Intratumoral injection of mRNA encoding survivin in combination with STAT3 inhibitor stattic enhances antitumor effects.

Intratumoral delivery of mRNA encoding immunostimulatory molecules can initiate a robust, global antitumor response with little side effects by enhancing local antigen presentation in the tumor and the tumor draining lymph node. Neoantigen-based mRNA nanovaccine can inhibit melanoma growth in mice by intratumoral injection. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune responses by secreting immunosuppressive agents, such as reactive oxygen species (ROS). Suppression of STAT3 activity by stattic may reduce MDSC-mediated immunosuppression in the TME and promote the antitumor immune responses. In this study, in vitro transcribed mRNA encoding tumor antigen survivin was prepared and injected intratumorally in BALB/c mice bearing subcutaneous colon cancer tumors. In vivo studies demonstrated that intratumoral survivin mRNA therapy could induce antitumor T cell response and inhibit tumor growth of colon cancer. Depletion of CD8+ T cells could significantly inhibit survivin mRNA-induced antitumor effects. RT-qPCR and ELISA analysis indicated that survivin mRNA treatment led to increased expression of receptor activator nuclear factor-κB ligand (RANKL). In vitro experiment showed that MDSCs could be induced from mouse bone marrow cells by RANKL and RANKL-induced MDSCs could produce high level of ROS. STAT3 inhibitor stattic suppressed activation of STAT3 and NF-κB signals, thereby inhibiting expansion of RANKL-induced MDSCs. Combination therapy of survivin mRNA and stattic could significantly enhance antitumor T cell response, improve long-term survival and reduce immunosuppressive tumor microenvironment compared to each monotherapy. In addition, combined therapy resulted in a significantly reduced level of tumor cell proliferation and an obviously increased level of tumor cell apoptosis in CT26 colon cancer-bearing mice, which could be conducive to inhibit the tumor growth and lead to immune responses to released tumor-associated antigens. These studies explored intratumoral mRNA therapy and mRNA-based combined therapy to treat colon cancer and provide a new idea for cancer therapy.

A photoluminescent hydrogen-bonded biomass aerogel for sustainable radiative cooling.

Passive radiant cooling is a potentially sustainable thermal management strategy amid escalating global climate change. However, petrochemical-derived cooling materials often face efficiency challenges owing to the absorption of sunlight. We present an intrinsic photoluminescent biomass aerogel, which has a visible light reflectance exceeding 100%, that yields a large cooling effect. We discovered that DNA and gelatin aggregation into an ordered layered aerogel achieves a solar-weighted reflectance of 104.0% in visible light regions through fluorescence and phosphorescence. The cooling effect can reduce ambient temperatures by 16.0°C under high solar irradiance. In addition, the aerogel, efficiently produced at scale through water-welding, displays high reparability, recyclability, and biodegradability, completing an environmentally conscious life cycle. This biomass photoluminescence material is another tool for designing next-generation sustainable cooling materials.

Photon-beam-inducing synthesis of a tunable porous graphene/Ti3C2Tx heterostructure for energy conversion-storage system.

Flexible electronic device requires a novel micro supercapacitors (MSCs) energy conversion-storage system based on two-dimensional (2D) materials to solve the problems of stiffness and complexity. Herein, we report a novel catalytic introduction method of graphene with adjustable porosity by high-energy photon beam. The graphene/Ti3C2Tx heterostructure was constructed by electrostatic self-assembly, has a high cycle life (98% after 8,000 cycles), energy density (11.02 mWh cm-3), and demonstrate excellent flexible alternating current line-filtering performance. The phase angle of -79.8° at 120 Hz and a resistance-capacitance constant of 0.068 ms. Furthermore, the porous graphene/Ti3C2Tx structures produced by multiple catalytic inductions allowed ions to deeply penetrate the electrode, thereby increasing the stacking density. The special "pore-layer nesting" graphene structure with adjustable pores effectively increased the specific surface area, and its superior matching with electrolyte solutions greatly improved surface-active site utilization. This work offers an alternative strategy for fabricating a 2D heterostructure for an MSC.

Nanotherapeutics targeting autophagy regulation for improved cancer therapy.

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.

Bridging Formal Shape Models and Deep Learning: A Novel Fusion for Understanding 3D Objects.

