Directional Cell Migration Guided by a Strain Gradient.

Strain gradients widely exist in development and physiological activities. The directional movement of cells is essential for proper cell localization, and directional cell migration in responses to gradients of chemicals, rigidity, density, and topography of extracellular matrices have been well-established. However; it is unclear whether strain gradients imposed on cells are sufficient to drive directional cell migration. In this work, a programmable uniaxial cell stretch device is developed that creates controllable strain gradients without changing substrate stiffness or ligand distributions. It is demonstrated that over 60% of the single rat embryonic fibroblasts migrate toward the lower strain side in static and the 0.1 Hz cyclic stretch conditions at ≈4% per mm strain gradients. It is confirmed that such responses are distinct from durotaxis or haptotaxis. Focal adhesion analysis confirms higher rates of contact area and protrusion formation on the lower strain side of the cell. A 2D extended motor-clutch model is developed to demonstrate that the strain-introduced traction force determines integrin fibronectin pairs' catch-release dynamics, which drives such directional migration. Together, these results establish strain gradient as a novel cue to regulate directional cell migration and may provide new insights in development and tissue repairs.

In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.

Application of Magnetic Materials Combined with Echo® Mass Spectrometry System in Analysis of Illegal Drugs in Sewage.

The aim of this study is to solve the problems of the complicated pretreatment and high analytical cost in the detection technology of trace drugs and their metabolites in municipal wastewater. A high-performance magnetic sorbent was fsynthesized for the enrichment of trace drugs and their metabolites in wastewater to develop a magnetic solid-phase extraction pretreatment combined with the acoustic ejection mass spectrometry (AEMS) analytical method. The magnetic nanospheres were successfully prepared by magnetic nanoparticles modified with divinylbenzene and vinylpyrrolidone. The results showed that the linear dynamic range of 17 drugs was 1-500 ng/mL, the recovery was 44-100%, the matrix effect was more than 51%, the quantification limit was 1-2 ng/mL, and the MS measurement was fast. It can be seen that the developed magnetic solid-phase extraction (MSPE) method is a good solution to the problems of the complicated pretreatment and analytical cost in the analysis of drugs in wastewater. The developed magnetic material and acoustic excitation pretreatment coupled with mass spectrometry analysis method can realize the low-cost, efficient enrichment, and fast analysis of different kinds of drug molecules in urban sewage.

Dihydropyridopyrazine Functionalized Xanthene: Generating Stable NIR Dyes with Small-Molecular Weight by Enhanced Charge Separation.

Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.

Superoxide Anion-Mediated Afterglow Mechanism-Based Water-Soluble Zwitterion Dye Achieving Renal-Failure Mice Detection.

Afterglow materials-based biological imaging has promising application prospects, due to negligible background. However, currently available afterglow materials mainly include inorganic materials as well as some organic nanoparticles, which are difficult to translate to the clinic, resulting from non-negligible metabolic toxicity and even leakage risk of inorganic heavy metals. Although building small organic molecules could solve such obstacles, organic small molecules with afterglow ability are extremely scarce, especially with a sufficient renal metabolic capacity. To address these issues, herein, we designed water-soluble zwitterion Cy5-NF with renal metabolic capacity and afterglow luminescence, which relied on an intramolecular cascade reaction between superoxide anion (O2•-, instead of 1O2) and Cy5-NF to release afterglow luminescence. Of note, compared with different reference contrast agents, zwitterion Cy5-NF not only had excellent afterglow properties but also had a rapid renal metabolism rate (half-life period, t1/2, around 10 min) and good biocompatibility. Unlike prior afterglow nanosystems possessing a large size, for the first time, zwitterion Cy5-NF has achieved the construction of water-soluble renal metabolic afterglow contrast agents, which showed higher sensitivity and signal-to-background ratio in afterglow imaging than fluorescence imaging for the kidney. Moreover, zwitterion Cy5-NF had a longer kidney retention time in renal-failure mice (t1/2 more than 15 min). More importantly, zwitterion Cy5-NF can be metabolized very quickly even in severe renal-failure mice (t1/2 around 25-30 min), which greatly improved biosecurity. Therefore, we are optimistic that the O2•--mediated afterglow mechanism-based water-soluble zwitterion Cy5-NF is very promising for clinical application, especially rapid detection of kidney failure.

A deficient MIF-CD74 signaling pathway may play an important role in immunotherapy-induced hyper-progressive disease.

