Intrinsic Response Research Articles

Robust intrinsic chirality empowered by pair of off-Γ accidental BICs in triangular lattice metasurface

Abstract Optical chiral metasurfaces with high-quality factor enhance light-matter interactions. However, intrinsic chirality based on breaking the symmetry-protected BIC hardly reveals strong circular dichroism (CD) against structural perturbations. Here, we propose a design of the intrinsic chirality empowered by a pair of off-Γ accidental BICs and demonstrate a robust intrinsic chiroptical response continuously exhibiting strong and sign-controllable transmitted CD up to 0.98 and stable high-quality factors under a wide range of perturbations of geometrical parameters. A triangular lattice with slant T-shaped meta-atom is employed to break all mirror symmetries. The at-Γ quality factor of the chiral resonance is enhanced by four C points and maintains in the range of 105 to 106. Our work is beneficial for designing chiral metasurfaces with a strong intrinsic chirality.

Time-Domain-Filtered Terahertz Nanoscopy of Intrinsic Light-Matter Interactions.

Terahertz (THz) technology holds great potential across diverse applications, including biosensing and information communications, but conventional far-field techniques are limited by diffraction. Near-field optical microscopy overcomes this barrier through a sharp tip that concentrates incident THz waves into nanometric volumes, detecting scattered near-field to reveal nanoscale optical properties. However, owing to the large THz wavelengths, resonant surface waves arising on the tip and cantilever obscure the intrinsic response. Here we combine near-field microscopy with THz time-domain spectroscopy and implement time-domain filtering with an elongated cantilever to eliminate this artifact, achieving intrinsic nanospectroscopy and nanoimaging. By applying this technique, we distinguish and characterize historical pigments of an ancient sculpture, such as vermilion and red lead, on the nanoscale. We also unravel deep-subwavelength localized resonance modes in THz optical antennas, demonstrating capabilities for THz nanophotonics. Our work advances THz nanoimaging and nanospectroscopy techniques to probe intrinsic nanoscale THz light-matter interactions.

Differential intrinsic firing properties in sustained and transient mouse alpha RGCs match their light response characteristics and persist during retinal degeneration.

Retinal ganglion cells (RGCs) are the neuronal connections between the eye and the brain conveying multiple features of the outside world through parallel pathways. While there is a large body of literature how these pathways arise in the retinal network, the process of converting presynaptic inputs into RGC spiking output is little understood. In this study, we show substantial differences in the spike generator across three types of alpha RGCs in female and male mice, the αON sustained, αOFF sustained and αOFF transient RGC. The differences in their intrinsic spiking responses match the differences of the light responses across RGC types. While sustained RGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient RGC type fired shortest action potentials enabling it to fire high-frequency transient bursts. The observed differences were also present in late-stage photoreceptor-degenerated retina demonstrating long-term functional stability of RGC responses even when presynaptic circuitry is deteriorated for long periods of time. Our results demonstrate that intrinsic cell properties support the presynaptic retinal computation and are, once established, independent of them.Significance Statement Spiking output from retinal ganglion cells (RGCs) has long been thought to be solely determined by synaptic inputs from the retinal network. We show that the cell-intrinsic spike generator varies across RGC populations and therefore that postsynaptic processing shapes retinal spiking output in three types of mouse alpha RGCs (αRGCs). While sustained αRGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient αRGC type fired shortest action potentials enabling them to fire high-frequency transient bursts. Computational modeling suggests that intrinsic response differences are not driven by dendritic morphology but by somatodendritc biophysics. After photoreceptor degeneration, the observed variability is preserved indicating stable physiology across the three αRGC types.

Predictors of self-care behaviors in hypertensive patients based on the protection motivation theory

IntroductionGlobally, hypertension is a significant public health concern and a leading cause of premature death. Since this disease is incurable, it is necessary to promote patients’ self-care behaviors to control it. The goal of this research was to identify the elements that influence self-care actions in individuals with hypertension, utilizing the Protection Motivation Theory (PMT) framework.MethodsA study was carried out in Omidiyeh, located in southern Iran, using a cross-sectional design, involving 397 adults with hypertension (198 females and 199 males) who were selected from comprehensive health centers using a stratified random sampling technique. Data was gathered through a demographic data collection form and a questionnaire created by the researcher, which was based on the PMT. Data were assessed utilizing SPSS 25 and AMOS 24 software, and various statistical tests including one-way ANOVA, Pearson correlation, multiple regression, independent t-test, and structural equation modeling were conducted.FindingsThe variables of intrinsic reward (r = 0.182), extrinsic reward (r = 0.288), and response cost (r = 0.126) showed a significant negative correlation with self-care behaviors. On the other hand, perceived susceptibility (r = 0.212), perceived severity (r = 0.110), self-efficacy (r = 0.555), and response efficacy (r = 0.424) demonstrated a significant positive correlation with self-care behaviors. Specifically, self-efficacy and response efficacy were the most powerful predictors of self-care behaviors, respectively.ConclusionThe results showed that several factors can forecast self-care behaviors in patients with hypertension. Researchers are recommended to incorporate PMT in educational interventions and concentrate on self-efficacy and response efficacy constructs.

