Latest ArticlesHymoins A–C (1–3), three unusual polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from the flowers of Hypericum monogynum. Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP. Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system, while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system. Their structures were established by extensive spectroscopic analysis, X-ray crystallography, and computational methods. The plausible biosynthetic routes for the compounds were also proposed. In oleic acid (OA)-induced HepG2 cells, all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8 µmol/L. Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.
Neuropathic pain (NP) is one of the most common pathological pain types and is associated with limited treatment options; moreover, it affects patients’ quality of life and causes a heavy social burden. Despite the emphasis on inhibiting neuronal apoptosis to relieve NP, the crucial role of a neuroinflammation is often overlooked. Therefore, refocusing on the regulation of microglia polarization to create a more conducive environment for neuron holds great potential in NP treatment. In recent years, small interfering RNAs (siRNAs) had become an attractive therapeutic option. However, an efficient loading and delivery system for siRNA is still in lack. In our study, a nanostructured tetrahedral framework nucleic acid loaded with the small interfering RNA C–C chemokine receptor 2 (T-siCCR2) was successfully designed and synthesized for use in NP rat model in vivo and in a lipopolysaccharide (LPS)-induced inflammatory environment in vitro. This nanoscale complex is endowed with structural stability and satisfactory delivery efficiency while assuring the silencing effect of siRNA-CCR2. In vivo, T-siCCR2 treatment exhibited favorable effects on pain relief and functional improvement in the NP animal model by directly targeting microglia. In vitro, T-siCCR2 counteracts LPS-induced inflammation by inhibiting the differentiation of microglia toward the M1 phenotype, thus playing a neuroprotective role. RNA sequencing was subsequently performed to elucidate the underlying mechanism involved. These results indicate that T-siCCR2 may serve as a potential treatment option for NP in the future.
Systemic administration of the anti-rheumatic drug methotrexate (MTX) for a long period of time may lead to therapeutic tolerance, various adverse effects, and potential harm to the immune system. Therapeutic nano-delivery carriers constructed based on biologically active phenols provide a promising approach to enhance the therapeutic effect of anti-rheumatic drugs. Caffeic acid, a natural compound with anti-inflammatory properties, holds significant potential in the treatment of diverse inflammatory conditions. In this paper, we first constructed a nano-delivery platform for MTX using caffeic acid-based polyphenol polymer Ph-CaA-OH (PCOH), and investigated the treatment of rheumatoid arthritis (RA) at low drug administration doses (2.5 mg/kg). PCOH nanoparticles (NPs) could inhibit lipopolysaccharidesstimulated macrophage inducible nitric oxide synthase (iNOS) expression and pro-inflammatory differentiation in vitro. In vivo imaging revealed the rapid accumulation and sustained presence of PCOH NPs at inflamed joints in collagen induced-arthritis (CIA) mice. Therapeutic evaluation of CIA mice demonstrated that MTX@PCOH NPs were superior to free MTX in reducing the progression of RA and decreasing the expression of multiple pro-inflammatory cytokines without significant toxic effects. By enhancing drug aggregation at inflammatory joints and capitalizing on the synergistic effects of active carriers, MTX@PCOH NPs effectively minimized the required drug dosage and mitigated toxic side effects in RA treatment. The application of PCOH NPs to RA treatment provides a new strategy for the development of safer and more effective anti-RA nanomedicines.
Oxygen evolution reaction (OER) is one of the most important half-reactions related to metal-air batteries, fuel cells, and water-splitting. Due to the sluggish kinetic and multi-electron transfer, catalysts appear to be particularly important for the OER. Knowing the reaction mechanism is fundamental to developing new catalysts and improving OER efficiency. In this work, phase transition and atomic reconstruction on CoO (111) plane were revealed through ex-situ diffraction methods and X-ray absorption spectroscopy. At the same time, the electronic state evolution of Co(Ⅱ)/Co(Ⅲ) during the OER process has also been concluded by analyzing the magnetic properties. This work shows that during the OER process, Co(Ⅲ) experiences surface electron rearrangement from IS (intermediate-spin state) to LS (low-spin state) and then returns to IS/HS (high-spin state) under high voltage region. This work provides a new view to reveal the reaction mechanism through the magnetic property and it can be extended to more magnetic 3d transition metals for future catalyst design.
The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety. The integration of glutathione (GSH)-activatable two-photon photodynamic therapy (TP-PDT) and chemodynamic therapy (CDT) offers the possibility to advance precision and efficacy in anti-cancer treatments. In this study, a GSH-activatable photosensitizer (PS), namely copper-elsinochrome (CuEC), is synthesized and utilized for combination second near-infrared (NIR-Ⅱ) TP-PDT/CDT. The Cu2+ acts as a “lock”, suppressing the fluorescence and 1O2 generation ability of EC in a normal physiological environment (“OFF” state). However, the overexpressed GSH in the tumor microenvironment acts as the “key”, resulting in the release of EC (“ON” state) and Cu+ (reduced by GSH). The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-Ⅱ (λ = 1000 nm) two-photon excitation, while Cu+ can generate highly toxic hydroxyl radicals (•OH) via Fenton-like reaction for CDT. Additionally, this process consumes GSH and diminishes the tumor’s antioxidant capacity, thereby augmenting the efficacy of combination therapy. The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-Ⅱ TP-PDT and CDT.