BACKGROUND: With the advent of immune checkpoint inhibitors (ICIs) therapies, a major breakthrough has been made in cancer treatment. However, instead of good results, some patients experienced a deterioration of their disease. This unexpected result is termed as hyper-progressive disease (HPD). The biology of HPD is currently not fully understood. METHODS: Isolation of CD3+ cells from peripheral blood mononuclear cells (PBMC) in healthy control, tumor patients receiving immunotherapy with or without immunotherapy-induced HPD, then conducted single-cell RNA sequencing (scRNA-seq). RESULTS: By analyzing scRNA-seq data, we identified 15 cell clusters. We observed developed-exhausted CD4+ T cells and regulatory T cells (Tregs) increasingly enriched in HPD group. Meanwhile, some effector T cells were decreased in HPD. The imbalance potentially contributes to the occurrence of HPD and poor clinical prognosis. In addition, we analyzed ligand-receptor interactions between subsets. The ligand-receptor interaction "CD74-MIF" was absent in HPD. However, in vitro experiment, we found that CD74 regulated effector function of effector CD8+ T cells. Overall, the article provides a primary study of immune profile in HPD.

Applications of Metal-Organic Frameworks in Water Treatment: A Review.

The ever-expanding scale of industry and agriculture has led to the gradual increase of pollutants (e.g., heavy metal ions, synthetic dyes, and antibiotics) in water resources, and the ecology and wastewater are grave problems that need to be solved urgently and has attracted widespread attention from the research community and industry in recent years. Metal-organic frameworks (MOFs) are a type of organic-inorganic hybrid material with a distinctive 3D network crystal structure. Lately, MOFs have made striking progress in the fields of adsorption, catalytic degradation, and biomedicine on account of their large specific surface and well-developed pore structure. This review summarizes the latest research achievements in the preparation of pristine MOFs, MOF composites, and MOF derivatives for various applications including the removal of heavy metal ions, organic dyes, and other harmful substances in sewage. Furthermore, the working mechanisms of utilizing adsorption, photocatalytic degradation, and membrane separation technologies are also briefly described for specific pollutants removal from sewage. It is expected that this review will provide inspiration and references for the synthesis of pristine MOFs as well as their composites and derivatives with excellent water treatment performance.

In Situ Growth of Three-Dimensional MXene/Metal-Organic Framework Composites for High-Performance Supercapacitors.

In this study, we propose a versatile method for synthesizing uniform three-dimensional (3D) metal carbides, nitrides, and carbonitrides (MXenes)/metal-organic frameworks (MOFs) composites (Ti3 C2 TX /Cu-BTC, Ti3 C2 TX /Fe,Co-PBA, Ti3 C2 TX /ZIF-8, and Ti3 C2 TX /ZIF-67) that combine the advantages of MOFs and MXenes to enhance stability and improve conductivity. Subsequently, 3D hollow Ti3 C2 TX /ZIF-67/CoV2 O6 composites with excellent electron- and ion-transport properties derived from Ti3 C2 TX /ZIF-67 were synthesized. The specific capacitance of the Ti3 C2 TX /ZIF-67/CoV2 O6 electrode was 285.5 F g-1 , which is much higher than that of the ZIF-67 and Ti3 C2 TX /ZIF-67 electrode. This study opens a new avenue for the design and synthesis of MXene/MOF composites and complex hollow structures with tailorable structures and compositions for various applications.

Chemical Kinetics of H-Atom Abstraction from Ethanol by HȮ2: Implication for Combustion Modeling.

As a renewable source of energy, ethanol has been widely used in internal combustion engines as either a gasoline alternative fuel or a fuel additive. However, as the chemical source term of the computational fluid dynamics simulation of combustors, there remains a disagreement in understanding the chemical kinetic mechanism of ethanol. The reaction mechanism of ethanol + HÈ®2 is a well-known crucial reaction class in terms of predicting the reactivity of ethanol as well as ethylene formation under engine-relevant conditions. However, the kinetic parameters of the reactions are basically extrapolated by analogy to the n-butanol + HÈ®2 system calculated by Zhou et al. (Zhou et al. Int. J. Chem. Kinet. 2012, 44 (3), 155-164). The reliability of such an analogy remains to be seen because no direct theoretical or experimental evidence is available in the literature to date. In this study, thermal rate coefficients of H-atom abstraction reactions for the ethanol + HÈ®2 system were determined by using both conventional transition-state theory and canonical variational transition-state theory, with the potential energy surface evaluated at the CCSD(T)/cc-pVTZ//M06-2x/def-TZVP level. The quantum-mechanical effects were corrected by the zero-curvature tunneling method at low temperatures (<750 K), and difference schemes of two Eckart functions were fitted to optimize the minimum energy path curves. Torsional modes of the -CH3 and -OH groups were treated by using the hindered-internal-rotation approximation. Furthermore, the rate coefficients of the title reaction were calculated at both the CCSD(T)/cc-pVTZ//M06-2x/def-TZVP and CCSD(T)/CBS//M06-2x/def-TZVP levels of theory with uncertainty of a factor of 3. Similar to the n-butanol + HÈ®2 system, the title system is dominated by α-site H-atom abstraction, but the rate coefficients of the three channels are slightly slower than that of the n-butanol + HÈ®2 system. In general, the new calculations show only a limited effect on the ethanol reactivity at low pressures and high temperatures (>1300 K), but they prevent the kinetic mechanisms from overpredicting ignition delay times under engine-relevant conditions.