Biological effects of radiation exposure in patients treated with X-ray guided endovascular aortic repair

Abstract Background X-ray guided cardiovascular interventions such as endovascular aortic repair (EVAR) expose patients and operators to significant amounts of repeated ionising radiation over a long period of time. The biological effect of such protracted radiation exposure is poorly understood. We have previously demonstrated a higher incidence of dicentric chromosome (DC) aberrations in high-volume endovascular interventionalists and differences in acute DNA damage in lymphocytes between individuals following in vitro irradiation. Studies suggested a higher incidence of cancer in patients who underwent EVAR compared with those who have had open aneurysm repair, but the evidence is inconclusive. Further work is required to evaluate the biological radiation risk of X-ray guided cardiovascular interventions. Purposes We aimed to examine radiation-induced genome instability from patients after complex EVAR. We also aimed to investigate the intrinsic response of each patient to radiation using biomarkers of acute DNA damage following in vitro irradiation of their blood and to correlate this response to the expression of radiation-responsive genes. Methods Lymphocytes were isolated from patients after complex (branched/fenestrated) EVAR and non-irradiated controls. DC, a type of chromosomal aberration caused by radiation exposure were enumerated. γ-H2AX, a marker of acute DNA damage/repair, was measured by immunofluorescence after in vitro irradiation at 0.2 Gy and 1 Gy, along with the expression of the radiation-responsive genes FDXR, CCNG1, P21 and PHPT1 using qPCR. Results 17 patients (82% male, median age 73[59 – 85years]) and 16 controls (56% male, median age 68[53 – 83years]) were recruited. The mean incidence of DC was 3.782 (95% CI 3.13 - 4.43) and 0.898 (95% CI 0.48 -1.32) per 1000 cells for patients and controls, respectively (P<0.0001). Patients had higher background of γ-H2AX foci than unexposed controls, (0.7056, 95% CI 0.316 - 1.10) vs (0.241 95% CI 0.077 - 0.405) per cell, P<0.05. FDXR expression was most increased following irradiation (P<0.0001), reaching a mean 13.1-fold and 11.4-fold increase at 4-hour and 24-hour time-point, respectively, but this upregulation was not significantly different between the two groups. Conclusion We have shown an increased frequency of chromosomal aberrations in patients after complex EVAR, a biological finding that may support a propensity to developing malignancies. Patients also have higher basal DNA damage/repair (γ-H2AX) activity. Expression of ferredoxin reductase, FDXR gene could be a potential radio-responsive biomarker to provide personalised biological dosimetry information for clinical monitoring. Our study further underlines the long-term radiation risk of X-ray guided cardiovascular interventions and the potential of biological assays that may guide personalised care.

Intrinsic dynamic shapes responses to external stimulation in the human brain.

Sensory stimulation of the brain reverberates in its recurrent neuronal networks. However, current computational models of brain activity do not separate immediate sensory responses from intrinsic recurrent dynamics. We apply a vector-autoregressive model with external input (VARX), combining the concepts of "functional connectivity" and "encoding models", to intracranial recordings in humans. We find that the recurrent connectivity during rest is largely unaltered during movie watching. The intrinsic recurrent dynamic enhances and prolongs the neural responses to scene cuts, eye movements, and sounds. Failing to account for these exogenous inputs, leads to spurious connections in the intrinsic "connectivity". The model shows that an external stimulus can reduce intrinsic noise. It also shows that sensory areas have mostly outward, whereas higher-order brain areas mostly incoming connections. We conclude that the response to an external audiovisual stimulus can largely be attributed to the intrinsic dynamic of the brain, already observed during rest.