This article describes a novel fusion of a generative formal model for three-dimensional (3D) shapes with deep learning (DL) methods to understand the geometric structure of 3D objects and the relationships between their components, given a collection of unorganized point cloud measurements. Formal 3D shape models are implemented as shape grammar programs written in Procedural Shape Modeling Language (PSML). Users write PSML programs to describe complex objects, and DL networks estimate the configured free parameters of the program to generate 3D shapes. Users write PSML programs to enforce fundamental rules that define an object class and encode object attributes, including shapes, components, size, position, etc., into a parametric representation of objects. This fusion of the generative model with DL offers artificial intelligence (AI) models an opportunity to better understand the geometric organization of objects in terms of their components and their relationships to other objects. This approach allows human-in-the-loop control over DL estimates by specifying lists of candidate objects, the shape variations that each object can exhibit, and the level of detail or, equivalently, dimension of the latent representation of the shape. The results demonstrate the advantages of the proposed method over competing approaches.

A wide-bandgap graphene-like structure C6BN with ultra-low dielectric constant.

This study introduces a new wide-bandgap graphene-like structure, denoted as C6BN, achieved by incorporating an eight-electron BN pair, substantially modifying its electronic properties. Utilizing extensive density functional calculations, we comprehensively analyzed the stability, electronic structure, mechanical properties, and optical-electrical characteristics of C6BN. Our investigations reveal the material's exceptional thermodynamic, mechanical, and dynamic stability. Notably, the calculated wide bandgap of 2.81 eV in C6BN, supported by analyses of energy levels, band structures, and density of states, positions it as a promising two-dimensional wide-bandgap semiconductor. Additionally, C6BN exhibits isotropic mechanical features, highlighting its inherent flexibility. Remarkably, our calculations indicate an ultra-low dielectric constant (k = 1.67) for C6BN, surpassing that of well-established third-generation semiconductors. Further exploration into the thermoelectric properties of C6BN demonstrates its promising performance, as evidenced by calculations of thermal conductivity (κ), power factor (P), and Seebeck coefficient (S). In summary, our findings underscore the significant potential of the proposed C6BN structure as a flexible two-dimensional material poised to drive future advancements in electronic and energy-related technologies.

High-Speed Electro-Optic Modulators Based on Thin-Film Lithium Niobate.

Electro-optic modulators (EOMs) are pivotal in bridging electrical and optical domains, essential for diverse applications including optical communication, microwave signal processing, sensing, and quantum technologies. However, achieving the trifecta of high-density integration, cost-effectiveness, and superior performance remains challenging within established integrated photonics platforms. Enter thin-film lithium niobate (LN), a recent standout with its inherent electro-optic (EO) efficiency, proven industrial performance, durability, and rapid fabrication advancements. This platform inherits material advantages from traditional bulk LN devices while offering a reduced footprint, wider bandwidths, and lower power requirements. Despite its recent introduction, commercial thin-film LN wafers already rival or surpass established alternatives like silicon and indium phosphide, benefitting from decades of research. In this review, we delve into the foundational principles and technical innovations driving state-of-the-art LN modulator demonstrations, exploring various methodologies, their strengths, and challenges. Furthermore, we outline pathways for further enhancing LN modulators and anticipate exciting prospects for larger-scale LN EO circuits beyond singular components. By elucidating the current landscape and future directions, we highlight the transformative potential of thin-film LN technology in advancing electro-optic modulation and integrated photonics.

(Ca0.25La0.5Dy0.25)CrO3 Ceramic Fiber@Biomass-Derived Carbon Aerogel with Enhanced Solute Transport Channels for Highly Efficient Solar Interface Evaporation.

The use of solar interface evaporation for seawater desalination or sewage treatment is an environmentally friendly and sustainable approach; however, achieving efficient solar energy utilization and ensuring the long-term stability of the evaporation devices are two major challenges for practical application. To address these issues, we developed a novel ceramic fiber@bioderived carbon composite aerogel with a continuous through-hole structure via electrospinning and freeze-casting methods. Specifically, an aerogel was prepared by incorporating perovskite oxide (Ca0.25La0.5Dy0.25)CrO3 ceramic fibers (CCFs) and amylopectin-derived carbon (ADC). The CCFs exhibited remarkable photothermal conversion efficiencies, and the ADC served as a connecting agent and imparted hydrophilicity to the aerogel due to its abundant oxygen-containing functional groups. After optimizing the composition and microstructure, the (Ca0.25La0.5Dy0.25)CrO3 ceramic fiber@biomass-derived carbon aerogel demonstrated remarkable properties, including efficient light absorption and rapid transport of water and solutes. Under 1 kW m-2 light intensity irradiation, this novel material exhibited a high temperature (48.3 °C), high evaporation rate (1.68 kg m-2 h-1), and impressive solar vapor conversion efficiency (91.6%). Moreover, it exhibited long-term stability in water evaporation even with highly concentrated salt solutions (25 wt%). Therefore, the (Ca0.25La0.5Dy0.25)CrO3 ceramic fiber@biomass-derived carbon aerogel holds great promise for various applications of solar interface evaporation.

