Improving Three-Photon Fluorescence of Near-Infrared Quantum Dots for Deep Brain Imaging by Suppressing Biexciton Decay.

Three-photon fluorescence microscopy (3PFM) is a promising brain research tool with submicrometer spatial resolution and high imaging depth. However, only limited materials have been developed for 3PFM owing to the rigorous requirement of the three-photon fluorescence (3PF) process. Herein, under the guidance of a band gap engineering strategy, CdTe/CdSe/ZnS quantum dots (QDs) emitting in the near-infrared window are designed for constructing 3PF probes. The formation of type II structure significantly increased the three-photon absorption cross section of QDs and caused the delocalization of electron-hole wave functions. The time-resolved transient absorption spectroscopy confirmed that the decay of biexcitons was significantly suppressed due to the appropriate band gap alignment, which further enhanced the 3PF efficiency of QDs. By utilizing QD-based 3PF probes, high-resolution 3PFM imaging of cerebral vasculature was realized excited by a 1600 nm femtosecond laser, indicating the possibility of deep brain imaging with these 3PF probes.

IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell-autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.

Enhancement Effects and Mechanism Studies of Two Bismuth-Based Materials Assisted by DMSO and Glycerol in GC-Rich PCR.

Polymerase chain reaction (PCR) has extensive bioanalytical applications in molecular diagnostics and genomic research studies for rapid detection and precise genomic amplification. Routine integrations for analytical workflow indicate certain limitations, including low specificity, efficiency, and sensitivity in conventional PCR, particularly towards amplifying high guanine-cytosine (GC) content. Further, there are many ways to enhance the reaction, for example, using different PCR strategies such as hot-start/touchdown PCR or adding some special modifications or additives such as organic solvents or compatible solutes, which can improve PCR yield. Due to the widespread use of bismuth-based materials in biomedicine, which have not yet been used for PCR optimization, this attracts our attention. In this study, two bismuth-based materials that are inexpensive and readily available were used to optimize GC-rich PCR. The results demonstrated that ammonium bismuth citrate and bismuth subcarbonate effectively enhanced PCR amplification of the GNAS1 promoter region (∼84% GC) and APOE (75.5% GC) gene of Homo sapiens mediated by Ex Taq DNA polymerase within the appropriate concentration range. Combining DMSO and glycerol additives was critical in obtaining the target amplicons. Thus, the solvents mixed with 3% DMSO and 5% glycerol were used in bismuth-based materials. That allowed for better dispersion of bismuth subcarbonate. As for the enhanced mechanisms, the surface interaction of PCR components, including Taq polymerase, primer, and products with bismuth-based materials, was maybe the main reason. The addition of materials can reduce the melting temperature (Tm), adsorb polymerase and modulate the amount of active polymerase in PCR, facilize the dissociation of DNA products, and enhance the specificity and efficiency of PCR. This work provided a class of candidate enhancers for PCR, deepened our understanding of the enhancement mechanisms of PCR, and also explored a new application field for bismuth-based materials.

Exploring the Inhibitory Effect of AgBiS2 Nanoparticles on Influenza Viruses.

Influenza viruses are respiratory pathogens that are major threats to human health. Due to the emergence of drug-resistant strains, the use of traditional anti-influenza drugs has been hindered. Therefore, the development of new antiviral drugs is critical. In this article, AgBiS2 nanoparticles were synthesized at room temperature, using the bimetallic properties of the material itself to explore its inhibitory effect on the influenza virus. By comparing the synthesized Bi2S3 and Ag2S nanoparticles, it is found that after adding the silver element, the synthesized AgBiS2 nanoparticles have a significantly better inhibitory effect on influenza virus infection than Bi2S3 and Ag2S nanoparticles. Recent studies have shown that the inhibitory effect of AgBiS2 nanoparticles on the influenza virus mainly occurs in the stages of influenza virus-cell internalization and intracellular replication. In addition, it is found that AgBiS2 nanoparticles also have prominent antiviral properties against α and ß coronaviruses, indicating that AgBiS2 nanoparticles have significant potential in inhibiting viral activity.

ß2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages.

Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that ß2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-ß1 (TGFß1). Inhibition of B2M attenuated GSC survival, self-renewal, and tumor growth. B2M-induced TGFß1 secretion activated paracrine SMAD and PI3K/AKT signaling in TAMs and promoted an M2-like macrophage phenotype. These findings reveal tumor-promoting functions of B2M and suggest that targeting B2M or its downstream axis may provide an effective approach for treating GBM. SIGNIFICANCE: ß2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGFß1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.

How Do Bismuth-Based Nanomaterials Function as Promising Theranostic Agents for the Tumor Diagnosis and Therapy?

The complexity of the tumor microenvironment and the diversity of tumors seriously affect the therapeutic effect, the focus, therefore, has gradually been shifted from monotherapy to combination therapy in clinical research in order to improve the curative effect. The synergistic enhancement interactions among multiple monotherapies majorly contribute to the birth of the multi-mode cooperative therapy, whose effect of the treatment is clearly stronger than that of any single therapy. In addition, the accurate diagnosis of the tumour location is also crucial to the treatment. Bismuth-based nanomaterials (NMs) hold great properties as promising theranostic platforms based on their many unique features that include low toxicity, excellent photothermal conversion efficiency as well as the high ability of X-ray computed tomography imaging and photoacoustic imaging. In this review, we will introduce briefly the main features of the tumor microenvironment first and its effect on the mechanism of nanomedicine actions and present the recent advances of bismuth-based NMs for diagnosis and photothermal therapy-based combined therapies using bismuth-based NMs are presented, which may provide a new way for overcoming drug resistance and hypoxia. In the end, further challenges and outlooks regarding this promising field are discussed accompanied with some design tips for bismuth- based NMs, hoping to provide researchers some inspiration to design safe and effective nanotherapeutic agents for clinical treatments of cancers.

