Latest ArticlesBirefringent crystals have gained increasing attention for versatile optical devices due to their inherent ability to modulate light polarization. However, the rational design of structures that exhibit high birefringence and deep-ultraviolet (DUV) transparency remains a formidable challenge. Here, a novel zinc borate birefringent crystal, Na2ZnB6O11 (NZBO), was identified by strategically assembling the π-conjugated [B3O7] functional units using the unprecedented antiparallel triangles formed by [ZnO3] motifs. Remarkably, through a tailored motif approach and optimized arrangement, NZBO achieves the largest birefringence (0.094) in the visible wavelength range among the borate-based crystals containing [B3O7] units, exceeding that of commercially available birefringent crystal MgF2 by approximately 8 times (0.012@532 nm). Furthermore, NZBO exhibits a notably short DUV absorption cutoff edge below 190 nm along with a wide band gap of 6.04 eV attributed to the elimination of dangling bonds. The origin of the optical anisotropy attributes of NZBO was elucidated through a combination of theoretical calculations and structural analyses. These findings highlight the good potential of NZBO in the manipulation of polarized light and offer valuable insights for tailoring new birefringent materials in the short-wave UV transparency region.
Ferroelectric plastic crystals have garnered significant attention in recent years due to their unique phase-transition behaviors and potential nonlinear optical properties. Nevertheless, most existing examples encounter challenges, such as inadequate transparency and diminished nonlinear optical signal, which constrain their broader applicability. In this study, we present a new ferroelectric plastic crystal, 1-azanorbornanium tetrachlorogallate, which crystallizes in the polar space group Pmc21 at room temperature and undergoes plastic phase transition at above 413 K. This phase transition endows this compound with nonlinear optical performance at polar room-temperature phase, while allowing highly-dynamic molecular rotation to provide excellent mechanical flexibility at high-temperature phase. Through hot-pressing the powder sample, a pressed tablet with an increased density that is 99.4% of crystallographic density (1.70 g/cm3) was obtained. Benefiting from the elimination of crystal grains, such a high-density tablet has significant improvements in light transmittance and second harmonic generation (SHG). Its SHG is increased by approximately 20 times and 6 times those of the loose powder form and referenced KH2PO4, respectively. This work demonstrated the potential of hot-pressing method on enhancing nonlinear optical performance of polar plastic crystals.
With the increasing demand for high-energy-density lithium ion batteries, it has become increasingly imperative to address the safety concerns associated with batteries. At present, the design of flame-retardant electrolytes has been widely studied. However, most strategies lack the discussion of battery-level safety, and have only conducted primary safety tests such as ignition. In this situation, it is necessary to analyze the intrinsic link between flame-retardant electrolytes and battery safety. This paper elucidates the role of flame-retardant electrolytes in the thermal runaway process of batteries and proposes a strategy to enhance the safety of batteries from the aspect of electrolytes. Then the thermal, electrochemical and interfacial stability characteristics of different flame-retardant electrolytes are analyzed in detail based on their structures, and the basic principles for the design of their solvent structures are pointed out to enhance electrochemical performance. Furthermore, a prospective summary of safety characterization at the material and battery level is presented, aiming to build a comprehensive battery safety characterization system. This review provides insights into the design of flame-retardant electrolytes for high safety batteries.