Tensile properties of SiC/SiC obtained from epoxy‐encapsulated minicomposites

AbstractThe current study investigates the tensile behavior of SiC/SiC minicomposites, focusing on the efficacy of epoxy encapsulation in extracting the intrinsic fiber bundle response. Three minicomposite types were examined: two with Hi‐Nicalon Type‐S fibers and one with Tyranno ZMI fibers. Tensile tests were performed on minicomposites and fiber tows, both bare and epoxy‐encapsulated, whereas interface properties were measured via fiber push‐in tests. The results demonstrate that epoxy encapsulation partially mitigates non‐uniform loading in minicomposites with discontinuous matrices. Theoretical limits on fiber bundle strength, estimated using micromechanical models based on weakest‐link statistics and shear lag theory, are similar to measured encapsulated tow strengths when failure occurs within the elastic regime of the epoxy. In some cases, microstructural defects such as fiber–fiber contacts and debonded coatings play important roles in limiting composite strengths relative to theoretical values. Although encapsulation does not always directly improve properties, it provides useful context for evaluating composite performance and exposing microstructural limitations unaccounted for in idealized models.

Porous flexible molecular-based piezoelectric composite achieves milliwatt output power density

Molecular ferroelectrics have made breakthrough progress in intrinsic piezoelectric response that can be on par with advanced inorganic piezoelectric ceramics. However, their successful applications in high-density energy harvesting and self-powered flexible devices have been great challenge, owing to the low elastic moduli, intrinsically brittle, and fracture proneness of such material systems under mechanical loading. Here, we have developed a flexible porous composite piezoelectric material by using soft thermoplastic polyurethane (TPU) and molecular ferroelectric materials. Benefiting from the porous structure of TPU, the flexible piezoelectric composites enable effectively large doping ratio (50%) of [Me3NCH2Cl]CdCl3 (TMCM-CdCl3) and highly efficient stress absorption, coupled with the excellent piezoelectric properties of TMCM-CdCl3, to realize a superior power density (636.9 µW cm−2 or 1273.9 µW cm−3). This output is 2000 times higher than that of flexible piezoelectric materials represented by poly(vinylidene fluoride) (PVDF). We believe that the outstanding performance of the porous composite piezoelectric material would pave a feasible way for real industrial applications of molecular ferroelectrics.

Dual-channel intrinsic and nonlinear chirality for an all-optical logic operation.

Chiral metasurfaces hold excellent performance in enhancing spin-dependent light-matter interaction, showing broad application prospects in areas such as chiral imaging, chiral light sources, and chiral sensing. However, utilizing resonant metasurfaces to achieve all-optical logic gates has not been reported yet. In this work, dual-channel intrinsic and nonlinear chiroptical responses are achieved on lithium niobate metasurfaces. The combination of bound states in the continuum (BICs) resonant modes with chiral metasurfaces has revealed its linear and nonlinear chirality. The metasurface achieves linear circular dichroism above 0.9 and nonlinear circular dichroism close to 0.9 on the dual-band. Based on the second-order nonlinear chiroptical response, multiple all-optical logic gates (including NOT, OR, NAND, AND, and NOR) can be realized on the chiral metasurfaces. Our results confirm the operability of resonant metasurfaces in realizing all-optical logic gates, offering a potentially promising approach for the development of new, to the best of our knowledge, all-optical logic devices.

Exploring the mechanisms of enhanced piezoelectric properties in (K,Na)NbO3 single crystals

(K,Na)NbO3 (KNN)-based piezoelectric materials are candidates for replacing Pb-based materials. However, the piezoelectric properties of existing KNN-based single crystals are still inferior to those of Pb-based relaxor ferroelectric single crystals. Moreover, the piezoelectric response mechanism of KNN-based single crystals remains unclear. In this study, (Li,K,Na)(Nb,Sb,Ta)O3:Mn (KNNLST:Mn) single crystals with an excellent piezoelectric coefficient d33 of approximately 778 pC/N were prepared. Systematically studies of intrinsic and extrinsic piezoelectric responses have revealed that the high d33 of KNNLST:Mn single crystals is related to the shear piezoelectric response of a single-domain state and irreversible domain wall motion of the engineering domains. Furthermore, the effect of the orthorhombic (O)-tetragonal (T) phase boundary on intrinsic and extrinsic piezoelectric response is systematically studied, and the impact mechanism is elucidated. The results indicate that a lower dielectric response and elastic constant limit the intrinsic shear piezoelectric response of KNNLST:Mn single crystals, and approaching the O–T phase boundary can enhance both intrinsic and extrinsic piezoelectric responses. This study improves our understanding of the structure-performance relationship in KNN-based single crystals and offers insights for optimizing piezoelectric properties in KNN-based materials.