Efficacy of Apagliflozin Plus Pentoxifylline in the Treatment of Early Diabetic Nephropathy and Its Effect on Serum Inflammatory Factors and Immune Function.

Objective: To explore the efficacy of dapagliflozin plus pentoxifylline in the treatment of early diabetic nephropathy and its effect on serum inflammatory factors and immune function. Methods: A total of 90 patients with early diabetic nephropathy who were admitted to Cangzhou Central Hospital from January 2019 to January 2022 were recruited and randomized (1:1) into a control group and an observation group using the random number table method. The control group was treated with dapagliflozin, and the observation group was treated with pentoxifylline plus dapagliflozin. The effectiveness of urinary α (1) microglobulin (α 1-mg) was determined by immunoturbidimetric method, and urinary ß (2) microglobulin (ß 2-mg) was determined. Urine creatinine was determined enzymatically, and the urinary microprotein albumin creatinine ratio (mAlb/Cr) was calculated. The levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] were detected. Before and after treatment, 3 mL of venous blood was drawn from the two groups of patients, and serum CD4+, CD8+, and CD4+/CD8+ levels were detected. The incidence of adverse reactions between the two groups was calculated. Results: Dapagliflozin plus pentoxifylline was associated with a higher effective rate than dapagliflozin alone (96.67% vs 81.67%) (RR 0·80 [95% CI 0·61-0.98]; P = .021). Dapagliflozin plus pentoxifylline led to lower renal function parameters versus dapagliflozin alone, in favor of the observation group (RR 0.67 [95% CI 0.66-0.88]; P = .032). After treatment, the serum levels of IL-6 and TNF-α in patients treated with dapagliflozin plus pentoxifylline were lower than counterparts treated with dapagliflozin (RR 0.62 [95% CI 0.51-0.78]; P = .037). After treatment, CD4+ and CD4+/CD8+ in the two groups were increased compared with baseline parameters, and the level of CD8+ was decreased ; the increase and decrease were greater in the observation group than in the control group (RR 0.70 [95% CI 0.71-0.96]; P = .044) (RR 0.53 [95% CI 0.41-0.78]; P = .033). The two groups demonstrated similar safety profiles with no statistical difference observed in the incidence of adverse reactions between the two groups (RR 0.73 [95% CI 0.73-1.08]; P = .051). Conclusion: Dapagliflozin plus pentoxifylline might be a promising alternative in the treatment of patients with early diabetic nephropathy, it significantly mitigates the body's inflammatory response, enhances immune function, attenuates the main clinical symptoms, with a high safety profile.

UAV-Borne Mapping Algorithms for Low-Altitude and High-Speed Drone Applications.

This article presents an analysis of current state-of-the-art sensors and how these sensors work with several mapping algorithms for UAV (Unmanned Aerial Vehicle) applications, focusing on low-altitude and high-speed scenarios. A new experimental construct is created using highly realistic environments made possible by integrating the AirSim simulator with Google 3D maps models using the Cesium Tiles plugin. Experiments are conducted in this high-realism simulated environment to evaluate the performance of three distinct mapping algorithms: (1) Direct Sparse Odometry (DSO), (2) Stereo DSO (SDSO), and (3) DSO Lite (DSOL). Experimental results evaluate algorithms based on their measured geometric accuracy and computational speed. The results provide valuable insights into the strengths and limitations of each algorithm. Findings quantify compromises in UAV algorithm selection, allowing researchers to find the mapping solution best suited to their application, which often requires a compromise between computational performance and the density and accuracy of geometric map estimates. Results indicate that for UAVs with restrictive computing resources, DSOL is the best option. For systems with payload capacity and modest compute resources, SDSO is the best option. If only one camera is available, DSO is the option to choose for applications that require dense mapping results.

Medium- and High-Entropy Rare Earth Hexaborides with Enhanced Solar Energy Absorption and Infrared Emissivity.