Traditional chemotherapeutic approaches lack selectivity and damage both cancerous and healthy cells. In contrast, cancer immunotherapy harnesses the host's immune system to selectively target and eradicate tumor cells, offering tremendous potential for the long-term suppression of tumor growth and preventing its recurrence. However, tumors often develop immune evasion by exploiting immune checkpoints, which regulate the immune system. Among these checkpoints, programmed death protein 1 (PD-1) and its ligand (PD-L1) have garnered significant interest because they play a key role in protecting the tumor cells from immune-mediated eradication. The approval of monoclonal antibodies (mAbs) that target PD-1/PD-L1 by the Food and Drug Administration (FDA) is a milestone in immunotherapy. Although mAbs have demonstrated remarkable success in treating skin melanomas, their efficacy against other solid tumors remains limited. There is a clear need to explore new approaches to enhance the efficacy of mAbs and find more effective checkpoint inhibitors. Metal-based drugs offer a new platform to address this challenge. This review highlights the recent progress in leveraging metal complexes as PD-1/PD-L1 inhibitors. We discussed metal-based agents used either alone or in combination with mAbs to boost the immune system. We also highlighted examples of metallodrugs encapsulated within the nanoparticles to augment the efficacy of immune checkpoint therapy. While research on metal-based complexes targeting PD-1/PD-L1 is still in its infancy, the examples presented here will serve as the basis for future discussions and efforts in this emerging field. We anticipate that ongoing research in targeting immune checkpoint blockade with innovative metal-based therapeutics will enhance the scope of treatment across a wide range of cancers.
In the process of tumor treatment, chemotherapy drugs have been widely used in clinical practice due to their broad-spectrum and significant therapeutic effects. However, the serious side effects caused by off-target effects also limit the actual efficacy of such drugs in clinical. Here, we developed a series of small molecule-drug conjugates (SMDCs) with carbonic anhydrase IX (CAIX)-targeted unit, which can deliver chemotherapy drugs to CAIX-positive cancer cells and release them in the tumor microenvironment. These SMDCs can quickly captured by the highly expressed CAIX on the tumor membrane, forming a high local concentration difference that allows SMDCs to enter the tumor cells faster. The optimized SMDC (CAIXi-R-HCPT) with ROS-sensitive linker showed higher cytotoxicity than Irinotecan. In MDA-MB-231 solid tumor-bearing mice, CAIXi-R-HCPT showed higher tumor/normal tissue (T/N) ratio than the corresponding SMDC and Irinotecan control and it also exhibited in vivo anti-tumor activity comparable to HCPT at the same dosage, and there was no significant weight loss. These findings emphasize the potential of CAIXi-R-HCPT as a promising anti-cancer SMDC that exhibits targeted delivery, tumor-specific release, and strong anti-tumor effects.
Heterodimerization of receptor tyrosine kinases (RTKs) plays unique roles in cell signaling and functions. However, engineering heterodimerization of multiple receptors remains largely unexplored. Herein, we developed an aptamer-based DNA Nano-windmill (TA3) to regulate heterodimerization of three different RTK families, simultaneously activating fibroblast growth factor receptor 1 (FGFR1), hepatocyte growth factor receptor (Met) and epidermal growth factor receptor (EGFR) signaling. It is the first DNA Nano-windmill that activates heterodimerization of FGFR1, Met and EGFR, leading to the down-stream signals transduction, such as the phosphorylation of protein kinase B (Akt) and extracellular regulated protein kinases (Erk), inducing the cell migration and proliferation. We further designed transformable DNA Nano-windmill (TMA) that can convert DNA Nano-windmill into DNA Nano-kite using complementary strands or small molecules to reduce the activation of specific receptor. We believe that the DNA Nano-windmill for heterodimerization of different RTK families have potential applications in biomedicine fields.
Understanding the mechanisms of virus infection is pivotal for the effective prevention and treatment of viral diseases. This review provides a comprehensive overview of the latest advancements in real-time monitoring of viral dynamics within established infection models. We begin by summarizing the recent progress in fluorescent probe and labeling techniques for real-time and in situ virus tracking. Next, we provide an in-depth analysis of the types and characteristics of virus infection models and discuss their respective advantages and limitations in virus tracking. Finally, we detail the recent progress in viral dynamics tracking across different infection models, illustrating how to use these models to monitor virus infection dynamics and discussing the meaningful biological information that can be acquired.