Incorporating Single-Copper Sites and Host Defense Peptides into a Nanoreactor for Antibacterial Therapy by Bioinspired Design

A sustainable solution to the dramatic spread of antibiotic resistance threatening public health security is the development of antibiotic-free antimicrobial substances. Inspired by natural host defense mechanisms involving amino-terminal copper−nickel binding motif (ATCUN) antimicrobial peptides (AMPs), we have designed and prepared an artificial complex (Cu@G-AMPs) incorporating single-atom Cu catalysts for antibacterial therapy. The substrate of the complex, formed from guanine doped with abundant heteroatoms, anchored single Cu atoms with a coordination number of 2 and an average bond length of 1.91Å. Interestingly, Cu@G-AMPs, exhibiting Fenton-like catalytic activity, caused the inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by generating and delivering reactive oxygen species (ROS) cargo. Mechanistically, the intrinsic stress response system of MRSA underwent an irreversible collapse when Cu@G-AMPs initiated its offensive program associated with non-specific targets. Furthermore, Cu@G-AMPs, which inherited the immunomodulatory properties of AMPs, sequentially carried out the functions of pulling edge closure, stabilizing granulation tissue, promoting collagen fiber proliferation, alleviating inflammation, and promoting neovascularization in wound areas infected by MRSA. Our results show that Cu@G-AMPs will provide a new perspective on untangling the complex regulatory networks that resistant bacteria have cultivated to deactivate commercial antibiotics.

Enhanced magnetoelectric response in Sc-doped BiFeO3-BaTiO3 Ceramics

In recent years, the single-phase BiFeO3-BaTiO3 multiferroic ceramics have gained attention for their magnetoelectric response above room temperature, but substantial endeavors to improve the property have yielded modest results. An optimized BiFe(1-x)ScxO3-BaTiO3 composition having magnetoelectric coefficient (αME) ∼ 567 mV/(cm·Oe)) measured at the resonant frequency (∼95 kHz) is reported in this work. The high αME is attributed to the combined effect of improved piezoelectric coefficient and enhanced ferromagnetism. Improved piezoelectricity is attributed to enhanced intrinsic response caused by the octahedral distortions, and enhanced ferromagnetism is induced by the destabilized cycloidal spin structure resulting from the octahedral distortions. Besides, the addition of Sc3+ can exhibit increased resistivity and reduced defect dipole effects, which is conducive to improving electric properties.

Bioinformatic-Experimental Screening Uncovers Multiple Targets for Increase of MHC-I Expression through Activating the Interferon Response in Breast Cancer.

Expression of major histocompatibility complex I (MHC-I) on tumor cells is extremely important for the antitumor immune response for its essential role in activating various immune cells, including tumor-specific CD8+ T cells. Cancers of lower MHC-I expression commonly exhibit less immune cell infiltration and worse prognosis in clinic. In this study, we conducted bioinformatic-experimental screening to identify potential gene targets to enhance MHC-I expression in breast cancer (BRCA). Through a combination of MHC-I scoring, gene expression correlation analysis, survival prognostication, and Cibersort tumor-infiltrated lymphocytes (TILs) scoring, we identify 144 genes negatively correlated with both MHC-I expression and TILs in breast cancer. Furthermore, we verified partially according to KEGG functional enrichment or gene-dependency analysis and figured out multiple genes, including PIP5K1A, NCKAP1, CYFIP1, DIS3, TBP, and EXOC1, as effective gene targets for increasing MHC-I expression in breast cancer. Mechanistically, knockout of each of these genes activated the intrinsic interferon response in breast cancer cells, which not only promoted MHC-I expression but also caused immunogenic cell death of breast cancer. Finally, the scRNA-seq confirmed the negative correlation of PIP5K1A et al. with TILs in breast cancer patients. Collectively, we identified multiple gene targets for an increase in MHC-I expression in breast cancer in this study.

