite longstanding research efforts, existing knowledge on dropwise freezing is still limited, as this phase‐change phenomenon is always accompanied by complex heat and mass transfer processes. Herein, drop‐freezing phenomena in condensation frosting are investigated under standard laboratory conditions of humidity and pressure, highlighting their distinctions from those under some limiting conditions. Condensate halos consisting of massive tiny droplets are observed to form, grow, and eventually fade in a well‐defined region around freezing supercooled drops on sufficiently hydrophobic surfaces with low thermal conductivities. The detailed halo evolution is very different from that reported previously in ultradry and low ambient pressure environments, and it shows no identifiable effect on the long‐term frost propagation. By combining optical and thermal imaging techniques, this study scrutinizes the halo pattern evolution involving multiphase transitions on timescales from milliseconds to seconds, assesses the halo characteristics at each stage, and elucidates the underlying mechanisms. The work expands the fundamental understanding of complex dropwise freezing dynamics, and relevant findings can provide important guidance for developing anti‐icing/frosting strategies.

Syn fibrils, a key pathological hallmark of Parkinson's disease, is closely associated with disease initiation and progression. Several small molecules are found to bind or dissolve α‐syn fibrils, offering potential therapeutic applications. Here, an innovative optical tweezers‐based, fluorescence‐combined approach is developed to probe the mechanical characteristics of α‐syn fibrils at the single‐molecule level. When subjected to axial stretching, local deformation within α‐syn fibrils appeared at forces above 50 pN. These structural alternations occurred stepwise and are irreversible, suggesting unfolding of individual α‐syn molecules or subdomains. Additionally, α‐syn fibrils exhibits high heterogeneity in lateral disruption, with rupture force ranging from 50 to 500 pN. The impact of different compounds on the structure and mechanical features of α‐syn fibrils is further examined. Notably, epigallocatechin gallate (EGCG) generally attenuates the rupture force of fibrils by wedging into the N‐terminal polar groove and induces fibril dissociation. Conversely, copper chlorophyllin A (CCA) attaches to four different sites wrapping around the fibril core, reinforcing the stability of the fibril against rupture forces. The work offers an effective method for characterizing single‐fibril properties and bridges compound‐induced structural alternations with mechanical response. These insights are valuable for understanding amyloid fibril mechanics and their regulation by small molecules.

In this study, an electret‐inspired, charge‐injected hydrogel called QOSP hydrogel (QCS/OD/SDI/PANI/PS/Plasma) that promotes scar‐free healing of bacteria‐infected burns through bioelectrical stimulation and immune modulation, is presented. The hydrogel, composed of quaternized chitosan (QCS), oxidized dextran (OD), sulfadiazine (SDI), polystyrene (PS), and polyaniline nanowires (PANI), forms a conductive network capable of storing and releasing electric charges, emulating an electret‐like mechanism. This structure delivers bioelectrical signals continuously, enhancing wound healing by regulating immune responses and minimizing fibrosis. In a mouse model of second‐degree burns infected with Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA), the hydrogel accelerates wound healing by 32% and reduces bacterial load by 60%, significantly inhibited scar formation by 40% compared to controls. QOSP hydrogel modulates the Th1/Th2 immune balance toward a Th1‐dominant antifibrotic state through quaternized chitosan, thereby reducing collagen deposition by 35%. Electro‐dielectric characterization reveals a dielectric constant of 6.2, a 34% improvement in conductivity (3.33 × 10⁻⁵ S/m) and a 30 °C increase in thermal stability. Proteomic analysis highlights a 50% down‐regulation of pro‐inflammatory and pro‐fibrotic pathways, suggesting a controlled immune response conducive to scar‐free healing. This study underscores the potential of bioelectrically active hydrogels as a novel approach for treating infected wounds prone to scarring.

Alzheimer's disease (AD) is a progressive and irreversible brain disorder with extensive neuronal loss in the neocortex and hippocampus. Current therapeutic interventions focus on the early stage of AD but lack effective treatment for the late stage of AD, largely due to the inability to replenish the lost neurons and repair the broken neural circuits. In this study, by using engineered adeno‐associated virus vectors that efficiently cross the blood–brain‐barrier in the mouse brain, a brain‐wide neuroregenerative gene therapy is developed to directly convert endogenous astrocytes into functional neurons in a mouse model of AD. It is found that ≈500 000 new neurons are regenerated and widely distributed in the cerebral cortex and hippocampus. Importantly, it is demonstrated that the converted neurons can integrate into pre‐existing neural networks and improve various cognitive performances in AD mice. Chemogenetic inhibition of the converted neurons abolishes memory enhancement in AD mice, suggesting a pivotal role for the newly converted neurons in cognitive restoration. Together, brain‐wide neuroregenerative gene therapy may provide a viable strategy for the treatment of AD and other brain disorders associated with massive neuronal loss.

