Protein-guided biomimetic nanomaterials: a versatile theranostic nanoplatform for biomedical applications.

Over the years, bioinspired mineralization-based approaches have been applied to synthesize multifunctional organic-inorganic nanocomposites. These nanocomposites can address the growing demands of modern biomedical applications. Proteins, serving as vital biological templates, play a pivotal role in the nucleation and growth processes of various organic-inorganic nanocomposites. Protein-mineralized nanomaterials (PMNMs) have attracted significant interest from researchers due to their facile and convenient preparation, strong physiological activity, stability, impressive biocompatibility, and biodegradability. Nevertheless, few comprehensive reviews have expounded on the progress of these nanomaterials in biomedicine. This article systematically reviews the principles and strategies for constructing nanomaterials using protein-directed biomineralization and biomimetic mineralization techniques. Subsequently, we focus on their recent applications in the biomedical field, encompassing areas such as bioimaging, as well as anti-tumor, anti-bacterial, and anti-inflammatory therapies. Furthermore, we discuss the challenges encountered in practical applications of these materials and explore their potential in future applications. This review aspired to catalyze the continued development of these bioinspired nanomaterials in drug development and clinical diagnosis, ultimately contributing to the fields of precision medicine and translational medicine.

Systematic pan-cancer analysis of RNF186 with potential implications in progression and prognosis in human cancer.

AIMS: Cancer remains a significant global public health issue. There is growing proof that Ring Finger Protein 186 (RNF186) may play a function in pan-cancer, however, this has not yet been thoroughly determined. This study aims to analyze RNF186 with potential implications in progression and prognosis in human cancer. MATERIALS AND METHODS: A comprehensive bioinformatics approaches combined with experimental verification were used across 33 types of cancers in this study to conduct a pan-cancer investigation of RNF186 from the perspectives of gene expression, prognosis, genomic alterations, immunological markers, gene set, and function. KEY FINDINGS: RNF186 is a valuable prognostic biomarker in several cancer types, especially breast invasive carcinoma (BRCA) and uterine corpus endometrial carcinoma (UCEC). The levels of RNF186 promoter methylation and genetic alterations may be responsible for some cancers' abnormal expression. Furthermore, RNF186 expression was determined to be associated with immune checkpoint genes. Analysis of RNF186-related genes revealed that proteasome and PI3K-AKT signaling pathway were primarily involved in the cellular function of RNF186. Additionally, our research first confirmed that RNF186 may function as an oncogene and contribute to cancer proliferation, migration and invasion in UCEC. In contrast, RNF186 may play an inhibitory role in BRCA progression. This function depends on the ligase activity of RNF186. SIGNIFICANCE: This study suggests that RNF186 is a novel critical target for tumor progression in BRCA and UCEC. It reveals that RNF186 may be associated with tumor immunotherapy, which may provide an effective predictive evaluation of the prognosis of immunotherapy.

Trauma THOMPSON: Clinical Decision Support for the Frontline Medic.

INTRODUCTION: U.S. Military healthcare providers increasingly perform prolonged casualty care because of operations in settings with prolonged evacuation times. Varied training and experience mean that this care may fall to providers unfamiliar with providing critical care. Telemedicine tools with audiovisual capabilities, artificial intelligence (AI), and augmented reality (AR) can enhance inexperienced personnel's competence and confidence when providing prolonged casualty care. Furthermore, implementing offline functionality provides assistance options in communications-limited settings. The intent of the Trauma TeleHelper for Operational Medical Procedure Support and Offline Network (THOMPSON) is to develop (1) a voice-controlled mobile application with video references for procedural guidance, (2) audio narration of each video using procedure mentoring scripts, and (3) an AI-guided intervention system using AR overlay and voice command to create immersive video modeling. These capabilities will be available offline and in downloadable format. MATERIALS AND METHODS: The Trauma THOMPSON platform is in development. Focus groups of subject matter experts will identify appropriate procedures and best practices. Procedural video recordings will be collected to develop reference materials for the Trauma THOMPSON mobile application and to train a machine learning algorithm on action recognition and anticipation. Finally, an efficacy evaluation of the application will be conducted in a simulated environment. RESULTS: Preliminary video collection has been initiated for tube thoracostomy, needle decompression, cricothyrotomy, intraosseous access, and tourniquet application. Initial results from the machine learning algorithm show action recognition and anticipation accuracies of 20.1% and 11.4%, respectively, in unscripted datasets "in the wild," notably on a limited dataset. This system performs over 100 times better than a random prediction. CONCLUSIONS: Developing a platform to provide real-time, offline support will deliver the benefits of synchronous expert advice within communications-limited and remote environments. Trauma THOMPSON has the potential to fill an important gap for clinical decision support tools in these settings.