Deformation behavior and constitutive equation of Sn-37Pb solder alloy at cryogenic temperature

In this work, the tensile property, ductile-to-brittle transition (DBT) mechanism and constitutive relations of 63Sn-37Pb (Sn-37Pb) solder alloy at cryogenic temperature were studied by uniaxial tensile experiments for different temperatures. The tensile strength of Sn-37Pb solder alloy increases from 38.2MPa (293K) to 178.9MPa (123K) and then declines to 145.2MPa (77K) with decreases of temperature, and its fracture elongation changes from 42.8% (293K) to 10.2% (77K). Mechanical behavior of Pb second phase in Sn-37Pb alloy at low temperatures is illustrated: when the temperature drops to 123K and below, the fracture failure of β-Sn matrix occurs in an open mode. As a result, Sn-37Pb solder alloy fails by brittle fracture mode. Anand model is adopted as a unified viscoplastic intrinsic law to describe the intrinsic relationship of Sn-37Pb solder alloys. Above 123K, Anand model can effectively fit the stress-strain curves of Sn-37Pb solder alloys. When the temperature lower than 123K, the deformation characters of Sn-37Pb solder alloys change from elasto-viscoplastic to elasto-plastic, and Anand model is unable to continue to fit the intrinsic relationship of Sn-37Pb solder alloys. Sn-37Pb solder alloy exhibits more obvious strain hardening at low temperature, and its low-temperature intrinsic response is successfully described by Hollomon’s equation. The research method of the solder alloy is of great significance to solve the reliability problem of low temperature electronic devices.

Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular anti-viral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing infiltrating immunosuppressive CD4 T and myeloid cells and stimulating granzyme expression in infiltrating T and NK cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

Sex-specific molecular signature of mouse podocytes in homeostasis and in response to pharmacological challenge with rapamycin

BackgroundSex differences exist in the prevalence and progression of major glomerular diseases. Podocytes are the essential cell-type in the kidney which maintain the physiological blood-urine barrier, and pathological changes in podocyte homeostasis are critical accelerators of impairment of kidney function. However, sex-specific molecular signatures of podocytes under physiological and stress conditions remain unknown. This work aimed at identifying sexual dimorphic molecular signatures of podocytes under physiological condition and pharmacologically challenged homeostasis with mechanistic target of rapamycin (mTOR) inhibition. mTOR is a crucial regulator involved in a variety of physiological and pathological stress responses in the kidney and inhibition of this pathway may therefore serve as a general stress challenger to get fundamental insights into sex differences in podocytes.MethodsThe genomic ROSAmT/mG-NPHS2 Cre mouse model was used which allows obtaining highly pure podocyte fractions for cell-specific molecular analyses, and vehicle or pharmacologic treatment with the mTOR inhibitor rapamycin was performed for 3 weeks. Subsequently, deep RNA sequencing and proteomics were performed of the isolated podocytes to identify intrinsic sex differences. Studies were supplemented with metabolomics from kidney cortex tissues.ResultsAlthough kidney function and morphology remained normal in all experimental groups, RNA sequencing, proteomics and metabolomics revealed strong intrinsic sex differences in the expression levels of mitochondrial, translation and structural transcripts, protein abundances and regulation of metabolic pathways. Interestingly, rapamycin abolished prominent sex-specific clustering of podocyte gene expression and induced major changes only in male transcriptome. Several sex-biased transcription factors could be identified as possible upstream regulators of these sexually dimorphic responses. Concordant to transcriptomics, metabolomic changes were more prominent in males. Remarkably, high number of previously reported kidney disease genes showed intrinsic sexual dimorphism and/or different response patterns towards mTOR inhibition.ConclusionsOur results highlight remarkable intrinsic sex-differences and sex-specific response patterns towards pharmacological challenged podocyte homeostasis which might fundamentally contribute to sex differences in kidney disease susceptibilities and progression. This work provides rationale and an in-depth database for novel targets to be tested in specific kidney disease models to advance with sex-specific treatment strategies.

Exploration of near room temperature magnetoelectric coupling in BaFe10Sc[formula omitted]O19:KNbO[formula omitted] composite

The consequential experimental endeavour has been undertaken to investigate and control the strain-mediated coupling of the magnetic and electric properties of the composite systems composed of Sc-doped BaFe12O19 and KNbO3. A distinct non-disperse ferroelectric-like anomaly is observed Tkink∼ 265 K, which concomitantly coincides with the magnetic Tcone transition. The observation of external magnetic field dependence dielectric response shows a noticeable decrease in permittivity values, indicating a negative magnetodielectric response. The maximum intrinsic magnetodielectric response is seen in the vicinity of room temperature with the magnetodielectric ratio of 5.4% @ 1 kHz. The linearity of −Δɛ′(H)% vs. M2 plot is phenomenologically described with the Ginzburg–Landau theory with the magnetoelectric coupling term γP2M2. The magnetoelectric coupling relies on strain to induce crystal deformations (flexomagnetoelectric response) on either the ferroelectric phase through magnetostriction or in the magnetic phase through the converse piezoelectric effect. Strain-induced changes in the magnetic as well as dielectric properties of the composites lead to strong magnetoelectric coupling to throw more light exploring a potential candidate for room-temperature multiferroic materials.