Metal-Based Nanomaterials: Work as Drugs and Carriers against Viral Infections.

Virus infection is one of the threats to the health of organisms, and finding suitable antiviral agents is one of the main tasks of current researchers. Metal ions participate in multiple key reaction stages of organisms and maintain the important homeostasis of organisms. The application of synthetic metal-based nanomaterials as an antiviral therapy is a promising new research direction. Based on the application of synthetic metal-based nanomaterials in antiviral therapy, we summarize the research progress of metal-based nanomaterials in recent years. This review analyzes the three inhibition pathways of metal nanomaterials as antiviral therapeutic materials against viral infections, including direct inactivation, inhibition of virus adsorption and entry, and intracellular virus suppression; it further classifies and summarizes them according to their inhibition mechanisms. In addition, the use of metal nanomaterials as antiviral drug carriers and vaccine adjuvants is summarized. The analysis clarifies the antiviral mechanism of metal nanomaterials and broadens the application in the field of antiviral therapy.

Recent advances in nanosized metal organic frameworks for drug delivery and tumor therapy.

Metal organic-frameworks (MOFs) are novel materials that have attracted increasing attention for applications in a wide range of research, owing to their unique advantages including their small particle size, porous framework structure and high specific surface area. Because of their adjustable size, nanoscale MOFs (nano-MOFs) can be prepared as carriers of biotherapy drugs, thus enabling biotherapeutic applications. Nano-MOFs' metal ion catalytic activity and organic group functional characteristics can be exploited in biological treatments. Furthermore, the applications of nano-MOFs can be broadened by hybridization with other materials to form composites. This review focuses on the preparation and recent advances in nano-MOFs as drug carriers, therapeutic materials and functionalized materials in drug delivery and tumor therapy based on the single/multiple stimulus response of drug release to achieve the targeted therapy, offering a comprehensive reference for drug carrier design. At the end, the current challenges and prospects are discussed to provide significant insight into the design and applications of nano-MOFs in drug delivery and tumor therapy.

Numerical simulation and field experiment study on onboard dust removal technology based on airflow-dust pollution dispersion characteristics.

To solve the problem of dust production by the caving coal seam on the weather side of a fully mechanized coal face with a large mining height, this study proposes coal cutter onboard dust removal technology for the first time. In this work, taking the 12511 fully mechanized coal face of the Bulianta Coal Mine with a large mining height as an example, a mathematical model was built to study the influence of the onboard dust collector on airflow-dust dispersion pollution and the key technological parameters of the dust collector, and field tests were performed for verification. The results of numerical simulation showed that the dust-carrying airflow, after being blocked by the coal cutter, dispersed in the lateral direction, leading to an increase of airflow velocity on the walkway side to 1.75 m s-1, and a dust concentration as high as 2500 mg m-3. At the same time, an airflow vortex area with the largest diameter of 3 m was formed near the surface of the coal cutter body, which attracted dust to gather there. However, after the application of the onboard dust removal technology, the lateral dispersion of dust-carrying airflow weakened, and the dust concentration on the walkway side was reduced to below 600 mg m-3. In addition, this technology also obviously reduced the influence scope of the vortex and the dust concentration area. It was also found that the installation height of the suction inlet of the dust collector and the air capacity had a large impact on the dust suppression efficiency. The optimum dust suppression efficiency was reached at an installation height of 1.15 m and air capacity of 120 m3 min-1. Field test verification demonstrated that the dust concentration on the walkway side could be reduced by as much as 49.3% with the application of the proposed onboard dust removal technology.

Robust and Cooperative Localization for Underwater Sensor Networks in the Existence of Malicious Anchors.

Precise and robust localization in three-dimensional underwater sensor networks is still an important research problem. This problem is particularly challenging if there are some malicious anchors among ordinary anchor nodes that will broadcast their locations falsely and deliberately. In this paper, we study how to self-localize large teams of underwater sensor nodes under the condition that some malicious anchor nodes mixed with ordinary anchors. Due to malicious characteristic of some deliberate anchor nodes, an iterative and cooperative 3D-localization algorithm for underwater sensor networks in the existence of malicious anchors is proposed in this paper. The proposed robust localization algorithm takes advantage of distributed reputation voting method within 1-Hop neighboring reference nodes to detect and eliminate malicious anchor nodes. Moreover, one kind of Minimum Mean Squared Error estimation based iterative localization method is applied to determine accurate location information. Additionally, we analyze and prove that our localization algorithm would have a bounded error when the number of malicious anchors is smaller than a certain threshold. Extensive simulation results are provided to demonstrate performance improvements comparing to traditional Minimum Mean Squared Error and Attack Resistant Minimum Mean Squared Error based localization methods in terms of localization accuracy and coverage ratio.