Staphylococcus epidermidis activates keratinocyte cytokine expression and promotes skin inflammation through the production of phenol-soluble modulins.

Staphylococcus epidermidis is a common microbe on human skin and has beneficial functions in the skin microbiome. However, under conditions of allergic inflammation, the abundance of S. epidermidis increases, establishing potential danger to the epidermis. To understand how this commensal may injure the host, we investigate phenol-soluble modulin (PSM) peptides produced by S. epidermidis that are similar to peptides produced by Staphylococcus aureus. Synthetic S. epidermidis PSMs induce expression of host defense genes and are cytotoxic to human keratinocytes. Deletion mutants of S. epidermidis lacking these gene products support these observations and further show that PSMs require the action of the EcpA bacterial protease to induce inflammation when applied on mouse skin with an intact stratum corneum. The expression of PSMδ from S. epidermidis is also found to correlate with disease severity in patients with atopic dermatitis. These observations show how S. epidermidis PSMs can promote skin inflammation.

The Notch Signaling Pathway Contributes to Angiogenesis and Tumor Immunity in Breast Cancer.

Breast cancer in women is the first leading tumor in terms of incidence worldwide. Some subtypes of BC lack distinct molecular targets and exhibit therapeutic resistance; these patients have a poor prognosis. Thus, the search for new molecular targets is an ongoing challenge for BC therapy. The Notch signaling pathway is found in both vertebrates and invertebrates, and it is a highly conserved in the evolution of the species, controlling cellular fates such as death, proliferation, and differentiation. Numerous studies have shown that improper activation of Notch signaling may lead to excessive cell proliferation and cancer, with tumor-promoting and tumor-suppressive effects in various carcinomas. Thus, inhibitors of Notch signaling are actively being investigated for the treatment of various tumors. The role of Notch signaling in BC has been widely studied in recent years. There is a growing body of evidence suggesting that Notch signaling has a pro-oncogenic role in BC, and the tumor-promoting effect is largely a result of the diverse nature of tumor immunity. Immunological abnormality is also a factor involved in the pathogenesis of BC, suggesting that Notch signaling could be a target for BC immunotherapies. Furthermore, angiogenesis is essential for BC growth and metastasis, and the Notch signaling pathway has been implicated in angiogenesis, so studying the role of Notch signaling in BC angiogenesis will provide new prospects for the treatment of BC. We summarize the potential roles of the current Notch signaling pathway and its inhibitors in BC angiogenesis and the immune response in this review and describe the pharmacological targets of Notch signaling in BC, which may serve as a theoretical foundation for future research into exploring this pathway for novel BC therapies.

Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway.

Objective: Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms. Methods: First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and ß-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and ß-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and ß-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis. Results: Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and ß-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and ß-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and ß-sitosterol produced similar outcomes. Conclusion: The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.

MnO2-coated porous Pt@CeO2 core-shell nanostructures for photoacoustic imaging-guided tri-modal cancer therapy.

We describe the synthesis of MnO2-coated porous Pt@CeO2 core-shell nanostructures (Pt@CeO2@MnO2) as a new theranostic nano-platform. The porous Pt cores endow the core-shell nanostructures with high photothermal conversion efficiency (80%) in the near-infrared region, allowing for photothermal therapy (PTT) and photoacoustic imaging (PA) of tumors. The combination of the Pt core and porous CeO2 interlayer enhances the separation of photo-generated electrons and holes, which is beneficial for the generation of singlet oxygen. With the porous structures of the cores and interlayers, the Pt@CeO2@MnO2 nanostructures are further loaded with an anti-cancer drug (doxorubicin, DOX). The degradation of the MnO2 shell in the tumor microenvironment (TME) can generate O2 for enhanced photodynamic therapy (PDT) and simultaneously trigger DOX release. PA imaging shows good accumulation and retention of DOX-loaded Pt@CeO2@MnO2 in tumors, which guides precise laser irradiation to initiate combined PTT and PDT. The synergistic PTT/PDT/chemotherapy demonstrated by DOX-loaded Pt@CeO2@MnO2 yields remarkable therapeutic outcomes in vitro and in vivo. Taken together, our DOX-loaded Pt@CeO2@MnO2 provides a new avenue for designing high-performance nano-platforms for imaging and therapeutics.

(Gold nanorod core)/(poly(3,4-ethylene-dioxythiophene) shell) nanostructures and their monolayer arrays for plasmonic switching.