State transition learning with limited data for safe control of switched nonlinear systems

Switching dynamics are prevalent in real-world systems, arising from either intrinsic changes or responses to external influences, which can be appropriately modeled by switched systems. Control synthesis for switched systems, especially integrating safety constraints, is recognized as a significant and challenging topic. This study focuses on devising a learning-based control strategy for switched nonlinear systems operating under arbitrary switching law. It aims to maintain stability and uphold safety constraints despite limited system data. To achieve these goals, we employ the control barrier function method and Lyapunov theory to synthesize a controller that delivers both safety and stability performance. To overcome the difficulties associated with constructing the specific control barrier and Lyapunov function and take advantage of switching characteristics, we create a neural control barrier function and a neural Lyapunov function separately for control policies through a state transition learning approach. These neural barrier and Lyapunov functions facilitate the design of the safe controller. The corresponding control policy is governed by learning from two components: policy loss and forward state estimation. The effectiveness of the developing scheme is verified through simulation examples.

Polypyrrole/iron-glycol chitosan nanozymes mediate M1 macrophages to enhance the X-ray-triggered photodynamic therapy for bladder cancer by promoting antitumor immunity

X-ray Photodynamic Therapy (XPDT) is an emerging, deeply penetrating, and non-invasive tumor treatment that stimulates robust antitumor immune responses. However, its efficacy is often limited by low therapeutic delivery and immunosuppressant within the tumor microenvironment. This challenge can potentially be addressed by utilizing X-ray responsive iron-glycol chitosan-polypyrrole nanozymes (GCS-I-PPy NZs), which activate M1 macrophages. These nanozymes increase tumor infiltration and enhance the macrophages' intrinsic immune response and their ability to stimulate adaptive immunity. Authors have designed biocompatible, photosensitizer-containing GCS-I-PPy NZs using oxidation/reduction reactions. These nanozymes were internalized by M1 macrophages to form RAW-GCS-I-PPy NZs. Authors' results demonstrated that these engineered macrophages effectively delivered the nanozymes with potentially high tumor accumulation. Within the tumor microenvironment, the accumulated GCS-I-PPy NZs underwent X-ray irradiation, generating reactive oxygen species (ROS). This ROS augmentation significantly enhanced the therapeutic effect of XPDT and synergistically promoted T cell infiltration into the tumor. These findings suggest that nano-engineered M1 macrophages can effectively boost the immune effects of XPDT, providing a promising strategy for enhancing cancer immunotherapy. The ability of GCS-I-PPy NZs to mediate M1 macrophage activation and increase tumor infiltration highlights their potential in overcoming the limitations of current XPDT approaches and improving therapeutic outcomes in melanoma and other cancers.

Enhancing Cell Aggregation and Migration via Double-Click Cross-Linking with Azide-Modified Hyaluronic Acid.

We present a novel approach to the formation of cell aggregates by employing click chemistry with water-soluble zwitterionic dibenzo cyclooctadiyne (WS-CODY) and azide-modified hyaluronic acid (HA-N3) as a linker to facilitate rapid and stable cell aggregation. By optimizing the concentrations of HA-N3 and WS-CODY, we achieved efficient cross-linking between azide-modified cell surfaces and HA-N3, generating cell aggregates within 10 min, and the resulting aggregates remained stable for up to 5 days, with cell viability maintained at approximately 80%. Systematic experiments revealed that a stoichiometric balance between HA-N3 and WS-CODY is important for effective cross-linking, highlighting the roles of both cell-surface azide modification and HA in the aggregate formation. We also investigated the genetic basis of altered cell behavior within these aggregates. Transcriptome analysis (RNA-seq) of aggregates postcultivation revealed a marked fluctuation of genes associated with 'cell migration' and 'cell adhesion', including notable changes in the expression of HYAL1, ICAM-1, CEACAM5 and RHOB. These findings suggest that HA-N3-mediated cell aggregation can induce intrinsic cellular responses that not only facilitate cell aggregate formation but also modulate cell-matrix interactions. We term this phenomenon 'chemo-resilience', The simplicity and efficacy of this click chemistry-based approach suggest it may have broad applicability for forming cell aggregates and modulating cell-matrix interactions in tissue engineering and regenerative medicine.