The development of a new generation of solid particle solar receivers (SPSRs) with high solar absorptivity (0.28-2.5 µm) and high infrared emissivity (1-22 µm) is crucial and has attracted much attention for the attainment of the goals of "peak carbon" and "carbon neutrality". To achieve the modulation of infrared emission and solar absorptivity, two types of medium- and high-entropy rare-earth hexaboride (ME/HEREB6) ceramics, (La0.25Sm0.25Ce0.25Eu0.25)B6 (MEREB6) and (La0.2Sm0.2Ce0.2Eu0.2Ba0.2)B6 (HEREB6), with severe lattice distortions were synthesized using a high-temperature solid-phase method. Compared to single-phase lanthanum hexaboride (LaB6), HEREB6 ceramics show an increase in solar absorptivity from 54.06% to 87.75% in the range of 0.28-2.5 µm and an increase in infrared emissivity from 76.19% to 89.96% in the 1-22 µm wavelength range. On the one hand, decreasing the free electron concentration and the plasma frequency reduces the reflection and ultimately increases the solar absorptivity. On the other hand, the lattice distortion induces changes in the B-B bond length, leading to significant changes in the Raman scattering spectrum, which affects the damping constant and ultimately increases the infrared emissivity. In conclusion, the multicomponent design can effectively improve the solar energy absorption and heat transfer capacity of ME/HEREB6, thus providing a new avenue for the development of solid particles.

Tunable double notch filter on a thin-film lithium niobate platform.

Tunable optical filters at the chip scale play a crucial role in fulfilling the need for reconfigurability in channel routing, optical switching, and wavelength division multiplexing systems. In this Letter, we propose a tunable double notch filter on thin-film lithium niobate using dual microring architecture. This unique integrated filter is essential for complex photonic integrated circuits, along with multiple channels and various frequency spacing. With only one loaded voltage, the device demonstrates a wide frequency spacing tunability from 16.1 to 89.9 GHz by reversely tuning the resonances of the two microrings while the center wavelength between the two resonances remains unaltered. Moreover, by utilizing the pronounced electro-optic properties of lithium niobate associated with the tight light confined nanophotonic waveguides, the device demonstrates a spacing tunability of 0.82 GHz/V and a contrast of 10-16 dB. In addition, the device has an ultracompact footprint of 0.0248 mm2.

Electrolyte Optimization Strategy: Enabling Stable and Eco-Friendly Zinc Adaptive Interfacial Layer in Zinc Ion Batteries.

Aqueous zinc ion batteries (AZIBs) have emerged as a promising battery technology due to their excellent safety, high capacity, low cost, and eco-friendliness. However, the cycle life of AZIBs is limited by severe side reactions and zinc dendrite growth on the zinc electrode surface, hindering large-scale application. Here, an electrolyte optimization strategy utilizing the simplest dipeptide glycylglycine (Gly-Gly) additive is first proposed. Theoretical calculations and spectral analysis revealed that, due to the strong interaction between the amino group and Zn atoms, Gly-Gly preferentially adsorbs on zinc's surface, constructing a stable and adaptive interfacial layer that inhibits zinc side reactions and dendrite growth. Furthermore, Gly-Gly can regulate zinc ion solvation, leading to a deposition mode shift from dendritic to lamellar and limiting two-dimensional dendrite diffusion. The symmetric cell with the addition of a 20 g/L Gly-Gly additive exhibits a cycle life of up to 1100 h. Under a high current density of 10 mA cm-2, a cycle life of 750 cycles further demonstrates the reliable adaptability of the interfacial layer. This work highlights the potential of Gly-Gly as a promising solution for improving the performance of AZIBs.

Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis.

Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment.

Nanomaterial-mediated modulation of the cGAS-STING signaling pathway for enhanced cancer immunotherapy.

Despite the current promise of immunotherapy, many cancer patients still suffer from challenges such as poor immune response rates, resulting in unsatisfactory clinical efficacy of existing therapies. There is an urgent need to combine emerging biomedical discoveries and innovations in traditional therapies. Modulation of the cGAS-STING signalling pathway represents an important innate immunotherapy pathway that serves as a crucial DNA sensing mechanism in innate immunity and viral defense. It has attracted increasing attention as an emerging target for cancer therapy. The recent advancements in nanotechnology have led to the significant utilization of nanomaterials in cancer immunotherapy, owing to their exceptional physicochemical properties such as large specific surface area and efficient permeability. Given the rapid development of cancer immunotherapy driven by the cGAS-STING activation, this study reviews the latest research progress in employing nanomaterials to modulate this signaling pathway. Based on the introduction of the main activation mechanisms of cGAS-STING pathway, this review focuses on nanomaterials that mediate the agonists involved and effectively activate this signaling pathway. In addition, combination nanotherapeutics based on the activation of the cGAS-STING signaling pathway are also discussed, including emerging strategies combining nanoformulated agonists with chemotherapy, radiotherapy as well as other immunomodulation in tumor targeting therapy. STATEMENT OF SIGNIFICANCE: Given the rapid development of cancer immunotherapy driven by the cGAS / STING activation, this study reviews the latest research advances in the use of nanomaterials to modulate this signaling pathway. Based on the introduction of key cGAS-STING components and their activation mechanisms, this review focuses on nanomaterials that can mediate the corresponding agonists and effectively activate this signaling pathway. In addition, combination nanotherapies based on the activation of the cGAS-STING signaling pathway are also discussed, including emerging strategies combining nanoformulated agonists with chemotherapy, radiotherapy as well as immunomodulation in cancer therapy,.

