Latest ArticlesAlzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder, marked by a variety of pathological hallmarks such as oxidative stress (OS), metal accumulation, and the aggregation of amyloid-beta (Aβ) proteins. Erucin, a natural compound present in cruciferous plants, has demonstrated promising therapeutic potential in modulating neurodegenerative diseases, hinting at its neuroprotective capabilities. In this study, we engineered an innovative intracellular protein delivery system centered around erucin. This delivery platform operates through a cell membrane perforation mechanism, enabling the swift translocation of target proteins into the cytoplasm. As a result, it substantially shortens the time required for the proteins to exert their functions. Significantly, this delivery system inherently possesses the capacity to inhibit Aβ aggregation. In PC12 cell models, the delivery of the antioxidant enzyme superoxide dismutase (SOD) successfully mitigated the OS triggered by Aβ aggregation and decreased cytotoxicity. This multifaceted therapeutic strategy holds great promise as an effective approach for the treatment of AD.
Aqueous zinc-ion batteries (AZIBs) have drawn numerous attention due to their low cost and environmental benefits. However, its commercialization process was hindered by issues, such as uncontrolled dendrite growth and parasitic side reactions. Inspired by the natural interaction between Zn2+ and amino acid chains in zinc finger proteins, we introduced L-proline (LP), a cost-effective additive, into the aqueous electrolyte to stabilize the Zn anode. In combination with experiments and theoretical calculation results, it is demonstrated that the LP additive tends to reshape the hydrated Zn2+ solvation sheath and weaken the free H2O activity, thereby restricting the water-induced parasitic reactions and drastic dendrite growth. Therefore, the Zn symmetrical cells with LP-containing electrolytes delivered an excellent superior electrochemical performance, including a long-term calendar lifespan of 3400 h at 2 mA/cm2 and nearly 450 h at 5 mA/cm2. Meanwhile, the as-assembled Zn||MnO2 full cells also showed desired cycling stability and rate performance with the assistance of LP additive, outperforming the ZnSO4 system. This intriguing bio-inspired strategy provides a valuable insight for improving the longevity of AZIBs and advancing their development in energy storage.
Aqueous zinc-ion hybrid capacitors (AZICs) combine the advantageous characteristics of the high energy density of aqueous zinc-ion batteries with the high power density of supercapacitors. However, their practical application is limited by the instability of the zinc anode and the relatively low capacity of the carbon cathode. To address these challenges, we propose the utilization of p-benzoquinone (BQ) as a bifunctional electrolyte additive. This additive adsorbs onto the zinc surface and modifies the Zn2+ solvation structure, effectively suppressing the growth of zinc dendrites and mitigating water-related side reactions. As a result, the lifespan of the zinc anode is significantly extended from 35 h to 1188 h at 0.5 mA/cm2 and 0.5 mAh/cm2, with a high average Coulombic efficiency of 99.30%. Additionally, the BQ additive enhances the specific capacity of the cathode through its rapid redox reactions on the cathode surface. The AZIC also demonstrates a notable increase in capacity, rising from 40 mAh/g to 140 mAh/g at 0.5 A/g, alongside improved rate performance and cycling stability. This study offers an efficient strategy to simultaneously address the stability and energy density limitations of AZICs.
The inappropriate use of antibiotics has led to the emergence of drug-resistant bacteria and the formation of persistent biofilms, rendering conventional antibiotics ineffective against these infections. To address this challenge, the enzyme-like activity of nanozymes, particularly those with photothermal effects, is being explored. However, the development of nanozymes is hindered by the complex synthesis processes involved and the consumption of reactive oxygen species (ROS) by reducing products in bacteria. This article presents an interesting strategy utilizing near-infrared laser-enhanced oxidase-like (OXD-like) activity of manganese dioxide nanoparticles (MnO2 NPs) to combat subcutaneous infections caused by methicillin-resistant Staphylococcus aureus (MRSA). MnO2 NPs, characterized by flower-like morphology and broad near-infrared absorption, exhibited favorable OXD-like activity and a stable photothermal effect. Experiments in vitro revealed that the combined high thermal effect and the substantial production of ROS effectively targeted MRSA and disrupted biofilm. The efficacy of MnO2 in vivo was validated through the establishment of a subcutaneous abscess model. Additionally, a series of biosafety tests, including routine blood tests and blood biochemistry analyses, confirmed the safety of MnO2 in vivo. Collectively, these findings suggest that combination therapy involving MnO2 presents a promising therapeutic approach for addressing infections associated with biofilms and drug-resistant bacteria.
An efficient skeletal editing for the construction of 2-benzodiazepines from benzo[c]oxepines was developed through atom-swapping of oxygen atom to the nitrogen atom. This reaction integrated the sequential ring-opening/substitution/ring-closing in the continuous manufacturing one-pot synthesis. The reaction conditions are mild, transition metal-free, simple-operated and the substrates are widely applicable. The anti-tumor activity of some synthesized 2-benzodiazepine compounds shows this atom-swapping skeletal editing through the deconstruction-reconstruction of heterocycles is attractive and effective in the discovery of new drug skeletons.