(Gold nanorod core)/(poly(3,4-ethylene-dioxythiophene) (PEDOT) shell) nanostructures are prepared by the surfactant-assisted oxidative polymerization of 3,4-ethylene-dioxythiophene on the surface of gold nanorods (NRs). The PEDOT shell exhibits distinct dielectric properties at doped and undoped states, which allows the manipulation of plasmonic responses of the Au nanorod core. The shift in plasmon resonance induced by the dedoping of PEDOT is found to be associated with the overlap between the plasmon resonance band of the core/shell nanostructure and the spectral region where the largest refractive index variation of PEDOT occurs, as well as with the type of the dedopant. Macroscopic two-dimensional (2D) monolayer arrays of core/shell nanostructures with controlled particle number densities are fabricated on indium tin oxide (ITO)-coated glass substrates by electrophoretic deposition. A reversible plasmonic shift of about 70 nm is obtained on the core/shell nanostructure monolayer array with a number density of around 18 particles per µm2. Our design of colloidal (Au nanorod core)/(PEDOT shell) nanostructures and their 2D monolayer arrays paves the way for the fabrication of high-performance plasmonic switches in large-scale practical usages as well as for the preparation of advanced, programmable chromic materials for a broad range of applications, such as smart windows, anti-counterfeiting tags, and medical and environmental sensors.

Polyaniline/Carbon Nanotubes Composite Modified Anode via Graft Polymerization and Self-Assembling for Microbial Fuel Cells.

Microbial fuel cells (MFCs) are promising devices for sustainable energy production, wastewater treatment and biosensors. Anode materials directly interact with electricigens and accept electrons between cells, playing an important role in determining the performance of MFCs. In this study, a novel carbon nanotubes (CNTs) and polyaniline (PANI) nanocomposite film modified Indium-tin oxide (ITO) anode was fabricated through graft polymerization of PANI after the modification of γ-aminopropyltriethoxysilane (APTES) on ITO substrate, which was followed by layer-by-layer (LBL) self-assembling of CNTs and PANI alternatively on its surface. (CNTs/PANI)n/APTES/ITO electrode with low charge transfer resistance showed better electrochemical behavior compared to the bare ITO electrode. Twelve layers of CNTs/PANI decorated ITO electrode with an optimal nanoporous network exhibited superior biocatalytic properties with a maximal current density of 6.98 µA/cm², which is 26-fold higher than that of conventional ITO electrode in Shewanella loihica PV-4 bioelectrochemical system. MFCs with (CNTs/PANI)12/APTES/ITO as the anode harvested a maximum output power density of 34.51 mW/m², which is 7.5-fold higher than that of the unmodified ITO electrode. These results demonstrate that (CNTs/PANI)12/APTES/ITO electrode has superior electrochemical and electrocatalytic properties compared to the bare ITO electrode, while the cellular toxicity of CNTs has an effect on the performance of MFC with (CNTs/PANI)n/APTES/ITO electrode.

Active Plasmonics: Principles, Structures, and Applications.

Active plasmonics is a burgeoning and challenging subfield of plasmonics. It exploits the active control of surface plasmon resonance. In this review, a first-ever in-depth description of the theoretical relationship between surface plasmon resonance and its affecting factors, which forms the basis for active plasmon control, will be presented. Three categories of active plasmonic structures, consisting of plasmonic structures in tunable dielectric surroundings, plasmonic structures with tunable gap distances, and self-tunable plasmonic structures, will be proposed in terms of the modulation mechanism. The recent advances and current challenges for these three categories of active plasmonic structures will be discussed in detail. The flourishing development of active plasmonic structures opens access to new application fields. A significant part of this review will be devoted to the applications of active plasmonic structures in plasmonic sensing, tunable surface-enhanced Raman scattering, active plasmonic components, and electrochromic smart windows. This review will be concluded with a section on the future challenges and prospects for active plasmonics.

Investigation of silk fibroin nanoparticle-decorated poly(l-lactic acid) composite scaffolds for osteoblast growth and differentiation.

Attempts to reflect the physiology of organs is quite an intricacy during the tissue engineering process. An ideal scaffold and its surface topography can address and manipulate the cell behavior during the regeneration of targeted tissue, affecting the cell growth and differentiation significantly. Herein, silk fibroin (SF) nanoparticles were incorporated into poly(l-lactic acid) (PLLA) to prepare composite scaffolds via phase-inversion technique using supercritical carbon dioxide (SC-CO2). The SF nanoparticle core increased the surface roughness and hydrophilicity of the PLLA scaffolds, leading to a high affinity for albumin attachment. The in vitro cytotoxicity test of SF/PLLA scaffolds in L929 mouse fibroblast cells indicated good biocompatibility. Then, the in vitro interplay between mouse preosteoblast cell (MC3T3-E1) and various topological structures and biochemical cues were evaluated. The cell adhesion, proliferation, osteogenic differentiation and their relationship with the structures as well as SF content were explored. The SF/PLLA weight ratio (2:8) significantly affected the MC3T3-E1 cells by improving the expression of key players in the regulation of bone formation, ie, alkaline phosphatase (ALP), osteocalcin (OC) and collagen 1 (COL-1). These results suggest not only the importance of surface topography and biochemical cues but also the potential of applying SF/PLLA composite scaffolds as biomaterials in bone tissue engineering.

