Latest ArticlesLithium–sulfur (Li–S) battery is considered as a promising next-generation high-energy-density battery. However, the cycle life of Li–S batteries is severely plagued by the instability of Li metal anodes. Improving Li deposition uniformity can mitigate the formation of inactive Li and the side reactions between Li polysulfides and Li metal anodes. Herein, 1-methyl-1-propylpyrrolidinium bis(fluorosulfonyl)imide (Py13FSI) is proposed as an additive to improve the uniformity of Li deposition in Li–S batteries. At a low concentration, Py13+ exhibits a lower reduction potential than Li ions. Py13+ can be adsorbed and accumulate on the surface protuberances of Li metal anodes, inducing the deposition of Li towards non-tip sites and improving the uniformity of Li deposition. With a high-loading cathode (4.1 mgS/cm2) and an ultrathin Li metal anode (50 µm), the cycle life of Li–S batteries is prolonged from 61 to 120 cycles via Py13FSI additives. Furthermore, a 401 Wh/kg Li–S pouch cell with Py13FSI additives undergoes 14 cycles. This work demonstrates the potential of improving Li deposition uniformity in Li–S batteries by appropriate electrolyte additives.
The severe threat of heavy metal pollution to ecological sustainability and human health has made the urgent development of efficient and environmentally friendly remediation technologies a necessity. Polyoxometalates (POMs), a class of unique metal-oxygen clusters with regulable structures and excellent properties, have emerged as promising candidates for removal of heavy metal ions. This review summarized the recent advances in POM-based functional materials (e.g., host-guest, heterojunction, and POM-based metal-organic frameworks) for heavy metal ion remediation (such as U(VI), Pb(II), and Cr(VI)). The removal mechanisms, including adsorption, chemical reduction, photocatalytic reduction, adsorption-photocatalysis synergy, as well as the chemical sensor or probe for heavy metal detection, have been highlighted. Additionally, the challenges in improving material recyclability, scaling up synthesis, and understanding the long-term environmental impact of POMs are identified, while future research directions toward sustainable, cost-effective, and multifunctional POM-based systems are proposed. This review provides a comprehensive overview of POM-based functional materials potential in addressing heavy metal pollution, offering insights for designing next-generation environmental remediation materials.
A series of highly rearranged labdane diterpenoids featuring previously unreported skeletons, including 9,18-cyclolabdanes (1 and 2), 1,10-seco-9,18-cyclolabdanes (3–5), 7,18-cyclolabdanes (6), and 1,10-seco-1,5-cyclolabdanes (7), along with seven novel labdanes (8–14), two novel halimane diterpenoids (15 and 16), and three known congeners (17–19), were isolated from Chinese liverwort Haplomitrium mnioides. Their structures were unequivocally determined through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. These diverse diterpenoids were biosynthesized through an aldol-type cascade process, using 19 as the starting material, distinguishing them from compounds generated via conventional carbocation rearrangement. Anti-inflammatory assays revealed that haploide O (15) and haplomitrenolide C (17) significantly inhibited the secretion of proinflammatory cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in vitro in concanavalin A (ConA)-induced murine spleen cells.
The application of Arsenic trioxide (ATO) has greatly improved the cure rates in patients with acute promyelocytic leukemia (APL) and has shown therapeutic effects in other leukemia types, as evidenced by an increasing number of preclinical trials. However, its clinical application is still limited due to a lack of understanding of the underlying mechanisms. In this report, we have demonstrated that ATO can induce pyroptosis and release damage-associated molecular patterns (DAMPs), such as high mobility group box 1 (HMGB1) and interleukin-1β (IL-1β). DAMPs can activate the immunogenic cell death (ICD) mechanism. Our study elucidated the pivotal role of pyroptosis and demonstrated the activation of the caspase-3/gasdermin E (GSDME) pathway both in vivo and in vitro upon ATO intervention. Proteomic analysis of cell supernatants revealed the release of the ICD-associated molecule HMGB1. Results from both in vitro and in vivo experiments collectively demonstrated that the release of HMGB1 is contingent upon GSDME-mediated pyroptosis. Furthermore, label-free quantitative proteomics in vivo indicated that ATO-induced pyroptosis activates natural killer cells (NKs) and promotes the release of granzyme B (GZMB). Our study is the first to demonstrate the synergistic interplay between pyroptosis and ICD mechanisms during ATO treatment, providing novel insights into the potential of ATO for immunotherapy and synergistic treatment approaches.
Multiple myeloma (MM) is the second most common hematological malignancy and still remains incurable. Selinexor (SEL) is the first-in-class exportin 1 (XPO1) inhibitor, and has demonstrated survival benefits in relapsed/refractory MM patients. Despite its therapeutic potential, dose-limiting toxicities frequently compromise SEL’s clinical utility and patients’ quality of life. In this work, to improve therapeutic efficacy and minimize side effects of SEL, we designed the monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelle-encapsulated nanoformulation for MM therapy. The mPEG-PCL-SEL micelle exhibited controlled release behavior and showed remarkable cytotoxicity in MM cells. Most importantly, in the orthotopic MM model, this micelle system exhibited impressive therapeutic efficacy at low dosages and significantly prolonged the survival of MM-bearing mice. Moreover, the mPEG-PCL-SEL micelle demonstrated a favorable safety profile with fewer gastrointestinal and constitutional symptoms. And we found that compared with the free-SEL, the mPEG-PCL-SEL micelle maintained the integrity of the intestinal barrier, and was more beneficial to the diversity of the intestinal microbiota, which may be related to the improved gastrointestinal tolerability, making it an effective and safe choice for MM treatment.