Three-dimensional porous Cu@Cu2O aerogels for direct voltammetric sensing of glucose.

Three-dimensional Cu@Cu2O aerogels with excellent electrocatalytic activity were prepared and used as electrode matrix for constructing novel electrochemical glucose sensors. The aerogels were obtained by adding a fresh solution of NaBH4 into a mixture of CuCl2 and NaOH aqueous solutions under stirring at room temperature. The aerogels were assembled with Cu or Cu2O nanoparticles. The materials show superfine spongy-like structures with large surface-to-volume ratio, numerous active sites and good solubility. The Cu@Cu2O aerogels show highly efficient electrochemical activity toward glucose oxidation with a relatively low-onset potential (0.25 V) in 0.1 M NaOH solution. This non-enzymatic glucose sensor offers a low detection limit of 0.6 µM (S/N = 3), a high sensitivity (195 mA M-1 cm-2), and two wide linear ranges (0.001-5.2 mM, 5.2-17.1 mM) at a working voltage of 0.6 V (vs. Ag/AgCl) in alkaline solution. While in neutral pH values, the respective data are a linear analytical range from 0.1 to 10 mM; a detection limit of 54 µM (S/N = 3) and a sensitivity of 12 mA M-1 cm-2 at scan rate of 100 mV s-1. The sensor possesses high selectivity, good reproducibility and long-time stability. It was utilized to determine glucose levels in (spiked) human serum samples, and satisfactory results were obtained. Graphical abstract Schematic presentation of a glassy carbon electrode modified with 3D porous Cu@Cu2O aerogels. The aerogels were obtained by a reduction reaction at room temperature (Scheme 1A). The aerogel networks were used to develop a highly sensitive electrochemical sensing platform for the detection of glucose (Scheme 1B).

A novel monopartite dsRNA virus isolated from the phytopathogenic fungus Ustilaginoidea virens strain GZ-2.

In this study, we describe a novel mycovirus isolated from Ustilaginoidea virens strain GZ-2, which was designated "Ustilaginoidea virens nonsegmented virus 2" (UvNV-2). The genome of UvNV-2 contains two overlapping open reading frames (ORFs). ORF1 encodes an unknown protein, and ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp), which is most closely related to that of Purpureocillium lilacinum nonsegmented virus 1 (PINV-1) and is likely to be expressed by a + 1 ribosomal frameshift within the sequence CCC_UUU_UAG. A phylogenetic analysis of the RdRp of UvNV-2 showed that UvNV-2 is an unclassified mycovirus.

Kinetics of Hydrogen Abstraction and Addition Reactions of 3-Hexene by ȮH Radicals.

Rate coefficients of H atom abstraction and H atom addition reactions of 3-hexene by the hydroxyl radicals were determined using both conventional transition-state theory and canonical variational transition-state theory, with the potential energy surface (PES) evaluated at the CCSD(T)/CBS//BHandHLYP/6-311G(d,p) level and quantum mechanical effect corrected by the compounded methods including one-dimensional Wigner method, multidimensional zero-curvature tunneling method, and small-curvature tunneling method. Results reveal that accounting for approximate 70% of the overall H atom abstractions occur in the allylic site via both direct and indirect channels. The indirect channel containing two van der Waals prereactive complexes exhibits two times larger rate coefficient relative to the direct one. The OH addition reaction also contains two van der Waals complexes, and its submerged barrier results in a negative temperature coefficient behavior at low temperatures. In contrast, The OH addition pathway dominates only at temperatures below 450 K whereas the H atom abstraction reactions dominate overwhelmingly at temperature over 1000 K. All of the rate coefficients calculated with an uncertainty of a factor of 5 were fitted in a quasi-Arrhenius formula. Analyses on the PES, minimum reaction path and activation free Gibbs energy were also performed in this study.