Active Electrochemical Plasmonic Switching on Polyaniline-Coated Gold Nanocrystals.

High-performance electrochemical plasmonic switching is realized on both single-particle and ensemble levels by coating polyaniline on colloidal gold nanocrystals through surfactant-assisted oxidative polymerization. Under small applied potentials, the core@shell nanostructures exhibit reversible plasmon shifts as large as 150 nm, a switching time of less than 10 ms, and a high switching stability.

Switching plasmon coupling through the formation of dimers from polyaniline-coated gold nanospheres.

Active modulation of the plasmon coupling in homodimers of polyaniline (PANI)-coated Au nanospheres is achieved by changing the proton-doping state of the PANI shell. Such a PANI-enabled modulation of the plasmon coupling in the dimers gives rise to remarkable spectral shifts, which show an exponential dependence on the interparticle gap distance. For the dimer with a 10 nm PANI shell thickness and a 0.5 nm gap distance, the shift of the stronger scattering peak in response to the active modulation reaches 231 nm. Electrodynamic simulations reveal that the shift of the dipolar bonding plasmon mode dominates the position variation of the stronger scattering peak for the dimers with different gap distances. Moreover, the quadrupolar bonding plasmon mode can be turned on and off by controlling the proton-doping state of the dimers with gap distances of less than ∼3 nm. These results are of high importance for fundamentally understanding the sensitivity of coupled plasmon resonance modes to the dielectric environment, as well as for designing active plasmonic devices with high modulation performances.

(Gold nanorod core)/(polyaniline shell) plasmonic switches with large plasmon shifts and modulation depths.

(Gold nanorod core)/(polyaniline shell) nanostructures are prepared for functioning as active plasmonic switches. The single core/shell nanostructures exhibit a remarkable switching performance, with the modulation depth and scattering peak shift reaching 10 dB and 100 nm, respectively. The nanostructures are also deposited on substrates to form macroscale monolayers with remarkable ensemble plasmonic switching performances.

Polyaniline nanofibers assembled on alginate microsphere for Cu2+ and Pb2+ uptake.

Polyaniline (PANI) nanofibers were assembled on the micro- or millimeter-scale calcium alginate (CA) beads by "competitive adsorption-restricted polymerization" approach. The CA beads made the dimensional expansion of PANI nanofibers evident, which overcame the serious aggregation of PANI nanofibers and benefited the practical operation of PANI nanofibers. Batch adsorption results showed that the millimeter-scale CA beads decorated by PANI nanofibers had high affinity to Cu(2+) and Pb(2+) in aqueous solutions. The removal percentages of Cu(2+) and Pb(2+) in aqueous solutions by this PANI/CA composite with milli/nano hierarchical structure surpassed 90% in a wide pH range from 3 to 7. Sorption of the two kinds of ions to PANI/CA composite sorbent agreed well with the Freundlich adsorption model. The adsorption kinetic results of Cu(2+) and Pb(2+) showed that the adsorption reached equilibrium within 120min and 40min, respectively. And their adsorption rates could be described by pseudo-second-order kinetics. The desorption percentages of Pb(2+) and Cu(2+) from this PANI/CA composite are 62% and 75%, respectively. The Pb(2+) and Cu(2+) removal capacity of the sorbent could be further reinforced when the diameter of CA beads turned from millimeter to micrometer.

CuO based inorganic-organic hybrid nanowires: a new type of highly sensitive humidity sensor.

The organic surfactant template method has been widely used for the preparation of CuO nanorods, nanotubes and nanowires. However, the surfactants in this system have no effect on the properties of the final products because they are flushed away. In this work, we used this method to synthesize a novel type of inorganic-organic hybrid nanowire via the hybridization between CuO and amphiphilic oligomer octadecyl, polyethylene glycol di-butenetrioate (O-B-EG-B). Here O-B-EG-B, as a structure director, was not flushed away but remained in the prepared hybrid nanowires because it was bound around CuO or entrapped in interior CuO. The hybrid nanowires showed CuO cores and P(O-B-EG-B) shells when the concentration of O-B-EG-B was 0.4 mg ml(-1), but exhibited P(O-B-EG-B) cores and CuO shells when the concentration of O-B-EG-B was 4.0 mg ml(-1). We found that the hybrid nanowires with P(O-B-EG-B) cores and CuO shells could sense a slight change in the relative humidity (RH) and respond by rapidly changing their conductivity. The resistance changed by about two orders of magnitude within the humidity range from 5% to 83.8%. Moreover, a humidity sensor based on this type of nanowire not only showed long-term stability but also exhibited excellent reversibility to moisture changes in air.