Zinc ions (Zn2+) play a crucial role in maintaining human health, and their imbalance has been associated with various diseases and environmental contamination. Although many fluorescent probes have been developed for Zn2+ detection, they often face challenges, including short emission wavelengths, narrow Stokes shifts, and particularly the poor selectivity. Here, aromatic rings with different electron densities including benzene, thiophene and furan rings, were introduced as aromatic π-conjugated bridges to connect dicyanoisophorone (DCI) and amide-di-2-picolylamine (DPA) based structures, and three probes L1, L2 and L3 for Zn2+ detection were developed. Our results demonstrated that compared with L1, L2 and L3, which inserting thiophene and furan rings, revealed near-infrared (NIR) emission at 651 nm, and a larger Stokes shift of 187 nm. Notably, different from L2, L3, which incorporated a furan ring with the highest electron density, exhibited the highest selectivity for Zn2+ with a low detection limit of 31 nmol/L. In addition, the binding mode of L3 with Zn2+ was confirmed in the form of an imidic acid tautomer. Furthermore, L3 was successfully applied in cellular imaging, validating its potential for in vivo bioimaging. This study presents a promising strategy for developing high-performance Zn2+ probes by simply modifying the aromatic π-conjugated bridges.
Density functional theory calculations were performed to investigate the iridium-catalyzed atroposelective intermolecular C-H silylation of 2-arylisoquinolines. The Ir(Ⅲ) hydride species was identified as the active catalyst species of the reaction. The computations show that the reaction occurs through the Ir(Ⅲ)/Ir(V) catalytic cycle. The C(sp2)-H oxidative addition represents the rate- and enantioselectivity-determining step. The distortion/interaction and structural analyses reveal that the BINEPINE skeleton of the PSiSi ligand creates an axially chiral pocket for the C-H oxidative addition, providing a ligand-enabled axial chirality transfer strategy responsible for the observed enantioselectivity. The match/mismatch in axial chirality between reacting 2-arylisoquinolines and the BINEPINE skeleton of the PSiSi ligand plays a key role in governing enantioselectivity.
Ferroptosis has emerged as a significant pathway in various pathological conditions. Studying the effects of inhibiting ferroptosis on liver injury is instrumental in gaining a deeper understanding of the mechanisms. This study the design and synthesis of a multi-channel near-infrared emitting fluorescent probe TXVQ. When the probe TXVQ responds to HSO3−, the fluorescence intensity at 500 nm of TXVQ increases with the addition of HSO3−. As the concentration of H2O2 increases, the fluorescence intensity of TXVQ at 600 nm is enhanced. Concurrently, as viscosity rises, the fluorescence intensity of the probe TXVQ at 725 nm will gradually increase. The probe TXVQ, with its ability to monitor HSO3−, H2O2 and viscosity through three distinct fluorescent channels, is advantageous for its application in the biological field. Subsequently, cellular experiments have demonstrated that the probe TXVQ can monitor changes in intracellular HSO3−, H2O2 and viscosity. At the cellular level, it is found that inhibiting ferroptosis had no alleviating effect on drug-induced liver injury (DILI), but it had a certain alleviating effect on acute kidney injury (AKI). In a murine model, the effects of ferroptosis inhibition on DILI and AKI indicate that inhibiting ferroptosis reduced kidney injury but not liver injury, highlighting its potential in kidney therapeutics. TXVQ can detect various levels of HSO3−, H2O2 and viscosity through three different fluorescent channels, making it a powerful tool for diagnosing and treating kidney diseases, as well as deepening the understanding of the role of ferroptosis in liver and kidney pathologies.
In this study, we report a palladium-catalyzed carbene C-H insertion reaction of non-activated arenes using N-tosylhydrazones as both carbene and olefin precursors. This method consists of a two-step, one-pot process, where the arenes are first thianthrenated and then undergo migratory insertion/β-H elimination with N-tosylhydrazones to form aryl alkenes. This highly site-selective C-H alkenylation of arenes demonstrates a relatively broad substrate scope and exhibits high tolerance for halogen substituents. Importantly, this transformation allows for the modification of the arene moiety in commercially available bioactive molecules, underscoring its significant potential for late-stage functionalization of arene-containing pharmaceuticals.
Colon cancer is one of the malignant tumors with high morbidity and mortality worldwide, and its etiology is closely related to high levels of hydrogen sulfide (H2S). To date, H2S-activated near-infrared (NIR) fluorescent (FL) probes with high tumor tropism are still scarce. In this work, we created a new NIR FL probes (Cy-DG) that enables colon cancer targeted imaging and rapid fecal optical analysis by introducing an H2S-recognition moiety and two D-glucosamine fragments on the scaffold of QCy7. Cy-DG exhibits excellent properties, including specific "off-on" response toward H2S, intense NIR emission at 703 nm, large Stokes shift (118 nm), and high sensitivity (limit of detection (LOD), 0.48 µmol/L). Notably, the presence of D-glucosamine allows Cy-DG to be preferentially taken up by cancer cells. After intravenous administration, Cy-DG was able to efficiently accumulate in a MC38 intestinal cancer model and sensitively detect endogenous H2S in vivo, showing 5.94-fold higher fluorescence intensity in small tumors < 5 mm. Furthermore, Cy-DG was successfully used to detect H2S in feces samples from colon cancer-bearing mice. We believe that Cy-DG has great potential as a powerful diagnostic tool for H2S-related disorder and stool examinations in the future.
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