Clinical efficacy of rhGM-CSF gel and medical collagen sponge on deep second-degree burns of infants: A randomized clinical trial.

BACKGROUND: This study aimed to observe clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, medical collagen sponge and rhGM-CSF gel in combination with medical collagen sponge on deep second-degree burns of head, face or neck in infants. METHODS: A total of 108 infants with deep second-degree burns on head, face or neck were randomly divided into rhGM-CSF group, medical collagen sponge group, and rhGM-CSF + medical collagen sponge group. The scab dissolving time, healing time, bacterial positive rate and Vancouver scar scale were evaluated and analyzed. RESULTS: The data analysis showed that scab dissolving time and healing time were shorter in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group, and the difference was statistically significant (P < .05). Bacterial positive rate was lower in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). After 3 months, score of Vancouver scar scale (scar thickness, pliability, pigmentation and vascularity) was less in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). CONCLUSION: rhGM-CSF gel in combination with medical collagen sponge is significantly effective in treating deep second-degree burns of head, face or neck in infants. This combination is beneficial for infection control, acceleration of scab dissolving and wound healing, and reduction of scar hyperplasia and pigmentation, which is worthy of clinical application and promotion.

Recent Progress of Wide Bandgap Perovskites towards Two-Terminal Perovskite/Silicon Tandem Solar Cells.

Perovskite/silicon tandem solar cells have garnered considerable interest due to their potential to surpass the Shockley-Queisser limit of single-junction Si solar cells. The rapidly advanced efficiencies of perovskite/silicon tandem solar cells benefit from the significant improvements in perovskite technology. Beginning with the evolution of wide bandgap perovskite cells towards two-terminal (2T) perovskite/silicon tandem solar cells, this work concentrates on component engineering, additives, and interface modification of wide bandgap perovskite cells. Furthermore, the advancements in 2T perovskite/silicon tandem solar cells are presented, and the influence of the central interconnect layer and the Si cell on the progression of the tandem solar cells is emphasized. Finally, we discuss the challenges and obstacles associated with 2T perovskite/silicon tandem solar cells, conducting a thorough analysis and providing a prospect for their future.

Highly Responsive Gate-Controlled p-GaN/AlGaN/GaN Ultraviolet Photodetectors with a High-Transmittance Indium Tin Oxide Gate.

This work presents highly responsive gate-controlled p-GaN/AlGaN/GaN ultraviolet photodetectors (UVPDs) on Si substrates with a high-transmittance ITO gate. The two-dimensional electron gas (2DEG) in the quantum well of the polarized AlGaN/GaN heterojunction was efficiently depleted by the p-GaN gate, leading to a high photo-to-dark current ratio (PDCR) of 3.2 × 105. The quantum wells of the p-GaN/AlGaN and AlGaN/GaN heterojunctions can trap the holes and electrons excited by the UV illumination, thus efficiently triggering a photovoltaic effect and photoconductive effect, separately. Furthermore, the prepared photodetectors allow flexible adjustment of the static bias point, making it adaptable to different environments. Compared to traditional thin-film semi-transparent Ni/Au gates, indium tin oxide (ITO) exhibits higher transmittance. Under 355 nm illumination, the photodetector exhibited a super-high responsivity exceeding 3.5 × 104 A/W, and it could even exceed 106 A/W under 300 nm illumination. The well-designed UVPD combines both the advantages of the high-transmittance ITO gate and the structure of the commercialized p-GaN/AlGaN/GaN high-electron-mobility transistors (HEMTs), which opens a new possibility of fabricating large-scale, low-cost, and high-performance UVPDs in the future.