Metabolism is a general term for a series of ordered chemical reactions in an organism used to maintain life, mainly divided into anabolic and catabolic metabolism. Nucleic acid therapy can not only precisely up-regulate and down-regulate the expression of target genes but also correct mutated disease-causing genes, which demonstrates irreplaceable and outstanding advantages in the treatment of metabolism-related diseases and has been applied to the clinical treatment of metabolism-related diseases. In this review, we introduce the structures of several major nucleic acid drugs and the mechanism of nucleic acid therapy. Subsequently, we describe the mechanisms of various biomolecular and tissue metabolisms and the etiology of metabolic disorders, classified according to metabolic substrates. We analyze the signal pathways and potential targets affecting the metabolism of each substrate and describe the nucleic acid drugs applied to these targets and their delivery technologies. This review aims to provide new ideas and targets for treating these diseases by investigating the role played by metabolism in developing diseases and providing guidance for the selection and design of nucleic acid drugs.
Photodynamic therapy (PDT) not only directly eradicates tumor cells but also boosts immunogenicity, promoting antigen presentation and immune cell infiltration. However, the robust antioxidant defense mechanisms within tumor cells significantly weaken the efficacy of photodynamic immunotherapy. Herein, a supramolecular hybrid nanoassembly is constructed by exploring the synergistic effects of the photodynamic photosensitizer (pyropheophorbide a, PPa) and the ferroptosis inducer (erastin). The erastin-mediated inhibition of system Xc− significantly downregulates glutathione (GSH) expression, amplifying intracellular oxidative stress, leading to pronounced cell apoptosis, and promoting the release of damage-associated molecular patterns (DAMPs). Additionally, the precise cooperation of PPa and erastin enhances ferroptosis efficiency, exacerbating the accumulation of lipid peroxides (LPOs). Ultimately, LPOs serve as a "find me" signal, while DMAPs act as an "eat me" signal, collectively promoting dendritic cell maturation, enhancing infiltration of the cytotoxic T lymphocytes, and eliciting a robust immune response. This study opens new horizons for enhancing tumor immunotherapy through simultaneous ferroptosis-PDT.
Controllable construction of organic heterostructures is key to developing supramolecular materials with sophisticated functions. Herein, block heterostructures with controllable shape and dimension have been successfully constructed from one molecular pair of Ir(Ⅲ) complexes 1 and 2 in H2O/CH3CN. Different volume ratios of H2O/CH3CN led to controllable morphologies of assemblies 1 from nanofibers (1NF) to nanosheets (1NS). Through reasonable experimental design, both 1NF and 1NS could be used as seeds to trigger the heterogeneous nucleation-elongation of 2. Finally, unprecedented dual control on the length and width of supramolecular block copolymers from the same monomer pair was realized smoothly. The corresponding heterogeneous nucleation-elongation process was confirmed by time-dependent UV–vis absorption spectra and emission spectra. The components of each segment of the fibrous and sheet-like block copolymers were identified by TEM, SEM, and CLSM. The results reveal that the previously unappreciated solvation effect can serve as a powerful tool to control the morphologies of heterostructures.
Diabetic liver injury is a widespread complication of diabetes and carries a high risk to liver function. Therefore, early diagnosis of diabetic liver injury is of great significance for providing quality of life for diabetic patients. Most of the activated dual-modal probes are usually activated by single factor stimulation, which greatly reduces the diagnostic accuracy of liver injury. Here, a novel cysteine (Cys)/homocysteine (Hcy) and viscosity-enhanced dual-modal probe DAL was developed for the first time to monitor diabetic liver injury and its repair process. In the presence of Cys/Hcy, the near-infrared fluorescence (NIRF) and photoacoustic (PA) signals of the probe DAL were activated, with further signal enhancement in high viscosity environments. This Cys/Hcy and viscosity cascade probe exhibits heightened sensitivity and enhanced anti-interference capabilities, contributing to the advancement of liver injury diagnosis accuracy. In addition, the probe DAL shows exceptional mitochondrial targeting ability, enabling sensitive monitoring of Cys/Hcy and viscosity alterations within mitochondria. Based on NIRF/PA dual-modal imaging technology, the probe was successfully used for the first time in a mouse diabetic liver injury model to evaluate the extent of liver damage and the repair process by tracking the levels of Cys/Hcy and viscosity. Therefore, the two-factor activated dual-modal probe developed in this study provides a powerful instrument for accurate diagnosis and efficacy evaluation of complications related to diabetes.
Mn-rich layered oxides are appealing cathodes for potassium ion batteries (PIBs) in view of their comprehensive virtues such as low cost, high energy density and mature craftsmanship. However, the insufficient covalency between transition metal (TM) and O usually induces irreversible structural evolution and cation migration during repeated insertion and extraction of K+, resulting in capacity loss, voltage fading and sluggish kinetics. Herein, an anion substitution strategy is proposed for a stable operation of layered oxide cathode by adjusting the valence electron layer structure between TM and O. The resultant strong TM−O skeleton can inhibit the occurrence of side effects derive from Ni4+ during the deep depotassium process, so as to achieve a gentle structural transition. Consequently, stable cycling performance of K0.39Mn0.77Ni0.23O1.9F0.1 (KMNOF) cathode is achieved with 77% capacity retention over 350 cycles at 100 mA/g, yielding high discharge capacity 93.5 mAh/g at 20 mA/g and significantly improved rate capability of 50.1 mAh/g at 500 mA/g, whereas irreversible structural evolution and rapid capacity fade with KMNO cathode. Finally, in situ/ex situ characterizations and theoretical computations sheds light on the charge transfer and structure evolution mechanisms of KMNOF.
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