Bacitracin has been extensively studied for its antibacterial application due to its excellent anti-Gram-positive bacterial properties. However, its application of conventional bacitracin has been limited because of its limited antibacterial activity against Gram-negative bacteria, especially negative bacilli. In this study, we designed and synthesized bacitracin-zinc nanodrugs (BPNDs) through zinc coordination self-assembly of bacitracin, which exhibit potent antibacterial effects not only against Gram-positive bacterial Staphylococcus aureus but also against Escherichia coli, a typical Gram-negative bacillus. The morphological and antimicrobial properties of the self-assembled BPNDs with different molar ratios of bacitracin to zinc ions were investigated. The bacterial biofilm experiments confirmed the biofilm scavenging effect of BPNDs, further expanding the application of this antimicrobial agent. In-depth cell viability experiments indicated that this antimicrobial activity might be related to the penetration of BPNDs into bacterial cell membranes. This study reveals that the zinc-coordinated peptide self-assembly strategy expands the antibacterial spectrum of conventional bacitracin, making it a potential candidate for novel antimicrobial drugs to address the bacterial resistance dilemma and provide stable alternatives for a wide range of biomedical and related industries.
The performance of photosensitizers determines the effect of photodynamic therapy (PDT). At present, most photosensitizers are developed from fluorescent dyes, but it is difficult to possess both the good photophysical properties and photosensitive efficiency. In this work, an efficient strategy was developed to construct a cyanine-based near infrared (NIR) photosensitizer, 2LBCy5.5, with an enlarged and twisted D-π-A-π-D structure by connecting two classical Cy5.5 dyes smartly with a dual-cationic benzo[1,2-b:4,5-b']dipyrrole group. The 2LBCy5.5 exhibited a maximum absorption at 802 nm with a great molar extinction coefficient of 4.2 × 105 L mol−1 cm−1, compared with its parent Cy5.5 (692 nm with a molar extinction coefficient of 2.5 × 105 L mol−1 cm−1). Furthermore, 2LBCy5.5 exhibited narrow energy gap of singlet-triplet (ΔES-T) accelerated the intersystem crossing process (1.21 ns−1) with a high triplet-excited-state quantum yield (26.1%) under 808 nm excitation, greatly contributing to reactive oxygen species (ROS) generation in type-Ⅰ PDT. The excellent anti-tumor ability of 2LBCy5.5 was realized both under normoxic and hypoxic conditions. This study provides an effective and powerful approach for designing cyanine photosensitizers with strong capabilities in both photophysical properties (e.g., NIR light-harvesting) and highly antitumor efficiency.
The photopharmacology incorporated with molecular photoswitches offers a promising solution to fundamentally address the problem of bacterial resistance, simultaneously realizes the spatiotemporal precision treatment through remote light control. However, most of reported photoswitchable drugs are limited by the need of ultraviolet (UV) light, which is often damaging and not suitable for tissue penetration. Therefore, the development of photopharmacological agents triggered by visible light, especially near-infrared (NIR) light is highly desirable for future photoswitchable antibiotics. Herein, a novel photopharmacological antibacterial agent DTE-FQ was designed and synthesized by the incorporation of dithienylethene (DTE) molecular photoswitch and fluoroquinolones (FQ) antimicrobial drug norfloxacin bridged by pyridinium group and flexible butyl chain. As expected, as-prepared DTE-FQ presents efficient photoswitching behavior in various solutions upon alternating irradiation with blue light (460–470 nm) and NIR light (730–740 nm). Simultaneously, it shows significant and reversible configurational transition by the synergistic effect of DTE photoswitch and flexible butyl chain. Most remarkably, DTE-FQ reveals an at least 4-fold difference in activity against Escherichia coli (E. coli) for ring-open and ring-closed isomers, and a distinct change in bacterial growth is observed by in situ irradiation with NIR light in the presence of E. coli. These results are further confirmed by the molecular docking to DNA gyrase. The chain-like configuration of DTE-FQ treated with NIR light, inserted between the double-stranded DNA restraining the replication of DNA. Whereas the coiled configuration obtained by blue light irradiation, remained in the vicinity of the double-stranded DNA showing weak antibacterial activity. As far as we know, it represents the first example of blue-/NIR light-triggered photopharmacological antibacterial agent based on DTE switch so far, indicating its potential for in vivo photopharmacological applications.
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