Magnetic dispersive solid-phase extraction based on modified magnetic nanoparticles for the detection of cocaine and cocaine metabolites in human urine by high-performance liquid chromatography-mass spectrometry.

An easy-to-handle magnetic dispersive solid-phase extraction procedure was developed for preconcentration and extraction of cocaine and cocaine metabolites in human urine. Divinyl benzene and vinyl pyrrolidone functionalized silanized Fe3 O4 nanoparticles were synthesized and used as adsorbents in this procedure. Scanning electron microscopy, vibrating sample magnetometry, and infrared spectroscopy were employed to characterize the modified adsorbents. A high-performance liquid chromatography with mass spectrometry method for determination of cocaine and its metabolites in human urine sample has been developed with pretreatment of the samples by magnetic dispersive solid-phase extraction. The obtained results demonstrated the higher extraction capacity of the prepared nanoparticles with recoveries between 75.1 to 105.7% and correlation coefficients higher than 0.9971. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.10 ng/mL. The proposed magnetic dispersive solid-phase extraction method provided a rapid, environmentally friendly and magnetic stuff recyclable approach and it was confirmed that the prepared adsorbents material was a kind of highly effective extraction materials for the trace cocaine and cocaine metabolites analyses in human urine.

[Research on Identification of Organic Gunshot Residue with Micro-Raman Spectroscopy].

A rapid approach for the nondestructive, accurate detection of organic gunshot residue was investigated. Raman microscopy was used to identify organic gunshot residue and the propellant in ammunition. The optimal excitation wavelength for the detection of organic particles using Raman spectroscopy was 473 nm. The Raman spectra of organic gunshot residue obtained using 473 nm laser excitation can effectively avoid the interference of fluorescence. The results demonstrated that the organic particles were mainly from the partially burned propellant particles. Meanwhile it was proved that the main component was basically consistent with the propellant except somehow damage in chemical structure or degree of crystallization with Raman spectra. The surface color of organic particles was mainly brassiness, dark gray. A lot of craters were distributed on the surface of organic particles. Spherical inorganic particles with metallic luster attached to the surface of organic particles can be regarded as the typical characteristics of gunshot residue.

Enhanced In Vitro Efficacy of Verbascoside in Suppressing Hepatic Stellate Cell Activation via ROS Scavenging with Reverse Microemulsion.

Numerous approaches targeting hepatic stellate cells (HSCs) have emerged as pivotal therapeutic strategies to mitigate liver fibrosis and are currently undergoing clinical trials. The investigation of herbal drugs or isolated natural active compounds is particularly valuable, due to their multifaceted functions and low risk of side effects. Recent studies have hinted at the potential efficacy of verbascoside (VB) in ameliorating renal and lung fibrosis, yet its impact on hepatic fibrosis remains to be elucidated. This study aims to evaluate the potential effects of VB on liver fibrosis by assessing its ability to inhibit HSC activation. VB demonstrated significant efficacy in suppressing the expression of fibrogenic genes in activated LX-2 cells. Additionally, VB inhibited the migration and proliferation of these activated HSCs by scavenging reactive oxygen species (ROS) and downregulating the AMPK pathway. Furthermore, a biosafe reverse microemulsion loaded with VB (VB-ME) was developed to improve VB's instability and low bioavailability. The optimal formulation of VB-ME was meticulously characterized, revealing substantial enhancements in cellular uptake, ROS-scavenging capacity, and the suppression of HSC activation.

Patterning ganglionic eminences in developing human brain organoids using a morphogen-gradient-inducing device.

In early neurodevelopment, the central nervous system is established through the coordination of various neural organizers directing tissue patterning and cell differentiation. Better recapitulation of morphogen gradient production and signaling will be crucial for establishing improved developmental models of the brain in vitro. Here, we developed a method by assembling polydimethylsiloxane devices capable of generating a sustained chemical gradient to produce patterned brain organoids, which we termed morphogen-gradient-induced brain organoids (MIBOs). At 3.5 weeks, MIBOs replicated dorsal-ventral patterning observed in the ganglionic eminences (GE). Analysis of mature MIBOs through single-cell RNA sequencing revealed distinct dorsal GE-derived CALB2+ interneurons, medium spiny neurons, and medial GE-derived cell types. Finally, we demonstrate long-term culturing capabilities with MIBOs maintaining stable neural activity in cultures grown up to 5.5 months. MIBOs demonstrate a versatile approach for generating spatially patterned brain organoids for embryonic development and disease modeling.