Selective delivery of imaging agents to pancreatic cancer cells (PCCs) within the highly desmoplastic tumors of pancreatic ductal adenocarcinoma (PDAC) represents a significant advancement. This approach allows for precise labeling of PCCs while excluding cancer‐associated fibroblasts (CAFs), thereby enhancing both research and diagnostic capabilities. Additionally, it holds the potential to target and eliminate PCCs precisely without harming the surrounding stromal cells in the PDAC tumor microenvironment (TME). In this study, DNA origami‐cyanine (Do‐Cy) nanocomplexes are synthesized to image KRAS‐mutant PCCs selectively in the PDAC TME. These Do‐Cy nanocomplexes are hypothesized to be internalized preferentially to KRAS‐mutant PCCs over CAFs via elevated macropinocytosis. Several designs of Do‐Cy nanocomplexes are synthesized and characterized their cellular uptake using both engineered in vitro and xenograft pancreatic cancer models. The results are further discussed for the implication of precision delivery of therapeutic and imaging agents to KRAS‐mutant cancers.

Cubane‐type metal clusters respond uniquely to stimuli like light and electric potential, resulting in behaviors such as crystal‐to‐crystal phase transitions. While structural adaptability is known to be linked to these responses, direct experimental evidence for the associated structural changes has been missing. This study addresses this gap by examining the structural dynamics of the copper(I) iodide cubane (Cu4I4(py)4, py = pyridine) upon photoexcitation using time‐resolved X‐ray liquidography. The results reveal: 1) 100 picoseconds (ps) after excitation, two distinct excited states—the cluster‐centered triplet (³CC) state and the (metal+halide)‐to‐ligand charge transfer triplet (³(M/X)LCT) state—are present; 2) the ³(M/X)LCT state decays with an apparent time constant of 1.21 ns, primarily transitioning to the ³CC state, with a small fraction undergoing decay to the ground state (GS); and 3) the ³CC state eventually returns to the GS. The molecular structures, provided for these states serve as benchmarks for theoretical studies. Importantly, the ³CC structure exhibits significant distortion in the Cu4I4 core and reduced symmetry, findings that are unanticipated by previous models. This comprehensive investigation deepens the understanding of the structural transformations occurring upon photoexcitation, with a potential impact on future applications of these compounds as versatile components in photosensitive metal–organic frameworks.

Integrin and focal adhesion can regulate cytoskeleton distribution to govern actin‐related force remodeling and play an important role in nuclear configuration and force‐sensing mechanotransduction of stem cells. However, further exploration of the interaction between actinin complex and myosin, kinetics, and molecular mechanism of cytoskeleton structures to nucleate within the engineered stem cells is vague. An extensive comprehension of cell morphogenesis, force remodeling, and nuclear force‐sensing mechanotransduction is essential to reveal the basic physical principles of cytoskeleton polymerization and force‐related signaling delivery. Advanced microarrays are designed to determine heterogeneous cell morphology and cell adhesion behaviors in stem cells. The heterogeneity from the engineered microarrays is transferred into nuclei to regulate nuclear configuration and force‐sensing mechanotransduction by the evaluation of Lamins, YAP, and BrdU expression. Tuning the activation of adhesion proteins and cytoskeleton nucleators to adjust heterogeneous cell mechanics may be the underlying mechanism to change nuclear force‐sensing configuration in response to its physiological mechanotransduction in microarrayed stem cells.

Extracellular matrix (ECM) viscoelasticity has emerged as a potent regulator of physiological and pathological processes, including cancer progression. Spatial confinement within the ECM is also known to influence cell behavior in these contexts. However, the interplay between matrix viscoelasticity and spatial confinement in driving epithelial cell mechanotransduction is not well understood, as it relies on experiments employing purely elastic hydrogels. This work presents an innovative approach to fabricate and micropattern viscoelastic polyacrylamide hydrogels with independently tuneable Young's modulus and stress relaxation, specifically designed to mimic the mechanical properties observed during breast tumor progression, transitioning from a soft dissipative tissue to a stiff elastic one. Using this platform, this work demonstrates that matrix viscoelasticity differentially modulates breast epithelial cell spreading, adhesion, YAP nuclear import and cell migration, depending on the initial stiffness of the matrix. Furthermore, by imposing spatial confinement through micropatterning, this work demonstrates that confinement alters cellular responses to viscoelasticity, including cell spreading, mechanotransduction and migration. These findings establish ECM viscoelasticity as a key regulator of epithelial cell mechanoresponse and highlight the critical role of spatial confinement in soft, dissipative ECMs, which was a previously unexplored aspect.

Laser‐induced graphene (LIG) has been so far obtained from polymer precursors and proposed for numerous applications, including various types of sensors and energy storage solutions. This study examines a radically different class of new precursors for LIG, distinct from polymers: inks and dyes. The identification of specific organic dyes present in commercial markers demonstrates that the aromatic structure, in conjunction with high thermal stability (residual weight > 20% at 800°C), are key factors for laser‐induced pyrolysis. Eosin Y is identified as an excellent LIG precursor, comparable with well‐known polyimide. The unique properties of dyes allow for dispersion in various media, such as acrylic binder. A dye concentration of 0.75 mol L⁻¹ in acrylic binder results in a conductivity of 34 ± 20 S cm⁻¹ for LIG. The composition and microstructure of LIG from dyes are thoroughly characterized, revealing peculiar features. A versatile “Paint & Scribe” methodology is introduced, enabling to integrate LIG tracks onto any wettable surface, and in particular onto printed and flexible electronics. A process for obtaining freestanding and transferrable LIG is demonstrated by dissolving acrylic paint in acetone and floating LIG in water. This advancement offers novel avenues for diverse applications that necessitate a transfer process of LIG.