Developing effective strategies to simultaneously suppress tumor thermotolerance and secondary inflammation remains a significant challenge in enhanced photothermal therapy (PTT). In this study, we developed a nitroreductase (NTR)-triggered multifunctional photothermal agent (m-SCy-DCF) by conjugating mitochondria-targeted sulfur-substituted hemicyanine to the anti-inflammatory diclofenac (DCF) through an NTR-cleavable linker. Upon activation in the hypoxic tumor microenvironment, m-SCy-DCF selectively accumulated in mitochondria and generated localized hyperthermia under laser irradiation. This process not only disrupted mitochondrial function but also suppressed the expression of heat shock proteins (HSPs). Simultaneously, the released DCF exerted potent anti-inflammatory effects, effectively reducing the levels of inflammatory cytokines in vivo. This dual suppression of tumor thermotolerance and inflammation induced immunogenic cell death and achieved effective tumor ablation, demonstrating the potential of m-SCy-DCF as a highly promising candidate for enhanced PTT.
Compared to synthetic chemical compounds, plant extracts derived from natural sources have emerged as the "new favorites" in the treatment and care of skin diseases due to their distinct advantages, including being environmentally friendly, sustainable, and safe. However, challenges such as poor solubility, limited permeability, and the barrier function of the stratum corneum significantly restrict the application of natural products in dermal drug delivery. Fortunately, advancements in nanotechnology offer promising solutions to overcome these challenges. Different skin diseases and treatments require the precise delivery of natural active ingredients to specific skin layers, and the unique structure of nanocarriers enables targeted delivery to achieve desired therapeutic outcomes. This paper begins by exploring the pathogenesis and therapeutic targets of common skin conditions, including atopic dermatitis (AD), psoriasis, decubitus ulcers, diabetic foot ulcers (DFUs), as well as applications in antioxidant therapies and anti-aging strategies. Furthermore, it provides a detailed overview of the depths and locations within the skin where active compounds must be delivered to exert their effects effectively. Subsequently, this review categorizes and examines natural products based on their therapeutic effects on various skin diseases. It then highlights the skin depths and specific sites that can be targeted by different delivery systems designed to enhance skin permeability, tailored to meet the needs of skin disease treatment or care. By addressing these aspects, this review aims to provide a valuable reference for advancing research on nano-delivery systems in the field of topical skin drug delivery for the treatment and management of skin diseases.
Macrophage membrane-camouflaged nanoparticles (MmNPs) are emerging as efficient nanoplatforms for targeted delivery to inflammatory sites, tumors, and infected tissues due to the innate characteristics of macrophages. This biomimetic strategy effectively addresses several limitations of traditional targeted drug delivery systems, offering improved biocompatibility, extended blood circulation, immune evasion, and site-specific homing. Compared to conventional functionalization methods, MmNPs provide a simplified method for creating multifunctional nanoparticles. In this review, we explore the origins and functions of macrophages, highlighting how MmNP platforms are leveraged for precise drug delivery. The latest applications of MmNPs in targeted delivery are summarized, focusing on their intrinsic targeting properties, membrane surface modifications and designs for environmental stimulus response. Finally, we discuss the prospects and challenges in translating MmNP technology from experimental settings to clinical applications, aiming to inspire continued innovation in the design of MmNP for precise and effective drug delivery strategies against complex diseases.
Macrophage-derived exosomes have demonstrated considerable potential for promoting bone regeneration. This study proposes a novel engineered therapeutic strategy that utilizes carbon monoxide releasing prodrugs (TG-Fe CORMs) to selectively induce M2 macrophage polarization, thereby enhancing the production of M2 macrophage-derived exosomes (CO-M2-Exos). These exosomes have been observed to significantly promote osteogenesis and accelerate alveolar bone regeneration through the microRNA-21/Lhx8 signaling pathway. Notably, these exosomes possess several advantageous characteristics, including their capacity for remarkable regenerative effects, low immunogenicity, and high cellular uptake, which renders them promising cell-free therapy for addressing alveolar bone defects. Moreover, the scalable production of CO-M2-Exos successfully overcomes the significant challenges associated with traditional exosome-based therapies, such as the complexity of cell culture processes, the instability of phenotype, and the low yield of exosome production. This engineered approach offers a reliable, efficient, and cost-effective solution for clinical translation, particularly for promoting alveolar bone regeneration in cases of severe bone atrophy following tooth extraction.
Globo-H is a tumor-associated carbohydrate antigen (TACA) that is overexpressed in various cancers, making it a promising target for anticancer vaccine development. However, traditional conjugate vaccines, such as those linked to keyhole limpet hemocyanin (KLH) or cross-reactive material 197 (CRM197), have demonstrated limited clinical efficacy. To address this limitation, we developed an innovative vaccine candidate by conjugating chemoenzymatically synthesized Globo-H to a mutant of bacteriophage Qβ (mQβ) virus-like particle. The resulting mQβ-Globo-H conjugate elicited significantly higher levels of anti-Globo-H IgG antibodies in mice compared to both KLH-Globo-H and CRM197-Globo-H conjugates. Furthermore, the antibodies produced by the mQβ-Globo-H conjugate exhibited strong binding to MCF-7 breast cancer cells and triggered potent complement-dependent cytotoxicity (CDC) against these cancer cells. In contrast, negligible antibody binding and CDC effects were observed against normal MCF-10A breast epithelial cells. This new conjugate vaccine also produced robust humoral responses in rabbits, with the resulting antibodies exhibiting high selectivity for human breast cancer tissues. These findings underscore the clinical translational potential of the mQβ-Globo-H conjugate vaccine.
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