Broccoli Improves Lipid Metabolism and Intestinal Flora in Mice with Type 2 Diabetes Induced by HFD and STZ Diet.

Globally, type 2 diabetes (T2DM) is on the rise. Maintaining a healthy diet is crucial for both treating and preventing T2DM.As a common vegetable in daily diet, broccoli has antioxidant, anti-inflammatory and anticarcoma physiological activities. We developed a mouse model of type 2 diabetes and carried out a systematic investigation to clarify the function of broccoli in reducing T2DM symptoms and controlling intestinal flora. The findings demonstrated that broccoli could successfully lower fasting blood glucose (FBG), lessen insulin resistance, regulate lipid metabolism, lower the levels of TC, TG, LDL-C, and MDA, stop the expression of IL-1ß and IL-6, and decrease the harm that diabetes causes to the pancreas, liver, fat, and other organs and tissues. Furthermore, broccoli altered the intestinal flora's makeup in mice with T2DM. At the genus level, the relative abundance of Allobaculum decreased, and that of Odoribacter and Oscillospira increased; At the family level, the relative abundances of Odoribacteraceae, Rikenellaceae and S24-7 decreased, while the relative abundances of Erysipelotrichaceae and Rikenellaceae increased.

A Multilayer Photothermal Superhydrophobic Anti-Icing Coating Applied to Asphalt Pavement with Remarkable Wear Resistance.

Superhydrophobic surfaces exhibit considerable potential in road anti-icing applications due to their unique water-repellent properties. However, the nanorough structure of superhydrophobic coatings is highly susceptible to degradation under wheel rolling in practical applications. To maintain effective hydrophobicity under prolonged exposure to wheel rolling, a multilayer superhydrophobic anti-icing coating was developed. This coating utilizes antifreeze protein (AFP)-modified emulsified asphalt as the substrate with carbon nanotubes (CNTs) and silicon carbide (SiC) as surface coatings. Experimental results indicate that the inclusion of AFP enhances the viscosity of the emulsified asphalt, thereby stabilizing the nanorough structure of the coating. Even after 100 cycles of sandpaper grinding and 500 wheel rolls, the coating maintains robust hydrophobic properties. Moreover, when the coating is worn away by long-term high-strength loads, the exposed AFP-modified emulsified asphalt layer continues to exhibit effective anti-icing capabilities, significantly prolonging the complete freezing time of water droplets on its surface. Additionally, the incorporation of CNTs and SiC enhances the photothermal conversion performance, further improving the anti-icing efficiency of the coating under light irradiation. Overall, this coating shows promise for application in road anti-icing strategies.

The potential role of CMC1 as an immunometabolic checkpoint in T cell immunity.

T cell immunity is critical for human defensive immune response. Exploring the key molecules during the process provides new targets for T cell-based immunotherapies. CMC1 is a mitochondrial electron transport chain (ETC) complex IV chaperon protein. By establishing in-vitro cell culture system and Cmc1 gene knock out mice, we evaluated the role of CMC1 in T cell activation and differentiation. The B16-OVA tumor model was used to test the possibility of targeting CMC1 for improving T cell anti-tumor immunity. We identified CMC1 as a positive regulator in CD8+T cells activation and terminal differentiation. Meanwhile, we found that CMC1 increasingly expressed in exhausted T (Tex) cells. Genetic lost of Cmc1 inhibits the development of CD8+T cell exhaustion in mice. Instead, deletion of Cmc1 in T cells prompts cells to differentiate into metabolically and functionally quiescent cells with increased memory-like features and tolerance to cell death upon repetitive or prolonged T cell receptor (TCR) stimulation. Further, the in-vitro mechanistic study revealed that environmental lactate enhances CMC1 expression by inducing USP7, mediated stabilization and de-ubiquitination of CMC1 protein, in which a mechanism we propose here that the lactate-enriched tumor microenvironment (TME) drives CD8+TILs dysfunction through CMC1 regulatory effects on T cells. Taken together, our study unraveled the novel role of CMC1 as a T cell regulator and its possibility to be utilized for anti-tumor immunotherapy.

Graphene-integrated mesh electronics with converged multifunctionality for tracking multimodal excitation-contraction dynamics in cardiac microtissues.

Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.